Department of Health and Human Services 

OFFICE OF 

INSPECTOR GENERAL 

Institutional Review Boards: 

Their Role in Reviewing Approved Research 

JUNE GIBBS BROWN 

Inspector General 

JUNE 1998 

OE.r-nl-97-nnl9n 
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. 

OEI’s Boston regional office prepared this report under the direction of Mark R. Yessian, Ph.D., 

Regional Inspector General. Principal OEI staff included: 

REGION HEADOUARTERS 

Laura C. McBride Lisa Foley 

Elizabeth A. Robboy 

Nathan P. Rouillard 

Dana M. Miller 

To obtain copies of this report, please call the Boston Regional Office at (6 17)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 review the performance of institutional review boards in reviewing ongoing research 

involving human subjects. 

BACKGROUND 

Role of Institutional Review Boards 

Institutional review boards (Irks) 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. 

Continuing Review: The Focus of This Report 

Continuing review can serve as a key safety net for human subjects. This protective role 

has become especially significant as many individuals have signed up to participate in 

research trials with little understanding of the risks involved or of the distinction between 

research and established therapy. Its importance has also been heightened as the research 

environment has become increasingly affected by marketplace pressures and as some 

protection lapses have occurred, causing harm to human research subjects. 

In this report, which is one of four we are issuing on IRBs, we address the IRBs’ 

continuing review function. Given our focus on the overall system of protections 

provided to human subjects, we did not carry out audits of IRBs or investigations of 

particular cases. To help us understand the big picture, we conducted an extensive review 

of Federal records and pertinent literature, held interviews and group discussions with 

many Federal officials and with representatives of about 75 IRBs; visited IRBs at 

6 academic health centers where extensive clinical research is taking place; attended IRE3 

meetings; and accompanied FDA inspectors on IRE3 site visits. 

FINDINGS 

The Continuing Review Conducted by IRBs Is of Limited Scope and Significance. 

Minimal Substantive Review of Reports. Once IRBs complete their reviews of initial 

research proposals, they often have little time left for continuing reviews. Thus, their 

i OEI-01-97-00190 IRBs: Continuing Review 
reviews of the annual reports, adverse-event reports, and protocol amendments submitted 

by research sponsors are often hurried and superficial. 

Minimal Field Presence. The continuing review that IRBs carry out is limited almost 

entirely to paperwork reviews. They rarely visit the research site to determine how the 

consent process is actually working or to review the records of active protocols. To 

varying degrees other parties do conduct on-site monitoring, but unlike the IRBs, they do 

not have a central mission of protecting human subjects. 

A Number of Factors Limit IRBs’ Capacity to Conduct Continuing Review. 

Heightened Workload Pressures. IRBs are inundated with research proposals. 

Working in competitive environments with major institutional cost pressures, many of 

them have been unable to add the staff and other resources to keep up with the workload 

increases. At the same time, volunteer IRB members, pressed to concentrate their time on 

revenue-enhancing clinical activities, find it more difficult to devote time to the boards. 

Limited Useful Feedback on Multi-Site Trials. A significant portion of the research 

being reviewed by IRBs is now part of multi-site trials. These trials often include an 

active monitoring component carried out by Data Safety Monitoring Boards (DSMBs) 

and/or by clinical audit teams. Such monitoring involves expert peer review of IRBapproved research. But, the DSMBs and audit teams rarely report their findings to IRBs. 

Limited Feedback on FDA Actions Against Investigators. Correspondence regarding 

FDA actions against research investigators is not routinely disclosed to IRBs. A number 

of IRB officials reported to us instances in which they heard about an FDA action 

indirectly, from other (often media) sources. Officials at FDA indicated that they are 

precluded from routinely disclosing such information by legal concerns under the Privacy 

Act. 

Limited IRB Expertise. IRBs find that they often have insufficient scientific expertise 

to assessthe results of active protocols. This can present particular vulnerabilities in the 

case of protocols that are not subject to peer review by other bodies. 

Limited Nonscientific and Noninstitutional Input. IRBs typically have minimal 

“outside” representation. This limitation deprives them of a valuable counterbalance 

during the continuing review process when important questions can be raised concerning 

the interests of human subjects. 

The Trust Factor. The IRB process is rooted in trust, assuming the best of intentions of 

investigators and sponsors. This tradition makes substantive continuing review suspect. 

It holds that the IRB’s job is to ensure protections upfront, not to serve as “watchdogs” or 

“police.” 

ii OEI-01-97-00190 IRBs: Continuing Review 
Federal Oversight of IRBs Provides Little Basis for Determining the Effectiveness of IRBs’ 

Continuing Review of Approved Research. 

Two agencies within the Department of Health and Human Services are responsible for 

the oversight of IRBs: the National Institutes of Health (NIH), through its Office for 

Protection from Research Risks (OPRR), and the Food and Drug Administration (FDA). 

The OPRR Oversight Focuses on Upfront Assurances. Only Rarely Does Its 

Oversight Involve On-site Assessments of IRB Performance. The assurance is an 

upfront document of an institution’s commitment to human-subject protections. It does 

not involve an assessment of performance. The OPRR is in a better position to make 

such assessments when it conducts for-cause site visits, but because of resource 

constraints it conducted only one such visit between April 1997 and May 1998. 

The FDA Oversight Focuses on Inspections. Its Reviews, However, Stress 

Procedural Compliance, with Only Minimal Attention Given to IRB Effectiveness. 

The FDA conducted just under 200 inspections in 1997. These inspections aim to ensure 

IRB adherence to Federal requirements and frequently result in deficiency notices to the 

IRBs. But here, too, there is little attention to assessing results. For instance, while FDA 

calls for IRBs to ensure that subjects understand the implications of their participation in 

research, FDA’s own inspection process does not enable it to determine how well IRBs 

are able to do that. 

CONCLUSION 

The IRBs’ limited efforts in conducting continuing review of active research is a serious 

national issue because it compromises their protection of human subjects. It inhibits their 

capacity to identify and address situations where unacceptable risks emerge, or research 

results prove to be too favorable to continue, or protocols stray beyond approved limits. 

It also inhibits their capacity to ensure that the subjects have sufficient understanding of 

the risks they may incur in the research process. 

With this conclusion, we do not claim that widespread abuses exist. We recognize the 

important contributions that IRBs have made and continue to make. The system of 

protections they provide is supported by many conscientious investigators committed to 

protecting human subjects and by many dedicated IRB members and staff doing their best 

under trying circumstances. But, our inquiry offers an important warning signal--one that 

could get stronger in view of current developments. These include Federal plans to 

increase significantly the numbers of subjects in clinical trials and various proposals that 

would give IRBs increased responsibility in the areas of genetics and confidentiality. 

This warning signal warrants a Federal response. We address the elements of such a 

response in our parallel inspection report entitled, Institutional Review Boards: A Time 

For Reform. 

. . . 111 031-01-97-00190 IRBs: Continuing Review 
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 Citizen’s 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. 

iv OEI-01-97-00190 IRBs: Continuing Review 
PAGE 

EXECUTIVE SUMMARY 

INTRODUCTION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..l 

IRBs: THE BASICS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 

IMPORTANCE OF CONTINUING REVIEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4 

FINDINGS 

The Continuing Review Conducted by IRBs Is of Limited Scope and Significance. . . . .7 

Numerous Factors Inhibit Their Capacity to Conduct Continuing Review ............ 9 

OPRR and FDA Pay Little Attention to IRB Effectiveness. ...................... 12 

CONCLUSION ............................................................ ..15 

APPENDICES 

A: Federal Requirements on IRB Continuing Review ......................... A-l 

B: Federal Oversight of IRBs ............................................. B-l 

C: Advertising to Recruit Human Subjects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . C-l 

D:Endnotes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . D-l 

031-01-97-00190 IRBs: Continuing Review 
INTRODUCTION 

PURPOSE 

To review the performance of institutional review boards in reviewing ongoing research 

involving 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 (HHS). Appendix A offers further 

background on the Federal requirements that apply to these boards, particularly with 

respect to their continuing review function. 

Prior Inquiries 

For about a quarter of a century, IRBs have been playing an important part in protecting 

human subjects enrolled in research projects. Almost from the start, however, prominent 

studies have drawn attention to some of their limitations. A 1983 Presidential 

Commission report raised concerns about the adequacy of the review procedures of some 

IRE&, about how well some of the members of these boards understood their roles, and 

about the commitment of some of the institutions to their Irks.’ Twelve years later, in 

1995, a Presidential advisory committee raised even stronger concerns about the 

adequacy of the IRB review process, especially for research involving greater than 

minimal risks, and about the effectiveness of Federal oversight strategies.’ In the 

following year, the General Accounting Office issued a report reinforcing these points 

and identifying numerous factors inhibiting IRB performance.3 

We, too, found particular reason to be concerned about IRB oversight in a recent inquiry 

of our own. In examining clinical trials involving four investigational medical devices, 

we discovered inadequacies related to IRB continuing review in each case. These 

inadequacies concerned serious matters such as the implantation of a device in three 

times the number of human subjects specified in the IRB-approved research protocol, the 

initiation of a research effort without changes that the IRB called for in the informed 

consent document, and the continuation of a research project for six weeks beyond when 

the IRB had suspended it.4 

This Inquiry and Report 

This inquiry builds on the prior reviews and, we hope, will contribute to the deliberations 

of the currently active Presidential advisory body examining the protections available to 

human subjects.5 This report is one of four that has resulted from our overall inquiry. A 

1 OEI-01-97-00190 IRBs: Continuing Review 
second report, Institutional Review Boards.. Promising Approaches, presents innovative 

approaches that IRBs have undertaken in six key areas of responsibility. A third, 

Institutional Review Boards: The Emergence of Independent Boards, indicates how those 

IRBs that are separate from research institutions are a growing force; it addresses the 

advantages and disadvantages associated with independent boards. A fourth report, 

Institutional Review Boards: A Time For Reform, serves as the big picture report, viewing 

the overall functioning of IRBs and presenting recommendations emerging from our 

inquiry. 

In this report, we focus on the continuing review function of the IRBs--that is, on the 

review activities they undertake subsequent to their initial approval of research protocols. 

We examined these review activities because of the concerns we noted in the previous 

section and because, as our inquiry progressed, we became increasingly aware of 

continuing review’s importance as a human-subject protection. We elaborate on that 

importance in the following section before we present our findings on the extent of 

continuing review that takes place, the factors inhibiting that review, and the nature of the 

Federal oversight of this process. 

Our 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;6 

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

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

raised on an electronic e-mail forum by those associated with IRBs; attendance at IRB 

meetings; site visits with FDA inspectors; and site visits to 6 IRBs based in academic 

health centers.7 At these centers, which are among the most heavily funded biomedical 

research centers in the country,’ we interviewed not only IRB administrators and 

members, but also many others in the parent institutions whose functions had a bearing 

on IRB performance. These included medical school deans; hospital vice presidents; 

heads of pertinent academic, administrative, and clinical committees or departments; 

attorneys; ethicists; and many others. 

We conducted this inspection in accordance with the Quality Standards for Inspections 

issued by the President’s Council on Integrity and Efficiency. 

2 031-01-97-00190 IRBs: Continuing Review 
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 198 1. 

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 OPRR’s 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 institution’s 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 FDA’s main mechanism for IRB oversight is the inspection process. The 

FDA also inspects research sponsors and scientists (known as research investigators). A more detailed 

explanation of the agencies’ oversight processes can be found in appendix B. 

3 OEI-01-97-00190 IRBs: Continuing Review 
IMPORTANCE OF 

CONTINUING REVIEW 

The IRBs’ ongoing review of research involving human subjects can serve as an 

important safety net for human subjects.’ It provides a means of addressing 

vulnerabilities that may not have been adequately identified and/or corrected during the 

initial review process. It also offers a way of addressing vulnerabilities that may have 

emerged during the course of the approved research. 

In recognition of the importance of continuing review, Federal regulations call for IRBs 

to conduct reviews “at intervals appropriate to the degree of risk, but not less than once 

per year, ” and specify that IRBs have the authority “to observe or have a third party 

observe the consent process and the research.“” On January 10, 1995, the Office for 

Protection from Research Risks (OPRR) in the National Institutes of Health reaffirmed 

this IRB responsibility through the issuance of a “Dear Colleague” letter to IRBs. That 

letter noted that continuing review must be “substantive and meaningful,” and elaborated 

on associated operational matters, most especially that the annual reviews must be 

completed within 1 year of a previous IRB review.” Similarly, on October 1, 1995, the 

FDA issued an Information Sheet to IRBs and clinical investigators that reinforced the 

importance of continuing review and sought to clarify the minimum requirements that 

IRBs have in that regard.12 

In recent years, the safety net role that continuing review represents may have become 

more important than ever. Four factors lead us to this conclusion. We wish to emphasize 

the importance of continuing review before presenting our findings. These factors are as 

follows: 

The Limits of Informed Consent 

Individuals who consent in writing to participate as a research subject do not necessarily 

understand the implications of their decision.13 They may not realize that the primary 

mission of research is to advance medical knowledge rather than to provide subjects with 

medical treatments. Further, they may develop unrealistic expectations about both the 

potential benefits and risks associated with their participation.‘4 The 1995 presidential 

advisory commission concluded that there was, indeed, “reason to worry” that such 

misunderstandings may be common.15 

On the front lines, the informed consent process is much more about forms--determining 

their content and making sure they are signed--than it is about ensuring understanding by 

the potential subjects. This limitation is widely corroborated in the literature,16 in 

convenings of IRB officials, and in our own discussions and site visits.” Many IRBs 

strive to see that consent forms are as informative and clear as possible. But these efforts 

often run against the grain as the forms become longer and more complex, serving more 

4 OEI-01-97-00190 IRBs: Continuing Review 
as documents to protect the institutions and the sponsors rather than the human subjects. 

Some IRBs also strive to encourage researchers to interact with potential subjects in ways 

that facilitate understanding. But, they generally have little basis for knowing how well 

they succeed in that regard.‘* 

The Blurring of Research and Treatment 

It is also the case, as the 1995 Advisory Commission underscored, that individuals who 

consent to participate as human research subjects do not necessarily distinguish research 

from standard therapy or treatment. In a survey of 1,882 randomly selected patients in the 

waiting rooms of 16 hospitals, the Commission found that 37 1 had been research 

subjects. Yet, almost 20 percent of these research subjects incorrectly stated that they 

were not and never had been research subjects. Worse yet, about 40 percent of the studies 

reviewed involving these individuals were experiments that posed greater than minimal 

risk. I9 

In recent years, potential human subjects themselves have often been the ones blurring the 

distinctions between research and treatment. Patients, especially those with lifethreatening diseases, have often placed more emphasis on gaining access to experimental 

efforts than on being protected from the harm they can cause.2o Yet some researchers 

have also been contributing to this blurring through their own tendency to emphasize the 

personal benefits rather than the risks of research (see appendix C) and/or through use of 

their own patients as human subjects. One researcher, who is also a member of an IRB, 

told us that over the years his own patients accounted for nearly all the subjects in his 

many studies and that this did not prove to be a problem because they trusted him. In 

contrast, another researcher, who was a participant in one of the commissions addressing 

human-subject protections, told us that physicians’ own patients represented one of the 

most vulnerable categories of subjects. 

The Changing Research Environment 

The research culture in which IRBs function has been significantly transformed over the 

past 20 years. As the proportion of industry sponsored research has increased, this culture 

has been increasingly shaped by the realities of the marketplace. Sponsors, with 

significant amounts of money at risk, emphasize the rapid development of products and 

seek to work with IRBs that will conduct their reviews quickly. At the same time, the 

parent institutions of many IRBs are eager to gain the revenue associated with large 

industry sponsored projects.21 While they tend to be careful not to jeopardize the role of 

the IRBs, they also expect them to respect the sponsors’ need for quick turnaround. 

These pressures to accelerate initial IRB reviews heighten the importance of continuing 

review as a safety net. So, too, does the emergence of newer kinds of research that have 

major implications for human subjects. This is especially true for genetics research 

which can produce sensitive and troubling information pertinent not only to a subject 

directly, but to a subject’s relatives, potential offspring, insurers, employers, and others. 

5 OEI-01-97-00190 IRBs: Continuing Review 
How access to such information is controlled and how well subjects are informed and 

counseled about it are vital matters that are certain to warrant continuing attention during 

the course of a research effort. 

The Protection Breakdowns Involving IRB-Approved Protocols 

The system of protections now in place is certainly much better than that which existed 

when the Federal requirements were first established in the 1970s. But even with these 

protections, lapses do occur and they serve to reinforce the need for continuing review. A 

few of these lapses have been highly publicized ones that resulted in significant harm, 

even death, to human subjects or have exposed them to unnecessary risks.22 Other lapses 

may remain unnoticed. In fact, in our previous study on investigational devices, we found 

reason for concern in 11 of the 20 sites we visited. These involved serious matters such 

as the implantation of a device in three times the number of human subjects specified in 

the IRB-approved research protocol, the initiation of a research effort without changes 

that the IRB called for in the informed consent document, and the continuation of a 

research project for six weeks beyond when the IRB had suspended it.23 

A number of the IRB officials we spoke with mentioned a continuing concern they have 

with “protocol creep,” wherein the number of human subjects, the drug doses, or some 

other aspect of the research ventures beyond that approved by the IRB. Some also 

expressed concern about whether, in research involving placebos, the IRB is getting 

sufficient up-to-date information about investigational treatments to ensure that the use of 

placebos remains justified. 

6 OEI-01-97-00190 IRBs: Continuing Review 
The Continuing Review Conducted by IRBs Is of Limited Scope 

and Significance. 

Minimal Substantive Review of Reports 

In accord with Federal regulations, IRBs receive and must review significant amounts of 

paperwork on active research projects. They must review annual reports, adverse-event 

reports, and amendments to research protocols. In each case, however, little substantive 

review tends to take place. 

Annual Reviews. The OPRR’s 1995 Dear Colleague letter on continuing review has had 

the intended effect of getting IRBs to pay more attention to annual reviews, but the 

attention has focused much more on complying with procedural requirements than on 

conducting substantive continuing review. Many IRBs find that with significant increases 

in the quantity of new research protocols to review, they have little time left for annual 

reviews. Not at all uncommon is the situation we found at one IRB meeting where the 

board relied on prior reviews of a primary reviewer and administrative staff and quickly 

approved several annual reviews in the last 15 minutes of 2’% hour meeting.24 

Many board members regard the annual review requirement as unproductive unless it has 

become apparent that there are significant problems concerning a protocol. Otherwise, 

they say it is unnecessarily duplicative of the initial review and even undermines the 

voluntary commitments that busy board members make to the IRBJ5 Along this line, 

some board members we spoke with regarded annual reviews as essentially a staff 

responsibility and gave little if any time to reviewing the annual reports prior to the board 

meetings. 

Adverse-Event Reports. The FDA requires that sponsors and investigators report to the 

FDA and participating IRBs any adverse events involving both serious and unanticipated 

effects on human subjects. As with the continuing review requirement, the Federal intent 

was to foster substantive review. But here, too, the reality has been quite different. The 

IRBs have, indeed, been receiving adverse-event reports (AERs). In fact, those IRBs that 

oversee projects that are part of large, multi-site trials are being inundated with them, as 

sponsors, eager to minimize liability exposure, choose to err on the side of reporting 

rather than not reporting. One IRB we visited had received several boxes of AERs within 

the past few weeks. Another indicated that it was receiving an average of 200 AERs a 

month. 

The IRB officials equate the review of AERs to that of looking for a needle in a 

haystack.26 They say that the reports seldom inform them of how many patients are 

enrolled in a multi-site trial and tend to include little if any analysis of the significance of 

7 OEI-01-97-00190 IRBs: Continuing Review 
the adverse event reported. Thus, the IRBs find themselves hard-pressed to use AERs as 

a tool of substantive oversight. Rarely does an AER lead to any IRB intervention 

concerning an active protocol. On the few occasions when it does, it is likely to involve 

some change in the way risks are explained on an informed consent form. In reviewing 

the last two meetings of the IRB, one IRB official calculated that the members had 

reviewed 32 AERs in one meeting and 21 in the other, none of them leading to any 

changes. This experience was not at all unusual at that IRB or at the others we contacted. 

Protocol Amendments. Federal regulations also call for sponsors and investigators to 

obtain IRB approval for any changes that they wish to make in research protocols. This 

results in a steady stream of amendments submitted to and reviewed by IRBs. 

Occasionally these changes will trigger a substantive review of a project but, they 

typically involve minor matters that are routinely processed. It is important to recognize 

that the IRB is highly dependent on investigators and sponsors to be attuned to changes in 

the course of a research project and to call for amendments when necessary. 

Minimal Field Presence 

The continuing review that IRBs do carry out is limited almost entirely to paperwork 

reviews by IRB members and staff. Although the IRBs have the authority to visit the 

research site as part of their continuing review, our inquiries and other studies indicate 

that they rarely visit the research site to determine how the informed consent process is 

actually working or to review the data and records of active protocols.27 This may be 

particularly worrisome with regard to independent IRBs, which are often located far from 

the research site. Five of the eleven independent boards we interviewed reported that 

they have no routine policy for visiting the research sites under their purview. 

On those few occasions when IRBs do become more directly involved in reviewing a 

research practice, the action tends to be triggered more by particular concerns that have 

come to their attention than by random reviews.28 As a result, IRBs typically have little 

basis to know for themselves how research teams approach the informed consent process, 

how well human subjects understand the implications of their participation in research, 

and how fully research teams remain true to the research design set forth in their 

approved protocols.29 

In this context, it is important to recognize that to varying degrees other parties do 

conduct reviews at the research site. These include commercial sponsors and/or the 

contract research organizations representing them, clinical research centers and/or other 

parts of the institution to which an IRB belongs, and, as we note in a subsequent section 

of this report, the monitoring bodies associated with multi-site clinical trials and federally 

funded cooperative-group trials. Unlike the IRBs, however, none of these parties has the 

protection of human subjects as its central mission. 

8 OEI-01-97-00190 IRBs: Continuing Review 
A Number of Important Factors Inhibit IRBs’ Capacity to Conduct 

Continuing Review. 

Heightened Workload Pressures 

IRBs of all sizes are facing major 

workload demands. These are 

generated in part by the significant 

numbers of adverse-event reports and 

protocol amendments submitted to 

them for review. But, the key force is 

a dramatic increase in the number of 

research protocols being submitted for 

initial review. Our study sites 

reported average increases of 42 

percent in initial reviews during the 

No Time for Chit-Chat 

The agendas of the IRJ3 review meetings at academic 

centers are packed, leaving busy reviewers little time 

to reflect on and debate issues raised by research 

protocols. As an illustration, at the sites we visited, 

the meetings typically lasted about 2% hours and 

included an average of 18 initial reviews, 9 expedited 

reviews, 43 protocol amendments, and 2 1 adverseevent reports. 

past 5 years, with the result that some of them are now reviewing more than 2,000 

protocols.30 This finding is in accord with that of a recent survey of academic health 

centers which found that their IRBs were reviewing an average of 297 proposals a year. 

Ten percent of them were reviewing 1,000 to 2,500 proposals annually.” 

Most IRBs appear to be struggling to keep up with these demands. In increasingly 

competitive environments where market developments are triggering greater cost 

pressures on health care institutions, many IRBs report that they have not been able to add 

the staff needed to respond to the demands. At the same time, IRB members, particularly 

in the large medical centers, find themselves increasingly pressured to concentrate their 

time on revenue-generating clinical activities, with the result that voluntary commitments 

to IRB work have become more difficult to meet.32 The IRBs cope with these 

developments, sometimes in innovative ways,33 but with a steady increasing flow of 

protocols to review, the time demands on members continue to mount.34 Summing up 

this situation, one experienced, well-informed IRB official commented: “Many IRBs, 

especially in large institutions, are on the verge of imploding.” 

These workload pressures jeopardize the protections afforded by IRBs. The General 

Accounting Office provided an alert in this regard when it noted in its 1996 report that 

IRBs may spend only one to two minutes of review per study, relying mainly on reviews 

conducted by primary reviewers prior to a board meeting.” Our own inquiry reinforces 

this concern and makes it especially clear that little time is left for conducting substantive 

continuing review or for educational outreach that can help the research community 

become more knowledgeable about the obligations and importance of human-subject 

protections. Such outreach, IRB officials note, can help ensure that investigators 

themselves serve as a continuing source of protection for human subjects and that 

applications submitted to the IRBs are properly completed. Many IRBs report that they 

spend a considerable amount of time on research protocols and informed consent forms 

that are flawed in various ways and must be sent back to the investigators for corrections. 

9 OEI-01-97-00190 IRBs: Continuing Review 
Limited Useful Feedback on Multi-Site Trials 

More and more of the research being reviewed by IRBs is part of national or even 

international multi-center trials funded by the Federal government or commercial 

sponsors.36 Many are vast, far-reaching operations. For example, the Pediatric Oncology 

Group funded by the National Cancer Institute conducts trials through more than 1,000 

researchers from over 100 sites in the U.S., Canada, and a few as far away as Europe.” 

Each of our study sites reported significant increases in the number of multi-center trials. 

At two sites, these trials constitute about one-half of the research overseen by the IRB.38 

These trials typically include an active monitoring component. For instance, since 1992, 

some of the cooperative-group projects funded by the National Cancer Institute (NCI) 

have required a Data Safety Monitoring Board (DSMB).39 These are independent bodies 

that include scientists expert in the area being investigated, statisticians, ethicists, and 

sometimes subject advocates. Their role is to analyze study data on a regular basis and to 

ensure patient safety through the analysis of adverse-event reports among other things. 

Many commercially sponsored trials also include DSMBs, especially if they involve large 

numbers of subjects. In these cases, however, there is no Federal requirement for a 

DSMB. 

The monitoring of multi-site trials also tends to involve on-site reviews. Sites 

participating in cooperative-group projects funded by the National Cancer Institute must 

be audited once every 36 months.40 These are highly substantive audits typically 

involving scientists, statisticians, and others. Other federally funded cooperative groups 

have similar requirements. Commercial sponsors also have an on-site review component 

(according to FDA requirements).4’ 

These monitoring efforts by DSMBs and audit teams represent substantive ongoing 

oversight of IRB-approved research. But, strikingly, little of what is learned is shared 

with IRBs. Neither the DSMBs nor the audit teams report their findings to the IRBs.~~ 

Their orientation and feedback is to the research sponsors and investigators. Only rarely 

do any of the results of this valuable peer review get to the IRBs to support their own 

continuing review responsibilities.43 

Limited Feedback on FDA Actions Taken Against Investigators 

The FDA conducts routine and directed inspections of research investigators. Directed 

inspections may be initiated as a result of complaints from subjects or others about 

human-subject violations, concerns about an investigator, or questions that arise from a 

review of the study data. Inspections can result in a variety of actions, such as the 

rejection of study data, letters to an investigator, or, at the extreme, a disqualification 

from participating in pre-market research. The FDA does not, on a routine basis, 

affirmatively disclose all correspondence to sponsors and IRBs. A number of IRB 

officials pointed this out to us and reported instances in which they heard about an FDA 

action indirectly, from other (often media) sources, about an action taken against a 

10 OEI-01-97-00190 IRBs: Continuing Review 
research investigator involved in one of their approved research plans. Officials at FDA 

indicated that legal restrictions under the Privacy Act preclude FDA from routinely 

disclosing all investigator-related correspondence to sponsors and IRBs on a routine 

basis. However, certain information, such as warning letters purged of trade secrets and 

confidential commercial information and the names of disqualified or restricted 

investigators, are available to the public on the FDA web site. In addition, certain 

information about the inspections, including classifications of FDA’s inspections, is 

available to the public through the Freedom of Information Act (FOIA). But overworked 

IICE& generally do not have the available time to regularly scan the web site to see if any 

of their investigators, often numbering in the hundreds, have been disciplined. Likewise, 

they might not know when to make a FOIA request to FDA about one of their 

investigators. The FDA is in the process of seeking approval to modify the relevant 

Privacy Act systems notice so that the sharing of this information with IRE& and sponsors 

will be made easier. 

Limited IRB Expertise 

The IRBs find that they often do not have sufficient scientific expertise on their boards to 

deal with the increasingly complex areas of research. They also often lack staff to 

adequately assessthe results of an active protocol. In contrast, the expertise represented 

on a DSMB or audit team tends to be geared specifically, at least in part, to the protocol 

under review. From time to time, IRBs will seek consultant assistance to fill the gap, but 

this can be costly and slow down a review process that is already overburdened. This 

deficiency is a significant source of concern to a number of IRB officials we met with. 

For the cooperative and commercial projects subject to peer review, these officials at least 

know that substantive continuing review is occurring in other places. But for the 

significant amount of IRB-approved research for which no such peer review takes place, 

this safety net does not exist. 

Limited Nonscientific, Noninstitutional Input 

The HHS and FDA regulations require that all IRBs have a minimum of five members. 

The regulations further stipulate that there be at least one member whose primary 

concerns are nonscientific and one who is not affiliated with the parent institution. 

Boards can satisfy both requirements with the appointment of a single individual who is 

not affiliated with the institution and who is not a scientist. The IRBs we spoke with 

typically had more than five members but seldom maintained a 1 to 5 ratio of “outside” 

members.44 More importantly, few seem to seek or be able, on a consistent basis, to 

recruit and maintain lay and/or nonaffiliated members who play an active, effective role 

in helping the IRB stay closely attuned to the perspectives and experiences of human 

subjects. Such members, once sufficiently experienced and trained, can provide an 

important counterbalance to scientific and institutional interests. This may be especially 

important during the continuing review process when important questions (including how 

the informed consent process is approached, whether human subjects understand 

11 OEI-01-97-00190 IRBs: Continuing Review 
sufficiently the risks associated with the research, and the adequacy of outreach efforts to 

diverse populations) can be raised concerning the interests of human subjects. 

The Trust Factor 

The IRB process is rooted in trust. The IRB reviews traditionally have been approached 

in a collegial manner assuming the best of intentions on the part of researchers and 

sponsors. This tradition makes substantive IRB continuing review suspect at best and 

counterproductive at worst. As one IRB member said: “Our job is to ensure humansubject protections upfront; we are not watchdogs.” Many IRB officials and much of the 

literature on IRBs warn that any movement toward “policing” could undermine the 

credibility that IRBs have developed over the yearsP5 These considerations are extremely 

important. The trust that exists is a strength of the system. Any erosion in it could, 

indeed, threaten human-subject protections. 

Yet, in subtle, but significant ways, this tradition of trust inhibits effective continuing 

review. It inhibits IRBs from identifying deviations in approved research plans, as we 

found in our previous study on investigational medical devicesc6 or from learning that 

many human subjects have little understanding of the informed consent forms they sign, 

as the Advisory Commission found in its 1995 review;47 or from finding maverick 

researchers who have not even submitted their research for IRB review, as one IRB found 

through the use of computer-assisted literature monitoring.48 How to achieve substantive 

continuing review along the lines represented by these examples while maintaining a core 

of trust with the research community may well be the most significant challenge facing 

IRBS. 

Federal Oversight of IRBs Provides Little Basis for Determining the 

Effectiveness of IRBs’ Continuing Review of Approved Research. 

As noted in our IRB primer on page 3, two agencies in the Department of Health and 

Human Services are responsible for the oversight of IRBs: the National Institutes of 

Health (NIH) through the Office for Protection from Research Risks (OPRR) and the 

Food and Drug Administration (FDA). These two agencies enforce what is essentially a 

common set of regulations. Appendix B provides an overview of their oversight 

mechanisms. 

The OPRR Oversight Focuses on Upfront Assurances. Only Rarely Does Its Oversight 

Involve On-site Assessments of IRB Performance. 

In the early years of Federal oversight, the assurance documents were relatively brief and 

the process of negotiating them was highly educational in nature!9 Over the years as the 

number of assurances (especially single project assurances) has grown and as IRB 

workloads have increased, the assurance documents have become much more extensive 

and the process more routinized. At present, the overall value of this process remains 

12 OEI-01-97-00190 IRBs: Continuing Review 
questionable. In institutions with multiple project assurances (MPAs), where about 75 

percent of NIH-funded research takes place, many of the IRB officials we spoke with 

reported that the assurance process does little to foster institutional commitments to IRB 

operations. At the same time, OPRR officials recognize that if they were to use this 

process to press for further institutional commitments to IRBs, the institutions might be 

much less likely to include all non-HHS funded research under their assurance. 

This assurance process, as it now functions, does not yield much information about the 

actual effectiveness of IRBs in providing continuing protections to subjects enrolled in 

approved protocols. The OPRR is in much better position to obtain such information 

when it conducts on-site reviews, either as part of a technical-assistance visit or 

noncompliance investigation. Indeed, the most substantive assessments of performance 

and the most forceful recommendations for improving performance that we have 

identified during our inquiry have occurred as part of investigations of IRBs that have 

been responsible for and/or involved in a significant and highly publicized lapse in 

human-subjects protections. Yet, OPRR informs us that because of resource limitations it 

conducted only one such visit between April 1997 and May 1998. Its investigations, of 

which about 75 are open at the current time, are almost always conducted from a distance. 

The FDA Oversight Focuses on Inspections. Its Reviews, However, Stress Procedural 

Compliance, with Only Minimal Attention Given to IRB Effectiveness. 

The FDA estimates that there are about 1,500 to 1,700 IRBs involved in reviewing 

research of FDA-regulated products, mostly pharmaceuticals.50 For this universe of IRBs, 

which includes most of the IRBs having assurances with OPRR, FDA conducts periodic 

inspection visits. In 1997, the FDA conducted just under 200 site visits (see appendix B). 

They are carried out by FDA inspectors who also have responsibilities for inspections 

focusing on food products, research sponsors, and even investigators. 

The on-site inspections focus almost entirely on determining IRB compliance with FDA 

regulations. They involve some interviewing of IRB leadership, but mainly a review of 

IRB records, including those of three IRB-approved studies. They examine the IRB’s 

conformance to discrete Federal mandates concerning matters such as attendance at board 

meetings, completeness of board-meeting minutes, annual protocol reviews, and informed 

consent forms. These and many other compliance issues examined can be important 

indicators of IRB performance, but they provide FDA with little direct feedback on the 

actual effectiveness of the IRB in protecting human subjects. For instance, FDA has 

issued an information letter to IRBs calling for them to make sure that individuals 

understand what they are consenting to when they agree to participate in a research effort. 

Yet, the FDA’s inspection process affords it little basis for determining if such 

understanding takes place; nor does it even review the adequacy of the IRB’s own 

mechanisms for making such a determination. 

The IRB inspections often do result in deficiency notices to the IRB. The most frequent 

of these concern inadequate compliance with various written procedures and with 

13 OEI-01-97-00190 IRBs: Continuing Review 
continuing review procedures. Most of these are not regarded by FDA as being of major 

significance and thus result in a request to the IRE3to take corrective action. In those 

instances where FDA identifies what it regards as a significant deficiency, it issues a 

warning letter to the IRB. The warning letter calls for an immediate IRE3response to 

FDA, spelling out how the identified problem will be corrected. 

14 OEI-01-97-00190 IRBs: Continuing Review 
The IRBs’ limited efforts in conducting continuing review of active research is a serious 

national issue because it compromises their protection of human subjects. It inhibits their 

capacity to identify and address situations where unacceptable risks emerge, or research 

results prove to be too favorable to continue, or protocols stray beyond approved 

parameters. The IRBs may not be vigilant enough to notice and to intervene on behalf of 

the subjects. It also inhibits their capacity to ensure that the subjects have adequate 

understanding of informed consent forms they have signed and that they recognize the 

distinctions between research and established therapy. 

In offering this conclusion, we do not claim that widespread abuses exist. We recognize 

the important contributions that IRBs have made and continue to make. The system of 

protections they provide revolves around the participation of many conscientious 

investigators committed to protecting human subjects and many dedicated IRB members 

and staff doing their best under trying circumstances. But, our inquiry provides an 

important warning signal, especially given the scope of the changes occurring in the IRB 

environment. These include current Federal plans to raise the level of NIH funding, 

which would significantly increase the number of human subjects participating in clinical 

trials, and proposals to give IRBs increased responsibility in the areas of genetic testing 

and confidentiality.51 The signal we present warrants careful attention and a Federal 

response. In our summative report, Institutional Review Boards.. A Time For Reform, we 

present recommendations on how the National Institutes of Health and the Food and Drug 

Administration could respond to the findings presented in this report and that emerge 

from our overall inquiry. 

15 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX A 

Federal Requirements on IRB Continuinp Review 

Institutional review boards’ role in protecting human subjects does not end after the 

completion of an initial review. An IRB is responsible for reviewing, and has the 

authority to monitor, a research protocol from the time of approval onward--until the 

close of the study. The Department of Health and Human Services, through the auspices 

of both OPRR and FDA, has specific requirements concerning how this review should be 

conducted.’ These are specified in the regulations and elaborated on in various agency 

issuances such as OPRR’s “Dear Colleague” letters and FDA’s information sheets. The 

regulations are intended to be used as minimum requirements and IRBs are encouraged to 

impose greater protections as they see fit. 

The continuing review process is multifaceted and involves both an annual review by the 

IRB and the ongoing review of amendments, modifications, and adverse event reports as 

they are received. What follows is a brief description of the elements of this process. 

Continuing Review 

A continuing review must be completed at “intervals appropriate to the degree of risk, but 

not less than once per year.“2 This interval has been interpreted as no less than 12 months 

from the date of initial review.3 The review must be completed by a convened board 

unless the protocol qualifies for an expedited review process. The review should include 

an assessment of the protocol and any amendments/modifications. A status report from 

the investigator containing such information as the number of subjects accrued, 

descriptions of any adverse events or withdrawals of subjects, new information pertaining 

to the study and the current informed consent document should also be reviewed.4 In 

particular, attention should be focused on determining whether the risk-benefit ratio 

remains adequate based on the new information and/or risks that were discovered. 

’ 45 C.F.R., sec. 46 (HHSOPRR) and 2 1 C.F.R., sec. 56 (FDA) 

Currently, 16 Federal departments and agencies abide by these regulations through the 

Common Rule for the protection of human subjects in research, effective August 19, 

1991. 

2Ibid. 

‘OPRR “Dear Colleague Letter”, 10 January 1995, Continuing Review--Institutional and 

Institutional Review Board Responsibilities. 

41bid, FDA Information Sheets, 1995. 

A-l 031-01-97-00190 IRBs: Continuing Review 
APPENDIX A 

Modifications and Adverse Event Reports 

Periodically, the IRB may receive amendments/modifications to active protocols. They 

may include a change in address of a sponsor or something more significant such as a 

change in the actual design of a protocol or eligibility requirements. The ongoing review 

of adverse-event reports is another integral and continuous task for IRBs. An adverse 

event is defined by the FDA as a serious experience by a subject that was not previously 

anticipated in nature or severity. “Serious” events include anything fatal, life-threatening, 

permanently disabling, or requiring in-patient hospitalization. See 21 C.F.R., sect. 3 12 

(for drug research) and 21 C.F.R., sec. 812 (for device research). They must be reviewed 

by the IRB or its representatives who can then require changes to the protocol. The 

required changes most often result in updating the informed consent document to more 

accurately explain risks to subjects. 

Monitoring 

An IRB has the authority to directly observe (or require a third-party to observe) both the 

consent process or the actual research.5 IRBs must also follow written procedures for 

determining which studies require verification from a source other than the investigator 

that no changes have occurred and for ensuring that any changes are not initiated without 

IRB review and approval.6 

’ 45 C.F.R., sec. 46 (HHS/OPRR) 

21 C.F.R., sec. 56 (FDA) 

6 Changes may be initiated before IRB approval if they are necessary to eliminate 

immediate hazards to subjects. See Ibid. 

A-2 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX B 

Federal Oversipht of IRBs 

There are an estimated 3,000-5,000 IRBs across the country. Two agencies within HHS 

are responsible for the oversight of IRBs: OPRR and FDA. Each agency has its own set 

of IRB regulations. Although there are many similarities between the two sets of 

regulations, the agencies’ processes for oversight are markedly different. 

The exact number of IRBs is unknown, in part because of each agency’s relationships 

with IRBs. The OPRR becomes aware of an IRB after an assurance is submitted naming 

the IRB as its source of review. Under a single project assurance (see below), the IRB 

has already reviewed and approved the protocol and the researchers are awaiting NIH 

funding. The FDA’s contact with IRBs comes only at the time of an Investigational New 

Drug or Investigational Device Exemption application. By this time, the IRB has already 

reviewed and approved the protocol and the research is being conducted. Because the 

exact number of IRBs is uncertain, the FDA acknowledges that it is difficult to exercise 

their regulatory oversight. 

Office for Protection from Research Risks (OPRR) 

Assurances 

The OPRR’s oversight of IRBs focuses on an upfront assurance. The assurance is a 

document specifying an institution’s commitment to the human-subject protections 

specified in Federal regulations. It outlines the organization and purview of the IRB in 

addition to its processes for reviewing protocols and other procedural issues. Research 

funded by HHS can only be conducted at a facility holding an assurance with OPRR. 

There are three types of assurances: 

Multiple Project Assurances (MPAs): The MPA allows institutions to conduct any 

number of HHS-funded research projects for an initial period of three years after which it 

can be renewed for 5 year intervals. Regulations require the MPA only for HHS-funded 

efforts, but most of the nearly 450 MPA institutions have extended the protections to all 

research being conducted at their institutions. Though a minority of IRBs hold MPAs, 

these institutions account for nearly 75 percent of NIH-funded research. 

Single Project Assurances (SPAS): For those institutions that do not have the high 

volume of protocols necessary to support the use of an MPA, a single project assurance is 

used. An institution must apply for an SPA for each project it wishes to conduct. This 

presents extra work for the institution as well as OPRR, who must not only review the 

institutional commitments to the IRB and human-subject protections, but also must 

review the research protocol and informed consent documents for each project assurance. 

Currently, there are approximately 3,000 active SPAS. 

B-l OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX B 

Cooperative Project Assurances (CPAs): The HHS funds approximately 25 

cooperative groups which conduct thousands of clinical trials across the country. An 

institution wishing to conduct any of the groups’ protocols that does not have an MPA can 

apply for a cooperative project assurance. The CPA can then be used for any number of 

cooperative projects. Currently, there are approximately 1,500 CPAs. 

The assurance application process is conducted entirely through document transmittals 

and phone communication. An institution wishing to apply for an assurance can receive a 

template from OPRR. After the institution tailors the template to its specific setting, it is 

submitted to OPRR. There, assurance branch officers will review the document.’ Any 

problems or suggestions are worked out through the institutional official(s) and the 

assurance officer before an approval decision is made. 

To ensure compliance, OPRR has the authority to limit, suspend, or withdraw an 

institution’s assurance or require special reporting. 

Investigations 

Compliance investigations are another component of OPRR’s oversight. The OPRR 

conducts investigations primarily on the basis of subject complaints, after becoming 

aware of incidents that appear to have resulted from protection breakdowns or from 

referrals within the department found as a result of audits2 The OPRR reports that the 

focus of the investigations has shifted in the past five years from micro-level to systemic 

solutions. There is no set investigational protocol as the corrective actions are prescribed 

according to the violation and the needs of the IRB. Since 1990, there have been 43 8 

investigations of which 360 are considered complete. However, the great majority of 

investigations occur through paper and phone communication. Only rarely does OPRR 

go on-site. Between 1990 and April 1996, OPRR went on site to investigate compliance 

only 18 times. In fact, OPRR conducted only one such visit between April 1997 and May 

1998 because of staffing problems.3 

‘For an SPA, the protocol and informed consent document must be reviewed as well as 

the assurance template. The OPRR reports that it spends much more time on SPAS even though 

more research projects and more subjects are involved under MPAs. 

2Less frequently, investigations are conducted as a result of suggestions from Congress or 

the media. 

’ “Technical-assistance” site visits are also conducted. These visits are intended to be an 

educational opportunity for IRBs and do not signal noncompliance. Between 1990 and April 

1996, 13 such visits were completed. 

B-2 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX B 

Food and Drug Administration (FDA) 

Inspections 

The FDA’s oversight of IRBs is one of many activities conducted in the process of 

evaluating the safety and effectiveness of the drugs, biologics, and devices it regulates. 

The goal of the monitoring process is to routinely inspect an IRB once every 5 years! 

However, inspections can also be conducted as a part of the product-approval process or 

because of possible noncompliance. There are three centers within FDA that are 

responsible for conducting inspections: Center for Drug Evaluation and Research 

(CDER), Center for Device and Radiologic Health (CDRH), and the Center for Biologics 

Evaluation and Research (CBER). An inspection can be generated by any of the centers, 

but the inspections are carried out by the same group of FDA inspectors in regional 

offices across the country. The following table illustrates FY 1997 data for each of the 

three centers, including the number of inspections and the number of official and 

voluntary actions indicated.5 

FY 1997 Inmection Data 

11Center 1 ft Tnrn~rtinnr 1 ff f3AT 1 

IICBERI 9 13141 n/a I n/a II 

lb= 1 149 I 5 1 124 1 68 1 31 II 

CDRH 36 0 1191 6 i 11 II 

Totals 194 I 8 1 147 1 74 1 42 11 

The inspection guidelines focus on ensuring compliance through the review of IRB 

records and examination of written procedures. Another component of the inspection is 

the tile review of at least three actual research studies approved by the IRB. The files are 

examined to determine such things as a timely continuing review, the use of the most 

current consent documents, the submission and review of adverse-event reports, and for 

4 This is difficult to achieve because of workload constraints; IRBs found previously to be 

significantly deficient are inspected more frequently. 

‘Actions taken are classified according to the strengthen of the action needed to correct 

the deficiencies noted. “Official action indicated” (OAI) is the most serious and warrants FDA 

action. “Voluntary action indicated” (VAI) signifies that the institution will correct the 

deficiencies and often report their progress to FDA at regular intervals. “No action indicated” 

(NAI) is used for inspections which do not reveal any significant deficiencies. 

B-3 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX B 

the presence of a quorum during voting procedures. Based on the results of the 

inspection, FDA has the authority to issue a ‘warning letter’ signifying serious deficiencies 

or enact administrative sanctions. 

Research investigators can also be inspected by FDA. Generally speaking, the inspections 

are designed to ensure data integrity and ensure human-subject protections to the extent of 

whether or not informed consent was signed and dated in a timely manner. 

B-4 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX C 

Advertisinp to Recruit Human Subiects 

When Federal human-subject protections were established in the 1970s a key principle 

was that there should be clear distinctions between research and therapy. Subjects should 

participate in research out of a desire to contribute to generalizable knowledge and they 

should understand that any personal benefits were secondary. Central to their 

participation was an assurance that they understood the risks inherently involved in 

research; their signature on the informed consent document was meant to convey this 

understanding. 

Over the past two decades this distinction has increasingly blurred due to changes in 

subjects’ and the investigators’ perceptions. Many potential subjects have begun to view 

access to research as their best hope for effective therapy and do not want regulators 

inhibiting such access out of a desire to protect them. At the same time, the growth of 

multi-site trials increased the importance of recruiting large numbers of research subjects. 

This, in turn, created increased attention to marketing approaches to attract these potential 

subjects as researchers and their sponsors began to emphasize the personal benefits that 

human subjects could gain from participation in research. An effect of these changes has 

been that the line between research and therapy has become increasingly blurred. As the 

Advisory Committee on Human Radiation Experiments noted: “there is reason to worry 

that participants in research may have unrealistic expectations both about the possibility 

that they will personally benefit from participation and about the discomfort, pain, and 

suffering that sometimes accompany some research.” The committee further stated that 

“it is important that in the informed consent process, it is clearly communicated to the 

potential subject . . .that the primary intent of ‘research’ is to advance medical knowledge 

and not to advance the welfare of particular subjects.“’ 

During the course of our inquiry, we identified and collected many advertisements 

seeking individuals to participate as human research subjects. These advertisements are 

readily accessible to potential subjects, being found in newspapers and on public 

transportation. In a few of these advertisements, even though the study’s experimental 

nature is mentioned, the accompanying language strongly implies that the procedure is 

treatment.* Even when this is not the case, the mention of research is either placed at the 

end of a long list of benefits or is embedded in language so enticing that the inevitable 

risks of research are easily overlooked. The advertisements cite an overwhelming array 

’ Advisory Committee on Human Radiation Experiments, Final Report, Washington DC: 

U.S. Government Printing Office, Chapter 18, Section 2 (1995). 

* It is important to note that research advertisements are not substitutes for the informed 

consent process. Participants must still sign an informed consent document after they contact the 

researchers and agree to participate. 

C-l 031-01-97-00190 IRBs: Continuing Review 
APPENDIX C 

of these benefits (see accompanying box and photos at the end of this appendix). In only 

one study did the advertisers stress the voluntary nature and not personal gain. Much 

more commonly, the 

advertisements supported 

the view that participation in 

research was an opportunity 

for the subject. 

The danger of these 

advertisements is that 

subjects may come to a 

research study with 

misconceptions. For 

example, a person may enter 

into research believing it 

will treat his or her 

depression, panic disorder, 

diabetes, etc. The allure of 

freedom from such an 

ailment is likely to be highly 

motivating. Persons may 

also become attracted to 

research participation by the 

promise of alleviation from 

financial as well as physical 

distress. They may be 

motivated by the promise of 

free treatment, free 

screening, or extra money. 

It is essential, therefore, that 

both the informed consent 

document and the individual 

involved in the recruitment 

of subjects are vigilant in 

making sure the risks 

involved in research are 

clear. But as we have noted 

in this report, IRBs devote 

little attention to how the 

Examples of Marketing Efforts Aimed at Recruiting 

Human Subjects 

DO YOU HAVE ASTHMA? 

If you qualify for any of our asthma studies, you can: 

- Learn to care for your asthma! 

- Receive free medications! 

- Receive up to $1,730! 

Women: Receive $271 O! 

Healthy, non-smoking/drug-free women (20-40) needed 

for USDA research study. Live-in 24 hrs/day for 78 days 

Speed or Cocaine? 

Need help getting clean? 

Free Treatment & Medication. 

Repeat Callers Welcome! !! Get Paid $$$ 

Women With PMS 

If you are between the ages of 18 and 40 and suffer from 

PMS (Premenstrual Syndrome), you may qualify to 

participate in a research study using an investigational 

drug for the treatment of PMS. 

If you qualify to participate you will receive: 

Free Medical Exams Free Pap Smears 

Free Labwork Study Medications 

Up to $455 for Time and Travel 

consent process works, focusing all too often solely on the document’s language. 

c-2 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX C 

The following two photos were taken on a Philadelphia subway car in January 1998. 

Photos courtesy of the OIG Office of Evaluation and Inspections, Philadelphia Regional Office 

c-3 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

ENDNOTES 

1. President’s Commission for the Study of Ethical Problems in Medicine and Biomedical and 

Behavioral Research, Implementing Human Research Regulations: Second Biennial Report on 

the Adequacy and Uniformity of Federal Rules and Policies, and of their Implementation, for the 

Protection of Human Subjects, Washington, D.C.: U.S. Government Printing Office, March 

1983. 

2. For more detailed explanations of these concerns see (a) Nancy E. Kass and Jeremy 

Sugarman, “Are Research Subjects Adequately Protected? A Review and Discussion of Studies 

Conducted by the Advisory Committee on Human Radiation Experiments,” Kennedy Institute of 

Ethics Journal, Vol. 6 (1996), No. 3, pp. 271-82. (b) The Advisory Committee on Human 

Radiation Experiments, Final Report, Washington D.C.: U.S. Government Printing Office, 1995. 

3. U.S. General Accounting Office, Scienttjk Research: Continued Vigilance Critical to 

Protecting Human Subjects, GAO/HEHS-96-72, March 1996. 

4. Department of Health and Human Services, Office of Inspector General, Investigational 

Devices: Four Case Studies (OEI-05-94-OOl OO), April 1995. 

5. The National Bioethics Advisory Commission was established by Presidential executive order 

on October 3, 1995. Its charter, issued in July 1996 by the Assistant to the President for Science 

and Technology, calls for it to focus its attention on: “A. Protection of the rights and welfare of 

human research subjects; and B. Issues in the managements and use of genetics information 

including but not limited to human gene patenting.” 

For some background on the Commission and its emergence, see Alexander Morgan Capron, 

“An Egg Takes Flight: The Once and Future Life of the National Bioethics Advisory 

Commission,” Kennedy Institute of Ethics Journal, Vol. 7, (March 1997) No. 1, pp. 63-80. 

6. These IRBs are reviewing research at institutions receiving over 1.4 billion dollars of active 

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. 

7. 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-intraining. 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.) 

8. These six institutions alone account for over half a billion dollars of active 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. 

D-l OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

9. It is important to note that while the IRB has a key responsibility for protecting human 

subjects, sponsors also have responsibility for the monitoring and oversight. According to 

2 1 C.F.R., sec. 3 12, sponsors are required to ensure proper monitoring of investigations and they 

are also required to select a monitor to oversee investigations through site visits. In addition, the 

sponsor may require reports from investigators. There is, however, little information sharing 

between sponsors and the IRB. 

10. See 45 C.F.R., sec. 46.109(e) and 21 C.F.R., sec. 56.109(e). 

11. Dear Colleague letter from Office of Protection from Research Risks, “Continuing Review-­

Institutional and Institutional Review Board Responsibilities,” 10 January 1995. 

12. FDA Information Sheets, “Continuing Review After Study Approval,” 1 October 1995. 

13. Several factors may contribute to the lack of understanding. In our previous study, where we 

conducted four case studies of medical devices, we found that the reading level of the informed 

consent documents related to each of the four medical devices ranged from college level to 

graduate level ability (Department of Health and Human Services, Office of Inspector General, 

Investigational Devices; Four Case Studies (OEI-05-94-OOl OO), April 1995). Compounding the 

difficult reading level may be deficiencies in the informed consent documents themselves. The 

Center for Drug Evaluation Research, located with the FDA, has found an increasing number of 

deficiencies in informed consent documents at the IRBs it inspected. In 1995, it found 24 

percent of IRBs inspected had informed consent documents deficiencies; in 1996, it found 28 

percent had deficiencies; and in 1997, it found 4 1 percent had deficiencies. 

14. A full and clear understanding of risks is especially important in Phase 1 clinical trials when 

relatively little is known about an intervention’s effect in humans and the aim of the research 

may well be to determine how much of a medication can be tolerated by humans. 

15. Advisory Committee on Human Radiation Experiments, Final Report, Washington, D.C.: 

U.S. Government Printing Office, 1995. 

16. For example, see (a) 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; (b) U.S. General Accounting Office, Scientzjic 

Research: Continued Vigilance Critical to Protecting Human Subjects, GAOIHEHS-96-72, 

March 1996; and (c) Philip J. Hilts, “Psychiatric Research Under Fire,” New York Times, 19 May 

1998. 

17. To a significant degree, we found that research investigators were quite removed from the 

informed consent process. In some of the larger departments, staff are primarily responsible for 

preparing the consent forms. 

18. IRB and Federal officials typically recognize the importance of the interactive process, but 

find the consent form itself as a more practical tool for review purposes. Indicative is the 

following comment of a Food and Drug Administration official in her testimony before 

D-2 031-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

Congress: “It is the interactive information exchange that is most important to the informed 

consent process. FDA focuses on the consent form during our inspections because it is the best 

evidence that we have of the basic information that was exchange during that process.” 

(Oversight of HHS: Bioethics and the Adequacy of Informed Consent, Hearing before the 

Subcommittee on Human Resources and Intergovernmental Relations of the Committee on 

Government Reform and Oversight, U.S. House of Representatives, 8 May 1997, Testimony of 

Mary Pendergast.) 

19. Advisory Committee on Human Radiation Experiments, Final Report, Washington, D.C. : 

U.S. Government Printing Office, 1995: Chapter 16, Section 3. 

20. See (a) Paul McNeil, The Ethics and Politics of Human Experimentation, New York: 

Cambridge University Press, 1993. (b) “Don’t Let It Happen Again,” The Economist, 17 May 

1997, pp. 27-28. (c) Michie Hunt, The FDA: Promoting Access to New Drugs, Biologics, and 

Medical Devices, National Health Policy Forum, The George Washington University, July 1997. 

21. These projects tend to be part of national or even international multi-site projects involving 

research in out-patient settings. They are subject to oversight mechanisms carried out by the 

sponsors themselves. But, they do not tend to have the level of safeguards and monitoring 

typically provided to patients in inpatient settings. 

22. See (a) Keith Epstein and Bill Sloat, “Drug Trials: Do People Know the Truth About 

Experiments?” The Plain Dealer, 15- 18 December 1996, Special Sunday Insert, pp. 2- 16; and 

(b) Oversight of HHS: Bioethics, and the Adequacy of Informed Consent, Hearing before the 

Subcommittee on Human Resources and Intergovernmental Relations of the Committee on 

Government Reform and Oversight, U.S. House of Representatives, 8 May 1997; and 

(c) Steve Stecklow and Laura Johannes, “Drug Makers Relied on Clinical Researchers Who Now 

Await Trial” The Wall Street Journal, 15 August 1997, pp. Al and A6. 

23. Department of Health and Human Services, Office of Inspector General, Investigational 

Devices: Four Case Studies (OEI-05-94-OOl OO), April 1995. 

24. The GAO report also noted the limited attention to continuing reviews. It indicated that in 

their reviews, IRBs relied heavily on investigators’ self-assessments. (U.S. General Accounting 

Office, Scienttfic Research: Continued Vigilance Critical to Protecting Human Subjects, 

GAO/HEHS-96-72, March 1996.) 

25. The situation differs somewhat for the independent IRBs. Board members of these IRBs are 

paid for their time. Whether or not they are any more or less favorable toward annual reviews, 

we do not know. 

26. Each report must be compiled, documented, and reviewed by the IRB. Also, the IRB must 

notify the investigator of any changes. 

27. In its 1996 report, the GAO stated that “IRB reviews generally do not involve direct 

observation of the research study or of the process in which a subject’s consent is obtained.” 

D-3 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

(U.S. General Accounting Office, ScientiJic Research.. Continued Vigilance Critical to 

Protecting Human Subjects, GAO/HEHS-96-72, March 1996.) 

Edgar and Rothman stated that “it is rare for an IRB to leave the confines of its committee room 

and 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.) 

These sentiments are echoed by McNeil in his book. (Paul McNeil, The Ethics and Politics of 

Human Experimentation, New York: Cambridge University Press, 1993, p. 244.) 

28. The National Commission that developed the current system of human protections in the 

1970s envisioned a much more proactive role for IRBs. In its report, it noted that IRBs may 

interview human subjects about their research experience or require that investigators provide 

subjects with a form through which they may report to the IRB their research experiences. It 

cautioned about observing the consent process, but noted that “certain research will warrant 

observation to assure the protection of subjects and in such cases IRBs have an obligation to take 

suitable measures.” It further noted that the documentation of informed consent should not be 

confused with the substance of informed consent and that in certain cases the IRB may well 

require that a neutral party be present to assist a potential human subject considering 

participation in a research effort. (Institutional Review Boards: Report and Recommendations of 

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

Research, 43 Federal Register, 10 November 1978, p. 56174.) 

The IRB regulations, which were adopted in 198 1, provide IRBs with the authority to “observe or 

have a third party observe the consent process and the research (45 C.F.R., sec. 46.109(e) and 

21 C.F.R., sec. 56.109(e)). 

29. Of particular note here is the Federal informed consent requirement which calls for 

investigators to seek informed consent “only under circumstances that provide the prospective 

subject or representative sufficient opportunity to consider whether or not to participate and that 

minimize the possibility of coercion or undue influence.” (See 21 C.F.R., sec. 50.20 and 

45 C.F.R., sec. 46.116) Without any direct observation or feedback by independent parties, it is 

extremely difficult for IRBs to ascertain that such circumstances exist at the time that human 

subjects provide their written consent. 

30. Three sites with 10 year data reported increases of over 80 percent. One reason for the 

escalating numbers may be that investigators, claiming that it is increasingly difficult to receive 

grants, are submitting more research protocols. The NIH requires IRB approval prior to funding 

decisions so IRBs may review a significant number of protocols that will not go on to be funded. 

3 1. Hayes et al., “A Survey of University Institutional Review Boards: Characteristics, Policies, 

and Procedures,” IRB, Vol. 17 (May-June 1996), No. 3, pp. l-6. 

This highlights the importance of academic medical centers to human-subjects research when 

compared to another survey of all hospitals with at least 400 beds which reported an average of 

D-4 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

84 proposals per year. (Jones et al., “Structure and Practice of Institutional Review Boards in the 

United States,” Academic Emergency Medicine, Vol. 3, August 1996, No. 8, pp. 804-809.) 

32. One former IRB member indicated that these pressures are particularly intense on physicians 

whose fields involve a significant amount of patient contact. As a result, IRBs are finding it 

especially difficult to recruit and retain physician members who regularly interact with patients 

and may be more attuned to their concerns. 

33. For a more detailed explanation, see our companion report: Department of Health and 

Human Services, Office of Inspector General, Institutional Review Boards: Promising 

Approaches, OEI-0 l-97-00 191. 

34. These demands apply both to the time spent outside of meetings in reviewing proposals and 

to the time spent during meetings discussing them. 

35. U.S. General Accounting Office, Scientific Research: Continued Vigilance Critical to 

Protecting Human Subjects, GAO/HEHS-96-72, March 1996. 

36. Since the 1950’s trial of poliomyelitis vaccine involving over a million school-age children, 

large randomized clinical trials conducted simultaneously at a network of sites across the country 

have become a standard in determining treatment effectiveness. These multi-center trials are 

becoming even more important as scientists’ and physicians’ knowledge of disease improves. 

Specific subpopulations of patient groups are being identified and are required to test more 

targeted treatments and drugs. Any one institution may only have a few patients in each group, 

rarely enough to statistically determine effectiveness. Therefore, data from small patient groups 

at sites around the country, or even the world, must be combined. 

37. Brad H. Pollock, “Quality Assurance for Interventions in Clinical Trials: Multicenter Data 

Monitoring, Data Management, and Analysis,” Cancer Supplement, Vol. 74, (1 November 1994) 

No. 9, pp. 2647-265 1. 

Furthermore, NIH funding alone for such cooperative group projects has increased almost tenfold in the past decade, from $49.2 million in 1985 to $419.2 million in 1994. (NIH Extramural 

Trends--FY 198.51994). 

Data available on the NIH website at http://www.nih.gov/grants/award/trends94/chapter 1.htm 

38. Multi-center trials may represent even larger percentages of active research at smaller 

institutions that do not have the patient base to support single-investigator studies. 

39. There are 11 cooperative research groups associated with NC1 alone. Each is a formal, freestanding entity which has its own board of directors, but is responsible for following federal 

guidelines. Each cooperative group oversees multiple protocols, ranging in number from 20 to 

well over 100. Other institutes at the NIH also have cooperative research groups with which they 

are associated. 

D-5 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

40. Approximately 700 to 800 audits of project sites are conducted annually. As another 

example, the Division of AIDS at the National Institute of Allergy and Infectious Disease at NIH 

contracts with a CR0 to monitor, four times a year, each clinical site it sponsors. 

41. Beyond these, some academic health centers, particularly in their cancer programs, are 

carrying out their own audit component. See the section entitled “Management of the Workload” 

in our companion report: Department of Health and Human Services, Office of Inspector 

General, Institutional Review Boards: Promising Approaches, OEI-0 l-97-00 191. 

42. The IRB at one large academic health center we visited reported that it has regularly been 

requesting DSMB data from the research sponsors and to this point has not been refused access 

to the data. We have not heard of others making such requests and having similar success. 

43. From time to time, the DSMBs and audit teams associated with cooperative-group projects 

will provide some information to OPRR if they have information they find to be particularly 

relevant to the IRB. The OPRR will then share the information with the IRB. Similarly, from 

time to time, some investigators or sponsors will share with the IRBs information or instructions 

they received from the DSMBs or audit teams. 

44. The IRB regulations require that “each IRB shall include at least one member who is not 

otherwise affiliated with the institution and who is not part of the immediate family of a person 

who is affiliated with the institution.” Since 1994, the FDA’s Division of Scientific 

Investigations in CDER began to put forth in some post-inspection letters and a few conference 

presentations the benefits of interpreting this regulation as a ratio. 

The independent IRBs tend to have more “outside” review members on their boards. While 

these members are paid for their review services, the great majority are not otherwise affiliated 

with the IRB or its parent institution and many are nonscientific members. 

45. “The presumption that informs the current so-called monitoring activities of most IRBs is 

that members of the institution are to be trusted until some contrary evidence is brought forward. 

If the IRB is obliged to function as a police force, it can only indicate to the community of 

investigators that it is operating from presumptions of distrust. Presumptions of distrust cost a 

lot of time and energy of IRB members, most of whom have no training in police work in the 

first place.” (Robert J. Levine, Ethics and Regulation of Clinical Research, Baltimore: Urban & 

Shwarzenberg, 1986, p. 348-349.) 

46. Department of Health and Human Services, Office of Inspector General, Investigational 

Devices: Four Case Studies (OEI-05-94-OOlOO), April 1995. 

47. See Advisory Committee on Human Radiation Experiments, Final Report, Washington, 

D.C.: U.S. Government Printing Office, 1995: Chapter 16, Section 3. 

48. For more information see Department of Health and Human Services, Office of Inspector 

General, Institutional Review Boards: Promising Approaches, (OEI-01-97-00 191). 

D-6 OEI-01-97-00190 IRBs: Continuing Review 
APPENDIX D 

49. The National Service Research Award Act of 1974 established the assurance as the primary 

mechanism by which the Department was to oversee research involving human subjects. 

(National Service Research Award Act of 1974, P.L. No. 93-348, sec. 474, 88 Stat. 342.) 

50. IRBs subject to FDA oversight only become known to the agency after an IND or IDE has 

been filed. Thus, the IRB has been operating for some time before the FDA becomes aware of its 

presence. The FDA has told us that the uncertainty in the number of IRBs subject to regulatory 

oversight is part of the problem in exercising that oversight. 

5 1. According to the President’s Budget for Fiscal Year 1999, the NIH, which is the flagship of 

the President’s Research Fund for America, would be increased by nearly half over five years. 

For more discussion, see Robert Pear, “Medical Research To Get More Money From 

Government,” New York Times, Saturday, 3 January 1998, pp. Al and A8. 

The Task Force on Genetic Testing calls for placing greater emphasis on the role of the IRB in 

evaluating genetic research protocols for the development of genetic protocols. (Eds. Neil A. 

Holtzman, and Michael S. Watson, Promoting Safe and Effective Genetic Testing in the United 

States: Final Report of the Task Force on Genetic Testing, NIH-DOE Working Group on Ethical, 

Legal, and Social Implications of the Human Genome Research, September 1997.) In addition, a 

recent Senate bill, S. 1921, would rely on the IRB to determine measures of confidentiality, such 

as whether subject identifiers should be retained. (S. 1921, 105’h Congress, sponsored by 

Senators Jeffords and Dodd) 

D-7 OEI-01-97-00190 IRBs: Continuing Review