Evidence-based Synthesis Program Department of Veterans Affairs

Health Services Research & Development Service

May 2012

Maintaining Research Integrity: 

A Systematic Review of the Role 

of the Institutional Review Board 

in Managing Conflict of Interest

Prepared for:

Department of Veterans Affairs

Veterans Health Administration

Quality Enhancement Research Initiative

Health Services Research & Development Service

Washington, DC 20420

Prepared by:

Evidence-based Synthesis Program (ESP) Center

West Los Angeles VA Medical Center

Los Angeles, CA

Paul G. Shekelle, MD, PhD, Director

Investigators:

Principal Investigator: 

Paul G. Shekelle, MD, PhD, Director

Co-Investigators: 

Alicia Ruelaz, MD

Isomi M. Miake-Lye, BA

Research Associate:

Jessica M. Beroes, BS

Medical Editor: 

Sydney Newberry, PhD
ii

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

PREFACE

Quality Enhancement Research Initiative’s (QUERI) Evidence-based Synthesis Program 

(ESP) was established to provide timely and accurate syntheses of targeted healthcare topics 

of particular importance to Veterans Affairs (VA) managers and policymakers, as they work to 

improve the health and healthcare of Veterans. The ESP disseminates these reports throughout 

VA.

QUERI provides funding for four ESP Centers and each Center has an active VA affiliation. The ESP 

Centers generate evidence syntheses on important clinical practice topics, and these reports help:

• develop clinical policies informed by evidence,

• guide the implementation of effective services to improve patient 

outcomes and to support VA clinical practice guidelines and 

performance measures, and 

• set the direction for future research to address gaps in clinical 

knowledge.

In 2009, the ESP Coordinating Center was created to expand the capacity of QUERI Central 

Office and the four ESP sites by developing and maintaining program processes. In addition, 

the Center established a Steering Committee comprised of QUERI field-based investigators, 

VA Patient Care Services, Office of Quality and Performance, and Veterans Integrated Service 

Networks (VISN) Clinical Management Officers. The Steering Committee provides program 

oversight, guides strategic planning, coordinates dissemination activities, and develops 

collaborations with VA leadership to identify new ESP topics of importance to Veterans and the 

VA healthcare system.

Comments on this evidence report are welcome and can be sent to Nicole Floyd, ESP 

Coordinating Center Program Manager, at nicole.floyd@va.gov.

Recommended citation: Shekelle PG, Ruelaz A, Miake-Lye IM, Beroes JM, Newberry S. 

Maintaining Research Integrity: A Systematic Review of the Role of the Institutional Review 

Board in Managing Conflict of Interest, VA-ESP Project #05-226; 2012.

This report is based on research conducted by the Evidence-based Synthesis Program 

(ESP) Center located at the West Los Angeles VA Medical Center, Los Angeles, CA 

funded by the Department of Veterans Affairs, Veterans Health Administration, Office 

of Research and Development, Quality Enhancement Research Initiative. The findings 

and conclusions in this document are those of the author(s) who are responsible for its 

contents; the findings and conclusions do not necessarily represent the views of the 

Department of Veterans Affairs or the United States government. Therefore, no statement 

in this article should be construed as an official position of the Department of Veterans 

Affairs. No investigators have any affiliations or financial involvement (e.g., employment, 

consultancies, honoraria, stock ownership or options, expert testimony, grants or patents 

received or pending, or royalties) that conflict with material presented in the report. 
1

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

EXECUTIVE SUMMARY

BACKGROUND

Ethical integrity in the conduct of health care research is essential for maintaining the public 

trust and support of such activities. Institutional Review Boards (IRBs) play a critical role in 

maintaining the ethical integrity of research by reviewing research protocols to ensure, among 

other things, that research participants receive safe and ethical treatment and provide informed 

consent, and that the potential for a conflict of interest is minimized. The purpose of this review 

was to catalog the literature on issues pertaining to IRBs, to identify the issue with the greatest 

number of published studies which might inform VA policy, and to assess the evidence regarding 

that issue, which were conflict of interest policies and the activities of the IRB. 

METHODS

This project was nominated by Ranjana Banerjea, HSR&D & HSR&D Research Best Practices 

Workgroup (RGP). The goal was to describe the evidence regarding areas of interest in the 

ethical conduct of research, with a particular focus on the IRB and quality improvement 

initiatives. Further discussions resulted in the following key questions:

Key Question #1. What has been published regarding the IRB, and each of the following issues:

• Quality improvement initiatives as research

• Conflict of interest

• Studies requiring approval of multiple IRBs

• Genetic issues

Key Question #2. What is the actual evidence regarding the issue with the largest literature which 

may inform VA policy? 

We searched the PubMed databases from 1/01/2000-2/11/2011 for articles related to our key 

questions. We limited the search to English language articles using search terms related to 

institutional review boards, informed consent, data use, conflict of interest, ethics, and quality 

improvement. We also completed related-article searches on four key articles. We also searched 

the websites of relevant organizations, including the Association of American Medical Colleges 

(AAMC), Public Responsibility in Medicine and Research (PRIM&R), and the Association for 

the Accreditation of Human Research Protection Programs, Inc (AAHRPP).

We screened titles and then abstracts, excluding any article not related to the topics listed in 

Key Question #1. Full articles that met the inclusion criteria were then sorted into the following 

categories: multi-center IRB; quality improvement as research; conflicts of interest; payments 

to patients, providers, or study participants (a potential for conflict of interest); genetics research 

(this category mostly pertained to data repositories and the ethics of using stored genetic material 

for subsequent studies); miscellaneous articles pertaining to Key Question #1; background 

articles; and rejected articles. 
2

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

DATA SYNTHESIS

After performing the search and sorting the articles that met our inclusion criteria, we then 

selected for detailed review the area for which we identified the greatest number of relevant 

published studies and for which no VA policies were already in place. Because of the nature of 

these studies, no quantitative synthesis was possible; therefore our synthesis is descriptive.

PEER REVIEW

A draft version of this report was reviewed by seven technical experts, as well as VA Central 

Office leadership. Reviewer comments were addressed and our responses were incorporated in 

the final report.

RESULTS

We reviewed 4,302 titles and abstracts from the electronic search and an additional 490 from 

related searches for a total of 4,792 references. After applying inclusion/exclusion criteria at the 

abstract level, we excluded 4,327 references. We retrieved 163 full-text articles and on the basis 

of further review, we excluded another 47 references. A total of 116 references were included in 

the current review.

Key Question #1. What has been published regarding the IRB, and each of the following issues:

•	 Quality improvement initiatives as research

•	 Conflict of interest

•	 Studies Requiring Approval of Multiple IRBs

•	 Genetic issues

We describe here the results of the search we performed. Our goal for this key question was to 

provide a broad “lay of the land” picture of the available evidence but not a critical synthesis of 

the evidence. 

Multisite Institutional Review Board Challenges 

We identified 41 articles that dealt with the challenges of having to submit a research protocol 

to IRBs at multiple institutions. Most were descriptive studies of how the same application was 

reviewed by different IRBs. VA has recently implemented a process whereby multi-site VA 

studies can be reviewed by a single, centralized IRB. Consequently, a detailed review of this 

issue would not be helpful to VA. The VA Central IRB does not review all protocols that require 

multiple IRB review. An issue remains that when a protocol is conducted at both the academic 

affiliate and VA facility, it has to be reviewed by both institutions unless the VA facility has an 

arrangement to delegate review to the academic affiliate. Further, industry-sponsored studies 

require multiple IRB reviews and VA prohibits the use of independent (commercial) IRBs. 

When Quality Improvement Initiatives Are Considered Research

Quality improvement is an increasingly important activity for health care organizations and also 

the subject of scholarly activity. Questions have been asked about what quality improvement 

activities constitute “research” in the context of requiring approval and oversight by an IRB. We 
3

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

identified 31 publications on this issue. However, because VA has recently developed policy on 

this issue, a detailed review would not be helpful.

Conflict of Interest

We identified 11 publications that dealt with potential conflict of interest (COI) in research, both 

by investigators and by IRB members. This issue was the one for which we identified the most 

articles; therefore we selected it for more detailed review (see Key Question #2).

Payment to Patients

We identified nine publications that dealt with the ethical issues surrounding paying patients to 

participate in research studies or paying heath care professionals to recruit patients into these 

studies. Four of these articles were descriptive studies about the payments to patients. Across 

studies, the amount of payment appeared unrelated to the magnitude of the procedures to be 

performed or the time to participate in the study. Payments to patients ranged widely, from $5 

to $2000, with a median of $155. Two studies by the same investigator assessed the potential 

reasons for payments to participants. The results indicate that investigators consider various 

factors in deciding whether and how much to pay study participants. 

Genetics

We identified eight publications that dealt with potential ethical issues in genetic studies for 

which an IRB was asked to rule. These issues consisted of consensus recommendations for 

informed consent and studies describing variation across institutions in genetic policies. 

Miscellaneous

Eighteen publications were potentially relevant to the IRB’s role in maintaining research 

integrity but did not fall into one of the existing categories. These studies were a mix of surveys 

about ethical issues, particularly challenging scenarios that might require special rules (such as 

practice-based research networks, palliative care, and nursing research) and methods to evaluate 

the workings of the IRB. 

Key Question #2. Detailed review of Conflict of Interest studies

COI, both financial and non-financial, is increasingly recognized as an important aspect of 

maintaining public trust in medical research. In reviewing the literature available on COI, 

we start with those studies that examined the goals of disclosure, in general, as well as what 

disclosure should include.

Purposes of Disclosure to the IRB

We identified four studies that dealt with the purposes of disclosure. Commonly reported goals 

included promoting informed decision making, respecting patients’ perceived right to know, 

establishing or maintaining trust, minimizing risk of legal liability, deterring troubling financial 

relationships, and protecting research participants’ welfare. 

Who Has Policies around Disclosure?

Three studies were descriptive assessments of various institutions’ COI policies. A conclusion 

common to all three studies was the wide variability in policies among institutions. 
4

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

Two studies were descriptive assessments of COI policies within a single IRB. Again a common 

conclusion was variability in the policies.

Persons or Interests Requiring Disclosure

Four studies were descriptive assessments of policies specifying which persons or entities were 

required to disclose COI. All policies required research investigators to disclose, but beyond that 

commonality, policies varied substantially on the requirement for family members (i.e., parents, 

siblings, “de facto spouses,” or other family members) of researchers to disclose COI. 

Party to Which Disclosure Must Be Made 

Five studies reported descriptive assessments of policies regarding the entities to whom 

disclosure needed to be made. All studies reported that all policies required disclosure to a 

university or institutional official or committee. Studies disagreed regarding disclosure to 

the IRB, varying from one percent of institutions requiring “initial” disclosure to the IRB, to 

60 percent of the “top 10” National Institutes of Health (NIH)-funded research institutions 

requiring disclosure to the IRB, to the IRB having “a role” in review of investigators’ financial 

relationships in about 75 percent of institutions. Differences in wording probably account for 

some of the differences in responses. 

One study surveyed IRB chairs about the persons to whom IRB members’ COI should 

be reported. Sixty-two percent answered that their IRB members reported their industry 

relationships to the IRB chair, 76 percent of respondents reported to the entire IRB, 53 percent of 

respondents reported to a group or individual within the organization but separate from the IRB, 

7 percent reported to an entity external to the IRB and the institution that it serves, and 2 percent 

reported to an unnamed ‘other.’ 

Managing Disclosure of Potential Conflicts of Interest

One study reported a descriptive assessment of how COI was managed. Within the policies of 

the 235 medical schools and other research institutions, disclosure was managed by divestment 

of interest (62 percent), withdrawal of the investigator from the project (61 percent), disclosure 

to the IRB or research subjects (0 percent), disclosure to the funding agency or sponsor (43 

percent), disclosure to journals publishing findings (2 percent), disclosure to collaborating 

researchers (1 percent), a modification of research plan (59 percent), monitoring of the project 

(66 percent), requirement for additional peer review (7 percent), or public disclosure (59 

percent). 

Monitoring Compliance

No studies were identified that described how compliance was monitored. 

Managing Noncompliance

Two studies described assessments of policies for managing noncompliance. As with other 

policies, policies for managing noncompliance varied widely.
5

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

Potential Harms of Disclosure 

One study surveyed investigators, IRB chairs, and COI Committees about the potential negative 

effects of disclosure. These effects included the belief that disclosure might affect participant 

recruitment and enrollment, expressed by 63 percent (5/8) of investigators, 78 percent (18/23) of 

IRB chairs, and 79 percent (11/14) of COIC chairs; the belief that disclosure ‘breaks down trust,’ 

expressed by, respectively, 63 percent, 26 percent, and 21 percent; the belief that disclosure 

lengthens informed consent documents by, respectively, 38 percent, 26 percent, 29 percent; and 

the belief that disclosure lengthens the informed consent process, by, respectively, 38 percent, 9 

percent, and 0 percent.

SUMMARY AND DISCUSSION

Key Question #1

The topic areas for which the largest number of studies has been published are the challenges 

of getting multiple IRB approvals for multi-site research studies and defining when quality 

improvement initiatives are considered research. Both are topic areas for which VA has recently 

implemented national policies designed to reduce complexity and uncertainty for researchers 

while maintaining appropriate safeguards for patients. These two topics account for 60 percent of 

the articles we identified. 

Of the remaining studies, the next most common topic of study was COI, which we designated as 

the focus of key question #2 for an in-depth review. A modest body of research has been devoted 

to studies of payments to providers or patients for participating in research; these studies indicate 

wide variability and little relationship between the time expected for participant involvement and 

the payment. 

We also identified a modest number of published studies about the ethics of genetic studies. This 

finding may be surprising, given the degree of interest in the topic in both professional and lay 

audiences. 

Key Question #2

With regard to COI, we identified a modest number of published studies, almost all of them 

descriptive and some with substantial limitations (such as low survey response rates or restriction 

of the sample to a small number of sites). Many more studies have examined COI among 

research investigators than among IRB members reviewing proposed research. Nevertheless, 

the available evidence indicates potentially worrisome variation in practice across sites. We 

identified variation in four domains:

1. Who needs to disclose?

Which members of the research project need to provide COI disclosures? This group 

could include principal investigator(s), co-investigators, research assistants, and other 

research staff.

2. What needs to be disclosed? 

This information includes not only direct financial interests, but also indirect financial 

support such as support for travel to attend meetings, and non-financial COI.

3. How distant a relationship may an individual have with an investigator and still be 
6

Maintaining Research Integrity: A Systematic Review of the Role 

of the IRB in Managing Conflict of Interest Evidence-based Synthesis Program

required to disclose COI? This group almost always includes a spouse, but could also 

include children, parents, siblings, or other extended family members.

4. To whom does the information need to be disclosed? The target could be a specific 

official or committee of the IRB, or potentially the research participants.

RECOMMENDATIONS FOR FUTURE RESEARCH

Maintaining high ethical standards of conduct in research, both for the investigator and for IRBs, 

is a high prority for VA, and not one where VA can or should merely react to problems when they 

are identified. Rather, VA should aim that research conducted at all VA insitutions is held to the 

same high standard, much as it has done with clinical care over the past 15 years. To do so, VA 

should:

1. Conduct a descriptive study of current COI practices for investigators and IRB members 

at all VA facilities, 

2. Use this information to determine which areas of current practices have unjustifiable 

levels of variation across sites,

3. Convene stakeholders to determine best practices for these processes,

4. Create VA-wide policy about these practices, and

5. Monitor implementation across facilities.

As an example, right now it is unknown whether VA facilities vary across the four dimensions 

of “who should disclose,” “what to disclose,” “how distant must an individual be related to 

an investigator to avoid disclosure,” and “to whom should COI be disclosed.” VA facilities 

may vary, possibly greatly, in these dimensions. VA has striven to provide, and patients have 

come to expect, one high standard of clinical care no matter which VA facility they visit. It is 

unreasonable for Veterans to expect differing ethical standards of research across VA facilities. 

Research-informed policy can ensure that COI disclosure be made as standard as clinical care, 

while allowing local flexibility when it is justified. Implicit in this statement is that defining 

standard COI policies, while a necessary condition, is not sufficient. Monitoring implementation 

is critical. AAHRPP has attempted to institute a common standard across VA facilities (at least 

those that are accredited) with response to a single disclosure threshold, disclosure from all 

individuals involved in the research, and management plans. One challenge is as a government 

agency VA must follow the government-wide ethics regulations that state federal employees 

may not have financial interests that relate to their work. All VA IRBs, that are accredited, have 

conflict of interest policies.

After this uniformity is accomplished, the next step will be to try and provide national VA 

guidelines on managing COI for individuals (investigators) and IRBs. While preservation of local 

autonomy is important for providing insitutions with the flexibility they need, some system-wide 

principles would be useful to help local sites inform COI management decisions. Non-financial 

COI will also need to be addressed at some point. Given the current imprecision with which nonfinancial conflicts are defined, the VA would best defer this topic until a greater degree of consensus 

is reached in the scientific community on how non-financial conflicts are defined.

Lastly, since many VA insitutions that conduct research have university affiliates, a potential 

complicating factor is the lack of harmony between VA COI and that of these university affliates.