Department  of Health  and  Human  Services 
OFFICE  OF 
INSPECTOR  GENERAL 
Institutional  Review  Boards: 

Promising  Approaches 

JUNE  GIBBS BROWN 
Inspector  General 
JUNE  1998 
OEI-01-91-00191  OFFICE  OF INSPECTOR  GENERAL 
The mission  of the Office  of Inspector  General (OIG),  as mandated by Public  Law  95-452,  is to 
protect the integrity  of the Department  of Health  and Human  Services programs  as well  as the 
health and welfare  of beneficiaries  served by them.  This statutory  mission  is carried out through 
a nationwide  program  of audits, investigations,  inspections,  sanctions, and fraud alerts.  The 
Inspector  General informs  the Secretary of program  and management problems  and recommends 
legislative,  regulatory,  and operational  approaches to correct them. 
Office  of Evaluation  and Inspections 
The Office  of Evaluation  and Inspections  (OEI)  is one of several components  of the Office  of 
Inspector  General.  It conducts  short-term  management  and program  evaluations  (called 
inspections)  that focus on issues of concern to the Department,  the Congress, and the public.  The 
inspection  reports provide  findings  and recommendations  on the efficiency,  vulnerability,  and 
effectiveness  of departmental  programs. 
OEIs Boston  regional  office  prepared this report  under the direction  of Mark  R. Yessian, Ph.D., 
Regional  Inspector  General.  Principal  OEI staff included: 
REGION  HEADQUARTERS 
Elizabeth  A. Robboy  Lisa Foley 
Nathan  P. Rouillard 
Laura C. McBride 
Dana M. Miller 
To obtain copies of this report, please call the Boston Regional Office at (617)565-1050. 
Reports are also available  on the World  Wide Web at our home page address: 
http://www.dhhs.gov/progorg/oei  EXECUTIVE  SUMMARY 
PURPOSE 
To identify  promising  approaches that institutional  review  boards use to enhance their 
effectiveness  and efficiency  in protecting  human subjects. 
BACKGROUND 
Role  of Institutional  Review  Boards 
Institutional  review  boards (IRBs)  play vital  roles in protecting  human research subjects. 
They review  initial  research plans to make certain that the plans provide  subjects with 
adequate opportunity  to provide  informed  consent and do not expose subjects to 
unreasonable  risks.  They also conduct  continuing  review  of approved research to ensure 
that human-subject  protections  remain  in force.  They carry out their initial  and 
continuing  review  functions  in accord with  Federal regulations  first established  in the 
1970s and applicable  to all research funded  by the U.S. Department  of Health  and Human 
Services or carried out on products  regulated  by the Food and Drug  Administration. 
In carrying  out their responsibilities,  IRBs  face challenges posed by a changing  research 
environment.  Advances  in genetics research, a proliferation  of large-scale trials,  and the 
blurring  definitions  of research and therapy  make research increasingly  complex  to 
review  and oversee.  Across the country  IRBs  are inundated  with  research plans and are 
under enormous pressure to review  them quickly.  At the same time, many are finding  it 
difficult  to recruit  and maintain  members.  Despite these challenges, many IRBs  have 
developed  innovative  strategies for reviewing  research plans and for providing 
educational  outreach.  Yet, in this environment  there is little  time for the sharing of 
promising  approaches among the thousands  of IRBs  in existence. 
Promising  Approaches:  The Focus of this  Report 
This report focuses on promising  approaches of IRBs.  One of 4 reports we are issuing  on 

IRBs,  it draws on interviews  and group  discussions  with  representatives  of about 

75 IRBs;  site visits to IRBs in 6 academic health centers where extensive clinical  research 

is taking  place; reviews  of Federal records and pertinent  literature;  and attendance at IRB 

meetings. 

The promising  approaches included  here address six key areas of responsibility  for IRBs. 

Within  each area, we have chosen promising  approaches that seem to have potential  for 

multiple  IRBs.  We recognize,  however,  that what works  well  in one IRB  may not 

necessarily  work  well  in another. 

i  OEI-01-97-00191 IRBs: Promising Approaches  PROMISING  APPROACHES 
Managing  the Workload 
To reduce workload  pressures, many institutions  are creating  multiple  IRBs  and/or 
increasing  the number  of IRB  meetings.  Some institutions  are creating  specialty  IRBs, 
such as dental, medical  or social science IRBs  to ensure that board members have 
sufficient  expertise to assess research plans.  Other institutions  maintain  general-purpose 
IRBs  but stagger their  meetings.  One IRB  staggers its four board meetings  so that there is 
an IRB  meeting  every week.  A research investigator  submitting  a research plan to this 
IRB  will  have his or her plan reviewed  by the first available  board.  The waiting  period  is 
generally  no longer  than one week. 
Providing  Educational  Outreach  to Research  Investigators 
To ensure that all research investigators  receive minimal  training  about human-subject 
protections,  some institutions  require their research investigators  to attend mandatory 
training  programs.  A dean at one institution  will  not sign off on approved research until 
investigators  have attended a 2-day workshop.  According  to IRB  staff, this method 
provides  a powerful  political  message to all investigators  about the importance  of human-
subject education.  Another  institution  requires all of its investigators  to complete  an on-
line tutorial  about human-subject  protections.  This tutorial,  which  takes an hour to 
complete,  provides  a base level of education  for a nominal  fee to the institution. 
Reviewing  Approved  Research 
Using  a third  party to oversee research is an effective  technique  for IRBs that do not have 
the time to observe the research process themselves.  One IRB  requires  a research 
intermediary  to interact  with  all psychiatric  patients involved  in research projects. 
Among  other things,  the research intermediary  discusses the consent form with  patients 
after the form has been signed to ensure that upon reflection,  patients continue  to want to 
participate  in the research.  Every few months, the research intermediary  reports to the 
IRB  about patients  concerns and the ways in which  the consent process and/or research 
could be made more efficient  and less obtrusive  for patients. 
Providing  Educational  Outreach  to IRB  Members 
Educating  IRB  members is an important  strategy for ensuring  that they have adequate 
expertise to assess research plans.  One IRB  sends its members literature  relevant to the 
research plan being discussed.  This approach has been particularly  beneficial  to help 
orient new members to the ethical issues they should consider  when reviewing  protocols. 
Another  IRB  devotes a portion  of each meeting to education.  A benefit  of this type of 
education,  according  to the IRB  director,  is the ripple  effect it can have with  other 
researchers in the institution.  For example, after a recent meeting  where AIDS  trials were 
discussed, two  of the physician  members shared the discussion  with  their residents. 
ii  OEI-01-97-00191 IRBs: Promising Approaches  Broadening  Perspectives  in the IRB  Review  Process 
A strategy for providing  thoughtful,  fair review  is to continually  maintain  contact with  the 
community  in which  the research takes place.  One IRB  established an Office  of Ethnic 
Diversity  in Research to help it identify  barriers the community  faces when participating 
in research and potential  strategies to overcome these barriers.  For example, many in the 
community  are unaware  of what being a research subject entails and they associate the 
hospital  with  treatment rather than research.  Through  community  outreach, the IRB  has 
become sensitive to the need to further  simplify  consent forms in order to impress upon 
potential  subjects that they are participating  in research. 
Evaluating  IRB  Effectiveness  and  Efficiency 
To improve  its operations,  one IRB  performed  a two-pronged  self-evaluation.  First, it 
convened a group of faculty  members to perform  a month-long  evaluation  of its 
operations.  Second, it hired an outside monitor  to assessresearch protocols  for regulatory 
compliance  and to interview  investigators  about their interactions  with  the IRB  and their 
experiences with  the review  process.  Both  evaluations  were helpful  in highlighting  areas 
that needed improvement,  such as increased resources for the IRB,  changes in the 
reporting  structure,  and more support from the University.  The resultant  changes have 
also helped to create better relations  between researchers and the IRB. 
CONCLUSION 
Despite the challenges posed by the new research environment,  IRBs  have employed 
many promising  approaches to enhance their effectiveness  and efficiency.  A key 
challenge  to the Federal government  is to find ways of giving  IRBs  the flexibility  to 
develop innovative  approaches while  at the same time holding  them accountable  for 
performance.  This is a matter we address in our summary report entitled,  Institutional 
Review Boards:  A Time For  Reform. 
COMMENTS  ON THE  DRAFT  REPORTS 
Within  the Department  of Health  and Human  Services, we received comments  on our 

four draft reports from the National  Institutes  of Health,  the Food and Drug 

Administration  and, jointly,  from the Assistant  Secretary for Planning  and Evaluation  and 

the Assistant  Secretary for Health.  We also solicited  and received comments  from the 

following  external parties:  the Applied  Research Ethics National  Association,  the 

American  Association  of Medical  Colleges,  the Consortium  of Independent  Review 

Boards, and Public  Citizens  Health  Research Group.  We include  the detailed text of all 

of these comments and our responses to them in appendix  D of our overview  report, 

Institutional  Review Boards;  A Time for  Reform (OEI-01-97-00193).  In the executive 

summary  of that report, we summarize the thrust of these comments and our responses. 

111  OEI-01-97-00191 IRBs: Promising Approaches  TABLE  OF  CONTENTS 
PAGE 
EXECUTIVE  SUMMARY 
INTRODUCTION  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..l 
IRBs:  THE  BASICS  . . . . . _. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 

PROMISING  APPROACHES 
ManagementoftheWorkload  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ...4 

Educational  Outreach to Research Investigators  ................................  8 

Continuing  Review  of Approved  Research  ...................................  12 

Educational  Outreach to IRB  Members  ......................................  15 

Broadening  Perspectives in the IRB  Review  Process  ...........................  17 

Evaluation  of IRB  Effectiveness  and Efficiency  ..............................  .20 

CONCLUSION  ............................................................  ..2  2 

APPENDICES 
A:Endnotes  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  A-l 
OEI-01-97-00191 IRBs: Promising Approaches  INTRODUCTION 
PURPOSE 
To identify  promising  approaches that institutional  review  boards use to enhance their 
effectiveness  and efficiency  in protecting  human subjects. 
BACKGROUND 
On page three we offer a primer  on IRBs:  why  they were established, what roles they 
perform,  how they are organized,  where they are located, and how they are overseen by 
the Department  of Health  and Human  Services. 
Establishment  of Institutional  Review  Boards 
In the 1970s  in the aftermath  of some widely  publicized  abuses involving  human subjects 
in clinical  research, the Federal government  began establishing  a set of requirements 
calling  for institutional  reviews boards (IRBs)  to protect  human subjects.  The IRB 
system was originally  envisioned  as a decentralized  system in which  research was to be 
overseen at the local level.  Most  of the early IRBs  were established in the large teaching 
hospitals  and medical  centers, where nearly  all clinical  research was conducted.  At the 
time that the regulations  were established, research studies were typically  conducted  by a 
single research investigate?  with  a few subjects. 
Challenges  Facing  Institutional  Review  Boards 
The environment  in which  IRBs  operate has changed significantly  in the past two 
decades.  Managed  care, with  its emphasis on cost control,  is squeezing research support 
at academic health centers and limiting  providers  time for administrative  duties such as 
IRB  participation.  The proportion  of research that is commercially  sponsored has grown? 
The locus of clinical  research has shifted from  single-site  trials to large multi-site  trials 
conducted  across the country,  even the world.4  Biomedical  research is constantly 
expanding  into new frontiers  such as gene testing  and gene therapy.  Many  of these new 
research directions  raise complicated  questions  about human-subject  protections  and 
challenge  our notions  of informed  consent.  When IRBs  were first established, research 
was viewed  as burdensome  rather than beneficial  to human subjects and something  to be 
protected  from.  Now,  many people with  lethal diseases are demanding  access to the most 
advanced treatments,  even when these treatments  are experimental. 
These changes have had a significant  effect on IRBs  across the country.  Many  are 
inundated  with  research proposals  and are overwhelmed  by adverse-event reports from 
sponsors.  Many  IRBs  are not sufficiently  supported  by their institutions.  A number  of 
IRBs  are having  difficulty  recruiting  and maintaining  members, particularly  physician 
1  031-01-97-00191 IRBs: Promising Approaches  members.  At the same time, they are under enormous  pressure to review  protocols 
quickly.  Despite these challenges,  many IRBs  have developed  innovative  approaches to 
improve  their effectiveness  and efficiency.  Yet, in this environment  there is little  time for 
the sharing of promising  approaches among the thousands of IRBs  in existence! 
This  Inquiry  and this  Report 
In the wake of many changes transforming  the world  of clinical  research, there is renewed 

interest in human-subject  protections  and the role of the IRB.  A  1995 report  issued by the 

Institute  of Medicine  (IOM)  recommended  a study on lessons learned about effective  IRB 

functioning.7  The National  Bioethics  Advisory  Commission  (NBAC)  is currently 

examining  the state of these protections  and is pursuing  information  about IRBs. 

This report, which  is one of four we are issuing  as part of a broad inquiry  of IRBs, 

focuses on promising  approaches of IRBs?  In determining  what to characterize  as a 

promising  approach, we depended on the judgements  of IRB  members and 

administrators,  consultations  with  IRB  experts, and our own judgement  of whether  the 

approach was significantly  different  and important  to warrant  attention.  The promising 

approaches included  here appear to have potential  in numerous  IRBs,  although  we 

recognize  that what works  well  in one IRB  may not necessarily  work  well  in another.  It is 

important  to acknowledge  that our highlighting  a promising  approach at one institution 

does not necessarily mean that other institutions  have not developed  similar  approaches. 

Many  of the issues raised in this report are addressed more fully  in our parallel  reports. 

One report, Institutional  Review Boards:  Their Role in Reviewing  Approved  Research, 

finds that IRBs  are devoting  minimal  attention  to their  continuing  review  responsibilities 

and identifies  key obstacles responsible  for that situation.  Another,  Institutional  Review 

Boards:  The Emergence of Independent  Boards,  finds that independent  IRBs  are 

becoming  a significant  force and addresses the advantages and disadvantages they 

present.  A third,  Institutional  Review Boards:  A Time For  Reform, provides  an overview 

of IRB  functioning  and presents recommendations  emerging  from our inquiry. 

Our overall  inquiry  draws on a rich variety  of sources.  These include  interviews  and 

group discussions with  representatives  of about 75 IRBs  of varying  sizes and auspices; 

government  documents and national  commission  reports produced  over the past 25 years; 

articles and books addressing human-subject  protections;  Federal records on IRBs; 

attendance at IRB  meetings;  site visits with  FDA  inspectors;  site visits to 6 IRBs based in 

academic health centers  where extensive research is taking  place;12 issues raised on an 

e-mail  forum  by those associated with  IRBs.  We focused on the IRB  system as a whole 

and on the environment  in which  IRBs  function.  We did not conduct  an audit of their 

operations,  nor did we carry out an investigation  of specific  IRBs  or of specific  research 

plans reviewed  by IRBs. 

We conducted  this study in accordance with  the Quality  Standards for  Inspections  issued 

by the Presidents Council  on Integrity  and Efficiency. 

2  OEI-01-97-00191 IRBs: Promising Approaches  INSTITUTIONAL  REVIEW  BOARDS:  THE  BASICS 
What  Do They  Do? 
The responsibilities  of IRBs fall  into two main categories: initial  review  and continuing  review  of research 
involving  human subjects. 
Initial  Review:  IRBs review  and approve a research plan before the research is carried out.  This review 
encompasses the research protocol,  the informed  consent document to be signed by subjects, any 
advertisements to be used in recruiting  subjects, and other relevant documents.  In carrying  out this review, 
the boards seek to ensure that any risks subjects may incur are warranted  in relation  to the anticipated 
benefits, that informed  consent documents clearly  convey the risks and the true nature of research, that 
advertisements are not misleading,  and that the selection of subjects is equitable  and justified.  IRBs focus 
much attention on the informed  consent document because it is the vehicle  for providing  information  to 
potential research subjects. 
Continuing  Review:  The continuing  review  process is multifaceted  and includes required reviews at an 
interval  appropriate to the degree of risk but not less than once per year.  In addition  to this continuing 
review,  study amendments and reports of unexpected adverse experiences by subjects are received 
periodically  and reviewed  to ensure that the risk-benefit  ratio of the research has not changed and remains 
acceptable. 
Why Were They  Established? 
As public  awareness and concern about the treatment of human subjects in research increased, the need for 
additional  review  mechanisms was evident.  These concerns grew from stories of the abuse of subjects during 
the World War II trials at Nuremberg,  the promotional  distribution  of thalidomide  resulting  in numerous 
children  born with  birth defects, the administration  of cancer cells to chronically  ill  and senile patients at a 
hospital in New York,  and others.  A 1966 article by Henry Beecher brought  prominent  attention to human 
research abuses in medical schools and hospitals  citing  22 cases involving  highly  questionable ethics.  The 
formal requirements for the establishment  of IRBs were outlined  in regulations  stemming from the National 
Research Act of 1974 and in FDA  regulations  issued in 1981. 
Where Are They  Located? 
An estimated 3,000-5,000  IRBs can be found across the country.  They are most commonly  associated with 
hospitals and academic centers.  Boards also exist in managed care organizations,  government  agencies (such 
as the National  Institutes  of Health, the Centers for Disease Control,  and State governments),  or as for-profit 
entities that are independent of the institutions  in which  the research takes place. 
How Are They  Organized? 
Federal regulations  require that boards have at least five members with  varying  backgrounds.  At least one 
member must have primarily  scientific  interests, one must have primarily  nonscientific  interests, and one must 
be otherwise unaffiliated  with  the institution  in which  the IRB resides.  A quorum, with  at least one member 
whose interests are primarily  nonscientific  present, is needed for voting. 
How Does the Department  of Health  and Human  Services (HHS)  Oversee Them? 
Two agencies within  HHS share responsibility  for IRB oversight:  the Office  for Protection from Research 
Risks (OPRR) in NIH  and the FDA.  The OPRRs main tool for oversight  is the assurance document.  Any 
institution  that intends to conduct HHS-funded  research must have an assurance on file with  OPRR.  The 
assurance is a written  statement of an institutions  requirements for its IRB and human-subject  protections. 
Institutions  consistently  conducting  multiple  HHS-supported  studies are eligible  for a multiple  project 
assurance (MPA)  which  can be renewed every five years.  Institutions  with  smaller HHS-funded  workloads, 
however, use a single project assurance (SPA) for each such project it conducts.  The OPRR also conducts a 
small number of site visits.  The FDAs  main mechanism for IRB oversight  is the inspection  process.  The 
FDA also inspects research sponsors and scientists (known  as research investigators). 
3  OEI-01-97-00191 IRBs: Promising Approaches  Management  of the  Workload 
Issue 
IRBs  across the country  are inundated  with  research proposals and related documentation. 
The number of proposals being submitted  to the IRB  has grown  significantly.  With  the 
emergence of large, multi-center  trials, the 
number  of adverse-event reports submitted  to  One IRB we visited  reported that between 
the IRB  has also risen dramatically.  The  1986 and 1996 the annual number of full-
escalating volume  of work,  combined  with  the  board reviews  increased from  1450 to 
increase in adverse-event submissions  has  2659, expedited reviews from 301 to 58 1, 
greatly  added to the paperwork  burden that  amendments from 435 to 1011, and 
adverse-event reports from 50 to 200. 
IRBs  face.  As the field  of clinical  trials 
becomes increasingly  competitive,  IRBs  are 
under enormous pressure to review  protocols  quickly.  The challenge  for these boards is 
to find mechanisms to review  protocols  thoroughly  and efficiently  in a way that does not 
place the thrust of the increased burden  on volunteer  members time. 
Federal  Reference Points 
The HHS regulations,  which  are overseen by the Office  of Protection  from Research 
Risks (OPRR)  in the National  Institutes  of Health  (NIH),  require that institutions  make 
provisions  for meeting  space and sufficient  staff to support the IRBs  review  and record 
keeping  duties. I3 The Food and Drug  Administration  (FDA)  regulations  have no such 
counterpart.  Both  sets of Federal regulations  require that an IRB  be composed  of a 
minimum  of five members.  There is no maximum  size.14 However,  OPRR cautions that 
while  an IRB  can have as many members as is necessary to perform  its duties effectively, 
care should be taken that the board does not become so large that its management 
becomes cumbersome.5  In their written  guidance to IRBs, neither FDA  nor OPRR go 
beyond  staffing  and membership  requirements  to address measures of efficiency,  such as 
turnaround  time or the ratio of protocols  to reviewers. 
Promising  Approaches 
Develop  an Institutional  Infrastructure  to Assist  Research  Investigators 
Support  for clinical  investigators,  which  can range from minimal  assistance to formal 
protocol  management, occurs at the departmental  level at many institutions.  The 
Massachusetts General Hospital  Cancer Center in Boston has developed a comprehensive 
centralized  protocol  management office  to assist researchers with  all aspects of the 
clinical  trial.  Sixteen research associates assist investigators  with  protocol  development, 
submission  to appropriate  departments,  and management.  The office  also provides 
4  OEI-01-97-00191 IRBs: Promising Approaches  education  for investigators,  and includes  a quality-control  function  to ensure regulatory 
compliance.  The IRB told us that protocol  management by the cancer center has 
dramatically  improved  IRB  efficiency.  Officials  in the cancer center say it has been vital 
to improving  investigator  awareness of how to run a good clinical  trial. 
In an effort  to strengthen the role of clinical  research, many institutions  are developing 
clinical  research programs  intended  to increase coordination  among offices responsible 
for clinical  research, provide  training  for investigators,  and strengthen biostatistical 
support and scientific  review.  It is too early to analyze the returns of these programs.  It is 
expected, however,  that these programs  should help the mission  of the IRB  through 
ensuring that protocols  submitted  to the IRB  are more complete  and have gone through 
appropriate  review  channels. 
Pre-review  Research  Protocols 
Many  institutions  are beginning  to initiate  methods of pre-review  in an effort to ensure 
that protocols  reviewed  at full-board  meetings are as complete  as possible.  A recent 
survey found that IRBs most commonly  reject proposals  because of improperly  designed 
consent forms (54 percent), poor study design (44 percent)  and scientific  merit (14 
percent).16 New  protocols  at Roswell  Park Cancer Institute  in Buffalo  are assigned to two 
members of the Scientific  Review  Committee  who check for missing  information, 
scientific  originality  and significance,  and for overall  scientific  merit.17 If the reviewers 
find problems  with  a protocol,  they contact the investigator  for clarification.  These 
problems  must be resolved before the protocol  can be presented to the full  board. 
Protocols  have improved,  as has efficiency,  since the Scientific  Review  Committee  was 
established a decade ago.  Staff at Roswell  Park Cancer Institute  believe that such a 
committee  would  be an asset at many institutions,  yet they warn that it would  require 
resources, committee  member time, and an another layer of review  for investigators. 
Pre-review  can also be done by IRB  members or outside experts.  At Albany  Medical 
Center in New  York,  an IRB  subcommittee  composed of three persons (two  primary 
reviewers  and a staff member)  resolves issues with  investigators  prior  to a full-board 
meeting.  This process greatly  reduces the meeting  length by eliminating  fact-finding  and 
one-on-one  discussions between the investigators  and IRB  members.  Using  this system, 
they have reduced the length of the IRB  meeting  by half, increased IRB  member 
attendance, and increased the time spent on human-protection  issues.  The Toledo 
Hospital  in Ohio relies on a statistician  to pre-review  protocols  for methodological  rigor 
and to help with  the consent form. 
Develop  Well-focused  Applications 
Many  IRBs  are revising  their protocol  application  forms in an effort to elicit  clearer and 
more complete explanations.  Protocols  that contain  complete  information  regarding  the 
conduct of a clinical  trial  are most meaningful  to IRB  reviewers  and allow  the board to 
function  with  maximum  efficiency.  Massachusetts General Hospital  in Boston has 
OEI-01-97-00191 IRBs: Promising Approaches  revised its form  so that  II 
investigators  are required to  Outline  of Points  to be Covered  in the Research Protocol 
check off information  Item  #2: Specific  Aims/Objectives 
detailing  when  informed 
Old protocol  application:   In outline  form, state clearly  the 
consent will  be obtained, by 
objectives of the research. 
whom,  and from whom. 
Childrens  Hospital  of Boston  Revised protocol  application:   The objectives should give a 
has also successfully  revised  concise statement of the hypotheses.  The study design should 
their application  form  (see  be capable of answering  these hypotheses.  In short, the 
question:  What will  be learned from the proposed study? 
box).  Other institutions  use 
should be answered.  Objectives  should appropriately 
techniques  such as including 
correspond to the phase of the study.  For each objective 
sample consent forms in the  listed, the protocol  should adequately address how the 
application  form, providing  answers are to be obtained.  Often questions arise because 
checklists  of information  that  protocols  are submitted with  objectives that are not 
answerable by the research proposed. 
must be included  with  the 
protocol  application,  and 
From Childrens  Hospital  of Boston Protocol Application, 
creating  a single form that can 
Committee on Clinical  Investigation 
accommodate  a variety  of 
types of research. 
Increase  the Number  of IRE3s and/or  the Number  of Meetings 
The mounting  workload  can be too much for one IRB  to handle.  For example, the 
University  of Rochester in New  York  used to have one IRB  to review  1,700 active 
protocols.  The institution  recently  created four boards (two  medical,  one behavioral,  and 
one dental) from the original  IRB  to divide  up the workload  and to ensure greater 
reviewer  expertise.  Another  option  is to have multiple,  general-purpose  IRBs and stagger 
the meetings.  For example, Washington  University  in Saint Louis  staggers the meetings 
of its four IRBs  so there is an IRB  meeting  every week.  Yet another approach is to rely 
on alternative  members.  At the University  of Kentucky  in Lexington,  each IRB  member 
on the medical  IRB  has an alternate who has a similar  medical  background.  Between  the 
members and the alternates, the University  of Kentucky  is able to hold an IRB  meeting 
four times a month. 
There are, however,  some concerns with  using these approaches.  Many  of these 
institutions  are struggling  with  issues of how  to ensure consistency  among the various 
IRBs,  how to attract a sufficient  number  of qualified  IRB  members and alternates, and 
how to ensure that specialty IRBs  do not focus solely  on the behavioral  or medical  aspects 
of a research proposal  at the exclusion  of other concerns. 
Require  Research  Investigators  to Assess the Importance  of Adverse-Event  Reports 
IRBs are deluged with  adverse-event reports from the multi-center  clinical  trials they 
oversee.  Many  of these reports are difficult  to interpret  because they are sent to IRBs  as 
individual  action reports and convey no trend information.  The University  of Nebraska 
6  OEI-01-97-00191 IRBs: Promising Approaches  Medical  Center IRB  at Omaha is one of a number of IRBs that require  investigators  to fill 
out an accompanying  adverse-event  report form to assist the IRB  in performing  a risk 
assessment. These forms seek investigators  advice concerning  the relationship  of the 
adverse event to the intervention,  whether  or not a change in a protocol  is necessary, and 
whether  or not information  about the adverse event is germane to consent and/or re-
consent.  The thinking  behind these forms is that investigators  are in the best position  to 
determine the significance  of adverse-event reports.  Furthermore,  it forces the 
investigators  to stay abreast of all adverse-events that they submit to the IRB. 
Employ  Technology  to Relieve  Burden  on IRB  Staff 
Using  an electronic  database can minimize  clerical  work,  assist the IRB  in keeping track 
of studies, and allow  for coordination  among multiple  IRBs.  Although  we found no IRBs 
that have the capability  to allow  investigators  to submit protocols  electronically,  many 
IRBs told us they are moving  in that direction.  New  database technology  will  allow  for 
efficiencies  such as on-line  adverse-event reporting,  electronic  interaction  with  other 
clinical  departments, and on-line  updates for research investigators  on the status of their 
protocols.  The hope is that by giving  investigators  better tools, IRBs  will  receive better 
protocols  thus allowing  for more time to be spent at full-board  meetings on human-
subject protection  issues.  While  many institutions  embrace the idea of employing 
technology  to relieve the burden  on IRB  staff, many cite the necessary financial 
investment  as a barrier. 
7  OEI-01-97-00191 IRBs: Promising Approaches  Educational  Outreach  to Research  Investigators 
Issue 
Research investigators  and their stafr8 must be well-informed  of the IRBs  role and 
significance  for the system of human-subject  protections  to work  effectively.  However, 
education  about human-subject  protections  is not necessarily  part of an investigators 
formal  education.  Investigators  often have incomplete  knowledge  of when and how 
research protocols  must be submitted.  In some cases, they may not be aware of what 
constitutes  adequate informed  consent or they may have difficulty  in distinguishing 
between clinical  care and research.  Since the late 1970s  a number of national 
commissions  and groups have called for a greater emphasis on investigator  education. 
Federal  Reference Points 
The OPRR Multiple  Project Assurance requires the institution  to make a copy of the 
assurance available to investigators  and staff.  In a Dear  Colleague  letter, the OPRR 
suggests that IRBs  make investigators  aware of policies  regarding  continuing  review  and 
women  and minorities  in research, but does not specify how this educational  outreach 
should occur.2o The FDA  Information  Sheets for IRBs  and Clinical  Investigators  provide 
no guidance to IRBs  on educational  outreach to investigators  and their  staff. 
Promising  Approaches 
Lectures,  Conferences  and Workshops 
At the University  of Washington  in Seattle, the IRB  director  conducts  25-30 presentations 
annually  to persons involved  with  human-subjects  research.  Compared  with  many of the 
IRBs we interviewed,  this represents a high volume  of educational  outreach. 
Approximately  one-third  of these presentations  are oriented  toward  faculty  members and 
research staff, the remaining  two-thirds  toward  graduate and post-doctoral  students.  Each 
seminar, which  lasts up to one and a half hours, addresses the history  of the IRBs,  major 
principles  of the Federal regulations,  and specifics the IRBs  look  for when reviewing 
protocols.  The sheer number  of presentations  conducted  means that most research 
investigators  interested in attending  a presentation  will,  most likely,  find  a convenient 
time to do so.  Ensuring  this convenience  demands a significant  commitment  from the 
director,  because each presentation  entails five to six hours of work  between the 
preparation,  and the presentation  itself. 
At the University  of Minnesota  Academic  Health  Center, research investigators  attended 
a mandatory  2-day course on the responsible  conduct  of research, a component  of which 
8  OEI-01-97-00191 IRBs: Promising Approaches  is human-subjects  protections.  The Dean of Medicine  will  not approve an investigators 
protocol  unless he or she has fulfilled  this requirement.  One IRB  administrator  told us 
that this type of education  sends a powerful  political  message to all investigators. 
The University  of Minnesota  also employs  a full-time  education  coordinator.  Working 
with  the various departments and deans to determine  the education  needs of investigators, 
she assesses,plans, and evaluates appropriate  educational  programs.  A large number of 
investigators  attend these educational  sessions.  As a result of these requirements,  the IRB 
has seen a heightened  awareness among researchers about the need to submit research 
proposals to the board.2  The IRB  has also noted an improvement  in important  aspects of 
the submitted  protocols,  for example, the consent document. 
At many institutions,  clinical  coordinators  handle the daily  tasks of research, (e.g., 
obtaining  informed  consent, maintaining  records, etc.)  As such, their education  is crucial 
to human subjects  protections.  However,  in many cases, coordinators  have little 
understanding  of what human-subject  regulations  are or why  they exist.  To address this 
problem,  Massachusetts General Hospital  (MGH)  has recently  begun offering  a 2-day 
course for coordinators  through  its Clinical  Research Program.  Topics  include:  roles and 
responsibilities  of the investigator,  sponsor, research staff, and coordinator;  U.S. 
regulations  and guidelines,  research documentation,  recruiting  subjects, and obtaining 
informed  consent.  Currently,  data does not exist to show the impact of the program,  but 
people at MGH  are enthusiastic  about it and are planning  to offer more courses for 
clinical  coordinators. 
On-line  Tutorials 
The NIH  requires completion  of an on-line  tutorial  for research investigators  and all other 
individuals  involved  with  human subjects research.  The tutorial  explains the purpose and 
history  of IRBs and practical  matters such as when research must be submitted  to the 
IRB.  This tutorial,  which  can be completed  at an investigators  convenience,  provides  a 
base level of knowledge  at low  cost; the only  significant  cost associated with  the tutorial 
is the initial  development  fee.  Because of this practice,  one official  states, ignorance  of 
the regulations  will  never be an excuse [at NIH].  The disk is a nuts and bolts  approach 
that any IRB  could use.  It is available  on the internet  at the NIH  home page?2 
Computer-assisted  Literature  Monitoring 
An IRBs  ability  to protect human subjects is reliant  on informed  and compliant 
researcher investigators  who are aware they must submit their protocols  to the IRB.  The 
University  of California  at San Diego  (UCSD)  recently  initiated  a computer-assisted 
literature  monitoring  program  to detect maverick  researchers.  Every week the UCSD  IRB 
runs a search of new publications  containing  the heading  human and an author address 
containing  the words  Diego  or Jolla.  Word matching  algorithms  are used to rank the 
similarity  of each citation  to the research projects  in the IRB  database.  If a tentative 
9  031-01-97-00191 IRBs: Promising Approaches  match of a publication  to a project  is 
An  Efficient  Means  of Improving 
made, a letter requesting  confirmation  of 
Awareness  and Compliance 
the match is sent to the investigator. 
Where no match can be made, a query 
Using computer-assisted  literature 
letter is sent to the investigator 
monitoring,  the University  of California  at 
requesting  he/she contact the IRB  office.  San Diego was able to identify  132 recent 
The program  has become so successful  publications  by UCSD researchers. Thirteen 
that investigators  are now preempting  of these had no record of being submitted to 
the IRB  by sending their abstracts before  the IRB and resulted in counseling  of the 
the IRB  runs its search.  To perform  research faculty  involved.  According  to the 
IRB, this  has been a valuable,  low cost 
computer-assisted  literature  monitoring, 
method of improving  awareness of and 
an IRB  does not necessarily  need 
compliance  with  human-subjects  regulations 
advanced computer  capability.  Private 
among faculty  members. 
vendors offer low-cost  search services; 
alternatively,  IRB  staff can run manual 
searches. 
Websites  and  Manuals 
An IRBs  staff may not have the time to conduct  conferences,  seminars or other 
interpersonal  education.  Websites and manuals are an alternative.  Once developed, they 
are effective  and low  cost educational  tools.  Websites have become a popular  method for 
sharing information  regarding  policy,  IRB  memberships,  meeting  dates, deadlines, and 
events.  At Baylor  University  in Texas, all investigators  receive a manual from the 
institution  that includes  topics such as the definition  of research, how to write  protocols, 
and requirements  of the IRB.  According  to the IRB  administrator,  the manual has been 
extremely  helpful.  For example, one anesthesiology  resident  called her to find out how to 
write  a research protocol.  She sent him the manual and four days later received back a 
beautifully-written  research protocol.  Responses from  other users have also been 
positive.  Making  websites and manuals available  for investigators  and their staff also 
frees up time for the IRB  staff as investigators  are less dependent  on them for 
information. 
Use of Standardized  Education  Language 
The University  of Nebraska  has developed  standardized  educational  language for the 
review  letters it sends out to investigators.  They have categorized  standardized 
statements into three broad areas: problems  with  protocols,  problems  with  informed 
consent documents,  and general-reminder  language.  A typical  problem  might  be that an 
investigator  has not clearly  indicated  how he/she intends to assess the subjects 
understanding  of the research.  In cases such as these, the IRB  will  send the investigator  a 
letter with  suggestions.  These suggestions are all kept coded on a computer.  At the 
stroke of a key, the administrator  can insert the language into a customized  letter.  The 
use of standardized  language can eliminate  a page and a half of typing  for the 
administrator.  The University  of Nebraska  has been using this method  for 15 years.  Over 
10  OEI-01-97-00191 IRBs: Promising Approaches  this time, the chair has been using fewer standardized  statements as investigators  are 
submitting  more complete  and well  thought  out protocols. 
Use of Explicit  Investigator  Assurances 
A research investigators  desire to be in compliance  with  Federal regulations  can easily be 
frustrated  by unclear explanations  of what these requirements  are.  One institution,  for 
example, had difficulties  with  investigators  making  modifications  to approved research 
without  IRE3consent.  Part of the problem  was a vague statement investigators  were 
required  to sign verifying  they met Federal regulations.  The statement failed to explain 
explicitly  what was entailed in compliance.  To solve this problem,  this institution  created 
a form that clearly  states the investigator  will: 
obtain  voluntary  and informed  consent of subjects, submit to the IRB  any 
adverse events, give progress reports, obtain prior  approval  from the IRE3before 
amending  or altering  the project  or before implementing  changes in the approved 
consent form, maintain  documentation  of IRE3 approval  for at least three years 
after the project  has been completed,  and treat subjects in a manner specified  in 
this form. 
According  to the IRE3administrator,  this practice  has been extremely  beneficial  in 
educating  investigators.  A greater number of investigators  are now aware that changes to 
an approved protocol  must also be reviewed  by the IRB. 
11  OEI-01-97-00191 IRBs: Promising Approaches  Continuing  Review  of Approved  Research 
Issue 
Continuing  review  of approved research is vital to the protection  of human subjects.  The 
mounting  workloads,  new advances in biomedical  research, and the growing  public 
interest in experimental  therapy  as a way to access medical  care make the continuing 
review  function  of IRBs  increasingly  important.  Our inquiry  and other studies indicate 
that due to heavy workloads  and lack of institutional  support many IRBs  devote only 
minimal  time to continuing  review  and to active oversight  of the informed  consent 
process.23 The current system of adverse-event reporting  contributes  to the difficulty 
many IRBs  face in adequately  overseeing  multi-center  trials. 
Federal  Reference Points 
The Federal regulations  outline  the minimum  requirements  for continuing  review  of 
approved protocols:  IRBs must conduct  periodic  review  of approved protocols  at intervals 
appropriate  to the degree of risk, but not less than once a year; and they have the authority 
to observe, or to have a third  party  observe, the consent process and the research.24 As 
such, the regulations  allow  for great flexibility  in the quantity,  quality,  and depth of 
continuing  review.  In an effort  to strengthen the continuing  review  function,  the FDA 
and OPRR have issued a number  of guidelines  in recent years.  In a 1995 guidance, the 
OPRR called for continuing  review  to be substantive  and meaningful. 
Promising  Approaches 
Involve  a Third  Party  in Overseeing  the Consent  Process 
Ensuring  that subjects are adequately  informed  about participating  in research is central to 
the mission  of the IRB.  Yet, our inquiry  and other studies found that although  IRBs have 
the authority  to observe, or to have a third  party observe, the consent process they rarely 
invoke this authority.  IRB  reviews  of informed  consent are limited  almost entirely  to 
paperwork  reviews.25 The following  are examples of ways in which  several IRBs, 
through  the use of a third  party,  actively  oversee the consent process.  Many  of these are 
in accord with  the recommendations  of the Advisory  Committee  for Human  Radiation 
Experiments.26 
A research intermediary  interacts with  all psychiatric  research subjects at the University 
of Texas Health  Science Center in Houston.27  Because it might  be considered  obtrusive 
in the subject-researcher  relationship,  the research intermediary  does not directly  observe 
the consent process.  Instead, she discusses the consent form with  a subject after the form 
has been signed to ensure that the subject understood  its terms and that upon reflection 
12  OEI-01-97-00191 IRBs: Promising Approaches  the patient continues  to want to 
Benefits  of Using a Research  Intermediary 
participate  in research.  According 
to the IRB,  patients who  go through 
The research intermediary  at the University  of Texas 
this process make better research  Health Science Center in Houston acts as a liaison between 
subjects because they are sure of  the subjects and the researchers.  Every few months she 
why  they are participating  and they  reports to the IRB about patients concerns and the ways in 
which  the consent process and/or research could be made 
are clear about their relationship  to 
more efficient  and less obtrusive  for patients.  The research 
investigators. 
intermediary  also shares with  the IRB how the consent 
process really  works, which  is something that many IRBs 
Patient advocates provide  additional  areunawareof. 
oversight  for subjects involved  in 
risky  and/or complex  protocols  at the Massachusetts  General Hospital  (MGH)  in Boston. 
Typically  they are involved  in gene therapy protocols,  Phase 1 studies;  and protocols  in 
which  decisions  about participating  in research must be made quickly.  Patient advocates 
observe the consent process to ensure that subjects understand  that they are voluntarily 
participating  in research.  Currently,  most of the patient  advocates are physicians. 
However,  MGH  is in the process of establishing  an Office  of Patient Advocates.  The 
advocates, most of whom  will  be trained  social workers,  will  be available  24 hours a day 
to oversee or participate  in the consent process. 
Some IRBs  have begun to require or recommend  counseling  of research subjects to 
ensure that they understand  the consequences of research.  Roswell  Park Cancer Institute 
in Buffalo  requires  genetic counselors  for cases in which  the implications  of genetic 
testing are not fully  addressed in the consent form.  The University  of Washington 
recommends  financial  counseling  for Phase 1 oncology  protocols,  where study expenses 
are often not covered by the research sponsor or the subjects  insurer. 
Review  Recent  Copies  of Signed  Consent  Forms 
At the reapproval  stage, investigators  at the University  of Kentucky  in Lexington  are 
required  to submit to the IRB  copies of signed consent forms for the two most recent 
subjects.  This allows  the IRB to check if the consent forms being used are the most 
updated and if they have been properly  signed.  The best indicator  of the efficacy  of this 
approach, according  to the IRB  director,  is that the IRB  has found problems  with  several 
investigators  consent forms.  A downside,  however,  to this approach is that subject 
confidentiality  is broken.  The IRB  members reviewing  consent forms for an AIDS  trial 
know  that those consenting  are HIV  positive.29  The IRB  director  believes that this 
practice  is a particularly  useful tool for large IRBs  which  are unable to review  all consent 
forms for each approved protocol. 
Develop  a Comprehensive  Continuing  Review  Form 
A well-focused  application  can assist an IRB  in providing  a thorough  and efficient  initial 
review.  Likewise,  a well  thought-out  continuing  review  form can assist an IRB  in 
identifying  potential  problems  or concerns in approved protocols.  The University  of 
13  OEI-01-97-00191 IRBs: Promising Approaches  Nebraska  Medical  Center IRB  at Omaha recently  revised its continuing  review  form  so 
that it asks more probing  questions (see box).30 The revised form requires that the 
investigator,  who  is most 
familiar  with  the protocol,  IRB  Application  for Continuing  Review  of Therapeutic  Research 
assist the IRB  in assessing 
Old continuing  review  application: 
the recruitment  of subjects: 
.  Did any subject suffer an unanticipated  adverse event or 
problems  and 
injury  during  the study?  Yes  No 
complications,  the process 
of consent, and the risk- New continuing  review  application: 
benefit  relationship.  As a  . 	 Did any subject suffer an unanticipated  adverse event which 
was reported to the IRB since the last IRE3review?  If the 
result of using this form, 
answer is yes, specify the number of reported events and 
the IRB  has been able to 
describe briefly  their nature and significance. 
detect, and avert, problems 
at the reapproval  stage.  . 	 Did any subject suffer an unanticipated  adverse event which 
has not vet been reported to the IRE% If the answer is yes... 
Establish  a Re-review 
. 	 Was there any increase in the frequency  of serious but 
Mechanism 
expected adverse events?  If the answer is yes... 
The Federal regulations  . 	 Since the last IRB review  were any serious external adverse 
require  that IRBs review  events reports submitted to the IRB?  If the answer is yes... 
approved protocols  at 
From the University  of Nebraska Medical  Center at Omaha 
intervals  appropriate  to the 
degree of risk but not less 
than once a year.  Yet, our inquiry  and other sources found that IRBs  typically  carry out 
the continuing  review  requirement  in a hurried  manner, generally  relying  on 
administrative  staff and on investigators  self-assessments.*  Unless there is cause for a 
thorough  review,  the IRB  generally  spends minimal  time discussing  approved protocols. 
To enhance the continuing  review  function,  several institutions  have established a re-
review  mechanism.  Childrens  Hospital  of Boston requires that on the third  anniversary 
of a protocols  initial  approval  investigators  submit the protocol  to the IRB  as an initial 
protocol.  This system forces investigators  to revise the protocol,  where necessary, and to 
compile  all amendments and adverse events into one document.  This approach can help 
IRB  members stay abreast of rapidly  changing  protocols.  The re-review  system is not a 
substitute  for meaningful  continuing  review,  but it helps to ensure that long-term 
protocols  receive scrutiny  at regular  intervals. 
14  OEI-01-97-00191 IRBs: Promising Approaches  Educational  Outreach  to IRB  Members 
Issue 
With the mounting  workload  pressure, few IRBs have the time or resources for 
educational  outreach to IRB  members.  Most IRBs  provide  minimal  orientation  for new 
members, usually  covering just the Federal regulations  and IRB  procedures.  Yet given 
the growing  complexity  of protocols,  ongoing  training  is increasingly  critical  for both the 
physician  and lay member.  New  areas of research, such as xenotransplantation  and gene 
therapy, raise complicated  ethical  questions that may not be immediately  apparent to 
many reviewers.  Several IRBs  told us that when they do offer  ongoing  member training, 
few physicians  have the time to attend. 
Federal  Reference Points 
The OPRR guidebook  states that IRB members and others charged with  the responsibility 
of reviewing  and approving  research should receive detailed training  in the regulations, 
guidelines,  and policies  applicable  to human-subject  research.33 The OPRR and FDA 
sponsor a number  of conferences  for IRB  members and administrators.34  The OPRR 
guidebook  explicitly  encourages IRBs to support their members in attending  workshops 
focused on IRB  functioning.  The FDA  Information  Sheets for IRBs  and Clinical 
Investigators  provide  no guidance  on educational  outreach to IRB  members. 
Promising  Approaches 
Provide  Protocol  Specific  Education 
Staff at the University  of Kentucky  in Lexington  believe that an IRB  gets the best results 
by tying  educational  outreach to the specific protocols  being reviewed.  When complex 
protocols  come up for review--for  example, those involving  genetic testing, AIDS,  or 
children--staff  members copy relevant pages of the OPRR guidebook  and send them to 
members.  According  to the IRB  director,  this approach is particularly  beneficial  to help 
orient new members to the ethical issues they should consider  when reviewing  protocols. 
A downside,  however,  of this type of education  is the requisite  resources and staff.  For 
this approach to work,  staff need to pre-screen protocols,  determine  relevant  literature, 
photocopy  and distribute  the necessary materials. 
Independent  Review  Consulting  in California  routinely  includes  several articles in each 
members  agenda packet.  Designed  to stimulate thought  and discussion  on a broad range 
of topics, the articles are culled  from both the lay and medical  press.  Topics  have 
included  health care management,  medical devices, and the inclusion  of women  and 
minorities  in clinical  trials,  as well  as consent and protocol  issues.  According  to the IRB 
15  OEI-01-97-00191 IRBs: Promising Approaches  director,  this approach has helped facilitate  openness among members and raise 
awareness. 
Use Portion  of IRB  Meeting  to Educate  Members 
At the University  of Texas Health  Science Center in Houston,  the first ten minutes  of 
each IRB  meeting  is devoted to the continuing  education  of IRB  members.  Recent topics 
have included  problems  in the designs of AIDS  studies, statistical  issues in study design, 
and ways of improving  the IRBs  efficiency.  One benefit  of this type of education  is the 
ripple  effect it can have with  other researchers in the institution.  For example, after a 
recent meeting where AIDS  trials were discussed, two of the physician  members shared 
the discussion  with  their residents.  According  to the IRB  coordinator,  the ongoing 
education  has been helpful  in increasing  members awareness of human-subject 
protections  and in maintaining  their tenure on and interest in the IRB. 
Host  Annual  Trainings  for  IRB  Members 
Western Institutional  Review  Board of Olympia  has hosted annual trainings  for  14 years. 
Originally  the trainings  were intended  for Western board members only.  Now  they have 
been opened it up to other IRB  members.  Last year, about 200 people attended the all day 
training  seminar.  Speakers at the seminars vary, but they generally  address the following 
topics:  someone from FDA  provides  an update on the regulations,  someone speaks on the 
ethical aspects of research, an investigator  speaks about the impact  of IRB  decisions  on 
research, and someone from a pharmaceutical  or device company  speaks about how  IRB 
rules and regulations  affect their business practices. 
According  to the IRB  director,  the annual training  sessions have been helpful  in making 
members feel secure in their decisions.  The sessions give members a chance to ask their 
questions of someone knowledgeable  and then allows  them to go back to their IRB  with 
confidence.  The training  sessions are also helpful  for giving  members a well-rounded 
picture  of the role of the IRB  and how  its decisions effect the parties involved. 
16  OEI-01-97-00191 IRBs: Promising Approaches  Broadening;  Perspectives  in  the IRB  Review  Process 
Issue 
Scientific  knowledge  is necessary but not sufficient  for the IRB  review  process.  The 
large number of scientists who  serve on IRBs  ensure ready access to medical  and 
methodological  knowledge  that is of great value to the IRB  in assessing the risks and 
benefits of research protocols  submitted  to it.  This specialized knowledge,  however,  can 
have a downside.  Investigators  may inadvertently  express a tendency  to stress the 
benefits rather than the risks of research, overlook  just how well  subjects understand the 
informed  consent document,  or give insufficient  attention  to the diversity  of subjects 
recruited.  The inclusion  of nonscientific  members, noninstitutional  members, and 
bioethicists  on IRBs can be an important  counterbalance  to these tendencies.  These 
members can help ensure the IRB  remains sensitive to the needs and concerns of subjects 
and thereby assists the IRB  in its goal of protecting  human subjects. 
Federal  Reference Points 
Of the five IRB  members required  by Federal regulations,  there must be at least one 
whose primary  concerns are in nonscientific  areas and one who is not otherwise  affiliated 
with  the institution.  In many IRBs,  one member fills  both roles.  The OPRR guidebook 
suggests that the nonaffiliated  member  should represent the local community,  should  not 
be vulnerable  to intimidation  by the professionals  on the IRE3,and their  services should be 
fully  utilized  by the IRB.6  The importance  of the nonscientific  and nonaffiliated 
members has been heightened  by recent guidance concerning  the inclusion  of women  and 
minorities  in research.37 
Promising  Approaches 
Enable  Nonscientific  and Noninstitutional  Members  to Play  a Significant  Role 
Given the importance  of achieving  a balance as noted above, we searched widely  for 
examples of IRBs with  innovative  approaches to recruiting,  training  and supporting  their 
nonscientific  and noninstitutional  members.38 Few came to our attention. 
We found that many IRBs  achieved some broadening  of perspectives by reaching  out 
within  their hospital  communities  to social workers,  attorneys, hospital  executives, and 
even IRB  administrative  staff.  These individuals,  however,  are affiliated  with  their 
research institutions  and strictly  speaking, are not unbiased outsiders.  Some of these 
same IRBs  indicated  they sought more outside members but with  little  success, noting  the 
difficulties  of finding  persons who  were willing  to work  long uncompensated  hours. 
17  OEI-01-97-00191 IRBs: Promising Approaches  Through  our research, we found  several examples of nonscientific,  noninstitutional 
members (that is, a single member who  satisfies the requirements  for having  a 
nonaffiliated  and a nonscientific  perspective  on the board) who had come to play an 
important  continuing  role in helping  the IRB  broaden its perspective.  In one case, the 
IRB  contributed  significantly  to this development  by funding  the members  participation 
at an IRB  conference.  More  typically,  the members drew  on the knowledge  and skills 
they brought  with  them to the IRB  and lessons they learned during  the course of their  IRB 
service.  These nonscientific,  noninstitutional  members told us they brought  a very 
different  voice to the IRBs  deliberations,  particularly  when they raised nettlesome  issues 
such as confidentiality  or the adequacy of researchers  efforts to reach out to diverse 
populations.  As non-researchers,  they also tend to assess the risk/benefit  ratio more 
critically.  They may view  research more from the vantage point  of a subject. 
Consequently,  they are able to understand the vulnerability  subjects often feel. 
The other IIU3 members and staff we spoke with  also stressed the importance  of the 
balancing  role played by these pro-active  community  members.  Yet, along with 
expressions of appreciation,  they voiced some apprehension  that these members can slow 
the deliberation  process--not  an insignificant  consideration  given the substantial  number 
of research protocols  that IRBs  must review. 
Include  a Bioethicist  on the IRB 
Bioethicists,  although  not a substitute  for nonscientific/nonaffiliated  members, also help 
to broaden an IRBs  perspective.  For many years, bioethicists  have participated  on the 
National  Institutes  of Health  IRBs.  Through  their training:  they have become sensitized 
to subtle yet significant  ethical  issues pertaining  to human-subjects  research.  Because of 
this, they can assist other RI3  members in identifying  and deliberating  on ethical  issues. 
Indeed, a recent survey highlighted  the usefulness of this program! 
As one bioethicist  we spoke with  noted, Its  not everyones  job  to be up on research 
ethics, but bioethicists  are trained to do that.  For example, bioethicists  at NIH  have 
raised issues about the clarity  of the informed  consent document  and its treatment  of the 
risk/benefit  ratio, about the distinction  of clinical  care from research, and about balancing 
attempts to bring  more women  and minorities  into research without  undue inducements. 
Some pointed  out, however,  that the specialized  education  of bioethicists  is both a benefit 
and a drawback.  While  on the one hand it makes them more efficient  in discovering 
subtle ethical  issues, it also makes them more likely  to focus on obscure ethical concerns 
which  are not necessarily  a consideration  in human-subject  protections.  One person we 
spoke with  at NIH  also mentioned  the possibility  that other IRB  members will  feel less 
compelled  to bring  up ethical concerns when the bioethicist  is present. 
Provide  Community  Outreach 
In response to the 1993 NIH  guidelines  on the inclusion  of women  and minorities  in 
research, the University  of Texas Health  Science Center IRB  in Houston  developed  and 
18  OEI-01-97-00191 IRBs: Promising Approaches  established an Office  of Ethnic 
Sample Questions  Asked of the Community 
Diversity  in Research (OEDR). 
The OEDRs  mission  is to 
1. If you did participate  in a research activity,  what kinds of 
broaden the communitys  problems did you encounter? 
understanding  of health-care 
2. What could the University  of Texas Health Science Center 
research, to help eliminate 
do to address the problems you have identified? 
cultural  and practical 
roadblocks  to participation  in 
3. What type of healthcare research would  you like us to 
research studies, to establish  study that would  be beneficial  to you, your community, 
and maintain  rapport  with  and/or your organization? 
community  leaders, and to 
4. Please list three things that you could think  of that would 
ascertain the areas in which  the 
improve  how people in your community  feel about 
community  would  like to see 
participating  in research. 
additional  research.  About 
twice  a month,  a member of the  Questionnaire  by the Office  of Ethnic  Diversity  in Research 
at the University  of Texas Health Science Center in Houston 
OEDR  makes presentations  to 
the community.  She is usually 
accompanied  by a health 
educator, an IRB  member, and/or an investigator  from the University.  Feedback from the 
OEDRs  field  visits is reported  to the IRB,  via the IRB  coordinator.  The OEDR  has 
helped the IRB  to identify  barriers to participating  in research and potential  strategies to 
overcome these barriers.  According  to the IRB  coordinator,  many in the community  are 
unaware of what being a research subject entails and they associate the hospital  with 
treatment rather than research.  This has made the IRB  sensitive to the need to further 
simplify  consent forms in order to impress upon potential  subjects that they are 
participating  in research. 
19  OEI-01-97-00191 IRBs: Promising Approaches  Evaluation  of IRB  Efficiency  and  Effectiveness 
Issue 
The IRB  process is too important  not to undergo periodic  evaluation.  Evaluations  can 
help an IRB  to determine  whether  it is effectively  protecting  human subjects, whether  it is 
operating  efficiently,  and whether  it has adequate authority.42  The answers to these 
questions are important  not only  for protecting  human subjects, but also for protecting 
institutions  and investigators  against liability.  Many  of the IRBs  we spoke with  expressed 
an interest in improving  their  effectiveness  and efficiency.  However,  given the time and 
resource constraints  they face, few are able to engage in evaluation  activities.  One IRB 
administrator  remarked  that, unfortunately,  many IRBs  and their  institutions  only become 
proactive  about ensuring  the integrity  of the process once a concern has been brought  to 
their attention. 
Federal  Reference Points 
Institutions  have some obligation,  though  not extensive, to perform  self-assessments.  The 

OPRR multiple  project  assurance requires offices of research administration  to perform 

procedural  and record-keeping  audits not less than once a year.43 The FDA  and OPRR do 

not require IRBs to perform  evaluations  of their effectiveness  or efficiency,  although  both 

encourage such activities.  The FDA  Information  Sheets for IRBs  and Clinical 

Investigators  include  a checklist  to help institutions  evaluate their own policies  and 

procedures; the OPRR guidebook  offers some points  for IRBs  to consider.44 By contrast, 

evaluation  requirements  are much stronger for research involving  animals.  All 

Institutional  Animal  Care and Use Committees  are mandated to conduct  reviews  of 

institutional  programs  and of animal facilities  at least once every six months. 

Promising  Approaches 
Perform  a Full-scale  Evaluation  of the Clinical  Research  Process 
In response to FDA  and OPRR concerns about alleged non-compliance  with  regulations, 

the University  of Minnesota  commissioned  two  evaluations.  The first evaluation  was 

performed  by an internal  faculty  advisory  committee  composed  of several researchers, an 

IRB  member, an administrator  from Grants and Contracts,  and a representative  from legal 

counsel.  The faculty  advisory  committee  spent a month  speaking with  IRB 

administrators  and chairs, researchers, legal counsel, and external  consultants  about IRB 

operations  and resources.  Based on their evaluation,  they recommended  changes in nine 

strategic areas. 

20  OEI-01-97-00191 IRBs: Promising Approaches  To further  assure itself that the process was functioning  well,  the University  of Minnesota 
hired  an outside monitor  to assessprotocols  that met internal  criteria  for risk.  These 
protocols  were assessed for their level of regulatory  compliance.  In addition,  the monitor 
interviewed  research investigators  about their  interactions  with  the IRB  and their 
experiences with  the IRB  process.  The monitor  reported  all results to the IRB,  including 
a set of recommendations.  While  the IRB  had the option  of using an internal  auditor  for 
this task, they felt it was critical  to bring  in an external monitor.  They felt that an external 
monitor  provided  a greater level of objectivity.  According  to the IRB,  responses to the 
monitor  were extremely  positive.  In fact, resource-permitting,  the IRB  would  like repeat 
this process in the future. 
The two  evaluations  were helpful  in highlighting  areas that needed improvement,  such as 
increased resources for the IRB,  changes in the reporting  structure, and more support 
from the University.  The resultant  changes have helped to create better relations  between 
researchers and the IRB.  In retrospect,  IRB  staff felt that if such an evaluation  had 
happened earlier it might  have prevented  difficulties  the IRB  was experiencing. 
Evaluate  a Specific  Aspect  of IRB  Functioning 
Santa Rosa Health  Care conducted  a year-long  evaluation  of its continuing  review 
procedures to ascertain its compliance  with  OPRR guidance and to ensure that subjects 
were receiving  updated toxicity  information  in the informed  consent document.45 As 
protocols  came up for reapproval,  the IRB  performed  an item-by-item  comparison  of 
toxicities  contained  in the local consent form to the toxicities  contained  in the consent 
form  supplied  by the research base.  They also performed  a comparison  of interim  reports 
to the toxicities  contained  in the local and sample consent forms, a review  of drug 
profiles,  and a review  of product  labeling  for approved drugs. 
The Santa Rosa Health Care IRB  discovered  that the majority  of protocols  had 
incomplete  informed  consents, that it had been lax in the critical  review  of initial 
submissions,  and that some interim  reports failed  to provide  necessary information  so that 
potential  risks to study participants  could  be adequately  assessed. As a result, the IRB 
revised the stringency  of its initial  review  of consent forms to include  a more thorough 
review  of the toxicities  listed.  The IRB  also compiled  a reference binder containing  a list 
of the more commonly  used chemotherapeutic  drugs.  According  to the IRB  chair, these 
steps were helpful  in strengthening  the IRB  review  process and were also instrumental  in 
heightening  investigator  awareness of the need to submit accurate informed  consent 
documents.  The evaluation  was, however,  extremely  resource-intensive.  The IRB  chair 
pointed  out that because his IRB  had a small workload  it was able to put such an 
extensive amount of time and effort  into the evaluation--something  that larger IRBs  might 
not have time for. 
21  OEI-01-97-00191 IRBs: Promising Approaches  CONCLUSION 
As we noted in the introduction,  many IRBs  are struggling  to keep pace in the rapidly 

changing  research environment.  Yet, despite the challenges posed by the new research 

environment,  a number  of IRBs  have developed  innovative  approaches to enhancing  their 

effectiveness and efficiency.  Many  of these approaches are catalogued  in this report. 

We did not independently  evaluate any approach highlighted  in this report.  An 

approachs inclusion  does not necessarily  mean that it receives our stamp of approval,  or 

that it is occurring  only  at the institution  we highlighted.  We intend to provide  a snapshot 

in time; it is not a definitive  study of all IRBs.  The report is intended to stimulate 

discussion among the Department,  IRBs,  and those groups interested in IRB  functioning. 

While  we have highlighted  the work  of many IRBs,  we may have omitted  some 

promising  approaches. 

A key challenge to the Federal government  is to find ways of giving  IRBs the flexibility 

to develop promising  approaches while  at the same time holding  them accountable  for 

performance.  This a matter we address in our summary report entitled,  InstitutionaZ 

Review Boards:  A Time For  Reform. 

22  OEI-01-97-00191 IRBs: Promising Approaches  APPENDIX  A 

Endnotes 
1. Over time, as clinical  research activities  spread to other settings, IRBs were established in 
these settings as well.  Institutional  review  boards now  exist in a variety  of institutions--including 
State governments,  the National  Institutes  of Health,  universities,  managed care organizations, 
contract-research  organizations,  and hospitals  (of all kinds).  Independent  IRBs have also arisen 
to review  research protocols. 
2.  Throughout  this report, the terms research investigator  and investigator  are used 
interchangeably.  They are used to denote persons leading  clinical  research studies. 
3.  The clinical  research market is roughly  a 4 billion  dollar  market.  It is estimated that about 75 
percent of clinical  research is industry-sponsored.  (Telephone  conversation  with  Kenneth  Getz, 
Director  of Center Watch, 26 May  1998.) 
4. 	 While this phenomenon  was true for drug studies, the situation  was reversed for medical 
device studies.  The intraocular  lenses studies involved  thousands of subjects.  Most  of the 
studies were conducted  at small community  hospitals. 
5.  Throughout  this report, the terms research plans  , research  proposals,  and protocols  are 
used interchangeably.  They are used to denote proposals  submitted  by research investigator  to 
the IRB  for review. 
6.  The primary  sources of interaction  among IRBs,  for those who  can afford the fees, are annual 
meetings hosted by Public  Responsibility  in Medicine  and Research (PRIM&R)  and Applied 
Research Ethics National  Association  (ARENA),  and FDA- and NIH-sponsored  conferences and 
guidance letters.  One successful forum  for communication  has been an electronic  mailing  list 
sponsored by the Office  of Research, Technology  and Information  at the Medical  College  of 
Wisconsin.  The goal of the forum  is to promote  discussion  of ethical, regulatory,  and policy 
concerns with  human-subjects  research.  This has provided  an opportunity  for over 720 IRBs to 
raise issues they are struggling  with  and to learn from  one another. 
7.  Ruth Ellen Bulger,  Elizabeth  Meyer  Bobby,  Harvey  V Fineberg,  editors, Societys Choices. 
Social and Ethical  Decision  Making  in Biomedicine,  (Washington,  DC: National  Academy  Press, 
1995) p. 182. 
8. 	 The National  Bioethics  Advisory  Commission  (NBAC)  was established by Executive  Order 
12975 on October  3, 1995.  Section 5 of the executive  order establishing  NBAC  states that as a 
first priority,  NBAC  shall direct its attention  to consideration  of protection  of the rights and 
welfare  of human research subjects. 
9.  Some of the promising  approaches we address are carried out, not by the IRB,  but by other 
parts of the institutions  of which  the IRB  is a part. 
A-l  OEI-01-97-00191 IRBs: Promising Approaches  10.  These IRBs  are overseeing research at institutions  receiving  over 1.4 billion  dollars  of Public 
Health  Service (PHS) awards.  As of March  1998, these institutions  received over 27 percent of 
the PHS dollars  awarded extramurally  for human subject research. 
11. We use the term academic  health centers  in accord with  the following  definition  offered by 
Blumenthal,  et al: One of 125 institutions  in the United  States that consist of at least a medical 
school and an owned or closely  affiliated  clinical  facility  in which  faculty  instruct  physicians-in-
training.  These centers classically  conduct  teaching,  patient care and, in many cases, research. 
(David  Blumenthal,  Eric G. Campbell,  Joel S. Weissman, The  Social Missions  of Academic 
Health  Centers,  New England  Journal  of Medicine,  Vol.  337,20  November  1997, No. 21, pp. 
1550-53.) 
12. These six institutions  alone account  for over half a billion  dollars  of Public  Health  Service 
(PHS) awards.  As of March  1998, these institutions  received over 11 percent of the total PHS 
dollars  awarded extramurally  for human subject research. 
13.45  C.F.R., sec. 46.103(b)(2). 
14. 45 C.F.R., sec. 46.107(a)  and 21 C.F.R.,  sec. 56.107(a). 

15.  Office  or Protection  from Research Risks, Protecting  Human  Research Subjects: 

Institutional  Review Guidebook  (U.S. Government  Printing  Office,  1993), ch. 1, sec. B, p. I-4. 

16.  Jeffrey S. Jones et al., Structure  and Practice of Institutional  Review  Boards  in the United 

States, Academic  Emergency Medicine,  vol. 3 (August  1996) no. 8,  pp. 804809. 

17.  This is in addition  to determining  that the scientific  design and methods are adequate for 

achieving  the stated objectives. 

18.  From here on, references to researchers  and investigators  will  apply to staff as well.  The 

education  of research staff is critical  as it is often the staff, not the investigators,  who  conduct the 

daily  business of administering  research. 

19.  These bodies include the National  Commission  for the Protection  of Human  Subjects of 

Biomedical  and Behavioral  Research, the Commission  on Research Integrity,  Applied  Research 

Ethics National  Association  (ARENA),  and the President in his 1997 remarks in apology  for the 

study done in Tuskegee. 

20.  Dear Colleague  letter from the Office  of Protection  from Research Risks,  Subject: 

Continuing  Review  -- Institutional  and Institutional  Review  Board Responsibilities, 

10 January 1995, and  Dear Colleague  letter from the Office  of Protection  from  Research Risks, 

Subject:  Inclusion  of Women and Minorities  in Research,  April  25, 1994. 

21.  According  to the IRBs we interviewed,  investigators  can be confused about what types of 

research need to be submitted to the IRB.  The growth  of managed care research, and 

A-2  OEI-01-97-00191 IRBs: Promising Approaches  particularly  quality  improvement  and outcomes research, is fueling  this confusion. 
22.  The Internet  address is http://helix.nih.gov:SOOl/ohsr/cbti. 
23.  A  1996 report by the U.S. General Accounting  Office  asserted that continuing  reviews  are 
typically  either superficial  or not done at all.  According  to OPRR officials,  IRBs have not always 
understood  the requirements  for continuing  review,  and, in other cases, IRB  workload  demands 
have reduced the quality  of this review.  In some cases, IRB  administrative  staff with  no 
scientific  expertise--not  IRB  members themselves--review  continuing  review  forms, ensuring 
only that the information  has been provided.  Heavy workload  also necessitates that IRBs rely 
largely  on investigators  self-assessments in conducting  continuing  reviews  (U.S. General 
Accounting  Office,  ScientiJic Research:  Continued  Vigilance  Critical  to Protecting  Human 
Subjects, GAO/HEHS-96-72,  March  1996, p. 17-l 8.)  Our companion  report also raises 
questions about the oversight  process.  For more information  see, U.S. Department  of Health  and 
Human  Services, Office  of Inspector  General, Institutional  Review Boards:  Their Role in 
Reviewing  Approved  Research, OEI-0 l-97-00  190. 
24.  45 C.F.R., sec. 46.109(e)  and 21 C.F.R., sec. 56.109(e). 
25.  Several recent articles and reports have pointed  out the limitations  to the informed  consent 
process.  In 1995, Harold  Edgar and David  J. Rothman  reported  that IRBs rarely require 
third-party  observers to oversee the consent process or to examine what actually  occurs in the 
consent process.  (Harold  Edgar and David  J. Rothman,  The Institutional  Review  Board and 
Beyond:  Future Challenges  to the Ethics of Human  Experimentation,  The Milbank  Quarterly, 
Vol.  73, 1995. No. 4, pp. 489-506.)  A  1996 U.S. General Accounting  Office  study found that 
IRB  reviews  generally  did not involve  the direct observation  of the research study or the 
informed  consent process.  (U.S. General Accounting  Office,  Scientific  Research.. Continued 
Vigilance  Critical  to Protecting  Human Subjects, GAO/HEHS-96-72,  March  1996, pp. 17-l 8.) 
According  to Reiser and Knudson,  the reasons for the infrequent  inclusion  of a third-party 

observer  include:  (1) that they would  interfere  with  the consent process; (2) that their presence 

would  imply  that investigators  are not trusted to obtain consent; and (3) that they would 

introduce  into the research a new problem--that  of finding  qualified  observers to handle oversight 

tasks such as gaining  knowledge  about the protocol,  learning  about the subject and the setting of 

research, and, most important,  bringing  an impartial  view to the analysis.  (Stanley Joel Reiser 

and Paula Knudson,  Protecting  Research Subjects after Consent:  The Case for the Research 

Intermediary,  IRB, March-April  1993, pp. lo- 11.) 

26.  Recommendation  10, part 2 of the Advisory  Commission  on Human  Radiation  Experiments 

calls for Mechanisms  for ensuring that the information  provided  to potential  subjects (1) clearly 
distinguishes  research from treatment,  (2) realistically  portrays  the likelihood  that subjects may 
benefit  medically  from their participation  and the nature of the potential  benefit,  and (3) clearly 
explains the potential  for discomfort  and pain that may accompany  participation  in research. 
A-3  OEI-01-97-00191 IRBs: Promising Approaches  Recommendation  10, part 5 calls for Mechanisms  for ensuring  that information  provided  to 
potential  subjects clearly  identifies  the financial  implications  of deciding  to consent to or refuse 
participation  in research.  (Advisory  Committee  on Human  Radiation  Experiments,  FinaZ 
Report,  Washington  DC: U.S. Government  Printing  Office,  1995). 
27.  For more information  about the use of a research intermediary,  see Stanley Joe Reiser and 
Paula Knudson  Protecting  Research Subjects after Consent:  The Case for the Research 
Intermediary,  IRB, March-April  1993, pp. lo- 11. 
28. 	 Phase 1 studies are the first of several required  clinical  trials.  Phase 1 trials test the safety of 
a drug or device on volunteer  human subjects. 
29.  The IRB  deals with  this by requiring  that investigators  tell subjects up front that their 
consent forms may be reviewed  by the IRB.  If this causes a problem  for a subject or investigator, 
the name of a subject can be deleted prior  to IRB  review. 
30.  For more information  about this continuing  review  form,  see Bruce Gordon  and Ernest 
Prentice,  Continuing  Review  of Research Involving  Human  Subjects:  Approach  to the Problem 
and Remaining  Areas of Concern,  IRB, Vol.  19, March-April  1997, No. 2, pp. 8-l 1. 
31.  45 C.F.R.,  sec. 46.109(e)  and 21 C.F.R., sec. 56.109 (e). 
32.  Based on a 1993 survey of IRBs,  Barbara Mishkin  commented  that Probably  the most 
troublesome  problem--and  the most frequent--was  the absence of substantive review  at the time 
of annual renewals.  In a number of IRBs, the staff review  annual review  reports primarily  to 
assure that one has been filed and that all spaces on an institutional  form have been filled  in.  In 
some instances, even that review  is poorly  performed,  and staff have submitted  to the IRB,  and 
the IRB  has actually  approved, submissions that are clearly  incomplete.  For example one IRB 
repeatedly  re-approved  protocols  for which  the principal  investigator  (PI) never provided  the IND 
(investigational  new drug) number assigned by the FDA  for a new drug under study.  Another 
IRB  repeatedly  processed forms on which  the PI failed to indicate  whether  the risks to human 
subjects were minimal,  moderate, or high.  Barbara  Mishkin,  Ethics,  Law  and Public  Policy, 
Professional  Ethics Report (a publication  of the American  Association  for the Advancement  of 
Science), Vol.  7, (Spring  1994), No. 2, pp. 4-6. 
33.  Office  of Protection  from Research Risks, Protecting  Human  Research Subjects. 
Institutional  Review Guidebook  (U.S. Government  Printing  Office,  1993), ch. 1, sec. B, p. I-7. 
34.  The OPRR sponsors an average of five national  educational  conferences per year. 
35.  Office  of Protection  from Research Risks, Protecting  Human  Research Subjects. 
Institutional  Review Guidebook  (U.S. Government  Printing  Office,  1993), ch. 1, sec. B, p. I-7. 
36.  Office  of Protection  from Research Risks, Protecting  Human  Research Subjects. 
Institutional  Review Guidebook  (U.S. Government  Printing  Office,  1993), ch. 1, sec. B, p. I-4. 
A-4  OEI-01-97-00191 IRBs: Promising Approaches  37. 	 The NIH  guidelines  are located in the Federal Register,  (59 Fed. Reg. 14,508, March  28, 
1994.)  The institutions  responsibility  is expanded upon in the OPRR Dear Colleague  letter, 
Subject:  Inclusion  of Women and Minorities  in Research,  April  25, 1994.  The FDA  guideline 
can be found  in a July 22, 1993 guidance  entitled  Guideline  for the study and evaluation  of 
gender differences  in the clinical  evaluation  of drugs. 
38.  Federal regulations  call for at least one IRB  member whose concerns are primarily  in 
nonscientific  areas and one member who  is not otherwise  affiliated  with  the institution.  Some 
IRBs rely on a single member to satisfy both requirements. 
39.  Many  IRBs hold their review  meetings during  business hours. 
40.  Many  of the persons chosen to serve as bioethicists  have a background  in science and/or 
ethics.  At the NIH,  education  is provided  for new consultants  through  a one day training  session. 
Continuing  education  and dialogue  occurs through  group meetings held on alternate months. 
4 1. A  1992 poll  of 127 NIH  IRB  members found 63 percent of those polled  believing  the 
bioethicist  on their board to be very helpful,  32 percent somewhat  helpful  and 5 percent not 
helpful.  In response to the question,  Does  the consultant  assist you in elucidating  or clarifying 
bioethics  issues, 80 percent of the members and 100 percent of the chairpersons  responded 
yes.  (Evan G. DeRenzo  and Frederick  0.  Bonkovsky,  Bioethics  Consultants  of the National 
Institutes  of Healths  Intramural  IRB  System: The Continuing  Evolution,  IRB, May-June  1993, 
pp. 9-10) 
42.  According  to Hayes: If,  in fact, IRBs  make mistakes from time to time, a thorough,  periodic 
evaluation,  particularly  one done externally,  would  help to refocus the groups mission  and 
objectives....  The IRB  process is simply  too important  not to include  a carefully  designed 
evaluation  process, which  can help boards stay on task and maintain  the quality  and objectivity  of 
their decisions.  (Gregory  J. Hayes, Steven C. Hayes, and Thane Dykstra,  A  Survey of 
University  Institutional  Review  Boards:  Characteristics,  Policies,  and Procedures,  IRB, vol.  17, 
May-June  1995, no. 3, pp. l-6) 
43.  OPRR Multiple  Project Assurance,  1997, Part 2, Section II. 
44.  The encouragement  for self-evaluation  can be found  in (1) the FDA  Information  Sheets for 
IRBs  and Clinical  Investigators,  1995, appendix  H, and (2) the Office  of Protection  from 
Research Risks, Protecting  Human  Research Subjects: Institutional  Review Guidebook  (U.S. 
Government  Printing  Office,  1993), ch. 1, sec. B, pp. I-7 through  I-8. 
45.  For more information  about this evaluation,  see Mary  S. Adams  and Dennis A. Conrad, 
Annual  Review:  Observed Deficiencies  and Suggested Corrections,  IRB, vol.  18, November-
December  1996, no. 6, pp. l-4. 
A-5  OEI-01-97-00191 IRBs: Promising Approaches