ii
EPA 600/R-08/062 

May 2008 

Scientific and Ethical Approaches for 

Observational Exposure Studies 

National Exposure Research Laboratory 

Office of Research and Development 

U.S. Environmental Protection Agency 

Research Triangle Park, NC 27711 

iii
iv
Notice 

This document has been subjected to the Agency’s peer and administrative review and has 

been approved for publication as an EPA document. Mention of trade names or commercial 

products does not constitute endorsement or recommendation for use. 

iii
Abstract 

Researchers conduct observational human exposure studies to understand how and the extent 

to which people come into contact with chemicals and environmental stressors in their everyday 

lives, through the air they breathe, the food and liquids they consume, and the things they touch. 

The U.S. Environmental Protection Agency’s (EPA’s) National Exposure Research Laboratory 

(NERL) has conducted observational human exposure studies for several decades and uses the 

information and data from these studies to improve the Agency’s understanding of human 

exposures to chemicals and other stressors and ultimately to support efforts to improve public 

health. Because these studies involve people as research participants, they are complex and raise 

numerous scientific and ethical issues that have to be addressed prior to and during their design 

and implementation. To ensure that EPA’s research continues to be based on the most up-to-date 

science and the highest ethical standards, the Agency has developed this document that contains 

state-of-the-science approaches for conducting observational human exposure studies. This 

document is not meant to represent an official Agency “guidance document” but, rather, serves as 

a resource tool and source of information for NERL and other researchers on which to rely as 

they develop and conduct observational human exposure studies. 

iv
Foreword 

This document is intended as a resource and reference for the U.S. Environmental Protection 

Agency’s (EPA’s) National Exposure Research Laboratory (NERL) scientists as they develop 

and implement observational human exposure studies. The authors recognize that this document 

also may prove to be useful to others involved in exposure science research, but the document is 

not meant to represent an official Agency “guidance document” and should not be used for that 

purpose. 

Observational human exposure studies involve the collection of information about individuals 

and the environment around them. NERL scientists and managers take the protection of human 

subjects who participate in these studies very seriously. The steps needed to ensure protection of 

the human subjects are often complex, and the specific actions will vary depending on the 

objectives of the study and details about the participants. 

This document does not provide solutions to all scientific and ethical issues that may arise as 

such studies are undertaken. That is, it is not possible to identify or address all potential issues in 

advance or to develop a comprehensive checklist for all such studies. Rather, this document 

attempts to present and discuss the types of issues that will need to be considered and addressed 

as NERL researchers plan and implement observational human exposure studies. The researchers 

will need to work with others⎯the study team, institutional review board members, EPA’s 

Human Subjects Research Review Official, the participants and their community, and other 

stakeholders⎯to identify and address all of the relevant issues for their particular study in order 

to ensure that the specific elements of the study will respect, safeguard, and protect the human 

research subjects. 

As EPA employees, NERL scientists face both regulatory and moral obligations to ensure the 

protection of the human subjects participating in observational research. The regulatory 

requirements are set forth in EPA’s human subjects regulations (40 CFR 26). NERL scientists are 

resolved to meet both the “letter” of the law as set forth in the regulations and also the “spirit” 

that derives from the most up-to-date thinking and consensus on these sensitive issues. This 

document provides information on regulatory requirements and the state of the science for a 

number of issues associated with observational human exposure studies to help NERL scientists 

meet their goal of conducting these studies based on the most up-to-date and sound science and 

the highest ethical standards. 

To gather information for the scientific and ethical approaches for observational human 

exposure studies, NERL convened an expert panel workshop on November 28 and 29, 2006, to 

discuss the state of the science. The 11-member panel discussed their ideas for the content of this 

document and the state of the science for various elements of observational human exposure 

studies. The panel agreed that the document planned by EPA should include the following six 

major topic areas: 

(1) identifying elements to be considered in study conceptualization, 

(2) ensuring protection of vulnerable groups, 

(3) addressing privacy and other concerns related to observational human exposure studies, 

(4) creating an appropriate relationship between the participant and investigator, 

v
vi

(5) building and maintaining appropriate community and stakeholder relationships, and 

(6) designing and implementing strategies for effective communication. 

The structure and content of the current document follow the recommendations of the Expert 

Panel. These recommendations include pragmatic steps that NERL scientists can undertake 

during the development and implementation of observational human exposure studies. 
Acknowledgments 

This document was developed through the joint efforts of many U.S. Environmental 

Protection Agency (EPA) staff. Roy Fortmann, Larry Cupitt, Kent W. Thomas, and Peter Egeghy, 

researchers in the National Exposure Research Laboratory, were primary authors of the 

document. Linda Sheldon provided input to the development of the document and contributed 

through discussions with the authors on issues associated with observational human exposure 

studies. Davyda Hammond assisted in the revision of the external review draft document. Larry 

Cupitt had primary responsibility for editing the document and coordinating the peer reviews. 

Internal EPA reviewers included Pamela Williams, Warren Lux, Michael Firestone, Gary Bangs, 

Julian Preston, Hugh Tilson, Ronald Williams, Cathy Fehrenbacher, and Deirdre Murphy. The 

EPA Human Studies Review Board, a Federal advisory committee, reviewed the external review 

draft document and provided advice and recommendations that were addressed in the final 

revision of the document. John Barton performed the copy edits of the external review and final 

drafts. Public comments solicited on the external draft were addressed in the final revision of the 

document. 

vii
Contents 

Notice ........................................................................................................................................ iii 

Abstract .........................................................................................................................................iv 

Foreword ..........................................................................................................................................v 

Acknowledgments ......................................................................................................................... vii 

Executive Summary .........................................................................................................................1 

1. Introduction, Purpose, and Scope................................................................................................7 

1.1. Observational Human Exposure Studies.............................................................................7 

1.2. Ethical Issues in Observational Human Exposure Studies..................................................8 

1.3. Purpose of This Document ................................................................................................11

1.4. Process for Developing the Document..............................................................................13 

1.5. Organization of the Document ..........................................................................................13 

2. Elements to Be Considered in Study Conceptualization and Planning.....................................17 

2.1. Scientific Value of a Proposed Observational Human Exposure Study............................18 

2.1.1. Defining the Study Problem..................................................................................18 

2.1.2. Justifying the Study ......................................................................................................19 

2.1.3. Identifying a Research Team To Plan and Implement the Study .................................20 

2.2. Ensuring Scientific Validity of the Research Study ..........................................................20 

2.2.1. Study Design .......................................................................................................20 

2.2.2. Feasibility ...........................................................................................................21 

2.2.3. Sample Size Determination...................................................................................22 

2.2.4. Representativeness of the Sample..........................................................................22 

2.2.5. Information Collection Rule .................................................................................23 

2.2.6. Quality Assurance Project Plan .............................................................................24 

2.2.7. The Study Design Document ................................................................................24 

2.3. Ethical Issues in Ensuring Fair Subject Selection .............................................................24 

2.4. Ensuring a Favorable Risk-Benefit Ratio..........................................................................25 

2.4.1. Designing in Benefits for the Participants..............................................................25 

2.4.2. Assessing Benefits and Risks of Study Participation...............................................25 

2.5. Independent Scientific and Ethical Review......................................................................26 

2.5.1. Scientific Peer Review .........................................................................................27 

2.5.2. Conflicts of Interest..............................................................................................27 

2.5.3. Develop the Human Subjects Protocol for Institutional Review Board Review.........28 

2.5.4. Ethical Review ....................................................................................................29 

2.5.5. Internal U.S. EPA Review of Scientific and Ethical Issues......................................29 

2.6. Informed Consent..............................................................................................................29 

2.7. Ensuring That Participant Behaviors Are Not Changed Adversely Because of 

Being in the Study ...........................................................................................................30 

2.8. Criteria and Standards for Monitoring Scientific and Ethical Issues ................................30 

3. Ensuring Protection of Vulnerable Groups ...............................................................................35 

3.1. Identification of Vulnerable Groups..................................................................................35 

viii
3.2. Justification for Involving Vulnerable Persons in Observational Research ......................36 

3.3. Minimal Risk and Vulnerable Groups...............................................................................37 

3.4. Research Involving Children.............................................................................................37

3.5. Women as Research Subjects............................................................................................38 

3.6. Other Potentially Vulnerable Groups ................................................................................39 

4. Privacy, Confidentiality, and Other Concerns Related to Observational 

Human Exposure Studies ..........................................................................................................41 

4.1. Privacy Issues....................................................................................................................41 

4.2. Confidentiality...................................................................................................................42 

4.2.1. Confidentiality of Information.............................................................................43 

4.2.2. Confidentiality of Participation............................................................................44 

4.3. Collateral Observations........................................................................................................44 

4.3.1. Potential Nonstudy Hazards in the Residence..............................................................44 

4.3.2. Collateral Observations with Mandated Reporting Requirements ..............................45 

4.3.3. Hazard Communication................................................................................................45 

4.3.4. Planning and Staff Training..........................................................................................46 

4.4. Third-Party Issues..............................................................................................................46 

4.4.1. Determining Whether a Third Party Is a Human Subject............................................47 

4.4.2. Informing Third Parties of Research Activities...........................................................47 

4.4.3. Research Results and Third Parties ..............................................................................47 

4.5. Data and Safety Monitoring and Oversight.......................................................................48 

5. Creating an Appropriate Relationship Between the Participant and Researcher ......................51 

5.1. Informed Consent..............................................................................................................52 

5.1.1. Information...................................................................................................................52 

5.1.2. Comprehension.............................................................................................................54 

5.1.3. Voluntary Participation ................................................................................................55 

5.2. Payments to Research Participants....................................................................................56 

5.2.1. Types and Amounts of Payments Offered in Research Studies...............................56 

5.2.2. Regulations and Guidance Regarding Payment to Research Participants.................58 

5.2.3. Payments When Children or Other Vulnerable Populations Are Involved...............59 

5.2.4. Payments in Observational Human Exposure Studies............................................61 

5.3. Research Rights and Grievance Procedures ......................................................................61 

5.3.1. Ombudsman.......................................................................................................61 

5.3.2. Community Advisory Board................................................................................62 

5.4. Creating a Supportive Environment for Research and Interaction....................................62 

5.5. Recruitment Strategies ......................................................................................................62 

5.6. Retention Strategies...........................................................................................................63 

5.7. Ensuring Recruitment or Retention Methods Will Not Lead to Unacceptable Risk.........64 

6. Building and Maintaining Appropriate Community and Stakeholder Relationships................67 

6.1. Approaches to Community Involvement...........................................................................68 

6.2. Issues in Community Involvement....................................................................................71 

6.2.1. Defining “Community”.......................................................................................71 

6.2.2. Identifying Who Represents the Community ........................................................71 

6.2.3. Building Relationships and Trust.........................................................................72 

6.2.4. Importance of Language and Communications with the Community ......................73 

6.2.5. Recognizing and Addressing Cultural Differences ...............................................73 

6.2.6. Honesty, Power Relationships, and Partnerships...................................................74 

6.2.7. Building a Lasting Infrastructure .........................................................................74 

6.3. Community Involvement in Observational Human Exposure Studies..............................75 

6.4. Identifying and Interacting with Other Stakeholders ........................................................75 

ix
x

7. Designing and Implementing Strategies for Effective Communication....................................81 

7.1 Communication Strategy and Implementation Plan..........................................................81 

7.2 Individuals and Groups Involved in the Communications ................................................82 

7.3 Communications Timetables⎯When To Communicate...................................................83 

7.4 Communicating at Different Levels ..................................................................................85 

7.5 Communications Materials................................................................................................85 

7.6 Informing the Study Participants and Communities..........................................................87 

7.7 Reporting Study Results to the Participant and Community.............................................87 

7.8 Reporting Unanticipated Results or Observations.............................................................90 

7.9 Anticipating and Responding to Criticism ........................................................................91 

7.10 Responding to the Media, Public Inquiries, and Other Stakeholders................................92 

Appendix A: Additional Discussion of Observational and Exposure Terminology and 

Examples of Previous NERL Observational Human Exposure Studies ......95 

Appendix B: The Process for Development of This Document: Description of the 

Expert Panel Workshop, the External Peer Review by the 

Human Studies Review Board, and Public Comment................................107 

Appendix C: Recommended Content of a Human Subjects Protocol .............................111

Appendix D: Recommendations for Enhancing Public Trust..........................................113

Appendix E: List of Acronyms and Abbreviations .........................................................115 

Appendix F: Glossary......................................................................................................117 
Executive Summary 

Scientists at the U.S. Environmental Protection 

Agency’s (EPA’s) National Exposure Research 

Laboratory (NERL) have conducted observational 

human exposure studies for several decades to 

understand how people come into contact with 

chemicals and other stressors in their everyday lives, 

through the air they breathe, the food and liquids they 

consume, and the things they touch. These studies are 

performed to determine what chemicals people are 

exposed to, the concentrations of the chemicals, the most 

important sources contributing to people’s exposures, 

the routes and pathways of exposure, and the factors that 

have the biggest impact on exposure. The studies help 

explain when, where, why, how, and how often people 

are exposed to chemicals and other stressors (e.g., 

allergens, viruses, mold, radiation, noise) in their 

everyday environments as they go about their daily 

activities. Information from these studies helps EPA 

improve the understanding of people’s exposures to 

chemicals and other stressors and, ultimately, supports 

EPA’s efforts to protect public health. 

NERL scientists and managers take the protection of 

human subjects very seriously. Because observational 

human exposure studies involve people as research 

participants, NERL researchers must act to ensure the 

protection of the human subjects throughout the study. 

Such studies are often complex, and the specific actions 

will vary depending on the objectives of the study, the 

details of the study design and human subjects research 

protocol, and the details about the participants and the 

communities in which they live. To ensure that the 

actions of NERL researchers will properly respect, 

safeguard, and protect the rights and welfare of the 

participants in their research, NERL scientists need to be 

knowledgeable about the scientific and ethical issues 

that may arise as they plan and conduct their research, 

and they also need to be diligent in the application of the 

most up-to-date and sound scientific approaches and of 

the highest ethical standards to their research. 

This document, therefore, was prepared by NERL 

scientists as a resource and reference for EPA’s NERL 

scientists as they develop and implement observational 

human exposure studies. The authors recognize that this 

document also may prove to be useful to others involved 

in exposure science research, but that this document 

does not meet the definition of an official Agency 

“guidance document” (it does not set forth “a policy on a 

statutory, regulatory or technical issue or an 

interpretation of a statutory or regulatory issue”) and 

should not be used for that purpose. 

As EPA employees, NERL scientists face both 

regulatory and moral and ethical obligations to ensure 

the protection of the human subjects participating in 

their observational research. The regulatory 

requirements are set forth in EPA’s human subjects 

regulations (40 CFR 26). The moral obligations derive 

from the ethical principles of biomedical ethics. NERL 

scientists and managers are resolved to meet both the 

“letter” of the law as set forth in the regulations and also 

the “spirit” that derives from the most up-to-date 

thinking and consensus on these sensitive issues. 

This document provides information on regulatory 

requirements and ethical issues to consider when 

performing human subjects research. Knowledge about 

these requirements and issues will help NERL scientists 

meet their goal of conducting observational human 

exposure studies based on the most up-to-date and sound 

science and the highest ethical scientific standards. 

The ethical and moral issues associated with human 

subjects research has long been the subject of a great 

deal of thought and discussion, both in the United States 

and abroad. Issues in biomedical ethics continue to be 

discussed and debated in today’s headlines. Spurred by 

the atrocities of World War II concentration camps and 

by the disclosure of unethical treatment of 

undereducated African-American men and other 

vulnerable groups by medical staff in the United States, 

the U.S. and world communities were prompted to 

establish ethical principles for medical and scientific 

experiments that involve people as participants. In the 

United States, the Belmont Report (U.S. DHEW, 1979) 

is the foundational document in the development of the 

1
ethics of human subjects research. This report lays out 

the fundamental ethical principles behind research that 

involves humans as research subjects. These three basic 

principles, (1) respect for persons, (2) beneficence, and 

(3) justice, have become the cornerstones for regulations 

involving human subjects. Ethicists have expanded on 

those principles since 1979, translating them into ethical 

requirements that any human subjects research must be 

both ethically acceptable and scientifically sound.1

EPA’s Science Advisory Board has affirmed, “Bad 

science is always unethical” (U.S. EPA, 2000). 

In an effort to ensure that NERL’s observational 

human exposure studies are founded on the ethical 

principles of respect for persons, beneficence and 

nonmaleficence, and justice and adhering to the principle 

that bad science is always unethical, scientists and 

managers from NERL have assembled this document as 

a resource and reference for NERL exposure scientists. 

These same scientists and managers have sought expert 

advice, including input from an expert panel workshop; 

review and comment on the external review draft of the 

document by the Human Studies Review Board (HSRB), 

a Federal advisory committee; public comment on the 

external review draft of the document; and public input 

about the state of the science for scientific and ethical 

approaches for design and implementation of 

observational human exposure studies. 

A number of references, both from the bioethics 

literature and from U.S. regulations, have proven useful 

to the authors as they have developed this document. 

Those references are listed in Table 1-4, which is 

replicated below. 

The authors also have relied extensively on the 

advice of an expert panel that convened in November 

2006 to provide advice and guidance about the structure 

and content of this document. The Expert Panel 

consisted of 11 nationally recognized authorities from 

diverse fields ― exposure science, environmental health, 

bioethics, epidemiology, community-based research, 

law, research in minority communities, public health, 

toxicology, pediatrics, and children’s environmental 

health. 

The Expert Panel Workshop resulted in suggestions 

for both the structure and the content of this document 

(ERG, 2007). Following the advice of the Expert Panel, 

this document is organized in seven sections. 

 

1 See, for example, the writings of Beauchamp and Childress in Principles of 

Biomedical Ethics (Beauchamp and Childress, 2001) and the discussion of 

“What Makes Clinical Research Ethical?” by Emanuel, Wendler, and Grady 

(Emanuel et al., 2000). 

Section 1. Introduction: The background for 

observational human exposure studies, the scope of 

this document, and the important scientific and ethical 

issues that are critical to human subjects and 

observational research. 

Section 2. Elements to be considered in study 

conceptualization: Incorporating ethical concerns into 

the scientific effort from the onset and integrating 

them throughout all phases of study planning and 

implementation. As shown in the text box below, the 

planning process involves the initial identification of 

the research question and justification of the research 

effort during the problem conceptualization phase. If 

human subjects research is justified for the study, the 

scientific and ethical approaches are described in the 

study design and the human subjects research 

protocol. The basic elements that should be included 

in the study design and in the human subjects research 

protocol are described, and researchers are advised to 

consider alternative and innovative study designs that 

maximize the benefits to the study participants and 

their community. Information is provided on both 

scientific peer review and ethical review, and the 

integration of the two. Mandated procedures for 

review by external peers, by Institutional Review 

Boards (IRBs), and by the EPA Human Subjects 

Research Review Official (HSRRO) are detailed. 

Define & Justify 

the Study

Planning 

& 

Scoping

Develop Study 

Design

Develop Human 

Subjects Protocol

Peer Review

Scientific & Ethical 

Review

IRB Review

Ethical & Scientific 

Review

HSRRO

Review

Independent 

Review

Agency 

HSRRO 

Review

Implement 

Study

&

Monitor 

Progress

Implement

& Monitor

Criteria OK 

Continue Study

Disapprove

No Study

Approve Conduct Study

Criteria Exceeded

Terminate Study

Problem 

Conceptualization

Stages in the Development of a NERL 

Observational Human Exposure Study

Develop Study 

Design

Develop Human 

Subjects Protocol

2
Table 1-4. Important References in Developing This Document: 

Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants 

Year Event/Report Description 

1979 The Belmont Report: Ethical 

Principles and Guidelines for 

the Protection of Human 

Subjects of Research (U.S. 

DHEW, 1979) 

The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively 

created National Commission for the Protection of Human Subjects of Biomedical and Behavioral 

Research. It is a statement of basic ethical principles and guidelines that should assist in resolving 

the ethical problems that surround the conduct of research with human subjects. The three basic 

ethical principles are (1) respect for persons, (2) beneficence, and (3) justice. 

1991 The Common Rule 

40 CFR 26, Subpart A 

The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” 

and was adopted by more than a dozen Federal departments or agencies in 1991. Each agency 

incorporated the policy into its own Code of Federal Regulations (CFR), with EPA adapting it in Title 

40 CFR Part 26, Subpart A. 

1993 The Institutional Review 

Board Guidebook (U.S. HHS, 

1993) 

The document is intended as a resource and a reference document for IRB members, researchers, 

and institutional administrators. It is not designed to tell IRBs whether or not specific protocols should 

be approved; rather, the Guidebook points out issues to which IRBs should pay attention and 

presents, wherever possible, areas where ethicists have arrived at a consensus on the ethical 

acceptability of a particular activity or method. 

2000 What Makes Clinical 

Research Ethical? (Emanuel 

et al., 2000) 

This journal article lays out seven areas of concern that need to be addressed if clinical research is 

deemed to be ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject 

selection, (4) favorable risk-benefit ratio, (5) independent review, (6) informed consent, and 

(7) respect for potential and enrolled subjects. 

2001 Principles of Biomedical 

Ethics:(Fifth Edition 

(Beauchamp and Childress, 

2001) 

A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, 

beneficence, and justice. The chapter on professional-patient relationships discusses issues 

important to privacy, confidentiality, and protection of subjects. The fifth edition is an update that 

reflects developments in philosophical analysis, as well as developments in science and medicine. 

2002 International Ethical 

Guidelines for Biomedical 

Research Involving Human 

Subjects (CIOMS, 2002) 

Developed by the Council for International Organizations of Medical Sciences particularly for use in 

developing countries, the guidelines relate mainly to ethical justification and scientific validity of 

research; ethical review; informed consent; vulnerability of individuals, groups, communities, and 

populations; women as research subjects; equity regarding burdens and benefits; choice of control in 

clinical trials; confidentiality; compensation for injury; strengthening of national or local capacity for 

ethical review; and obligations of sponsors to provide health care services. 

2003 Protecting Participants and 

Facilitating Social and 

Behavioral Sciences 

Research (NRC, 2003) 

This NRC publication targets policymakers, research administrators, research sponsors, IRB 

members, and investigators. It examines three key ethical issues: (1) obtaining informed, voluntary 

consent from prospective participants; (2) guaranteeing the confidentiality of information collected 

from participants, which is a particularly challenging problem in social sciences research; and 

(3) using appropriate review procedures for minimal-risk research. 

2005 Ethical Considerations for 

Research on HousingRelated Health Hazards 

Involving Children, (NRC & 

IOM, 2005) 

This National Research Council and Institute of Medicine report reviews the challenges and ethical 

issues in conducting housing-related health hazards research in the wake of the Maryland Court of 

Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has led to substantial 

controversy and confusion. The ruling highlighted a range of potential ethical concerns, such as 

issues involving adequacy of informed consent, parents' perception of risk, duties of researchers to 

child subjects and their parents, the role of IRBs, and the authority of parents to provide permission 

for their children to participate in research. This report offers much needed recommendations and 

practical guidance for the ethical conduct of this type of research. 

2006 EPA adds Additional Human 

Subjects Protections at 

40 CFR 26 

EPA added additional human subjects protections in the Code of Federal Regulations to govern its 

actions. Subparts B through D apply to research conducted or supported by EPA and are directly 

applicable to NERL and this document. Subpart B prohibits research involving intentional exposure 

of children, pregnant women (and their fetuses), or nursing women. Subparts C and D provide 

additional protections for observational research involving pregnant women and their fetuses 

(Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use 

of third-party human research data. 

2008 International Ethical 

Guidelines for 

Epidemiological Studies

(CIOMS, 2008) 

This document builds on the CIOMS (2002) document (see above) and extends the discussion to 

address the special features of epidemiological studies. 

3
Section 3. Ensuring protection of vulnerable groups: 

Protections afforded by EPA’s human subjects rules 

and the ethical concerns of involving such groups in 

observational research. Special requirements for the 

protection of potentially vulnerable groups, including 

children, prisoners, pregnant women, handicapped 

persons, mentally disabled persons, and economically 

or educationally disadvantaged persons, throughout 

the planning and implementation process are 

described. 

Section 4. Addressing privacy and other concerns 

related to observational human exposure studies: 

Ethical issues and regulatory requirements concerning 

privacy, including third-party involvement and 

observations of nonstudy hazards. Unlike clinical 

research that is conducted in an institutional setting, 

observational human exposure studies take place in 

the participants’ “personal” environments as they go 

about their everyday lives, presenting an even greater 

challenge in meeting the ethical obligation to respect 

the privacy of the participants. 

Section 5. Creating an appropriate relationship between 

participant and investigator: Issues surrounding 

recruitment, informed consent, payment, and the 

researcher’s need to support the welfare of the 

participants. An appropriate relationship built on 

openness and trust requires strong and effective 

bidirectional communication. Informed consent 

ensures that the participant understands the range of 

risks associated with participation and the voluntary 

nature of participation, and provides essential 

protections to the participant. Recent observations by 

various national and international review committees 

on the appropriate level of payment to research 

participants are presented. This is a complex ethical 

issue, balancing the issue of fairness against the 

possibility of undue influence and the loss of free 

consent. Other topics include participant recruitment, 

retention strategies, research rights, and grievance 

procedures. 

Section 6. Building and maintaining appropriate 

community and stakeholder relationships: Involving 

the community in the research effort to improve the 

research both scientifically and ethically. Various 

approaches are discussed related to issues such as 

defining the community, identifying who represents 

the community, recognizing and addressing cultural 

differences, and the importance of language, power 

relationships, and partnerships. 

Section 7. Designing and implementing strategies for 

effective communication: Ongoing, interactive 

dialogue among researchers, participants, the 

community, stakeholders, and the public to establish 

effective communications and to foster a relationship 

of trust. To facilitate information dissemination to 

participants, communities, and stakeholders, this 

section of the document describes communication 

strategies, implementation plans, communication 

groups, timetables, communication materials, and 

other tools available to researchers. 

This document does not and, indeed, could not 

provide solutions to all scientific and ethical issues that 

may arise as observational human exposure studies are 

undertaken. No document could identify and address all 

potential issues in advance, nor is it possible to develop 

a comprehensive checklist for all such studies. Rather, 

this document attempts to present and discuss the types 

of ethical and scientific issues that will need to be 

considered and addressed as NERL researchers plan and 

implement observational human exposure studies. The 

researchers will need to work with others ― the study 

team, IRB members, EPA’s HSRRO, the participants 

and their community, and other stakeholders ― to 

identify and address all of the relevant issues for any 

particular study. The authors are confident that this 

document will be helpful to NERL scientists in their 

endeavors to assure that all of NERL’s observational 

human exposure studies will respect, safeguard, and 

protect the participants in that research. 

References 

Beauchamp TL, Childress, JF (2001). Principles of 

Biomedical Ethics: Fifth Edition. New York, NY: Oxford 

University Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 

Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: 

http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.

html [accessed 12 June 2007]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2008). International Ethical Guidelines 

for Epidemiological Studies. World Health Organization. 

Geneva, Switzerland. Available: 

http://www.cioms.ch/080221feb_2008.pdf [accessed 25 

April 2008]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines 

for Biomedical Research Involving Human Subjects. World 

Health Organization. Geneva, Switzerland. Available: 

4
5

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed 12 June 2007]. 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 

Clinical Research Ethical? JAMA 20:2701-2711. 

ERG (Eastern Research Group) (2007). Report on the 

Workshop to Discuss State-of-the-Science Approaches for 

Observational Exposure Measurement Studies. Held in 

Durham, North Carolina on November 28-29, 2006. Final 

Report: January 25, 2007. (PB2007-108905). 

NRC (National Research Council) (2003) Protecting 

Participants and Facilitating Social and Behavioral 

Sciences Research. Washington, DC: The National 

Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=10638

[accessed 12 June 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

U.S. DHEW (U.S. Department of Health, Education, and 

Welfare) (1979) The Belmont Report: Ethical Principles 

and Guidelines for the Protection of Human Subjects of 

Research. National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral Research. 

Available: http://ohsr.od.nih.gov/guidelines/belmont.html 

[accessed 12 June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (2000) 

Comments on the Use of Data from the Testing of Human 

Subjects: A Report by the Science Advisory Board and the 

FIFRA Scientific Advisory Panel. United States 

Environmental Protection Agency, Science Advisory Board, 

EPA-SAB-EC-00-017. Available: 

http://yosemite.epa.gov/sab/SABPRODUCT.NSF/E3AE0F3

0D7430436852571A7005325E8/$File/ec0017.pdf [accessed 

12 June 2007]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

12 June 2007]. 
6
SECTION 1

Introduction, Purpose, and Scope 

Observational human exposure studies are an 

important research tool for understanding people’s 

contact with pollutants and other stressors in the 

environment, that is, their exposure.2

 Such studies allow 

researchers to collect information about people’s 

exposures to chemicals and other stressors under realworld conditions during their normal day-to-day 

activities. Exposures occur through the air we breathe, 

the food we eat, the water and beverages we drink, and 

the surfaces that we touch as we go about our daily 

routines. To understand and characterize people’s 

exposures to chemicals, two things have to be known: 

(1) the concentrations of the chemicals in the 

environment that people inhale, ingest, or touch; and (2) 

the human activities that bring people into contact with 

the media containing the chemicals.3

 This document 

addresses issues associated with observational human 

exposure studies that are conducted by the National 

Exposure Research Laboratory (NERL) of the U.S. 

Environmental Protection Agency (EPA) in an effort to 

understand and characterize the exposures that people 

encounter as they go about their daily lives. 

Because observational human exposure studies 

involve human participants, they are complex in their 

design and implementation. As in all research involving 

human participants, observational human exposure 

studies carry both regulatory obligations for the 

protection of human subjects (40 CFR 26) and ethical 

obligations to the study participants: namely, to respect 

 

2 Exposure, as it is used throughout this document, is a technical term that is 

defined as the “contact of a chemical, physical, or biological agent with the 

outer boundary of an organism [e.g., a person]. Exposure is quantified as the 

concentration of the agent in the medium in contact integrated over the time 

duration of that contact.” (The definition is taken from Guidelines for 

Exposure Assessment [EPA/600/Z-92/001, May 1992]). See the Glossary for 

more information and the definition of additional terms. 3

 The term “chemical” is used in this document as a surrogate term for all 

stressors, including chemical, physical, or biological agents.

their autonomy, to not inflict harm (nonmaleficence), to 

avoid harm and to maximize their benefits (beneficence), 

and to treat all participants fairly (justice) (See, for 

example, Principles of Biomedical Ethics, Beauchamp 

and Childress, 2001). Ethical obligations have to be 

carefully considered as they relate to the scientific 

elements of these studies. Therefore, it is important that 

researchers recognize and understand these obligations 

and use the most up-to-date scientific and ethical 

approaches in the design and implementation of 

observational human exposure studies. 

1.1 Observational Human Exposure Studies 

As we are using the term in this document, 

“observational human exposure studies” are studies that 

involve the collection of environmental samples, data, 

and information from study participants in their 

everyday environments as they go about their normal 

activities. These are studies where the NERL researchers 

do not intentionally try to control the study variables or 

outcomes, but instead merely observe both the variables 

and the outcomes. They involve neither the deliberate 

exposure of participants nor the control of environmental 

conditions in a way that impacts the participants’ 

naturally occurring exposures. This scientifically based 

definition needs to be distinguished at the outset from 

the broader regulatory term “observational” so that the 

scope and limits of this document are clear. EPA 

Regulation 40 CFR 26 (Protection of Human Subjects) 

at Subpart B, first, defines research involving intentional 

exposure of a human subject as “a study of a substance 

in which the exposure to the substance experienced by a 

human subject participating in the study would not have 

occurred but for the human subject’s participation in the 

study” [40 CFR 26.202(a)]. It then goes on at Subpart C 

to define observational research as “any human research 

that does not meet the definition of research involving 

intentional exposure of a human subject” (40 CFR 

7
26.302). By defining “observational” so broadly, a 

regulatory category is created that encompasses a range 

of study types whose only common feature is that they 

do not entail “intentional exposure” as defined in the 

regulations. Moreover, some of these “observational” 

study types do not involve the study of exposures at all 

but rather “observe” other sorts of phenomena. The 

observational human exposure studies with which we are 

concerned here, on the other hand, are exposure studies, 

but they represent a narrower group of studies as defined 

scientifically at the beginning of this paragraph. 

Although they would generally be expected to fall within 

the regulatory category of “observational research”, they 

are not synonymous with it. (For a more thorough 

discussion of the scientific and regulatory meanings of 

observational and exposure, with examples, please see 

Appendix A.) 

Observational human exposure studies are 

performed for many different purposes. They have been 

used extensively in the fields of social behavioral, 

economic, biological, medical, epidemiological, and 

exposure research to collect information that relates one 

or more variables (e.g., exposure to a chemical) to its 

result (e.g., the concentration of an exposure biomarker 

in blood). There are many examples of observational 

human exposure studies that have been conducted over 

the past decade, and the reader is referred to the Journal 

of Exposure Science and Environmental Epidemiology

and to Environmental Health Perspectives for examples 

of the objectives, designs, and results of these studies. 

NERL researchers have conducted and relied on 

observational human exposure studies for more than 

three decades. Examples of studies conducted or funded 

by NERL are listed in Appendix A, Table A-1. Common 

goals in those studies included those that follow. 

• Identify which chemicals or other stressors that people 

are exposed to during their normal activities in the 

environments that they occupy. 

• Measure the concentrations of the chemicals to which 

people are exposed. 

• Identify the most important routes and pathways of 

exposure. 

• Identify the factors that impact people’s exposures 

(i.e., determine the when, why, how, and how much 

that people are exposed to chemicals in the 

environment). 

These studies involve many different types of data 

collection efforts and typically include observations, 

measurements, and information on the following items. 

• Chemical concentrations in environmental media (air, 

water, soil, floor dust, and dust on surfaces) 

• Chemical concentrations in the diet (food and 

beverages). 

• Biomonitoring (measurements of biomarkers of 

exposure in urine, blood, and saliva) 

• Time, location, and activity information 

• Information on personal activities, product use, diet, 

occupation, and other factors that may impact 

exposure 

• Information on the characteristics of the environments 

that study participants occupy (homes, schools, 

offices, public access buildings, etc.) 

The information obtained in observational human 

exposure studies is used to better understand people’s 

contact with chemicals in the environment and to 

improve exposure assessments and risk assessments. 

This information is also essential for developing risk 

mitigation strategies and for developing educational 

materials and programs for reducing exposures and risks 

to chemicals or other stressors in the environment (see 

Table 1-1). 

1.2 Ethical Issues in Observational Human 

Exposure Studies 

By definition, observational human exposure studies 

involve human subjects. Whenever their research 

involves human subjects, EPA researchers are required 

to ensure the protection of the study participants by 

complying with the Agency’s human subjects rules as 

set forth in 40 CFR 26. 

The Common Rule (Subpart A of the rules) 

represents basic regulatory actions (common to more 

than a dozen Federal departments or agencies) that are 

intended to ensure the protection of all human subjects. 

The central requirements of the Common Rule are 

twofold: 

(1) that people who participate as subjects in covered 

research are selected equitably and give their fully 

informed, fully voluntary written consent; and 

(2) that proposed research be reviewed by an 

independent oversight group referred to as an 

institutional review board (IRB) and approved only if 

risks to subjects have been minimized, and risks are 

reasonable in relation to anticipated benefits, if any, to 

the subjects and to the importance of the knowledge that 

may realistically be expected to result. 

8
EPA has adopted additional protections for children 

and pregnant or nursing mothers in Subparts B through 

D. These sections apply to all research either conducted 

or funded by EPA and are, therefore, directly applicable 

to NERL’s observational human exposure studies.4

Subpart B prohibits EPA from conducting or supporting 

research that involves intentional exposure of “a 

pregnant woman (and, thereby, her fetus), a nursing 

woman, or a child.” NERL researchers conducting (or 

funding) observational human exposure studies must 

comply with all of these regulatory requirements, 

including seeking review and approval by an IRB and by 

the Agency’s Human Subjects Research Review Official 

(HSRRO) before beginning any human subjects 

research. EPA’s human subjects rules also define a 

variety of fundamental terms⎯from “human subject” to 

“research” to “intentional exposure” to “observational 

research.” Understanding these regulatory definitions is 

vital for NERL researchers to comply with the 

regulatory requirements.5

To more effectively ensure the protection of human 

subjects, NERL scientists and managers need to 

understand the ethical principles and issues that 

prompted the development of the regulatory 

requirements in the first place and to be knowledgeable 

 

4

 Subparts K, L, M, O, P, and Q of 40 CFR 26 set basic ethical requirements 

that have to be met if human subjects data from a person or group external to 

EPA and not funded by EPA (a third party) are to be used by EPA in specified 

rulemaking actions. These subparts do not apply to NERL researchers and 

will not be discussed further in this document. 

5

 The Glossary (Appendix F) lists definitions for a number of important terms; 

definitions that come from the regulatory language are identified with their 

specific CFR citation. 

about the most recent thinking and guidance on 

protection of human subjects. 

The Belmont Report (U.S. DHEW, 1979) is a 

foundational document in the development of the ethics 

of human subjects research in the United States. Because 

of the adverse publicity and political embarrassment 

arising from the unethical treatment of AfricanAmerican men in the Tuskegee Syphilis Study, Congress 

passed the National Research Act of 1974, which called 

on the Department of Health, Education, and Welfare 

(DHEW) to codify its rules on human subjects research 

and established the National Commission for the 

Protection of Human Subjects of Biomedical and 

Behavioral Research. The commission was charged with 

identifying the basic ethical principles that should 

underlie human subjects research. The commission 

published the Belmont Report in 1979. This report 

established three basic principles: (1) respect for 

persons; (2) beneficence; and (3) justice, which have 

become the cornerstones for regulations involving 

human subjects (see Table 1-2). 

In 1981, the Department of Health and Human 

Services (HHS) issued regulations based on the Belmont 

Report. Ten years later, the core HHS regulations 

(Subpart A) were adopted by almost all of the Federal 

departments and agencies that conducted or sponsored 

human subjects research as the “Common Rule.” 

Since 1991, ethical thought and regulatory processes 

for the protection of human subjects have continued to 

evolve and grow. For example, many ethicists expand 

the elements contained in the principle of beneficence 

from the Belmont Report into two principles: 

(1) beneficence, meaning to prevent or remove harm and 

Table 1-1. Examples of the Impact of Observational Human Exposure Studies on Pollution Levels and Regulatory Actions

Pollutant Observational Study Result Impact/Action/Result

Particulate Matter (PM) Observational panel studies demonstrated 

the appropriateness of ambient measurement 

of fine particles as a surrogate for a 

population’s longitudinal exposure to fine PM.

Resolved questions in NAS review of PM science and provided a 

“generally consistent finding that ambient particle concentrations are 

a key determinant of the longitudinal variation in personal exposure.” 

(NRC, 2004). These results have been instrumental in support of the 

National Ambient Air Quality Standard for PM (U.S. EPA, 1999).

Volatile Organic Compounds 

(VOCs)

EPA's Total Exposure Assessment 

Methodology (TEAM) studies found levels of 

about a dozen common organic pollutants to 

be 2- to 5-times higher inside homes than 

outside. Use of products containing organic 

chemicals may result in very high and 

persistent pollutant levels.

EPA, States, and the Consumer Product Safety Commission worked 

together to influence manufacturers to voluntarily reduce emissions of 

toxic chemicals from consumer products, building materials, and 

furnishings, and to develop mitigation strategies and educational 

materials to teach people how to reduce their contact with chemicals 

indoors. As a result, contact with toxic chemicals indoors has been 

reduced (see www.cpsc.gov/CPSCPUB/PUBS/450.html).

Formaldehyde Studies found elevated formaldehyde levels 

indoors and helped identify indoor sources.

EPA worked with HUD, CPSC, and other agencies to limit 

formaldehyde in building or consumer products and to educate the 

public on how to reduce exposures (see www. 

epa.gov/iaq/formalde.html).

9
to maximize the possible benefits; and 

(2) nonmaleficence, meaning not to inflict harm 

(Beauchamp and Childress, 2001). 

In 2000, Emanuel, Wendler, and Grady considered 

the ethical principles involved in clinical research and 

proposed seven ethical requirements to be addressed in 

research with humans (Emanuel et al., 2000). Their 

published article specifically addressed clinical research, 

but the issues are similar for observational human 

exposure studies. Their ethical requirements are 

summarized and briefly explained in Table 1-3. The 

requirements are a logical extension of the ethical 

principles enunciated in the Belmont Report and 

manifest themselves in additional requirements for 

social or scientific value; for processes to ensure the 

scientific integrity of the research; and for independent 

review of the design, the subject population, and the 

risk-benefit ratio. The principle of respect for subjects 

also includes additional emphasis on the welfare of the 

subjects. 

More recently, there has been increased scrutiny and 

discussions of the ethics of research involving human 

participants,6

 and a number of respected institutions 

 

6

 The term “human participants” often is used in this document. It denotes the 

importance of the study participant being actively engaged in a partnership 

with the researchers to address the objectives and goals of the study. The term 

should be considered to be synonymous with the term “human subject” as 

used in the Common Rule and in documents used to describe regulatory 

requirements for studies involving human subjects. 

have addressed many important scientific and ethical 

issues on this topic, including the National Research 

Council (NRC) in its report, Protecting Participants and 

Facilitating Social and Behavioral Sciences Research 

(NRC, 2003), a joint NRC and Institute of Medicine 

(NRC & IOM, 2005) committee in the report on Ethical 

Considerations for Research on Housing-Related Health 

Hazards Involving Children; the Council for 

International Organizations of Medical Sciences 

(CIOMS) under the World Health Organization in its

International Ethical Guidelines for Biomedical 

Research Involving Human Subjects (CIOMS, 2002) and 

in the International Ethical Guidelines for 

Epidemiological Studies (CIOMS, 2008); and the 

National Ethics Advisory Committee of New Zealand in 

the Ethical Guidelines for Observational Studies: 

Observational Research, Audits and Related Activities

(NEAC, 2006). 

Table 1-2. The Belmont Report— 

Principles and Recommendations 

Ethical Principle Regulatory Manifestation 

Respect for Persons 

• Individuals should be 

treated as autonomous 

agents. 

• Persons with diminished 

autonomy are entitled to 

protection. 

Informed Consent 

• Subjects must be given the 

opportunity to choose what will or 

will not happen to them 

• The consent process must include 

(1) information, 

(2) comprehension, and 

(3) voluntariness 

Beneficence 

• Human subjects should 

not be harmed. 

• Research should 

maximize possible 

benefits and minimize 

possible harms. 

Assessment of Risks and 

Benefits 

• The nature and scope of risks and 

benefits must be assessed in a 

systematic manner. 

Justice 

• The benefits and risks of 

research must be 

distributed fairly. 

Selection of Subjects 

• There must be fair procedures and 

outcomes in the selection of 

research subjects.

Table 1-3. Seven Ethical Requirements for 

Clinical Research 

From Emanuel, Wendler, and Grady (2000) 

Requirement Explanation 

Social or 

scientific value 

Evaluation of a treatment, intervention, or theory 

that will improve health and well-being or 

increase knowledge 

Scientific 

validity 

Use of accepted scientific principles and 

methods, including statistical techniques, to 

produce reliable and valid data 

Fair subject 

selection 

Selection of subjects so that stigmatized and 

vulnerable individuals are not targeted for risky 

research, and the rich and socially powerful are 

not favored for potentially beneficial research 

Favorable riskbenefit ratio 

Minimization of risks; enhancement of potential 

benefits and risks to the subject are 

proportionate to the benefits to the subject and to 

society 

Independent 

review 

Review of the design of the research trial, its 

proposed subject population, and risk-benefit 

ratio by individuals unaffiliated with the research 

Informed 

consent 

Provision of information to subjects about the 

purpose of the research and its procedures, 

potential risks, benefits, and alternatives, so that 

the individual understands this information and 

can make a voluntary decision whether to enroll 

and continue to participate 

Respect for 

potential and 

enrolled 

subjects 

Respect for subjects by 

• permitting withdrawal from the research, 

• protecting privacy through confidentiality, 

• informing subjects of newly discovered risks 

or benefits, 

• informing subjects of results of the research, 

and 

• maintaining welfare of subjects. 

10
11

Collectively, these documents have reaffirmed the 

basic ethical principles asserted in the Belmont Report 

and have attempted, in some cases, to expand scientific 

and ethical reasoning and understanding to define 

approaches for dealing with additional elements of 

human subjects research. These additional elements, 

which often have been identified because of specific 

incidents or case studies, include issues such as those 

described below. 

• Payment to participants⎯How much is adequate and 

fair, without being an undue inducement? 

• Non-study hazards⎯What is the researcher’s 

responsibility to identify hazards in the home that are 

not part of the study? 

• Third-party issues⎯Are there people other than the 

participant who may be impacted during the study and 

by the study results? If so, what needs to be done to 

protect their interests and to respect them as persons? 

• Community involvement⎯How should the 

community be involved in the design and 

implementation of studies? 

These documents, together with EPA’s regulatory 

requirements for the protection of human subjects, serve 

as important references for the subsequent sections of 

this document (see Table 1-4). 

1.3 Purpose of This Document 

This document is meant to serve as a resource of 

current scientific and ethical information for NERL 

researchers as they develop and conduct observational 

human exposure studies. The increased scrutiny of 

research studies involving human participants makes it 

imperative that researchers ensure that their research 

protocols for protection of human subjects in 

observational human exposure studies incorporate the 

most up-to-date ethical approaches. Protocols for 

protecting study participants in research studies have 

been developed by experts in both academia and various 

Federal agencies and adopted by the research 

community because they ensure that observational 

research meets the highest ethical and scientific 

standards. However, because ethical and scientific 

approaches for human subjects research continue to be 

refined and evolve over time, there is a continuing need 

to evaluate the latest approaches and ensure that 

researchers are using state-of-the-science approaches in 

their design and implementation of such studies. 

The purpose of this document is to provide 

information that researchers in EPA’s Office of 

Research and Development’s NERL can use in the 

design and implementation of observational human 

exposure studies to ensure the protection of the human 

study participants. It is intended to be a resource tool for 

NERL’s exposure science researchers, but it is not 

intended to serve as a “guidelines” document or a “howto” checklist. This document does not meet the Office of 

Management and Budget (OMB) definition for an 

official Agency “guidance document” (“Guidance 

document - an agency statement of general applicability 

and future effect, other than a regulatory action ... that 

sets forth a policy on a statutory, regulatory or technical 

issue or an interpretation of a statutory or regulatory 

issue” [U.S. OMB, 2007]). The authors, as researchers, 

perceived the need to provide this document for 

themselves, their co-workers, and their collaborators, but 

do not presume to speak for the whole of the Agency. 

The authors have tried to (1) identify major areas and 

elements of observational human exposure studies for 

which ethical issues need to be considered, (2) provide 

information on the state of the science for selected 

approaches for applying ethical principles to the conduct 

of these studies, and (3) provide sources of information 

that researchers can use in the design and 

implementation of these studies. 

The emphasis of this document is to identify and 

discuss ethical issues and approaches in observational 

human exposure studies. As the document title implies 

and as discussed in Section 2, scientific and ethical 

issues are intrinsically bound together in research 

involving human subjects. Therefore, it is essential that 

scientific and ethical issues be considered together, not 

separately. In this document, scientific issues and 

approaches are discussed as they relate to and impact 

ethical issues. However, it is beyond the scope of this 

document to present a comprehensive discussion of the 

scientific approaches for observational human exposure 

studies. To include a comprehensive discussion of 

scientific approaches in this document would reduce the 

utility of the document by increasing the complexity of 

the presentation and the length of the document. 

This document does not provide solutions to all 

scientific and ethical issues that may arise as such 

studies are undertaken. That is, it is not possible to 

identify or address all potential issues in advance or 

develop a comprehensive checklist for all such studies. 

Rather, this document attempts to present and discuss 

the types of issues that will need to be considered and 

addressed as NERL researchers plan and implement 

observational human exposure studies. The researchers 

will need to work with others⎯the study team, IRB 

members, EPA HSRRO, the participants and their 

community, and other stakeholders⎯to identify and 
Table 1-4. Important References in Developing This Document: 

Some Recent Developments in Defining the Ethics of Conducting Research Involving Human Participants 

Year Event/Report Description 

1979 The Belmont Report: Ethical 

Principles and Guidelines for 

the Protection of Human 

Subjects of Research (U.S. 

DHEW, 1979) 

The Belmont Report attempts to summarize the basic ethical principles identified by the legislatively 

created National Commission for the Protection of Human Subjects of Biomedical and Behavioral 

Research. It is a statement of basic ethical principles and guidelines that should assist in resolving 

the ethical problems that surround the conduct of research with human subjects. The three basic 

ethical principles are (1) respect for persons, (2) beneficence, and (3) justice. 

1991 The Common Rule 

40 CFR 26, Subpart A 

The Common Rule is a short name for “The Federal Policy for the Protection of Human Subjects” 

and was adopted by more than a dozen Federal departments or agencies in 1991. Each agency 

incorporated the policy into its own Code of Federal Regulations (CFR), with EPA adapting it in Title 

40 CFR Part 26, Subpart A. 

1993 The Institutional Review 

Board Guidebook (U.S. HHS, 

1993) 

The document is intended as a resource and a reference document for IRB members, researchers, 

and institutional administrators. It is not designed to tell IRBs whether or not specific protocols should 

be approved; rather, the Guidebook points out issues to which IRBs should pay attention and 

presents, wherever possible, areas where ethicists have arrived at a consensus on the ethical 

acceptability of a particular activity or method. 

2000 What Makes Clinical 

Research Ethical? (Emanuel 

et al., 2000) 

This journal article lays out seven areas of concern that need to be addressed if clinical research is 

deemed to be ethically acceptable: (1) social or scientific value, (2) scientific validity, (3) fair subject 

selection, (4) favorable risk-benefit ratio, (5) independent review, (6) informed consent, and 

(7) respect for potential and enrolled subjects. 

2001 Principles of Biomedical 

Ethics:(Fifth Edition 

(Beauchamp and Childress, 

2001) 

A classic text in biomedical ethics. Core chapters discuss respect for autonomy, nonmaleficence, 

beneficence, and justice. The chapter on professional-patient relationships discusses issues 

important to privacy, confidentiality, and protection of subjects. The fifth edition is an update that 

reflects developments in philosophical analysis, as well as developments in science and medicine. 

2002 International Ethical 

Guidelines for Biomedical 

Research Involving Human 

Subjects (CIOMS, 2002) 

Developed by the Council for International Organizations of Medical Sciences particularly for use in 

developing countries, the guidelines relate mainly to ethical justification and scientific validity of 

research; ethical review; informed consent; vulnerability of individuals, groups, communities, and 

populations; women as research subjects; equity regarding burdens and benefits; choice of control in 

clinical trials; confidentiality; compensation for injury; strengthening of national or local capacity for 

ethical review; and obligations of sponsors to provide health care services. 

2003 Protecting Participants and 

Facilitating Social and 

Behavioral Sciences 

Research (NRC, 2003) 

This NRC publication targets policymakers, research administrators, research sponsors, IRB 

members, and investigators. It examines three key ethical issues: (1) obtaining informed, voluntary 

consent from prospective participants; (2) guaranteeing the confidentiality of information collected 

from participants, which is a particularly challenging problem in social sciences research; and 

(3) using appropriate review procedures for minimal-risk research. 

2005 Ethical Considerations for 

Research on HousingRelated Health Hazards 

Involving Children, (NRC & 

IOM, 2005) 

This National Research Council and Institute of Medicine report reviews the challenges and ethical 

issues in conducting housing-related health hazards research in the wake of the Maryland Court of 

Appeals ruling in the case of Grimes v. Kennedy Krieger Institute that has led to substantial 

controversy and confusion. The ruling highlighted a range of potential ethical concerns, such as 

issues involving adequacy of informed consent, parents' perception of risk, duties of researchers to 

child subjects and their parents, the role of IRBs, and the authority of parents to provide permission 

for their children to participate in research. This report offers much needed recommendations and 

practical guidance for the ethical conduct of this type of research. 

2006 EPA adds Additional Human 

Subjects Protections at 

40 CFR 26 

EPA added additional human subjects protections in the Code of Federal Regulations to govern its 

actions. Subparts B through D apply to research conducted or supported by EPA and are directly 

applicable to NERL and this document. Subpart B prohibits research involving intentional exposure 

of children, pregnant women (and their fetuses), or nursing women. Subparts C and D provide 

additional protections for observational research involving pregnant women and their fetuses 

(Subpart C) and for children (Subpart D). Subparts K through M and O through Q apply to EPA’s use 

of third-party human research data. 

2008 International Ethical 

Guidelines for 

Epidemiological Studies

(CIOMS, 2008) 

This document builds on the CIOMS (2002) document (see above) and extends the discussion to 

address the special features of epidemiological studies. 

12
address all of the relevant issues for their particular 

study to ensure that the specific elements of the study 

will safeguard and protect the human research subjects. 

In addition to being an information resource for 

NERL researchers, this document provides useful 

information for contractors and grantees funded by 

NERL to consider during the design and implementation 

of their exposure science research. Although not its 

intended audience, this document also may prove to be 

useful to other researchers, within and outside of EPA, 

who are involved in observational human exposure 

studies. 

1.4 Process for Developing the Document 

This document was written by exposure science 

researchers in EPA’s NERL, with substantial input from 

experts within and outside of the Agency. Information 

relevant to the process and the document has been 

routinely posted on the EPA Web site at 

http://www.epa.gov/nerl/sots. 

NERL staff began this work by hosting a series of 

stakeholder meetings in the summer of 2006 to seek 

input on the content and format of the document. In 

November 2006, NERL convened an expert panel to 

provide its advice and guidance about the scope and 

content of this document. The Expert Panel consisted of 

11 nationally recognized authorities in diverse fields: 

exposure science, environmental health, bioethics, 

epidemiology law, community-based research, research 

in minority communities, public health, toxicology, 

pediatrics, children’s environmental health, etc. Details 

about the Expert Panel and the workshop can be found in 

Appendix B. The summary report from the Expert Panel 

may be accessed online at 

http://www.epa.gov/nerl/sots/workshop-report.pdf. 

The structure and content of the current report 

follow the recommendations of the Expert Panel. 

Specifically, the Expert Panel recommended that this 

document should include the following six major topic 

areas: 

(1) elements to be considered in study 

conceptualization, 

(2) ensuring protection of vulnerable groups, 

(3) addressing privacy and other concerns related to 

observational human exposure studies, 

(4) creating an appropriate relationship between the 

participant and investigator, 

(5) building and maintaining appropriate community 

and stakeholder relationships, and 

(6) designing and implementing strategies for effective 

communication. 

These recommendations include pragmatic steps that 

NERL scientists can undertake during the development 

and implementation of observational human exposure 

studies. Note that each step may require consideration 

and application of multiple ethical and scientific 

principles, and the same ethical principle may be 

fundamental to several of the topic areas. As a result, the 

same ethical principle may be discussed in several 

sections throughout this document. 

Using the advice of the Expert Panel, an internal 

review draft of the document was written. Based on the 

comments from internal EPA reviewers, the internal 

review draft was revised, and an external review draft 

was prepared. The external review draft was submitted 

for peer review by EPA’s Human Subjects Review 

Board (HSRB), a Federal advisory committee consisting 

of a panel of experts chartered to review and advise the 

Agency on the scientific and ethical underpinnings of 

human subjects research efforts. The external review 

draft also was announced in the Federal Register and 

made available for public review and comment. The 

document subsequently was revised in response to 

comments from the HSRB and from the public in 

preparation for publication and release as an EPA report. 

EPA’s response to comments was posted to the draft 

report’s docket (EPA-HQ-ORD-2007-0972) at 

www.regulations.gov. 

1.5 Organization of the Document 

The document is organized along the lines that the 

Expert Panel recommended. It has seven sections, an 

introduction followed by a section addressing each of the 

major topic areas. The content of each section also is 

based on recommendations from the Expert Panel 

Workshop. Because the authors concluded that the 

discussion for each topic area needed to be complete in 

and of itself (i.e., capable of standing independently 

without having to reference other sections), there may be 

some issues or topics that are discussed in several 

sections. Appendixes include additional descriptions of 

NERL observational human exposure studies, details 

about the process for developing this document, a list of 

acronyms and abbreviations, a glossary, and other 

supplemental information. The main body of the 

document includes the following sections. 

• Introduction, Purpose, and Scope (Section 1) lays out 

the background for observational human exposure 

studies, the scope of the document, and some of the 

important scientific and ethical issues that are critical 

to human subjects and observational research. 

13
• Study Conceptualization and Planning (Section 2) 

establishes that ethical concerns are to be incorporated 

in the scientific effort from the very beginning and 

includes ethical issues such as justifying the study 

because of its social and scientific merit and ensuring 

scientific validity and independent review. 

• Protection of Vulnerable Groups (Section 3) discusses 

some of the special protections afforded to vulnerable 

groups by EPA’s human subjects rules and the ethical 

issues of involving such groups in observational 

research. 

• Ensuring Privacy and Confidentiality (Section 4) lays 

out the ethical issues and the regulatory requirements, 

including observations of nonstudy hazards and the 

recently discussed issues of third-party involvement or 

concerns. 

• The Relationship Between the Participant and the 

Researcher (Section 5) builds on the ethical principles 

of respect for persons and beneficence to discuss the 

issues around recruitment, informed consent, 

payment, and the researcher’s need to support the 

welfare of the participants. 

• Community and Stakeholder Relationships (Section 6) 

begins with the principles of fairness, justice, and 

equity and of respect for persons to develop 

approaches to demonstrate respect for culture and to 

empower the participants’ community to endure, 

including the need to build trust in the community and 

with stakeholders through open and honest 

communications and legitimate power sharing. 

• Strategies for Effective Communication (Section 7) 

builds on the presumption of an ongoing, interactive 

dialogue and exchange of ideas between researchers 

and the participants, community, and stakeholders and 

focuses on steps that the researcher needs to take for 

effective communications. The section discusses 

communication strategies, implementation plans, 

communication tools, reporting of results, and 

approaches for effective communications, two-way 

communications between the researchers, participants, 

community, and other stakeholders. 

References 

Beauchamp TL, Childress, JF (2001). Principles of 

Biomedical Ethics: Fifth Edition. New York, NY: Oxford 

University Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 

Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/

40cfr26_06.html [accessed 12 June 2007]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2008). International Ethical Guidelines 

for Epidemiological Studies. Geneva, Switzerland: CIOMS. 

Available: http://www.cioms.ch/080221feb_2008.pdf

[accessed 25 April 2008]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines 

for Biomedical Research Involving Human Subjects. 

Geneva, Switzerland: CIOMS. Available: 

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed 12 June 2007]. 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 

Clinical Research Ethical? JAMA 283(20): 2701-2711. 

NEAC (National Ethics Advisory Committee) (2006). Ethical 

Guidelines for Observational Studies: Observational 

research audits and related activities. Wellington, New 

Zealand: Ministry of Health. Available: 

http://www.neac.health.govt.nz/moh.nsf/indexcm/neacresources-publications-ethicalguidelines. 

NRC (National Research Council) (2004) Research Priorities 

for Airborne Particulate Matter: IV. Continuing Research 

Progress. Washington, DC: The National Academies Press. 

Available: 

http://books.nap.edu/openbook.php?record_id=10957

[accessed 16 August 2007]. 

NRC (National Research Council) (2003) Protecting 

Participants and Facilitating Social and Behavioral 

Sciences Research. Washington, DC: The National 

Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=10638

[accessed 12 June 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

U.S. DHEW (U.S. Department of Health, Education, and 

Welfare) (1979) The Belmont Report: Ethical Principles 

and Guidelines for the Protection of Human Subjects of 

Research. National Commission for the Protection of 

Human Subjects of Biomedical and Behavioral Research. 

Available: http://ohsr.od.nih.gov/guidelines/belmont.html

[accessed 12 June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (1999). 

Air Quality Criteria for Particulate Matter. Environmental 

Protection Agency, National Center for Environmental 

Assessment, Office of Research and Development. 

EPA/600/P-99/002. 

14
15

U.S. EPA (U.S. Environmental Protection Agency) (1992). 

Guidelines for Exposure Assessment. Environmental 

Protection Agency, Risk Assessment Forum. EPA/600/Z92/001. Available: 

http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_

id=429103 [accessed 15 April 2008]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

12 June 2007]. 

U.S. OMB (U.S. Office of Management and Budget) (2007). 

Final Bulletin for Agency Good Guidance Practices, 

Section I(3). Federal Register 72:16 (25 January 2007) p. 

3432. Available: 

http://www.whitehouse.gov/omb/fedreg/2007/012507_good

_guidance.pdf [accessed 6 December 2007]. 
16
SECTION 2

Elements to Be Considered in 

Study Conceptualization and Planning 

Consideration of the scientific and ethical 

approaches for observational human exposure studies 

begins at the very beginning of the study and continues 

throughout it. Because such studies involve human 

participants, researchers will have to consider the ethical 

issues associated with the regulatory requirements for 

human subjects review and approval. Beyond that, 

however, ethical principles and issues should be an 

integral part of all elements of the study and should be 

included as soon as a study is proposed. 

In laying out seven requirements for determining 

whether a research trial is ethical, Emanuel, Wendler, 

and Grady (Emanuel et al., 2000) listed the requirements 

in rough chronological order, from conception of the 

research to formulation of the plan and protocol to 

implementation of the research study. This section 

follows their outline as this document highlights areas 

that NERL exposure science researchers should consider 

as they develop plans for an observational human 

exposure study. Table 2-1 shows the ethical 

requirements and the topics in this section relevant to 

each requirement. 

The first stage in the research process is to 

understand the state of exposure science and EPA’s 

programmatic needs for exposure data. NERL scientists 

and managers must decide whether an observational 

human exposure study is necessary and justified to meet 

the Agency’s need. If so, then NERL staff will begin to 

plan for a study. A variety of important issues will need 

to be considered (identifying and enlisting stakeholders 

and community representatives, forming a research 

team, maximizing benefits for participants, precluding 

conflicts of interest, etc.). 

The planning phase will culminate in the 

development of a science-based study design in an 

ethically sound human subjects research protocol. 

Adhering to the principal that “Bad science is always 

unethical” (U.S. EPA, 2000), the research must first be 

judged to be scientifically sound to meet ethical 

standards. Peer review by independent and 

knowledgeable experts will be used by NERL to assess 

the scientific validity of its proposed research. But 

passing scientific peer review is just the first hurdle: 

sound science is not necessarily ethical. NERL’s 

observational human exposure studies also must meet 

both the ethical requirements set forth in human subjects 

regulations and the ethical standards demanded of 

responsible researchers by their peers and society. Peer 

review will focus on the study design and the science but 

also necessarily will incorporate relevant ethical 

considerations. IRB review will focus on ethics and the 

protection of the human research participants but also 

necessarily will incorporate evaluation of the adequacy 

of the study design and other relevant aspects of the 

science. The principle that unsound science is unethical 

science demands that exposure of human subjects to any 

research risk whatsoever, even minimal risk, cannot be 

justified if the research will not answer the scientific 

questions that motivated the research in the first place. 

After independent reviews evaluate both the 

scientific and ethical aspects of the proposed research, 

EPA policy requires that the proposed study undergo 

internal EPA review, and that the human subjects 

research protocol undergo evaluation by the Agency’s 

Human Subjects Research Review Official (HSRRO). 

The HSRRO, located in the EPA Office of the Science 

Advisor, ensures that Agency studies comply with the 

Common Rule and all directives of 40 CFR 26 providing 

guidance and principles to govern Federal agency 

sponsored human subject research.. Only after HSRRO 

approval can any research actually begin. As the NERL 

study is implemented, project data and concerns of the 

participants will be monitored on a continuing basis and 

compared with previously established standards and 

17
criteria to evaluate whether the study is on target for 

meeting its objectives, or if some unforeseen 

circumstances indicate that the study should be stopped 

immediately on either scientific or ethical grounds. 

2.1 Scientific Value of a Proposed 

Observational Human Exposure Study 

NERL’s planning for an observational human 

exposure study begins with an assessment of the state of 

exposure science and of EPA’s programmatic needs for 

exposure data. NERL scientists and managers must 

decide whether an observational human exposure study 

is necessary scientifically and whether it is justified to 

meet the Agency’s need. 

2.1.1 Defining the Study Problem 

Observational studies historically have been 

performed for many different purposes and in many 

different fields of research—social behavioral, 

economic, biological, medical, epidemiological, and 

exposure science. NERL has used observational human 

exposure studies to understand how people come into 

contact with pollutants in their everyday lives, with the 

ultimate goal of protecting public health. NERL’s 

exposure research program addresses critical science 

needs directly related to Agency goals for protection of 

human health. The research program is driven by key 

exposure science questions that may be generated from a 

number of different sources, including legislative 

mandates (e.g., the Food Quality Protection Act, the 

Table 2.1. Seven Requirements for Determining Whether a Research Trial is Ethical 

From Emanuel, Wendler, and Grady (2000) 

Requirement Explanation Topics in this Section 

Social or 

scientific value 

Evaluation of a treatment, intervention, or theory that 

will improve health and well-being or increase 

knowledge 

Defining the study problem 

Justifying the study 

Identifying a research team 

Scientific validity Use of accepted scientific principles and methods, 

including statistical techniques, to produce reliable 

and valid data 

Study design 

Feasibility 

Sample size determination 

Representativeness of the sample 

Information collection rule 

Quality assurance 

Study design document 

Fair subject 

selection 

Selection of subjects so that stigmatized and 

vulnerable individuals are not targeted for risky 

research, and the rich and socially powerful are not 

favored for potentially beneficial research 

Ethical issues in fair subject selection 

Favorable riskbenefit ratio Minimization of risks; enhancement of potential 

benefits and risks to the subject are proportionate to 

the benefits to the subject and to society 

Designing in benefits for participants 

Assessing benefits and risks of study participation 

Independent 

review 

Review of the design of the research trial, its 

proposed subject population, and risk-benefit ratio by 

individuals unaffiliated with the research 

Scientific peer review 

Conflicts of interest 

Developing the protocol for ethical review 

Ethical review 

EPA review of scientific and ethical issues 

Informed 

consent 

Provision of information to subjects about the 

purpose of the research, its procedures, potential 

risks, benefits, and alternatives, so that the individual 

understands this information and can make a 

voluntary decision whether to enroll and continue to 

participate 

Informed consent 

Ensuring that participant behaviors are not adversely changed 

Respect for 

potential and 

enrolled subjects 

Respect for subjects by 

• permitting withdrawal from the research, 

• protecting privacy through confidentiality, 

• informing subjects of newly discovered risks or 

benefits, 

• informing subjects of results of the research, and 

• maintaining welfare of subjects 

Establishing criteria and standards for monitoring scientific and 

ethical issues during a study 

18
Clean Air Act, the Safe Drinking Water Act), program 

offices or research planning groups in the Agency, 

scientific peers and researchers, or collaborators. 

Communities also may identify concerns about 

exposures in their locales. NERL’s observational human 

exposure studies collect data to improve exposure and 

risk assessments, to develop risk management strategies, 

and to substantiate informational and educational 

materials for use by EPA program offices (e.g., Office of 

Pollution Prevention and Toxic Substances, Office of 

Air and Radiation, Office of Children’s Health 

Protection). 

 Emanuel et al. (2000) contend that an ethical 

research study must provide a worthwhile social or 

scientific value. Ideally, observational human exposure 

studies can provide both a scientific value and a social 

value to the participants and their community when 

feasible. Whenever possible, researchers should work 

with communities to develop studies that can help 

address community problems and maximize the benefit 

to the participants and the community, both of which 

also assume a burden for participation in a research 

study. 

The study problems addressed in past observational 

human exposure studies conducted or supported by 

NERL have varied substantially, as described in 

Appendix A of this document. As shown in Table A-1, 

NERL’s studies have addressed exposures to particulate 

matter (PM), air toxics, persistent organic chemicals, and 

nonpersistent chemicals including pesticides. The studies 

have examined single routes of exposure (air) and 

multimedia exposures, including dietary exposure. The 

studies range from small-scale pilot studies to large 

probability-based samples. They have included crosssectional, longitudinal, and convenience samples. Table 

A-1 demonstrates that many of the studies are small in 

scale and were intended to test a methodology to see if it 

may prove useful for a subsequent large-scale 

probabilistic human exposure research effort. Both 

small-scale and large-scale human exposure studies do 

involve human subjects. This means that the studies 

must meet both ethical standards and regulatory 

requirements. Regardless of the study’s scale, the 

scientific study design must be technically sound and 

appropriate to meet the objectives of the study. But the 

nature and objectives of the scientific inquiry will be 

different when the study is designed to test a 

methodology versus when the study is intended to 

measure a representative distribution of people’s 

exposures. Defining the study problem is a critical and 

fundamental first step in the scientific process, because it 

will establish the objectives that the research will be 

designed to achieve and the uses to which the research 

data will be put. The details of the scientific design of 

the study will naturally be strongly influenced by the 

objectives that the research is intended to meet. 

2.1.2 Justifying the Study 

Justification of any human study includes both a 

scientific and an ethical justification. In the list of seven 

ethical requirements that must be met for human subjects 

research to be considered ethically acceptable, four of 

those requirements, (1) respect for subjects, (2) informed 

consent, (3) favorable risk-benefit ratio, and (4) fair 

subject selection, are founded on the traditional ethical 

principles enunciated in the Belmont Report and 

codified in the Common Rule (Emanuel et al., 2000). 

But three requirements, (1) social or scientific value, 

(2) scientific validity, and (3) independent review, apply 

directly to the scientific aspects of the study. Similarly, 

Guideline 1 from the CIOMS (2002) document reiterates 

the foundational principle that “scientifically invalid 

research is unethical.” Beyond the traditional ethical 

expectations of respect for, protection of, and fairness to 

the research subjects, CIOMS requires investigators and 

sponsors to ensure that the research be “scientifically 

sound,” that it “conform to generally accepted, scientific 

principles,” and that all researchers be “qualified” and 

“competent.”7

 Text Box 2-1 identifies a number of 

elements that should be considered in justifying an 

observational human exposure study. As discussed 

below, a critical element to support justification of both 

the scientific and ethical elements of a study is the use of 

independent scientific and ethical peer review. 

 

7 Guideline 1 states “research can be ethically justifiable only if it is carried 

out in ways that respect and protect, and are fair to, the subjects of that 

research and are morally acceptable within the communities in which the 

research is carried out. Moreover, because scientifically invalid research is 

unethical in that it exposes research subjects to risks without possible benefit, 

investigators and sponsors must ensure that proposed studies involving human 

subjects conform to generally accepted scientific principles and are based on 

adequate knowledge of the pertinent scientific literature.” The commentary on 

the guideline goes on to say, “Among the essential features of ethically 

justified research involving human subjects, including research with

identifiable human tissue or data, are that the research offers a means of 

developing information not otherwise obtainable, that the design of the 

research is scientifically sound, and that the investigators and other research 

personnel are competent. The methods to be used should be appropriate to the 

objectives of the research and the field of study. Investigators and sponsors 

must also ensure that all who participate in the conduct of the research are 

qualified by virtue of their education and experience to perform competently 

in their roles. These considerations should be adequately reflected in the 

research protocol submitted for review and clearance to scientific and ethical 

review committees.”

19
Text Box 2-1. Elements to be Considered in 

Justifying a Study

• The research problem and questions to be addressed in the 

study 

• The objectives of the study or the hypotheses to be tested 

• A discussion of why human participants are required for the 

study, including a discussion of alternative designs that were 

considered 

• Available information on the need for the study (i.e., it is not 

redundant and the research question has not been already 

answered) 

• Available information from the scientific literature 

demonstrating the relevance of the proposed study 

• A discussion of the general technical approach and scientific 

soundness of the approach 

• An assessment of the needed competencies and 

qualifications of all personnel involved in conducting the 

research 

• The likelihood of success in meeting the study goals and 

objectives (including an evaluation of the accuracy, precision, 

and quality assurance of the data needed to attain the study 

goals and objectives) 

• Justification for the investment of time and money

2.1.3 Identifying a Research Team 

To Plan and Implement the Study 

Once the study problem has been defined and 

justified, the next step in developing the research study 

is to form the research team. The team should be diverse, 

including the technical experts (e.g., exposure 

researchers, statisticians, chemists), stakeholders, and 

representatives and members of the community in which 

the study likely will be performed. Information on 

identifying potential conflicts of interest among 

researchers early in the planning stage is discussed in 

Section 2.5.2. For scientific, ethical, and practical 

reasons, the community should be appropriately 

involved throughout the study, including throughout the 

planning phase. Information on identifying and engaging 

community members in the process is described in 

Section 6 of this document. The joint NRC-IOM 

committee reviewing ethical issues for research 

conducted in the homes and communities of the 

participants (like much of NERL’s human exposure 

research) concluded that “When researchers discuss a 

planned study with community representatives, 

understand their concerns and needs, and respond to 

them, protocols can be strengthened both scientifically 

and ethically” (p. xii, NRC & IOM, 2005). 

2.2 Ensuring Scientific Validity of the 

Research Study 

To facilitate scientific and ethical review, the 

research team members should develop a comprehensive 

and detailed study design that describes the technical 

approach for the observational study. Although the 

format and scope may vary depending on the specific 

study, there are a number of basic elements generally 

included in the study design. 

Translating the information developed in defining 

the problem and justifying the study into a real, 

workable, feasible study design and human subjects 

protocol is an iterative process involving input from all 

of the members of the research team. Scientific and 

technical expertise is required to assure the scientific 

integrity of the research, including developing the 

conceptual model8

 for the effort and devising a reliable 

sampling and analysis plan. Stakeholder input is critical 

to assuring that the generalizable research information 

from the study actually will be applicable for addressing 

the study problem. Community input is particularly 

important during the planning stage because the 

community representatives can provide valuable 

information about the community members (the future 

study cohort), the cultures of the community, community 

values, community concerns, feasibility of working in 

the community, information needed to develop the 

technical approach, and information on important factors 

like pollutant sources and other stressors in the 

community. (Additional considerations for 

communicating and working with both the participants 

and the community in which they live are the topics of 

Sections 5 through 7 of this document.) 

In developing the study design and the human 

subjects protocol, the research team often will have to 

deal with a variety of complex issues, including how to 

maximize benefits for participants, the community, and 

the stakeholders, and how to ensure the integrity, 

generalizability, and representativeness of the study. 

2.2.1 Study Design 

In epidemiology, the concept of study design has 

been structured to include (1) experimental studies, like 

drug trials, where the variables are isolated and 

controlled (See discussion on experimental studies in 

Appendix A.) and (2) observational studies where the 

variables are not controlled intentionally, but are simply 

 

8 A conceptual framework or model is often an effective approach to describe 

the relationship between the predicted exposures of the population and the 

population stressors, laying out the predicted pathways and routes of exposure 

(e.g., see Cohen Hubal et al., 2000). A conceptual model often is illustrated by 

a block diagram that represents the major scientific processes and interactions. 

The model is often very useful in developing an analysis plan that describes 

the hypotheses or objectives of the study, identifies the data needed to address 

the objectives, and specifies the analyses that will be done to test the 

hypotheses or address the objectives. 

20
observed along with the outcome or response measures. 

Clearly, the NERL human exposure observational 

studies (see Table A-1) fall into the latter category. Such 

studies may be cross-sectional studies (where a subset of 

the population is observed at the same time); cohort 

studies (which measure the same variables and response 

measures in a group of people repeatedly over time); 

case control studies (where the observed population is 

separated into two groups based on the outcome or 

response measure [the case group and the control group], 

and exposure variables between the two groups are 

analyzed for differences); or studies that combine 

approaches. The research may collect data from the 

participants once (e.g., in a large-scale, randomized 

design to collect a representative sample of the 

population, like many of the National Human Exposure 

Assessment Survey [NHEXAS] studies); over a few 

days (e.g., NERL’s Particulate Matter [PM] panel 

studies); from a cohort in different seasons or years (e.g., 

NERL’s Detroit Exposure Aerosol Research Study 

[DEARS]; the NHEXAS study in Maryland); or a series 

of cross-sectional studies repeated one after another with 

a different group of participants each time. (This latter 

case often is necessitated to minimize time and expenses 

associated with being in the field and because of 

limitations of sampling equipment or field technicians to 

assist in the collection of the data.) 

Although much of the literature on study design 

involves experimental studies (like drug trials), there is 

much that can be learned about the design of 

observational studies in epidemiology, including 

understanding their strengths and weaknesses. Web sites, 

like “Epidemiology for the Uninitiated” (Coggin et al., 

1997, available at www.bmj.com/epidem/epid.html), 

provide useful basic information on important topics for 

observational studies and their design. 

The specific details of the study design and the 

sampling approach to be used will depend very much on 

the objectives to be achieved in the study. Based on the 

objectives, a good study design must first clearly state 

the research question (or hypothesis to be tested) and 

must also define in advance what outcome or response 

measure will be used to test the question or hypothesis. 

Study designs that are vague or which propose to test 

some outcome measures against a variety of potential 

factors do not represent sound science. Statistically, a 

correlation is likely to be found between an outcome and 

some factor if enough factors are tested—whether there 

is an actual biological or physical relationship or not. 

This highlights the importance of statistics as an integral 

part of the study design process. Including individuals 

with appropriate statistical knowledge and experience on 

the research team from its very beginning is critical to a 

scientifically sound study design. (See, for example, 

Dallal, 2001, “Some Aspects of Study Design” in The 

Little Handbook of Statistical Practice at 

www.StatisticalPractice.com, and at www.tufts.edu/~gda

llal/LHSP.HTM). 

The study design must carefully consider each item 

of data or information that is to be collected during the 

study and how the data will be used in the analysis. All 

of the data needed to complete the analysis and test the 

hypothesis must be collected, otherwise the research 

objectives cannot be met, and the study should not go 

forward. Alternatively, data that are unrelated to the 

study analysis should not be collected. Collection of 

such data imposes a burden on both the participants and 

research staff with no known potential for benefit. 

Collecting, validating, and archiving such data wastes 

time and money and inappropriately burdens the 

participants. If there is no solid analysis plan for a 

particular data item, such data should not be collected. If 

the researchers actually believe that some factor may 

represent a potentially overlooked variable, then they 

should collect the information to test that hypothesis 

correctly. But, just collecting the data “while we can,” 

with no plan for how to analyze and use the data, wastes 

resources, imposes unnecessary burden, and often proves 

tempting as a statistical correlation hunt. Finally, the 

study design must be described in sufficient detail to be 

properly evaluated. Preparation of the study design 

document is described in a later section, but the 

overriding goal is to provide enough information to 

allow proper review of the science behind the study 

design by the research team, the scientific peer 

community, and the IRB panel members. 

2.2.2 Feasibility 

The authors consider the evaluation of the feasibility 

of accomplishing the study to be one of the most critical 

components of the development of the study design. 

Evaluating the feasibility of the research project involves 

considering not only whether there are sufficient 

resources to accomplish the study, but whether or not the 

study is feasible from a scientific and ethical perspective. 

If the research team concludes that the study is not 

feasible, there will be no further effort to develop the 

study. There may be practical limitations that preclude 

conduct of the study as initially conceived. Because 

“scientifically invalid research is unethical” 

(Guideline 1, CIOMS, 2002), it is essential that scientific 

and ethical considerations be considered together. Text 

21
Box 2-2 includes some examples of the types of 

questions that may be asked when evaluating the 

feasibility of a study. 

2.2.3 Sample Size Determination

One critical issue in assuring that an observational 

human exposure study is scientifically valid (and, 

thereby, not invalid and unethical) is the issue of sample 

size. EPA’s Science Advisory Board has stated, “Bad 

science is always unethical; research protocols that are 

fundamentally flawed, such as those with sample sizes 

inadequate to support reasonable inferences about the 

matter in question, are unjustifiable” (p. 2, U.S. EPA, 

2000). 

A study has to have an adequate size to meet the 

study objectives. If the sample size is too small, the 

results may not be statistically significant, and the results 

may not be either valid or generalizable. Such a result 

would be a waste of resources or cause undue burden on 

study participants without generating the intended 

generalizable knowledge that will benefit society. On the 

other hand, if the study sample size is larger than 

necessary to meet a study objective, this also may result 

in a waste of resources or the imposition of needless 

burden on participants. 

Sample size determination is an important step in 

planning a study, but it can be a difficult task (Lenth, 

2001). Sample size determination also may be 

confounded by other issues that will reduce the number 

of measurements that may be used in the analysis. For 

example, participants in a longitudinal study may “drop 

out” over time (some may move, others may tire of 

participation, etc.), so that the number of participants at 

the end of the study will be less than the number that 

started the study. The study design must account for the 

attrition of participants over time and plan ahead to 

recruit enough participants to ensure that a statistically 

useful number of participants complete the study. Often 

NERL scientists have used historical retention rates to 

estimate the sample size needed for a study. (See 

discussion of retention rates in NHEXAS publications.) 

In addition, some participants or their environments 

may not have concentrations above the detection limit. 

Depending on the nature of the research question, data 

below the analytical detection limit may, or may not, be 

useful in addressing the research question: sample size 

may need to be increased to account for missing values 

and values below detection. Pilot studies and 

environmental studies (with no participants as human 

subjects) may prove useful in understanding the range of 

concentrations to be expected and may provide insight 

into how to adjust the sample size appropriately. In 

surveys, like NERL’s National Human Activity Pattern 

Survey (NHAPS) for example, some randomly selected 

participants simply may refuse to participate, decreasing 

the number of samples and perhaps biasing the data. 

It is critical that sample size be determined at the 

time of study conceptualization and planning and not 

after the study already has been conducted. Researchers 

must include experts with the appropriate statistical 

expertise on the research team at its very inception. For 

additional information and insight, readers should refer 

to biostatistics books, Web sites, and other references 

(Lenth, 2001; Castelloe, 2000; Kraemer and Thiemann, 

1987; Van Belle and Fisher, 2004; Wackerly et al., 2001; 

Dallal, 2001) about this very important topic. 

2.2.4 Representativeness of the Sample 

In addition to concerns about the sample size being 

sufficient to provide statistically significant results, 

researchers also must be concerned about the individuals 

who participate in a study and of what group or 

population they may be representative. Research, as 

defined in the Common Rule, is “a systematic 

investigation ... designed to develop or contribute to 

generalizable knowledge.” How “generalizable” the 

Text Box 2-2. Is the Study Feasible? 

• What are the sample size requirements? Can enough 

participants be enrolled into the study from the proposed 

community, considering the eligibility criteria and anticipated 

response rate? What is the predicted retention rate if this is a 

repeated measurements study? Is that acceptable? 

• Is the research question well defined, and can we measure the 

variables and the outcome metrics? 

• Are the measurement methods specific and accurate enough 

to accomplish the research? 

• Does the analysis plan provide results to test the research 

questions and to meet the study objectives? 

• Will the community be receptive to this study? 

• Are there cultural mores, societal values, or other factors 

associated with the community that would make it difficult to 

conduct the study in the community? Is the study morally 

acceptable to the community? 

• Is there a community structure that will allow the research 

team to engage the community in the study? 

• What is the burden on the community? 

• What is the burden on the participants? Is it acceptable? 

• What is the risk-benefit balance? Is it acceptable, considering 

the burden on the participants? 

• Are there sufficient resources available to conduct a study of 

this size? 

• Are resources available for community outreach and sustained 

interactions with the community? Are resources available to 

support community members involved in the study? 

22
results of an observational study may be depends on the 

representativeness of the sample (the participants). A 

review of former NERL studies (Table A-1) shows a 

wide variety of approaches to selecting the participants, 

both probability sampling and nonprobability sampling. 

Some of the studies have involved randomized sampling 

(e.g., NHAPS, NHEXAS), selecting a cohort of interest 

and then using a randomized sample (e.g., Children’s 

Total Exposure to Persistent Pesticides and Other 

Persistent Organic Pollutants [CTEPP], DEARS) or a 

convenience sample (e.g., some panel studies), 

purposeful selection (judgment sampling) by the 

research team (for methods testing studies), recruiting 

the whole population in a locale or of a particular cohort 

(e.g., as proposed for the National Children’s Study 

[NCS]), or simply a convenience sample (in small pilot 

studies). 

The approach used to select the participants has 

depended on the objectives of the study. Research to 

understand and describe the distribution of exposures in 

the general population (like NHEXAS) or of the 

population or cohort in a particular state or region (like 

CTEPP or Agricultural Health Study [AHS]), has 

required a large number of randomly-selected 

participants. Randomized selection is recognized as a 

valid statistical method to get a sample that is 

representative of the larger population from which the 

participants were selected. Pilot studies performed to 

evaluate a method or to estimate the likely range of 

exposure concentrations often have employed either 

purposeful sampling, where the researchers use 

information on the relevant characteristics of the 

population to select those participants who will exhibit a 

wide range of activity levels or potential exposure 

concentrations, or convenience sampling, where the 

researchers select the most accessible members of a 

population 

NERL’s observational human exposure studies also 

have routinely collected information about the 

participants’ activities by using questionnaires and 

surveys. Survey design is both a science and an art 

because the design of surveys is based on statistics and 

science, but designing a good and effective questionnaire 

is often an art that requires understanding the individuals 

being surveyed. Text Box 2-3 identifies some of the 

areas of art involved in designing an effective 

questionnaire. 

Understanding the process for selecting participants 

and the statistical-scientific requirements of 

questionnaire design are both components of survey 

sampling and design. A variety of references can provide 

the researcher with information about the issues in 

survey sampling and design. (See 

http://home.ubalt.edu/ntsbarsh/Business-stat/statdata/Surveys.htm and www.statpac.com/surveys/, for 

example.) But the research team must include or have 

access to the appropriate survey statistics expertise as it 

plans the research study. 

2.2.5 Information Collection Rule 

As Federal employees, NERL researchers also must 

be aware of Information Collection Rule requirements. 

The Paperwork Reduction Act stipulates that every 

Federal agency must obtain approval from OMB before 

collecting the same or similar information from 10 or 

more members of the public. An Information Collection 

Request (ICR) is required if the same or similar 

information is being collected from 10 or more nonFederal respondents within a 12-month period, even if 

the information collection is voluntary. Generally, any 

survey, questionnaire, monitoring, reporting, or 

recordkeeping requirement imposed on non-Federal 

respondents by EPA will require an ICR. Information 

collections associated with all cooperative agreements 

funded by the EPA require an ICR. When an ICR is 

required, it must be approved by OMB before the 

collection begins, regardless of whether the collection of 

information is mandatory, voluntary, or required to 

receive a benefit. The principal investigator must prepare 

an ICR and submit it to the appropriate Office of 

Environmental Information Desk Officer. 

An ICR 

• describes the information to be collected, 

• provides justification for why the information is 

needed, and 

• estimates the time and cost for the public to answer 

the request. 

Information about ICRs and their requirements is 

available to NERL and other EPA staff members at 

http://intranet.epa.gov/icrintra/index.html. 

Text Box 2-3. Questionnaire Considerations 

• Questions should be simple and in a language the individual 

can understand. 

• Questions should be unambiguous. 

• Questions should be relevant to the study. 

• Questions should not be too personal. 

• The questionnaire should be as short as possible. 

• The questions should not be leading (e.g., internally 

suggestive of the answer). 

• Questions should follow a logical order. 

23
2.2.6 Quality Assurance Project Plan 

Data of unknown or uncertain quality can undermine 

the scientific integrity of a study and render an otherwise 

sound study invalid. NERL scientists must be diligent in 

the implementation of the procedures and processes 

specified in a well-developed quality assurance project 

plan (QAPP). A discussion of quality assurance 

programs and QAPPs is outside of the scope of this 

document. There are many good references on the topic, 

including the EPA Web site, www.epa.gov/quality/. 

2.2.7 The Study Design Document 

The study design document should contain sufficient 

detail to allow independent review and assessment of the 

scientific soundness of the study and the approaches that 

will be followed to ensure that the study meets the 

highest scientific and ethical standards. The research 

team can meet regularly to specifically evaluate the plan. 

It should be noted that a study design is not the same as 

an implementation plan. The latter includes an even 

greater level of detail describing how the study will be 

performed and includes protocols and operating 

procedures. Text Box 2-4 lists a number of elements that 

may be appropriate to include in a study design. 

2.3 Ethical Issues in Ensuring 

Fair Subject Selection 

One of the ethical principles of human subjects 

research is that selection of participants should be fair. In 

Section 2.2.4, the discussion centers on understanding 

what population or cohort the participants in a research 

study represents, and how such a selection may be 

influenced by the research questions and study 

objectives. That consideration actually represents the 

first component of ensuring that subject selection is fair. 

That is, the scientific goals of the study should be the 

primary basis for determining what groups or individuals 

should be recruited and enrolled in a study. Participants 

should not be recruited either because of privilege or 

because of vulnerability or their inability to look out for 

their own interests properly. Similarly, groups or 

individuals should not be excluded peremptorily without 

consideration of the risks and benefits to them as 

individuals. Section 3 of this document discusses 

protection of vulnerable groups and concludes that 

NERL researchers should include vulnerable groups in 

observational human exposure studies only if their 

participation is critical to the success and applicability of 

the research. Even then, EPA and NERL researchers will 

have to meet stringent standards for protecting the rights 

and safety of the vulnerable participants. “The essence of 

fairness in human subjects research is that scientific 

goals, considered in dynamic interaction with the 

potential for and distribution of risks and benefits, 

should guide the selection of subjects.” (Emmanuel et al, 

2000). On the other hand, as discussed in Section 3, 

many study problems specifically address exposures of 

vulnerable groups to chemicals and other stressors. 

Researchers should not avoid research studies that will, 

Text Box 2-4. Elements That May Be Included in a 

Study Design 

• Introduction and background, including the purpose and scope 

of the study

• The desired outputs and outcomes of the study, including the 

objectives and the hypotheses to be tested

• A brief description or overview of the study

• The technical approach and conceptual model that accounts for

– sources of the chemicals being studied;

– potential routes and pathways of exposure; 

– factors that may impact exposure and other relevant 

stressors; 

– selection and characteristics of the study participants; 

eligibility criteria; and recruitment, retention, and payment 

approaches; 

– justification for sample size, the methodology for selecting 

participants, and the sampling methods; 

– characteristics of the community in which the study will be 

performed; 

– environmental conditions, factors, or end points to be 

measured, including sampling and analysis approaches and 

methods (with description of expected performance); 

– survey design and questionnaires and other survey 

instruments, as applicable (with description of prior use and 

validation in similar studies); 

– pilot studies that may be undertaken; 

– quality assurance project plan and quality control; 

– timeframe for the study; 

– exposure scenarios to be considered; 

– burden of the study on the participants; 

– resources available; and 

– feasibility 

• Discussion of alternative study designs and approaches 

considered and reasons for rejecting other approaches and 

selecting the one proposed 

• An analysis plan that considers 

– Information and data needs, including data storage, security, 

access, and release; 

– nature of the measurement data (e.g., variability, quality 

assurance); 

– how the collected data will be used, and how the proposed 

analyses will address objectives of the study; and 

– hypotheses to be tested and statistical power and sample 

size required to test the hypotheses 

• Resources required or available 

• Project organization and management, including team members 

and roles and responsibilities

• Schedule

24
of necessity, include vulnerable groups to address the 

study hypotheses or objectives simply to avoid the more 

stringent requirements for working with these groups. 

2.4 Ensuring a Favorable Risk-Benefit Ratio 

2.4.1 Designing in Benefits for the Participants 

Study designs vary depending on the objectives of 

the study, existing knowledge on the research question, 

and the hazard being studied (NRC & IOM, 2005). 

Recent ethical discussions about study designs in human 

subjects research (cf., Recommendation 7.1, p. 143, 

NRC & IOM [2005] and Emanuel et al. [2000]) support 

the development of innovative study designs to 

maximize the benefit9

 to the study participants, as well 

as to the community and the greater society beyond. 

Observational human exposure studies generally collect 

data that contribute to generalizable knowledge that will 

benefit the community and society as a whole, but they 

often do not provide obvious direct benefit to study 

participants. Therefore, it is important to include 

elements in the study design that can offer benefits to the 

participants wherever possible. This is not always 

straightforward, but one way that participants, as well as 

communities, can benefit from these studies is by 

incorporating strong educational components into the 

conduct of the research. For example, brochures, videos, 

and other materials that educate study participants on 

safety around the home or on how to reduce their 

exposure to chemicals can be distributed during the 

study. EPA’s program offices, including the Office of 

Children’s Health Protection, the Office of Pollution 

Prevention and Toxics, the Office of Pesticide Programs, 

the Office of Drinking Water, and others have Web sites 

with substantial amounts of informational and 

educational materials available that could be distributed 

to study participants. Other organizations, such as the 

American Lung Association, the American Cancer 

Society, the American Academy of Pediatrics (AAP), 

and various environmental groups, have materials of 

which study participants may not be aware that could be 

used as educational materials when relevant. 

In addition, approaches that provide direct benefits 

to study participants will need to be tailored to the 

particular study population and community. Feedback 

from potential participants in focus groups and input 

from community representatives may be useful in 

identifying these approaches. 

 

9

 Payment to participants is never considered a benefit of a study. 

2.4.2 Assessing Benefits and Risks of Study 

Participation 

For all research involving human participants, the 

Common Rule requires researchers to ensure that 

potential risks “are reasonable in relation to the 

anticipated benefits,” and that risks are minimized (40 

CFR 26.111). It is most useful if the assessment of 

benefits and risks is begun early in the scoping and 

planning phase of a study. 

Unlike some biomedical research that involves the 

study of interventions or procedures that hold out the 

prospect of direct diagnostic, therapeutic, or preventative 

benefit for the study participants, observational human 

exposure studies often do not have a similar prospect of 

direct benefit to the participant. Therefore, the riskbenefit balance is based on the balance between the risks 

to the participants and the expected benefits to society 

(generalizable knowledge). The risks to participants 

must be reasonable [40 CFR 26.111(a)(2)] in relation to 

the importance of the knowledge gained. This 

assessment of the risk-benefit balance, therefore, needs 

to be performed in the initial planning of the study to be 

included in the justification for the study (Section 2.2). 

If there is no prospect of direct participant benefit, 

and the study participants are children, moreover, EPA is 

permitted to conduct or support only those observational 

human exposure studies that meet both the regulatory 

definition of “observational” and the regulatory 

definition of “minimal risk.” The latter is defined in the 

Common Rule at 40 CFR 26.102(i) and reiterated in 

Subpart D of the EPA Rule at 40 CFR 26.402(g): 

“Minimal risk means that the probability and magnitude 

of harm or discomfort anticipated in the research are not 

greater in and of themselves than those ordinarily 

encountered in daily life or during the performance of 

routine physical or psychological examinations or tests.” 

In applying this definition, EPA adheres to the 

consensus standard that the reference population for this 

definition is normal children living in safe, healthy 

environments. In its discussion of the perception of risks 

and benefits, the NRC & IOM (2005) report on housing 

health hazards in children notes that the children 

participating in these studies may be at risk for physical 

harms or adverse health outcomes because they live in 

housing (or otherwise occupy environments) with health 

hazards. However, such risks are not introduced by the 

research but, rather, would be present whether or not the 

children were involved in a research study. As a 

consequence, the study still would meet the regulatory 

criteria for minimal risk as long as the research itself

introduced no risks over and above those minimal risks 

25
experienced by normal children living in safe healthy 

environments. 

However, the existence of greater than minimal 

background risks that are not introduced by the research, 

nonetheless, raises additional ethical considerations. The 

joint NRC & IOM Committee on Research on HousingRelated Health Hazards Involving Children discussed 

the ethical arguments that arise when scientists conduct 

research that observes children in poor-quality housing. 

They point out that a researcher’s first duty of 

beneficence under the Common Rule requires that the 

risks of the research actions be proportionate to 

[“reasonable in relation to”; 40 CFR 26.111(a)(2)] the 

benefits of the research, and that the risks be minimized. 

They acknowledge, however, that some have argued that 

the “best interests of the child” also obligates researchers 

to “rescue” children from harm and to provide better 

living conditions. They conclude that, properly applied, 

the ethical principle of beneficence does indeed direct 

researchers who observe serious harms to child subjects 

to take steps to try to prevent the harms. However, they 

also argue that the researcher’s duty does not extend to 

“personally and directly prevent harm by removing the 

child from the harmful environment” (p. 60, NRC & 

IOM, 2005). They conclude instead that “it is unrealistic 

and unfair to hold individual research investigators 

responsible for ameliorating the social circumstances 

that they study” and that “a nuanced balancing of the 

benefits and risks of research” is an ethically sound 

approach that is firmly established in Federal regulations 

(p. 60, NRC & IOM, 2005). Balancing the ethical 

obligation to mitigate risks or harms observed during 

research with the reasonable limits on an investigator’s 

moral responsibility for the social circumstances 

surrounding the research will be the subject of later 

sections of this document, particularly Section 4.3.1. 

Assessing the risks and benefits of the research 

study can be very difficult for the researchers, especially 

because the researchers and the community or 

participants may perceive the risks and benefits quite 

differently. (See the discussion in NRC & IOM [2005], 

for example.) To understand the community’s 

perspective better, the researcher may find it helpful to 

discuss the assessment of risks and benefits with 

members of the research team, community 

representatives, and relevant stakeholders. The research 

team should consider the use of a community advisory 

board (CAB) to provide input to the assessment of the 

risks and benefits of the study. The group could include 

individuals who are representative of the population to 

be studied, community representatives, exposure 

scientists, and bioethicists. The group should include 

experts familiar with the human subjects research 

regulations, preferably including someone who has 

served on IRBs. Obtaining input from the group can be 

accomplished by submitting the study concept and 

general study design to the group for review and 

feedback, even before a full study design has been 

developed. (See the discussions of CABs in Sections 5 

and 6.) Ultimately, it will be the review by the members 

of the IRB that will determine whether the balance is 

appropriate and justifiable. 

2.5 Independent Scientific and 

Ethical Review 

Because issues of science and ethics are intrinsically 

bound together in human subjects research (Emanuel et 

al., 2000; CIOMS, 2002), it is important that scientific 

and ethical reviews be considered together, not 

separately. Scientific reviews are performed to ensure 

the scientific soundness of the study, whereas ethical 

reviews are performed to ensure proper action and the 

protection of the human subjects in a research study. A 

study that is not scientifically sound could expose study 

participants to unnecessary risk or inconvenience and 

burden, with no additional societal benefits (i.e., no 

increase in generalizable knowledge). EPA’s Science 

Advisory Board has stated that “bad science is always 

unethical” (U.S. EPA, 2000), and CIOMS declares that 

“scientifically invalid research is unethical” (CIOMS, 

2002).10 It is clear, therefore, that the ethical review has 

to consider the scientific aspects of the study also. 

There may be multiple levels of review during 

development of the study design and human subjects 

research protocol for an observational human exposure 

study. The research team is responsible for the design of 

the study and for ensuring that adequate peer review is 

 

10 CIOMS (2002) Guideline 2 asserts “Ethical review committees—All 

proposals to conduct research involving human subjects must be submitted for 

review of their scientific merit and ethical acceptability to one or more 

scientific review and ethical review committees. The review committees must 

be independent of the research team, and any direct financial or other material 

benefit they may derive from the research should not be contingent on the 

outcome of their review. The investigator must obtain their approval or 

clearance before undertaking the research. The ethical review committee 

should conduct further reviews as necessary in the course of the research, 

including monitoring of the progress of the study.” The CIOMS document 

continues, “According to the Declaration of Helsinki (Paragraph 11), medical 

research involving humans must conform to generally accepted scientific 

principles, and be based on a thorough knowledge of the scientific literature, 

other relevant sources of information, and adequate laboratory and, where 

indicated, animal experimentation. Scientific review must consider, inter alia, 

the study design, including the provisions for avoiding or minimizing risk and 

for monitoring safety. Committees competent to review and approve scientific 

aspects of research proposals must be multidisciplinary.” 

26
performed to evaluate both the scientific and ethical 

approaches for the study. Following completion of a 

draft study design, researchers should engage a diverse 

group of experts to review the study design and human 

subjects aspects. The scope of the study should dictate 

the level of the review (i.e., internal or external 

independent peer review). A small pilot study to 

evaluate measurement methods or to collect screening 

level data in preparation for a large study may not 

require as extensive review as a larger study. 

When the scientific soundness of the study has been 

evaluated and found to be feasible, and the final study 

design is completed, the human subjects research 

protocol should be developed and submitted to the IRB 

for review and approval. For studies conducted or 

supported by EPA, additional review and certification of 

the human subjects research protocol is required by EPA 

Order 1000.17 A1. (available online at 

www.epa.gov/oamrtpnc/forms/1000_17a.pdf). Review 

and approval of the protocol and associated documents 

must be obtained from EPA’s HSRRO, located in the 

EPA Office of the Science Advisor, before any work 

begins. Any changes made to the protocol after IRB 

approval must be submitted to and approved by the IRB. 

2.5.1 Scientific Peer Review 

For all studies, regardless of the scope, the research 

team should solicit review and comment on the scientific 

approach by experts external to the research team. A 

peer review panel consisting of individuals who were not 

involved in the design of the study can be formed to 

review the scientific soundness of the study. It is 

important for the panel to consist of individuals with 

experience and background appropriate to the study and 

to include members with knowledge of the ethical 

principles for protection of human subjects in these types 

of studies. The panel also would benefit from including 

someone with sufficient background and expertise in 

statistics to evaluate whether the study design, sample 

size, and proposed data analyses are appropriate and 

adequate to address the study objectives or test the 

hypotheses. For small studies, the peer review panel may 

consist of individuals within the organization conducting 

the study if they have not been involved in developing 

the study design. For larger and complex studies, it is 

recommended that an external peer review panel be 

convened to review both the scientific and ethical 

soundness of the study design. 

For research conducted or sponsored by NERL, 

human subjects research efforts will undergo both a 

scientific review and an ethical review. The director of 

the division conducting or funding the observational 

research is the manager with the primary responsibility 

for ensuring that the scientific and the ethical reviews are 

conducted, and that the review comments are properly 

addressed. The study design will be reviewed for 

scientific quality by independent and knowledgeable 

reviewers. Depending on the scope of the study, the 

appropriate NERL associate director or the NERL 

laboratory director will make the final determination 

about (1) the process for selecting scientific peer 

reviewers (including the range of disciplines to be 

included), (2) the nature and scope of the review process 

(e.g., charge to the reviewers and scope of the review; 

letter reviews, convening a peer panel, or both; the size 

and nature of the panel review; etc.), and (3) the 

adequacy of the responses to the scientific review. 

2.5.2 Conflicts of Interest 

It is recommended that potential conflicts of interest 

among researchers or study participants be identified at 

all stages of study planning and implementation, but 

particularly early in the study during the planning stage. 

There can be many sources of potential conflicts of 

interest, including sources of project funding, pressures 

to publish, consulting arrangements of the investigators, 

employment of investigators’ family members with 

affected parties, participation in affected advocacy 

groups, collaborations or relationships with experts on 

the IRB or other independent review committees, 

institutional conflicts for any contractors who may be 

involved, or a wide range of other situations. 

Any situations that constitute actual conflicts of 

interest and all potential or apparent conflicts of interest 

must be reported to the IRB for their review and 

resolution. The CIOMS (2002) guidelines for research 

protocols involving human subjects specify that all 

sponsors of the research be identified, and that the 

protocol include actions to disclose and address potential 

conflicts of interest. Concerns about conflicts of interest 

also need to be identified and discussed with the 

researchers, community, and other stakeholders to make 

a determination of the existence of conflicts, and how 

they should be avoided or handled. 

Even if actual conflicts of interest do not exist, 

researchers should recognize that there can be perceived 

conflicts of interest that can be just as damaging as real 

conflicts of interest. Perceptions by participants, 

community members and representatives, stakeholder 

groups, and the public may be substantially different 

from the reality of the situation. This is especially likely 

to occur when external sources, such as industry, are 

27
involved in funding research. Even though researchers 

may develop agreements with funding organizations that 

ensure researcher autonomy, a perception may exist that 

the funding organization will bias the study (Resnik and 

Wing, 2007). Concerns about perceived conflicts of 

interest should be discussed with the IRB and other 

relevant review committees, in addition to the 

researchers, the community, and other stakeholders. The 

IRB must be made aware of any circumstances that may 

give rise to actual conflicts of interest or to the 

appearance or perception of a conflict of interest. The 

IRB’s recommendations about how to resolve any such 

conflicts must be strictly adhered to by NERL 

researchers. 

2.5.3 Develop the Human Subjects 

Protocol for IRB Review 

IRBs may have specific format requirements for 

their human subject research protocols. Traditionally, the 

human subjects research protocols for research 

conducted or funded by NERL have included 

descriptions of the project, including title and description 

of the research; the duration of the project; the type of 

data to be collected; the objectives of the study; the 

number of samples; a description of the participants and 

participant recruitment procedures; the informed consent 

procedures and forms; estimates of participant risk and 

burden, an assessment of benefits and the risk-benefit 

ratio; and actions to protect the participants. CIOMS has 

developed a comprehensive list of items that they 

recommend for inclusion in a human subjects research 

protocol (Appendix 1, CIOMS, 2002). Many of the 

items that they identify are also useful for observational 

human exposure studies. (The CIOMS items can be 

found in Appendix C of this document.) The authors 

recommend that anyone developing a human subjects 

protocol for observational human exposure studies 

review and utilize the CIOMS list of topics, as 

appropriate. Text Box 2-5 identifies a number of topics 

that should be considered in development of the human 

subjects research protocol. 

In addition, the authors’ experience leads them to 

suggest that three additional topics beyond those from 

the CIOMS (2002) document also may need to be 

considered in a human subjects protocol: (1) approaches 

to minimize changes in participant behavior because of 

participation in the study (see Section 2.3.4); 

(2) approaches to minimize therapeutic misconception 

(see Section 5.4.1); and (3) actions to involve the 

community in a community-based participatory research 

Text Box 2-5. Potential Topics in a 

Human Subjects Research Protocol 

1. Title 

2. Summary in lay language 

3. Justification for the study 

4. Ethical issues and proposed resolution 

5. Summary of previous research 

6. Affirmation of Belmont Principles and 40 CFR 26 compliance

7. Previous history or use of the protocol 

8. Information on the location and demographics of research 

9. Information on funding organization, researcher partners, 

and collaborators 

10. Names, qualifications, and experience of investigators 

11. Objectives, hypotheses, assumptions, and variables 

12. Study design 

13. Sample size and power and statistical analysis plan 

14. Criteria and justification for subject selection 

15. Justification for use of vulnerable groups, if any 

16. Process of recruitment 

17. Actions to involve the community in a community-based 

participatory research program 

18. Description and explanation of any and all interventions 

19. Measurements or data to be collected 

20. Any clinical or other tests 

21. Rules or criteria for removing subjects or terminating the 

study 

22. Adverse events and unanticipated problems⎯reporting and 

responses 

23. Potential benefits to subjects or others 

24. Expected benefits of the research to the population 

25. Informed consent process and responsibilities 

26. Protections for the consent/assent of vulnerable participants 

27. Efforts to minimize “therapeutic misconception” 

28. Approaches to minimize changes in participant behavior 

29. Payments 

30. Plans for informing subjects about items that could affect 

subjects’ willingness to continue in the study 

31. Plans to inform subjects about the results of the study 

32. Privacy and confidentiality 

33. Security of personal information and when, how, and by 

whom private information can be revealed 

34. All foreseen uses of personal data or biological materials 

35. Procedures for data and safety monitoring and oversight of 

the study and the criteria for identifying, reporting, and 

responding to adverse events, including ethical breaches, 

environmental measures in excess of reporting standards, 

and collateral observations, and criteria for prematurely 

terminating the study if necessary 

36. A list of the references cited in the protocol 

37. The source and amount of funding 

38. Protocols for dealing with financial or other conflicts of 

interest 

39. Schedule 

40. Arrangements with sponsors regarding publication rights and 

procedures 

41. Reasons for not publishing the study findings 

42. Procedures for preventing falsification of data 

28
(CBPR) effort, as appropriate (see Section 6, especially 

Section 6.10). 

2.5.4 Ethical Review 

In the United States, ethical reviews of studies 

involving human subjects are performed by IRBs. The 

Common Rule specifies requirements (40 CFR 26.107 – 

115) for IRB membership, IRB functions and operations, 

IRB review of research, and other details related to IRB 

review and approval of research. Emanuel states that 

“the independent ethical review of [human subjects 

research] should involve individuals with training in 

science, statistics, ethics, and law, as well as reflective 

citizens who understand social values, priorities, and the 

vulnerability and concerns of potential subjects” 

(Emanuel et al., 2000). It is beyond the scope of this 

document to include detailed discussions on IRB 

membership, operations, processes, etc. The reader is 

referred to the Common Rule, as well as a number of 

other available references (e.g., OHRP, 2007; CFR, 

2006; U.S. HHS, 1993; NRC, 2003). 

It is essential that research with human subjects be 

carried out or strictly supervised by suitably trained, 

qualified, and experienced investigators. For all research 

subject to the Common Rule, these qualified researchers 

are expected to prepare a human subjects research 

protocol (as in Section 2.5) and to submit the protocol to 

be ethically and scientifically appraised by one or more 

suitably constituted IRBs, independent of the 

investigators. 

There are a number of other issues associated with 

IRBs that may impact researchers conducting 

observational human exposure studies. As an example, 

there has been concern about the transparency of IRBs. 

Questions have been raised about what information the 

IRB should make available to the public regarding 

membership on the IRB for review of individual 

projects, the discussions held with the researchers, the 

IRB’s concerns about the research protocol, the 

researchers’ response, etc. Should this information be 

documented in files that the researchers can make 

available to the participants, community, stakeholders, 

and the public? At the present time, there is no clear 

approach as to how to address these issues. Because 

these issues are associated with the IRB, not the 

researcher, it is outside the scope of this document to 

recommend approaches for IRBs to address these 

concerns. IRB processes and procedures will continue to 

evolve as recommended by various committees and 

workgroups (e.g., as reported in NRC & IOM, 2005; 

NRC, 2003; U.S. HHS, 1993). 

All human subjects research conducted or sponsored 

by NERL is subject to both the 40 CFR 26 requirements 

and procedures set forth in EPA Order 1000.17 Change 

A1 (www.epa.gov/oamrtpnc/forms/1000_17a.pdf). The 

EPA order establishes as policy that all research will 

comply with the Common Rule and with the order. All 

human research studies must be reviewed and approved 

by the EPA HSRRO before the work can begin. 

In NERL, the director of the division conducting or 

funding the research is the manager with the primary 

responsibility for developing the human subjects 

research protocol and for having that protocol reviewed 

by an independent IRB acceptable to the EPA HSRRO. 

The protocol also will be reviewed by the NERL 

HSRRO and by the appropriate NERL associate director 

before it is submitted to the IRB. Under 40 CFR 26.109, 

the IRB can demand changes to the research protocol 

and is the final authority for approving or disapproving 

the research activity. 

2.5.5 Internal EPA Review of Scientific and 

Ethical Issues 

After IRB approval is obtained, the division director 

will be the primary manager responsible for preparing a 

request for review and approval or exemption of the 

human subjects research by the EPA HSRRO. The 

division director will ensure that the request is consistent 

with EPA Order 1000.17 A1 and all other policies or 

procedures that the EPA HSRRO may have established. 

The EPA HSRRO shall be the final authority for 

approving or disapproving the research effort. The EPA 

HSRRO may request additional reviews or establish 

additional policies and procedures for seeking review 

and approval. No human subjects research will 

begin⎯not even recruiting of potential 

participants⎯until the EPA HSRRO has approved or 

exempted the research. 

2.6 Informed Consent 

Informed consent is discussed extensively in 

Section 5 of this document. The major focus is that 

informed consent is a process, not a form, that “should 

be an on-going, interactive dialogue between research 

staff and research participants involving the disclosure 

and exchange of relevant information, discussion of that 

information, and assessment of the individual’s 

understanding of the discussion” (Recommendation 4.1, 

IOM, 2002). These comments emphasize how important 

true two-way communication is to comprehension, the 

second pillar in the informed consent process. Informed 

consent is built on three “pillars:” (1) information; (2) 

29
comprehension; and (3) voluntary participation, or 

“voluntariness” (U.S. DHEW, 1979). Informed consent 

requires “provision of information to subjects about the 

purpose of the research, its procedures, potential risks, 

benefits, and alternatives, so that the individual 

understands this information and can make a voluntary 

decision whether to enroll and continue to participate” 

(Emanuel et al., 2000). 

2.7 Ensuring That Participant Behaviors Are 

Not Changed Adversely Because of Being 

in the Study 

The goal of observational human exposure studies is 

to collect information on people’s exposures to 

chemicals in their real-world environment as they carry 

on their normal daily activities. Researchers who 

conduct these studies, however, recognize that 

participation in a study may affect behavior. This cannot 

always be avoided, as simply agreeing to participate in a 

study may impact the participant’s activities and 

schedules. For example, this occurs when technicians 

visit homes to collect samples or when participants are 

asked to collect samples (e.g., food, urine), or to 

complete surveys, activity logs, or questionnaires. These 

types of changes in behavior may or may not affect the 

outcome of the study. 

Some changes in behavior can affect the study 

outcome. The Hawthorne Effect is a well-recognized 

phenomenon. It is an effect on an outcome variable 

caused by the fact that the participants of the study know 

they are participating in the study. The Hawthorne Effect 

originally referred to the increase in worker productivity 

observed when a worker is singled out and made to feel 

important; the increased productivity was not related to 

the environmental factors that were being studied. The 

effect was described based on a series of industrial 

productivity studies from 1927 to 1932. Similarly, some 

changes in participant behaviors may change the 

observations, measurements, and conclusions from 

observational human exposure studies. For example, 

participants may do more cleaning in their home because 

they do not want the researchers to think they are poor 

housekeepers; this could affect the measurement of 

environmental concentrations in the home. In a study of 

chemicals from consumer products, participants may 

think that because the researchers are studying the 

products, the products must be harmful. Therefore, study 

participants may elect not to use the products during the 

study in the same manner as they would normally. 

Alternatively, prospective participants may choose to 

use more of the household product to qualify for the 

study. As a result, the participant’s exposure to the 

chemicals could be either more or less than “normal.” 

Any change in a participant’s behavior that is related 

to the research question being addressed in the study 

may impact the study results. Researchers should try to 

anticipate how a study may impact participant behaviors 

and ensure that the study design and implementation 

protocols do not cause changes in behavior that may 

cause harm to a participant during a study. A number of 

study elements with the potential to influence 

participants’ behavior are listed in Text Box 2-6. 

It is very difficult to predict in advance how these 

elements may be interpreted and acted on by the 

participants. Researchers may learn from the experiences 

of others, including the “lessons learned” from experts 

and their publications. They may wish to engage the 

community representatives (see Section 6) in a thorough 

discussion of the issue. Community-based focus groups 

or pilot studies also may demonstrate how the various 

elements of the study may have an unintended impact. 

Additionally, researchers can be very careful in the 

informed consent process (see Section 5.1), to ensure 

that participants not only know, but that they understand 

the facts of the study (Gilbert, 2006), and that they 

comprehend that the goal is to observe and measure the 

participant’s exposures during their normal, everyday 

activities. 

2.8 Criteria and Standards for Monitoring 

Scientific and Ethical Issues 

Ethical requirements do not end when the 

participants sign the consent form and agree to 

participate. Indeed, as was stated above, informed 

consent is a process, not a form, and the process is an 

on-going dialogue between participants and researchers 

that continues throughout the study and beyond. In 

discussing respect for both potential and enrolled 

Text Box 2-6. Study Elements That 

Could Affect People’s Behavior 

• Eligibility criteria 

• Recruiting approach and materials 

• Enrollment approach 

• Payments 

• Retention strategy 

• Types of measurements made and data collected 

• Protocols for data collection 

• Protocols for visits to homes 

• Interactions with participants 

• Communications 

30
subjects, Emmanuel et al. (2000) identify five actions 

that demonstrate respect for subjects, including 

(1) permitting withdrawal from the research, 

(2) protecting privacy through confidentiality, 

(3) informing subjects of newly discovered risks or 

benefits, 

(4) informing subjects of results of other relevant 

research, and 

(5) maintaining welfare of subjects. 

The authors conclude that these requirements can be 

met by diligent exercise of data and safety monitoring 

and oversight of the research effort. (Data and safety 

monitoring and oversight also are discussed throughout 

Section 4, but especially in Section 4.5 entitled “Data 

and Safety Monitoring and Oversight” and in 

Section 7.8, “Reporting Unanticipated Results and 

Observations.” The reader also is referred to those 

sections.) 

Creation of data and safety monitoring and oversight 

organization and procedures, combined with careful 

consideration of actions to ensure the ethical protection 

of participants, is perhaps the most important aspect of 

planning and implementing an observational human 

subjects study. The monitoring must include both the 

technical aspects of the study—like planning for actions 

if unsafe environmental conditions are observed—and 

also the ethical aspects of the study, such as those items 

listed above. The team of people involved in data and 

safety monitoring and oversight have to establish and 

implement mechanisms to get feedback on a continuing 

basis from the participants, in addition to monitoring and 

reviewing the scientific data. 

CIOMS recommends that all human subjects 

research protocols contain “A description of the plans 

for statistical analysis of the study, including plans for 

interim analyses, if any, and criteria for prematurely 

terminating the study as a whole if necessary” 

(Appendix A, CIOMS, 2002). To be consistent with this 

recommendation, the research team will need to develop 

and implement an approach for monitoring the scientific 

and ethical issues during the study, so that changes can 

be made to the study, or the study can be stopped if 

necessary. Criteria and standards need to be established 

against which study activities and results can be 

evaluated, and these criteria and standards need to be 

incorporated into the study design, the human subjects 

research protocol, and the QAPP. 

In developing an approach to monitor scientific and 

ethical issues during the study, the research team may 

choose to 

• identify the individual, team, advisory committee, or 

data safety monitoring board (DSMB) responsible for 

monitoring the progress and results of the study; 

• develop roles and responsibilities; 

• develop a schedule and timeline for the activities to be 

conducted; 

• develop goals for interim data analysis and prepare an 

analysis plan; 

• identify what data will be analyzed, how it will be 

processed and validated, and who will perform the 

analyses; 

• develop a plan for reporting interim results to the 

research team; 

• develop standards for reporting scientific and ethical 

issues to the research team; or 

• develop criteria for evaluating scientific and ethical 

issues that arise during the study. 

In a well-designed observational study for which the 

research team has adequately prepared, it is unlikely that 

there will be scientific issues requiring that the study be 

stopped. Nonetheless, it is important for criteria to be 

established for when the study needs to be changed or 

terminated. An example might be the participant 

retention rate. In a study with repeated measurements, a 

certain sample size is required to obtain statistically 

significant results. If the retention rate is poor, and too 

many participants drop out of the study, it may not be 

possible to meet the study objectives, and early 

termination of the study may be warranted (see Text 

Box 2-7 for issues that warrant early termination). 

However, it is anticipated that the study design would 

include contingency planning (for example, related to 

replacement). 

Developing criteria for study elements that may have 

associated ethical concerns as a study progresses will no 

doubt be more difficult than reviewing the measurement 

data. Nonetheless, assuring the ethical safety of the 

participants is critically important. There are no standard 

formulas for dealing with ethical concerns. For example, 

if the privacy of a number of study participants is 

compromised by a technician conducting the 

measurements in their homes, what criteria should be 

used to evaluate the severity of the issues? How many 

landlord-participant problems are too many before the 

study needs to be changed to exclude participants who 

rent their dwellings? Despite the challenges, the team of 

people involved in the data and safety monitoring and 

oversight effort should work diligently, with input from 

the community, to establish open and continuing 

channels of communication with participants, the 

community, and stakeholders – with the goal of ensuring 

that their involvement in the research effort is, and 

31
remains to be, based on the three pillars of informed 

consent: (1) that the parties are fully informed of all of 

the relevant and useful information, (2) that the 

information is understood by the parties, and (3) that all 

parties continue to participate voluntarily. With diligent 

effort to continue an open dialogue with the involved 

parties – combined with thoughtful review and oversight 

of the technical study results and procedures – the 

monitoring and oversight team can ensure that 

participants are free to withdraw from the research at any 

time; are fully informed about the technical study 

results; understand any new information about relevant 

risks and benefits; and that the privacy and 

confidentiality of the subjects is properly protected. 

Through these efforts, the monitoring and oversight team 

will ensure that the welfare of the research subjects 

remains a focus of the study effort. 

References 

Castelloe, JM (2000). Sample size computations and power 

analysis with the SAS system. Paper 265-25 in Proceedings 

of the 25th Annual SAS Users Group International 

Conference. Cary, NC: SAS Institute, Inc. Available: 

http://support.sas.com/rnd/app/papers/powersamplesize.pdf

[accessed 16 April 2008]. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 

Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/

40cfr26_06.html [accessed 12 June 2007]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines 

for Biomedical Research Involving Human Subjects. 

Geneva, Switzerland: CIOMS. Available at 

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed 12 June 2007]. 

Coggon D, Rose G, Barker DJP (1997). Epidemiology for the 

Uninitiated, Fourth Edition. London: BMJ Publishing 

Group Ltd. Available at 

http://www.bmj.com/epidem/epid.html [accessed 29 

January 2008]. 

Cohen Hubal EA, Sheldon LS, Zufall, MJ, Burke JM, Thomas 

KW (2000). The challenge of assessing children’s 

residential exposure to pesticides. Journal of Exposure 

Analysis and Environmental Epidemiology 10(6 part 2): 

638-649. 

Dallal, GE (2001). Some aspects of study design. In The Little 

Handbook of Statistical Practice at 

www.StatisticalPractice.com, and at 

http://www.tufts.edu/~gdallal/STUDY.HTM [accessed 29 

January 2008] 

Emanuel EJ, Wendler D, Grady C (2000). What Makes 

Clinical Research Ethical? JAMA 283(20): 2701-2711. 

Gilbert, SG (2006). Supplementing the traditional institutional 

review board with an environmental health and community 

review board. Environmental Health Perspectives 114(10): 

1626-1629. 

Kraemer HC, Thiemann S (1987). How Many Subjects? 

Statistical Power Analysis in Research. Newbury Park, CA: 

Sage Publications. 

Lenth RV (2001). Some practical guidelines for effective 

sample size determination. American Statistician 55(3): 

187-193. Available: 

http://www.stat.uiowa.edu/techrep/tr303.pdf [accessed 13 

June 2007]. 

NRC (National Research Council) (2003). Protecting 

Participants and Facilitating Social and Behavioral 

Sciences Research. Washington, DC: The National 

Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=10638

[accessed 12 June 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

Text Box 2-7. Examples of Issues That May Cause a 

Study To Be Stopped Early 

• Participant recruiting and enrollment⎯low response rates, 

disproportionate enrollment of select groups, problems 

associated with advertising, inadequate selection criteria 

• Informed consent⎯difficulties with the process and materials, 

poor comprehension 

• Participation⎯poor response to questionnaires, poor 

compliance with researcher requests in data collection 

activities 

• Burden⎯higher than predicted 

• Changes in participant behaviors⎯potential changes because 

of participation in the study 

• Grievances⎯participant issues 

• Retention⎯high dropout rates 

• Community issues⎯poor interactions, lack of support 

• Third-party issues⎯problems with landlords, spouses, or 

others 

• Collateral observations⎯identification of nonstudy hazards, 

difficulty reporting 

• Unanticipated results⎯high contaminant concentrations 

measured, unexpected results

• New data indicating that participation in the study (or 

observations measured in the study) represent a risk to 

participants or others

32
33

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

OHRP (Office for Human Research Protections) (2007). U.S. 

Department of Health and Human Services [Online]. 

Available: http://www.hhs.gov/ohrp/ [accessed 13 June 

2007]. 

Resnik DB, Wing S (2007). Lessons learned from the 

Children's Environmental Exposure Research Study. Am J 

Public Health 97(3): 414-8. 

U.S. DHEW (U.S. Department of Health, Education, and 

Welfare) (1979). The Belmont Report: Ethical Principles 

and Guidelines for the Protection of Human Subjects of 

Research. Washington, D.C.: National Commission for the 

Protection of Human Subjects of Biomedical and 

Behavioral Research. Available: 

http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 

June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (2000). 

Comments on the use of data from the testing of human 

subjects: A report by the Science Advisory Board and the 

FIFRA Scientific Advisory Panel. Environmental Protection 

Agency, Science Advisory Board. EPA-SAB-EC-00-017. 

Available: 

http://www.epa.gov/scipoly/sap/meetings/1999/november/e

c0017.pdf [accessed 16 April 2008]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

12 June 2007]. 

Van Belle G, Fisher L (2004). Biostatistics: A Methodology 

for the Health Sciences (2nd Edition) Hoboken, NJ: John 

Wiley & Sons. 

Wackerly DD, Mendenhall W, Scheaffer RL (2001). 

Mathematical Statistics with Applications (6th Edition). 

Pacific Grove, CA: Duxbury Press.
34
SECTION 3

Ensuring Protection of Vulnerable Groups

Concern for the protection of vulnerable groups is 

fundamental to modern ethical thought and guidelines. 

The Belmont Report was “meant to provide broad 

principles that could be used to generate specific rules 

and regulations in response to [U.S.] research scandals 

such as Tuskegee and Willowbrook.11 It focuses on 

informed consent, favorable risk-benefit ratio, and the 

need to ensure that vulnerable populations are not 

targeted for risky research” [emphasis added] (Emanuel 

et al., 2000). 

The Common Rule requires IRBs to assure that 

“additional safeguards have been included in the study to 

protect the rights and welfare of these [vulnerable] 

subjects” [at 40 CFR 26.111(b) in CFR, 2006a]. If an 

observational human exposure study includes vulnerable 

research participants, it is essential that the investigators 

be cognizant of the special issues and requirements of 

research involving vulnerable populations. Researchers 

have to justify the involvement of vulnerable 

populations in the research study and include the 

appropriate safeguards for protection of their safety and 

welfare. The Common Rule protections are discussed 

further in the IRB guidebook (U.S. HHS, 1993). EPA 

regulations include not only the general protections for 

vulnerable populations found in the Common Rule 

(Subpart A) but also define additional protections for 

children and for pregnant or nursing women (and their 

fetus or nursing child) in Subparts B, C, and D (CFR, 

2006a). 

The section begins by identifying or defining 

vulnerable groups and then discusses ethical issues that 

 

11 For more information about these and other research scandals, see Ethical 

and Policy Issues in Research Involving Human Participants, Vol. I, Report 

and Recommendations of the National Bioethics Advisory Commission, 

Bethesda, MD, August, 2001. See p. 153 for information about the 

Willowbrook State School experiments. The report is available at 

www.bioethics.gov/reports/past_commissions/nbac_human_part.pdf

(Accessed September 3, 2007). 

may be important in conducting observational human 

exposure studies involving those groups, especially 

children and pregnant women. The discussions about the 

ethical issues are based largely on EPA’s human subjects 

regulations and on the recommendations from the 

Council for International Organizations of Medical 

Sciences document, International Ethical Guidelines for 

Biomedical Research Involving Human Subjects

(CIOMS, 2002). 

3.1 Identification of Vulnerable Groups

In the United States, human subjects regulations 

(45 CFR 46 and 40 CFR 26) do not formally define 

vulnerable populations. Instead, the Common Rule gives 

examples of potentially vulnerable groups (see Text Box 

3-1). In addition, HHS extends added human subjects 

protections to pregnant women, human fetuses, 

neonates, prisoners, and children as vulnerable groups 

(45 CFR 46, Subparts B, C, and D, see CFR, 2006b). 

Analogous but somewhat more stringent protections for 

children, pregnant or nursing women, and fetuses are 

specified in Subparts B, C, and D of the EPA Rule (40 

CFR 26). The regulations do not preclude other groups 

from being considered vulnerable, however, and the 

National Institutes of Health (NIH), in its Human 

Participant Protections Education for Research Teams 

online tutorial (NIH, 2002), lists students or employees 

and terminally ill or comatose patients as potentially 

vulnerable groups. 

CIOMS defines vulnerable persons as those who are 

relatively (or absolutely) incapable of protecting their 

own interests. Vulnerability here refers to a substantial 

incapacity to protect one’s own interests owing to such 

impediments as lack of capability to give informed 

consent, lack of alternative means of obtaining medical 

care or other expensive necessities, or being a junior or 

subordinate member of a hierarchical group. Vulnerable 

persons may have insufficient power, intelligence, 

resources, strength, or needed attributes to protect their 

35
own interests (CIOMS, 2002) (see Text Box 3-2). 

Because of their incapacity to protect their own interests, 

ethically perceptive researchers will plan and implement 

special provisions for the protection of the rights and 

welfare of the vulnerable persons. 

Although Federal regulations define vulnerability in 

terms of the person’s ability to protect their own 

interests or particular sensitivity to risks because of 

physical condition, the lay public may perceive a broader 

definition of vulnerability as it relates to education, 

economics, social status, and other factors. As shown in 

Text Boxes 3-1 and 3-2 and described above, the 

concept of vulnerability is broader than that presented in 

the Common Rule. It is not adequate to simply check the 

list in Text Box 3-1 to identify if a potentially vulnerable 

group is included in an observational study. The 

researchers should assess the potential vulnerability of a 

study population within the study by evaluating the 

characteristics (e.g., socioeconomic status) of the study 

population within the context of the study by considering 

the various design elements of the study, as discussed in 

Section 2. 

3.2 Justification for Involving Vulnerable 

Persons in Observational Research 

The Common Rule requires IRBs to ensure that the 

selection of subjects is equitable [40 CFR 26.111(a)(3)] 

and instructs the IRB to consider the “purposes of the 

research and the setting in which the research will be 

conducted.” CIOMS goes further and recommends that 

“Special justification is required for inviting vulnerable 

individuals to serve as research subjects” (CIOMS, 

2002).12 

 

12 In the commentary on Guideline 13 in CIOMS (2002), the committee states 

that the central problem presented by plans to involve vulnerable persons as 

research subjects is that such plans may entail an inequitable distribution of 

the burdens and benefits of research participation. Classes of individuals 

conventionally considered vulnerable are those with limited capacity or 

freedom to consent or to decline to consent. They are the subject of specific 

guidelines in the CIOMS document (Guidelines 14 and 15) and include 

children, and persons who, because of mental or behavioral disorders, are 

incapable of giving informed consent. Ethical justification of their 

involvement usually requires that 

• the research could not be carried out equally well with less vulnerable 

subjects; 

• the research is intended to obtain knowledge that will lead to improved 

diagnosis, prevention, or treatment of diseases or other health problems 

characteristic of, or unique to, the vulnerable class—either the actual 

subjects or other similarly situated members of the vulnerable class; 

• research subjects and other members of the vulnerable class from which 

subjects are recruited will ordinarily be assured reasonable access to any 

diagnostic, preventive, or therapeutic products that will become available 

as a consequence of the research; 

• the risks attached to interventions or procedures that do not hold out the 

prospect of direct health-related benefit will not exceed those associated 

Text Box 3-1. Potentially Vulnerable Groups 

Identified in U.S. Regulations 

Common Rule: 

Examples of vulnerable 

groups 

(40 CFR 26) 

• Children 

• Pregnant women (and their 

fetuses) 

• Nursing women (and their 

neonates) 

• Prisoners 

• Handicapped persons 

• Mentally disabled persons 

• Economically disadvantaged 

persons 

• Educationally disadvantaged 

persons 

EPA extends stringent 

protections to these 

groups 

(40 CFR 26) 

• Children 

• Pregnant women (and their 

fetuses) 

• Nursing women (and their 

neonates 

HHS extends additional 

protections to these 

groups 

(45 CFR 46) 

• Children 

• Pregnant women and fetuses 

• Nursing women and neonates 

• Prisoners 

Additional vulnerable 

groups in NIH training 

materials 

• The terminally ill 

• Students and employees 

• Comatose patients 

Text Box 3-2. Potentially Vulnerable Groups 

Identified in International Guidance 

(Council for International Organizations of 

Medical Sciences, 2002)

• Junior or subordinate members of a hierarchical group; 

examples include employees, students, members of the armed 

forces, police, and others who work for, or closely with researchers; they may have expectations of preferential 

treatment if they agree to participate or fear of disapproval or 

retaliation if they refuse to participate in a study. 

• Elderly persons, who may acquire attributes that define them 

as vulnerable with advancing age. 

• Residents of nursing homes. 

• People receiving welfare benefits or social assistance. 

• People with low or no incomes (poor and unemployed). 

• Homeless persons. 

• Nomads. 

• Refugees or displaced persons. 

• Some ethnic and racial minority groups. 

• People with incurable diseases (in clinical studies). 

• The politically powerless. 

• Members of communities unfamiliar with modern medical 

concepts (applies to clinical studies) 

36
CIOMS recommendations, although written to 

address biomedical research, also generally are 

applicable to observational human exposure studies. The 

authors of this document consider the CIOMS 

requirement that the research could not be carried out 

equally well with less vulnerable subjects to be 

particularly important. EPA and NERL researchers 

should include vulnerable groups in observational 

human exposure studies only if their participation is 

critical to the success and applicability of the research. 

Even then, EPA and NERL researchers will have to meet 

stringent standards for protecting the rights and safety of 

the vulnerable participants. For example, EPA 

regulations governing observational research with 

children are even more stringent than the CIOMS 

guideline. If such research does not hold out the prospect 

of direct benefit to the child, no increase whatsoever 

over minimal risk is permitted. 

However, many observational human exposure 

studies are developed specifically to study the exposures 

of selected vulnerable groups to chemicals and other 

environmental stressors in everyday environments. So, 

researchers should be prepared to address the issues 

associated with vulnerable groups in observational 

research. Furthermore, as discussed in Section 3.4, there 

has been increased concern in recent years that exclusion 

of vulnerable groups from research studies is not ethical. 

Failure to conduct research with vulnerable groups may 

deprive them of the benefits of research. NIH, for 

example, has a policy (NIH, 1998) with a goal of 

increasing participation of children in research. 

3.3 Minimal Risk and Vulnerable Groups 

EPA has codified protections for children, pregnant 

or nursing women, and fetuses in Subparts B, C, and D 

of the EPA human subjects rule (40 CFR 26). Subpart B 

strictly prohibits research involving intentional exposure 

of children or pregnant or nursing women (and, 

therefore, exposure of her fetus). 

EPA’s regulations do allow for observational 

research involving fetuses and pregnant women (40 CFR 

26 Subpart C) or children (40 CFR 26 Subpart D) but 

with additional protections in place and with strict 

limitations on research that presents more than minimal 

 

 with routine medical or psychological examination of such persons unless 

an ethical review committee authorizes a slight increase over this level of 

risk (Guideline 9); and, 

• when the prospective subjects are either incompetent or otherwise 

substantially unable to give informed consent, their agreement will be 

supplemented by the permission of their legal guardians or other 

appropriate representatives. 

risk (CFR, 2006a).13 When considering vulnerable 

groups, The Institutional Review Board Guidebook (U.S. 

HHS, 1993) states that “IRBs should therefore determine 

whether the proposed subject population would be more 

sensitive or vulnerable to the risks posed by the research 

as a result of their general condition or disabilities. If so, 

the procedures would constitute more than minimal risk 

for those subjects.” 

When conducting observational human exposure 

studies, it is recommended that researchers consult these 

regulations and guidebooks. NERL researchers also will 

need to ensure that all of the requirements in Subparts B, 

C, and D of the EPA Human Subjects Rule are met. 

3.4 Research Involving Children 

Children long have been recognized as a vulnerable 

group in research studies. EPA and HHS both extend 

special protections to children (CFR, 2006a,b). There are 

many books, reports, and research manuscripts that 

specifically address issues associated with research 

involving children (e.g., NRC & IOM, 2005; IOM, 

2004; Kodish, 2005; NRC, 2003; AAP, 2003). 

CIOMS has drafted guidelines for including children 

in biomedical research (Guideline 14, CIOMS, 2002). 

The guidelines require an investigator to provide the 

assurances shown in Text Box 3-3 before undertaking 

research involving children. 

The participation of children in some observational 

human exposure studies is critical to characterizing 

children’s exposures to chemicals in the environment. It 

is well recognized that children are not “little adults,” 

and that their exposures to chemicals differ (and, in 

13 Minimal risk is defined at 40 CFR 26.102(i) and again at 40 CFR 

26.402(g). It “means that the probability and magnitude of harm or discomfort 

anticipated in the research are not greater in and of themselves than those 

ordinarily encountered in daily life or during the performance of routine 

physical or psychological examinations or tests.” 

Text Box 3-3. Assurances Required by CIOMS Before 

Research Involving Children May Begin 

• the research might not equally well be carried out with adults; 

• the purpose of the research is to obtain knowledge relevant to 

the health needs of children; 

• a parent or legal representative of each child has given 

permission; 

• the agreement (assent) of each child has been obtained to the 

extent of the child’s capabilities; and 

• a child’s refusal to participate or continue in the research will be 

respected.

37
some cases, are higher) from those of adults. Children 

are behaviorally and physiologically different from 

adults. Their interaction with their environment, through 

activities such as playing on floors, mouthing of hands 

and objects, and handling of food, may increase contact 

with contaminated surfaces. Children have 

proportionately higher breathing rates, relative surface 

area, and food intake requirements that also may 

increase exposure. Differences in absorption, 

metabolism, storage, and excretion may result in higher 

biologically effective doses to target tissues. Immature 

organ systems may be more susceptible to toxicological 

challenges. Windows of vulnerability, when specific 

toxicants may permanently alter the function of an organ 

system, are thought to exist at various stages of 

development. Because the factors influencing children’s 

exposures to chemicals are not characterized well 

(Cohen Hubal et al., 2000), it is sometimes important 

that observational human exposure studies involve 

children. 

Because children are so vulnerable, there long has 

been concern about including them in research studies, 

and biomedical research often excluded children. 

However, in recent years, there has been concern that 

excluding children from research is not ethical. NIH’s 

Policy and Guidelines on the Inclusion of Children as 

Participants in Research Involving Human Subjects

(NIH, 1998) has a goal of increasing participation of 

children in research. The policy of NIH is that children 

must be included in all human subjects research 

conducted or supported by NIH, unless there are 

scientific and ethical reasons not to include them. 

Proposals or applications to NIH for research have to 

present an acceptable justification if children will be 

excluded from a research study. Of course, as discussed 

above, if the research topic is irrelevant to children, the 

CIOMS guidelines would recommend that they be 

excluded from the research. 

Observational human exposure studies conducted by 

NERL are not expected to involve greater than minimal 

risk. It will be the responsibility of the NERL 

researchers to present adequate information for the IRB 

to demonstrate that the research does not involve greater 

than minimal risk. Researchers designing observational 

research studies should carefully evaluate the risks and 

benefits specific to their study and the participants 

involved. In developing the study design and human 

subjects protocols, researchers need to ensure that the 

protocols ensure the protection of the rights and welfare 

of the participant children, and that risks and harm are 

minimized. The perception of risks and benefits, both by 

the individual and by the family or community, may 

influence the risk-benefit determination. It may prove 

useful for the research team to consult with other 

experienced researchers who have conducted similar 

studies and with members of the IRB to ensure that the 

information included in the human subjects research 

protocol is adequate for the IRB’s review. 

It is recommended that researchers consider all of 

the potential issues associated with involvement of 

children in their studies in developing the study design 

and research protocols, including the role of the family. 

EPA’s human subjects rule for observational research 

not involving greater than minimal risk to children (40 

CFR 26.404) (i.e., the kinds of observational human 

exposure studies that NERL exposure research is likely 

to entail) focuses on obtaining assent of the children and 

permission of their parents or guardians. But the role of 

the family goes far beyond their involvement in the 

informed consent process. In observational human 

exposure studies, even when children are the 

participants, the parents or guardian play a key role in 

the collection of data and information during the study. 

For studies with very young children, family members 

supply all of the information relevant to the child. NERL 

researchers need to ensure that both the child and the 

parents or guardians and other caregivers are informed 

fully and are willing participants. Without their willing 

participation, the research cannot be successful. 

3.5 Women as Research Subjects 

Women are routinely included as research 

participants in observational human exposure studies. 

However, pregnant women and their fetuses are 

vulnerable groups and require special protections. EPA’s 

human subjects rule prohibits intentional dosing studies 

and provides additional controls for observational 

research (40 CFR 26, Subparts B and C). 

CIOMS (2002) includes two guidelines for 

biomedical research involving women as research 

subjects. The first of these, number 16, states that 

women should not be excluded from biomedical 

research because of the potential for becoming pregnant 

during a study. The document continues, “A general 

policy of excluding from such clinical trials women 

biologically capable of becoming pregnant is unjust in 

that it deprives women as a class of persons of the 

benefits of new knowledge derived from the trials.” The 

second relevant CIOMS guideline, number 17, asserts 

that, if involved in a research study, pregnant women 

should be fully informed, and included only if the 

38
research benefits pregnant women and is thoroughly 

supported by reliable evidence in animal studies. 

Although the CIOMS guideline specifically 

addresses biomedical research, the ethical concepts 

behind the guidelines generally may be applicable to 

observational human exposure studies. EPA’s human 

subjects rule is completely consistent with the HHS rule 

in adding additional protections for pregnant women and 

fetuses involved in observational research (40 CFR 

26.304 and 45 CFR 46.204). These additional 

protections (specified in 45 CFR 46.204 subparagraphs a

through j) reflect the CIOMS recommendations by 

requiring: availability of data from previously conducted 

studies to assess the risk to pregnant women and fetuses; 

scientific necessity for inclusion of pregnant women and 

fetuses (i.e., providing benefit to the woman or fetus, or 

producing important, but otherwise unobtainable, 

biomedical knowledge); that risk is reduced to the least 

possible level for achieving the objectives of the 

research; and other protections. 

3.6 Other Potentially Vulnerable Groups 

HHS specifies additional protections for prisoners as 

a potentially vulnerable group in Subpart C of 45 CFR 

26. Additional requirements for other vulnerable groups 

in research studies are not specifically defined in either 

EPA’s or HHS’ human subjects rules. Nonetheless, other 

groups (as discussed in Section 3.1) may be considered 

to be vulnerable and, as such, may warrant additional 

consideration and protection as required in the Common 

Rule. For these other potentially vulnerable groups, such 

as employees, students, handicapped persons, mentally 

disabled persons, and economically or educationally 

disadvantaged persons, nursing home residents or 

otherwise incapacitated elderly, etc., the Common Rule 

requires researchers and IRBs to fully evaluate the 

protocols to ensure that the safety and welfare of the 

groups will be protected. As discussed in Section 3.1, It 

also should be noted that, although Federal regulations 

define vulnerability in terms of the ability to protect 

one’s own interests, the lay public may perceive a 

broader definition of vulnerability as it relates to 

education, economics, social status, and other factors. 

The researcher should evaluate vulnerability in this 

broader context to ensure that adequate safeguards are 

included for potentially vulnerable populations that do 

not meet the definition of the Federal regulations. 

References 

AAP (American Academy of Pediatrics) (2003). Pediatric 

Environmental Health. (2nd Edition). Elk Grove Village, IL: 

American Academy of Pediatrics. 

CFR (Code of Federal Regulations) (2006a). 40 CFR Chapter 

I Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: 

http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.

html [accessed 12 June 2007]. 

CFR (Code of Federal Regulations) (2006b). 45 CFR Subtitle 

A Department of Health and Human Services Part 46 

Protection of Human Subjects. U.S. Code of Federal 

Regulations. Available: 

http://www.access.gpo.gov/nara/cfr/waisidx_06/45cfr46_06.ht

ml [accessed 13 June 2007]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines 

for Biomedical Research Involving Human Subjects. 

Geneva, Switzerland: CIOMS. Available at 

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed 12 June 2007]. 

Cohen Hubal EA, Sheldon LS, Burke JM, McCurdy TR, Berry 

MR, Rigas ML, Zartarian VG, Freeman NCG (2000). 

Children’s exposure assessment: a review of factors 

influencing children’s exposure, and the data available to 

characterize and assess that exposure. Environ Health 

Perspect 108(6): 475-486. 

Emanuel EJ, Wendler D, Grady C (2000). What makes 

clinical research ethical? JAMA 283(20): 2701-2711. 

IOM (Institute of Medicine) (2004). Ethical Conduct of 

Clinical Research Involving Children. Washington, DC: 

The National Academies Press. Available: 

http://www.nap.edu/catalog.php?record_id=10958 [accessed 

16 April 2008]. 

Kodish E (Ed.) (2005). Ethics and Research with Children: A 

Case-Based Approach. New York: Oxford University Press. 

NBAC (National Bioethics Advisory Commission) (2001). 

Ethical and Policy Issues in Research Involving Human 

Participants, Volume I: Report and Recommendations of the 

National Bioethics Advisory Commission. Bethesda, MD: 

National Bioethics Advisory Commission. Available: 

http://www.bioethics.gov/reports/past_commissions/nbac_h

uman_part.pdf [accessed 3 September 2007]. 

39
40

NIH (National Institutes of Health) (2002) Human Participant 

Protections Education for Research Teams [online tutorial]. 

NIH (National Institutes of Health) (1998). NIH Policy and 

Guidelines on The Inclusion of Children as Participants in 

Research Involving Human Subjects. Available: 

http://grants.nih.gov/grants/guide/notice-files/not98-

024.html [accessed 13 June 2007]. 

NRC (National Research Council) (2003). Protecting 

Participants and Facilitating Social and Behavioral 

Sciences Research. Washington, DC: The National 

Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=10638

[accessed 12 June 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

12 June 2007]. 
SECTION 4

Privacy, Confidentiality, and Other Concerns Related 

to Observational Human Exposure Studies 

Observational human exposure studies are designed 

to describe people’s contact with pollutants as they go 

about their everyday lives. Of necessity then, these 

studies take place in the locations that participants often 

consider to be personal and private. Clinical research 

studies generally are conducted in a research facility, a 

clinic, a hospital, or some other institutional or medical 

setting. Survey research may be conducted by mail, over 

the phone, or in another “neutral” setting. But, 

observational human exposure studies are conducted in 

the participants’ “personal” environment⎯their home, 

daycare center, school, vehicle, workplace, or other 

environments that people occupy during their routine 

daily activities. This difference in the research setting 

means that researchers involved in observational human 

exposure studies have an even greater challenge in 

meeting the ethical obligation to respect the privacy of 

the participants. 

When exposure science researchers like those at 

NERL enter a home to carry out their studies, the 

“expectations and constraints may be strikingly different 

than when research is carried out in a medical setting” 

(p. 64, NRC & IOM, 2005). The legal precept of 

freedom from unreasonable search and seizure and the 

historic and deeply rooted principle that “a man’s home 

is his castle” contribute to a belief in the “sanctity of the 

home” (see the discussion on pp. 62-66, NRC & IOM, 

2005). 

The joint NRC and IOM report Ethical 

Considerations for Research on Housing-Related Health 

Hazards Involving Children discusses the ethical issues 

associated with entering a participant’s home to conduct 

research and explores the researchers’ responsibilities 

that derive from conducting research in people’s homes 

(NRC & IOM, 2005). These housing-related discussions 

are particularly relevant to observational human 

exposure studies, which often include environmental and 

biological measurements in people’s homes or personal 

locations. Many of the topics identified in that report are 

discussed in this section (Text Box 4-1). 

4.1 Privacy Issues

Privacy refers to an expectation that a person is free 

from intrusion into personal matters and is free from the 

presence or view of others. The Institutional Review 

Board Guidebook defines privacy as “control over the 

extent, timing, and circumstances of sharing oneself 

(physically, behaviorally, or intellectually) with others” 

(U.S. HHS, 1993). Beauchamp and Childress find that 

the right to privacy is based on the principle of respect 

for autonomy. “We often respect persons by respecting 

their autonomous wishes not to be observed, touched, or 

intruded upon.... A loss of privacy occurs if others use 

any of several forms of access, including intervening in 

zones of secrecy, anonymity, seclusion, or solitude” (pp. 

295-296, Beauchamp and Childress, 2001). 

Text Box 4-1. Topics in Section 4 

Privacy Issues 

Confidentiality 

 Confidentiality of Information 

 Confidentiality of Participation 

Collateral Observations 

 Potential Nonstudy Hazards in the Residence 

 Collateral Observations with Mandated Reporting 

Requirements 

 Hazard Communication 

 Planning and Staff Training 

Third-Party Issues 

 Determining Whether a Third Party is a Human Subject 

 Informing Third Parties of Research Activities 

 Research Results and Third Parties 

Data and Safety Monitoring and Oversight

41
Although research participants may agree to allow 

researchers to enter their home or other zone of personal 

space to conduct their research measurements, they have 

not abrogated their right to privacy. “When individuals 

voluntarily grant others some form of access to 

themselves, their act is an exercise of the right to 

privacy, not a waiver of that right” (p. 297, Beauchamp 

and Childress, 2001). Researchers should remember that 

they are guests in the homes for a specific purpose. 

“When people visit a home, there are social expectations 

about what is acceptable behavior. People who are 

invited into a home are expected to be sensitive to and 

respectful of the host’s customs and values” (p. 65, NRC 

& IOM, 2005). 

By their very nature, observational human exposure 

studies encroach on the privacy of a research participant. 

Entry in a participant’s home (or other personal zones) 

does represent a loss of privacy, but researchers should 

be careful to ensure that their presence does not become 

a violation of the individual’s right to privacy. The 

relationship between the researcher and the participant 

may be complicated, and there may be conflicts between 

the researcher’s role and their ethical obligations (NRC 

& IOM, 2005). In entering a participant’s personal 

space, it may be difficult, or impossible, to avoid making 

observations unrelated to the research question, thereby 

further intruding on the participant’s personal privacy. 

Indeed, there may be ethical and legal obligations for the 

researchers to respond to those observations. Beauchamp 

and Childress suggest that “policies carefully specify the 

conditions of access that will and will not count as a loss 

of privacy or a violation of the right to privacy. The 

policy should accurately define the zones that are 

considered private and not to be invaded, and should 

also identify interests that legitimately may be balanced 

against privacy interests” (Beauchamp and Childress, 

2001). 

Observational human exposure studies also may 

infringe on the privacy of other individuals, for example, 

other members of the participant’s family or household. 

Researchers should strive to minimize the intrusion and 

loss of privacy and to show respect for the privacy of 

study participants and third parties at all times (see Text 

Box 4-2 for a list of relevant privacy issues). It is 

incumbent on the researcher to recognize privacy issues 

in the design and implementation of the research study. 

The NRC & IOM report suggests that researchers 

anticipate the ethical issues that arise from conducting 

research in a person’s home, and that they take steps to 

correct them (1) by thinking through the issues as part of 

the study design; (2) by discussing the issues during the 

informed consent process; and (3) by ensuring that the 

frontline staff that enter a participant’s home 

“understand their role as members of the research team, 

how that role differs from the role of neighbor or friend, 

and how they should respond when they make 

observations that are not part of the protocol” (p. 66, 

NRC & IOM, 2005). 

4.2 Confidentiality 

Confidentiality and privacy are not the same thing. 

Confidentiality refers to limits on the dissemination of 

information disclosed by a person in a special 

professional relationship, such as the doctor-patient 

relationship or the participant-researcher relationship 

(Beauchamp and Childress, 2001). The Institutional 

Review Board Guidebook defines confidentiality as 

“pertains to the treatment of information that an 

individual has disclosed in a relationship of trust and 

with the expectation that it will not be divulged to others 

without permission in ways that are inconsistent with the 

understanding of the original disclosure” (U.S. HHS, 

1993). Emanuel et al. (2000) state that one way to 

respect the privacy of the participants is “by managing 

the information in accordance with confidentiality 

Text Box 4-2. Privacy Issues 

• Researchers should develop an anticipatory plan for how to 

deal with privacy issues during the study. The plan should 

include a list of potential observations that could be of concern 

and a plan for how they will be handled. 

• The plan needs to address both the legal and ethical 

obligations of the researcher in response to situations where 

privacy is compromised. 

• Privacy issues will vary depending on the culture of the 

population being studied. What one individual or group may 

find as an invasion of privacy, another group may not have a 

concern about. 

• Privacy issues involve individual participants and may extend 

to third parties, including the community. 

• Researchers may find a meeting with community 

representatives to learn about the community residents and 

potential privacy issues to be helpful. Community 

representatives can help the researcher identify potential 

privacy issues and offer advice on how to address them. 

• Researchers may wish to respect the privacy of occupants 

sharing the study participant’s household or other study 

locations by providing advance notification of study visits and 

by giving them the opportunity not to be present during those 

visits. 

• Field staff should be trained on how to minimize breaches of 

privacy and how to handle privacy issues. 

• The informed consent process and form should address how 

the researcher will handle privacy issues such as collateral 

observations of household hazards 

42
rules.” Confidentiality in research also may extend to 

limiting dissemination of the knowledge that an 

individual is participating in a research study. 

As part of the research planning process, researchers 

are responsible for developing procedures to protect 

confidentiality and to define limits on the researcher’s 

ability to provide or protect confidentiality. Explaining 

plans or procedures for protecting confidentiality and 

their limits14 to prospective research participants is an 

integral part of the informed consent process. 

4.2.1 Confidentiality of Information

Many types of information may be collected in 

observational human exposure studies. Information may 

be collected through questionnaires, staff observations of 

residential or other environments, diaries, personal 

sample collection, environmental or residential sample 

collection, and collection of biological specimens. 

Measurement data from the collected samples become 

part of the information for a participant. The specific 

information to be obtained to address the research 

questions should be determined in the development of 

the study design and research protocol. 

Disclosure of information that can be linked to an 

individual may cause harm or distress to that individual. 

Researchers are responsible for developing safeguards to 

protect the confidentiality of information and physical 

samples collected from research participants (see, for 

example, Guideline 18, CIOMS, 2002). 15

Researchers also should be aware that certain 

combinations of information from a study may 

sometimes lead to the indirect identification of the 

individual. Certain combinations of demographic 

information, for example, may make it relatively simple 

 

14 Beauchamp and Childress (2001) discuss when one may be ethically 

justified in infringing on an individual’s privacy and confidentiality⎯for 

example, because of risks to others evidenced by biomarkers of infectious 

disease. They also discuss similar ethical issues that may arise in regard to 

genetic data. CIOMS (2002) Guideline 18 provides suggestions for 

safeguarding or disclosing genetic information. If exposure scientists 

collaborate with medical researchers or epidemiologists and obtain such 

information, they need to be cognizant of the relevant ethical issues and of the 

CIOMS guidelines. 

15 Guideline 18 states, “The investigator must establish secure safeguards of 

the confidentiality of subjects’ research data. Subjects should be told the 

limits, legal or other, to the investigators’ ability to safeguard confidentiality 

and the possible consequences of breaches of confidentiality.” Additional 

CIOMS commentary on the confidentiality guideline states, “Prospective 

subjects should be informed of limits to the ability of researchers to ensure 

strict confidentiality and of the foreseeable adverse social consequences of 

breaches of confidentiality. Some jurisdictions require the reporting to 

appropriate agencies of, for instance, certain communicable diseases or 

evidence of child abuse or neglect. . . . These and similar limits to the ability 

to maintain confidentiality should be anticipated and disclosed to prospective 

subjects.” 

to identify an individual. Precise geographic location 

information may be sufficient to pinpoint a residence. 

Researchers may use several strategies to reduce the 

likelihood of indirect identification when study results 

are reported (see, also, Text Box 4-3). 

• Redact from publications, reports, or public data sets 

information that might be used to indirectly identify a 

research participant. 

• Generalize exact information; for example, replace 

birth date with age or year of birth or classify age as 

part of a range. 

• Aggregate information across individuals; for 

example, only report data in cells of sufficient size to 

make individual linkages unlikely. 

• Reduce the specificity of geographic coordinate 

information to a level that a specific residence or other 

location can not be identified. 

 Another step that can help protect confidentiality is 

to obtain a Certificate of Confidentiality. Certificates of 

Confidentiality are issued by NIH (2002) to protect 

identifiable research information from forced disclosure. 

They allow the investigator and others who have access 

to research records to refuse to disclose identifying 

information on research participants in any civil, 

criminal, administrative, legislative, or other proceeding, 

whether at the Federal, State, or local level. Certificates 

of Confidentiality may be granted for studies collecting 

information that, if disclosed, could have adverse 

consequences for subjects or damage their financial 

standing, employability, insurability, or reputation. By 

protecting researchers and institutions from being 

Text Box 4-3. Approaches for Protecting 

Personally Identifiable Information 

• Developing procedures for safeguarding information prior to 

collecting the information 

• Ensuring that data or samples are anonymous by not 

collecting or by destroying identifying information or linkages 

• Restricting access to identifying information to only those 

requiring access 

• Assigning codes to participants, data, and samples rather than 

using identifiers 

• Physically separating identifying information and linkage files 

from other study information 

• Securing identifying information in locked files with limited 

access 

• Restricting identifying information from computers that are 

networked with other computers or electronic systems 

• Restricting identifying information from computers that are not 

kept in secure locations with limited access 

• Training research staff members on human subject protection 

and on information security procedures 

43
compelled to disclose information that would identify 

research subjects, Certificates of Confidentiality help 

achieve the research objectives and promote 

participation in studies by assuring confidentiality and 

privacy to participants. Any research project that collects 

sensitive, personally identifiable information and that 

has been approved by an IRB is eligible for a certificate. 

Identifying information is broadly defined as any item or 

combination of items in the research data that could lead 

directly or indirectly to the identification of a research 

subject. 

Federal funding is not a prerequisite for a certificate. 

A Certificate of Confidentiality does not diminish, 

however, the investigator’s need to protect the 

personally identifiable information as described above. 

4.2.2 Confidentiality of Participation

In some types of research, the knowledge that a 

person is participating in a particular research study 

could, potentially, put the participant at risk for harm or 

distress. This topic is discussed in The Institutional 

Review Board Guidebook, with special emphasis on 

behavioral and social research that deals with sensitive 

topics (U.S. HHS, 1993). The guidebook describes the 

need for additional safeguards to protect and prevent 

disclosure of the identity of participants, including the 

use of Certificates of Confidentiality for sensitive 

matters. 

Observational human exposure studies often pose 

particular challenges with regard to limiting 

dissemination of the knowledge of an individual’s 

participation in the study. Visiting the research 

participant’s residence to collect samples or to make 

observations will necessitate informing other family 

members or occupants about the visit and study 

procedures. Research participants may be asked to wear 

personal monitors over time periods ranging from a day 

to a week or more. Wearing these devices in public 

places, schools, or workplaces may identify them as a 

study participant or generate questions regarding the 

activity. Field staff visits to the participant’s home or 

setting up outdoor sample collection devices around the 

home also might disclose their participation. And, in 

some cases, third parties outside of the home have to be 

asked for permission or be informed that monitoring 

activities are taking place. 

Researchers and IRBs should consider whether 

knowledge of an individual’s participation by others 

might create potential for harm or distress in an 

observational human exposure study. Such risks might 

be limited to possible discomfort in attracting unwanted 

attention; this may be particularly true for adolescents. 

However, in some cases, the potential risks could be 

greater, for example, in cases where participation could 

provoke an adverse reaction from a landlord or 

employer. Oftentimes study protocols can be structured 

to minimize these potential risks. Through the informed 

consent process, prospective participants should be made 

aware of the limits of the researcher’s ability to protect 

knowledge of their participation in the study and of the 

possible risks of disclosure. 

4.3 Collateral Observations 

In the course of conducting an observational human 

exposure study, research staff may observe potentially 

unsafe conditions or situations that are unrelated to the 

research study. Such “collateral observations” may 

involve physical hazards in the study participant’s 

residential environment or evidence of situations, such 

as child abuse, that have to be reported to proper 

authorities. In preparing for the research study, it is 

recommended that researchers carefully plan for possible 

collateral observations, including their identification, 

staff training, and hazard communication and reporting. 

This may be a major element in the data and safety 

monitoring and oversight for the study. The informed 

consent process should reflect procedures used to 

manage collateral observations. Potential participants 

should be informed of situations in which confidentiality 

might be breached, such as statutory requirements for 

reporting abuse or imminent harm to self or others. 

4.3.1 Potential Nonstudy Hazards in the 

Residence 

Research staff conducting observational human 

exposure studies often will spend time in and around 

study participant residences. In the course of visiting a 

residence or conducting study-related observations, 

research staff may observe potential hazards unrelated to 

the research being performed (see Text Box 4-4). Some 

hazards may be associated with the potential for physical 

injury, whereas others may be related to exposure to 

chemical or biological agents. Some situations may be 

potential hazards only for young children, whereas other 

conditions may present potential hazards for all residents 

or occupants. 

The NRC & IOM recommend that researchers 

should consider such foreseeable observations and 

potential hazards in advance, develop responses to the 

risks, and submit the proposed plans to the IRB for 

review to ensure that they are appropriate “in the context 

of the research and the affected community.” The NRC 

44
& IOM also advise that field staff should be trained in 

how to assess and respond to such risks 

(Recommendations 7.3 and 7.4, NRC & IOM, 2005). 

For other behaviors and risks that have not been 

specifically identified in advance, procedures should be 

included in the data and safety monitoring and oversight 

provisions of the study design and research protocol to 

address these issues. The fundamental ethical principle 

of beneficence would motivate researchers who observe 

serious harms to take steps to try to prevent those harms, 

even for observations that are not directly related to the 

study. The steps that they may take can range from 

immediate action to prevent an imminent and serious 

danger to statutory reporting of observations (see 

Section 4.3.2) to reporting the observation to the data 

and safety monitoring and oversight authority for advice 

on how to respond (see Section 4.5). (The reader is also 

referred to pages 59-61 and 134-144 of the NRC & IOM 

[2005] report for a more thorough discussion of 

researchers’ responsibilities in such cases.) 

4.3.2 Collateral Observations with 

Mandated Reporting Requirements 

Some collateral observations may have statutory 

requirements for reporting to designated authorities. 

Examples of such observations include 

• observed child or elder abuse or evidence of such 

abuse or neglect, 

• statements or actions of intent to harm self or others, 

and 

• certain communicable diseases. 

Because different reporting statutes pertain in 

different states, it is necessary for researchers to learn 

and understand the applicable reporting requirements for 

the study location. In the case of abuse, it is also 

important to understand what actions or situations are 

considered abusive in a particular state. Although direct 

physical harm or violence might be obvious to a research 

staff member, there are other conditions of neglect that 

might be more difficult to recognize or to know when to 

report. 

Study participants should be made aware of statutory 

requirements for reporting collateral observations as part 

of the informed consent process. Researchers should 

include the reporting requirements in the informed 

consent form (discussed in Section 5) and should ensure 

that the study participant fully comprehends this 

information and the impact on their privacy and 

confidentiality. 

4.3.3 Hazard Communication 

It is difficult for researchers to determine when and 

how to communicate with study participants or third 

parties about collateral observations related to potential 

hazards. A hazard might present such an imminent threat 

to health or safety that staff would need to communicate 

immediately with the participant or take action to 

mitigate the threat. In some cases, such as instances of 

abuse with attendant statutory reporting requirements, it 

may be necessary to breach confidentiality. More often, 

however, a potential hazard identified as a result of 

collateral observation may not be an imminent threat or 

pose a potential risk that is situation dependent or is 

related to third parties. A number of considerations in 

hazard communication come into play regarding 

confidentiality, privacy, the ability of the researcher to 

provide accurate and effective information regarding the 

hazard and hazard mitigation, and the ability of the study 

participant or others to effectively mitigate the hazard 

without unintended adverse consequences. The National 

Academy of Sciences Committee on Ethical Issues in 

Housing-Related Health Hazard Research Involving 

Children, Youth, and Families discussed many of these 

issues in depth (NRC & IOM, 2005). 

Different communities, cultures, or demographic 

groups can have different risk perceptions, which may 

affect how collateral observations are assessed and 

reported from one study location to the next. The AAP 

Committee on Environmental Health has prepared 

information regarding perception, identification, and 

communication of environmental health risks (AAP, 

2003). Researchers likely will benefit from including 

community members on the research team in developing 

the study design and research protocol or from 

consultation with community boards regarding 

identification of hazards and hazard communication. 

Text Box 4-4. Potential Hazards that Might Be 

Encountered in a Residential Environment 

• Unsecured firearm 

• Uncovered electrical outlets 

• Unprotected stairways 

• Missing child-protective cabinet latches 

• Lack of window guards 

• Missing or inoperable smoke alarm 

• Housing code violations 

• Chipping or flaking paint—potential for lead exposure in older 

homes 

• Malfunctioning or unvented combustion appliances—potential 

for carbon monoxide exposure 

• Unsecured poisons or other dangerous products 

• Excessive mold growth 

45
It is important that any advice that the researcher 

might provide to study participants regarding hazard 

mitigation should be carefully considered. 

Considerations in recommending an action may include 

whether the mitigation approach has been shown to be 

effective, whether the study participant can understand 

and effectively implement the action, and whether 

unintended adverse consequences might result from 

taking an action. In some cases, it may be reasonable to 

refer the participant to another organization that can 

provide expert advice or assistance. 

4.3.4 Planning and Staff Training 

As part of the study planning process and protocol 

development, it is important that researchers be 

cognizant of the kinds of collateral observations that 

might occur in the implementation of the study protocol 

and to develop plans as to how such observations would 

be handled. Researchers may choose to include a 

systematic approach in hazard identification, such as 

using a home-hazard checklist that becomes an ancillary 

part of the study protocol. Alternatively, collateral 

observations could be handled on a case-by-case basis. 

Staff experience and training is a critical 

consideration for managing collateral observations. Staff 

members that visit study participant residences may not 

have expertise or experience in identifying many of the 

potential hazards without adequate training. All staff 

involved in a study, particularly those responsible for 

field data collection, should be trained on identification 

and reporting of collateral observations. This training 

should be study specific and likely will include, but not 

be limited to 

(1) identification of actions (e.g., child abuse) that have 

(state-specific) statutory reporting requirements, 

(2) conditions of neglect that may adversely impact 

study participants or third parties, 

(3) environmental hazards and situations that may be 

associated with imminent harm (e.g., combustible 

materials near an open flame, unsecured firearms 

accessible to very young children), 

(4) policies and procedures for reporting or intervention 

by members of the research team, and 

(5) local and state reporting requirements. 

It is advisable that this training be developed in 

consultation with community representatives who can 

provide input on potential hazards and situations that 

may be encountered in the study community, local 

norms and attitudes about potential interventions and 

reporting, and local agencies available to assist on these 

types of issues. It is also especially important to consider 

staff experience and training in hazard communication. 

Consistency in communication is very important, and 

researchers may decide to use materials prepared by 

other organizations that have expertise regarding a 

particular hazard. 

Another important element of planning for field data 

collection and training of research staff is on hazards and 

situations that the field staff may encounter during their 

field work. Although the previous discussion highlights 

the need to be prepared to report potentially negligent or 

illegal behaviors, these same behaviors may place the 

research staff in imminent danger during the conduct of 

their work in residences and communities. The research 

team should develop a plan for identifying potential 

situations, hazards, and dangers that may place the 

research team at risk of imminent harm. This should 

generally involve working with community 

representatives to identify the hazards and situations that 

may be of concern. For example, a researcher’s 

observation of illegal drugs in a study residence may 

place the researcher in potential danger. Similarly, if 

studies are conducted in areas with high crime rates, 

researchers need to be aware of the potential dangers and 

have a plan for addressing them. In some cases, 

situations may arise because of to inadvertent actions. 

For example, if an area has a high rate of daytime breakins, the presence of researchers in the area may trigger 

calls to local authorities when the researchers, who are 

strangers, are observed in the neighborhood. Feedback 

from the community representatives should be solicited 

when developing a plan for responding to situations such 

as these. Comprehensive training should be developed 

for research field staff to assist them in identifying 

potentially dangerous situations and in responding to 

such situations. 

4.4 Third-Party Issues 

 Third-party issues can arise in observational human 

exposure studies in two ways. First, the study may 

collect limited information about or related to 

individuals other than the study participants. Second, 

study activities may affect or involve people or 

organizations other than the study participants. 

Examples of activities that may involve or affect 

third parties in observational human exposure studies 

could include, but are not limited to the following types. 

• Asking the participant about demographic, 

occupational, smoking, or product use information for 

other household members 

• Collecting residential environmental samples in 

multiperson households 

46
• Collecting environmental samples in common areas of 

multifamily housing units 

• Collecting personal or environmental samples in a day 

care, school, health care, or occupational setting 

• Measuring chemical occurrences or concentrations 

that may be of interest or import to other household 

members or to the community 

• Collecting activity or dietary information about a 

community 

It is important for researchers and research staff to 

understand whether and to what extent the research 

involves or affects third parties, and how third-party 

involvement might affect the study participants. Several 

examples of possible third-parties are listed in Text Box 

4-5. Study planning; IRB review; and communication 

before, during, and after the study should take thirdparty issues into account. 

4.4.1 Determining Whether a Third Party 

Is a Human Subject 

 It is up to the IRB to determine whether a third 

party is a human subject afforded human subject 

protections under the Common Rule. A third party 

would meet the Common Rule definition of a human 

subject [40 CFR 26.102(f)] if individually identifiable 

private information about them is collected (CFR, 2006). 

When this occurs, the informed consent of the third party 

must be obtained, or, if certain criteria are met, the IRB 

may determine that informed consent may be waived. It 

can be difficult to determine whether information about 

a third party is both individually identifiable and private. 

Discussions of this issue and recommendations for 

determining whether third-party information is 

identifiable and private have been submitted to the HHS 

Office of Human Research Protections by NIH (2001) 

and by the National Human Research Protections 

Advisory Committee (NHRPAC, 2002). 

Whether or not a third party is determined to be a 

human subject, the researcher should treat research 

information about a third party as confidential. 

4.4.2 Informing Third Parties of 

Research Activities 

Obtaining permission from or informing third parties 

of certain types of activities may be needed in some 

observational human exposure studies. For example, 

household members living with a study participant need 

to be informed about home study visits and residential 

sample collection activities. Study activities that occur 

outside of the participant’s home or yard may require 

informing or gaining permission from third parties. A 

study may include collection of environmental samples 

(i.e., ambient air, dust, soil) from outdoor common areas 

of multifamily housing where the study participant lives. 

Issues regarding privacy, permission, and payments for 

third parties in housing-related studies have been 

discussed in the NRC & IOM (2005) report. 

Observational human exposure studies also may 

include cases when study participants are asked to 

collect personal samples (i.e., wearing a personal air 

monitor) over a time period that includes time they 

spend in a school, day care, or workplace. Such 

monitoring might require informing or gaining 

permission from an organization’s staff or an employer. 

In each case, the researcher and IRB have to consider 

whether obtaining permission from or informing a third 

party is appropriate and, if so, to define the procedures 

for doing so. The researcher and IRB have to also 

consider the potential impact of third-party knowledge 

of research activities on confidentiality and risk for the 

study participant and have to ensure that it is clearly and 

fully explained in the informed consent process. 

4.4.3 Research Results and Third Parties 

Prior to initiating a research study, researchers 

should consider whether research results may be 

provided to third parties. In some studies, there may be 

reasons to inform household members living with a 

study participant about specific residential measurement 

results. In community research studies, aggregated or 

summary research results may provide a benefit to the 

community. In this case, it would be beneficial to seek 

out the advice of community representatives regarding 

results reporting prior to the study. Researchers also 

should determine whether there are State or local 

reporting requirements for some types of measurement 

results above specified action levels (i.e., blood-lead 

levels, heavy metal concentration in soil). It is important 

that the researcher and IRB ensure that confidentiality 

and privacy of study participants are carefully 

Text Box 4-5. Possible Third-Parties in 

Exposure Studies 

• Household members not enrolled in the study 

• Relatives 

• Care givers for children or elders 

• School staff 

• Employers 

• Other members of the community 

• Building managers or facility operators 

• Landlords 

47
considered in any case where reporting study results to 

third parties is contemplated or may be required. Ideally, 

the informed consent process would make clear whether, 

under what conditions, and how research results might 

be provided to third parties. 

4.5 Data and Safety Monitoring and 

Oversight 

The Common Rule requires for IRB approval that, 

“When appropriate, the research plan makes adequate 

provision for monitoring the data collected to ensure the 

safety of subjects.” [40 CFR 26.111(a)(6)]. 

Data and safety monitoring plans (DSMPs) are 

developed and applied in all clinical trial research 

studies. Clinical trials are prospective studies designed to 

answer specific questions about the effects or impact of 

particular biomedical or behavioral interventions. The 

DSMPs are used to insure the safety of participants, the 

validity of data, and appropriate termination of studies 

for which significant risks or benefits have been 

uncovered or when it appears that the trial cannot be 

concluded successfully (NIH, 1998; NCI, 2001; U.S. 

FDA, 2001). Depending on the study scope and potential 

risks and benefits, a data safety monitoring board 

(DSMB) may be created to assess procedures for data 

and safety monitoring and to independently assess safety 

and outcomes on an ongoing basis during the study. 

Formal independent monitoring boards or 

committees, like DSMBs, have not seen widespread use 

in observational human exposure studies, although much 

of the information included in DSMPs often has been 

captured in the research protocols. Researchers and IRBs 

may, however, consider using monitoring and oversight 

boards to help assure participant safety and research 

integrity in observational human exposure studies, 

particularly in complex longitudinal studies and in 

studies that include vulnerable subjects. 

At least two NIH institutes have developed 

guidelines for monitoring and oversight in the 

observational research that they sponsor. 

(1) The National Heart, Lung, and Blood Institute 

(NHLBI) has developed an interim policy on the 

creation and role of observational study monitoring 

boards (OSMBs) for observational research 

sponsored by that institute (NHLBI, 2007). OSMBs 

may be established for large or complex studies on a 

case-by-case basis. The role of the OSMB is “to help 

assure the integrity of the study by closely 

monitoring data acquisition for comprehensiveness, 

accuracy, and timeliness; and monitoring other 

concerns such as participant confidentiality.” 

(2) The National Eye Institute (NEI) has developed 

guidelines for data monitoring and oversight 

committees (DMOCs) for observational research 

(NEI, 2001). The role of the DMOC is to “assist the 

NEI and the study investigators in protecting the 

interests of study participants and in preserving the 

integrity and credibility of the study.” 

When appropriate, formal procedures for routine 

monitoring of scientific and ethical issues will need to be 

incorporated into observational research and approved 

by the IRB to ensure participant safety and the integrity 

of the research. Even though most observational human 

exposure studies are considered low-risk, there is often a 

need to determine whether appropriate threshold values 

for biological or environmental levels of chemicals exist 

or can be determined that, if the threshold value is 

exceeded, it would trigger reporting or other actions. The 

safety of measurement procedures and equipment also 

has to be considered. Unanticipated adverse events also 

may be encountered in observational research. 

Participant consent and understanding of the research 

effort, participant recruitment, participant retention, and 

data accuracy and quality should all be monitored to 

ensure the scientific integrity of research results. 

The authors already have discussed (Section 2.8) the 

needs (1) to establish, in advance, criteria and standards 

for monitoring the research program in regard to both 

scientific and ethical issues; (2) to establish who will 

monitor and oversee the research progress (the 

monitoring and oversight authority, be it an individual, 

team, or review committee); and (3) to establish the 

roles, responsibilities, and authorities of the researchers 

and of the monitoring and oversight authority. The 

planning also should include steps to meet the IOM 

recommendations that researchers should “anticipate 

risks and behaviors that may be observed in the home... 

[and] develop anticipatory plans that specify how to 

assess and respond to risks when they are identified, and 

educate their staffs about the plan” (Recommendation 

7.3, p. 144, NRC & IOM, 2005). 

Once the procedures and organization for monitoring 

and oversight of the observational study are approved by 

the IRB, it is the responsibility of the researchers and of 

the monitoring and oversight authority to ensure that the 

planned actions are implemented. Implementation of the 

monitoring and oversight function may include the 

following items. 

• Ensuring that procedures for identifying, reporting, 

and responding to anticipated or unanticipated adverse 

events and safety issues are in place and are being 

followed 

48
• Assessing and responding to risks when they are 

identified 

• Evaluating the performance and knowledge of the 

staff regarding identification of potential risks and the 

actions they should take 

• Implementing procedures for monitoring the informed 

consent process, participant behaviors, participant 

recruitment, participant retention, procedures to 

protect privacy and confidentiality, and other human 

requirements for adherence to the research protocol 

and compliance with ethical standards and with EPA’s 

human subjects rules 

• Ensuring that measurements and samples are collected 

as planned, and that data are reported on a timely basis 

• Evaluating whether the observed measurements 

exceed the pre-established threshold values and, if so, 

ensuring that reporting procedures and plans to 

respond to the potential risks are completed on a 

timely basis 

• Ensuring that quality assurance plans that define 

procedures for assessing and ensuring study protocol 

compliance are being met 

• Ensuring data quality targets are met through 

independent internal or external auditing requirements 

• Taking all warranted oversight actions to ensure the 

safety of the participants and the integrity of the study, 

including terminating the research study if appropriate 

References 

AAP (American Academy of Pediatrics Committee on 

Environmental Health) (2003). Pediatric Environmental 

Health. (2nd Edition). Elk Grove Village, IL: American 

Academy of Pediatrics. 

Beauchamp TL, Childress JF (2001). Principles of Biomedical 

Ethics. (5th Edition). New York, NY: Oxford University 

Press. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter 

I⎯Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: 

http://www.access.gpo.gov/nara/cfr/waisidx_06/40cfr26_06.

html [accessed August 2007]. 

CIOMS (Council for International Organizations of Medical 

Sciences) (2002). International Ethical Guidelines for 

Biomedical Research Involving Human Subjects. World 

Health Organization. Geneva, Switzerland. Available: 

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed June 2007]. 

Emanuel, EJ, Wendler D, Grady C (2000). What makes 

clinical research ethical? JAMA 283(20): 2701-2711. 

NCI (National Cancer Institute) (2001). Essential Elements of 

a Data and Safety Monitoring Plan for Clinical Trials 

Funded by the National Cancer Institute. Available: 

http://www3.cancer.gov/rrp/dsm_ess.html [accessed April 

2007]. 

NEI (National Eye Institute) (2001). National Eye Institute 

Guidelines for Data Monitoring and Oversight of 

Observational Studies. Available: 

http://www.nei.nih.gov/funding/datastudies.asp [accessed 

April 2007]. 

NHLBI (National Heart Lung and Blood Institute) (2007). 

Monitoring Boards for Data and Safety (Interim Policy). 

Policy effective date: 14 May 2007. Available: 

http://public.nhlbi.nih.gov/ocr/home/GetPolicy.aspx?id=8

[accessed September 2007]. 

NHRPAC (National Human Research Protections Advisory 

Committee) (2002). Clarification of the status of third 

parties when referenced by human subjects in research. 

Available: 

http://www.hhs.gov/ohrp/nhrpac/documents/third.pdf

[accessed April 2007]. 

NIH (National Institutes of Health) (2002). Extramural 

Projects - Application Instructions (03/15/2002) - Detailed 

Application Instructions for Certificate of Confidentiality 

Involving Extramural Research Projects. Certificates of 

Confidentiality. Available: 

http://grants.nih.gov/grants/policy/coc/index.htm. [accessed 

April 2007] 

NIH (National Institutes of Health) (2001). Protection of third 

party information in research: Recommendations of the 

National Institutes of Health to the Office for Human 

Research Protections. Available: 

http://bioethics.od.nih.gov/nih_third_party_rec.html

[accessed March 2007]. 

NIH (National Institutes of Health) (1998). NIH Guide: NIH 

Policy for Data and Safety Monitoring. Available: 

http://grants.nih.gov/grants/guide/notice-files/not98-

084.html [accessed April 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed June 2007]. 

49
50

U.S. FDA (U.S. Food and Drug Administration) (2001). Draft 

Guidance for Clinical Trial Sponsors on the Establishment 

of Clinical Trial Data Monitoring Committees. U.S. 

Department of Health and Human Services, Food and Drug 

Administration, Rockville, MD. Available: 

http://www.fda.gov/cber/gdlns/clindatmon.pdf. [accessed 

April 2007]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

June 2007]. 
SECTION 5

Creating an Appropriate Relationship Between 

the Participant and Researcher 

In observational human exposure studies, the 

researcher and the participant routinely interact with 

each other, often in the participant’s home or other 

private setting and often repeatedly over a number of 

days. The nature and setting of the interactions mean that 

exposure researchers should give special consideration 

to the many scientific and ethical issues that shape the 

relationship between participants and the researchers. In 

these studies, it is recommended that a strong 

relationship, built on openness and trust, should be 

developed between the researcher and participant. The 

nature of that relationship and the ethical principles 

underpinning an appropriate relationship are the focuses 

of this section of the document. 

This relationship should be established on the ethical 

values of respect for the participant’s autonomy and 

respect for their welfare. Emanuel and his co-authors 

find that these two ethical values translate into specific 

responsibilities for an ethical researcher in regard to 

informed consent and respect for potential and enrolled 

subjects (Emanuel et al., 2000). They describe the ethical 

principles for these responsible actions thusly, “Respect 

for potential and enrolled subjects is justified by multiple 

principles including beneficence, nonmaleficence, and 

respect for persons. Permitting subjects to withdraw and 

providing them additional information learned from the 

research are key aspects of respecting subject autonomy. 

Protecting confidentiality and monitoring well-being are 

motivated by respect for persons, beneficence, and 

nonmaleficence.” Section 4 already has described some 

of the particular concerns regarding privacy, 

confidentiality, and other issues related to observational 

human exposure studies. This section further describes 

elements of the relationship between researchers and 

participants that are important to consider and address 

during design and implementation of a study. 

Of course, the relationship between the researchers 

and the individual participants does not exist in isolation. 

The researcher-participant relationship may influence 

and be influenced by the relationship with the 

community in which the participant lives. Good, twoway communications are critical for the development 

and nourishment of an appropriate researcher-participant 

relationship. Although those two topics are the subject of 

the next sections of this document, elements from those 

topics unavoidably will color the discussions in this 

section as well. 

Researcher training is a key component for 

conducting research that incorporates human subject 

protections and fosters appropriate researcher-participant 

relationships. Most organizations require basic human 

subjects training on the essential elements for processes 

and procedures for research with human subjects. More 

in-depth training will improve researcher understanding 

in areas of the informed consent process, observational 

techniques, community-based research, and other topic 

areas. Such training will benefit principal investigators 

throughout the research study from the design stage 

through communication of research results. Training is 

also important for staff that will work directly or 

indirectly with research participants or their samples and 

data. This document can be used as both a training tool 

for researchers as well as a resource for designing 

training courses. There are a number of sources of 

training on human subjects protection. The 

Collaborative Institutional Training Initiative (CITI, 

http://www.citiprogram.org/) is a subscription service 

providing research ethics education to many institutions. 

Other training, such as that provided by the National 

Cancer Institute (http://cme.cancer.gov/clinicaltrials/lear

ning/humanparticipant-protections.asp) and the U.S. 

Department of Health and Human Services 

51
(http://www.hrsa.gov/humansubjects/default.htm), are 

available on-line. 

5.1 Informed Consent 

In observational human exposure studies, informed 

consent ensures that the participant accurately 

understands the range of risks and benefits (if any) 

associated with participation; emphasizes the voluntary 

nature of their participation; and provides essential 

protections to the participant. The three “pillars” of the 

informed consent process are (1) information; 

(2) comprehension; and (3) voluntary participation, or 

“voluntariness” (U.S. DHEW, 1979). Informed consent 

requires “provision of information to subjects about the 

purpose of the research, its procedures, potential risks, 

benefits, and alternatives, so that the individual 

understands this information and can make a voluntary 

decision whether to enroll and continue to participate” 

(Emanuel et al., 2000). 

The NRC & IOM document Ethical Considerations 

for Research on Housing-Related Health Hazards 

Involving Children (NRC & IOM, 2005) contains a 

comprehensive and very useful discussion of informed 

consent procedures and requirements in Chapter 6. The 

IOM report, Responsible Research: A Systems Approach 

to Protecting Research Participants, also includes a 

thoughtful discussion of participant-investigator 

interactions and the informed consent process (IOM, 

2002). CIOMS also includes recommendations for both 

the process and content of informed consent (CIOMS, 

2002). Some of the important points from those 

documents are summarized in Text Box 5-1, but the 

reader should refer to those documents for additional 

information about this topic. 

Federal regulations governing research that is either 

Federally conducted or Federally funded (i.e., all human 

subjects research at NERL) are codified in the Common 

Rule. The regulations set forth requirements for both the 

content of an informed consent and the process for 

obtaining and documenting an individual’s informed 

consent (see Text Box 5-2).16 General regulatory 

requirements for the elements of informed consent are 

codified in the Common Rule at 40 CFR 26.116(a)(1)-

(8) (CFR, 2006). The regulations also prescribe the use 

of a written consent form and describe how informed 

consent is to be documented (at 40 CFR 26.117). The 

regulatory requirements for informed consent highlight a 

number of issues that a NERL researcher needs to 

 

16 An IRB may waive informed consent under some very limited conditions. 

See 40 CFR 26.116(c) and (d). 

consider in developing and administering the informed 

consent process and the consent form document. The 

discussion of these issues, arising from regulatory 

requirements or identified in recent writings on ethical 

considerations in human subjects research, is grouped 

below, under the three pillars of informed consent: 

(1) information, (2) comprehension, and (3) voluntary 

participation. 

5.1.1 Information 

Some items that researchers should keep in mind as 

they provide information to the study participants are 

summarized below. These items may be based on 

regulatory requirements or currently may be 

recommendations as ethical “best practices.” 

Text Box 5-1. Recommendations for Informed Consent

In the United States and Internationally 

(1) Revitalize Informed Consent (IOM, 2002) 

 Informed consent is a process, not a form. It is an on-going, 

interactive dialogue between research staff and research 

participants with disclosure and exchange of relevant 

information, including assessment of understanding. 

 Ethics Review Boards should ensure that the focus of both the 

informed consent process and the consent forms is on 

informing and protecting participants, not the research 

institution. 

 (2) Strengthen Process of Parental Permission and 

Children’s Assent if Children Are Involved in Research

(NRC & IOM, 2005) 

 The process begins with a community-based discussion and 

concludes with an assurance that individual parents 

understand the essential elements of the research. 

 Educate parents on issues critical to informed decision making 

and assess their degree of understanding. 

 Use informational materials in the form that is most 

appropriate to convey information to potential participants. 

 Consult with community representatives to ensure that 

information is complete, clear, and understandable, and that 

any payment will not be exploitive. 

 Expand the perspective about what information about risks 

and benefits is needed to make an informed choice. 

 Ethically, it is critical to assure that participants and parents 

understand the crucial features of the research effort. 

(3) Informed Consent Is a Decision To Participate by an 

Informed, Competent Individual Without Undue Coercion, 

Influence, or Intimidation (CIOMS, 2002) 

 Informed consent is a process that takes time and resources. 

 It is not a ritual recitation of text from a form but informative 

communication in language that suits the individual’s level of 

understanding. 

 Consent is ethically obtained, considering language and 

cultural issues, and is documented. 

 Material changes in conditions or procedures require that 

informed consent be renewed. 

 Consent should explain how samples will be used in current 

research, and, if applicable, how samples may be used in 

future research. 

52
• The information “shall be in language understandable 

to the subject” (40 CFR 26.116). This may require 

forms to be written and administered in different 

languages during a study. For example, the National 

Children’s Study (NCS) plans to produce all consent 

materials in English and Spanish, with other 

translations made available as needed (NCS, 2007). 

Ethically, “language understandable to the subject” 

goes beyond simply using the appropriate language; 

the researcher is compelled also to consider 

readability and vocabulary (e.g., avoiding jargon or 

terminology that may be clear to the researcher but 

which may confuse or intimidate the potential subject) 

if the information is to be understandable. 

• Information may be presented orally in addition to an 

appropriately written document (40 CFR 26.117). 

Participants often find discussions with research staff 

more useful than written consent forms (p. 103, NRC 

& IOM, 2005). NCS plans to pilot test an interactive, 

computer-based audio/video consent tool and to 

compare it with traditional written informed consent 

approaches (NCS, 2007). 

• The information being discussed, including the 

explanation of the purpose of the research and the 

description of the study procedures, should be written 

or discussed at a level that the participant can 

understand.17 The National Institutes of Health 

recommends writing consent forms as “plain language 

documents that explain the research in an honest, 

straightforward way” and suggest that doing so will 

help enhance public trust (Recommendation 11, NIH, 

2005). 

• The consent form should contain sufficient 

information to describe the study procedures, but not 

so much information that it causes confusion and 

results in the participant not understanding the study. 

There is not agreement on what the appropriate level 

of information is. IRBs do not agree on the level of 

information; some require lengthy descriptions of the 

study, whereas others prefer concise information. 

Ultimately, the IRB dictates the language of the 

informed consent document, and the researcher will 

need to comply. It will benefit the researcher to 

discuss the consent process with their IRB when they 

develop the consent form document and process (p. 

108, NRC & IOM, 2005). 

• In observational human exposure studies, information 

about the risks of the hazards being studied needs to 

be conveyed to the participants during the consent 

process. Information should be provided to the study 

participant on what hazards pertinent to the topic of 

the study may be present in the participant’s 

environment, particularly those microenvironments 

being studied, what hazards will continue to exist in 

those microenvironments after the research is 

completed, and how those hazards may adversely 

affect the participant’s health (NRC & IOM, 2005). 

• The informed consent process should describe 

whether any study results will be provided to 

 

17 A survey of IRBs found that their readability standards ranged from 5th- to 

10th-grade level (Paasche-Orlow et al., 2003). Interestingly, the same report 

found that, 92% of the time, the sample consent forms provided by the IRBs 

did not meet their own readability standards. The NRC & IOM report (p. 107, 

NRC & IOM, 2005) discusses an NCI effort to simplify informed consent 

forms by using text targeted at 8th-grade reading level. More information 

about the NCI template may be found at 

www.nci.nih.gov/clinicaltrials/understanding/simplification-of-informedconsent-docs/page2 (accessed September 12, 2007). 

Text Box 5-2. Common Rule Requirements: 

Elements of Informed Consent 

(1) An explanation of the purposes of the research 

(2) The expected duration of the subject's participation 

(3) A description of the procedures to be followed and 

identification of any experimental procedures 

(4) A description of any reasonably foreseeable risks or 

discomforts to the subject 

(5) A description of any reasonably expected benefits to the 

subject or others 

(6) A disclosure of appropriate alternative procedures that might 

be advantageous to the subject 

(7) A description of the extent that confidentiality will be 

maintained 

(8) For research involving more than minimal risk, an 

explanation about whether compensation or medical 

treatments are available if injury occurs 

(9) An explanation of whom to contact with questions about the 

research or to report a research-related injury 

(10) A statement that participation is voluntary, refusal to 

participate will involve no penalty, and the subject may 

discontinue participation at any time without penalty or loss 

of benefits to which the subject is otherwise entitled 

(11*) A statement that the particular treatment or procedure may 

involve risks to the subject (or to the embryo or fetus, if the 

subject is or may become pregnant) that are currently 

unforeseeable 

(12*) Anticipated circumstances under which the subject's 

participation may be terminated by the investigator without 

regard to the subject's consent 

(13*) Any additional costs to the subject that may result from 

participation in the research 

(14*) The consequences of a subject's decision to withdraw from 

the research and procedures for orderly termination of 

participation by the subject 

(15*) A statement that significant new findings developed during 

the course of the research that may relate to the subject's 

willingness to continue participation will be provided to the 

subject. 

(16*) The approximate number of subjects in the study 

* Included if appropriate [40 CFR 26.116(b)] 

53
participants and, if so, how and when (p. 101, NRC & 

IOM, 2005). 

• For studies involving children as participants, it 

generally is regarded as desirable that the informed 

consent process should involve both parents 

(assuming that there are two competent parents 

available), and that the consent of both parents be 

obtained, if possible. The IRB may decide that the 

permission of one parent is sufficient, but only when 

certain risk-benefit conditions are met.18 

• For studies involving children as participants, it is 

desirable for those children with sufficient capacity to 

be involved in the consent process. Moreover, it is 

generally accepted that the child’s assent be obtained 

whenever this is developmentally possible and 

otherwise appropriate. Under both the EPA Rule and 

the HHS Rule, the IRB is responsible for determining 

that adequate provisions have been made for soliciting 

the assent of the children when, in the judgment of the 

IRB, the children are capable of providing assent. 

Assent, however, may be waived in those restricted 

circumstances in which consent may be waived under 

the Common Rule. Those circumstances and the 

required IRB documentation are described in the 

Common Rule at 40 CFR 26.116(d). 

• The consent form should clearly state that 

participation is voluntary and that study participants 

may “discontinue participation at any time without 

any penalty or loss of benefits to which the subject is 

otherwise entitled” [40 CFR 26.116(a)(8)]. If a subject 

chooses to withdraw from a study, the consequences 

of their decision and the process for orderly 

withdrawal should be clearly explained [40 CFR 

26.116(b)(4)]. 

• The consent form should address any foreseeable 

potential future use of samples and data (CIOMS, 

2002). For example, effects of environmental 

exposures on gene expression are potentially very 

important. Therefore, biologic specimens for DNA 

analysis may be obtained from participants in future 

studies. But, it is recognized that human genomic data 

are private, intimate, and sensitive, and they create 

 

18 See the EPA Rule at 40 CFR 26.406(b) for observational research with 

children and the HHS Rule at 45 CFR 46.408(b) for all research with children. 

Under the EPA Rule, greater than minimal risk observational research with 

children that does not hold out the prospect of direct benefit to the child is not 

permitted under any circumstances. Under the HHS Rule, greater than 

minimal risk research involving children without the prospect of direct benefit 

is permitted in very limited circumstances, but the consent of both parents is 

required in those cases (unless one parent is deceased, unknown, incompetent, 

or not reasonably available, or when only one parent has legal responsibility 

for the care and custody of the child). 

special concerns about the potential for 

discrimination, stigmatization, and impact on future 

employment or insurance. The informed consent 

process needs to explain what the plans may be for 

such specimens and recognize the rights of the 

subjects to decide about any such future use, including 

having the material destroyed. The informed consent 

process needs to explicitly discuss obtaining 

permission from participants on behalf of themselves 

and their child to obtain specimens for genetic 

analysis. 

5.1.2 Comprehension 

Research participants frequently fail to understand 

the research protocols in which they agree to participate 

(NRC & IOM, 2005). In considering the ethical issues 

raised by the Grimes v. Kennedy Krieger case, the NRC 

& IOM committee “realized that the crucial issue 

regarding consent was not what information was 

contained in the consent forms, but rather what the 

parents understood about the study and the hazards 

present in the home before and after the study” (p. 19, 

NRC & IOM, 2005). The committee laments that “IRBs 

place their attention on consent forms rather than on the 

process of providing and discussing information” (p. 

103, NRC & IOM, 2005). The IOM recommends that 

“the informed consent process should be an on-going, 

interactive dialogue between research staff and research 

participants involving the disclosure and exchange of 

relevant information, discussion of that information, and 

assessment of the individual’s understanding of the 

discussion” (Recommendation 4.1, IOM, 2002). These 

comments emphasize how important true two-way 

communication is to comprehension, the second pillar in 

the informed consent process. 

The following items are a variety of issues 

concerning comprehension that NERL scientists should 

keep in mind as they develop an informed consent 

process in collaboration with the research team, the IRB 

and other peer reviewers, and EPA’s HSRRO. These 

items may be based on regulatory requirements or may 

simply be recommendations as ethical “best practices.” 

• Researchers need to assume responsibility for 

developing an interactive dialogue with participants 

for the exchange and discussion of relevant 

information as a part of the informed consent process, 

not just for conveying information. The dialogue 

should be ongoing, continuing throughout the research 

project (IOM, 2002). 

• The consent form and its content are only one part of 

the overall consent process. An equally important part 

54
is how information is conveyed to the participant 

outside of the written form itself. Participant 

comprehension is contingent on all elements of a 

comprehensive consent process that involves ongoing 

information exchange between researchers and 

participants, as well as a written informed consent 

document (NRC & IOM, 2005). 

• The most effective way to improve comprehension is 

by talking one-on-one with study participants. 

“Having a study team member or a neutral educator 

spend more time talking one-on-one to study 

participants appears to be the most effective way of 

improving research participants’ understanding” 

(Flory and Emanuel, 2004). 

• The information being exchanged (e.g., explanation of 

the purpose of the research, description of the study 

procedures) should be written at a level that the 

participant can understand (NRC & IOM, 2005). 

• The researcher should describe the benefits of 

participation in the study [40 CFR 26.116(a)(3)], but 

should not promise any outputs or outcomes that he or 

she cannot deliver. Participants often misunderstand 

the purpose of the research. The researchers also 

should attempt to reduce the likelihood of “therapeutic 

misconception”19 or related misunderstandings in 

which the participant anticipates a benefit that does 

not really exist, such as reduction of the hazard in an 

observational study (NRC & IOM, 2005). 

• The consent procedure should include some test of the 

participants to demonstrate that they truly understand 

the information that is being conveyed (IOM, 2002). 

• Tools to assess comprehension have been developed, 

but, as described in NRC & IOM (2005), there are no 

standard mechanisms for assessing comprehension. 

Tests for appropriate grade-level language can be 

performed, but additional comprehension testing 

should be considered as well (Flory and Emanuel, 

2004). 

• Researchers need to develop innovative approaches to 

improve comprehension. Multimedia, such as video or 

graphics, may be used but have had limited success in 

the past (NRC & IOM, 2005; Flory and Emanuel, 

2004). NCS currently is developing a highly 

sophisticated video consent tool that may be able to 

 

19 Therapeutic misconception is a term that refers to an inaccurate 

understanding on the part of a research participant that a direct therapeutic 

benefit will be provided by virtue of participation in a clinical trial. 

Researchers performing observational human exposure studies should be 

aware of the potential for misunderstandings to arise that are analogous to the 

misunderstanding represented by the therapeutic misconception. Ensuring 

comprehension of the study and its expected results is important to this issue. 

serve as a model going forward. The video 

presentation will include embedded questions to 

assess the participant’s understanding of the key 

elements of NCS and what their participation will 

involve (NCS, 2007). 

• Development of written materials with appropriate 

languages and comprehension levels is only part of 

the communication challenge. In communities where 

languages other than English are spoken, it will be 

important that the research team be able to 

communicate orally with participants, often in ad hoc 

situations. Research protocols should address how 

translations will be accomplished. The use of 

untrained persons such as co-workers usually will not 

meet requirements for full understanding of human 

subject protections. Researchers should make plans 

for trained staff or trained community members, 

associated or affiliated with the research study, to be 

available for translations. 

5.1.3 Voluntary Participation 

The third pillar of informed consent is voluntary 

participation. The Belmont Report emphasizes that 

participants “should understand clearly the range of risk 

and the voluntary nature of participation” [emphasis 

added]. The ethical principles of respect for persons and 

their autonomous decisions morally obligate the 

researcher to ensure that an individual’s decision to 

participate in a human research study is truly voluntary 

and uncoerced (Emanuel et al., 2000). A number of 

study characteristics may affect whether the participant’s 

actions are truly voluntary. 

• Access to study-dependent benefits or care that would 

otherwise not normally be received may impair 

voluntariness. 

• Voluntary participation also may be compromised 

when there is an existing relationship between the 

researcher and participants, such as employer and 

employee or teacher and student. 

• Restricted voluntariness may be an intrinsic part of 

belonging to certain vulnerable groups, including 

children, prisoners, handicapped persons, mentally 

disabled persons, and economically or educationally 

disadvantaged persons, or members of the military, for 

example. When research participants come from such 

groups, additional protections to insure voluntariness 

in the context of the research may be required (see 

also 40 CFR 26, Subparts B, C, and D). 

• Payments as incentives may have undue influence and 

are discussed below. 

55
• Whether payments will lead to a coerced decision to 

participate often is difficult to determine without input 

from people from similar socioeconomic backgrounds 

as the participants (p. 111, NRC & IOM, 2005). 

Researchers should work with community 

representatives to develop a consent process that will 

be maximally effective in providing information, 

ensuring and documenting comprehension, and 

ensuring that participation is voluntary (also see 

Section 6). 

Researchers should remember that obtaining 

informed consent should be “an on-going, interactive 

dialogue . . . involving the disclosure and exchange of 

relevant information” (IOM, 2002): it is not simply 

having a consent form signed. The process is most 

effective when the researcher spends time with potential 

participants to discuss the study and to answer questions. 

5.2 Payments to Research Participants 

The decision whether to pay research participants, 

including the appropriate level of payment,20 is a 

complex ethical issue. Monetary or nonmonetary 

payments are not ethical if they constitute an undue 

inducement for participants to assume research risks that 

they would not otherwise accept. On the other hand, it 

may be ethically appropriate to offer reasonable 

payments in some research studies. Indeed, payment of 

human subjects for their participation in scientific 

research is a common practice in the United States, with 

a history of well over 100 years (Grady, 2005). The 

difficulty for researchers and IRBs is that there is often 

little clear and uniform guidance for determining what 

constitutes “undue inducement” or “reasonable” 

payment for any particular research study, population, 

and level of risk. Additional considerations regarding 

payment to participants arise when working with 

vulnerable populations, including children. 

 

20 There are many terms that may be found in the literature to describe both 

monetary and nonmonetary payments, like payment, remuneration, 

compensation, recompense, incentive, inducement, reimbursement, and 

reward. Each of these words has its own definition, and each word also may 

carry specific connotations. In general, these terms refer to money or other 

items that “are often given to acknowledge the time and inconvenience of 

participating in research or to reimburse participants for any costs they incur. 

The term compensation is often used in the context of compensation for 

research-related injuries” (p. 112, NRC & IOM, 2005). The authors have 

chosen to use “payment” as the general term for monetary and nonmonetary 

items provided to research subjects for their participation in the research. They 

may occasionally refer to compensation for research-related injuries, but the 

text should make it clear when they do. 

5.2.1 Types and Amounts of Payments Offered 

in Research Studies 

Payments have been offered in a wide variety of 

research studies, ranging from clinical trials to 

behavioral and social research to observational human 

exposure studies. Payments can take various forms, 

including monetary payments (e.g., cash, gift 

certificates, reimbursement for expenses), nonmonetary 

payments (e.g., gifts, valuable information), or nothing 

at all (e.g., for a sense of altruism). Grady (2005) has 

described payment for the participation of research 

subjects as serving from one to four purposes: (1) an 

incentive, (2) compensation, (3) reimbursement, or 

(4) reward. Text Box 5-3 describes the roles that 

payments may serve, together with potential advantages 

and disadvantages or ethical concerns. The text comes 

mostly from Grady (2005) but builds also on the NRC & 

IOM document and other writings. (A number of authors 

have addressed issues associated with payments, 

including Ackerman, 1989; Dickert et al., 2002; 

Emanuel 2004; Erlen et al., 1999; Fry et al., 2005; 

Grady, 2005; Grady et al., 2005; Iltis et al., 2006; IOM, 

2004; NRC & IOM, 2005; Russell et al., 2000; 

VanderWalde, 2005; Weise et al., 2002; Wendler et al., 

2002). A number of specific issues or concerns 

regarding participant payments have been identified. 

Many researchers and ethicists argue that it is often 

appropriate to provide reasonable payment and have 

done so for many years. In the view of an NRC expert 

panel, the principles of “justice, fairness, and gratitude 

support payment to those who bear the burdens of 

research on behalf of society” (NRC, 2004). 

Direct reimbursement may be made to participants 

for out-of-pocket expenses for costs directly associated 

with participation in a study. These might include 

transportation costs, parking fees, or child care costs. 

When payment for time and burden is provided, it is 

often in the form of monetary payments. Different 

approaches may be considered for determining 

reasonable amounts for payment, including a set 

payment for each visit, a small daily payment, payment 

at the prevailing minimum hourly wage, or payment at 

some other hourly rate appropriate for the 

community⎯perhaps a prevailing rate for unskilled 

labor (Emanuel, 2004). Incentives to encourage 

enrollment are sometimes used when participants will 

receive little or no direct benefit from the research and 

can take the form of monetary or non-monetary 

payments. Incentives are kept modest so as not to impart 

undue influence. Researchers need to consider the 

possible effects of incentive payments on the potential 

56
for differential recruitment that could result in bias in the 

study sample. 

Determining appropriate level of payments or 

incentives for participants in a research study is 

complex. “No bright line distinguishes proper and 

reasonable payments to parents and children from 

payments that are inappropriate” (p. 214, IOM, 2004). 

The ethical issue is at what level might a payment 

change from being an incentive (an encouragement) to 

participate and become an inducement (the cause or 

reason) for participation. Many research organizations 

and IRBs do not have written policies or guidelines 

regarding the determination of reasonable payment. 

Decisions often are made based on the level of 

discomfort and burden, costs to participants, and 

population characteristics. However, large differences in 

payment levels have been found even in multisite studies 

in which the same protocol is administered across all 

sites. 

Grady et al. (2005) performed a survey of practices 

for paying research participants in the United States in 

Phase 1 to 4 clinical trials and physiologic, behavioral, 

and other types of research. Across 467 studies of 

varying complexity that included payments, the median 

Text Box 5-3. Payments for Participation of Research Subjects 

(based on Grady, 2005) 

Payment Serves As Amount Determined By Potential Advantages Potential Disadvantages 

Incentive Supply and demand; market 

rates 

(a) More rapid recruitment 

(b) Completion bonuses encourage 

subject retention and high 

completion rate 

(c) Possibility of profit for participants 

(d) Little or no financial sacrifice by 

subject 

(a) Undue inducement possibly resulting 

in incomplete assessment of risks 

and benefits by subject; subject 

concealing information to ensure 

enrollment and retention 

(b) Competition between studies; better 

funded studies more likely to meet 

recruitment goals 

(c) Different levels of payment at 

different locations for multicenter 

research because of supply and 

demand 

Standardized “wage” for time 

and effort, suggested to be 

commensurate with wages for 

unskilled, but essential jobs; 

additional payment for extra 

burdens such as endurance of 

uncomfortable procedures 

(a) Recognizes contributions of 

participants 

(b) Uniform payment across studies 

(c) Equal pay for equal work 

(d) Less risk of undue inducement 

(a) May have little impact on recruitment

(b) Might undercompensate some 

subjects in relation to regular wage 

and preferentially attract others 

Compensation 

Provide “wage” for time and 

effort; base level of payment 

on some small fraction of 

participant’s or the 

community’s income, or on an 

appropriate hourly rate for the 

location, or on community-input 

about the appropriate level of 

payment 

(a) Recognizes contributions of 

participants 

(b) Decreases potential that payment 

would be undue inducement in 

some communities or locations 

and insufficient in others 

(c) Provides equivalent payment for 

participation across communities 

and locations (markets) 

(d) Less risk of undue inducement 

across study 

(a) Different levels of payment at 

different locations in multicenter 

research or in different communities 

(b) Unequal pay for equal work may 

violate one’s sense of justice 

Reimbursement Actual out-of-pocket cost to 

participant related to 

participation, such as parking, 

transportation, child care, cost 

of food samples, etc. 

(a) Lowers barriers to participation 

(b) Reduces burden and impact of 

research on participants 

(a) Few disadvantages 

(b) Possible differences in costs 

experienced by different participants 

Reward Token of appreciation at end of 

study 

(a) Expresses gratitude for 

contribution made 

(b) Not market dependent 

(c) Avoids undue inducement 

(a) Probably no impact on recruitment 

(b) No basis for consistency 

57
payment was $155 (mean $266, range $5 to $2,000). The 

basis for dollar amounts was infrequently described, 

with 19% of the payments based on time, and 12% based 

on the procedures. In a model of payment factors, 

studies with some prospect of therapeutic benefit, studies 

having at least one invasive procedure, and studies with 

greater numbers of clinic visits were significantly 

associated with higher dollar amounts. About 9.5% of 

the studies offered completion bonuses, and a similar 

percentage offered escalating payments for followup 

study visits. 

5.2.2 Regulations and Guidance Regarding 

Payment to Research Participants 

There is little specific guidance regarding payments 

in Federal human research regulations. The Common 

Rule and additional human subjects protections do not 

directly address payments to research participants, but 

the regulations do discuss providing additional 

safeguards for subjects vulnerable to coercion or undue 

influence [40 CFR 26.111(b)]. The NIH IRB guidebook 

advises IRBs to determine whether the rewards offered 

for participation in research constitute undue influence 

(U.S. HHS, 1993). According to the IRB guidebook 

undue inducement might blind prospective subjects to 

risks, impair their ability to exercise proper judgment, or 

may cause people to lie or to withhold information that 

would make them ineligible to enroll or continue 

participation. 

The U.S. Food and Drug Administration (FDA) has 

provided guidance for investigators and IRBs for clinical 

research studies (FDA, 1998). The guidance states that 

“payment to research subjects for participation in studies 

is not considered a benefit, it is a recruitment incentive.” 

FDA expects payments to accrue as the study progresses 

and not to be contingent on completing the study, 

although a “small proportion as an incentive for 

completion of the study is acceptable.” The guidance is 

concerned with the issue of coercion or undue influence, 

and it recognizes the IRB as the responsible party for 

deciding what is or is not acceptable. 

The U.S. Office of Management and Budget (OMB) 

develops standards and guidelines for statistical surveys 

performed by the Federal government. Under Guideline 

2.3.2, OMB states that, while incentives are not typically 

used in Federal surveys, agencies may consider use of 

respondent incentives if they believe incentives would 

be necessary to use for a particular survey to achieve 

data of sufficient quality for their intended use (OMB, 

2006a). OMB requires that agencies provide a 

justification for giving incentives to respondents. Some 

of the factors cited by OMB to be addressed include 

those particularly relevant to observational human 

exposure studies, including unusual reporting burdens 

(keeping data logs for extended periods, coordinating 

study team visits, participating in a medical examination, 

etc.), complex study designs (such as studies requiring 

ongoing participation of respondents), and past 

experience, especially when there is evidence of attrition 

or poor response rates (OMB, 2006b). Although OMB 

primarily considers incentives with regard to survey 

response rates and data quality, researchers need to 

consider payments to participants, including 

participation incentives, in the broader context discussed 

in this section. 

CIOMS also provides guidance and commentary on 

this issue in the International Ethical Guidelines for 

Biomedical Research Involving Human Subjects (2002). 

Guideline 7 and the associated commentary emphasize 

that payments to subjects for expenses incurred because 

of their participating in a research study are legitimate. 

The guideline also allows payment for inconvenience 

and time spent, so long as the payments or other direct 

benefits are not “so extensive as to induce prospective 

subjects to consent to participate in research against their 

better judgment.” 

The approaches of HHS, FDA, and CIOMS above 

are consistent in not considering payments to be a 

benefit to research participants when considering risks 

versus benefits. All of the guidelines recognize the 

legitimacy of some recompense, but they all are 

concerned with the issue of undue influence. “Payments 

or rewards that undermine a person’s capacity to 

exercise free choice invalidate consent” (CIOMS, 2002), 

and voluntariness is a pillar of legitimate informed 

consent. 

Text Box 5-4 lists some of the concerns about, and 

the reasons for, payment of participants. 

IRBs have considerable discretion with regard to 

payments and consider payments with regard to the 

specific circumstances of the research and of the 

population being studied. The issue of recompense can 

be a difficult but legitimate ethical issue involving 

weighing the different ethical principles of justice and 

fairness against the concerns about undue influence and 

the invalidation of consent. Ethical review committees, 

including IRBs, need to consider many factors when 

determining when it is appropriate to offer payments to 

research participants and the level and form of payments 

when they are appropriate. Review committees also 

should consider how and when information on payments 

is communicated to prospective study participants. 

58
5.2.3 Payments When Children or Other 

Vulnerable Populations Are Involved 

It is essential that special care be taken with regard 

to payments when members of vulnerable populations 

are included in research studies. Vulnerable populations 

may include children and adolescents, those with 

cognitive impairments because of medical conditions or 

age, economically disadvantaged persons, and prisoners. 

These populations often are not capable of making 

autonomous, fully informed decisions regarding risks 

and benefits, or they may be particularly vulnerable to 

undue influence resulting from the offer of a payment for 

research participation. In addition, payments made 

directly to parents or guardians could alter judgment 

regarding the best interests of minor or incompetent 

persons in their care. 

The ethical concern is that too high a payment may 

“undermine free and informed consent by leading 

parents to expose their children to unacceptable risks” 

(NRC & IOM, 2005). The NRC & IOM committee 

recognized that some commentators argued that children 

should never be paid, and that parents ought not to be 

paid to enroll their children in research. Yet, on balance, 

the committee felt that “reimbursement for expenses and 

some modest payment for time spent in research 

activities is thus justified on the grounds of fairness” (p. 

112, NRC & IOM, 2005). 

Similarly, the IOM Committee on Clinical Research 

Involving Children found that “certain types of 

payments to parents or adolescents are usually if not 

always acceptable, for example, reimbursement for 

reasonable expenses that are necessary for research 

participation. The specifics may vary, but examples of 

reasonable expenses are costs of transportation to the 

research site, parking, lodging, meals, and babysitting. 

Other payments are never appropriate in pediatric 

research, for example, paying parents for the use of their 

child in research” (pp. 225-6, IOM, 2004).21

The IOM committee recommends establishing 

policies on acceptable and unacceptable types of 

payments. They also recommend that the policies 

disclose any recompense in a full and open process,22

while not overemphasizing any recompense. 

Although the NRC & IOM Committee on Ethical 

Issues in Housing-Related Health Hazard Research 

Involving Children and the IOM Committee on Clinical 

Research Involving Children both concluded that it is 

appropriate to reimburse expenses or compensate for 

time or inconvenience, neither committee endorsed 

incentive payments to parents. In Europe, too, incentive 

payments to induce parents to allow their children to 

 

21 The IOM Recommendation 6.2 states, “In addition to offering small gifts or 

payments to parents and children as gestures of appreciation, investigators 

may also—if they minimize the potential for undue influence—act ethically to 

reduce certain barriers to research participation when they 

• reimburse reasonable expenses directly related to a child’s participation in 

research 

• provide reasonable, age-appropriate compensation for children based on 

the time involved in research that does not offer the prospect of direct 

benefit, and 

• offer evening or weekend hours, on-site child care, and other reasonable 

accommodations for parental work and family commitments.” 22 In recommending an open process, the IOM committee chose to reject the 

arguments from the American Academy of Pediatrics that “any token payment 

to children for participating in research should not be discussed with them 

until after research is completed for fear of unduly influencing their decisions 

(AAP, 2003).... On balance, the committee agrees that it is best to mention 

token or other payments during the permission and assent processes” (p. 215, 

IOM, 2004). 

The IOM Recommendation 6.1 states, “Institutional review boards, research 

institutions, and sponsors of research that includes children and 

adolescents should adopt explicit written policies on acceptable and 

unacceptable types and amounts of payments related to research 

participation. These policies should specify that investigators 

• Disclose the amount, the recipient, the timing, and the purpose (e.g., an 

expense reimbursement or a token of appreciation to a child) of any 

payments as part of the process of seeking parents’ permission, and, as 

appropriate, children’s assent to research participation; 

• Avoid emphasis on payments or descriptions of payments as benefits of 

participating in research during the permission or assent procedures; and 

• Obtain institutional review board approval for the disclosure of 

information about payments in advertisements and in permission and 

assent forms and procedures.” 

Text Box 5-4. Weighing the Ethical Issues 

About Payments 

Concerns about Payments Reasons for Payments 

• Payments may compromise 

voluntary participation. 

• Participants may accept risks 

they would not otherwise 

accept. 

• Participants may continue in a 

research study beyond a point 

they might ordinarily have 

withdrawn. 

• Payments may differentially 

encourage research 

participation by economically 

disadvantaged people. 

• The offer of payments may 

cause guardians or parents to 

not act in the best interests of 

incompetent persons or children 

in their care. 

• Persons in different 

circumstances may view the 

same amount of payment quite 

differently. 

• Payments may alter the 

composition of the study sample 

and potentially could 

compromise study integrity. 

• Recognizing participant 

contributions to the 

research and knowledge 

gained 

• Providing reimbursement 

for direct and indirect 

participant costs 

• Providing reasonable 

payment for the time and 

effort associated with 

participation in research 

• Providing incentives for 

participation in studies 

with low risk but no or few 

direct benefits 

• It is the just and fair thing 

to do for those who bear 

burdens of research on 

behalf of society. 

59
participate in research are unacceptable. The European 

Union requires that clinical trials on minors be 

undertaken only if “no incentives or financial 

inducements are given except compensation” (European 

Parliament, 2001). 

Payment for participation of children in research 

also is discussed in the literature. Diekema (2005) 

emphasizes the need to ensure that payments do not 

distort parental decisionmaking and do not tempt parents 

to consider other issues than the welfare of their child. 

Similarly, Menikoff (2005) suggested that there need to 

be relatively robust protections in place to ensure that 

families do not change their behaviors to participate in a 

study. He suggested that these may include determining 

payment as a percentage of a family’s income and 

developing criteria for documenting that behaviors have 

not changed to be eligible for participation in a study. He 

suggested that, for a study of pesticides, potential study 

participants provide documentation (such as receipts) 

that they routinely have been using a commercial 

pesticide service. This may be difficult for potential 

participants to do if they do not save receipts, and it 

would exclude all potential participants who purchase 

products and apply pesticides themselves. This likely 

would affect the study objectives and generalizability of 

the data collected. A survey of investigators (Iltis et al., 

2006) found that payments were made in 52% of the 

pediatric research studies surveyed, and that payment 

practices varied, as did the reasons for decisions 

regarding payments. They found a range of payment 

values separated across cash, gifts, items, vouchers, and 

other categories. A survey of IRBs (Weise et al., 2002) 

found that payment for participation in research was 

allowed by 66% of responding institutions, but that 

many IRBs did not have specific policies, and that there 

was considerable variability regarding the basis for 

decisions on payments in studies with children. The 

types of payments included money, certificates, and 

bonds with large ranges in the amounts of payments for 

approved pediatric research. This research shows a lack 

of consistency and the need for guidance and 

institutional policies that describe acceptable and 

unacceptable payments and the basis for the amount of 

any payments. 

The NRC & IOM Committee on Ethical Issues in 

Housing-Related Health Hazard Research Involving 

Children described many of the ethical considerations, 

practices, and policies regarding payments (NRC & 

IOM, 2005) for research conducted in the participants’ 

homes, rather than in a clinical facility. The research 

setting is similar to the setting of most observational 

human exposure studies, and the committee’s 

commentary and recommendations are also relevant. The 

committee notes that it would be unfair to expect 

families to make considerable sacrifices to participate in 

a time-consuming activity designed to advance 

generalizable scientific knowledge, rather than benefit 

themselves directly, and that payment for reimbursement 

of expenses and modest payment for time spent in 

research activities is justified on the grounds of fairness. 

But the committee then warns that if payments are too 

high, they may distort parents’ decisions about enrolling 

their children. The committee also found that “how the 

payment is made may also result in undue influence. For 

example, if payment for a long-term follow-up study is 

made in a lump sum and only if the subjects complete 

the entire study, then it could constitute an undue 

influence to stay in the study. If, on the other hand, the 

money is paid weekly, the effect would not constitute an 

undue influence.” 

The NRC & IOM committee recognizes that the 

issue of payment for participation in research is 

controversial. They also discuss how “countervailing 

ethical guidelines” may complicate the issues even more. 

Citing Wendler et al. (2002), the NRC & IOM 

committee points out that payments that are trivial for 

some families may be substantial for low-income or 

disadvantaged families. “Yet to pay economically 

disadvantaged families less than more affluent families 

for participating in the research is unfair because it 

requires similar sacrifices of time and inconvenience 

from both” (p. 113, NRC & IOM, 2005). Similar ethical 

quandaries can arise in multisite studies with differing 

costs for living. If the same payment is used in high-cost 

cities as in low-cost areas, the payment may be 

inadequate to gain sufficient enrollment in the high-cost 

area, whereas the same dollar amount may be “coercive” 

in the low-cost area. The NRC & IOM committee notes 

that a similar situation can arise when a study enrolls 

participants from diverse socioeconomic backgrounds. 

There are social justice concerns that poorer people 

might incur a disproportionate share of research risk and 

burden if payments induce unequal participation rates in 

the population. Decisions regarding payment for 

research participation will require careful consideration 

by IRBs when economically disadvantaged people may 

be enrolled. Community advisory boards (CABs) can be 

very important in helping researchers and IRBs 

determine what is appropriate with regard to payments 

within their community. 

60
5.2.4 Payments in Observational Human 

Exposure Studies 

Observational human exposure studies most often 

involve minimal risks to study participants and few 

direct benefits, but may require considerable time and 

burden for participation. Study requirements can include 

multiple in-home visits; the burden of wearing personal 

air monitors for one or more 24-hour period; preparing 

and providing duplicate diet samples; collection of 

environmental samples inside and outside the home; 

completing questionnaires, food diaries, and timeactivity diaries; and providing urine, blood, saliva, or 

hair samples. Monetary payments often have been 

included in these studies, with the level of payment 

related to the number of study days or visits or the 

specific kinds of environmental and biological samples 

and information that are collected or provided. Payment 

for direct participant costs has been included in some 

studies, such as a reasonable payment for providing 

researchers with duplicate diet samples. 

NERL scientists should review the commentary and 

recommendations in the literature before devising a 

payment program as part of a research protocol, 

especially the two recent National Academies of Science 

documents, Ethical Issues in Housing-Related Health 

Hazard Research Involving Children (NRC and IOM, 

2005) and Ethical Conduct of Clinical Research 

Involving Children (IOM, 2004). They should seek 

guidance from EPA’s HSRRO to determine EPA’s latest 

policies and guidance in this regard. Input also should be 

sought from community representatives to ensure that 

any payment is adequate to compensate for expenses and 

reward participation, but that the payment is not so high 

as to constitute undue influence or coercion in the 

community. If the study includes several followup visits 

over a long term, NERL researchers should ensure that 

payment is made incrementally as the NRC & IOM 

committee suggested. NERL scientists also should adopt 

the IOM Recommendations 6.1 and 6.2, including 

ensuring that any payment should be for appropriate 

purposes and age-appropriate, and that the process 

should be open and fully disclosed, while not overly 

emphasizing payments during the recruiting or informed 

consent phases. The final decisions about the ethics of 

payments rest with the IRB, which will review, modify 

as needed, and approve the research protocol, and with 

the EPA HSRRO, who has final authority to approve, 

modify, or disapprove all of NERL’s human subjects 

research efforts. 

5.3 Research Rights and Grievance 

Procedures

Protecting the research rights of participants and 

providing independent access to information regarding 

those rights and to grievance procedures is an important 

element in developing and maintaining appropriate 

participant-investigator relationships. As part of the 

informed consent process, the Common Rule requires 

“An explanation of whom to contact for answers to 

pertinent questions about the research and human 

subjects’ rights, and whom to contact in the event of a 

research-related injury to the subject” [40 CFR 

26.116(a)(7)]. 

Information about the research often best can be 

answered by the researcher. However, it may benefit 

researchers and participants if information about the 

research can be obtained from or confirmed by a trusted 

independent person or organization. Participants also 

need to know how they can contact someone, 

independent from the researcher, who can answer 

questions concerning the rights of research participants 

and provide information on grievance procedures and 

research-related injuries. These questions could be 

addressed to the IRB, an ombudsman, an ethics 

committee, or other knowledgeable administrative body. 

Consent documents are expected to have at least two 

names with appropriate telephone contact 

information⎯one that can provide information 

regarding the research and another that can provide 

information regarding their rights as research 

participants. Grievance procedures should be structured 

so that grievances reach the approving IRBs and 

sponsoring organizations. 

5.3.1 Ombudsman 

An ombudsman is a neutral independent advocate 

for research participants (and their families or guardians, 

where applicable). Institutions and IRBs may 

recommend or require the use of an ombudsman in 

certain types of research studies, particularly those 

seeking to study vulnerable populations. Ombudsmen 

can fill several roles as participant advocates. They may 

be an independent source of information regarding the 

study. They may be present during the informed consent 

process to ensure that risks, benefits, and study 

requirements are communicated correctly and 

understood by potential participants or their guardians. 

An ombudsman may be used in studies involving 

prisoners or military personnel to ensure that there is no 

coercion to participate. And the ombudsman may 

61
communicate problems or grievances raised by research 

participants to the IRB and sponsoring organization. 

5.3.2 Community Advisory Board 

CABs can help ensure that participant rights are 

considered and addressed during the study design and 

can play an important role in monitoring the research 

process. Community members may choose to seek 

information about the study from the advisory panel, as 

an independent entity, before deciding whether to enroll. 

Representatives from such advisory boards can be 

included in the research team that designs the study (see 

Section 2.3). The role of CABs is more fully discussed 

in Section 6. 

5.4 Creating a Supportive Environment for 

Research and Interaction 

It is recommended that researchers and institutions 

strive to create a supportive environment for research 

and interaction with research participants and 

communities. At the personal level, this means 

researchers building trust with individuals and treating 

them with respect. Following the IOM recommendations 

about the informed consent process⎯that it “should be 

an on-going, interactive dialogue between research staff 

and research participants involving the disclosure and 

exchange of relevant information, discussion of that 

information, and assessment of the individual’s 

understanding of the discussion” (Recommendation 4.1, 

IOM, 2002)⎯should go a long way in establishing a 

supportive environment with the individual participants. 

At the community level, engagement of the community 

throughout the design, conduct of the study, and followup will support trust-building and positive interactions. 

Developing and providing this kind of support can be 

challenging in large-scale studies, and particularly those 

that cross communities or are conducted across large 

geographic areas. Institutions need to recognize the need 

for, and value of creating supportive research 

environments by providing adequate funding because 

effective interaction takes considerable time and effort. 

Many of the factors that create a supportive 

environment for research participants are described in 

the Report and Recommendations on Public Trust in 

Clinical Research for the NIH Director from the 

Director’s Council of Public Representatives (COPR)

(NIH, 2005). Although the advice from this workshop 

was developed in the context of NIH-supported clinical 

research, many of the recommendations are applicable to 

observational human exposure studies and human 

subject research in general. A summary of 

recommendations from the report for enhancing public 

trust is provided in Appendix D. The recommendations 

are focused on the following areas. 

• Building trust through community partnerships 

• Building relationships with patients (participants) 

(True partnerships with patients may not be possible, 

but bidirectional relationships must be enhanced.) 

• Building partnerships with community providers 

• Building trust in scientists 

• Building trust in the (EPA) and scientific research. 

5.5 Recruitment Strategies 

Many strategies are used to select and recruit people 

into research studies requiring human participation. The 

IRB is responsible for reviewing the selection process to 

ensure that it is, above all, equitable. The requirement 

for IRB review is stated in 40 CFR 26.111(a)3. 

Selection of subjects is equitable. In making this 

assessment, the IRB should take into account the 

purposes of the research and the setting in which the 

research will be conducted and should be particularly 

cognizant of the special problems of research 

involving vulnerable populations, such as children, 

prisoners, pregnant women, mentally disabled 

persons, or economically or educationally 

disadvantaged persons. 

The IRB guidebook is an excellent resource for 

consideration of concerns and elements for equitable 

participant selection (U.S. HHS, 1993). It states that 

“Defining the appropriate group of subjects for a 

research project involves a variety of factors⎯

requirements of scientific design, susceptibility to risk, 

likelihood of benefit, practicability, and considerations 

of fairness.” The IRB guidebook raises a number of 

points to consider in the process for selection of human 

participants (see Text Box 5-5). 

Various participant recruitment strategies may be 

used depending on the type of research being performed 

and the population of interest. This section addresses the 

strategies and approaches for identifying and contacting 

people and subsequent recruitment into a research study. 

Sampling design approaches and issues, such as 

statistical issues regarding representative and nonrandom 

sampling designs, oversampling of subpopulations, and 

environmental justice considerations are part of the 

study design process described in Section 2 and are 

critical for deciding which recruitment approaches will 

be used. 

62
Some of the common approaches for identifying and 

making initial contact with potential participants include, 

but are not limited to 

• direct telephone or in-person contact with a person 

selected through a statistical sampling process to 

obtain a representative sample of the population being 

studied; 

• use of print or other media advertisements, often used 

to recruit people in a community with specific 

characteristics; 

• advertisement or word-of-mouth contacts through 

community groups, civic organizations, or other types 

of organizations; and 

• recruitment at physicians’ offices, hospitals, and 

clinics or at churches, schools, or other social 

institutions, either in person or through the use of 

advertisements or study brochures. 

CABs can be consulted regarding proposed 

approaches for recruitment in community-based 

research. All procedures and materials for participant 

recruitment are reviewed and approved by the IRB prior 

to implementation. Some of the materials prepared for 

recruitment might include the following. 

• Recruitment scripts⎯prepared scripts used for inperson or telephone study information and recruitment 

contacts 

• Printed materials⎯brochures, flyers, newspaper 

advertisements, letters, and information articles 

• Audio/visual materials⎯radio and television scripts, 

video segments, public service announcements 

• Internet postings⎯study announcements and 

information, links to study materials, links to related 

information. 

The IRB reviews all recruitment material to ensure 

that it does not adversely affect the informed consent 

process, is consistent with the study protocol, and is 

likely to result in equitable participant selection. IRBs 

will carefully consider how information regarding 

payment for participation is presented to potential 

participants so as not to create undue influence. 

Participant recruitment may be performed directly 

by the researcher or staff members of the researcher’s 

organization, or other individuals or organizations may 

be asked to recruit or make initial informational contacts 

with potential participants. All persons involved in 

recruiting must adhere to the procedures and materials 

approved by the IRB. It is recommended that sponsoring 

organizations should not pay recruiters on a perindividual basis to minimize the likelihood that 

individual recruiters will put undue pressure on potential 

participants to enroll. 

5.6 Retention Strategies

Some observational human exposure studies require 

only a single visit or a single set of visits with a 

participant over a relatively short time period (e.g., 24 

hours or 1 week). Other studies may involve repeated 

interaction with participants over longer periods of time. 

Longitudinal study designs require retention strategies 

that ensure that adequate sample sizes are maintained for 

meeting study objectives. It is recommended that 

researchers and IRBs evaluate the level of burden in 

longitudinal studies and ensure that retention strategies 

are not likely to create conditions of coercion or undue 

influence. 

Some of the common strategies for maintaining high 

retention rates in longitudinal studies are listed in Text 

Box 5-6. 

Text Box 5-5. IRB Guidebook Issues on 

Identifying Subjects 

1. Who will bear the burden? Who will reap the benefits? 

2. Is there a disproportionate burden on any single group? 

3. Is the proposed subject population required or justified? 

4. Are there susceptible groups of people who should be excluded 

from the research? 

5. Are anticipated benefits distributed fairly? Do others have a 

greater need to receive any of the anticipated benefits? 

6. Are the research burdens distributed fairly? 

7. Will any special physiological, psychological, or social 

characteristics of the subject group pose special risks for them?

8. Would it be possible to conduct the study with other, less 

vulnerable subjects? 

9. Has the selection process overprotected potential subjects who 

are considered vulnerable (e.g., children, cognitively impaired, 

economically or educationally disadvantaged persons, patients 

of researchers, seriously ill persons), so that they are denied 

opportunities to participate in research? 

10. If the subjects are susceptible to pressures, are there 

mechanisms to reduce the pressures or minimize their impact? 

Text Box 5-6. Common Strategies for Maintaining High 

Retention Rates in Longitudinal Studies 

• Developing and maintaining a strong study identity 

• Building participant trust 

• Communicating regularly with participants 

• Providing feedback that is of use to participants 

• Maintaining confidentiality 

• Incorporating active participant tracking mechanisms 

• Maintaining reasonable levels of burden 

• Providing periodic tokens of appreciation 

• Providing reasonable levels of payment at each time point, 

sometimes including escalating payments or a higher final 

payment for completion of all study activities

63
It is important that strategies that use payments to 

encourage retention should be carefully scrutinized 

against the possibility that they will result in undue 

influence or diminish voluntary participation. Payments 

that cover expenses and for time and burden at each visit 

have to be reasonable, and researchers and IRBs should 

consider whether the cumulative level of payments over 

time or the use of escalating payments or final bonus 

payments might present undue influence on 

decisionmaking regarding participation. Participants 

have to feel capable of withdrawing from participation at 

any time, and escalating payments or completion 

bonuses can impact decisions to withdraw. Withholding 

all payment until all study visits are completed or 

making payment contingent on completing all activities 

is not an acceptable practice in most longitudinal studies 

because it can diminish the capacity for voluntary 

participation. (See the discussion about payment issues 

in long-term studies in Section 5.2.3.) 

People are more likely to continue active 

participation in longitudinal studies when they believe 

that the research is important, and that they are making a 

valuable contribution, are receiving regular feedback, 

and are treated with courtesy and respect by researchers. 

Observational human exposure studies sometimes 

involve substantial burdens of time and effort. Over long 

periods, this level of burden can reduce retention. It may 

be necessary to develop novel methods that reduce 

participant time and effort or to focus the study design so 

that fewer study procedures are implemented at any time 

point. Because the time needed to analyze samples, 

verify results, and perform data analyses can be long, it 

may be difficult to provide timely feedback to 

participants in observational human exposure studies. 

Researchers might consider including simple measures 

that can provide immediate and useful information of 

value to participants to encourage continued 

participation. Effective use of these strategies will 

reduce the need for higher payments to encourage 

retention. 

5.7 Ensuring Recruitment or Retention 

Methods Will Not Lead to Unacceptable 

Risk

Researchers and IRBs need to ensure that the 

procedures and materials used to recruit and retain study 

participants in observational human exposure studies do 

not “undermine free and informed consent by leading 

parents to expose their children to unacceptable risks. 

(NRC and IOM, 2005)” Payments in these studies 

should not be so high that they would cause an undue 

inducement for a participant to use a product they would 

not normally use or to perform an activity that they 

would not normally perform. Not only would this bias 

the study results but may lead to higher than normal 

levels of exposure. Alternatively, the act of studying one 

set of conditions or activities in an observational human 

exposure study could lead participants to assume that 

those conditions or activities involve substantial risk. In 

response, they subsequently may change their activities 

in ways that could lead to possibly higher risks. The 

potential for such unintentional outcomes is difficult for 

researchers to gauge but requires researcher caution in 

how information and results are conveyed. However, if 

the informed consent process is truly “an on-going, 

interactive dialogue . . . involving the disclosure and 

exchange of relevant information,” then such 

misunderstandings should be minimized. 

References

AAP (American Academy of Pediatrics Committee on 

Environmental Health) (2003). Pediatric and 

Environmental Health. (2nd Edition). Elk Grove Village, 

IL: American Academy of Pediatrics. 

Ackerman TF (1989). An ethical framework for the practice of 

paying research subjects. IRB 11(4):1-4. 

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 

Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/

40cfr26_06.html [accessed 12 June 2007]. 

CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines 

for Biomedical Research Involving Human Subjects. World 

Health Organization. Geneva, Switzerland. Available: 

http://www.cioms.ch/frame_guidelines_nov_2002.htm

[accessed 12 June 2007]. 

Diekema DS (2005) “Payments for Participation of Children 

in Research.” Chapter in: Kodish, E, Editor. Ethics and 

Research with Children: A Case-Based Approach. New 

York, NY: Oxford University Press. 143-160. 

Dickert N, Emanuel E, Grady C (2002). Paying research 

subjects: an analysis of current policies. Ann Intern Med

136(5):368-373. 

Emanuel EJ (2004). Ending concerns about undue 

inducement. J Law Med Ethics 32(1):100-105. 

Emanuel, EJ, Wendler D, Grady C (2000). What makes 

clinical research ethical? JAMA 283(20): 2701-2711. 

64
Erlen JA, Sauder RJ, Mellors MP (1999). Incentives in 

research: ethical issues. Orthop Nurs 18(2):84-87. 

European Parliament (2001). On the approximation of the 

laws, regulations, and administrative provisions of the 

Member States relating to the implementation of good 

clinical practice in the conduct of clinical trials on medicinal 

products for human use. Directive 2001/20/EC Article 4(d) 

of the European Parliament and of the Council of 4 April 

2001. 

Flory J, Emanuel E (2004). Interventions to improve research 

participants’ understanding in informed consent for 

research: a systematic review. JAMA 292(13):1593-1601. 

Fry CL, Ritter A, Baldwin S, Bowen KJ, Gardiner P, Holt T, 

Jenkinson R, Johnston J (2005). Paying research 

participants: a study of current practices in Australia. J Med 

Ethics 31:542-547. 

Grady, C (2005) Payment of clinical research subjects. J Clin 

Invest 115:1681-1687. 

Grady C, Dickert N, Jawetz T, Gensler G, Emanuel E (2005). 

An analysis of U.S. practices of paying research 

participants. Contemp Clin Trials 26:365-375. 

Iltis AS, DeVader S, Matsuo H (2006). Payments to children 

and adolescents enrolled in research: a pilot study. 

Pediatrics 118(4):1546-1552. 

IOM (Institute of Medicine) (2004). Ethical Conduct of 

Clinical Research Involving Children. Marilyn J. Field and 

Richard E. Behrman (eds). Washington, DC: The National 

Academies Press. 

IOM (Institute of Medicine) (2002). Responsible Research: A 

Systems Approach to Protecting Research Participants. 

Daniel D. Federman, Kathi E. Hanna, and Laura Lyman 

Rodriguez (eds). Washington, DC: The National Academies 

Press. 

Menikoff J (2005). Of babies, bugs, and bombast: A look 

behind the crash-and-burn of the CHEERS pesticide study. 

Med Res Law Policy Rep 4(14):586-512. 

NCS (National Children’s Study) (2007) Research Plan, 

Volume 1, Version 1.1, June 20, 2007. Available: 

www.nationalchildrensstudy.gov/research/research_plan/upl

oad/Research_Plan_Volume_1.pdf [accessed 12 September 

2007.]. 

NIH (National Institutes of Health) (2005). Report and 

Recommendations on Public Trust in Clinical Research for 

the NIH Director from the Director’s Council of Public 

Representatives (COPR). National Institutes of Health, 

Director’s Council of Public Representatives, January 14, 

2005. Available: http://copr.nih.gov/reports/public_trust.asp

[accessed 12 June 2007]. 

NRC (National Research Council) (2004) Research Priorities 

for Airborne Particulate Matter: IV. Continuing Research 

Progress. Washington, DC: The National Academies Press. 

Available: 

http://books.nap.edu/openbook.php?record_id=10957

[accessed 16 August 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

OMB (Office of Management and Budget). (2006a). Standards 

and Guidelines for Statistical Surveys. Section 2.3, Data 

Collection Methodology. 

http://www.whitehouse.gov/omb/inforeg/statpolicy/standard

s_stat_surveys.pdf

OMB (Office of Management and Budget). (2006b). 

Questions and Answers When Designing Surveys for 

Information Collection. Office of Information and 

Regulatory Affairs. January, 2006. 

http://www.whitehouse.gov/omb/inforeg/pmc_survey_guidanc

e_2006.pdf

Paasche-Orlow MK, Taylor HA, Brancati FL (2003). 

Readability standards for informed-consent forms as 

compared with actual readability. N Engl J Med 348(8):721-

6. 

Russell ML, Moralejo DG, Burgess ED. (2000). Paying 

research subjects: participants' perspectives. J Med Ethics

26(2):126-30. 

U.S. DHEW (U.S. Department of Health, Education, and 

Welfare) (1979). The Belmont Report: Ethical Principles 

and Guidelines for the Protection of Human Subjects of 

Research. Washington, D.C.: National Commission for the 

Protection of Human Subjects of Biomedical and 

Behavioral Research. Available: 

http://ohsr.od.nih.gov/guidelines/belmont.html [accessed 

June 2007]. 

U.S. FDA (U.S. Food and Drug Administration) (1998). 

Information Sheets: Guidance for Institutional Review 

Boards and Clinical Investigators 1998 Update. U.S. Food 

and Drug Administration, Washington, DC. Available: 

http://www.fda.gov/oc/ohrt/irbs/toc4.html [accessed May 

2007]. 

U.S. HHS (U.S. Department of Health and Human Services) 

(1993). Protecting Human Research Subjects: Institutional 

65
66

Review Board Guidebook. Office for Human Research 

Protections. Available: 

http://www.hhs.gov/ohrp/irb/irb_guidebook.htm [accessed 

12 June 2007]. 

VanderWalde A (2005). Undue inducement: the only 

objection to payment? Am J Bioethics 5(5):25-27. 

Weise KL, Smith ML, Maschke KJ, Copeland L (2002). 

National practices regarding payment to research subjects 

for participating in pediatric research. Pediatrics

110(3):577-582. 

Wendler D, Rackoff JE, Emanuel EJ, Grady C (2002). The 

ethics of paying for children’s participation in research. J 

Pediatr 141(2):166-171. 
SECTION 6

Building and Maintaining Appropriate Community and 

Stakeholder Relationships 

Community engagement promotes active 

community involvement in the processes that shape 

research strategies and the conduct of research studies. 

In developing this document, NERL held an expert panel 

workshop to identify the content and organization of this 

document (ERG, 2007). That panel of experts concluded 

that the need to engage the community in observational 

research was based on the ethical principles of (1) 

respect for persons, which manifests itself in both a 

respect for the individual and, through respect for the 

community, their culture; (2) fairness, resulting in efforts 

to assure equity in resources, burden, and benefits; and 

(3) beneficence, including “empowering the community 

to endure.” 

Involving the community in the research effort can 

improve the research both scientifically and ethically. In 

the document, Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children, 

the joint NRC-IOM committee found that community 

involvement was a “guiding theme” of their findings 

(NRC & IOM, 2005). Because the researchers were 

working in the homes and communities of the 

participants, they faced issues that were different from a 

clinical setting. They were challenged to think about the 

fundamental ethical principles in the context of the 

research setting and about how those ethical principles 

should be interpreted in that setting. “When researchers 

discuss a planned study with community representatives, 

understand their concerns and needs, and respond to 

them, protocols can be strengthened both scientifically 

and ethically” (p. xii, NRC & IOM, 2005). Just as was 

described in Section 5, where the informed consent 

process was described as needing to be “an on-going, 

interactive dialogue between research staff and research 

participants involving the disclosure and exchange of 

relevant information, discussion of that information, and 

assessment of the individual’s understanding of the 

discussion” (Recommendation 4.1, IOM, 2004), so, too, 

the process of community involvement should be a 

process of effective two-way communication. These 

NRC & IOM comments emphasize how critical 

effective, bidirectional communication is to the scientific 

and ethical foundation of a research study in such a 

setting. 

EPA has established a public involvement policy to 

“improve the content of the Agency’s decisions and 

enhance the deliberative process” (U.S. EPA, 2003) (see 

Text Box 6-1). The policy is focused largely on Agency 

decisionmaking processes (e.g., rulemaking, permit 

issuance, Superfund remediation, etc.), whereas observational human exposure studies are intended to provide 

data to inform those decisionmaking efforts. 

Nonetheless, the Agency policy may be helpful in 

planning for community involvement in observational 

human exposure studies. The policy is intended to 

promote mutual trust and openness between EPA and the 

public, to improve the quality of the Agency’s actions, 

and to promote the public’s involvement in the Agency’s 

mission of promoting human health and the 

environment. The policy identifies seven basic steps for 

effective public involvement and offers guidance for 

implementing public involvement at EPA. 

Text Box 6-1. Seven Basic Steps for 

Public Involvement at EPA 

1. Plan and budget for public involvement activities. 

2. Identify the interested and affected public. 

3. Consider providing technical or financial assistance to 

facilitate involvement. 

4. Provide information and outreach to the public. 

5. Conduct public consultation and involvement activities. 

6. Review and use input, and provide feedback to the public. 

7. Evaluate public involvement activities . 

67
6.1 Approaches to Community Involvement 

Community involvement can take many forms. The 

forms of community involvement are not mutually 

exclusive, and researchers may use several approaches 

for seeking community involvement. The nature and 

extent of community involvement reasonably would 

depend on the nature of the research itself and the 

affected community. In Section 2, the authors discussed 

some reasons for involving the community early in the 

research planning and scoping process and the benefits 

that community involvement may bring to the research 

effort. “Community residents can be involved in the 

research process as research staff, through community 

consultation and review, membership on community 

advisory boards, and involvement in a community-based 

participatory research process” if that is used (p. 83, 

NRC & IOM, 2005). In addition, IRBs may seek 

additional community representation on the IRB panel. 

The Centers for Disease Control and Prevention 

(CDC) recommends nine governing principles for 

engaging communities in health-related research (see 

Text Box 6-2). Health research is a “privileged and 

empowered activity in that the researchers have special 

access to resources and sensitive information about 

people and, through the analysis and presentation of 

findings, are able to influence the way people think and 

have considerable influence on decisions regarding the 

allocation of resources” (CDC, 1997). Regardless of the 

approach utilized to involve the community in research, 

whether the process employs community-based 

participatory research (CBPR) or another community 

engagement method, researchers should guide their 

interactions with community members using these 

underlying principles to promote the aforementioned 

ethical principles of respect of persons, fairness, and 

beneficence. 

One form of community involvement is to include 

qualified members of the community on the research 

staff. Section 2 advocates community representatives as 

part of the research team. Paid research staff members 

from the community could serve as valuable consultants 

for protocol development and research design, including 

how to collect the data, how to recruit and retain 

participants, and how to interpret and disseminate the 

results. However, including paid research staff from the 

community may introduce a conflict of interest among 

community members: community representatives may 

feel a greater allegiance to the researchers providing the 

payment and be less inclined to uphold the interests of 

the community. In addition, the community may come to 

view the paid research staff from the community as 

“outsiders.” To help alleviate these potential issues, 

researchers should ensure an equitable distribution of 

paid research work among different communities within 

the larger community as to not promote a perceived bias 

among community members. Additionally, when 

possible, researchers should make efforts to provide 

payments to community members employed as research 

staff through community partner organizations to 

prevent conflict of interest issues. Refer to Section 5 for 

further discussion on remuneration of community 

members as research participants. 

Furthermore, institutional and community partners 

need to ensure that anyone involved as part of the 

research team has the requisite research and social skills. 

Researchers often place a greater emphasis on scientific 

over social skills and may, in turn, assume that they have 

Text Box 6-2. Community Engagement Principles for 

Researchers 

(From CDC, 1997) 

Requirement Explanation 

Clarity Clear communication of the study objectives, 

research goals, and the populations or 

communities of interest. 

Knowledge of 

the Community 

Familiarity with the economic conditions, 

political structures, demographics, history, past 

research experiences, and research perceptions 

of the community. 

Visibility Travel to the community, interact with formal 

and informal leadership, and establish 

relationships to build trust. 

Acceptance Acknowledge, without judging, the assets and 

deficits of the community. 

Partnership Balanced discussion and shared 

decisionmaking among participants concerning 

risks, responsibilities, expectations, benefits, 

and investment. 

Respect Value the diversity of culture, history, beliefs and 

opinions within the community for improved 

understanding. 

Asset Utilization Identify and mobilize community assets to 

improve scientific credibility of the interpretation 

and dissemination of results. 

Flexibility Anticipate changes within the community in 

regard to perceived benefits of research and 

stakeholder interest and additional time and 

resource needs. 

Commitment Prepare to engage the community beyond the 

constraints of the research projects, before and 

after, to promote longevity of the relationship for 

future research . 

68
the necessary expertise to conduct research in 

community settings. Likewise, research staff from the 

community should have knowledge of research 

fundamentals. Education and training targeted at both 

the institutional researcher and the community 

researcher may, respectively, improve the competence of 

researchers to work with communities and the scientific 

literacy of the public. 

A recent NERL study, the Detroit Exposure and 

Aerosol Research Study (DEARS), included community 

members as paid members of the research team. The 

community researchers were instrumental in recruiting 

study participants from the seven study neighborhoods 

in Detroit that required multiple door-to-door visits to 

the homes of potential participants to discuss the 

DEARS study. The success of DEARS was dependent 

on researchers developing strong relations with 

community leaders and State and local organizations. 

A second approach to community involvement is to 

seek community consultation and review. Researchers 

may periodically meet with community residents in a 

process of “engagement, dialogue, and feedback” (Dula, 

1994) to discuss research plans, research progress, and 

results. The objective is to seek a dialogue with 

community residents to promote co-learning and asset 

sharing between the researchers and the community. 

Effective communication⎯open, honest, jargon free⎯is 

imperative to the successful use of this approach. 

Effective communication ensures that the community 

has a voice in the research process for the expressed 

purpose of increasing the community’s trust and 

engagement in the research, the applicability of the 

research to the community’s needs, and the benefit of the 

research to the community. Authentic community 

consultation embraces the “experiential knowledge of 

the average citizen” (Leung et al., 2004). When 

developing research budgets and timescales, researchers 

who plan to incorporate community consultation and 

review in the research process should take into account 

the additional expenses and time necessary for 

community marketing efforts and travel. 

 Corburn (2002) describes a successful community 

participation in an EPA exposure assessment in 

Brooklyn, NY. He explains how a shift of focus from 

risk assessment to exposure assessment may provide an 

opportunity for community engagement to improve the 

technical assessment. Listed among the specific factors 

integral to the assessment’s success are the incorporation 

of local, nonexpert information by community groups 

during the consultation and review process that was used 

to modify the conventional risk assessment process and 

the inclusion of community-based organizations on the 

scientific research team as contributors to the data 

collection, modeling, and interpretation processes, where 

they provided data and expertise not available through 

traditional research frameworks (Corburn, 2002). 

Community advisory boards (CABs) also have been 

used as an approach for getting the community involved 

in the research effort. A CAB could be formed to serve 

as a liaison between participants and researchers. In 

particular, CABs can advise the researchers about 

community concerns and assist in the development of 

materials to explain the study to potential participants. 

CABs should be sufficiently large to ensure a diversity 

of community views, perspectives, and attitudes. 

Representatives from the board may be selected for 

participation on the research team. In Section 5, it was 

noted by the authors that such a board could function as 

an oversight committee in case of any participant 

grievances. According to Quinn (2004), the success of 

CABs “lies in the ability of the researchers and CABs to 

form a true partnership, enabling their different voices to 

be heard equally.” Creating a CAB may be perceived as 

“window dressing” and, in fact, harm relationships with 

the community if researchers are not truly open to 

working with the CAB. 

O’Fallon and Dearry (2002) describe how the Tribal 

Efforts Against Lead (TEAL) partnership collaborated 

with EPA to clean up and minimize exposure to toxins 

from a Superfund site in Ottowa County, OK. The 

TEAL project utilized the services of a CAB, which 

included representatives from several local tribes, to 

ensure that the research would be responsive to the needs 

and concerns of the tribal residents. The CAB facilitated 

the researchers interactions with the target communities 

“by helping the investigators interpret data and distribute 

information to the communities” and “developing and 

conducting the training” of the community members on 

risk reduction strategies. The value of the research to the 

TEAL target communities would have been diminished 

had a CAB not been formed to assist the researchers 

with specific best practices to use when engaging the 

tribal members and the appropriate tribal leadership 

structures. 

Another potential approach to involve the 

community is to use a CBPR approach, wherein the 

community is actively involved in each step of the 

research process, including sharing of decisionmaking 

power and resources. This will impact decisions about 

study design, study methods, dissemination of findings, 

and resulting actions. “Under the principles of 

community-based participatory research, research must 

69
address the concerns, needs, and priorities of the 

communities where it is conducted and lead to actions 

and changes that benefit the community” (p. 86, NRC & 

IOM, 2005). Information about CBPR approaches can 

be found online at the HHS Web sites 

http://www.ahrq.gov/clinic/epcsums/cbprsum.htm and 

http://www.ahrq.gov/research/cbprrole.htm. 

Israel et al. (2005a) reviewed the results of CBPR 

efforts at six Children’s Centers co-funded by EPA and 

the National Institute of Environment Health Sciences. 

They found that considerable commitment of resources 

and time are needed for the approach to be successful, 

and the translation of research findings into interventions 

and policies is of the utmost importance. Community 

partners played little role in defining the research topics 

and data analysis, but were vital to disseminating the 

findings to the community. Keeler et al. (2002) describe 

using CBPR methods to evaluate personal and 

community-level exposures to particulate matter among 

asthmatic children in Detroit. The research partnership, 

Community Action Against Asthma (CAAA), consisted 

of representatives from local health organizations, 

community environmental advocacy groups, State and 

local governmental agencies, and academia. The CAAA 

partnership credits community involvement as active 

research partners in the research process with the success 

of the project to acquire “more relevant exposure data 

for the study of children in urban neighborhoods” and to 

provide “immediate knowledge and understanding of the 

outcomes and results of the combined environmental 

health analysis to the communities” (Keeler et al., 2002). 

There are, however, several drawbacks to utilizing 

CBPR methods that researchers should consider before 

developing a CBPR project. CBPR is time consuming 

(develop partnership, establish and agree on research 

aims and objectives, disseminate results to the 

community using appropriate methods, and review 

manuscripts and presentations) and not conducive to 

situations where rapid decisions are necessary given a 

tight timeline. Weighing the research need versus the 

community’s desire for an intervention is the greatest 

source of tension in conducting CBPR (Israel et al., 

2005b). 

One additional opportunity for community input 

may involve participation on an IRB. IRBs are required 

by the Common Rule to have members who are sensitive 

to “community attitudes” [40 CFR 26.107(a)]. How they 

meet this obligation is totally at their discretion, and 

NERL researchers have no influence. There have been a 

number of recent articles in the literature about IRBs that 

have envisioned a need for more regulatory reform 

(Ledford, 2007). Ideally, the IRB should take into 

account the views of the community. Quinn (2004) 

argues for extending protections now reserved for 

individuals to groups (populations and communities) 

through CABs. Her argument is that there are “ethical 

issues related to research with communities that are 

distinctly different from the ethical issues related to 

research with individuals.” CAB members have to be 

educated on human subjects’ protections, should 

represent their communities honestly, and need to be 

willing to interact with researchers on complex research 

issues. 

Gilbert (2006) goes even further. He suggests 

supplementing or even replacing traditional IRBs with 

environmental health and community review boards 

(EHCRBs). He argues that traditional IRBs are 

inadequate for the review of community-based research 

because they were developed to address issues related to 

individuals involved in research projects, not 

communities. He proposes EHCRBs that combine the 

fundamental and ethical concept of traditional IRBs with 

an expanded ethical construct of dignity, veracity, 

sustainability, and justice, with added emphasis on 

community. He envisions that an EHCRB would 

function as an IRB with the requirements and 

responsibilities for review for the protection of human 

subjects, plus the additional role for review of 

community issues associated with the research project. 

Gilbert’s recommendation for EHCRBs is consistent 

with the recommendations of the authors of the NRC & 

IOM report who recommended that “Institutional review 

boards that review housing health hazards research 

involving children should ensure that those boards have 

the necessary expertise to conduct a complete and 

adequate review, including expertise on research 

involving children and community perspectives” (NRC 

& IOM, 2005). 

Involving community representatives in the IRB 

process is challenging for IRBs, however. One challenge 

could be the need to provide sufficient training to 

community members about the IRB process and the 

regulations governing IRBs. This can be significant if 

members sit on an IRB for a limited time to review 

specific community-based studies. In some cases, IRBs 

may invite community members to participate in the IRB 

process as nonvoting members to solicit the community 

perspective. This approach, which would be totally at the 

discretion of the IRB, might reduce the burden on the 

community representative by reducing training 

requirements. 

70
6.2 Issues in Community Involvement 

There are a number of issues that need to be 

addressed in any efforts to ensure community 

involvement. The Expert Panel that was convened to 

advise NERL about scientific and ethical issues in 

observational human exposure studies discussed a 

number of challenges (ERG, 2007). The topics that the 

expert panel identified as issues are discussed below. 

6.2.1 Defining “Community” 

“Community” refers to a group of people united by a 

shared attribute, and the attributes can be wide-ranging, 

such as geography, culture, social characteristics, values, 

interests, traditions, or experiences (ERG, 2007). 

Community can be defined broadly (as a system of 

interrelated groups operating to meet the needs of its 

members) or more narrowly (as the population from 

which study participants are selected). For observational 

field studies, the Expert Panel from the workshop 

suggested the narrow definition. A narrow definition 

allows social and cultural factors to be included but 

excludes government agencies, industry, and others who 

do not necessarily represent the interests of the 

participants (ERG, 2007). 

Central to the definition of a community is a sense 

of “who is included and who is excluded from 

membership” (NRC & IOM, 2005). A person may be a 

member of a community by choice, as with voluntary 

associations, or by virtue of their innate personal 

characteristics, such as age, gender, race, or ethnicity 

(NRC & IOM, 2005). As a result, individuals may 

belong to multiple communities at any one time. When 

initiating community engagement efforts, one should be 

aware of these complex associations in deciding which 

individuals to work with in the targeted community. 

Quandt et al. (2001) discuss a CBPR research 

project, Preventing Agricultural Chemical Exposure in 

North Carolina Farmworkers, where the process of 

defining a community was complicated by language, 

ethnic and racial stereotypes, and lack of organization. 

Many of the affected farmworkers originated outside the 

United States from several different Spanish-speaking 

countries and possessed contradicting viewpoints on 

research and the utility of community organization. 

Moreover, the community organization tailored for this 

farmworker demographic did not include enough 

members to adequately populate the study. The 

researchers utilized multiple approaches, including 

community forums, community advisory councils, and 

public presentations, to identify a diverse, yet viable, 

community within the broader farmworker population. 

Through this process of using multiple participatory 

strategies to define the community, a sense of 

community was nurtured among the farmworkers 

collectively (O’Fallon and Dearry, 2002). 

Understanding and describing a community (CDC, 

1997) involves exploring factors related to

• people (including socioeconomics and demographics, 

health status, and cultural and ethnic characteristics),

• location (geographic boundaries),

• commonalities (including shared values, interests, and 

motivating forces), and

• power relationships (including formal and informal 

lines of authority and influence, stakeholder 

relationships, and resource flows). 

It is important to distinguish between stakeholders 

and the community, but both should be engaged at some 

point in the course of a study. Stakeholders are groups or 

organizations that may affect, be affected by, or perceive 

themselves to be affected by a decision or activity. 

Stakeholders may have a direct or indirect interest in the 

“matter” of interest. They may include individuals; 

environmental, social, or community nongovernment 

organizations (NGOs); government entities; businesses; 

and industry. Stakeholders include business, industry, 

and various levels of government. A critical difference 

between the community and stakeholders is that the 

community has a right to speak for its own interests, but 

stakeholders cannot represent or speak for the 

community. Although relationships with stakeholders 

can, at times, be confrontational, stakeholders often 

provide useful information and expertise. When 

stakeholders and the community members overlap in 

particular individuals, it is important to distinguish the 

role in which the individual is acting (ERG, 2007). 

6.2.2 Identifying Who Represents the 

Community 

To sufficiently represent the community, an 

individual has to have not only the right to speak for the 

community’s interests (a right afforded by legitimate 

membership in the group) but also should be able to 

describe those interests on behalf of the community. 

Identifying those who represent the community is not 

simply a matter of identifying the most vocal activists 

because those individuals do not necessarily represent 

the interests of the entire community. In fact, several 

individuals may be necessary to adequately represent the 

diversity of viewpoints within a community; in such 

cases, a CAB may be appropriate (ERG, 2007). One of 

the researcher’s first steps should be asking the potential 

participants from the community who they see as a 

71
legitimate representative (i.e., someone who can speak 

for them). Corburn cites an example of a locale in 

Brooklyn, NY, that contained individuals with widely 

different backgrounds. It was impossible to identify 

appropriate spokespeople, or even to define the nature of 

the community, without talking with community 

members (Corburn, 2007). 

The NRC & IOM (2005) Report also discusses the 

issue of who can represent the identified community. 

Some communities may have a formal governmental 

structure and a recognized political authority (e.g., 

Native American tribes). Other communities may have 

clearly identifiable leaders (e.g., religious communities), 

whereas still other communities have no formal 

leadership structure at all. Whether there is a legitimate 

political authority or some other hierarchal leadership 

structure, the goal is to seek community input as to who 

best represents the interests of the community with 

regard to the proposed research project, rather than 

selecting those who are favorable to the research project. 

The NRC & IOM report cautions against the ethically 

questionable practice of seeking out population 

spokespeople and research participants whose positive 

response to a research plan can be predicted in advance 

and refers the reader to an article on this topic by Juengst 

(2000). 

With multiple sources of leadership and authority in 

many communities, careful consideration should be 

given to what aspect of the community a particular 

person will represent, and what efforts may be needed to 

ensure that the entire range of views in a community are 

obtained. Researchers should consider reaching out to 

multiple organizations such as churches, social service 

agencies, community-based organizations, and tenant 

and other community advocacy groups. 

6.2.3 Building Relationships and Trust 

A key first step in developing trust is to establish a 

relationship with the community before the study. Trust 

must be built; it cannot be assumed. This relationship 

involves not only listening to community input but 

actually taking it into consideration (ERG, 2007). A long 

history of research with no direct benefits and no 

feedback of results to the community, however, has 

contributed to a general mistrust of researchers by 

community members (Israel et al., 1998). Moreover, the 

recurring abuse of trust in communities is a reality that 

researchers should be aware of when attempting to build 

a long-term relationship (Minkler and Wallerstein, 

2003). Past ethical failures have created distrust among 

some communities and have produced great challenges 

for current community organizers. Although it may seem 

self-evident, researchers need to remember that ethical 

action, during all phases of the research, is necessary for 

developing and maintaining the trust of communities 

(Perkins and Wandersman, 1990; CDC, 1997). 

Developing trust is a difficult and time-consuming 

process. Israel et al. (2005b) suggest a number of ways 

partners can gain each other’s trust. First, partners can 

show respect by seriously considering the ideas and 

opinions of others. Second, trustworthiness can be 

demonstrated by following through with those things 

that each partner commits to. Third, partners have to 

respect confidentiality. Fourth, they recommend 

attending to each other’s interests and needs by 

participating in activities beyond the specific work of the 

partnership.23 A history of prior positive working 

relationships is also beneficial (Israel et al., 1998). 

Trust cannot be separated from respect. Potential 

participants need to see researchers fostering respect for 

community members and leaders to gain trust. For 

example, meeting with key community leaders and 

groups in their surroundings helps to build trust for a 

true partnership. Such meetings provide organizers of 

engagement activities with more information about the 

community, its concerns, and factors that will facilitate 

and constrain participation. Once a successful rapport is 

established, the meetings and exchanges with 

community members can become an ongoing and 

substantive partnership (ERG, 2007). 

One mechanism for helping to build trust may be a 

contract with the community. A community contract 

outlines the roles and expectations of both the researcher 

and the community. Living up to these agreements 

builds trust with all partners, and the establishment of 

the agreement helps reduce misunderstandings. 

Contracts or memorandums of understanding that outline 

the roles and expectations of the researcher and the 

community are discussed in both Minkler and 

Wallerstein (2003) and Israel et al. (2005b). An example 

outlining expectations in a partnership with tribal 

communities is presented in Appendix E of Minkler and 

Wallerstein (2003), whereas an example discussing 

access to data and authorship issues is presented in 

Appendix I of Israel et al. (2005b). An example of a 

memorandum of understanding between the University 

of Michigan School of Public Health, Detroiter’s 

Working for Environmental Justice, the Detroit Hispanic 

 

23 For a more detailed description of each of the suggestions 

for enhancing trust, please see Chapter 3 of Israel et al. (2005). 

72
Development Corporation, and the Warren Conner 

Development Coalition for a study investigating asthma 

is available at http://depts.washington.edu/ccph/pdf_files

/MOU10.pdf. 

Work within communities involves a considerable 

investment of researchers’ and residents’ time. It should 

be an ongoing, interactive exchange of information and 

ideas between the researchers and the community 

members, where voices are both heard and honored. 

Trust is fostered when all interested parties feel that they 

have influence, and that their input contributes to the 

community effort. The collaborations should be 

inclusive of the entire community, including those 

members with incompatible interests and perceptions. If 

participation, influence, and benefits are limited only to 

some of the partners, then distrust is likely, and the 

potential benefits of community involvement may be 

lost. Being inclusive can create some organizing 

challenges, but the benefit of effective community 

involvement “has the potential to lead to greater 

understanding of community perspectives of the risk and 

benefits of research, improve informed consent, increase 

study enrollment, enhance data validity and quality, and 

build trust for research” (NRC & IOM, 2005). 

6.2.4 Importance of Language and 

Communications with the Community 

Even when all partners and community members are 

speaking the same language, some terms are not 

necessarily understood by all. Communications with 

participants should be reviewed by all partners to ensure 

that the language used will be appropriate for all 

participants. At times, one method to communicate 

research findings will not fit all community members 

and partners. Even among the partners, understanding 

each other’s meanings is essential, so that all partners 

can move forward with a common understanding (Israel 

et al., 2005b). 

Furthermore, Minkler and Wallerstein (2003) note 

that “research must be produced, interpreted, and 

disseminated to community members in clear, useful, 

and respectful language.” Researchers, and especially 

researchers in a government agency, may have their own 

distinct lexicon. Researchers should be careful to avoid 

acronyms, jargon, or technical terms that may obscure 

the meaning or intimidate participants who are not 

familiar with the terms. Communicating in “plain 

language” to “explain the research in an honest, 

straightforward way” will help build a strong 

relationship with the community and the participants and 

also help enhance public trust (Recommendation 11, 

NIH, 2005). 

Culturally sensitive communication is necessary to 

developing effective research partnerships with 

communities. To develop effective communications, 

researchers must understand key aspects of the cultures 

influencing the intended audience and build that 

understanding into the communication strategy (Tillman, 

2002). The symbols, metaphors, visuals (including 

clothing, jewelry, and hairstyles), types of actors, 

language, and music used in communication materials 

all convey culture. Discussions with community 

members can assist researchers in identifying messages 

and images that resonate across groups or suggesting 

situations in which different messages or images are 

likely to work best. 

As discussed above and in Sections 5 and 7, 

communication materials must be tailored for each 

individual community and must be written in a language 

and at a reading level that will ensure comprehension. 

Many IRBs require materials to be prepared at a 5th 

grade reading level. Researchers should evaluate the 

reading level of all data collection instruments and study 

communication materials and should objectively 

measure comprehension in pretests prior to use in the 

study. Similarly, if translations of materials are required, 

certified translating services should be used to ensure 

accuracy and comprehension. 

6.2.5 Recognizing and Addressing 

Cultural Differences 

Building and maintaining appropriate community 

and stakeholder relationships requires acknowledgment 

of the diversity within communities with regard to many 

factors, including, but not limited to, race/ethnicity, 

religious beliefs, heritage, and lifestyles. Different 

groups in the study area may have different cultural 

norms and practices. The researchers should take these 

issues into consideration as they work in the community. 

Community partners can help researchers design the 

study to be attentive to the increasing heterogeneity of 

community groups (Minkler and Wallerstein, 2003, 

Chapter 4) and to the different boundaries of privacy 

(crucial when designing sampling strategies) of different 

groups (Israel et al., 2005b, Chapter 11). 

Vega (1992) provides a thorough discussion of the 

theoretical and pragmatic implications of cultural 

diversity for community research and explains that 

researchers should interact with communities using 

methods that promote understanding and demonstrate 

sensitivity and competence in working with diverse 

73
cultures (e.g., with respect to class, gender, ethnicity, 

race, age, and sexual orientation). To aid in this process, 

researchers should include sufficient time in their project 

timeline to interact and dialogue with the community 

before the study begins to understand the cultural issues 

that may affect the research. Researchers and the results 

of their work are expected to promote a strengthening of 

the community; however, it should be recognized that, 

given the heterogeneity and the diverse views within a 

community, the study findings potentially may conflict 

with the desires of the community or may promote 

feelings of anger or distrust among members of the 

community with each other. Enlisting the services of a 

third-party evaluator/mediator may be useful for 

sustaining positive relations between all research 

participants and the community at large. 

The Research Triangle Park Particulate Matter Panel 

Study (Williams et al., 2003), a NERL investigation of 

PM and related pollutants involving African-Americans 

in North Carolina, demonstrated an effective strategy for 

using communication to address cultural differences 

between the community and research personnel. Before 

beginning the research, the study design included time 

and a budget for building collaborations with 

organizations having close ties with the AfricanAmerican community to establish trust between the 

community and research team. Using input from the 

community partner organizations, the researchers 

developed a systematic communication plan to establish 

rapport with the community and to guide interaction 

between study participants and the key study personnel. 

A well-designed and culturally sensitive communication 

plan was integral to the success of the study. Eighty 

percent of the original participants completed the fourseason study (Williams et al., 2003). 

6.2.6 Honesty, Power Relationships, and 

Partnerships 

The NRC & IOM report (NRC & IOM, 2005) 

describes a relational paradigm that acknowledges that 

research is part of a broader societal context, with the 

conduct of research often mirroring a system in which 

power is unequally and perhaps unfairly distributed. The 

trust and mutual commitment required from the 

researchers and the community are subject to the overall 

power relations in society.24 The Expert Panel convened 

to discuss the content of this document recognized that 

 

24 A discussion of the evolution of theories on power relations, including the 

contribution of feminism, poststructuralism, and postcolonialism, can be 

found in Minker and Wallerstein (2003, Chapter 2). 

the researchers have a variety of forms of power that 

needed to be understood and acted on ethically (ERG, 

2007). One form of power is resources, both funds and 

access to resources and decisionmakers. Other forms of 

power may be more subtle, including expertise, which 

can intimidate or limit a participant’s choices. Peer 

pressure, fear of intimidation, expectations of benefits 

from the research, and power to stigmatize the 

community all, whether real or perceived, can influence 

the relationship between the researcher and the 

community. Many forms of power may be tipped toward 

the researcher, but the community often has power in the 

form of knowledge about the community that can impact 

the quality of the research effort. An ethical balance of 

power can lead to benefits for all partners (ERG, 2007). 

In describing principles in Methods in CommunityBased Participatory Research for Health, Israel et al.

(2005b) describe CBPR as facilitating “a collaborative, 

equitable partnership in all phases of research, involving 

an empowering and power-sharing process that attends 

to social inequalities.” One way to address the inequities 

is to ensure that the roles and responsibilities are 

mutually acceptable to all parties. Researchers involved 

in CBPR should recognize and address the inequalities, 

thereby promoting trust, mutual respect, open 

communication, information sharing, collaborative 

decisionmaking, and resource sharing. 

It is important that researchers recognize that 

partnerships with the community are ongoing processes 

that need to be monitored and maintained. As a study 

progresses, the dynamics of the partnership may change 

as roles and responsibilities for the partners change. All 

partners need to be willing to make the investment of 

time and resources necessary to maintain an effective 

partnership. 

6.2.7 Building a Lasting Infrastructure 

Infrastructure is anything that builds the capacity of 

the community by providing its members with skills and 

resources. Infrastructure building ideally occurs 

throughout the project and should be included in the 

overall plan (ERG, 2007). When involving the 

community in the planning process, investigators need to 

be forthright regarding funding limitations and research 

expectations, such as publication and dissemination of 

results. The community needs to be made aware of the 

ephemeral nature of funding, even if it results in 

apprehension toward involvement. 

Researchers should communicate early on those 

issues that will become important once the research has 

been completed, such as sustainability. Frankness is 

74
required to cultivate the community’s confidence and 

expertise over time. Because so much time and 

investment is involved in building an appropriate 

relationship with the community, researchers may wish 

to continue their relationship with the community even 

after the study has ended. Researchers should remain 

accessible for technical support related to the subject of 

the research. Helping community members identify new 

funding opportunities and assisting with the writing of 

grant applications are two examples of potential 

continued relationships. Many private sponsoring 

institutions already recognize the importance of enduring 

commitment and have used a variety of approaches, 

often involving funding, to ensure that these 

relationships are able to continue (ERG, 2007). The 

challenge will be for universities and Federal agencies to 

be able to establish similar funding mechanisms. 

The objective of capacity building is to involve 

members of the community in certain roles (e.g., 

performing interventions), training them to perform 

some of the functions initially performed by the research 

team. Certain research grants specifically support this 

type of training. Training can be reciprocal, and allowing 

the community to train the researchers (for example, in 

cultural sensitivity) not only fosters respect but also can 

lead to important new understanding. 

Another important step is to formalize the 

relationship between the community and the institution 

conducting or sponsoring the research, not just between 

the community and the individual researcher. 

Institutional relationships can survive even if individual 

researchers leave. Institutions may be reluctant to build 

enduring relationships with communities if they do not 

see long-term financial value in this investment. 

Researchers may be able to get more support from their 

institutions if they can document their successes (ERG, 

2007). 

6.3 Community Involvement in 

Observational Human Exposure Studies 

Observational human exposure studies, like those 

conducted by NERL, benefit from community 

involvement. Scientific rigor apart from ethical 

considerations fails as good science. Community 

involvement in research ensures that ethical standards 

are a priority in the study design and are pursued by the 

researchers throughout the study. The form and extent of 

community involvement will vary, depending on the 

scope and utility of the research effort. The nature of the 

community⎯the population from which the participants 

are selected⎯often will vary considerably from one 

study to the next, ranging from a small group involved in 

a pilot study to a randomized, representative sample of 

the whole population. As a result, the nature of the 

community involvement also will depend on the 

particulars of the study. The typical lack of direct benefit 

from observational human exposure studies may mean 

that many research efforts cannot meet all of the 

principles of CBPR. Nonetheless, community 

involvement should be included in observational human 

exposure research efforts to the fullest extent possible. 

As the NRC & IOM committee observes (p. 98, NRC & 

IOM, 2005): 

Community involvement, though time and resource 

intensive, is a necessary and useful component of... 

research with the potential to enhance trust and 

increase the relevance of research to affected 

communities. Thus, attention to the issues raised by 

the community and consideration of the most 

appropriate method of community involvement for a 

given research project is warranted. 

NERL researchers also should consider the 

recommendations set forth in the NRC & IOM report 

(Recommendation 5.1, p. 98, NRC & IOM, 2005) as 

they develop their research plans and protocol. 

Researchers...should describe in their protocols and 

IRB submissions how they have involved and will 

continue to involve the affected community in the 

research project, justify the lack of such involvement, 

and report how they have responded to any 

community concerns. 

Researchers and the members of the communities in 

which they work should recognize, however that the 

primary role of the researcher is to be an advocate for the 

science, not an advocate for the community. Although 

being an advocate for the community is desirable, and in 

many projects achievable, it should be recognized that 

resource constraints and potential conflicts of interest 

may impact the researcher’s ability to advocate for the 

community, particularly if it involves regulatory 

activities of the Agency. 

6.4 Identifying and Interacting with 

Other Stakeholders 

Like community involvement, stakeholder 

involvement in a research study can take many forms. 

Also like community involvement, researchers should 

engage stakeholders in their studies early in the planning 

stages. The relationship between the researchers and 

various stakeholders should be maintained during the 

study. How this relationship is maintained can be 

expected to vary with different stakeholders and may 

75
change as the study progresses. Stakeholders can provide 

useful information and perspective during the planning 

and implementation of observational human exposure 

studies. 

Stakeholders may include individuals, NGOs, 

businesses, industry, and various government entities or 

agencies with jurisdiction over or interest in the 

community. Stakeholders are a separate entity apart from 

the community, although they may conduct business or 

operate within the community or have a direct or indirect 

interest in the community’s activities. Even though they 

are not able to speak for the community, stakeholders 

may have knowledge of impacts and ideas about how to 

interpret and use the results of proposed research studies. 

Such knowledge may prove very helpful as part of the 

research planning and scoping (ERG, 2007). Including a 

variety of stakeholders in the planning process provides 

insight that comes from reconciling the disparate 

perspectives of different stakeholders. 

Observational human exposure studies conducted or 

supported by NERL may have many potential 

stakeholders, both internally in EPA and outside of the 

Agency. Internal stakeholders include the ORD Office of 

the Science Advisor, the Office of Science Policy, other 

laboratories and centers in ORD that may be interested 

in the study and its results, program offices, and the 

regional offices. Outside of the Agency, other Federal, 

State, and local agencies may be stakeholders. For 

example, CDC may be interested in biomonitoring 

studies. State agencies will be stakeholders when 

research is done in their state. Examples of NGOs that 

may be external stakeholders include the Natural 

Resources Defense Council, Environmental Defense, 

American Lung Association, American Academy of 

Pediatrics, American Chemistry Council, and literally 

hundreds of other organizations with interests in 

environmental or public health issues. Researchers 

should identify potential stakeholders and communicate 

with them early in the planning stages of a study if they 

are determined to be appropriate. Identifying the 

appropriate stakeholders who have a legitimate interest 

in the study will be done on a study-by-study basis and 

should be done in consultation with the research team, 

the community representatives, and senior management. 

In EPA, the Office of Public Affairs can assist in 

identifying contacts in stakeholder groups. 

The concept of “stakeholder” has been discussed in 

management literature since the 1980s. Mitchell et al. 

(1997) have developed an approach for identifying the 

relevant stakeholders through an assessment of their 

power, legitimacy, and urgency. Such an approach may 

be useful for identifying stakeholders to be involved in 

the research studies. In describing CBPR, Israel et al.

(2005b) discuss the need to examine the advantages and 

disadvantages of extending membership beyond the 

“community of identity” at the outset. For example, they 

discuss the relative merits of including representatives of 

the agricultural industry in a study of farmworkers 

because of industry’s possible role in policy change and 

weigh their inclusion against the concerns that the true 

voice of the farmworkers may not be heard under such 

conditions. They also describe a possible solution of 

creating separate partnership groups. O’Fallon and 

Dearry (2002) explain the benefits of including diverse 

stakeholders for the dissemination of results. 

Successful interactions with stakeholders will 

require effective communication strategies and 

materials, as is discussed in the following section. After 

relevant stakeholders have been identified, they should 

be contacted to inform them of the proposed research 

study and to determine their interest in the study. If the 

stakeholders express an interest in participating, the 

research team should develop a plan for interacting with 

the stakeholders that includes roles and responsibilities, 

activities, and timelines that are mutually agreeable to 

the team, community representatives, and the 

stakeholders. There needs to be a clear agreement on the 

plan with all parties involved. Failure to have such an 

agreement may lead to misunderstandings of the roles of 

the stakeholders. As planning for the study proceeds, the 

plan for stakeholder involvement should be updated to 

reflect activities and timelines for longer term 

engagement. 

When developing relationships with stakeholders, 

researchers also should ensure that participation of the 

stakeholder in the study, regardless of level of 

participation, does not result in actual or perceived 

conflicts of interest. This should be addressed in the plan 

and agreement for stakeholder involvement. 

References

CDC (Centers for Disease Control and Prevention) (1997). 

Principles of Community Engagement. ATSDR Committee 

on Community Engagement. Available: 

http://www.cdc.gov/phppo/pce/ [Accessed Oct. 2007]. 

Corburn J (2007). Community knowledge in environmental 

health science: co-producing policy expertise. Environ Sci 

Policy 10(2):150-161. 

Corburn J (2002). Environmental justice, local knowledge, 

and risk: the discourse of a community-based cumulative 

exposure assessment. Environ Mngt 29(4):451-466. 

76
Dula A (1994). African American suspicion of the healthcare 

system is justified: What can we do about it? Camb Q 

Healthc Ethic 3(3):347-357. 

ERG (Eastern Research Group) (2007). Report on the 

Workshop to Discuss State-of-the-Science Approaches for 

Observational Exposure Measurement Studies. Held in 

Durham, North Carolina on November 28-29, 2006. Final 

Report: January 25, 2007. (PB2007-108905). 

Gilbert SG (2006). Supplementing the traditional institutional 

review board with an environmental health and community 

review board. Environ Health Perspect 114(10):1626-9. 

IOM (Institute of Medicine) (2004). Ethical Conduct of 

Clinical Research Involving Children. Marilyn J. Field and 

Richard E. Behrman (eds). Washington, DC: The National 

Academies Press. 

Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, 

López J, Butz A, Mosley A, Coates L, Lambert G, Potito 

PA, Brenner B, Rivera M, Romero H, Thompson B, 

Coronado G, Halstead S (2005a). Community-based 

participatory research: lessons learned from the Centers for 

Children's Environmental Health and Disease Prevention 

Research. Environ Health Perspect 113(10):1463-71. 

Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005b). 

Methods in Community-Based Participatory Research for 

Health. San Francisco, CA: Jossey-Bass. 

Israel BA, Schulz AJ, Parker EA, Becker AB (1998). Review 

of community-based research: assessing partnership 

approaches to improve public health. Annu Rev Public 

Health 19:173-202. 

Juengst ET (2000). Commentary: What “community review” 

can and cannot do. J Law Med Ethics 28(1):52-54. 

Keeler G, Dvonch T, Yip F, Parker E, Israel B, Marsik F, 

Morishita M, Barres J, Robins T, Caldwell W, Sam M 

(2002). Assessment of personal and community-level 

exposures to particulate matter among children with asthma 

in Detroit, MI, as part of Community Action Against 

Asthma. Environ Health Perspec 110(Suppl 2): 173–181. 

Ledford H (2007). Human Subject Research: Trial and Error. 

Nature 448(7153): 530-532. 

Leung MW, Yen IH, Minkler M (2004). Community-based 

Participatory Research: a promising approach for increasing 

epidemiology’s relevance in the 21st century. Int J 

Epidemiol 33(3):499-506. 

Minkler M, Wallerstein N (eds) (2003). Community-Based 

Participatory Research for Health. San Francisco, CA: 

Jossey-Bass. 

Mitchell RK, Agle BR, Wood DJ (1997). Toward a theory of 

stakeholder identification and salience: defining the 

principle of who and what really counts. Acad Manage Rev

22(4):853-886. 

NIH (National Institutes of Health) (2005). Report and 

Recommendations on Public Trust in Clinical Research for 

the NIH Director from the Director’s Council of Public 

Representatives (COPR). National Institutes of Health, 

Director’s Council of Public Representatives, January 14, 

2005. Available: http://copr.nih.gov/reports/public_trust.asp

[accessed June 2007]. 

NRC & IOM (National Research Council and Institute of 

Medicine) (2005). Ethical Considerations for Research on 

Housing-Related Health Hazards Involving Children. 

Washington, DC: The National Academies Press. Available: 

http://books.nap.edu/catalog.php?record_id=11450

[accessed 12 June 2007]. 

O’Fallon LR, Dearry A (2002). Community-based participatory research as a tool to advance environmental health 

sciences. Environ Health Perspect 110 Suppl 2:155-9. 

Perkins DD, Wandersman A (1990). You’ll have to work to 

overcome our suspicions: the benefits and pitfalls of 

research with community organizations. Soc Policy

21(1):32-41. 

Quandt S, Arcury T, Pell A (2001). Something for everyone? 

A community and academic partnership to address 

farmworker pesticide exposure in North Carolina. Environ 

Health Perspect 109 Suppl 3:435-441. 

Quinn SC (2004). Ethics in public health research: protecting 

human subjects: the role of community advisory boards. Am 

J Public Health 94(6):918-22. 

Tillman, L. (2002). Culturally sensitive research approaches: 

an African-American perspective. Educ Researcher 31(9):3-12. 

U.S. EPA (U.S. Environmental Protection Agency) (2003). 

Public Involvement Policy of the U.S. Environmental 

Protection Agency. EPA 233-B-03-022. Available: 

http://www.epa.gov/publicinvolvement/pdf/policy2003.pdf

[Accessed 26 Sep 2007]. 

Vega WA (1992). Theoretical and pragmatic implications of 

cultural diversity for community research. Am J Commun 

Psychol 20(3):375-91 

Williams R, Suggs J, Rea A, Leovic K, Vette A, Croghan C, 

Sheldon L, Rodes C, Thornburg J, Eijire A, Herbst M, 

Sanders W (2003). The Research Triangle Park particulate 

matter panel study: PM mass concentration relationships. 

Atmos Environ 37:5349-5363. 

77
Additional Information Resources 

Blumenthal DS (2006). A community coalition board creates a 

set of values for community-based research. Prev Chronic 

Dis 3(1):1-7. Available: 

http://www.cdc.gov/pcd/issues/2006/jan/pdf/05_0068.pdf

[accessed 12 June 2007]. 

Coleman CH, Menikoff JA, Goldner JA, Dubler NN (2005). 

The Ethics and Regulation of Research with Human 

Subjects. Newark: LexisNexis. 

Davies EF (2001). Early and meaningful community 

involvement. U.S. Environmental Protection Agency, Office 

of Solid Waste and Emergency Response. Washington, DC. 

OSWER Directive No. 9230.0-99, October 12. Available: 

http://www.epa.gov/superfund/policy/pdfs/early.pdf

[accessed 12 June 2007]. 

NACCHO (National Association of County and City Health 

Officials). Turning Point: Collaborating for a New Century 

in Public Health, see 

http://www.naccho.org/topics/infrastructure/TurningPoint.cf

m [Specifically, Fourteen Policy Principles for Advancing 

Collaborative Activity Among and Between Tribal 

Communities and Surrounding Jurisdictions. 

http://archive.naccho.org/documents/TP-policyprinciples.pdf ]. 

U.S. CDC (Centers for Disease Control and Prevention). 

Preventing Chronic Disease [online serial] Available: 

http://www.cdc.gov/pcd/ . 

U.S. EPA (U.S. Environmental Protection Agency) (2005). 

Superfund Community Involvement Handbook. 

[Specifically, chapters 1 through 3.] EPA 540-K-05-003, 

Available: 

http://www.epa.gov/superfund/community/cag/pdfs/ci_hand

book.pdf 

U.S. EPA (U.S. Environmental Protection Agency) (1999). 

Risk Assessment Guidance for Superfund: Volume I – 

Human Health Evaluation Manual. Supplement to Part A. 

Community Involvement in Superfund Risk Assessments. 

EPA/540/R-98/042, OSWER 9285.7-01E-P, PB99-963303. 

U.S. EPA (U.S. Environmental Protection Agency) (2000). El 

Superfund Hoy Día: La Estimación de Riesgos: Como 

Lograr la Participación de La Communidad. U.S. 

Environmental Protection Agency, Office of Solid Waste 

and Emergency Response. Washington, DC. EPA 540-K99-005, OWSER 9200.2-26K, PB99-963230. Available: 

http://www.epa.gov/superfund/community/today/pdfs/riskfs-0203.pdf 

U.S. EPA (U.S. Environmental Protection Agency) (2001). 

Improved Science-Based Environmental Stakeholder 

Processes: A Commentary by the EPA Science Advisory 

Board. EPA-SAB-EC-COM-01-006. EPA Science Advisory 

Board. Washington, DC. Available: 

http://yosemite.epa.gov/sab/sabproduct.nsf/CEE3F362F1A1

344E8525718E004EA078/$File/eecm01006_report_appnae.pdf

U.S. EPA (U.S. Environmental Protection Agency) (2003). 

Framework for Cumulative Risk Assessment. Washington, 

DC: United States Environmental Protection Agency. 

EPA/600/P-02/001F. Available: 

http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=54944 . 

U.S. EPA (U.S. Environmental Protection Agency) (2003). 

Framework for Assessing Risks of Environmental Exposure 

to Children. Washington, DC. Available: 

http://cfpub2.epa.gov/ncea/cfm/recordisplay.cfm?deid=22521. 

U.S. EPA (U.S. Environmental Protection Agency) (2005). 

Guidance on Selecting Age Groups for Monitoring and 

Assessing Childhood Exposures to Environmental 

Contaminants. Risk Assessment Forum, Washington, D.C. 

EPA/630/P-03/003F. Available: 

http://cfpub.epa.gov/ncea/cfm/recordisplay.cfm?deid=146583. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 

Considerations for Developing Alternative Health Risk 

Assessment Approaches for Addressing Multiple 

Chemicals, Exposures, and Effects. External Review Draft. 

71 FR 16306. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 

Paper on Tribal Issues Related to Tribal Traditional 

Lifeways, Risk Assessment, and Health and Well Being: 

Documenting What We’ve Heard. The National EPA-Tribal 

Science Council. Available: 

http://epa.gov/osp/tribes/tribal/TribalIssues.pdf. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 

EPA’s Public Involvement Policy. Available: 

http://www.epa.gov/publicinvolvement/policy2003/index.htm. 

U.S. Food and Drug Administration (FDA). Exception from 

informed consent requirements for emergency research. 21 

CFR § 50.24 

University of Kansas Community Tool Box. Available: 

http://ctb.ku.edu/en/tablecontents/. 

University of Washington Community-Campus Partners for 

Health, Available: 

http://depts.washington.edu/ccph/index.html. 

Veazie MA, Teufel-Shone NI, Silverman G, Connolly A, 

Warne S, King B, et al. (2001). Building community 

capacity in public health: The role of action-oriented 

partnerships. J Public Health Manag Pract 7(2):21-32. 

78
79

U.S. EPA, Office of Environmental Justice 

Resources: 

Executive Office of the President. (1997). Environmental 

Justice: Guidance under the National Environmental Policy 

Act. Council on Environmental Quality, pp. 7-17). 

Available: 

http://epa.gov/compliance/resources/policies/ej/ej_guidance

_nepa_ceq1297.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2006). Future mechanisms to enhance stakeholder 

involvement and engagement to address environmental 

justice: A letter report. Available: 

http://epa.gov/compliance/resources/publications/ej/nejac/st

akeholder-involv-9-27-06.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2004). Environmental justices and federal facilities: 

Recommendations for improving stakeholder relations 

between federal facilities and environmental justice 

communities. Waste and Facility Siting Subcommittee, 

Federal Facilities Working Group. Available: 

http://www.epa.gov/compliance/resources/publications/ej/n

ejac/ffwg-final-rpt-102504.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2004). Meaningful involvement and fair treatment by tribal 

environmental regulatory programs. Indigenous Peoples 

Subcommittee. Available: 

http://epa.gov/compliance/resources/publications/ej/nejac/ip

s-final-report.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2000). Guide on consultation and collaboration with Indian 

tribal governments and the public participation of 

indigenous groups and tribal members in environmental 

decision making. Indigenous Peoples Subcommittee. 

Available: 

http://www.lm.doe.gov/env_justice/pdf/ips_consultation_gu

ide.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2000). NEJAC May 200 Meeting Report. Environmental 

Justice and Community-Based Health Model Discussion. 

Available: 

http://epa.gov/compliance/resources/publications/ej/nejac/co

mmunity-based-health-recom-report.pdf

NEJAC (National Environmental Justice Advisory Council) 

(2000). The model plan for public participation. The Public 

Participation and Accountability Subcommittee. EPA300/K-00-001. Available: 

http://epa.gov/compliance/resources/publications/ej/nejac/m

odel-public-part-plan.pdf

U.S. EPA (U.S. Environmental Protection Agency). (2008). 

The Environmental Justice Strategic Enforcement 

Assessment Tool (EJSEAT). Available: 

http://www.epa.gov/compliance/resources/policies/ej/ejseat.html

U.S. EPA (U.S. Environmental Protection Agency). (2006). 

Environmental Justice Collaborative Problem-Solving 

Cooperative Agreement Program FACT SHEET. Office of 

Environmental Justice. Available: 

http://www.epa.gov/compliance/resources/publications/ej/fa

ctsheets/fact-sheet-ej-cps-grants-6-13-06.pdf

U.S. EPA (U.S. Environmental Protection Agency). (2004). 

Toolkit for assessing potential allegations of environmental 

justice. (Section 3.3). Office of Environmental Justice. 

EPA-300/R-04-002. Available: 

http://epa.gov/compliance/resources/policies/ej/ejtoolkit.pdf

U.S. EPA (U.S. Environmental Protection Agency). (1995). 

The EPA’s Environmental Justice Strategy. Available: 

http://epa.gov/compliance/resources/policies/ej/ej_strategy_

1995.pdf
80
SECTION 7

Designing and Implementing Strategies for 

Effective Communication 

Successful implementation of observational human 

exposure studies requires effective communications 

between the researchers, study participants, community 

representatives, community members, stakeholders, and 

the public. The previous two sections established the 

need for communications that are “on-going, interactive 

dialogue...involving the disclosure and exchange of 

relevant information, discussion of that information, and 

assessment of the individual’s understanding of the 

discussion” (Recommendation 4.1, IOM, 2002). NIH 

advocates “plain language” that explains the research “in 

an honest, straightforward way” (Recommendation 11, 

NIH, 2005). Indeed, strong relationships can be built 

with participants, the community, and stakeholders only 

if there are clear and effective communications between 

the researchers and the community. The previous section 

illustrates, also, that effective communication is 

bidirectional; it involves listening as well as “speaking.” 

The ethical value of respect for persons, including 

respect for one another’s autonomy and welfare, 

demands that researchers, participants, community 

members, and stakeholders strive to establish effective 

communications and to foster a relationship of trust and 

respect. The researchers should make a commitment to 

effective communications and make the appropriate 

investment of time and resources to ensure that the 

communications are at an appropriate level and are truly 

effective. Researchers should regard communications as 

intrinsic to the ethical basis for the study. 

With the ethical basis for bidirectional 

communication assumed as a given, and the need for 

open and honest bidirectional communications having 

been well established in the previous sections that 

discussed relationships between the researchers and the 

participant (Section 5) and the researchers and the 

community (Section 6), this section discusses strategies 

and tools that researchers may find useful in developing 

effective communications. The focus in this section is 

primarily from the perspective of “getting the word out,” 

because that is the aspect of communication most under 

the control of the researchers. Nonetheless, effective 

communications will be bidirectional and involve 

effective listening. Researchers should keep in mind that 

it is as important to listen to the participants, community, 

and other stakeholders as it is for the researchers to 

provide them with information using the approaches 

described in this section. 

7.1 Communication Strategy and 

Implementation Plan

Fundamental to achieving effective communications 

are a communications strategy and implementation plan. 

In general, the goal of the communication strategy and 

plan is to clearly define how effective bidirectional 

communications will be achieved in the study. Specific 

goals should be developed based on the specifics of the 

study design, the study population, the community, and 

the stakeholders. The plan will describe who will be 

involved in the communications, what communications 

are required, and how the communications will be 

performed. The communication strategy and 

implementation plan should be developed early in the 

planning stages of a study. The communication plan, 

however, needs to be dynamic, with revisions and 

updates occurring throughout the study and in 

collaboration with the community and stakeholders. 

Text Box 7-1 lists elements that should be included 

in a communication plan. The communication strategy 

should be developed based on the goals of the study and 

an understanding of the background, education, 

attitudes, and opinions of the stakeholders and the 

community that will be involved in the many different 

aspects of the study from the initial conceptualization to 

the final reporting of the study results. 

81
 Careful planning is required to develop a 

communication plan that will be effective. The research 

team has to invest the time and resources necessary to 

develop and implement the plan. They also should 

recognize that the communication plan is essential for 

conducting the study and is just as important as the study 

design, human subjects research protocol, or QAPP. The 

observational study, if properly justified as described 

earlier, provides a social and scientific value and brings 

benefit to society (and perhaps the participants); it 

should be a program that the researchers want to discuss 

and explore with the public. The communication plan 

and strategy provide the researchers with an opportunity 

to create effective bidirectional communications with the 

participants, community, and stakeholders. They are not 

simply a way to “avoid problems” with the community, 

stakeholders or the media nor only a plan for reacting to 

“negative” feedback. 

Recognizing that the communication strategy must 

address the bidirectional nature of communications with 

the study participants and the community to be effective, 

it is important that the communication strategy and 

implementation plan be developed in collaboration with 

the community and other stakeholders. As discussed in 

previous sections, members of the community in which 

the study will be performed will provide valuable input 

into the development of the communication strategy by 

providing information about the community culture, 

norms, attitudes, perceptions, etc. They will provide, not 

only expertise about the community, but also 

experiences and lessons learned about previous 

communications activities in the community. It is 

important to engage community representatives and 

stakeholders early in the process of development of the 

communication strategy, the implementation plan, and 

the communication tools. 

 Researchers also may find it helpful to seek 

guidance on how to communicate more effectively, 

especially because that is not a routine part of their 

training or experience. They may consult and learn from 

communications specialists in their organization. In 

addition, a wide variety of resources are available. For 

example, the Federal Communicators Network (FCN) 

(www.fcn.gov) has prepared a “communicators guide” 

that offers advice on how to communicate—in plain 

language, in easily digestible “chunks,” and in a form 

that will be used. They emphasize that “good 

communication is difficult because it requires a lot of 

effort, time, and patience” (FCN, 2001). Some tips from 

the guide to help federal communicators get their point 

across are listed in Text Box 7-2. 

7.2 Individuals and Groups Involved in the 

Communications 

An effective communication plan will identify and 

involve all of the individuals and relevant groups that 

should be included in the communications efforts. When 

conducting observational human exposure studies, this 

list may be quite long. Although researchers may desire 

to limit the number of individuals and groups involved 

to keep the effort as simple and focused as possible, they 

need to ensure that all potential stakeholders are 

identified. The communication plan should identify all 

groups, including community organizations and 

stakeholders, involved in a study, their roles and 

responsibilities in the study, how communications will 

be developed with each group, and the timing of the 

communications. It is likely that most studies will 

involve the individuals, community groups and 

stakeholders shown in Text Box 7-3. 

Text Box 7-1. Elements in a Communication Plan 

• Background information description (overview) of the study, 

relevant historical background information, statement of 

communication needs, and identification of communication 

opportunities and issues 

• Purpose and goals of the communication strategy 

• List of individuals and groups involved in the communications, 

plus relevant demographics and other information to profile the 

groups 

• Strategy and approach for achieving the goals, including a 

statement of the primary message to be conveyed and 

descriptions of the communication channels 

• Activities and materials to achieve the goals of specific 

elements of the plan to be performed 

• Timetable 

• Roles and responsibilities 

• Resources needed (budget) 

• Measures of effectiveness 

Text Box 7-2. Tips for Getting Your Point Across 

• Be prepared. 

• Be confident. 

• Stay focused on your conversation and your listener. 

• Maintain eye contact with your listeners. 

• Make sure your listeners are following you by asking them for 

questions or feedback. 

• Do not lose your temper or get over-emotional. 

• Speak slowly and calmly; don’t raise your voice. 

• Speak clearly and concisely. 

• Get to the point; do not ramble. 

• Be kind, compassionate, and empathetic. 

• Be honest; do not play games. 

• Be assertive but tactful 

82
The study participants are a key group involved in 

communications during a study and are easily identified. 

Similarly, it is generally not difficult to identify the third 

parties associated with the study participants, because 

these groups must be identified when considering ethical 

issues in the study and when developing the human 

subjects research protocol. Research teams should ensure 

that the communication strategy includes the strategy 

and approach for third-party communications. 

As discussed in Section 6, it is critical that 

community representatives are identified early in the 

scoping and planning phase of the study. It is important 

that researchers are informed about the community in 

which they will conduct the study and understand the 

unique characteristics and culture of the community and 

the potential study participants to develop effective 

bidirectional communications. When possible, 

researchers should identify other research organizations 

who have worked in the community and attempt to 

gather information from them on the nature of the 

community, who represents the community, and what 

communication strategies have been used previously in 

the community. Understanding how the community 

defines itself or thinks of itself is critical to establishing 

effective communications. 

Identification of all relevant stakeholder groups may 

be more difficult. As defined in Section 6, the term 

stakeholder is used here to identify a person or group 

who has a valid interest in an activity or decision, but 

who does not speak directly for the community or the 

participants. There may be many organizations who 

consider themselves as stakeholders that represent the 

interests of the community, the participants, or the 

research problem. For example, there are many nonprofit 

organizations that advocate for the protection of 

children’s health. When conducting an observational 

study involving children, the research team should 

identify those groups that could have an interest in the 

study. They need to be identified in the communication 

plan, and an approach needs to be developed for 

communicating with them about the study. There are 

many sources of information on potentially interested 

stakeholder groups. This information can be obtained 

from the research team based on similar studies, the 

participants, the community representatives, sponsoring 

organizations, and “umbrella” organizations for various 

advocacy groups. The Internet has made identification of 

the various stakeholder groups easier and is a source of 

information on goals of the groups and contact 

information. Approaches for communications with these 

and other groups on the list are discussed further in the 

following subsections. 

Researchers should recognize that identifying and 

involving all pertinent community and stakeholder 

groups in their observational human exposure studies is 

important for effective communications and the potential 

success of the study, but that there is the potential for the 

group to become so large that it becomes difficult to 

manage. Large groups not only have the potential for 

impeding progress on a research effort simply because of 

the logistics of the interactions within the group, but, 

also, because of the potential for conflict between the 

groups. It is essential, therefore, that researchers attempt 

to maintain stakeholder groups of manageable size and 

be prepared to deal with potential conflict within the 

groups. There is extensive literature available on conflict 

management, but it is outside of the scope of this 

document to recommend specific approaches or 

literature references. 

7.3 Communications Timetables⎯When 

To Communicate

Communications begin with the initial 

conceptualization of the study and continue through the 

reporting of the study results and beyond. Even after a 

study has ended, followup communications may 

continue with the study participants, the community, the 

scientific community, and the public. It is beyond the 

scope of this document to lay out timetables for 

communications in observational human exposure 

studies because timing will differ with each study. The 

following discussion highlights a few of the issues 

associated with the timing of communications to ensure 

Text Box 7-3. Individuals and Groups 

Involved in Communications 

• Principal investigator—the researcher with ultimate 

responsibility for the study 

• Research team 

• Study participants 

• •Third parties associated with study participants (e.g., spouse, 

children, landlords) 

• Community representatives 

• Community members 

• Governments (local, State, and Federal) 

• Study institution management 

• Study sponsors or funding organization 

• Organizations with interest in the participants, the community, 

or the research question 

• Stakeholders that may be impacted by the results of the study 

• The scientific community 

• Media 

• The general public 

83
that they are effective. This section also does not discuss 

communications among the research team, research 

organization, or study sponsors. 

Researchers should begin the dialogue with the 

community as soon as possible during study 

conceptualization and planning. Once the community in 

which the study will be performed is identified, 

community representatives should be identified and 

contacted to discuss the potential study and to get input 

on how the study may be designed. As discussed in 

Section 6, the observational human exposure studies 

discussed in this document are generally not CBPR. 

Although the study objectives or hypotheses have been 

defined and the general approach has been developed, 

the community still can provide valuable input about 

their environmental or public health concerns. Again, as 

discussed earlier, the planning for the study should be 

flexible enough to incorporate community concerns 

where feasible. Recognizing that many observational 

human exposure studies will not be able to address all of 

the community’s concerns, it is important that the 

communications with the community accurately convey 

the value, merit, and benefits from the study that will be 

relevant to the community. 

Press releases can serve as useful tools for informing 

communities about upcoming studies and for identifying 

stakeholders. Assuming that community representatives 

have been identified early in the development of the 

study design and communications strategy, and that 

community buy-in for the study has been gained, 

researchers can work with community leaders and 

community members to develop press releases and other 

communication tools. Press releases can serve multiple 

purposes. They provide information to potential 

community representatives who may not have been 

identified by the researchers as potential collaborators in 

the study. They provide publicity that will inform 

community members about potential contacts by the 

research team (e.g., in a random sample design). They 

provide information to public interest and advocacy 

groups who may feel that they are stakeholders who 

should be involved in the study. Press releases also 

provide the transparency for the study and the research 

team that is essential for building trust. 

Studies also should be announced to stakeholders 

and the public (via the media, community interactions, 

or other means) well in advance of study 

implementation. Large grants expected to have 

significant impact in communities often are announced 

by EPA at the research institution receiving the grant 

and in press releases to the local media. These studies, 

therefore, are publicized at a very early stage. 

Cooperative agreements, which are another mechanism 

by which the government funds some research projects, 

are announced in the same way. Cooperative agreements 

and studies performed by EPA researchers receive 

additional public notice when they are reviewed by the 

Office of Management and Budget (OMB) under the 

Paperwork Reduction Act. All studies involving 

collection of survey information from more than nine 

people are reviewed by OMB. This involves submission 

of an Information Collection Request (ICR) to OMB, 

announcement of the ICR in the Federal Register, and 

an opportunity for public comment. A docket is 

established specifically to facilitate public comment. 

This process results in widespread publication of 

upcoming government research studies through scrutiny 

by concerned stakeholder groups who routinely review 

the announcements in the Federal Register. 

Prior to the start of data collection in a community, 

relatively large-scale communications may be required. 

These communications may involve notifications to 

public safety officials about the presence of the research 

team in the community, press releases to local media 

outlets about the study, and meetings with community 

groups to provide details about data collection activities. 

It is essential that the research team fosters 

continuing bidirectional communications with the 

participants, community, and stakeholder groups 

throughout the study to maintain transparency, trust, and 

interest in the study. This can be aided by providing 

project progress reports and interim results to the 

participants and the community through community 

meetings, mailings, or Web sites. In observational 

human exposure studies with repeated measurements 

over seasons or years, routinely meeting with 

participants can serve as a mechanism for providing 

study information to the participants and receiving 

feedback from the participants and the community about 

the study and their roles in it. Effective bidirectional 

communication with participants can be expected to 

improve their participation in the study (e.g., in 

completing surveys and collecting personal samples) and 

for improving retention in longitudinal studies. 

However, it is essential that the researcher recognize the 

implications of such meetings on privacy and 

confidentiality issues for the participants and develop 

communications to advise the participants of these 

issues. 

Community meetings also are effective for 

maintaining communications throughout a study. They 

provide the opportunity to disseminate information to 

84
community representatives and to obtain feedback. They 

also provide an opportune setting for news releases to 

the media to maintain or increase interest in the study. 

7.4 Communicating at Different Levels

The diversity of interested people and groups often 

means that communications materials should be 

developed at different levels of scientific literacy. In any 

case, the materials should all be written in “plain 

language” that is honest and straightforward. Stableford 

and Mettger (2007) state that “plain language embodies 

clear communication.” Many researchers mistakenly 

believe that the term means just using simple words, or 

worse, ‘‘dumbing things down.’’ It actually refers to 

communications that engage and are accessible to the 

intended audience. 

A 1998 Presidential memorandum required that 

“plain language” be used in all governmental 

communications with the public. That memorandum 

stated, “By using plain language, we send a clear 

message about what the Government is doing, what it 

requires and what services it offers. Plain language saves 

the Government and the private sector time, effort, and 

money.” Plain language is reader friendly and designed 

to increase the participant’s understanding of the 

communication material. It serves as a means by which 

lay audiences can access and understand scientific 

information. Researchers desiring to use plain language 

in their verbal and written communications with 

communities must decide on key messages to include 

and delete unnecessary descriptive, bureaucratic, or 

jargon-filled language. Researchers should use words 

that commonly are understood, rather than difficult 

abstract terms and concepts. A friendly, conversational 

tone is used to engage the lay audience, rather than a 

formal, scholarly tone that distances the community. 

Stableford and Mettger (2007) argue that proficiency in 

creating appropriate plain language materials is an 

acquired skill that requires knowledge and experience. 

“It is both an art and a science, requiring the ability to 

simultaneously think about the cognitive, emotional, and 

visual appeal of the piece as well as applying researchbased strategies to ensure a truly easy-to-read and 

understand print material.” 

The Department of Health and Human Services 

(HHS) has developed a Web site that specifically 

address the issues related to “plain language” (see 

http://www.health.gov/communication/literacy/plainlang

uage/PlainLanguage.htm). The site includes a list of 

references and other helpful resources. 

To maintain community engagement through the 

research process, it is critical that communications are at 

the appropriate level, and that materials are written at a 

reading level that is appropriate to the audience. For the 

nonscientist, many IRBs and other groups target 

materials to be used with participants and communities 

at a reading level no higher than the 8th grade to improve 

the likelihood of comprehension. In some communities, 

however, other factors, like primary languages other than 

English, educational disadvantages, etc., may require 

communications materials to be written in alternate 

languages and at different reading levels. The issue is 

comprehension, as was discussed in Section 5.1.2. 

Empirical testing of communication methods and 

content is essential to ensure comprehension (Health 

Canada, 2006). 

Researchers also should recognize that in this 

information age, dissemination of informational 

materials may be rapid and widespread. Therefore, even 

documents intended for scientific peers may benefit by 

including summary information in an executive 

summary or preface that a lay reader can understand. 

7.5 Communications Materials 

Researchers need to communicate clearly with the 

many groups listed in Section 7.2 to develop their 

relationship with the participants in the study, to develop 

their partnership with the community, to gain support 

from stakeholders, and to inform the public. To achieve 

the multiple purposes of communications during a 

research study and to communicate with many diverse 

groups, a variety of communications materials may need 

to be developed. Different materials have different 

purposes and different types of information to be 

communicated. Because of diversity in interested 

individuals and groups with respect to education, 

cultures, information needs, etc., the format and content 

of communication materials likely will need to be 

diverse. Text Box 7-4 list activities and materials that 

may be helpful in facilitating communications. 

By definition, communication is an exchange of 

information. This has to be the primary goal of 

communication activities. The accuracy and 

completeness of the information transferred is important. 

There are many different ways to communicate, the 

effectiveness of which varies substantially. The way in 

which the information is conveyed is as important as the 

information itself. Effective communication should 

promote trust and credibility. Peters et al. (1997) found 

that three determinants, namely, (1) knowledge and 

expertise, (2) openness and honesty, and (3) concern and 

85
care, were important factors determining perceptions of 

trust and credibility. Therefore, the approach to 

communication in observational human exposure studies 

should consider these factors, and communication 

materials should be developed with these factors in 

mind. 

 When developing communication materials, the 

researcher should consider the needs of the reader, 

listener, or viewer with respect to content, scope, style, 

and the level at which the materials are written. There 

are many sources of information on design of 

informational materials, such as flyers or brochures. For 

example, Alderson (1995) provides an example of the 

recommended content and style for information leaflets 

(that also may be flyers or brochures) for pediatric 

medical research. She suggests that leaflets be provided 

to parents of children who will be study participants that 

can be read to the children. She recommends that these 

be provided at the time that the parent is being informed 

of the study, prior to requesting the informed consent. 

The content of the leaflet would include the following 

topics. 

• Nature and purpose of the research

• Anticipated benefits of the research

• Risks, harms, costs, and inconvenience to the 

participant

• Assurance that the participant freely can refuse to 

participate in or withdraw from the study

• Details about remuneration

• Names of the project sponsors and the researchers

• Contact information for the researchers

• Respect for privacy and confidentiality

Leaflets and brochures that contain this information 

provide a tool for communication with study 

participants. However, these materials need to be written 

carefully using everyday terms that the average 

nonresearcher can understand. The brochure should be 

written in a friendly style that conveys the intent of the 

researcher to engage the reader as a collaborator on the 

study, not as a study “subject,” who will be told to do a 

series of tasks while participating in the study. 

These same leaflets and brochures can be used to 

inform other groups that either may be involved or 

interested in the study, such as community 

representatives, stakeholder organizations, the media, 

and the general public. The researcher should ensure that 

any brochure developed for the study includes accurate 

and complete information that is less likely to be 

misinterpreted by anyone who might pick up the 

brochure. Brochures and flyers that are used to announce 

a study or are used as recruiting tools should be carefully 

written in plain language to ensure that there is not a 

perception of activities that are unethical. For example, 

if flyers announcing a study state that study participants 

will be compensated, the flyer needs to ensure that the 

compensation is not the focus of the flyer, and that the 

payment does not appear to be excessive and coercive 

(see Section 5.2). Flyers announcing a study generally 

do not include the dollar amounts of payment. 

Researchers need to have similar concerns about all 

of the communication materials that are developed, 

regardless of the type of material, whether it is a direct 

mailing, a Web site, a news release, or a set of questions 

and answers (Q&As) used to respond to media or 

stakeholder inquiries. In developing the communication 

materials, the research staff should seek the assistance, 

advice, and input of people in their organization and 

community groups with experience in developing such 

materials. With all of these materials, the researchers 

should be concerned with how the materials could be 

misinterpreted, and whether there could be a perception 

that the study would not meet the highest scientific and 

ethical standards. In this age of rapid communications 

and increased accessibility to information, it is essential 

that communication materials are well developed, 

accurate, and understandable to all audiences that may 

read them. 

Research study Web sites are especially useful for 

communicating information about observational human 

Text Box 7-4. Activities and Materials That 

May Be Useful in a Communication Plan 

• Flyers 

• Web sites 

• Brochures 

• Interviews 

• Newsletters 

• Focus groups 

• Presentations 

• Direct mailings 

• Press releases 

• Questions and answers 

• Desk statements (government) 

• Abstracts 

• Study reports 

• Talking points 

• Community meetings 

• Stakeholder meetings 

• Technical presentations 

• Study participant meetings 

• Scientific meeting presentations 

• Peer-reviewed scientific journal manuscripts 

• Final reports describing the total research effort 

86
exposure studies. Web sites should be developed early in 

the study to disseminate information to stakeholders and 

the community. Additionally, the sites can be set up with 

participant-only pages to provide more detailed 

information to study participants, including information 

on study protocols that require participant assistance 

(e.g., protocols for collecting urine samples, 

time/activity log entries). However, researchers need to 

ensure that Internet access is available to their intended 

audience and be prepared to provide alternative 

communication tools for those without such access. 

The plan for disseminating information from the 

study should be developed in the early design phases of 

the study and should be included in the study design 

document. Sufficient resources, both time and funding, 

need to be budgeted for this activity. 

7.6 Informing the Study Participants and 

Communities

Effective communications require that all parties, 

researchers and participants alike, involved in the 

communication understand the content and context of 

the information being exchanged. “When researchers 

discuss a planned study with community representatives, 

understand their concerns and needs, and respond to 

them, protocols can be strengthened both scientifically 

and ethically” (p. xii, NRC & IOM, 2005). 

Comprehension is one of the key pillars of informed 

consent, and it means that participants understand the 

key elements of the research. The most effective way to 

improve comprehension is by talking one-on-one with 

study participants. 

To accomplish that, the researchers need to make a 

commitment to communicating with both the study 

participants and the community to inform them of the 

study and provide training as appropriate. This can 

require a substantial investment of time and resources, 

but it is critical to the success of the study. 

Working with study participants to inform them 

about the study and the scientific basis of the study will 

have many benefits. The more educated the participant is 

about the purpose of the study and the activities to be 

performed during the study, the more likely the 

participant will be to develop a beneficial researcherparticipant relationship. By taking the time to inform the 

participant, the researcher demonstrates his or her 

commitment to the participant and conveys the 

importance or value of their participation in the study. If 

the researcher-participant relationship is well developed, 

the participant will have a higher level of trust in the 

researcher and will be likely to have more interest in the 

study and a positive outcome. If such a relationship is 

developed and the participant is informed about the 

study goals, the participant will take part more readily 

and effectively in the specific study activities. For 

example, a study participant who understands why 

time/activity information is critical to understanding 

exposure is likely to do a better job completing a 

time/activity log than a participant with no interest in the 

outcome of the study. In addition, an informed 

participant may have good suggestions for improving the 

study and the interactions with the participants and the 

community that the researchers should listen to and 

adopt. Developing the researcher-participant relationship 

and informing the participants also should improve 

retention in longitudinal, repeated measures studies 

because the participant feels that he or she is 

collaborating with the researcher and is not merely a 

study “subject.” 

 Similarly, providing information on the research 

study to the community should provide significant 

benefits in terms of support to the research team and 

working with the team to facilitate the study in their 

community to address both the scientific issues and the 

community’s concerns. If community leaders understand 

the research problem, the study goals, and the study 

activities, they can more effectively articulate the 

community’s concerns to the researchers and integrate 

those issues into the study design. This will enhance 

their work with the research team during the design 

phase and will enable them to more effectively advise 

and assist during the implementation of the study.

7.7 Reporting Study Results to the 

Participant and Community

Researchers need to develop the approach for 

reporting results to the participants, community, 

stakeholders, media, and others during the initial 

planning of the study. There are not well-developed 

guidelines for when and how to report study results 

(Parkin, 2004). In her systematic review of guidelines 

and frameworks for reporting study results, Parkin 

determined that locating guidance may be difficult and 

time consuming for researchers. She found agreement on 

the importance of disseminating study results to produce 

public health benefits, but there is not a consensus on 

when and how results should be reported to either 

communities or study participants. Although she did not 

identify well-developed guidance documents, she did 

identify some common themes. The first was that 

researchers are becoming aware of the importance of 

systematic planning of the research communications, 

87
planning that needs to be done early in the study. 

Second, organizations are recognizing the importance of 

communicating with communities. And, third, research 

professions are recognizing the importance of research 

communication and their responsibilities. 

There is a large body of literature on processes for 

risk communication (e.g., see Covello et al., 1989, 2007; 

U.S. HHS, 2002; ASTDR, 2007). Processes for risk 

communication are highly relevant to reporting results 

from observational human exposure studies, even though 

they may not include measurements of health outcomes 

or risk assessments. 

HHS has prepared a useful document entitled 

Communication in a Crisis: Risk Communication 

Guidelines for Public Officials, 2002. It is available 

online and in hard copy and includes a chapter on 

communicating complex, scientific, and technical 

information (U.S. HHS, 2002). They recommend using 

clear, nontechnical language, avoiding jargon, and 

putting technical terms into frames of reference that the 

public or other listeners can understand. 

 Covello and Allen (1988) described seven cardinal 

rules for risk communication (Text Box 7-5) that are still 

quite applicable today. More recently, Covello et al. 

(2007) have developed a “message mapping” approach 

for risk communication. Message mapping is a process 

to anticipate the questions likely to be asked after an 

incident and to prepare clear and concise answers to the 

anticipated questions in advance. The approach builds on 

an understanding of current communications practices 

(e.g., short messages averaging 27 words, soundbites of 

around 9 seconds, the most frequently asked questions 

after an incident) and typical human responses to crisis. 

The report lays out a series of steps to develop short, 

clear key messages to address stakeholder concerns in 

advance. 

 The report also provides useful approaches for 

effectively communicating the messages in times of 

crisis. It emphasizes that during a crisis, “people judge 

the messenger before the message and they base their 

judgment in terms of trust.” In times of crises, opinions 

about trustworthiness hinge largely on perceptions of 

caring and empathy, whereas competence and expertise 

are key factors when there is little or no stress. Figure 7- 

1 is taken from the Covello et al. (2007) report and 

represents the relative importance of various factors in 

influencing whether or not people trust a speaker in 

times of crisis. Many of the principles and processes for 

crisis communications are applicable for communication 

of research results from observational human exposure 

studies, and the reader should consult the risk 

communication literature. 

ATSDR (2007) has A Primer on Health Risk 

Communication Principles and Practices available 

online. Because ATSDR generally responds to 

environmental issues identified by individuals or 

communities, their guidance focuses on communicating 

with individuals and communities that perceive an 

imminent or significant health risk because of a problem 

in the community. Because ATSDR often enters a 

community after a potential problem has been identified, 

ATSDR communications are often reactive, by 

necessity, rather than proactive. 

Health Canada (2006) has recently published The 

Strategic Risk Communications Framework. The focus 

of the effort is always the stakeholders. Health Canada’s 

Text Box 7-5. Seven Cardinal Rules of 

Risk Communication 

(Covello and Allen, 1988) 

1. Accept and involve the public as a partner. 

2. Plan carefully and evaluate your efforts. 

3. Listen to the public’s specific concerns. 

4. Be honest, frank, and open. 

5. Work with other credible sources. 

6. Meet the needs of the media. 

7. Speak clearly and with compassion. 

88
process aims to involve the interested and affected 

parties at all points in a “dialogue-based” 

communication process. (See Text Box 7-6). 

 Guidance on risk communication strategies and 

practices consistently stresses the importance of 

obtaining input and feedback from community 

representatives, who can assist in developing approaches 

that place the results in relevant contexts for the 

community and the participant. 

 One of the difficulties in reporting results to 

participants and communities is timely reporting because 

it generally takes a long time to complete both the 

chemical and data analyses in large studies. Researchers 

desire to report fully validated and analyzed data to 

study participants and to the community. But, delay in 

reporting data can create a number of difficulties. 

Participants may move before they receive results. They 

also may lose interest in the study, or more importantly, 

lose trust in the researchers and the scientific research 

community if they do not receive their results in a timely 

manner. Similar problems may occur in the community 

as community leaders and representatives change. 

Community representatives may have expectations for 

data and information that researchers cannot achieve. 

Therefore, it is important that researchers clearly 

communicate with the participants and the community 

about what results will be provided and when they will 

be delivered so that expectations do not differ from 

“reality.”

Reporting study results from observational human 

exposure studies can be particularly challenging because 

data on exposure concentrations and the factors 

impacting exposure may be difficult to relate to a health 

outcome that is relevant to the study participant. Health 

effects data is often lacking for the concentrations at 

which chemicals or their metabolites are measured in 

environmental or biological media. This is especially 

true for studies of many chemicals for which acceptable 

occupational exposure levels have been established, but 

for which there are not environmentally relevant 

standards for low-level exposures. Williams (2004) 

describes an approach for communication using 

comparative risk analyses. She describes intrachemical 

comparisons, interchemical comparisons, comparisons to 

background levels of risk, comparisons to theoretical 

risk or safety levels, and risk comparisons to other 

actions or activities. Williams also includes an extensive 

list of references for guidelines and other information on 

risk communication. Readers of this document should 

refer to her manuscript to determine which approach 

may be applicable to their particular study. 

 During longitudinal studies with repeated 

measurements over months, seasons, or years, it is 

important that researchers commit to providing interim 

and ongoing results to participants and the community as 

the study proceeds. It is important to maintain the 

researcher-participant relationship throughout the study. 

This can be facilitated by keeping study participants 

informed of the study progress and of the interim results 

Researchers also should recognize that there may be 

potential risks to the study participants, third parties, or 

the community because of results generated from a study 

(refer to Text Box 7-7). Therefore, providing 

information to communities has to be done thoughtfully 

and with appropriate preparation. Processes should be 

developed that provide participants with the option to 

receive, or decline, study results. Researchers should 

work with community groups to determine how study 

results should be disseminated to the community and 

what communications strategies should be used. 

There are a variety of methods for providing study 

results to participants and the community. Fact sheets 

can be used to describe the study and provide general 

Text Box 7-6. Steps in Health Canada’s Risk 

Communication Framework 

1. Identify the issue and its context—define the opportunity and 

characterize the situation. 

2. Assess the risks and benefits—assess stakeholder perception 

of the risks, benefits, and tradeoffs. 

3. Identify and analyze options—assess how stakeholders 

perceive the options. 

4. Select a strategy—develop and pretest strategies, risk 

communications plans, and messages. 

5. Implement the strategy—implement risk communications. 

6. Monitor and evaluate results—evaluate risk communications 

effectiveness. 

Text Box 7-7. Potential Harms of Sharing Research 

Results with Participants 

(Fernandez, Kodish, and Weijer, 2003) 

• Incorrect or harmful decisions based on uncertain or unreliable 

results 

• Causing distress for those participants who did not benefit 

from the research 

• Rekindling old memories and emotions, especially in the 

setting of serious illness 

• Emotional distress among community members 

• Possible discrimination in obtaining employment or insurance 

for a participant identified by the research to be at high risk of 

developing complications 

• Financial costs to participants and to researchers 

89
study findings to the community and stakeholders. 

Individualized fact sheets can be used to disseminate 

results to the individual participants. Meetings with 

study participants have been used to disseminate study 

information. Community meetings also can be used to 

provide updates on study progress and general results. 

Examples of the processes and the materials used for 

dissemination of information are included in case studies 

described by Israel et al. (2005) and others conducting 

CBPR studies. 

Overall study results generally are disseminated in 

peer-reviewed journal manuscripts and study reports. 

The availability of results published in manuscripts and 

reports has been greatly enhanced by posting them on 

Internet Web sites. For example, all EPA reports are 

now available electronically via EPA’s National Service 

Center for Environmental Publications Web site 

(http://www.epa.gov/ncepihom/). 

7.8 Reporting Unanticipated Results or 

Observations 

The previous subsection discussed reporting of 

routine results from observational human exposure 

studies. The communication plan should include 

processes and procedures for the dissemination of the 

study results. Additionally, the communication plan 

needs to integrate with the data and safety monitoring 

and oversight plans for the study and include a plan for 

reporting unanticipated results or observations. 

Unanticipated results may include measurements of a 

chemical at a concentration that exceeds what is 

considered to be an “acceptable” level in environmental 

media or biological fluids. Unanticipated observations 

might include observation of the use of a chemical not 

approved for indoor use, storage of chemicals in 

inappropriate containers, storage of chemicals in places 

accessible by children, etc. Unanticipated results or 

observations may be directly related to the research 

question being addressed in the study (e.g., 

measurements of pesticide residues in a home) or 

nonstudy hazards (e.g., frayed electrical cords that may 

pose a hazard to young children and residences). 

Section 4 discusses issues that may affect privacy and 

confidentiality. Section 4.3 covers collateral 

observations of nonstudy-related hazards, including 

those that States may mandate must be reported. 

Section 4.5 discusses the need for data and safety 

monitoring and oversight, including the development of 

plans to report and react to anticipated or unanticipated 

adverse events or conditions. 

As part of the study implementation plan and the 

communication plan, researchers should develop a 

protocol for how to identify contaminant measurements 

and exposures of “concern” that should be reported to 

the study participant as quickly as possible because of 

the potential risk associated with the exposure (see 

Section 4.5, Data and Safety Monitoring and Oversight, 

and also Section 2.7.1, Establishing Criteria and 

Standards for Monitoring Scientific and Ethical Issues 

During a Study.) The plan needs to include the protocol 

for making the determination and the criteria that will be 

used as the threshold or “trigger” for reporting. The 

plans should describe how the results will be reported to 

the participants and what additional action will be 

undertaken to assist the participant in reducing their 

exposures. The first step in developing the protocol is to 

identify what measurement will be used to identify 

exposures of concern. In observational human exposure 

studies, this will generally be the chemical measurement 

in either environmental or biological samples. For 

example, measurement of lead concentration in blood 

would be an appropriate exposure metric if the research 

question being addressed involves lead exposure. The 

measurement is relatively simple and can be performed 

with a short turnaround time. Similarly, measurements 

of chemicals in blood may be appropriate for other 

persistent chemicals that have relatively long half-lives 

in blood. For nonpersistent chemicals, biomarkers of 

exposure measured in urine or saliva may be appropriate 

metrics to identify exposures of concern. For some 

chemicals (e.g., PM, volatile organic compounds 

[VOCs], ozone), biomarkers of exposure either are not 

available or difficult to measure or interpret. In these 

cases, measurements in environmental media may be the 

best exposure metric. Whatever metric is chosen, it is 

important that the chemical analyses can be performed 

relatively quickly to reduce such exposures as quickly as 

possible. 

The second, and more difficult, step in developing 

the reporting protocol is to determine the level of 

concern that triggers reporting of the concentration to the 

study participant. For some environmental media, such 

as drinking water, EPA (2007) has established maximum 

contaminant levels that can be used as triggers for 

reporting. For example, if the researcher measures a 

level of arsenic in drinking water above 0.010 mg/L, he 

or she would be expected to report the level to the study 

participant. For other environmental media, such as air, 

there are few applicable standards. The National 

Ambient Air Quality Standards might be used for the 

criteria pollutants. Guidelines for occupational 

exposures, such as threshold limit values (TLVs) and 

90
biological exposure indices (BEIs) published by the 

American Conference of Governmental Industrial 

Hygienists (ACGIH, 2008) also may be used. TLVs are 

not standards; ACGIH formulates a conclusion on the 

level of exposure that the typical worker can experience 

without adverse health effects. Many people would 

argue that the TLVs are not conservative enough for the 

average population, particularly not for vulnerable 

lifestages (e.g., children, the elderly) and TLVs are only 

for exposure by inhalation. WHO (2005) also publishes 

air quality guidelines. These types of guidelines can be 

used to advise study participants if their exposures are 

high relative to the guidelines. Reporting levels should 

be conservative, but not so low that reporting the level to 

the participant causes unwarranted concern and stress. 

For other environmental media measured in 

observational human exposure studies, such as house 

dust or surface wipes, the measurement results cannot be 

used easily to estimate exposures, and they are a poor 

metric if used alone. 

An alternative approach to comparison of 

measurement results against available guidelines and 

standards is the comparison of measurements in 

biological fluids to measurement data available from the 

National Health and Nutrition Examination Survey 

(NHANES). For example, results of measurements of 

chemicals or their metabolites in urine or blood can be 

compared to different percentiles (e.g., the 95th) 

reported in the NHANES national reports (CDC, 2005). 

This type of comparison shows that the participant’s 

measurements are at the high end of the distribution of 

the NHANES data, suggesting that action may need to 

be taken to mitigate exposures. However, researchers 

need to be judicious in the selection of the exposure 

metric. Biomarkers in blood and biomarkers in urine can 

be very different exposure metrics and may represent 

different aspects of the exposure event. A similar 

approach could be taken with measurements of 

chemicals in environmental media if there are 

sufficiently large databases available for comparison. 

For many chemicals and many media such databases are 

not available. In some NERL studies, one comparison 

approach that has been used is to compare an 

individual’s environmental media measurements to the 

50th, 75th, or 95th percentile concentrations for the 

entire study population, so that the participant can 

evaluate his or her measurement results relative to those 

of the other study participants. 

A more complex approach than using simple data 

comparisons is to calculate a reporting level defined as a 

chemical or metabolite concentration indicative of an 

absorbed dose greater than that of a target level (for 

example one-tenth) of a lifetime reference dose (RfD) 

level. For a pesticide, the absorbed dose could be 

estimated from the urinary pesticide metabolite level 

using an approach similar to the methodology published 

by Fenske et al. (2000). This deterministic approach to 

dose estimation allows direct back-calculation of doses 

from urinary metabolite concentrations using few 

assumptions and is consistent with current pesticide 

regulatory procedures for risk assessment. When using 

this approach, the research team will need to determine 

how conservative the reporting level should be, as there 

are no guidelines available for using this approach. If the 

concentrations of a metabolite measured in a study 

participants’ urine level are indicative of elevated 

exposures (i.e., above the reporting level), the 

researchers would be expected to report the information 

to the participants and provide information or local 

contacts that could assist in helping the participants 

identify sources of exposure and reduce their exposures. 

Although this would seem to be a reasonable approach 

for some classes of chemicals, the authors are not aware 

of reports of the use of this approach in the scientific 

literature. 

7.9 Anticipating and Responding to 

Criticism

As discussed in other parts of this document, in spite 

of researchers best intentions, there may be situations 

that arise in which people’s perceptions of the study 

design or implementation plan are not accurate, or their 

opinions and beliefs about the ethical issues associated 

with a study may not be in agreement with those of the 

research team and others involved in the study (e.g., the 

peer review panel, the IRB). Just as it is not 

unreasonable to expect differences in opinion on 

scientific approaches to an observational study, it is not 

unreasonable to expect differences of opinion on ethical 

approaches. The researchers, therefore, should be 

prepared to respond to criticism. The implementation 

plan and the communication plan should address how 

the research team should anticipate study elements that 

may be criticized. During study conceptualization, the 

research team should develop a list of potentially 

controversial study elements (many of which are 

discussed in this document). For each study element, the 

research team should describe how the ethical 

approaches to the study element were evaluated and 

selected. Both the process and the rationale for selection 

of a particular approach should be documented. At each 

step in the study planning and review process, the 

91
research team should document discussions related to 

the specific element, considerations that were made, 

actions taken, and justification for the actions. Input 

from research team members, internal reviewers, 

external reviewers, community members, and others 

involved in the study should be documented for these 

controversial study elements. Similarly, for potentially 

controversial study elements, the review and actions by 

the IRB should be documented. All of this information 

should be compiled for potential use to prepare a set of 

Q&As that can be used by the research team and 

sponsoring organization to respond to criticism. When 

responding to criticism, establishing trust and credibility 

are essential, as discussed previously. The public’s 

perception of trust and credibility is determined by the 

public’s perceptions of the researchers’ knowledge and 

expertise, openness and honesty, and concern and care 

(Peters et al., 1997). These factors are important to 

consider in developing the information and approach 

that will be used to respond to criticism. 

There is a large volume of information available on 

“crisis communication” that the reader can use to 

develop a plan for anticipating and responding to 

criticism (e.g., FCN, 2001; ATSDR, 2007; U.S. HHS, 

2002). The key is to be proactive and have a plan before 

any criticism is raised. 

7.10 Responding to the Media, Public 

Inquiries, and Other Stakeholders

Like crisis communications, the communication plan 

should include detailed plans for how to interact with the 

stakeholders, the media, and the public. Standard 

approaches have been developed for effective 

communications (e.g., the Federal Communicators 

Network's Communicators Guide [FCN, 2001]) with the 

media and will not be included in this document. A 

proactive plan, open and transparent communications, 

and easily to comprehend information will ensure 

effective communications with stakeholders and the 

public. 

References

American Conference of Governmental Industrial Hygienists 

(ACGIH) (2008). TLV/BEI Resources. Available: 

http://www.acgih.org/tlv/. 

Alderson P (1995). Will you help us with our research? Arch 

Dis Child 72(6):541-42. 

Anderson B, Hall B (1995). Parents’ perceptions of decision 

making for children. J Law Med Ethics 23(1):15-9. 

ATSDR (Agency for Toxic Substances and Disease Registry) 

(2007). A Primer on Health Risk Communication Principles 

and Practices [online publication]. Available: 

http://www.atsdr.cdc.gov/risk/riskprimer/ [accessed 12 June 

2007]. 

CDC (Centers for Disease Control and Prevention) (2005). 

Third National Report on Human Exposure to 

Environmental Chemicals. National Center for 

Environmental Health, Atlanta, GA, NCEH Pub. No. 05-

0570. Available: 

http://www.cdc.gov/exposurereport/pdf/thirdreport.pdf

[accessed 12 June 2007]. 

Covello V, Allen F (1988). Seven Cardinal Rules of Risk 

Communication. OPA-87-020. U.S. Environmental 

Protection Agency, Office of Policy Analysis, Washington, 

DC. Distributed by the Pennsylvania Dept. of 

Environmental Resources. Available: 

http://www.epa.gov/stakeholders/pdf/risk.pdf [accessed 12 

June 2007]. 

Covello VT, McCallum DB, Pavlova M (eds) (1989). Effective 

Risk Communication: the role and responsibility of 

Government and Non-Government Organizations. New 

York. NY: Plenum Press. 

Covello V, Minamyer S, Clayton K (2007). Effective risk and 

crisis communication during water security emergencies 

summary report of EPA sponsored message mapping. 

EPA/600/R-07/027. National Homeland Security Research 

Center, Office of Research and Development, U.S. 

Environmental Protection Agency, Washington, DC. 

Available: 

http://www.epa.gov/nhsrc/pubs/reportCrisisCom040207.pdf

FCN (Federal Communicators Network) (2001). 

Communicators Guide For Federal, State, Regional, and 

Local Communicators by the Federal Communicators 

Network. Available: 

http://www.publicforuminstitute.org/activities/2002/fcn/co

mmguid.pdf [accessed 12 June 2007]. 

Fenske RA, Kissel JC, Lu C, Kalman DA, Simcox NJ, Allen 

EH, Keifer MC (2000) Biologically based pesticide dose 

estimates for children in an agricultural community. 

Environ Health Persp 108(6):515-20. 

Fernandez CV, Kodish E, Weijer C (2003). Informing study 

participants of research results: an ethical imperative. IRB

25(3):12-19. 

Health Canada (2006). The Strategic Risk Communications 

Framework. Available: 

http://www.riskcommunications.gc.ca [accessed 18 

September 2007]. 

92
93

IOM (Institute of Medicine) (2002). Responsible Research: A 

Systems Approach to Protecting Research Participants. 

Daniel D. Federman, Kathi E. Hanna, and Laura Lyman 

Rodriguez (eds). Washington, DC: The National Academies 

Press. 

Israel BA, Eng E, Schulz AJ, Parker EA (eds) (2005). 

Methods in Community-Based Participatory Research for 

Health. San Francisco, CA: Jossey-Bass. 

NIH (National Institutes of Health) (2005). Report and 

Recommendations on Public Trust in Clinical Research for 

the NIH Director from the Director’s Council of Public 

Representatives (COPR). National Institutes of Health, 

Director’s Council of Public Representatives, January 14, 

2005. Available: http://copr.nih.gov/reports/public_trust.asp

[accessed June 2007]. 

Parkin RT (2004). Communications with research participants 

and communities: foundations for best practices. J Expo 

Anal Environ Epidemiol 14(7):516-23. 

Peters RG, Covello VT, McCallum DB (1997). The 

determinants of trust and credibility in environmental risk 

communication: an empirical study. Risk Anal 17(1):43-54. 

Stableford S and Mettger W (2007). Plain language: a 

strategic response to the health literacy challenge. J Public 

Health Pol 28:71–93. 

U.S. HHS (Department of Health and Human Services) 

(2002). Communicating in a Crisis: Risk Communication 

Guidelines for Public Officials, 2002. Available: 

http://www.riskcommunication.samhsa.gov/index.htm

[accessed 13 June 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (2007). 

Drinking Water Contaminants. Environmental Protection 

Agency. Available: 

http://www.epa.gov/safewater/contaminants/index.html

[accessed 13 June 2007]. 

Williams PR (2004) Health risk communication using 

comparative risk analyses. J Expo Anal Environ Epidemiol 

14(7):498-515. 

World Health Organization (2005). WHO Air Quality 

Guidelines Global Update 2005. Available: 

http://www.euro.who.int/Document/E87950.pdf [accessed 

13 June 2007]. 

Additional Information Resources 

Reckelhoff-Dangel C, Petersen D (2007). Risk Communication in Action: The Risk Communication Workbook. 

EPA/625/R-05/003. National Risk Management Research 

Laboratory, Office of Research and Development, U.S. 

Environmental Protection Agency, Cincinnati, OH. 

Available: 

http://www.epa.gov/nrmrl/pubs/625r05003/625r05003.pdf

[accessed 18 September 2007]. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 

Considerations for Developing Alternative Health Risk 

Assessment Approaches for Addressing Multiple Chemicals, 

Exposures, and Effects. External Review Draft. 71 FR 

16306. 

U.S. EPA (U.S. Environmental Protection Agency) (2006). 

Paper on Tribal Issues Related to Tribal Traditional 

Lifeways, Risk Assessment, and Health and Well Being: 

Documenting What We’ve Heard. The National EPA-Tribal 

Science Council. Available: 

http://epa.gov/osp/tribes/tribal/TribalIssues.pdf. 

U.S. PHS (Public Health Service) (1995) Risk 

communication: working with individuals and communities 

to weigh the odds. Prevention Report. Feb/Mar. Available: 

http://odphp.osophs.dhhs.gov/pubs/prevrpt/Archives/95fm1.

htm. 
94
Appendix A 

Additional Discussion of Observational and Exposure Terminology and 

Examples of Previous NERL Observational Human Exposure Studies 

The authors recognize that the words “observational 

human exposure studies” may convey a variety of 

meanings to different people. The word exposure is 

often interpreted differently by different people; 

similarly, the word observational may have a variety of 

interpretations. The following discussion regards 

potential meanings of those terms and describes what the 

authors of this document mean when they use the term 

observational human exposure studies. 

Exposure 

Exposure, as it is used throughout this document, is 

a technical term that is defined as the “contact of a 

chemical, physical, or biological agent with the outer 

boundary of an organism (e.g., a person) (U.S. EPA, 

1992). Exposure is quantified as the concentration of the 

agent in the medium in contact integrated over the time 

duration of that contact.” 

As the authors use the term, exposure is only the 

quantification of the “contact” as defined above. The 

word itself carries no connotation of intent, and it is not

equivalent to intentional exposure, dose (dosing), or 

intentional dosing. A review of the dictionary definition 

of exposure shows that the word has many different 

meanings, and shades of meaning, in common, everyday 

English. However, when the authors use the word in this 

text it is being used in the technical sense that is defined 

above. 

The authors’ understanding of the word exposure is 

illustrated in Figure A-1. This graphic is a paradigm that 

ORD uses in formulating its human health research 

program. The graphic illustrates that exposure occurs at 

the intersection of both the chemical, physical, or 

biological agent and the person who is exposed. To 

understand exposure, one must understand the 

distribution of the “agent” throughout the environment 

over time and combine that understanding with 

knowledge about the location and activities of people 

that bring them into contact with the agent. Knowledge 

about the distribution of the agent in space and time 

generally involves measurements and data collection 

about environmental conditions external to the person. 

Knowledge about the person’s behaviors requires 

collection of personal information or observations of 

their location and activities. Understanding exposure, 

including the pathways, routes, duration, frequency, and 

magnitude of the exposure, requires combing both types 

of information. 

See the Glossary, Appendix F, for more information 

and the definition of additional and related terms. 

Observational 

Observational human exposure studies, as used in 

the context of this document, involve only the collection 

of environmental or biological samples and information 

for the purpose of quantifying the contact between the 

participant and the agent being studied. Observational 

human exposure studies are inherently the process of 

watching people in context—in their natural 

environment, doing routine activities—and collecting the 

95
samples and relevant information from them and from 

their surroundings to measure and calculate the 

exposures that occurred in the same context. 

Scientific Study Design: From a scientific study 

design perspective, an observational study of the sort 

being considered in this document is one where the 

researcher does not control the variables but, rather, 

observes both the variable and the outcome and tries to 

infer the relationship between the variable and the 

outcome. This contrasts with a controlled study where 

the researcher isolates and controls one or more 

variables in a systematic way to assess the impact of 

changes in the variables on an outcome measure. 

Consider the intervention study examples cited in the 

section on regulatory distinctions below (cleaning a 

house to reduce exposure in the residence and wearing a 

particle mask to reduce exposure to smoke from forest 

fires). In those cases, participants would be assigned 

either to receive the intervention (treatment) or not (the 

control group). The outcomes (exposures) would be 

measured and compared between the two groups to 

assess the effectiveness of the intervention. Similarly, 

drug trials would randomly assign participants to receive 

either a test medication or a placebo. The medical 

outcome (e.g., pain relief, blood pressure, cholesterol 

levels in blood) would then be measured for all 

participants, and the outcomes compared between the 

treated group (getting the test medication) and the 

control group (receiving the placebo). 

Controlled studies are often desirable in science 

because, when properly designed, they provide 

unambiguous estimates of the impact of unique variables 

on the outcome (even if the impact of one variable could 

normally be overwhelmed by other factors) and 

eliminate the need for alternate explanations of the 

experimental results (because other factors are held 

constant). However, controlled studies are not always 

possible. They may be unethical (e.g., to “treat” a group 

of women with abortions to test if there is a linkage 

between having had an abortion and breast cancer), 

impractical (e.g., to follow a cohort large enough to yield 

statistically significant results in a test of rare side 

effects to a medication), or just impossible to accomplish 

(e.g., to measure nutritional levels of a population in the 

middle of a war zone). 

As a consequence, much medical research is 

observational in the scientific sense being considered 

here. Public health data represent observations of health 

outcomes, but the factors that may have led to or 

influenced those outcomes are not under the control of 

any researcher. Observational techniques long have been 

used in medical studies to infer information about the 

impacts of certain factors on health outcomes. 

Commonly used techniques include cohort studies, casecontrol studies, cross-sectional studies, case reports, case 

series, and descriptive studies (NEAC, 2006; 

Vandenbroucke et al., 2007). 

Observational human exposure studies as used in 

this document are considered to be observational from a 

scientific study design perspective because the variables 

leading to exposure are not controlled by the researchers. 

Most of the observational human exposure studies 

conducted by NERL to date have been cross-sectional 

studies (sometimes repeated several times). While a 

particular variable may not be controlled by the 

researcher, the study design (e.g., selection of the 

population to be studied, location of the research, data 

selection to exclude confounding factors) can sometimes 

influence the range of values over which a variable may 

be observed. For example, NERL’s observational human 

exposure studies to understand exposure to PM (see 

www.epa.gov/heasd/sources/projects_completed/pm_pa

nel_studies.htm and www.epa.gov/heasd/sources/project

s/a3a_understanding_airshed_sources.htm) have 

traditionally excluded homes with smokers from the 

study population to avoid cigarette smoke as a 

confounding factor in the studies. 

Observational Studies in Market Research, 

Ethnography, and the Common Vernacular:

Observational market research can involve covert 

observation, overt observation, or researcher 

participation. Covert observation is said to have a “key 

advantage” that “the respondent or consumer is unaware 

that they are being observed, allowing their behavior to 

be observed naturally” (see 

http://www.asiamarketresearch.com/glossary/observatio

nal-research.htm). This means that the subject’s behavior 

will be natural and uncontaminated by the researcher’s 

presence. On the other hand, covert observation may be 

construed to be deceitful and ethically questionable. 

Overt observations involve sampling surveys, polls, 

interviews, focus groups, etc. Validity of the data 

obtained this way may be shaded by people’s natural 

tendency to behave or respond ideally when they know 

they are being watched. Motorists routinely slow down 

when they think they are being observed by the police. 

Finally, the researcher may participate in the activity 

being observed. Ethnography is a long-term 

investigation of a group (often a culture) that is based on 

observations made while immersed in and, useually, 

participating in that group. “Ethnography provides a 

detailed exploration of group activity and may include 

96
literature about and/ or by the group.” (See 

http://writing.colostate.edu/guides/research/observe/com

3a1.cfm). One obvious problem with immersion 

techniques is that the researcher may lose his or her 

objectivity. 

In the common language use of the term 

observational research, it appears to the authors that 

some people understand the term to imply that the 

observations are both benign and often covert, that is, 

without interaction with the persons being studied. That 

is not the case in NERL’s observational human exposure 

studies. The research often takes place in and around the 

homes of the participants. Often, the research involves 

asking the participant to answer a questionnaire and to 

provide personal samples (e.g., urine, blood). Collection 

of survey information and personal urine and blood 

samples cannot be done covertly, and collecting a blood 

sample is not considered to be benign. 

Observational Research in NERL: NERL’s 

observational human exposure studies entail the 

collection of environmental or biological samples, data, 

and information from study participants and their 

surroundings in their everyday environments, as they go 

about their normal activities, for the purpose of 

quantifying the contact between the participant and the 

agent being studied. As such, the studies are designed to 

meet the regulatory definition of observational research 

in the CFR. NERL’s studies also meet the scientific 

definition of an observational study, because the variable 

being studied, exposure to some agent, is not controlled 

by the NERL scientists. The observations are not covert, 

and they may or may not be noninvasive (e.g., 

sometimes blood samples may be collected). 

Because NERL’s observational human exposure 

studies meet the definition of human subjects research as 

set forth in the Common Rule, there is also a regulatory 

requirement to meet the ethical and scientific standards 

set forth in EPA’s human subjects regulations and in 

Agency rules. The research protocol must be evaluated 

and approved by an IRB and by EPA’s Human Studies 

Research Review Official (HSRRO) before any human 

subjects research effort can take place. But, even more 

compelling to NERL managers and scientists is the fact 

that NERL cannot conduct observational human 

exposure studies without the participation of willing 

individuals. Indeed, without the research participants, 

NERL’s human exposure research would be nothing. 

This intimate involvement of research subjects in 

NERL’s research imposes moral and ethical obligations 

to deal with participants respectfully and to ensure their 

safety, protection, and well-being. 

Regulatory Distinction Between Intentional 

Exposure and Observational Research 

Intentional Exposure: The CFR states, “Research 

involving intentional exposure of a human subject

means a study of a substance in which the exposure to 

the substance experienced by a human subject 

participating in the study would not have occurred but 

for the human subject’s participation in the study” [40 

CFR 26.202(a)]. This definition sets forth two 

requirements regarding an intentional exposure: (1) the 

exposure has to be to a substance that is being studied, 

and (2) at least one aspect of the exposure to the 

substance being studied has to be attributable to the 

subject’s participation in the study. 

The first requirement means the objective of the 

study must be to understand the impact or exposure of 

the substance being studied. In observational human 

exposure studies, like those that NERL conducts, the 

research protocol may require the use of isopropyl 

alcohol or some other chemical to collect a personal 

sample (e.g., to sterilize the puncture site immediately 

prior to collection of a personal sample of blood drawn 

by a trained phlebotomist). Indeed, it would be both 

unethical and bad medical practice not to sterilize the 

puncture site before drawing blood. But this requirement 

does not constitute intentional exposure because the 

research is not the study of isopropyl alcohol but of 

some other agent. Incidental exposures to chemicals like 

isopropyl alcohol still must be considered from a safety 

perspective, pass both scientific and ethical review, and 

be approved by the IRB, but such incidental exposures 

do not constitute intentional exposure. 

The second requirement is that the exposure as 

experienced by the subject “would not have occurred but 

for the human subject’s participation in the study.” The 

two primary ways in which intentional exposure studies 

commonly meet this definition are by the direct 

introduction of the study substance into the research 

environment under the control of the research protocol 

or by scripting the participants’ activities in such a way 

that their contact with the study substance is determined 

by the research. Although either would be sufficient to 

meet the regulatory definition, many, if not most, 

intentional exposure studies attempt to control both. 

Because “exposure is quantified as the concentration of 

the agent in the medium in contact integrated over the 

time duration of that contact,” intentional exposure 

studies are usually more scientifically robust if both the 

concentration of the agent and the duration of the 

exposure are controlled by the research. 

97
Observational Research: In the language of the 

Code of Federal Regulations, “observational research

means any human research that does not meet the 

definition of research involving intentional exposure of 

a human subject” (40 CFR 26.302). 

By this definition, observational research

encompasses all human research that does not meet the 

definition of intentional exposure. As a consequence, it 

is a broad regulatory category that includes a variety of 

research domains, including human research that does 

not involve the study of exposures at all. This regulatory 

definition of observational is sufficiently broad, 

moreover, that it encompasses study types that this 

document is not intended to address. For example, it 

may be possible to design an intervention study that does 

not bring about or script in any way the participants’ 

exposure to a substance, but rather reduces or mitigates 

it. (Consider a study to test whether professional 

cleaning of the carpets, floors, walls, and other surfaces 

in a home might lead to a lower exposure to a residential 

contaminant or a study to determine if wearing a particle 

mask would reduce an individual’s exposure to smoke 

from forest fires.) Such a study might meet the 

regulatory definition of observational research (Note: 

The final decision in regard to whether any EPA study 

meets the definition of observational research resides 

with the Agency’s HSRRO), but it would not meet the 

authors’ intentions regarding “observational human 

exposure studies” as they are defined in this document. 

An intervention study, such as described in these two 

examples, does not involve observing people’s 

exposures in their everyday environments, as they go 

about their normal activities. In an intervention study, 

either the participant’s environment (cleaning of the 

household surfaces) or their behavior (wearing a particle 

mask) has been manipulated by the researcher. Secondly, 

the objective of these studies is not to understand 

exposures in everyday environments but would use 

changes in exposure to test the effectiveness of an 

intervention strategy. Such a study is not addressed in 

this document. 

Observational human exposure studies, as used by 

the authors of this document, generally meet the 

regulatory definition of observational research. But, not 

all studies meeting the CFR definition of observational 

research would be considered by the authors to be 

observational human exposure studies. 

Examples of NERL Observational 

Human Exposure Studies 

NERL and its predecessor organizations have 

conducted observational human exposure studies since 

1980. Table A-1 lists many of those that NERL has 

conducted, supported, or participated in since 1980. The 

table gives the name of the study, dates, sample size, 

then type of study, a brief explanation of the research, 

and NERL’s role therein. The table represents a variety 

of first-party or second-party research efforts. In many 

cases, NERL staff would design, oversee, and, if 

possible, participate directly in the study (first-party), 

but often contractor support would be needed to 

accomplish the field sampling or some of the sample 

analysis. In other cases, NERL researchers would solicit 

proposals for exposure research to be conducted to 

address specific exposure issues and then would fund 

researchers in academia or at nonprofit institutions to 

design and conduct the research (second-party research). 

In a few cases, grants might already be in place with 

research institutions, and NERL simply would augment 

the pre-existing funding to expand the exposure 

component (second-party). Some other cases involve 

research efforts initiated by other Federal agencies with 

which NERL would collaborate and participate in 

directly (first-party). 

An examination of the entries in the table shows that 

most of the agents being studied were chemicals, often 

air pollutants or pesticides. A few of the entries indicate 

that other agents, for example, molds and fungi or other 

microbes, were the subject of the study. The largest 

number of the studies involved small numbers of 

participants and often were designed to determine 

whether or not a method for collecting exposure-related 

data or samples was feasible or burdensome. Most of the 

smaller studies used convenience samples. Studies, like 

DEARS, CTEPP, NHEXAS, and TEAM, which 

involved large numbers of participants, employed 

randomized or probability-based approaches for 

selecting participants. 

Table A-2 shows the types of samples that often 

have been collected in NERL’s observational human 

exposure studies. Some of the samples, like air 

concentrations or surface wipes, allow NERL staff to 

determine the concentration of the studied chemicals in 

the environmental media with which the participants 

may come into contact. Other items, like time activity 

diaries or videotaping children to measure the amount of 

hand-to-mouth activity, allow NERL researchers to 

understand how people may come into contact with the 

agent and to estimate the duration or frequency of a 

98
99

potential exposure. Still other measures, like personal 

samplers or biological samples, represent an attempt to 

determine a time-integrated measure of exposure. NERL 

staff put all of this information together to estimate an 

individual participant’s exposure, either through 

relatively direct measures of exposure or through 

algorithms that combine the media concentrations 

measurements and the activity data. 

References

CFR (Code of Federal Regulations) (2006). 40 CFR Chapter I 

Environmental Protection Agency Part 26 Protection of 

Human Subjects. U.S. Code of Federal Regulations. 

Available: http://www.access.gpo.gov/nara/cfr/waisidx_06/

40cfr26_06.html [accessed 12 June 2007]. 

NEAC (National Ethics Advisory Committee) (2006). Ethical 

Guidelines for Observational Studies: Observational 

research audits and related activities. Wellington, New 

Zealand: Ministry of Health. Available: 

http://www.neac.health.govt.nz/moh.nsf/indexcm/neacresources-publications-ethicalguidelines. 

U.S. EPA (U.S. Environmental Protection Agency) (1992), 

Guidelines for Exposure Assessment. Environmental 

Protection Agency, Risk Assessment Forum, EPA/600/Z92/001. Available: 

http://www.epa.gov/nceawww1/raf/pdfs/exposure.pdf

[accessed 1 May 2008]. 

Vandenbroucke JP, von Elm E, Altman DG, Gøtzsche PC, 

Mulrow CD, et al. (2007). Strengthening the Report of 

Observation Studies in Epidemiology (STROBE): 

explanation and elaboration. PLoS Medicine 4(10): e297. 

doi:10.1371/journal.pmed.0040297.
Table A-1. Examples of Observational Human Exposure Studies Conducted or Funded by NERL 

or Its Predecessor Organizations 

Study Date Size Type Brief Description NERL Role 

Total Exposure 

Assessment 

Methodology 

(TEAM) Studies 

1980-1984 400 

Households 

Three-stage 

stratified 

probability 

selection, 

crosssectional 

The TEAM study was designed to develop and demonstrate 

methods to measure human exposure to toxic substances in 

air and drinking water. The goals were to develop methods to 

measure individual total exposure (from air, food, and water) 

and the resulting body burden of toxic and carcinogenic 

chemicals and to apply these methods within a probabilitybased sampling framework to estimate exposures and body 

burdens of urban populations in several U.S. cities. Air 

sampling measured personal exposure to airborne toxic 

chemicals in indoor air and in exhaled breath. Related 

objectives were to determine the relationships between 

personal, indoor, and outdoor, and blood, urine, and exhaled 

breath concentrations; determine the variability of VOC 

concentrations within a home; and determine seasonal and 

multiyear variability. The study was conducted in New Jersey, 

North Carolina, and North Dakota in three phases. 

EPA designed and 

run, contractor 

conducted 

Additional 

TEAM Studies 

1987 51 in LA area, 

17 in NJ, 

and 75 in 

Baltimore 

Convenience 

sample 

A separate VOC TEAM study was carried out in Baltimore, 

MD: Baltimore lacks the petroleum and chemical 

manufacturing plants present in most of the previous TEAM 

study sites and is more representative of many U.S. cities. 

Focused studies were also conducted in New Jersey and Los 

Angeles to further explore the sources and factors 

contributing to personal VOC exposures identified in the 

earlier TEAM studies. 

EPA designed and 

run, contractor 

conducted 

Nonoccupationa

l Pesticides 

Exposure Study 

(NOPES) 

1986-1988 259 Probability 

selection, 

mainly crosssectional, 

partly 

longitudinal 

First attempt to develop a methodology for measuring the 

potential exposure of the general population to common 

household pesticides using probability-based sampling; 

questionnaire data collection; and personal monitoring of air, 

drinking water, food, and dermal contact. Conducted in 

Jacksonville, FL, and Springfield and Chicopee, MA, to 

capture high- and low-pesticide-use areas, respectively. 

EPA designed and 

run, contractor 

conducted 

Nine-Home 

Children’s Pilot 

Study 

1990 9 Convenience 

pilot study 

to test 

methodology 

A 9-home pilot study was conducted to evaluate monitoring 

methods in the field that may be used to assess the potential 

exposures of children aged 6 months to 5 years to pesticides 

found in the home environment. Newly developed methods 

were tested for measuring pesticide residues in indoor air, 

carpet dust, outdoor soil, and on children's hands. Information 

also was collected on household characteristics, pesticides 

used and stored at the residence, and children's activities. 

EPA designed and 

run, contractor 

conducted 

Particle Total 

Exposure 

Assessment 

Methodology 

(PTEAM) Study 

1990 178 Probability A study of nonsmokers age 10 years and older in Riverside, 

CA, in which indoor, outdoor, and personal monitoring of 

integrated particle mass over 12-hour day and night periods 

was conducted for PM10 and PM2.5. Polycyclic aromatic 

hydrocarbon and phthalate measurements were collected 

indoors and outdoors at a subset of 125 homes. A separate 

monitoring site provided ongoing 12-hour measurements of 

ambient particles throughout the study (48 days). Reference 

PM10 and dichotomous samplers were used at this site in 

addition to personal and stationary monitors identical to those 

used for participant monitoring. Nighttime and daytime recall 

time-activity questionnaires, as well as household 

questionnaires, were administered to each selected subject 

and household, respectively, and meteorological and air 

exchange rate data were recorded for each monitored home. 

EPA designed and 

run, contractor 

conducted 

National Human 

Activity Pattern 

Study (NHAPS) 

1992-1994 9,386 Probability 

(national 

random 

dialing) 

This survey collected 24-hour activity diaries and other 

questionnaire data from participants from 48 states. It was 

conducted as a next-day telephone recall interview. 

EPA designed and 

run, contractor 

conducted 

100
Table A-1. (Continued)

Study Date Size Type Brief Description NERL Role 

Agricultural 

Health Study 

(AHS) 

1993-

present; 

PES 1999-

2003 

84 applicators 

and a subset 

of family 

members in 

PES 

AHS survey 

is a 

longitudinal 

study of 

pesticide 

applicators in 

two states. 

PES, led by 

NERL, was a 

crosssectional 

study. 

A large-scale, long-term ongoing study of Iowa and North 

Carolina pesticide applicators and farm families. This 

collaborative effort involving the National Cancer Institute 

(NCI), the National Institute of Environmental Health Sciences 

(NIEHS), the National Institute for Occupational Safety and 

Health (NIOSH), and the U.S. Environmental Protection 

Agency (EPA) examines how lifestyle habits, genetic factors, 

and agricultural exposures contribute to the risk of disease 

using questionnaire survey data from 89,658 participants. This 

is the largest, most comprehensive study of agricultural health 

ever conducted in the United States. The interagency exposure 

assessment study (Pesticide Exposure Study (PES)), led by 

NERL, was performed to assess exposures and exposure 

classification procedures used in the epidemiological study. 

Collaboration with 

other agencies; 

NERL led a 

contractorconducted 

substudy called 

the Pesticide 

Exposure Study. 

The National 

Human 

Exposure 

Assessment 

Survey 

(NHEXAS)—

Overview 

1995-1998 See specifics 

in entries 

below. 

A Federal interagency research effort coordinated by EPA and 

consisting of four demonstration studies using probabilitybased sampling designs conducted in partnership with other 

Federal agencies (CDC, FDA, and NIST), universities, and 

research institutions. Household environmental and personal 

samples were collected and questionnaires were administered. 

Biological media, including blood and urine, also were sampled 

and monitored for parent contaminants or their metabolites. 

The studies were undertaken to evaluate total human exposure 

to multiple chemicals on a community and regional scale with 

the following aims: provide a baseline of the normal range of 

exposure to chemicals in the general population; identify 

subgroups of the general population that are likely to be highly 

exposed; and evaluate and improve the accuracy of models 

developed to predict exposure to chemicals. 

EPA oversaw 

general design for 

the research, then 

solicited, evaluated 

and funded the 

individual studies 

(see below). 

Details of research 

were established 

by recipients. 

NHEXASArizona 1995-1998 179 

Households 

Probability, 

crosssectional 

The NHEXAS-Arizona study sampled residences determined 

by a population-based probability research design for the total 

population of Arizona and measured metals, pesticides, and 

volatile organic compounds (VOCs). The study was conducted 

by a consortium composed of the University of Arizona, 

Battelle Columbus, and the Illinois Institute of Technology. 

Designed and 

conducted by 

award recipient 

(see above). 

NHEXASMaryland 1995-1996 80 

Households 

Probability, 

longitudinal 

The study sampled residences of Baltimore and four adjacent 

counties and measured metals, pesticides, and polycyclic 

aromatic hydrocarbons (PAHs). Data collection occurred up to 

6 times over 1 year for each of the participating households. 

The study was conducted by Harvard University, Emory 

University, Johns Hopkins University, and Westat. The study 

investigated temporal variability in multimedia, multipollutant 

exposures. 

Designed and 

conducted by 

award recipient 

(see above). 

NHEXASRegion 5 1995-1997 250 

Households 

Probability, 

crosssectional 

The Region 5 study was conducted in EPA's Region 5 (Ohio, 

Michigan, Illinois, Indiana, Wisconsin, and Minnesota), and 

included personal exposure, residential concentration, and 

biomarker measurements of metals and VOCs. The study was 

conducted by the Research Triangle Institute (RTI) and the 

Environmental and Occupational Health Sciences Institute 

(EOHSI). 

Designed and 

conducted by 

award recipient 

(see above). 

Minnesota 

Children’s 

Pesticide 

Exposure Study 

(MNCPES) 

1997 102 Children Probability, 

crosssectional 

Multimedia study of children 3-13 years conducted in 

Minnesota to evaluate children's pesticide exposure in urban 

and rural areas. The study provides exposure, environmental, 

and biologic data relating to multipathway exposures of 

children for four primary pesticides (chlorpyrifos, malathion, 

diazinon, and atrazine), 14 secondary pesticides, and 13 

polynuclear aromatic hydrocarbons (PAHs). This study 

complements and extends the populations and chemicals 

included in the NHEXAS-Region 5 study. 

Designed and 

conducted by 

award recipient 

(see above). 

101
Table A-1. (Continued)

Study Date Size Type Brief Description NERL Role 

Particulate 

Matter (PM) 

Panel Studies 

1998-2001 200 

Individuals 

(5 to 63 per 

study) 

Longitudinal A series of longitudinal studies in a number of U.S. cities 

conducted by EPA or by organizations sponsored through the 

National Exposure Research Laboratory (NERL). A primary 

goal was to determine the relationships between personal 

exposures to particles and associated gases relative to 

stationary outdoor monitor concentrations in high-risk 

subpopulations and to identify human activity patterns that 

might contribute to personal exposure. The investigators varied 

study locations, monitoring seasons, and study populations. 

Susceptible subpopulations of interest included chronic 

obstructive pulmonary disease (COPD) patients, individuals 

with cardiovascular disease, the elderly, asthmatics, and 

African Americans with hypertension. Panels of healthy 

individuals also were included. Because the elderly is the 

subpopulation most sensitive to health effects associated with 

PM exposures, the majority of subjects were over age 65. 

NERL conducted 

one panel study 

with contractor 

support; funded 

and collaborated 

on others with 

Harvard School of 

Public Health, 

University. of 

Washington, and 

NYU. 

Dietary Intake of 

Young Children 

(DIYC) 

1999-2000 3 Homes Convenience Performed in the Raleigh, NC, area in homes with children 1 to 

3 years old. Homeowners reported either professional or self 

applications of diazinon. Goals of the study were to evaluate 

methods to measure excess dietary exposures resulting from 

food-handling activities by young children during eating and to 

assess whether the Children’s Dietary Intake Model (CDIM) 

accurately represents total dietary exposures of children. Study 

resulted in refinements of model parameters for transfer and 

activity. 

NERL designed, 

contractor 

conducted 

Children’s 

Pesticide PostApplication 

Exposure Study 

(CPPAES) 

1999-2001 10 Homes Convenience, 

multiday pilot 

study to test 

methodology 

Observational measurement study of exposure to chlorpyrifos 

among children 2-5 years of age in urban New Jersey homes 

following crack and crevice treatment by a professional 

applicator. Study investigated decay of pesticide levels over 

time, transfer of pesticide from microenvironmental media to 

child, and factors that affect transfer. Dermal transfer evaluated 

with surface wipes, hand wipes, dermal wipes, cotton 

garments, and videotaping. 

NERL funded the 

Environmental and 

Occupational 

Health Sciences 

Institute (EOHSI). 

Develop Risk 

Assessment and 

Define Some 

Risk 

Management 

Options for 

Exposure of 

Children to Toxic 

Mold Using 

Stachybotrys 

chartarum as an 

Example 

2000 8 cases and 

8 controls 

Case control 

study 

Physicians at Case-Western Reserve treating children with 

idiopathic pulmonary hemorrhage evaluated the nature of the 

fungus found in homes of the afflicted and control children to 

determine if Stachybotrys was a potential factor in the illness. 

Three of the 8 cases, and none of the controls, had 

Stachybotrys strains that potentially were implicated. 

NERL staff 

collaborated with 

Case-Western 

Reserve University 

by conducting lab 

analysis for 

Stachybotrys. 

Children’s Total 

Exposure to 

Persistent 

Pesticides and 

Other Persistent 

Organic 

Pollutants 

(CTEPP) 

2000-2001 257 

Households 

Randomized, 

crosssectional 

The largest children’s exposure study undertaken to date. It 

examines aggregate exposures of children 18 months to 5 

years to pollutants commonly found in everyday environments. 

The major objectives were to quantify children’s aggregate 

exposures, apportion exposure pathways, and identify 

important exposure media. Participants were recruited from 12 

urban and rural counties in North Carolina and Ohio using a 

random digit dialing method. Monitoring was performed at both 

daycare centers and homes. Samples collected include food, 

beverages, indoor air, outdoor air, hand wipes, dust, soil, 

transferable residues, floor and surface wipes, and urine. The 

samples were analyzed for more than 40 pollutants, including 

insecticides, phthalate esters, phenols, polychlorinated 

biphenyls, and PAHs. 

NERL designed, 

contractor 

conducted 

Car-Related 

Occupational 

PM and Air 

Toxics Exposure 

to Patrolmen 

Study (COPP) 

2001 9 Convenience, 

longitudinal 

Scientists monitored air pollutants inside and outside vehicles 

of healthy highway patrol officers in North Carolina while 

troopers were on patrol for 9-hour shifts and examined 

cardiovascular effects. The findings indicated that people 

driving in motor vehicles are exposed to PM2.5 and other 

pollutants generated from motor vehicles, and that these 

exposures appear to cause cardiovascular changes. 

EPA designed and 

conducted with 

contractor support 

102
Table A-1. (Continued)

Study Date Size Type Brief Description NERL Role 

First National 

Environmental 

Health Survey of 

Child Care 

Centers (CCC) 

2001 168 Child care 

centers 

Probabilitybased 

selection on 

national scale

A collaborative study with the Department of Housing and 

Urban Development (HUD) and the Consumer Product Safety 

Commission (CPSC) of pesticide use and young children’s 

(less than 6 years old) potential exposure to pesticides and 

other pollutants in institutional childcare centers. This national 

study used multistage sampling with clustering. Indoor wipe 

and outdoor soil samples were analyzed for pesticides, lead, 

and allergens (mold/fungi). Pesticide use practices and 

application information were obtained from the commercial 

pest control applicators serving the centers. 

HUD and CPSC 

study. NERL 

collaborated and 

conducted analysis 

of molds/fungi and 

helped with lead 

and pesticide 

measurements. 

A Pilot Study 

Examining 

Translocation 

Pathways 

Following a 

Granular 

Application of 

Diazinon to 

Residential 

Lawns (PET) 

2001 6 Households Convenience, 

multiday pilot 

study to test 

methodology 

for exposure 

measurements 

Observational pilot exposure measurement study of residential 

exposures after homeowner had routinely applied granular 

formulation diazinon-containing turf treatment to residential 

lawns. Study was performed near Raleigh, NC, and was 

preceded by a 1-home methodology feasibility study. Purpose 

was to evaluate methods for assessing pet-borne transfer, 

translocation and exposure pathways, and decay rates. 

EPA conducted 

with contractor 

support 

Biological and 

Environmental 

Monitoring for 

Organophosphate and 

Pyrethroid 

Pesticide 

Exposures in 

Children Living 

in Jacksonville, 

FL (JAX) 

2001 9 Households 

in NERL 

exposure 

component 

Convenience, 

crosssectional 

The objectives of this investigation in Jacksonville, FL, were to 

(1) assess organophosphate (OP) and pyrethroid pesticide 

exposures in a group of 4- to 6-year-old children from 

Jacksonville by measuring the urine metabolite levels, 

(2) identify possible sources of these pesticides through 

screening measurements and pesticide inventories, and 

(3) examine the relationship between environmental and 

biological levels. The Duval County Health Department 

(DCHD) collected urine samples for CDC from 200 children 

visiting six public health clinics in Jacksonville, and collected 

environmental screening samples at approximately 25% of 

these children’s homes. A detailed aggregate exposure 

assessment at 9 homes was overseen by NERL and involved 

collection of surface wipes, transferable residues, air, duplicate 

diet, cotton garment samples, and urine samples. A timeactivity diary of the children’s activities was included. 

Multiagency effort; 

NERL was a 

participant and led 

the 9-home 

exposure 

component. 

Exposure 

Assessment for 

CommunityAcquired 

Legionnaires 

Disease 

2001 21 Case-control Work with Veteran’s Administration hospital staff. Cases of 

Legionnaires Disease were evaluated for potential for 

exposure from residential drinking water taps. In about 24% of 

the tested cases, homes were found to have Legionella 

bacteria in water taps at home, compared to their absence in 

other cases and in controls 

NERL funded IAG 

with VA to conduct 

study. 

Center for the 

Health 

Assessment of 

Mothers and 

Children of 

Salinas 

Quantitative 

Exposure 

Assessment 

Study 

(CHAMACOS) 

2002 20 Children Convenience Incidental pesticide exposure measurement study of 

farmworkers’ children ages 5 to 35 mo. Purpose is the 

evaluation of methods for aggregate exposure measurements 

and the evaluation of pathways of exposure and important 

factors that affect exposure. Measurements include pesticide 

distributions in microenvironments where children spend time, 

transfer of pesticides from microenvironmental media to child, 

and factors that affect transfer. 

EPA grant to UC 

Berkeley; NERL 

augmented the 

existing research 

effort. 

Feasibility of 

Macroactivity 

Approach To 

Assess Dermal 

Exposure 

(Daycare) 

2002 9 Daycare 

centers 

Convenience Study identified daycare centers with previously established 

contracts for routine monthly pesticide applications and 

conducted screening sampling in each to evaluate the 

distributions of transferable pesticide residues on floor surfaces 

where children spend time. One daycare was selected for 

intensive measurements, and children from different age 

groups volunteered to wear full-body cotton suits for short time 

periods while their activities were videotaped. 

NERL designed, 

contractor 

conducted 

103
Table A-1. (Continued)

Study Date Size Type Brief Description NERL Role 

Tampa 

Asthmatic 

Children's Study 

(TACS) 

2002 9 Residences Convenience 

sample, pilot 

study to test 

methods. 

Pilot study on methods for measuring personal, indoor 

residential, outdoor residential, and ambient combustionrelated products, particulate matter, and air toxics. The study 

identified microenvironmental factors affecting penetration of 

pollutants into homes and reduction of exposures to pollutants 

for asthmatic children (0-5 years of age). 

NERL designed, 

contractor 

conducted 

Pilot Study To 

Evaluate Data 

Collection 

Methods for 

Young 

Children’s and 

Household 

Activities 

2004 3 Homes Convenience, 

pilot study to 

test 

methodology 

Pilot aggregate exposure study of three homes to assess 

burden of alternative exposure sample collection methods. 

NERL designed, 

contractor 

conducted 

Detroit Exposure 

and Aerosol 

Research Study 

(DEARS) 

2004-2007 150 Randomized 

household 

selection with 

qualification 

criteria; 

longitudinal 

Recruitment from seven distinct neighborhoods in Detroit 

required strong community relations and partnership with State 

and local organizations. This study monitored for air pollutants 

at the personal level and evaluates how well centrally located 

(ambient) monitors represent exposure at the residential and 

personal level. Sampling is for 5 days duration in summer and 

again in winter. 

NERL designed 

and run; with 

contractor support 

and collaborators 

such as the 

University of 

Michigan 

Accelerometer 

Pilot Study 

2004 9 Convenience, 

pilot study to 

test 

methodology 

Nine children <24 months old and their primary caregivers 

participated in this study to (a) determine if very young children 

will wear an accelerometer for relatively long periods of time 

and comply with the protocol for its use, (b) evaluate how well 

a caregiver can estimate the activity level of his/her infant or 

toddler when completing an exposure-oriented time-activity 

diary, and (c) compare accelerometer count output with 

caregiver-provided estimates of children's activity level. 

NERL designed 

and run, with 

contractor support 

Pilot Study of 

Waterborne 

Infections 

2005 1296 Convenience, 

all volunteers 

from 

community 

using public 

water supply 

Measure antibodies in people’s saliva for antibodies to 

Cryptosporidium, Noroviruses, Rotaviruses, Helicobacter 

pylori, and Toxoplasma gondii before and after installation of 

an ultraviolet treatment system for a public water supply. Also 

served as test of methodology for detecting people’s prior 

exposure to infectious agents. 

EPA planned 

research (NERL is 

a collaborator), 

contractor 

conducted 

104
105

Table A-2. Types of Samples Collected in NERL Observational Human Exposure Studies 

Samples or Data Exposure Concern and Typical Type of Analysis 

Environmental Media 

Air pollutants Air pollutants being inhaled. Collect samples from central site, outside residence, and inside residence to assess 

pollutants in various locales. Measure gaseous and particle-bound pollutants. 

Soil Estimate track in and subsequent dermal or inhalation contact. Analyze for metals, pesticides, etc. 

House dust Dust from carpets and floors that may result in dermal contact or reentrainment and inhalation. Analyze for 

pesticides, metals, and tracers of outdoor sources. 

Surface wipes Dermal contact, children’s hand to mouth, and contact with food and subsequent ingestion. Analyze for metals and 

pesticides. Examine eating and food preparation areas too. 

Transferable residues Similar to surface wipes, using a surrogate for the transfer from the surface to the skin. 

Duplicate diet Use to assess ingestion exposures from food. Exact duplicate of amount and items eaten by participant and 

analyzed for pesticides, metals, etc. Includes drinking water samples as part of diet or other beverages consumed. 

Handled food Finger foods like cheese or luncheon meets that have been prepared and processed identically to foods children 

might eat to evaluate how much pollution may be removed from surfaces and ingested with the food. 

Human Activity Data 

Time-activity diaries Recall diaries to account for all times and activities in a day. Information includes location and activities. 

Activity loggers Device used to assess the nature of a person’s activities. Portable nephelometers have been used to keep up with 

people’s activities by showing when they were near PM sources. Accelerometers to measure level of activity of 

children at play. GIS and inertial devices to try to measure locations as a function of time of day. 

Questionnaires Query participants about things like daily activities for themselves or their children; housing characteristics;

participant characteristics, including occupation, diet, smoking habits, hobbies, etc.; and recent use of pesticides or 

other consumer products. 

Videotaping Use videos to measure frequency and duration of mouthing activities in children. 

Household inventories Inventory consumer products in house. Use items to ask about usage frequency and history. 

Researcher observations Information about open doors and windows (air exchange), heating and cooking sources, pets, and other activities 

that may lead to potential exposures may be observed. 

Personal or Biological Samples 

Urine Urinary excretion of pollutants and their contaminants give important information about the nature of prior 

exposures and their magnitude. 

Personal air monitors Individual wears samplers on his/her person while going about normal activities to measure pollutants in breathing 

zone of individual. 

Hand wipes Hand wipes remove contaminants from skin surface. Analyze for pesticides, metals, organic chemicals, and use 

values to estimate dermal exposure and hand-to-mouth ingestion of pollutants. 

Dermal surrogates Participant may wear cotton garments or socks as a collector. Clothing is analyzed for pesticides, metals, organic 

chemicals, etc. Measured contaminant quantities are used to estimate potential for dermal exposure. 

Saliva samples Test for antibodies to infectious agents, suggesting prior exposure and infection by microbial agent. 

Blood Some epidemiological studies that NERL scientists have collaborated on have collected blood samples. 

 
106
Appendix B 

The Process for Development of This Document: 

Description of the Expert Panel Workshop (November 28 and 29, 2006), 

the External Peer Review by the HSRB (October 21-24, 2007), 

and Public Comment 

Expert Panel Workshop 

An Expert Panel Workshop was convened in 

Durham, NC, on November 28 and 29, 2006. An ad hoc 

panel of experts was assembled to discuss issues 

associated with the preparation of this document prior to 

beginning its first draft. The workshop was coordinated 

by ERG, Inc., who was also responsible for compiling 

information from the workshop in a final workshop 

report, available on the Scientific and Ethical 

Approaches for Observational Exposure Studies 

(SEAOES) Web site at www.epa.gov/nerl/sots. 

The charge to the Expert Panel Workshop members 

was as follows. 

The panel is asked to consider these issues prior to 

the workshop in preparation for discussion during 

this workshop meeting: 

1. Provide recommendations on the content and 

organization of the document. 

a. Identify the major scientific and ethical 

areas/issues in the design and 

implementation of observational human 

exposure measurement studies that should 

be considered for inclusion in the document. 

b. Identify specific elements in each of these 

major areas that should be considered for 

inclusion in the document. 

c. Provide recommendations on the type and 

level of information that should be 

considered for inclusion in the document 

when describing state-of-the-science 

approaches, methods, techniques, or 

standards. 

d. Provide recommendations on the criteria 

that should be considered when evaluating 

and identifying the state-of-the-science for 

the approaches, methods, techniques, or 

standards. 

2. Provide recommendations and listings of sources 

of information for developing the document 

including case studies where available. 

3. Identify at least ten specific elements of the 

design and implementation of these studies that 

the panel considers to have the most uncertainty 

with regard to the “state-of-the-science,” discuss 

these elements, and provide recommendations on 

state-of-the-science approaches for them. 

The following individuals were members of the Expert 

Panel. 

Timothy Buckley (Chair) 

Division of Environmental Health Sciences 

School of Public Health 

Ohio State University 

Columbus, OH 

Sophie Balk 

Attending Pediatrician 

Children’s Hospital at Montefiore 

Professor of Clinical Pediatrics 

Albert Einstein College of Medicine 

Bronx, NY 

David Carpenter 

Director, Institute of Health and Environment 

University of Albany, SUNY 

Rensselaer, NY 

107
Giselle Corbie-Smith 

Department of Social Medicine 

University of North Carolina 

Chapel Hill, NC 

Alan Fleischman 

Senior Advisor 

The New York Academy of Medicine 

New York, NY 

Natalie Freeman 

Center for Environmental and Human Toxicology 

Department of Physiological Sciences 

University of Florida 

Gainesville, FL 

Loretta Jones 

Healthy African American Families 

Los Angeles, CA 

Bruce Lanphear 

Professor of Pediatrics and of Environmental Health 

Division of General and Community Pediatrics 

Cincinnati Children’s Hospital Medical Center 

Cincinnati, OH 

Michael Lebowitz 

Arizona Health Sciences Center 

Colleges of Public Health and Medicine 

University of Arizona 

Tucson, AZ 

Jerry Menikoff 

Department of History and Philosophy of Medicine 

University of Kansas Medical Center 

Kansas City, KS 

Rebecca Parkin 

Associate Dean for Research and Public Health Practice 

Professor of Environmental and Occupational Health 

School of Public Health and Health Service 

George Washington University Medical Center 

Washington, DC 

Review by the EPA Human Studies Review 

Board and Public Comment 

The process for developing this document included 

the following steps after the Expert Panel Workshop. 

• A draft document was written by NERL researchers. 

• The draft document was distributed to internal EPA 

staff for review and comment (see Acknowledgements 

for the list of reviewers). 

• The draft document was revised to address internal 

reviewer comments; an external review draft 

document was prepared. 

• The availability of the external review draft document 

for public comment was announced in a Federal 

Register notice. 

• An EPA docket was opened, and the external review 

draft document was available for public comment for 

45 days. 

• The external review draft document also was provided 

to EPA’s Human Studies Review Board (HSRB) for 

review and comment (see 

http://www.epa.gov/osa/hsrb/ for information on the 

HSRB). 

• The review by HSRB was announced in a Federal 

Register notice. 

• HSRB met October 21-24, 2007, and discussed the 

document during the meeting. 

• HSRB provided EPA with comments on the document 

in their final report of the October meeting. 

The charge to the HSRB for the SEAOES document 

review was that shown just below. 

Draft Document on Scientific and Ethical 

Approaches for Observational 

Exposure Studies 

Charge to the Human Studies Review Board 

(October 4, 2007) 

Observational human exposure studies are 

performed to collect information about individuals 

and the environment around them in order to better 

understand people’s exposures. These studies 

typically involve measurements of chemicals in the 

food people eat, the water they drink, the air they 

breathe and dust on the surfaces they touch. In 

addition, information about the study participants and 

their homes, work environments and activities are 

collected, as well as biomonitoring samples. It is 

important to understand why and how people are 

exposed to chemicals in the environment for EPA to 

fulfill its mission to protect human health. 

108
109

EPA scientists and their managers take the Cha

protection of human subjects who participate in their 

observational studies very seriously. The steps 

needed to ensure protection of the human subjects are 

often complex, and the specific actions will vary 

depending on the objectives of the study, details 

about the participants, and the communities in which 

the studies are performed. 

This document is intended as a resource and 

reference for scientists in EPA’s Office of Research 

and Development (ORD) National Exposure 

Research Laboratory (NERL) as they develop and 

implement observational human exposure studies. 

The authors recognize that this document may also 

prove to be useful to others involved in exposure 

science research, but the document is not meant to 

represent an official Agency “guidance document” 

and should not be used that way. This document does 

not provide solutions to the scientific and ethical 

issues that will undoubtedly arise as such studies are 

undertaken: no document could provide all of the 

answers in advance or develop a comprehensive 

checklist for all such studies. Rather, this document 

attempts to identify the types of issues that will need 

to be considered and addressed as NERL researchers 

plan and implement observational human exposure 

studies. The researchers will need to work with others 

– the study team, IRB members, EPA Human 

Subjects Research Review Official (HSRRO), the 

participants and their community, and other 

stakeholders – to identify and address all of the 

relevant issues for their particular study in order to 

ensure that the specific elements of the study will 

safeguard and protect the human research subjects. 

rge to the Human Studies Review Board 

The draft document on Scientific and Ethical 

Approaches for Observational Exposure Studies 

consists of the following seven sections: 

1. Introduction 

2. Elements to be Considered in Study 

Conceptualization and Planning 

3. Ensuring Protection of Vulnerable Groups 

4. Privacy, Confidentiality, and Other Concerns 

Related to Observational Human Exposure 

Measurement Studies 

5. Creating an Appropriate Relationship Between 

Participant and Investigator 

6. Building and Maintaining Appropriate Community 

and Stakeholder Relationships 

7. Designing and Implementing Strategies for 

Effective Communication 

The Human Studies Review Board is asked to 

address the following questions for each section of 

the draft document: 

1. One of the goals of the document is identify the 

major scientific and ethical areas and issues that 

researchers should address in the design and 

implementation of observational human exposure 

measurement studies, with the emphasis on the 

areas requiring ethical considerations. Does each 

section identify the major areas and issues where 

ethical considerations should be addressed? 

2. The document is intended to serve as a reference 

and resource of information that researchers can 

use in the design and implementation of 

observational exposure studies. For each section, 

are there additional sources of information that 

should be considered for inclusion? 

3. Is the information presented accurately and clearly 

in each section?
110
Appendix C 

Recommended Content of a Human Subjects Protocol 

The Council for International Organizations of Medical 

Sciences (CIOMS, 2002) has developed a comprehensive 

list of items that they recommend for inclusion in a 

human subjects research protocol. Many of the items 

that they identify are also useful for observational human 

exposure studies. 

Items Relevant to Observational Human 

Exposure Studies 

(1) The title of the study 

(2) A summary of the proposed research in lay or 

nontechnical language 

(3) A clear statement of the justification for the study 

(4) The investigators’ views of the ethical issues and 

considerations raised by the study and, if 

appropriate, how it is proposed to deal with them 

(5) A summary of previous studies on the research 

problem, including unpublished studies known to 

the investigators, and information on previously 

published research on the topic 

(6) A statement that the principles of the Belmont 

Report and requirements specified in 40 CFR 26 

will be implemented 

(7) An account of previous submissions of the protocol 

for ethical review and their outcomes 

(8) A brief description of the sites where the research is 

to be conducted, including information about the 

adequacy of facilities for the safe and appropriate 

conduct of the research, and relevant demographic 

and epidemiological information about the 

population to be studied 

(9) The names and addresses of the funding 

organization, research partners, and collaborators 

(10) The names, addresses, institutional affiliations, 

qualifications, and experience of the principal 

investigator and other investigators 

(11) The objectives of the study, its hypotheses or 

research questions, its assumptions, and its 

variables 

(12) A detailed description of the design of the study 

(13) The number of research subjects needed to achieve 

the study objective, and how this was determined 

statistically 

(14) The criteria for inclusion or exclusion of potential 

subjects and justification for the exclusion of any 

groups on the basis of age, sex, social or economic 

factors, or other reasons 

(15) The justification for involving as research subjects 

any persons with limited capacity to consent or 

members of vulnerable social groups and a 

description of special measures to minimize risks 

and discomfort to such subjects 

(16) The process of recruitment (e.g., advertisements) 

and the steps to be taken to protect privacy and 

confidentiality during recruitment 

(17) A description and explanation of any and all 

interventions 

(18) The measurements to be performed in the study, 

including environmental and biological sample 

collection, and other data and information that will 

be collected 

(19) If applicable, clinical and other tests involving the 

study participants that are to be carried out 

(20) The rules or criteria according to which subjects 

may be removed from the study or the study may be 

terminated 

(21) The methods of recording and reporting adverse 

events or reactions, and provisions for dealing with 

complications 

(22) The potential benefits of the research to subjects 

and to others 

(23) The expected benefits of the research to the 

population, including new knowledge that the study 

might generate 

111
(24) The means proposed to obtain individual informed 

consent and the procedure planned to communicate 

information to prospective subjects, including the 

name and position of the person responsible for 

obtaining consent 

(25) When a prospective subject is not capable of 

informed consent, satisfactory assurance that 

permission will be obtained from a duly authorized 

person, or, in the case of a child who is sufficiently 

mature to understand the implications of informed 

consent but has not reached the legal age of 

consent, that knowing agreement, or assent, will be 

obtained, as well as the permission of a parent, or a 

legal guardian or other duly authorized 

representative. 

(26) An account of any economic or other compensation 

or incentives to prospective subjects to participate, 

such as offers of cash payments, gifts, or free 

services or facilities, and of any financial 

obligations assumed by the subjects, such as 

payment for medical services 

(27) The plans and procedures and the persons 

responsible for communicating to subjects 

information arising from the study (on harm or 

benefit, for example) or from other research on the 

same topic that could affect subjects’ willingness to 

continue in the study 

(28) The plans to inform subjects about the results of the 

study 

(29) The provisions for protecting the confidentiality of 

personal data and respecting the privacy of subjects, 

including the precautions that are in place to 

prevent disclosure of the results of a subject’s 

genetic tests to immediate family relatives without 

the consent of the subject 

(30) Information about how the code, if any, for the 

subjects’ identity is established; where it will be 

kept; and when, how, and by whom it can be broken 

in the event of an emergency 

(31) Any foreseen further uses of personal data or 

biological materials 

(32) A description of the plans for statistical analysis of 

the study, including plans for interim analyses, if 

any, and criteria for prematurely terminating the 

study if necessary 

(33) A list of the references cited in the protocol 

(34) The source and amount of funding of the research, 

including the organization that is sponsoring the 

research and a detailed account of the sponsor’s 

financial commitments to the research institution, 

the investigators, the research subjects, and, when 

relevant, the community 

(35) The arrangements for dealing with financial or 

other conflicts of interest that might affect the 

judgment of investigators or other research 

personnel, including informing the institutional 

conflict-of-interest committee of such conflicts of 

interest; the communication by that committee of 

the pertinent details of the information to the ethical 

review committee; and the transmission by that 

committee to the research subjects of the parts of 

the information that it decides should be passed on 

to them 

(36) The time schedule for completion of the study 

(37) Particularly in the case of an industrial sponsor, a 

contract stipulating who possesses the right to 

publish the results of the study and a mandatory 

obligation to prepare with and submit to the 

principal investigators the draft of the text reporting 

the results 

(38) The circumstances in which it might be considered 

inappropriate to publish findings, such as when the 

findings of any study may present risks to or 

stigmatize the interests of a community or 

population or of a racially or ethnically defined 

group of people 

(39) A statement that any proven evidence of 

falsification of data will be dealt with in accordance 

with the policy of the sponsor to take appropriate 

action against such unacceptable procedures 

Source: CIOMS (The Council for International Organizations of 

Medical Sciences) (2002). International Ethical Guidelines for 

Biomedical Research Involving Human Subjects. World Health 

Organization. Geneva, Switzerland.

112
Appendix D 

Recommendations for Enhancing Public Trust 

Although the Report and Recommendations on Public 

Trust in Clinical Research for the NIH Director from the 

Director’s Council of Public Representatives (COPR)

was developed in the context of NIH-supported clinical 

research, many of the recommendations are applicable to 

observational human exposure studies. A summary of 

recommendations from the report is provided below. 

Building Trust Through Community 

Partnerships 

Recommendation 1: Incorporate into the NIH 

mission and philosophy that it values the involvement 

of the community in research and create language 

that expresses this value. 

Recommendation 2: Encourage change in the 

culture of the scientific community to ensure that 

medical research is viewed in the context of a longterm commitment to the community, not a one-time 

research study. 

Recommendation 3: Investigate ways to provide 

mechanisms that allow for follow-up health care 

when a clinical trial or treatment ends. 

Building Relationships with Patients 

(Participants) (True partnerships with 

patients may not be possible, but 

bidirectional relationships must be 

enhanced.) 

Recommendation 4: Educate and reorient the 

current research community to the importance of 

treating the public as a partner in the research 

process. 

Recommendation 5: Set the expectation across 

the entire research community, NIH funded research 

and beyond, that study results and outcomes should 

be shared with the research participants and the larger 

community promptly and consistently. This will 

ensure translational research. 

Building Partnerships with Community 

Providers 

Recommendation 6: Take action to interest 

community providers in clinical research and 

maintain their involvement. 

Recommendation 7: Provide incentives (not just 

financial) for primary health care providers and 

community specialists to play a role in clinical trials. 

Building Trust in Scientists 

Recommendation 8: Engage researchers, 

educators, and academic institutions in incorporating 

the public's perspective consistently at every level of 

training and in both the conduct of clinical research 

and the publication of findings from that research. 

Recommendation 9: Focus on educational 

strategies to help patients and communities better 

understand clinical research. This will help scientists 

because educating the public will empower and 

prepare individuals to be informed partners in the 

clinical research process. An informed and trusting 

public will enhance research participation. 

Building Trust in the NIH and Scientific 

Research 

Recommendation 10: Continue to develop and 

fund efforts to build a national identity for the NIH 

based on what NIH does best—research and 

education—as a basis for enhancing public trust in 

clinical research. 

Recommendation 11: Review the role and impact 

of Institutional Review Boards and other patient 

protections in the clinical research process because 

the public views these protections as less effective 

than they should be. 

Recommendation 12: Document and publish 

“best practices” from efforts to reengineer the clinical 

research enterprise as soon as the NIH begins to see 

results, so that progress in improving public trust in 

medical research grows rapidly and steadily. 

Source: NIH (National Institutes of Health) (2005). Report and 

Recommendations on Public Trust in Clinical Research for the NIH 

Director from the Director’s Council of Public Representatives 

(COPR). National Institutes of Health, Director’s Council of Public 

Representatives, January 14, 2005. Available: 

http://copr.nih.gov/reports/public_trust.asp [accessed 12 June 2007]. 

113
114
Appendix E 

List of Acronyms and Abbreviations 

AAP American Academy of Pediatrics 

ACGIH American Conference of Governmental Industrial Hygienists 

AHS Agricultural Health Study 

ATSDR Agency for Toxic Substances and Disease Registry 

BEI biological exposure index 

CAB community advisory board 

CBPR community-based participatory research 

CDC Centers for Disease Control and Prevention 

CFR Code of Federal Regulations 

CIOMS Council for International Organizations of Medical Sciences 

COPR National Institutes of Health Director’s Council of Public Representatives 

CPSC Consumer Product Safety Commission 

CTEPP Children’s Total Exposure to Persistent Pesticides and Other Persistent Organic 

Pollutants 

DEARS Detroit Exposure and Aerosol Research Study 

DHEW U.S. Department of Health, Education, and Welfare 

DMOC data monitoring and oversight committee 

DNA deoxyribonucleic acid 

DSMB data safety monitoring board 

DSMP data and safety monitoring plan 

EHCRB environmental health and community review board 

EPA U.S. Environmental Protection Agency 

ERG Eastern Research Group 

FCN Federal Communicators Network 

FDA Food and Drug Administration 

HHS U.S. Department of Health and Human Services 

HSRB Human Studies Review Board 

HSRRO Human Subjects Research Review Official 

HUD U.S. Department of Housing and Urban Development 

ICR information collection request 

IOM Institute of Medicine 

IRB institutional review board 

NAS National Academy of Sciences 

NBAC National Bioethics Advisory Commission 

NCI National Cancer Institute 

NCS National Children’s Study 

NEI National Eye Institute 

NEJAC National Environmental Justice Advisory Council 

NERL National Exposure Research Laboratory 

115
116

NGO Nongovernmental organization 

NHANES National Health and Nutrition Examination Survey 

NHAPS National Human Activity Pattern Study 

NHEXAS The National Human Exposure Assessment Survey 

NHLBI National Heart, Lung, and Blood Institute 

NHRPAC National Human Research Protections Advisory Committee 

NIH National Institutes of Health 

NRC National Research Council 

OHRP Office for Human Research Protections 

OMB Office of Management and Budget 

OSMB observational study monitoring board 

PM particulate matter 

Q&As questions and answers 

QAPP quality assurance project plan 

RfD reference dose 

SEAOES Scientific and Ethical Approaches for Observational Exposure Studies 

TEAL Tribal Efforts Against Lead 

TEAM Total Exposure Assessment Methodology 

TLV threshold limit value 

VOC volatile organic compound 

WHO World Health Organization 
Appendix F

Glossary 

Agent. A chemical, mineralogical, biological, or 

physical entity that may cause deleterious effects in an 

organism after the organism is exposed to it 

[EPA/600/Z-92/001, May 1992]. 

Assent. A child’s affirmative agreement to participate in 

research. Mere failure to object should not, absent 

affirmative agreement, be construed as assent [45 CFR 

46.402(d)]. 

Autonomy. The capability and capacity to govern 

oneself. 

Beneficence. The ethical obligation to maximize 

benefits and to minimize harms. This principle gives rise 

to norms requiring that the risks of research be 

reasonable in light of the expected benefits, that the 

research design be sound, and that the investigators be 

competent both to conduct the research and to safeguard 

the welfare of the research subjects. Beneficence further 

proscribes the deliberate infliction of harm on persons; 

this aspect of beneficence is sometimes expressed as a 

separate principle, nonmaleficence (do no harm). 

Child. A person who has not attained the age of 18 

years [40 CFR 26.202(a)] 

Collateral observations. Potentially unsafe hazards, 

conditions, or situations unrelated to the research study 

that are observed by the research staff 

Common Rule. The Common Rule is a short name for 

“The Federal Policy for the Protection of Human 

Subjects.” It was adopted by more than a dozen Federal 

departments or agencies in 1991, with EPA adapting it in 

Title 40 CFR Part 26 Subpart A. 

Community-based participatory research (CBPR). 

Collaborative research with a community in which the 

community is involved in all phases of the research. 

A fundamental concept is that the research aims to 

combine knowledge with action and to achieve social 

change to improve health outcomes and eliminate health 

disparities. 

Confidentiality. The keeping safe or not redisclosing 

by one of the parties in a confidential relationship 

information that originally was disclosed in the 

confidential relationship 

Environmental justice. The fair treatment and 

meaningful involvement of all people regardless of race, 

color, national origin, or income with respect to the 

development, implementation, and enforcement of 

environmental laws, regulations, and policies 

Exposure. Contact of a chemical, physical, or 

biological agent with the outer boundary of an organism 

(e.g., a person). Exposure is quantified as the 

concentration of the agent in the medium in contact 

integrated over the time duration of that contact. (The 

definition is taken from Guidelines for Exposure 

Assessment [EPA/600/Z-92/001, May 1992]). 

Exposure concentration. The exposure mass divided 

by the contact volume or the exposure mass divided by 

the mass of contact volume depending on the medium 

Exposure duration. The length of time over which 

continuous or intermittent contacts occur between an 

agent and a target. For example, if an individual is in 

contact with an agent for 10 minutes per day for 300 

days over a 1-year time period, the exposure duration is 

1 year. 

Exposure event. The occurrence of continuous contact 

between an agent and a target 

Exposure pathway. The course an agent takes from the 

source to the target 

Exposure route. The way an agent enters a target after 

contact (e.g., by ingestion, inhalation, or dermal 

absorption) 

117
Human subject. A living individual about whom an 

investigator (whether professional or student) 

conducting research obtains: (1) data through 

intervention or interaction with the individual, or (2) 

identifiable private information [40 CFR 26.102(f)] 

Informed consent. A potential participant’s 

autonomous authorization to participate in the research. 

The three pillars of valid informed consent are 

(1) information, (2) comprehension, and (3) voluntary 

participation. 

Institutional review board (IRB). An IRB established 

in accord with and for the purposes expressed in EPA’s 

Policy for Protection of Subjects in Human Research 

conducted and supported by EPA [40 CFR 26.102(g)] 

Justice. The ethical obligation to treat each person in 

accordance with what is due to him or her. In the ethics 

of research involving human subjects, the principle 

refers primarily to distributive justice, which requires the 

equitable distribution of both the burdens and the 

benefits of participation in research. Differences in 

distribution of burdens and benefits are justifiable only if 

they are based on morally relevant distinctions among 

persons. 

Minimal risk. The probability and magnitude of harm 

or discomfort anticipated in the research are not greater 

in and of themselves than those ordinarily encountered 

in daily life or during the performance of routine 

physical or psychological examinations or tests [40 CFR 

26.102(i)]. 

Nonmaleficence. The proscription of deliberate 

infliction of harm on persons 

Observational human exposure study. Studies that 

involve collection of human exposure data (including 

environmental, biological, survey, activity, and various 

other forms of data) under real-world field conditions 

during normal participant day-to-day activities, with no 

additional exposures to the chemical being studied 

because of participation in the study. The studies involve 

interaction with study participants but do not involve 

intervention or manipulation of the factors being studied, 

and there is no attempt by the researcher to affect the 

outcome. 

Observational research. Any human research that does 

not meet the definition of research involving intentional 

exposure of a human subject [40 CFR 26.302] 

Privacy. Control over the extent, timing, and 

circumstances of sharing oneself (physically, 

behaviorally, or intellectually) with others 

Research. A systematic investigation, including 

research development, testing, and evaluation, designed 

to develop or contribute to generalizable knowledge 

Research involving intentional exposure of a human 

subject. A study of a substance in which the exposure 

to the substance experienced by a human subject 

participating in the study would not have occurred but 

for the human subject’s participation in the study [40 

CFR 26.202(b)] 

Respect for persons. A fundamental ethical value that 

is the basis of much of modern bioethical thought and 

regulation. The concept incorporates at least two 

fundamental ethical considerations, namely (1) respect 

for autonomy, which requires that those who are capable 

of deliberation about their personal choices should be 

treated with respect for their capacity for selfdetermination; and (2) protection of persons with 

impaired or diminished autonomy, which requires that 

those who are dependent or vulnerable be afforded 

security against harm or abuse. 

Source. The origin of an agent for the purposes of an 

exposure assessment 

Stakeholder. A person or group who has a valid 

interest in an activity, who can affect or is affected by 

the activity, and who stands to gain or lose depending on 

the decisions implemented 

Stressor. Any entity, stimulus, or condition that can 

modulate normal functions of the organism or induce an 

adverse response (e.g., agent, lack of food, drought) 

Vulnerability. A substantial incapacity to protect one’s 

own interests owing to such impediments as lack of 

capability to give informed consent, lack of alternative 

means of obtaining medical care or other expensive 

necessities, or being a junior or subordinate member of a 

hierarchical group. Accordingly, special provision must 

be made for the protection of the rights and welfare of

vulnerable persons. 

Vulnerable groups. Populations extended additional 

human subjects protections, such as children, individuals 

with questionable capacity to consent, prisoners, fetuses 

and pregnant women, the terminally ill, students and 

employees, and comatose patients, etc. 

118