Human Subjects Research: HHS Takes Steps to Strengthen		 
Protections, But Concerns Remain (23-MAY-01, GAO-01-775T).	 
								 
At the federal level the Department of Health and Human Services 
(HHS) is seeking to strengthen protection of human subjects in	 
biomedical research by enhancing the visibility of its human	 
subjects protection activities, improving its monitoring of	 
compliance with relevant regulations by institutions and	 
investigators, and strengthening enforcement of those		 
regulations. HHS has also issued new guidance and is collecting  
information intended to improve oversight and monitoring at the  
institutional level. HHS activities directed at the investigator 
level consist largely of educational efforts to heighten	 
investigators' awareness of and compliance with ethical policies 
and practices in conducting research. Overall, HHS' actions	 
appear promising, but GAO has some concerns about the pace and	 
scope of HHS' efforts to ensure the safety and protection of	 
participants in clinical trials.				 
-------------------------Indexing Terms------------------------- 
REPORTNUM:   GAO-01-775T					        
    ACCNO:   A01073						        
  TITLE:     Human Subjects Research: HHS Takes Steps to Strengthen   
             Protections, But Concerns Remain                                 
     DATE:   05/23/2001 
  SUBJECT:   Biomedical research				 
	     Safety regulation					 
	     Safety standards					 
	     Ethical conduct					 
	     Informed consent (medical law)			 

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GAO-01-775T
     
This statement was prepared for a hearing before the Senate Committee on
Health, Education, Labor, and Pensions, Subcommittee on Public Health, that
was originally scheduled for May 23, 2001.

Statement Of Janet Heinrich Director, Health Care- Public Health Issues

United States General Accounting Office

GAO May 2001 HUMAN SUBJECTS

RESEARCH HHS Takes Steps to Strengthen Protections, But Concerns Remain

GAO- 01- 775T

Page 1 GAO- 01- 775T

May 23, 2001 Considerable attention to the protection of human subjects in
biomedical research was sparked in the mid- 1990s following disclosures of
federally sponsored experiments in which research investigators did not
properly obtain the consent of the subjects. 1 Congressional concern was
heightened after the death in September 1999 of Jesse Gelsinger, an 18-
year- old participant in a gene transfer trial funded by the National
Institutes of Health (NIH) in the Department of Health and Human Services
(HHS).

Responsibility for the protection of human subjects in biomedical research
exists at three levels: at the federal level are agencies, such as HHS; at
the institutional level are research institutions, including universities
and academic medical centers; and at the individual investigator level are
physicians, scientists, and other professionals. Each level plays a role in
meeting federal requirements for protecting human research subjects or in
ensuring that the requirements are met. However, with the Gelsinger death
and other instances of research misconduct, questions are being raised about
the progress of federal efforts to ensure the safe and ethical conduct of
biomedical research.

This summer we will report in more detail on federal efforts to protect
human subjects in biomedical research, including efforts to address
financial conflict of interest issues. This statement focuses on HHS?
efforts to date to address human subjects protection issues at the federal,
institutional, and individual investigator levels and on areas of concern
that remain. My comments are based on interviews with key officials at HHS
agencies and other organizations, reviews of recent reports on human
subjects protection, and an analysis of relevant HHS regulations and
policies. We conducted our work from September 2000 through May 2001 in
accordance with generally accepted government auditing standards.

In summary, at the federal level HHS is seeking to strengthen protection of
human subjects in biomedical research by enhancing the visibility of its
human subjects protection activities, improving its monitoring of compliance
with relevant regulations by institutions and investigators, and
strengthening enforcement of those regulations. HHS has also issued new

1 Advisory Committee on Human Radiation Experiments, Final Report
(Washington, D. C.: Oct. 1995). Scientific Research: Continued Vigilance
Critical to Protecting Human Subjects (GAO/ HEHS- 96- 72, Mar. 1996).

Page 2 GAO- 01- 775T

guidance and is collecting information intended to improve oversight and
monitoring at the institutional level. HHS activities directed at the
investigator level consist largely of educational efforts to heighten
investigators? awareness of and compliance with ethical policies and
practices in conducting research. Overall, HHS? actions appear promising,
but we have some concerns about the pace and scope of the department?s
efforts to ensure the safety and protection of participants in clinical
trials.

A significant proportion of biomedical research is conducted through
clinical trials, which involve testing new drugs, devices, or treatments
with human subjects. Many of these trials are spread across hundreds of
sites, sometimes at sites outside of the United States, and are performed
not only in academic medical centers but also by physicians and other
providers in the community. Although there are no comprehensive data on the
number of individuals enrolled in research studies, this number has likely
increased as federal spending for medical and health research has doubled in
recent years and industry spending has been growing even faster.

The principal federal policy for protecting human research subjects is
called the Common Rule. It is a set of requirements, embodied in regulation,
agreed to by 17 federal departments and agencies, including HHS, 2 and
applies only to federally funded or sponsored research. Broadly speaking,
the Common Rule focuses on

 obtaining the research subject?s voluntary, informed consent by
specifying, among other things, that subjects must be told of the expected
benefits and potential risks to which they could be exposed;

 setting criteria for review panels- known as institutional review boards
(IRB) 3 -that are responsible for performing initial and ongoing reviews of
research; and

 obtaining a formal written assurance of compliance with federal standards
from institutions engaged in research studies.

2 HHS regulations contain additional protections not included in the Common
Rule for research involving certain vulnerable populations- namely, pregnant
women, children, fetuses, subjects of in vitro fertilization research, and
prisoners.

3 Some IRBs are associated with particular universities or research
institutions. Others are independent for- profit or not- for- profit
entities. Background

Common Rule Requirements for Protecting Human Subjects in Federally
Supported Scientific Research

Page 3 GAO- 01- 775T

A federal agency cannot change the Common Rule without the agreement of the
other 16 agencies that agreed to and are governed by the rule. Thus, to
adapt regulations to emerging ethical issues or new scientific developments,
some agencies have issued their own regulations or guidance, which has
produced a varied array of policies across the federal agencies.

Major responsibility for federal oversight of human subjects protection in
HHS- related clinical research rests with three entities: the Office for
Human Research Protection (OHRP), NIH, and the Food and Drug Administration
(FDA). OHRP oversees all research conducted or funded by HHS that uses human
subjects. OHRP?s oversight activities are directed chiefly at HHS- supported
research, including research conducted at universities, hospitals, and other
medical and behavioral research institutions. One of OHRP?s principal duties
is to approve and renew an institution?s ?assurance,? which is a written and
signed agreement that details the terms of the institution?s promise to
comply with federal human subjects protection requirements and policies. In
addition, OHRP investigates problems involving noncompliance with human
subjects protection that have been identified at institutions and conducts
occasional on- site evaluations.

NIH, the principal federal agency that provides funds for biomedical
research, is charged with ensuring that the research it funds is in
compliance with HHS regulations and with any additional terms it negotiates
with an individual research institution. NIH also issues its own guidelines
for certain aspects of human subjects research, such as data and safety
monitoring and the education of investigators.

FDA is responsible for ensuring the protection of the rights and welfare of
human subjects enrolled in research on the products it regulates- drugs,
medical devices, biological products, 4 foods, and cosmetics. It oversees
public and private research investigators, sponsors of research, such as
pharmaceutical companies and biotechnology companies, and IRBs that review
FDA- regulated research. Some of this research is not federally funded and
thus does not fall under the Common Rule, but FDA has

4 A ?biological product? means ?a virus, therapeutic serum, toxin,
antitoxin, vaccine, blood, blood component or derivative, allergenic
product, or analogous product, . . . , applicable to the prevention,
treatment, or cure of a disease or condition of human beings? (42 U. S. C.
Section 262( i)). Structure in Place to

Oversee Human Subjects Protections in HHSRelated Research

Page 4 GAO- 01- 775T

adopted a separate set of human subjects protection regulations that are
similar, but not identical, to the Common Rule that apply to the research on
products it regulates. A primary concern for FDA is assuring the quality and
integrity of research data involved in the testing or licensing of medical
products. FDA enforces compliance with its regulations through on- site
inspections of IRBs, clinical investigators, and sponsors.

In recent years, a number of concerns have been raised about human subjects
protection. In a 1996 study, we found that various time, resource, and other
pressures had reduced or threatened to reduce the effectiveness of oversight
by federal agencies and IRBs. 5 Two years later, a series of reports issued
by the HHS Office of the Inspector General (OIG) confirmed the intense
pressures on IRBs and the limitations of their effectiveness and made
specific recommendations for action. 6 In April 2000, the OIG reported that
HHS had taken few actions in response to these recommendations. 7

In 1999 the National Bioethics Advisory Commission (NBAC) was asked to
conduct a thorough review of the federal oversight system for human subjects
protection. 8 NBAC has released a series of drafts of its report entitled
?Ethical and Policy Issues in Research Involving Human Participants? and is
scheduled to issue a final report in the summer of 2001. NBAC?s report is
expected to address all federal oversight for research involving human
participants, and NBAC is not expected to limit its recommendations to areas
within HHS? purview.

5 GAO/ HEHS- 96- 72. 6 Institutional Review Boards: A Time for Reform (OEI-
01- 97- 00193, 1998); Institutional Review Boards: The Emergence of
Independent Boards (OEI- 01- 97- 00192, 1998); Institutional Review Boards:
Promising Approaches (OEI- 01- 91- 00191, 1998); Institutional Review
Boards: Their Role in Reviewing Approved Research (OEI- 01- 97- 00190,
1998).

7 Protecting Human Research Subjects: Status of Recommendations (OEI- 01-
97- 00197, 2000). 8 NBAC was established in October 1995 to advise the
National Science and Technology Council and other government entities
regarding bioethical issues arising from research on human biology and
behavior. Recent Studies

Highlighting Human Subjects Protection Concerns

Page 5 GAO- 01- 775T

In response to concerns raised by Congress and the research community, HHS,
in particular, three of its components- OHRP, NIH, and FDA- has begun
several initiatives to enhance the protection of subjects in HHSfunded and
FDA- regulated research. These efforts are largely in the initial stages of
implementation.

HHS has taken steps to give the issue of human subjects protection greater
prominence. Until recently, NIH?s Office for Protection from Research Risks
(OPRR) was responsible for oversight and enforcement of regulations when HHS
funding was involved. Because the office was located at NIH, it was not
clear that its authority extended beyond NIHfunded research. There was also
the perception that its autonomy was compromised by its location within an
agency that also funds research. To address these concerns about authority
and autonomy, HHS established OHRP in the Office of the HHS Secretary,
Office of Public Health and Science in June 2000, enhancing the status and
visibility of human subjects protection activities. OHRP assumed the human
subjects protection functions of the former OPRR. OHRP has a 2- year plan to
organize and coordinate the department?s diverse human subjects protection
activities and reengineer the system for protection of human subjects in
research.

In March 2001, FDA formally elevated and centralized its human subjects
protection activities by creating the Office for Human Research Trials and
locating it in the Office of the Commissioner. At FDA, human subjects
protection activities previously were diffuse, dispersed across various
centers and the Office of the Commissioner. The new office is involved with
intra- agency coordination of policy, education, and oversight relating to
human subjects protection. OHRP, FDA, and NIH officials told us they are now
working together more closely to coordinate and utilize resources for human
subjects protection activities.

The three HHS components have also sought to improve the mechanisms they use
to conduct oversight and enforcement activities related to human subjects
protection. To reduce regulatory burden and enhance its oversight
capabilities, OHRP has recently revised its assurance process. The research
community had concerns about the assurance approval and renewal processes.
They contended that the processes had been unnecessarily burdensome and
created disproportionate workload demands on HHS and research institution
staff who are needed to meet other, equally important and time- consuming
human subjects protection HHS Components

Seek to Improve Their Diverse Federal Oversight Efforts

Efforts to Enhance Visibility of Human Subjects Protection Activities

Efforts to Improve Oversight, Compliance, and Enforcement

Page 6 GAO- 01- 775T

requirements. To address these problems, OHRP undertook, as one of its first
major initiatives, implementation of a simplified assurance process that is
less administratively burdensome. The streamlined assurance process, which
is currently being phased in, is designed to reduce the paperwork burden
that characterized the former process.

OHRP, in collaboration with FDA, has initiated IRB registration as another
step to improve its ability to conduct oversight and facilitate compliance.
Previous HHS efforts to monitor IRBs and communicate with them about
policies and guidance had been hampered because HHS did not have a
comprehensive list of all IRBs, estimated to number in the thousands. As
part of the new assurance process, institutions will be required to register
their IRBs. 9 Registration will enable HHS to build an IRB database, which
will facilitate the identification of and communication with officials who
actively review projects using human subjects.

OHRP also seeks to enhance IRB compliance by adopting a monitoring and
quality improvement strategy intended to prevent problems before they occur.
We and others have reported that this office?s predecessor made few site
visits to review compliance. Those conducted, moreover, were ?for cause,?
that is, in response to complaints of noncompliance. OHRP has plans to
conduct quality improvement evaluations (although not necessarily through
site visits) at every major medical school in the United States within the
next 18 months, insofar as resources permit. OHRP seeks to expand its
compliance activities through enhanced coordination and communication with
FDA?s inspection program. In fiscal year 2000, NIH also began a process of
not- for- cause site visits, intended to assess institutional understanding
of federal policies and regulations (including those involving human
subjects protection), minimize or eliminate noncompliance, and foster a
productive partnership between NIH and its grantee institutions. To date, it
has completed 10 of these visits; NIH officials told us that more are
planned for fiscal year 2001.

HHS is also considering ways to address the research community?s concerns
that its range of options for enforcement of regulations is too limited. In
the event that serious violations are uncovered, OHRP can restrict or
suspend an institution?s assurance. Such an action would

9 This registration procedure seeks for the first time to register all IRBs
overseeing HHSfunded research, whether independent or based at academic
institutions. The new procedures do not, however, require all IRBs to
register. FDA intends to require registration by all IRBs that are subject
to its regulation.

Page 7 GAO- 01- 775T

seriously disrupt ongoing research at that institution because federally
funded human subjects research cannot be conducted without an assurance in
place. FDA can withhold approval of new studies, withhold approval for
enrollment of new subjects, and terminate studies. FDA can also issue
warning letters and restrict or disqualify investigators, IRBs, or
institutions from conducting or reviewing research. As a granting agency,
NIH can place a restriction on an award if the grantee institution is not in
compliance with regulations. Nonetheless, some critics have argued that
there are too few sanctions to match the range of violations that occur.
Acknowledging this problem, HHS is considering a proposal for legislation
that would enable FDA to levy civil monetary penalties for violations of the
informed consent process and other important research practices.

HHS has taken some actions to improve the review and monitoring of clinical
trials by research institutions. HHS has taken steps to improve
institutional research reviews while reducing IRB workload by issuing
guidance regarding adverse events and financial relationships. It is also
initiating efforts to develop standards for evaluating IRBs.

Recent HHS guidance regarding IRB use of information from other entities
involved in monitoring research has the potential to improve IRB reviews and
reduce their workload. Our 1996 report noted that workload and other demands
impaired IRB oversight, and subsequent studies found that review of adverse
event reports presents a particular challenge to IRBs. Adverse event reports
describe untoward occurrences experienced by research subjects during the
course of a clinical trial. IRBs have been overwhelmed by large numbers of
adverse event reports from investigators, as can happen when clinical trials
are conducted at multiple sites. IRB review can be difficult because adverse
event reports can lack key information, such as whether the individual
experiencing the adverse event was part of the trial?s treatment group or
control group. One mechanism that is sometimes used to help evaluate data
collected during a trial is data and safety monitoring boards (DSMB). These
are special committees composed of statisticians and other scientists that
monitor information about the safety and effectiveness of clinical trials
and that may recommend that a trial be continued or stopped. Because DSMBs
have access to adverse event data, they are in a good position to assess
Recent and Planned

Protection Efforts Involve Strengthening Oversight Performed by Research
Institutions

Efforts to Improve Institutional Review and Monitoring of Research

Page 8 GAO- 01- 775T

certain risks to subjects. Until recently, however, IRBs were to review a
clinical trial?s adverse event reports even if a DSMB had also evaluated
them.

In May 2000, OHRP?s predecessor issued guidance stating that an IRB, in its
continuing reviews of a trial, could rely on a statement by a DSMB attesting
that it had reviewed a trial?s adverse event reports, interim findings, and
any recent literature that may be relevant to the research. This policy
expedites the IRB?s own review of adverse event reports, thus freeing IRB
resources to concentrate more appropriately on assessments of other
potential study risks. Recognizing the potential benefits of DSMBs, both NIH
and FDA are taking steps to encourage their use when appropriate. For
example, NIH, which had issued guidance in 1998 directing the use of DSMBs
in certain NIH- funded multisite trials, 10 issued new guidance in June 2000
suggesting in part that DSMBs be used for additional studies, such as early-
stage clinical trials that employ particularly high risk interventions or
use vulnerable populations. FDA, which recommended DSMBs for certain studies
in 1998 guidance, is currently developing additional guidance on their use,
which is expected to be released for comment this summer.

HHS? anticipated guidance on financial relationships may also facilitate the
ability of IRBs to appropriately review research. In today?s environment,
financial relationships sometimes exist between investigators, institutions,
and industry sponsors. 11 These relationships have the potential to
inappropriately influence the professional judgment and independence of
those responsible for the protection of human subjects. In particular, they
can affect the study?s recruitment, enrollment, conduct, and analyses of
results in ways that would financially benefit the investigator or
institution, and IRBs must ensure that such financial relationships do not
pose a risk for human subjects. As financial relationships continue to
multiply, IRBs may need to address an increasingly complex range of issues
associated with possible conflicts of interest. Some research institutions
have special committees to examine financial relationships in

10 NIH?s 1998 guidance reaffirmed a 1979 policy directing the use of DSMBs
in certain NIHfunded multisite trials. 11 The Bayh- Dole Act (P. L. 96- 517,
Section 6( a)), which was designed to allow universities, not- for- profit
corporations, and small businesses to patent and commercialize their
federally funded interventions, has fostered ties between industry and
clinical investigators.

Page 9 GAO- 01- 775T

detail, and these committees may be able to supplement IRB review in this
area. 12 In January 2001, HHS developed Draft Interim Guidance on Financial
Relationships, which discussed points that IRBs and other participants in
the research process should consider when addressing issues of financial
interests and human subjects protection. This document generated a broad
range of reactions and debate, and HHS is currently revising the document to
address those comments.

HHS has initiated efforts to develop standards for accreditation and
evaluation of IRBs, standards that might help improve performance by
allowing assessment of strengths and weaknesses. The OIG has stated that
oversight at the federal or institutional level is not geared toward
evaluating IRB effectiveness and that little is known about how well IRBs
are accomplishing their mission to protect human subjects. As a first step
toward evaluating the effectiveness of IRBs, HHS requested that the
Institute of Medicine (IOM) explore the option of accreditation for IRBs and
other human research protection entities. IOM released its report in April
2001, recommending pilot testing of accreditation by nongovernmental
organizations. 13 , 14 HHS also asked IOM to conduct an analysis, scheduled
for completion in 2002, of the structure and functioning of IRBs and other
entities involved in ensuring protection of human subjects and to develop
criteria for evaluating their performance. These efforts constitute a
preliminary step toward establishing benchmarks for IRB performance.

12 Institutions receiving research funds from the Public Health Service or
the National Science Foundation are required to have policies and procedures
to examine financial relationships. Institutions must ensure that any
significant relationships are managed, reduced, or eliminated.

13 IOM, Preserving Public Trust, Accreditation and Human Research
Participant Protection Programs (Washington, D. C.: National Academy Press,
2001). 14 NIH plans to have its intramural human subjects program evaluated
later this year using draft accreditation standards issued by the
Association for the Accreditation of Human Research Protection Programs. The
Department of Veterans Affairs has contracted with the National Committee
for Quality Assurance to develop an accreditation process for the IRBs it
uses. Efforts to Develop

Standards for IRBs

Page 10 GAO- 01- 775T

HHS has efforts under way to improve investigators? understanding of and
compliance with human subjects protection requirements. The efforts focus on
instructing clinical trial investigators on the ethical conduct of research,
including pertinent regulations, proper ways to obtain informed consent from
research subjects, and obligations to report adverse events.

HHS has taken several recent actions to inform investigators about human
subjects protection policies and practices. We, OHRP, and OIG have all noted
that educational programs are critical to ensuring that investigators
understand their responsibilities to protect human subjects. Some recent
instances in which investigators violated informed consent or adverse event
reporting may have been due to a lack of understanding of key issues by
investigators. In June 2000, NIH established an education requirement for
all investigators submitting NIH applications for grants and proposals
involving human subjects. Effective October 1, 2000, NIH grantees are
required, as a condition of project funding, to attest to having received
training- through on- line workshops, published materials, or live
presentations- on the protection of human subjects. In February 2001, OHRP
held an educational ?summit? of key agency officials and representatives of
the research community to develop an educational initiative, possibly as a
public- private partnership. 15 HHS has taken some steps to improve
awareness through education, which build on previous educational efforts
sponsored by OHRP?s predecessor. This past year, FDA, OHRP, the Department
of Veterans Affairs, and others jointly sponsored educational workshops on
human subjects protection in Washington, D. C., and Newark, New Jersey, and
held a town meeting in Dallas, Texas for investigators, IRBs, and others on
human subjects protection issues. Plans are in place for continuing these
joint educational workshops and town meetings in the coming year. In
addition, FDA is conducting educational programs for clinical investigators,
jointly sponsored with industry and academic representatives.

HHS has some plans to address concerns relating to investigators? practice
of obtaining informed consent. Experts have suggested that some
investigators may tend to emphasize the disclosure of information and
documentation of consent, rather than ensuring that participants fully
understand the risks and benefits of the study and that their participation
is voluntary. Over the years, HHS components have provided information

15 The summit was co- hosted by the Office of Research Integrity, a separate
HHS component that directs research integrity activities on behalf of the
HHS Secretary. HHS Initiates Efforts

to Raise Investigators? Awareness of Human Subjects Protections

Page 11 GAO- 01- 775T

and guidance on informed consent. For example, OHRP?s predecessor discussed
informed consent in its IRB Guidebook and other supplemental materials.
NIH?s institutes and centers have provided guidance to their grantee
investigators and to in- house clinical researchers and IRBs. FDA informed
consent guidance has been issued to IRBs and clinical investigators in the
form of ?Information Sheets.? While the guidance and information on informed
consent are extensive, NBAC has suggested that in general, the federal
guidance continues to emphasize documenting the subject?s consent rather
than focusing on the ethical practices for obtaining this consent.

FDA officials told us they are revising all of the agency?s Information
Sheets for investigators and IRBs, including the guidance on informed
consent. The revised guidance is intended to emphasize the importance of
informed consent as a process of achieving understanding and voluntary
participation. It will also address issues involved in obtaining consent
from study participants who might not be able to provide consent on their
own behalf. Beginning in 1999, NIH has funded 12 studies on informed consent
and research ethics. The studies include an evaluation of the cognitive
ability required to comprehend different aspects of a research project and
an analysis of how potential participants weigh risks and benefits; the
results are not yet available.

Some HHS efforts are aimed at improving investigators? understanding of
adverse event reporting obligations. Although the ultimate responsibility
for reporting adverse events in clinical research lies with investigators,
they have sometimes misunderstood their responsibilities because there are
inconsistencies between HHS and FDA regulations and guidance. These differ
in what is to be reported, the entity to which it should be reported, and
the required time frames for reporting. NIH is planning to make its adverse
event reporting requirements- as they apply to gene transfer research-
compatible with those of FDA. 16

16 In the specific area of human gene transfer research, the NIH has special
guidelines regarding reporting of serious adverse events that are different
from FDA?s requirements.

Page 12 GAO- 01- 775T

Although problems with the oversight of human subjects protection have
received increasing attention since the 1990s, it is only recently that HHS
has made a concerted effort to address these issues. We have some concerns,
however, that the pace of some actions is too slow and that gaps remain at
each of the three levels of oversight we reviewed.

At the agency level, for example, HHS has not increased OHRP?s budget in
proportion to the office?s increased scope of work- including its quality
improvement evaluations at medical schools- and the office has not been able
to hire the staff it planned to because of the federal hiring freeze that
went into effect in early 2001. OHRP is still addressing a backlog of
compliance cases. In addition, NIH appears to have lost momentum regarding
its not- for- cause site visits. In the first two- thirds of fiscal year
2001, it has not made any not- for- cause site visits. FDA officials told us
that HHS has not finalized a legislative proposal that, if enacted, would
broaden FDA?s authority to apply civil monetary penalties for investigator
violations. Furthermore, FDA units that monitor and inspect clinical trials
are seeking additional resources. According to an FDA acting associate
commissioner, in 2000 the agency inspected fewer than 800 clinical
investigators, or about 2 percent of an estimated 35,000 clinical sites.
Although the agency has asked for additional resources to allow it to
increase the number of inspections by 275, this would extend the inspections
by less than 1 percentage point.

At the research institution level, HHS? efforts to support IRBs and enhance
their performance appear promising, but the subject of financing IRBs
remains largely unexplored. Although institutions bear the ultimate
responsibility for supplying needed resources for IRBs, HHS can help
facilitate the appropriate allocation of resources by providing information
about resource benchmarks. HHS officials have acknowledged that little is
known about the actual cost of the human subjects protection process, and
there is debate about what constitutes appropriate funding and what the
sources of funding should be. A Regulatory Burden Working Group at NIH has
begun to study IRB operations and intends to address these financing
questions. In addition, while HHS has begun to examine the issues relating
to financial conflicts of interest at research institutions, it is not yet
clear how, or how quickly, the department plans to move to address these
serious concerns.

At the investigator level, HHS has taken little action to improve the
informed consent process and to clarify adverse event reporting
requirements. A year ago, HHS announced that it would issue new guidance on
informed consent, but it has not yet done so. OHRP officials Concerns Remain

Regarding the Pace and Scope of HHS? Actions to Protect Human Subjects

Page 13 GAO- 01- 775T

told us that other issues, such as implementing the new assurance process
and educational initiatives, have higher priority and that they need time to
get expert and public input on the informed consent process and how it can
be improved. Despite concerns about problems with adverse event reporting
and confusion among investigators over differing requirements, HHS has not
yet taken any steps to address these concerns. The only announced plans to
improve this process have been limited to harmonizing the gene transfer
research reporting requirements.

The actions of HHS components to improve oversight are in the right
direction, but in some areas, the extent of change could be greater. At the
three key levels of human subjects protection- federal agency, research
institution, and individual investigator- more could be done to fill the
gaps in protection efforts.

For future contacts regarding this testimony, please call me at (202)
5127119 or Marcia Crosse at (202) 512- 3407. Individuals making
contributions to this statement are Anne Dievler, Romy Gelb, Kristen Joan
Anderson, and Hannah Fein. Concluding Remarks

GAO Contacts and Acknowledgments

(290070) This statement was prepared for a hearing before the Senate

Committee on Health, Education, Labor, and Pensions, Subcommittee on Public
Health, that was originally scheduled for May 23, 2001.
*** End of document. ***