Department  of  Health  and  Human  Services 
OFFICE  OF 
INSPECTOR  GENERAL 
Institutional  Review  Boards: 
The  Emergence  of Independent  Boards 
JUNE GIBBS BROWN 
Inspector  General 
JUNE 1998
-
031-01-97-00192  OFFICE  OF INSPECTOR  GENERAL 
The mission  of the Office  of Inspector  General (OIG),  as mandated by Public  Law  95-452,  is to 
protect the integrity  of the Department  of Health and Human  Services programs  as well  as the 
health and welfare  of beneficiaries  served by them.  This statutory  mission  is carried out through 
a nationwide  program  of audits, investigations,  inspections,  sanctions, and fraud alerts.  The 
Inspector  General informs  the Secretary of program  and management problems  and recommends 
legislative,  regulatory,  and operational  approaches to correct them. 
Office  of Evaluation  and Inspections 
The Office  of Evaluation  and Inspections  (OEI)  is one of several components  of the Office  of 
Inspector  General.  It conducts  short-term  management and program  evaluations  (called 
inspections)  that focus on issues of concern to the Department,  the Congress, and the public.  The 
inspection  reports provide  findings  and recommendations  on the efficiency,  vulnerability,  and 
effectiveness of departmental  programs. 
OEIs Boston  regional  office  prepared this report under the direction  of Mark  R. Yessian, Ph.D., 
Regional  Inspector  General.  Principal  OEI staff included: 
REGION  HEADOUARTERS 
Dana M. Miller  Lisa Foley 
Nathan P. Rouillard 
Elizabeth  A. Robboy 
Laura C. McBride 
To obtain copies of this report, please call the Boston Regional Office at (617)565-1050. 
Reports are also available  on the World  Wide Web at our home page address: 
http://www.dhhs.gov/progorg/oei  EXECUTIVE  SUMMARY 
PURPOSE 
To describe the role of independent  institutional  review  boards in ensuring  protections  for 
human subjects of clinical  research. 
BACKGROUND 
Role of Institutional  Review  Boards 
Institutional  review  boards (IRBs)  play vital roles in protecting  human research subjects. 
They review  initial  research plans to make certain that the plans provide  subjects with 
adequate opportunity  to give their 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. 
Over the past 25 years, thousands of IRBs  have formed to help ensure human-subject 
protections.  At first, most were in large academic centers, where most of the federally 
funded research still  occurs.  As research spread to other settings and as commercially 
sponsored research increased, IRBs  arose in different  environments  such as community 
hospitals,  managed care organizations,  and government  agencies.  A few emerged as 
independent  entities working  outside of institutions  where research is performed. 
Independent  Boards:  The Focus  of This  Report 
This report focuses on independent  IRBs,  about which  little  has been published.  One of 
4 reports we are issuing  on IRBs,  it draws primarily  on the interviews  we held with 
representatives  of 11 independent  IRBs.  In addition,  it relies on information  gathered 
from interviews  and group discussions with  representatives  of about 60 other IRBs;  site 
visits to 6 IRBs;  reviews  of Federal records; and attendance at IRB  meetings. 
FINDINGS 
Independent  IRBs  Are  Playing  an Increasingly  Prominent  Role  in the Research 
Community. 
While  There  are Relatively  Few  of Them,  Their  Number  has been Growing. 

Although  one dates back to 1968, most were established  in the 1980s and 90s.  It appears 

that at least 15, and perhaps quite a few more, are now operating. 

1  031-01-97-00192  Independent  IRBs  They  Oversee  an Increasing  Number  of Research  Plans.  In the last 2 years, 
independent  IRBs we contacted  reported  an average increase of approximately  36 percent 
in initial  protocols  reviewed.  The largest and oldest of the independent  IRBs  reviewed 
more initial  protocols  in 1997 than did many IRBs  in academic health centers. 
They  are Now  Reviewing  HHS-Sponsored  Research.  Prior to 1995, all such research 
was being overseen by IRBs  at the institutions  where the research occurred.  In that year, 
some HHS  grantees first gained Federal approval  for an independent  board to serve as 
their IRB.  At present, independent  boards are responsible  for at least 12 HHS-funded 
projects. 
They  are Becoming  More  Involved  with  Hospital-Based  Research.  Some act as the 
IRB  of record for hospitals.  Some provide  consultation  to hospital-based  IRBs.  One has 
contracted  with  a major medical  center to review  all commercially  sponsored protocols 
for that centers IRB. 
Independent  IRBs  Offer  Advantages  That  Institutional  IRBs  Find  Difficult  to 
Match. 
They  Are  Geared  to Quick  Decisions  on Research  Plans.  Independent  IRBs  are 
organized  to respond to commercial  sponsors  expectations  for timely  reviews.  On 
average, those we interviewed  reported  that they could provide  initial  research protocol 
decisions in about 11 days.  For the academic health centers we reviewed,  the average 
was about 37 days. 
They  Provide  a Detached  Source  of Expertise.  Independent  IRBs  are not affiliated 
with  the institutions  whose research they review  and are unlikely  to have collegial 
relationships  with  the investigators.  This detachment  facilitates  research plan review 
without  institutional  or collegial  biases. 
They  Can  Provide  Unified  Reviews  for  Multi-Site  Trials.  For such trials,  an 
independent  IRB  can serve as a single entity  reviewing  the applicability  of a specific 
research plan to various  sites.  This eliminates  the complications  that result from multiple, 
local IRB  reviews.  It also facilitates  analysis of adverse-event reports from various  sites. 
Yet,  The Use of Independent  IRBs  Raises Concerns. 
They  Are  Not  Local  Review  Bodies.  Local  review  is a long-established  principle  of 
human-subject  protection.  Familiarity  with  the conditions  of the institution,  the 
investigators,  and the local community  have been viewed  as vital to effective  human-
subject protection.  Concerns  about independent  IRBs  ability  to provide  local review 
have inhibited  their participation  in federally  sponsored research.  The independent  IRBs 
ii 
OEI-01-97-00192  Independent  IRBs  have sought to ease such concerns by keeping  abreast of the research sites circumstances 
through  site visits, local contacts, newspaper  clipping  services, and other means. 
They  May  Be Subject  to Conflicts  of Interest.  Some IRB  officials  are concerned that 
independent  IRBs,  almost all of which  are for-profit  enterprises, may compromise  the 
review  process to please their sponsors/customers  and to advance their financial  well-
being.  Yet, these officials  also express concern that in an increasingly  competitive 
environment,  all IRBs  are subject to conflicting  pressures that could compromise  their 
core mission. 
They  Heighten  Concerns  about  IRB  Shopping.  Sponsors who are unhappy  with  the 
reviews  of one independent  IRB  may seek out another that they expect to be more 
accommodating.  The independent  IRBs themselves may not know  if a sponsors  research 
plan has been turned down,  or found  lacking,  by another IRB. 
CONCLUSION 
We offer two  concluding  observations  that have broad significance  for the Federal system 
of human-subject  protections. 
First, independent  IRBs have become a noteworthy  part of the IRB  landscape.  They 
provide  some competition  to IRBs  in academic health centers and other settings and, in so 
doing,  contribute  to a marketplace  ethic--one  that is quite different  from that 20, or even 
10 years ago.  This development  presents opportunities  in that it encourages more timely 
and innovative  approaches to review.  At the same time, competitive  pressures on IRBs 
present dangers that can compromise  human-subject  protections. 
Second, independent  IRBs raise important  questions  for Federal oversight.  How  can the 
Federal government  best ensure that independent  IRBs  help protect human research 
subjects?  That the emerging  competition  does not compromise  safeguards?  That 
independent  IRBs  advantages and efficiencies  are not undercut  by unnecessary Federal 
regulation?  Such questions underscore the importance  of understanding  the effectiveness 
of IRBs--whether  they are independent  or part of research organizations.  We address this 
matter in our summary report, Institutional  Review Boards.. A Time For Reform. 
COMMENTS  ON THE  DRAFT  REPORTS 
Within  the Department  of Health  and Human  Services, we received comments on our 

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

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

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 

. . . 

111  OEI-01-97-00192  Independent  IRBs 
 Boards, and Public  Citizens  Health  Research Group.  We include  the detailed text of all 
of these comments and our responses to them in appendix  D of our overview  report, 
Institutional  Review Boards:  A Time for  Reform (OEI-01-97-00193).  In the executive 
summary of that report, we summarize  the thrust of these comments and our responses. 
IV  OEI-01-97-00192  Independent  IRBs  PAGE 
EXECUTIVE  SUMMARY 

INTRODUCTION  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .._......... 
 ...............  1 
IRBs:  THE  BASICS  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 
 ...............  3 
FINDINGS 

Independent  IRBs  are Playing  an Increasingly  Prominent  Role  . . . . 
 ...............  4 
They Offer Advantages  to Research Sponsors . . . . . . . . . . . . . . . . . . 
 ...............  5 
They Raise Concerns  . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 
 ..............  6 
CONCLUSION  . . . . .._...........................__........... 
 ...............  8 
APPENDICES 

A:  Endnotes............................................ 
 . . . . . . . . . . . .  A-l 
OEI-01-97-00192  Independent  IRBs  INTRODUCTION 
PURPOSE 
To describe the role of independent  institutional  review  boards in ensuring  protections  for 
human subjects of clinical  research. 
BACKGROUND 
On page three we provide  a primer  on institutional  review  boards (IRBs).  We explain 
why  they were established, what roles they perform,  how they are organized,  where they 
are located, and how the Department  of Health  and Human  Services (HHS)  oversees 
them. 
A number  of studies of IRBs have been undertaken,  the most thorough  of which  was 
published  in 1978.  Since then, 
however,  sweeping  changes have 
transformed  the economics  and  IndeDendent  IRBs 
organization  of clinical  research.  An 
These boards are not part of any organization  in 

increase in the commercial  funding  of 
which  research is conducted. 

clinical  research has changed the 
culture  of research and has driven the  They are hired by research sponsors (most often 

demand for independent  IRBs.  pharmaceutical  and device manufacturers)  and 

Research has evolved from the single- investigators  to review  research plans. 

site model--with  one hospital-based 
Most are for-profit  entities. 

clinical  investigator  and a few 
subjects--to  multi-site  projects  Some are owned by other organizations  (such as 

involving  numerous private-practice  or  contract research organizations  that place 

clinic-based  physicians  and,  clinical  studies for research sponsors). 

sometimes, thousands of subjects2 
Some offer consultation,  training,  and other 

services in addition  to traditional  IRB services. 

In the midst of the many changes that 
are transforming  the clinical  research  Board members are paid for their work,  either 

environment,  a renewed interest in  on a per-meeting basis, an hourly  basis, a per-

protocol-reviewed  basis, or some combination 

human-subject  protections  and the role 
thereof. 

of the IRB  has arisen.  A  1995 report 
issued by the Institute  of Medicine 
(IOM)  called for an examination  of the effectiveness  of the IRB  system?  Another  1995 
report,  issued by a Presidential  advisory  committee,  raised a number of concerns about 
the performance  of IRBs!  A  1996 report  from the U.S. General Accounting  Office 
suggested that continued  vigilance  over human subject research should remain  a priority 
for the research community  and agencies charged with  oversight.5  The National 
1 
OEI-01-97-00192  Independent  IRBs  Bioethics  Advisory  Commission  is examining  the current  state of human-subject 
protections  and has pursued information  about IRBs.~  These and other reviews,  however, 
have given only passing attention  to independent  IRBs. 
This  Inquiry  and This  Report 
This report, which  is one of four that we are issuing  on IRBs,  focuses on the independent 
IRBs.  It describes their growing  presence and the major  advantages and disadvantages 
attributed  to them.  The report is designed to complement  its three companion  reports. 
One, Institutional  Review Boards:  Their Role in Reviewing  Approved  Research, finds that 
IRBs  devote minimal  attention  to continuing  review  and identifies  key obstacles to such 
review.  Another,  Institutional  Review Boards.. Promising  Approaches,  presents 
innovative  efforts that IRBs  have undertaken  in six key areas of responsibility.  A third, 
Institutional  Review Boards:  A Time For  Reform, provides  a summary  of IRB  functioning 
and presents recommendations. 
Our inquiry  draws on a variety  of sources.  Of particular  relevance to this report were our 
interviews  with  independent  IRB  officials.  We held a group  discussion  with  members of 
the Consortium  of Independent  IRBs  (CIRB)  and conducted  telephone  interviews  with 
representatives  of the 10 IRBs that are CIRB  members and 1 independent  IRB  that is not 
a CIRB  member.  We also drew on interviews  and group discussions  with  representatives 
of about 60 additional  IRBs;~ 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. 
We conducted this inspection  in accordance with  the Quality  Standards for  Inspections 
issued by the Presidents  Council  on Integrity  and Efficiency. 
2 
OEI-01-97-00192  Independent  IRBs   INSTITUTIONAL  REVIEW  BOARDS:  THE  BASICS 
What  Do They  Do? 
The responsibilities  of IRBs fall  into two main categories: initial  review  and continuing  review  of research 
involving  human subjects. 
Initial  Review:  IRBs review  and approve a research plan before the research is carried out.  This review 
encompasses the research protocol,  the informed  consent document to be signed by subjects, any 
advertisements to be used in recruiting  subjects, and other relevant  documents.  In carrying  out this review, 
the boards seek to ensure that any risks subjects may incur are warranted  in relation  to the anticipated 
benefits, that informed  consent documents clearly  convey the risks and the true nature of research, that 
advertisements are not misleading,  and that the selection of subjects is equitable and justified.  IRBs focus 
much attention on the informed  consent document because it is the vehicle  for providing  information  to 
potential  research subjects. 
Continuing  Review:  The continuing  review process is multifaceted  and includes required reviews at an 
interval  appropriate to the degree of risk but not less than once per year.  In addition  to this continuing 
review,  study amendments and reports of unexpected adverse experiences by subjects are received 
periodically  and reviewed  to ensure that the risk-benefit  ratio of the research has not changed and remains 
acceptable. 
Why  Were  They  Established? 
As public  awareness and concern about the treatment of human subjects in research increased, the need for 
additional  review  mechanisms was evident.  These concerns grew from stories of the abuse of subjects during 
the World War II trials at Nuremberg,  the promotional  distribution  of thalidomide  resulting  in numerous 
children  born with  birth defects, the administration  of cancer cells to chronically  ill  and senile patients at a 
hospital  in New York,  and others.  A 1966 article by Henry  Beecher brought prominent  attention to human 
research abuses in medical schools and hospitals citing  22 cases involving  highly  questionable ethics.  The 
formal requirements for the establishment of IRBs were outlined  in regulations  stemming from the National 
Research Act of 1974 and in FDA regulations  issued in 1981. 
Where  Are  They  Located? 
An estimated 3,000-5,000  IRBs can be found across the country.  They are most commonly  associated with 
hospitals and academic centers.  Boards also exist in managed care organizations,  government  agencies (such 
as the National  Institutes  of Health, the Centers for Disease Control,  and State governments),  or as for-profit 
entities that are independent of the institutions  in which  the research takes place. 
How  Are  They  Organized? 
Federal regulations  require that boards have at least five members with  varying  backgrounds.  At least one 
member must have primarily  scientific  interests, one must have primarily  nonscientific  interests, and one must 
be otherwise unaffiliated  with  the institution  in which  the IRB resides.  A quorum, with  at least one member 
whose interests are primarily  nonscientific  present, is needed for voting. 
How  Does  the  Department  of Health  and  Human  Services  (HHS)  Oversee  Them? 
Two agencies within  HHS share responsibility  for IRB oversight:  the Office  for Protection from Research 
Risks (OPRR) in NIH  and the FDA.  The OPRRs main tool for oversight  is the assurance document.  Any 
institution  that intends to conduct HHS-funded  research must have an assurance on file with  OPRR.  The 
assurance is a written  statement of an institutions  requirements  for its IRB and human-subject  protections. 
Institutions  consistently  conducting  multiple  HHS-supported  studies are eligible  for a multiple  project 
assurance (MPA)  which  can be renewed every five years.  Institutions  with  smaller HHS-funded  workloads, 
however,  use a single project assurance (SPA) for each such project it conducts.  The OPRR also conducts a 
small number of site visits.  The FDAs  main mechanism for IRB oversight  is the inspection  process. The 
FDA also inspects research sponsors and scientists (known  as research investigators). 
3  OEI-01-97-00192  Independent  IRBs  FINDINGS 

Independent  IRBs  are Playing  an Increasingly  Prominent  Role in 
the Research Community. 
While  There  are Relatively  Few  of Them,  their  Number  has been Growing. 
The exact number of independent  IRBs  is not known,  but the Consortium  of Independent 
IRBs  estimates that there are at least 15, and perhaps quite a few more.  While  1 of these 
independent  IRBs  dates to 1968, at least 10 were established after 1980, and 4 of these 
were established after 1990.  The increasing  number  of independent  IRBs  parallels  an 
increasing  number of research protocols  being put forward  by commercial  sponsors.8 
They  Oversee  an Increasing  Number  of Research  Plans. 
The number of research plans that the independent  IRBs  review  is considerable  and 
growing.  In the last 2 years, independent  IRBs  we contacted reported  an average increase 
in initial  reviews  of approximately  36 percent.  In 1997, the independent  IRBs  we 
surveyed conducted  an average of 256 initial  reviews.  The largest and oldest of them 
reviewed  over a 1,000 initial  protocols  and conducted  over 4,000 continuing  reviews  in 
1997, a caseload comparable  with  many IRBs  in academic health centers. 
The great preponderance  of the research that independent  IRBs  oversee is sponsored by 
either pharmaceutical  or device manufacturers  and is conducted  in physician  offices 
outside of hospitals,  medical  clinics,  or commercial-research  facilities.  A growth  of 
research in such independent-investigator  sites has contributed  to the increase in the 
number of protocols  that these IRBs  review. 
They  are Now  Reviewing  HHS-Sponsored  Research. 
Independent  IRBs  are increasingly  being used for HHS-funded  clinical  studies.  In these 
cases, a research institution  must obtain  a single project  assurance from  OPRR.  It was 
not until  1995 that OPRR began granting  assurances for projects that involved 
independent  IRBs.  It has continued  this practice  in subsequent years, so that at least 
12 such assurances are now  in place.  The number  is likely  to increase in the years 
ahead.  
They  are Becoming  More  Involved  with  Hospital-Based  Research. 
Independent  IRBs become increasingly  attractive to some hospitals  as the quantity  and 
complexity  of their own IRBs  workloads  increase.  Four of the 11 independent  IRBs 
with  which  we spoke already act as IRBs  of record for one or more hospitals.  One, in 
fact, had established a contract  with  a major academic health center IRB  to review  all 
commercially  sponsored research plans for that IRB.  A few other large research 
4 
031-01-97-00192  Independent  IRBs  institutions  have separated their commercially  sponsored research from the Federal 
assurance requirements  that apply to all HHS-funded  research, thereby  giving  the 
institution  greater flexibility  in contracting  with  independent  IRBs  if it so chooses.  Many 
of the experienced  IRB  officials  with  whom  we spoke noted that such separations are 
becoming  increasingly  likely  and present good market opportunities  for independent 
IRBS. 
Independent  IRBs  Offer  Advantages  That  Institutional  IRBs  Find 
Difficult  to Match. 
They  Are  Geared  to Making  Quick  Decisions  on Research  Plans. 
To commercial  sponsors, time is money.  Sponsors expect IRBs  to do their work 
properly,  but to do it quickly  as well.  Independent  IRBs  are organized  to meet this 
expectation.  It is widely  recognized,  by research sponsors and in the IRB  community 
more generally,  that they provide  research sponsors with  timely  responses to their 
submissions.2  Thus, for instance, the independent  IRBs  we contacted reported that, on 
average, they were able to provide  research sponsors with  an approval  or disapproval 
decision  for initial,  non-expedited  research protocols  in an average of about  11 days.  By 
contrast, the IRBs  in academic medical  centers that we visited  reported  decisions  in an 
average of about 37 days. 
Independent  IRBs  have an inherent  advantage in meeting  timeliness  expectations  because 
they hire their board members with  the understanding  that the members will  be regularly 
available to conduct  reviews.13 Hospital  IRB  members, in contrast, are almost always 
volunteers  with  many competing  demands for their time.  Not  surprisingly,  independent 
IRBs tend to meet more frequently  and can meet with  minimal  notice.  The independent 
IRBs we contacted reported  holding  multiple  board meetings  each month.  One 
independent  IRB  reported  that it holds four meetings a week.  Academic  health centers 
and hospitals  generally  are hard-pressed to match that.i4 
They  Provide  a Detached  Source  of Expertise. 
Independent  IRBs  are staffed by people who have no affiliation  with  the institutions 
whose research plans they review  and who  are unlikely  to have collegial  relationships 
with  the investigators  whose work  they review.15 Thus, the independent  IRBs  can operate 
without  being influenced  by concerns about the financial  well-being  or prestige of the 
institution  that employs  them or the career interests of colleagues.  One hospital  official, 
who has worked  with  independent  and hospital-based  IRBs,  underscored  the importance 
of such detachment, pointing  out that it leads to greater objectivity.  IRB  officials  in other 
settings, however,  are wary  of such a conclusion. 
5 
OEI-01-97-00192  Independent  IRBs  They  Provide  Unified  Reviews  for  Multi-site  Trials. 
Some multi-site  trials involve  research sites that do not have their own IRBs  or do not 
require  that all local research be overseen by the sites own IRB.  In such cases, 
independent  IRBs  can serve as a single entity  reviewing  the applicability  of a specific 
research plan to various sites.(j This unified  review  eliminates  the complications  that 
result from multiple,  local IRB  reviews  of a sponsors  research plan.  It also facilitates 
analysis of adverse-event reports submitted  from  individual  sites and, in so doing,  can 
enhance protections  for human subjects. 
Yet,  the Use of Independent  IRBs  Raises Concerns. 
They  Are  Not  Local  Review  Bodies. 
In the 1970s  when the current infrastructure  of Federal protections  for human research 

subjects was established and when relatively  few national  multi-site  trials were underway, 

local review  was regarded as essential.  In one of its key reports, the National 

Commission  for the Protection  of Human  Subjects of Biomedical  and Behavioral 

Research concluded: 

...the rights of subjects should be protected  by local review  committees  operating 
pursuant to federal regulations  and located in institutions  where research 
involving  human subjects is conducted.  Compared  to the possible alternatives  of 
a regional  or national  review  process, local committees  have the advantage of 
greater familiarity  with  the actual conditions  surrounding  the conduct  of research. 
Such committees  can work  closely  with  investigators  to assure that the rights  and 
welfare  of human subjects are protected  and, at the same time, that the application 
of policies  is fair to the investigators.17 
The OPRRs  recent decision to grant assurances involving  independent  IRBs  is based 
largely  on the IRBs  commitments  to stay well-informed  about local sites.  In response to 
OPRR and other concerned parties, the independent  IRBs point  to a variety  of ways in 
which  they keep abreast of the site circumstances.  These include  site visits,  local 
contacts, relationships  with  local IRBs,  newspaper  clipping  services, and other means. 
Many  in the IRB  field remain unconvinced  that such compensatory  efforts  allow  for 
adequate local representation. 
They  May  Be Subject  to Conflicts  of Interest. 
Some IRB  officials  are concerned that an independent,  for-profit  IRB  might  compromise 
its review  process to advance the financial  well-being  of the firm.  Such concerns are 
heightened  to the extent that corporate-equity  owners  or employees  serve on the IRB 
review  boards and are sustained to some extent by the fact that reviewers  are paid for 
their  services.  The NIH  policy  for HHS-funded  research reviews  by for-profit  IRBs  is to 
prohibit  equity  owners from participating  in the review  process.  There is no such policy 
6 
OEI-01-97-00192  Independent  IRBs  for industry-sponsored  studies submitted  to FDA.  As we noted earlier, the great 
preponderance  of research overseen by independent  IRBs  is sponsored by either 
pharmaceutical  or device manufacturers. 
A contrast is often made with  the academic health center, where,  some IRB  officials  say, 
a long established research culture  allows  for greater IRB  independence.  In an 
increasingly  competitive  research environment,  however,  in which  those centers are 
seeking to maximize  clinical  research revenues, the IRBs  in these centers can also 
experience conflicting  pressures. 
They  Heighten  Concerns  about  IRB  Shopping. 
For research that is not federally  funded,  sponsors have considerable  discretion  in their 
choice of an IRB.  A problem  here is that if one IRB  finds  fault with  the sponsors 
research plan, the sponsor might  then contract with  another IRB  without  informing  it of 
the prior  boards  determinations.  While  applicable  to all IRBs,  this vulnerability  is 
particularly  germane to independent  IRBs  since nearly  all the proposals  they review  are 
not federally  funded.  Some representatives  of these boards emphasized this point to us 
and felt there was a good case for a Federal requirement  that when  submitting  a research 
plan for review,  sponsors must inform  the IRB  of any prior  IRB  reviews  of that plan. 
7 
OEI-01-97-00192  Independent  IRBs  CONCLUSION 
This report  does not afford us a basis for assessing how  well  independent  IRBs  are 
performing.  But, it does lead us to two  concluding  observations  that have broader 
significance  for the Federal system of human-subject  protections. 
First, independent  IRBs have become a noteworthy  part of the IRB  landscape.  They give 
research sponsors an alternative  to the traditional,  well-established  IRBs.  Particularly  for 
non-federally  funded research, they allow  for these sponsors to engage in some shopping 
to determine  what IRBs best meet their needs.  In that sense, they serve as competition  to 
the longer  established IRBs,  especially  those in academic health centers, and contribute  to 
a marketplace  ethic--one  that is quite different  from the ethic of 20 or even 10 years ago 
when IRB  activity  was carried out within  a more clearly  defined  research culture.  This 
development  presents both opportunities  as well  as dangers.  On the one hand, it 
encourages IRBs  to undertake more timely  and innovative  approaches to their review 
processes.  On the other hand, the competitive  pressures to satisfy research sponsors can 
lead some IRBs to be less vigilant  in protecting  human subjects. 
Second, independent  IRBs raise important  questions  for Federal oversight.  How  can the 
Federal government  best ensure that independent  IRBs  afford  necessary protections? 
That the emerging  competition  does not compromise  safeguards?  That the advantages 
and efficiencies  offered by independent  IRBs  are not undercut  by unnecessary Federal 
prescriptions?  Such questions underscore the importance  of having  a good understanding 
of the actual effectiveness of IRBs,  whether  they are independent  or part of an 
organization  that conducts research.  This is a matter we address in our summary report, 
entitled,  Institutional  Review Boards.. A Time For  Reform. 
8 
OEI-01-97-00192  Independent  IRBs  APPENDIX  A 

1. The National  Commission  for the Protection  of Human  Subjects of Biomedical  and 
Behavioral  Research contracted  with  the Survey Research Center of the University  of Michigan 
to conduct  a study that focused on IRB  review  procedures  and research projects  reviewed  in 
1974-1975 at a representative  sample of 6 1 of the more than 420 institutions  that had DHEW 
assurances.  The study methodology  entailed  interviews  with  more than 3900 people involved 
with  the IRBs  (including  IRB  members, researchers whose protocols  were reviewed  by IRBs,  and 
research subjects.)  According  to Paul M. McNeil,  this study is still the most thorough  of any on 
record  in any country  (Paul M. McNeil,  The Ethics  and Politics  of Human  Experimentation, 
Cambridge:  Cambridge  University  Press, 1993, p. 86). 
2. 	 This evolution  in research mainly  applies to studies involving  investigational  drugs.  In the 
case of medical  devices some large, multi-site  studies were already underway  in the late 1970s. 
3.  Ruth Ellen  Bulger,  Elizabeth  Meyer  Bobby,  Harvey  V Fineberg,  editors, Societys Choices. 
Social  and Ethical  Decision  Making  in Biomedicine,  (Washington,  DC: National  Academy  Press, 
1995) p. 182. 
4. 	 Advisory  Committee  on Human  Radiation  Experiments,  Final  Report,  Washington  DC:  U.S. 
Government  Printing  Office,  1995. 
In that same year, a report from the HHS  Office  of Inspector  General raised concerns about IRBs 
ability  to monitor  ongoing  clinical  trials  and about the extent to which  effective  linkages  exist 
among hospital  committees,  offices,  and departments  to adequately provide  protection  for human 
subjects enrolled  in clinical  research.  (Department  of Health  and Human  Services, Office  of 
Inspector  General, Investigational  Devices;  Four  Case Studies, OEI-05-94-00100,  April  1995.) 
5.  U.S. General Accounting  Office,  ScientiJic Research:  Continued  Vigilance  Critical  to 
Protecting  Human  Subjects, GAOIHHS-96-72,  March  8, 1996, p. 3. 
6. 	 The National  Bioethics  Advisory  Commission  (NBAC)  was established by Executive  Order 
12975 on October  3, 1995.  Section 5 of the executive  order establishing  NBAC  states that as a 
first priority,  NBAC  shall direct its attention  to consideration  of protection  of the rights  and 
welfare  of human research subjects. 
7.  These IRBs  are overseeing research at institutions  receiving  over 1.4 billion  dollars  of Public 
Health  Service (PHS) awards.  As of March  1998, these institutions  received over 27 percent of 
the PHS dollars  awarded extramurally  for human subject research. 
8.  The FDA  suggests that the reason for more independent  IRBs  stems from  a change in FDAs 
regulations  in 198 1. For a further  elaboration,  see FDAs  Comments  on the Draft  OIG Report 
(appendix  D) in our summary report entitled,  Institutional  Review Boards.. A Time For  Reform. 
A-l 
031-01-97-00192  Independent  IRBs  9.  A recent survey of academic health centers found that their  IRBs  were reviewing  an average 

of 297 proposals  a year.  (Hayes et al., A  Survey of University  Institutional  Review  Boards: 

Characteristics,  Policies,  and Procedures,  IRB, Vol.  17, May-June  1996, No. 3, pp. 1-6.) 

A second survey, this one of hospitals  with  at least 400 beds, reported that IRBs  reviewed  an 

average of 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.) 

10.  Independent  IRBs:  Subject Protection  and Client  Service Are the Keys, 

Bio/Pharmaceutical  Outsourcing  Report,  (October  1997) Vo12,  Number  10, p. 1. 

11.  The FDA  has long accepted independent  IRBs  as part of the clinical  research landscape and 

has audited independent  IRBs. 

12.  Independent  IRBs:  Subject Protection  and Client  Service Are the Keys, 

Bio/Pharmaceutical  Outsourcing  Report,  (October  1997) Vo12,  Number  10, p. 1. 

13.  Of the seven IRBs  that provided  us with  information  on this topic,  four reported that they 

paid IRB  members for each meeting  attended; one paid members for each protocol  reviewed; 

another compensated members a base amount for each meeting  plus an additional  amount for 

meeting agenda items that surpassed the fixed number;  and the seventh used a mixed 

compensation  system whereby  most IRB  members were paid for each meeting  attended, but 

some members were paid an hourly  rate for either meeting  attendance or review  of adverse event 

reports and Investigational  New  Drug  safety reports. 

14.  Some of the independent  IRB  officials  we contacted  also suggested that the research 

protocols  they receive, which  are mostly  from pharmaceutical  and device manufacturers,  tend to 

be carefully  prepared and do not require much revision  or clarification.  The sponsors and their 

agents, hoping  to bring  products  for FDA  approval,  tend to be well  aware of FDAs  requirements 

concerning  IRB  review  and gear their submissions  accordingly. 

15.  When an institution  lacks its own IRB,  researchers could  be tempted to establish a board for 

the sole purpose of reviewing  a few proposals.  Such situations  could jeopardize  human-subject 

protections  because these IRBs would  lack sufficient  expertise.  Independent  IRBs  are an 

alternative  in such instances. 

16. Hospital  IRBs  that serve multi-hospital  systems are also able to provide  unified  reviews  for 

sites that are part of their  system. 

17. Institutional  Review Boards:  Report  and Recommendation  of the National  Commission for 

the Protection  of Human  Subjects of Biomedical  and Behavioral  Research, 43 Federal Register, 

30 November  1978, p. 56186. 

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OEI-01-97-00192  Independent  IRBs