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Regulatory History
THERE ARE MANY ACCOUNTS that trace the evolution of U.S. poli-
cies and regulations for human research participant protection
in federally funded research generally and in experimental bio-
medical research specifically. For example, the report of the Advisory
Committee on EIuman Radiation Experiments (1996) provides a very
informative history of regulation and human protection issues in ra-
diation experiments and other biomedical research, covering not only
the U.S. Department of Health and Human Services (DHHS), but also
the U.S. Departments of Defense, Energy, and Veterans Affairs. But
nowhere is there a comprehensive history of human participant pro-
tection in social, behavioral, and economic sciences (SBES) research.
Problems in such research have generally not received as much media
attention as those in clinical trials and other biomedical experiments;
also, the diversity of research questions and methods under the um-
brella of SBES research is so broad as to make it difficult to construct
a thorough-going history (see Chapter 21.
fine are not able to make up for the lack of a comprehensive his-
to~y here. Our summary below focuses on key events in federal policy
making and regulation for SBES research from the end of World War
II through the present.) Our discussion identifies five major periods,
the end dates of which mark significant events in the development of
regulations, major disputes, and media attention.
The history of federal regulation for human research participant
protection shows relatively less emphasis on issues of protecting the
confidentiality of information from individual respondents, in contrast
to the attention devoted to such issues as the definition of research in-
volving human participants and the elements of informed consent. Im-
~Key sources that we consulted for this history include Advisory Committee on
Human Radiation Experiments (1996:Ch. X); Beauchamp et al. (1982:Ch. 1); Gray
(1982); McCarthy (1998); National Bioethics Advisory Commission (2001:App.C). Mc-
Carthy (1998) covers attitudes toward and problems with human research participant
protection in the United States prior to 1945. See Appendix A for changes in regulatory
language from 1974 to the present on such topics as minimal risk, criteria for institu-
tional review board (IRB) review, basic elements of informed consent, exempt research,
and others.
59
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60 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
portent developments in confidentiality protection, which we consider
a major concern for much SBES research, have mainly occurred in
federal statistical agencies and SEES data archives. More recently, ex-
plicit federal confidentiality regulations have been enacted for research
that uses medical records from health care providers and insurers. We
review the history of confidentiality protection at the beginning of our
discussion of confidentiality issues in Chapter 5.
FROM 1945 TO 1966
The biomedical experiments performed by Nazi researchers during
World War II focused attention on the ways in which human partici-
pants could be seriously harmed by research. Many unwilling partici-
pants suffered permanent injury, shortened life expectancy, psycholog-
ical trauma, and even death in these experiments (e.g., measuring how
long humans could survive in ice water). The second Nuremberg Mil-
itary Tribunal condemned such research as a crime against humanity.
In 1947 the judges proposed a list of ten principles, the "Nuremberg
Code," which researchers should be obligated to respect in conducting
medical experiments that involve human subjects. The code called for
voluntary consent, minimization of harm, and a determination that the
research benefits outweighed the risks to participants (see Annas and
Grodin, 19921.
Biomedical research exploded in scope and volume after the war.
Professional organizations and government agencies began to develop
codes of ethics for human research participant protection that reflected
the Nuremberg Code. In 1953-1954 the National Institutes of Health
(NIH) established an ethics review committee (the Medical Advisor
Board) for intramural research at its clinical center and adopted a pol-
icy that all human research participants at the center must provide
informed consent, although written consent was not always required
for sick patients. By the mid-1960s many biomedical research orga-
nizations had voluntarily established ethics review mechanisms. But
instances of unethical research kept coming to light, and public pres-
sure built for explicit government regulation.
The thalidomide tragedy spurred congressional action, as did reve-
lations at congressional hearings about the common practice in which
doctors gave patients samples of experimental drugs without the pa-
tient knowing the experimental nature of the drugs or consenting to
their use. The 1962 Kefauver-Harris amendments to the Food, Drug,
and Cosmetic Act required informed consent in testing of experimen-
tal drugs, although consent was not required if it was deemed by the
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REGULATORY HISTORY
61
physician to be infeasible or not in the patient's best interest. Reports
of other questionable research, including a 1963 study in which poor
elderly patients at the Jewish Chronic Disease Hospital in New York
City were injected with live cancer cells without their consent, led the
U.S. Public Health Service (USPHS) to develop a policy on human re-
search participant protection that was issued in 1966.
The 1966 USPHS policy required that every research institution re-
ceiving grant dollars from the agency establish a committee to review
federally funded research projects for conformance with human partic-
ipant protection. On December 12, 1966, in response to questions, the
U.S. surgeon general issued a "clarification" of the USPHS policy, mak-
ing explicit that review committees (the forerunners of IRBs) were to
review "all investigations that involve human subjects, including inves-
tigations in the behavioral and social sciences." With regard to SEES
research, he said (Memorandum from the Surgeon General to Heads
of Institutions Receiving Public Health Service Grants, December 12,
1966; quoted in Gray, 1982:3311:
There is a large range of social and behavioral research
in which no personal risk to the subject is involved. In these
circumstances, regardless of whether the investigation is
classified as behavioral, social, medical or other, the issues
of concern are the fully voluntary nature of the participation
of the subject, the maintenance of confidentiality of infor-
mation obtained from the subject, and the protection of the
subject from misuse of the findings....
ESBES research] may in some instances not require the
fully informed consent of the subject or even his knowledge-
able participation.
The original USPHS policy, as Gray (1982:331) notes, "contained no
systematic analysis of the ethical issues at stake in research involving
human subjects." Nor did the surgeon general explain why or under
what circumstances informed consent in SEES research might not be
required.
FROM 1966 TO 1974
The years subsequent to the first USPHS policy guidelines saw con-
tinued interest in and attention to human research participant protec-
tion issues among regulators, researchers, and members of Congress.
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62 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
Federal Government Activity
In 1971, in response to requests for clarification and evidence of
highly variable implementation of the USPHS policy, the U.S. Depart-
ment of Health, Education, and Welfare (DHEW)2 published "The In-
stitutional Guide to DEIEW Policy on Protection of Human Subjects."
This guide, known as the "Yellow Book," defined "risk" as exposure
to the possibility of harm, including physical, psychological, sociolog-
ical, or other harms, "beyond the application of those established and
accepted methods necessary to meet [participants'] needs." (This state-
ment distinguished research activities from activities to provide a ser-
vice, such as medical treatment.) The Yellow Book explicitly identi-
fied kinds of possible harm that could arise in research conducted with
such typical SBES methods as interviews, observations, and secondary
analysis of existing data, including "varying degrees of discomfort, ha-
rassment, invasion of privacy, or... a threat to the subject's dignity
through the imposition of demeaning or dehumanizing conditions."
The Yellow Book discussed methods for protecting against disclo-
sure of confidential data. It stated that IRBs should make sure that sec-
ondary analysis was "within the scope of the original consent." Such
consent could be oral or written, obtained "after the fact following de-
briefing," or could be "implicit in voluntary participation in an ade-
quately advertised activity." There was no repetition of the surgeon's
general statement allowing less than fully informed consent under some
circumstances.
Building on the Yellow Book, DHEW issued comprehensive regu-
lations in May 1974 for the protection of human research participants
(45 Code of Federal Regulations [CFR] 46), which stated that the de-
partment would not support any such research unless first reviewed
and approved by an IRB.3 4 IRBs were to determine whether human
subjects were at risk (defined as the possibility of "physical, psycho-
logical, or social injury"; whether risks were outweighed by benefits
to the subjects and the importance of the knowledge sought; whether
the rights and welfare of subjects were adequately protected (although
2DHEW was the predecessor agency to DHHS.
3 The 1974 regulations referred to a "committee" and not to an IRB; the IRE ter-
minology was adopted in a subsequent 1975 amendment to the Public Health Service
Act.
4 Later in 1974 DREW published regulations for additional protections for pregnant
women and fetuses and for prisoners; these regulations were revised in 1978 following
the report of the National Commission for the Protection of Human Subjects of Biomed-
ical and Behavioral Research (see below); they became subparts B and C of 45 CER
46, while the basic regulations became subpart A. Additional protections for children in
subpart D were first codified in 1983.
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REGULATORY HISTORY
63
there was no specific language about privacy or confidentiality pro-
tection); and whether "legally effective informed consent" would be
obtained by "adequate and appropriate methods." Informed consent
was to be documented in writing. While the regulations included pro-
visions for waiver of written consent, they were difficult to understand
and appeared to be very narrowly drawn.
The regulations specified that IRBs were to include at least five
members of varying backgrounds, including individuals who were able
to "ascertain the acceptability of proposals in terms of institutional
commitments and regulations, applicable law, standards of professional
conduct and practice, and community attitudes." Gray (1977), among
others, argued that this language could give IRBs license to object to
research on political rather than ethical grounds.
A government staff member (Tropp, 1979, 1982) later asserted that
the pressure of congressional action (see below) resulted in hasty publi-
cation of the 1974 regulations, which were formulated primarily by the
health components of DHEW, without participation from other agen-
cies that supported SEES research and knew the SBES research com-
munity. Further intradepartmental negotiation was planned to pro-
duce regulations appropriate for all types of research, but it did not
take place.
National Research Act
During this period, public concern about unethical biomedical ex-
periments escalated. Two experiments in particular captured public
attention. In the Willowbrook study, from 1956 to 1972, children who
were residents of the Willowbrook (Staten Island, New York) State
School for the Retarded were injected with a form of hepatitis. Par-
ents, in order to have their children admitted to the only available
area of the school, the research wing, had to consent to the study
(see Beecher, 19701. In the Tuskegee, Alabama study, begun in 1932,
USPHS physicians followed several hundred African-American men
who had syphilis. No treatment was given to these men even after the
discovery of penicillin. The study was not discontinued until 1973 (see
Jones, 19811. The Willowbrook study had been reviewed by an ethics
committee, and the Tuskegee study apparently had also had such a
review, but neither study was stopped until the media reports and sub-
sequent public reactions.
In 1973 Senator Edward Kennedy (D-MA) held hearings and intro-
duced legislation to establish an independent National Human Experi-
mentation Board to regulate all federally funded research with human
participants, not just that funded by DHEW. However, this approach
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64 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
did not garner sufficient support, so Senator Kennedy introduced in-
stead what became the National Research Act of 1974. The act en-
dorsed the regulations about to be promulgated by DHEW (see above)
and established a National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research. The commission
was charged to review the IRB system and to advise DHEW and the
Congress about ethical issues in research involving vulnerable popu-
lations, such as pregnant women, fetuses, children, prisoners, and in-
stitutionalized mentally ill or retarded people. The commission was to
identify basic ethical principles for research with human participants
and to recommend ways to ensure that research studies followed these
principles.
FROM 1974 TO 1981
National Commission
The National Commission for the Protection of Human Subjects of
Biomedical and Behavioral Research conducted its work over a 4-year
period. In addition to holding hearings and commissioning papers,
it contracted with the University of Michigan for an in-depth study of
the IRB system at a sample of 61 institutions, involving interviews with
several thousand IRB members, researchers, and research participants
(Cooke, Tannenbaum, and Gray, 1978; see also Appendix D).
This survey offered three major findings: (1) by comparison with a
study for 1969 (Barber et al., 1973),IRBs had become much more ac-
tive in requiring modifications in proposed research, particularly with
regard to informed consent;5 (2) the selection of participants seemed
to distribute risks and benefits fairly evenly among various popula-
tion groups; and (3) researchers, as well as IRB board members, sup-
ported the IRB system overall. The study also revealed two prob-
lems: First, not only did virtually all modifications to informed con-
sent procedures deal with consent forms and not the process, but also
IRB-modified consent forms were not more complete or easier to read
than other forms. Second, the support for the IRB system among
SBES researchers was somewhat less strong than among biomedical
researchers (see below).
The commission's report on IRBs was issued in 1978; it supported
the basic IRB system and made numerous recommendations to streng-
5The Barber et al. (1973) study, the first to survey IRB operations, interviewed a
single individual at each of 300 institutions with a biomedical IRB, 70 percent of which
had existed prior to the 1966 USPHS requirement. It found that relatively few IRBs ever
required modifications of protocols: 34 percent had never modified or rejected a project.
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REGULATORY HISTORY
65
then and clarify its scope and procedures. Recommendations included:
definitions of "research" and "human subject;" an expedited review
procedure whereby IRBs could delegate the review of minimal-risk
protocols to the chair or a subset of IRB members; an expanded list
of types of information to disclose to obtain informed consent; and
a clearer specification of the conditions under which written consent
could be waived. The commission also recommended that IRBs should:
determine that study methods are appropriate (i.e., review protocols
for scientific soundness); determine that adequate procedures are in
place to protect privacy and protect data confidentiality; not consider
possible future harm from research results in making risk-benefit deter-
minations;6 and provide an opportunity for investigators to respond in
person or in writing to IRB decisions. Finally, the commission recom-
mended that DHEW should issue regulations applicable to all research
over which it had regulatory authority and that Congress should pass
legislation to cover human participants in all research over which the
federal government might have regulatory authority.7
In 1979 the commission issued the landmark Belmont report, which
articulated three basic principles for research studies involving hu-
mans: respect for persons, beneficence, and justice. This report quickly
became the bedrock on which subsequent work on protecting human
research participants was built.
SBES Activity
In both this period and earlier, the SBES research community de-
voted considerable attention to participant protection issues. A liter-
ature review conducted for a 1982 volume on Ethical Issues in So-
cial Science Research (Beauchamp et al., 1982) turned up more than
3,500 relevant citations. First and most prominent in the literature
was Herbert C. Kelman, who published a collection of early papers in
1968 as A Time to Spealc. Other leading publications in the years 1967-
1980 covered such topics as ethical dilemmas in SBES research, ethics
of social experimentation, legal issues in SBES research, politics and
SBES research, ethics of social intervention, ethical issues in behav-
ior modification, studying deviance, and confidentiality protection (see
Beauchamp et al., 1982:6-7,37-381.
6 Such harm could occur, for example, when results are unfavorable to a population
group to which research participants belong.
7 Congress never acted on this recommendation; legislation is pending at present
that would extend federal protections to all research involving human participants (see
"Developments Since 1991," below).
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66 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
BOX 3-1
Examples of Ethically Troubling SBES Research from the 1 970s
Milgram's (1974) "Obedience to Authority"
Summary Stanley Milgram, a social psychologist, carried out an experiment in the
1 960s in which volunteers were recruited to be "teachers" who were asked to administer
an electric shock of increasing intensity to a "learner" for each mistake made during
the experiment. The fictitious story given to these "teachers" was that the experiment
was exploring effects of punishment (for incorrect responses) on learning behavior.
The "teacher" was not aware that the Learner" in the study was an actor who merely
indicated discomfort as the "teacher" increased the (fake) electric shocks. When the
"teacher" asked whether increased shocks should be given, he or she was verbally
encouraged to continue. Sixty percent of the "teachers" obeyed orders to punish the
"learner" to the very end of the 450-volt scale; no subject stopped before reaching
300 volts. Many subjects were distressed by what they were asked to do. Subjects
were debriefed at the end of the experiment and offered counseling if they wanted to
examine their own behavior and feelings. Milgram later carried out variations of this
same experiment.
Commentary Milgram's experiments aroused intense controversy
about the conditions under which it is appropriate to use deception,
particularly when the consequence is intense (although apparently
transitory) psychological stress and even when subjects are informed
about the deception at the conclusion of the experiment. Milgram
subsequently resurveyed his original subjects, most of whom said they
supported the experimentation because it provided important information
about how ordinary people could be induced to behave in reprehensible
ways in response to a recognized authority, but this finding did not stop
the controversy.
Humphreys' (1975) "Tearoom Trade"
Summary Laud Humphreys, a graduate student in sociology, conducted a study for
his dissertation of homosexual behavior among men of high social standing in a large
Midwestern city. Pretending to be gay and a lookout for the police, he observed men
entering a public rest room in a city park, confirmed that they engaged in anonymous
homosexual acts, recorded their license tag numbers, obtained their names from a
contact in the Bureau of Motor Vehicles, and confirmed their identity and social status. A
year later he disguised himself and interviewed them in their homes about their personal
lives under the pretext of conducting a social health survey. When his dissertation was
published, many of the men and their families were able to recognize themselves from
the details that were reported about them. Humphreys' research had the perhaps
beneficial result that police stopped raiding "tea rooms" when they learned that many of
the men frequenting them were not people they wanted to arrest.
Commentary Had the Common Rule been in effect at the time of
"Tearoom Trade," his research would not likely have been approved.
Given the stigma attached to homosexuality, the study would not be
categorized as minimal risk, and, therefore, deception could not be used
(see Box A-9 in Appendix A on the criteria for waiver of informed consent).
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REGULATORY HISTORY
67
BOX 3-1 (continued)
Whether norms have changed to the extent that such a study might be
viewed as minimal risk today is not clear; however, informed consent
would certainly be required before study results could be published, and
other changes in study procedures would undoubtedly be required before
it could be approved.
Zimbardo's (1971) Stanford Prison Experiment
Summary In summer 1971 psychologist Philip G. Zimbardo studied the reactions of
male volunteers (Stanford University students) to a mock prison environment in which
some of them were assigned roles as prisoners, others as guards. The experiment
elicited such strong reactions from the participants, including abuse of some "prisoners"
by some "guards," that Zimbardo halted the 2-week study after only 6 days (see Faden
and Beauchamp, 1986:178-179; hitp:/www.prisonexp.org [4/10/03]).
Commentary This study did not involve deception. Whether such a study
would be approved today is unclear. Evidence from Milgram, Zimbardo,
and others that strong negative reactions are not uncommon would likely
make IRBs reluctant to approve further research of this type. However,
an investigator could propose steps to minimize risk, such as planning
prompt interventions of the type that were implemented by Zimbardo in
the prison experiment, that could make the study acceptable, and it would
have the potential to achieve important results for understanding social
interactions in stressful situations.
Social scientists and other researchers also engaged in vigorous de-
bates about the ethics of particular research projects, including the
Milgram "obedience to authority" experiments, Humphreys' study of
the "tearoom trade," and Zimbardo's study of prison behavior (see Box
3-11. None of these projects caused long-lasting physical harm to any
participant, but there was concern that they may have caused strong
short-term psychological effects and perhaps even long-lasting psycho-
logical trauma. However, for none of them, to our knowledge, has
there been any documented lasting harm to participants.
As a consequence of these debates and the growing concern with
human participant protection in SBES research, both the American
Anthropological Association and the American Sociological Associa-
tion adopted new codes of ethics in 1971. The American Psychological
Association, which had first adopted a code of ethics for clinical work
and research in 1953, sponsored extensive research and discussion on
ethical issues specific to psychological research and adopted a revised
ethics code in 1973 (Faden and Beauchamp, 1986; see also Chapter 41.
With regard to the 1974-1978 work of the national commission,
there is no available evidence that concerns about SEES research
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68 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
BOX 3-2
SBES Concerns in the 1 970s
Problems of 1974 IRB Regulations for SBES Research
· IRBs' insistence on wriffen consent when it was not needed and would damage the
research.
· Infringements of academic freedom resulting from IRBs' application of risk-benefit
criteria.
· The general lack of fit between the regulations and the ethical issues that arise in
some types of research (e.g., ethnography).
The failure of the regulations to address explicitly certain issues (e.g., deception,
privacy, confidentiality of data, and the use of research for teaching purposes) and
certain types of research (e.g., fieldwork or evaluation research).
· The conflict that can develop between writlen consent requirements and researchers'
responsibility to assure confidentiality of the identify of subjects.
· The lack of clear definition of the applicability of the regulations (e.g., just what is a
human subject).
· The harm to research that can result from application of consent requirements to
certain research, such as observational studies in public places and studies based on
existing records.
· The use of IRBs to protect vested interests (e.g., the alleged tendency of IRBs in some
medical schools and hospitals to discourage social research within their walls).
· Some IRBs' lack of reasonable flexibility in interpreting regulatory language.
· Some IRBs' lack of qualifications to review certain types of studies.
· The application of review requirements to research not funded by the federal
government.
.
.
The lack of appeal procedures.
SOURCE: Verbatim quotes from Gray (1982:354) of testimony provided to the National
Commission for the Protection of Human Subjects of Biomedical and Behavioral
Research.
played a part in its formation (the "behavioral research" part of its title
was not explicitly defined in its charter). As specified by Congress,
the commission membership included six people who were not re-
searchers and five who were: three physicians and two psychologists
were chosen to fill the researcher slots. Although the commission did
not represent the breadth of SBES expertise (or biomedical expertise,
for that matter), it did seek input from SBES researchers. Most of their
concerns, according to Gray (1982:335), "pertained to harm done to re-
search interests while providing no benefit to the interests of subjects"
(see Box 3-21. There were differing viewpoints: a paper commissioned
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REGULATORY HISTORY
69
from a sociologist who served as chair of an IRB that primarily re-
viewed SBES research argued that current regulations did not impede
research, provided they were interpreted reasonably (Barber, 19791;
a paper commissioned from another sociologist argued that existing
regulations did not properly address issues of informed consent and
confidentiality in SBES research (Reiss, 19791.
Data from the University of Michigan survey conducted for the com-
mission revealed that almost all researchers believed the IRB system
had helped protect human participants (at least to some extent), al-
though higher percentages of SBES researchers than of biomedical
researchers were critical of the system in some respects. For exam-
ple, excluding IRB board members, 54 percent of SBES researchers
agreed that the IRB system had impeded the progress of research at
their institution (at least to some extent), compared with 43 percent of
biomedical researchers (Gray, 1 9 82 :Table 1 6 .2~. ~
1979 Proposed Revision of Regulations
In response to the national commission's recommendations, the
NIH Office for Protection from Research Risks (OPRR) drafted a re-
vision of 45 CFR 46, which was published for comment in the Federal
Register in August 1979.9 The proposed revision raised a firestorm in
the SBES research community. The major problem appears to have
been that the regulations proposed to extend the IRB system to all re-
search involving human participants at institutions that received
DHEW funds, regardless of whether the particular protocol was funded
by DHEW, and to studies in all fields that sought generalizable knowl-
edge by using methods that collected information by which living or
dead individuals could be identified. (See Boxes A-1 and A-3 in Ap-
pendix A, which trace changes in language on applicability of the reg-
ulations and the definition of human subject, respectively.) This broad
scope could have subjected standard historical, document-based re-
search, interviews with public officials, observation of behavior at pub-
lic events, and other such studies to IRB review, including student and
investigator studies funded by the research institution itself or by an-
other federal agency and not DHHS. Furthermore, IRB review was
explicitly to consider the appropriateness of the research methods for
Researchers who were IRB members were much less likely to agree that the system
impeded research (30 percent of SBES IRB board members did so, as did 26 percent of
biomedical IRB board members).
9OPRR was established in the office of the NIH director in the early 1970s; it su-
perceded the Institutional Relations Branch of the Division of Research Grants, which
formerly had responsibility for oversight of human research participant protection (Mc-
Carthy, 1998:313).
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70 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
the objectives of the research and the field of study (see Box A-6 in
Appendix A).
The proposed revised regulations included provisions for IRBs to
exempt certain types of research from review and to review other kinds
of research by an expedited procedure (see Boxes A-4 and A-5 in Ap-
pendix A). The intent of these provisions was to exempt or expedite
much SBES research, such as that conducted by surveys, public ob-
servation, and study of documents. The exemption provisions were
restricted to research in which it was not possible to identify the hu-
man subjects (Alternative A) or that presented no or only minimal po-
tential for invasion of privacy (Alternative B). Similarly, the expedited
review procedures were restricted to minimal-risk projects in speci-
fied categories, and the proposed definition of minimal risk set a high
standard namely, that risks of harm be no greater than those experi-
enced in the daily lives of healthy individuals (see Box A- 11 in Appendix
A). SBES researchers argued that all of these features of the proposed
regulations subjected too many projects to full-scale review by an IRB
when such review was not necessary or useful or even (in some argu-
ments) constitutional.
On the positive side, the proposed regulations responded to some
SBES concerns that had been expressed in testimony before the na-
tional commission. Specifically, provisions were added to require IRB
review to consider the adequacy of proposed data confidentiality pro-
tections, to enable IRBs to modify some or all of the elements of in-
formed consent, and to enable IRBs to waive the requirement for writ-
ten documentation of consent (see Boxes A-6, A-9, and A-10 in Ap-
pendix A). These generally well-received changes (which remained in
the revised regulations) were overshadowed, however, by the negative
reactions to provisions that SBES researchers viewed as inimical to
good research.
Patullo (1982:373) characterizes the ensuing period until January
1981, when 45 CFR 46, subpart A, was revised, as follows:
For eighteen months, hundreds of individuals, some prin-
cipally concerned with maintaining a healthy research en-
terprise and some alarmed at basic incursions upon accus-
tomed freedoms, devoted thousands of hours to persuading
those who write the regulations that single-minded concen-
tration on precluding every possibility of harm to subjects
had produced a proposal that threatened much greater so-
cial harm than it might possibly prevent.~°
~°Patullo was among those who argued against the 1979 proposed regulations on the
basis that they threatened research and also among those who argued that the regula-
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REGULATORY HISTORY
71
The head of OPRR, which drafted the regulations, gave his view of
this tumultuous period as follows (McCarthy, 1984:8-91:
Threats and epithets were hurled at us from many sides.
These comments can be summarized as follows: 'Social and
behavioral research is essentially harmless to individuals
and benign to society. If you do not accept this view. . . we
will organize ourselves to see that you and your misguided
staff are drawn and quartered.' The charges were led by
Ithiel de Sola Pool [1979, 1980], who insisted that... our
four pages of fine print in the Federal Register were about to
lay waste to the First Amendment of the Constitution....
Friendly champions of social and behavioral sciences
showed us how to back away from our unpopular positions
while continuing to offer what we felt were reasonable pro-
tections for the dignity and rights of subjects involved in so-
cial and behavioral research to say nothing of saving the
face and the jobs of OPRR staff.
What were the indignities to subjects that we felt needed
attention? The Wichita jury bugging case, the tearoom trade
research, the decision of a Georgia court concerning Medi-
caid co-payment experiments and our own unpleasant
memories of Psychology 101 and Sociology 102, when we
felt we had better humor our professors... so we 'volun-
teered' as research subjects rather than risk grade discrimi-
nation!
We discovered that we could write exemptions for broad
categories of social and behavioral research categories in
which subjects' behavior seemed to us little different than
the commerce of daily life. It has been estimated that up
to 80~o of social and behavioral research funded by our De-
partment is now exempt. For the rest, we thought it not
unreasonable to concern Institutional Review Boards with
matters of privacy and confidentiality, and with efforts to
protect unsuspecting and vulnerable subjects.
The final regulations, issued in January 1981 by DHHS (which re-
placed DHEW in May 1980) responded both to the recommendations
of the national commission (see above) and the concerns raised by
SEES researchers. With regard to the latter, the regulations somewhat
narrowed the definition of a human subject and provided for certain
tions were developed without evidence that SEES research caused physical harm (see
Oakes, 2002:7).
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72 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
kinds of human subjects research to be exempt from IRB review. A
"human subject" was defined as "a living individual about whom an
investigator (whether professional or student) conducting research ob-
tains (1) data through intervention or interaction with the individual,
or (2) identifiable private information" fitalics added]. This definition
excluded some SEES research from IRB review, such as observational
studies in which private information was not obtained and studies of
information from past public records. In addition, the regulations
provided that four categories of human subjects research could be ex-
empted by an IRB from review (see Box A-4 in Appendix A):
research in educational settings on new or established instruc-
tional strategies and techniques, curricula, or classroom manage-
ment methods;
.
research involving educational tests, if identifiers cannot be linked
to the subjects;
· survey and interview research and observational research, unless
identifiers are being collected, disclosure could be damaging to
the participant, and the data pertain to sensitive subject behavior;
and
studies using existing data, documents, records, and the like, if
these materials are publicly available or if the data will not be
recorded in a manner that would allow linkage with individuals.
Finally, backing off from the 1979 proposal, the regulations applied
only to research sponsored by DHHS, although language was included
indicating DHHS's concern that the interests of all human research
participants, regardless of funding source, be protected at institutions
that received DHHS funding. Also backing off from the 1979 pro-
posal, the regulations excluded a requirement for IRB review of the
appropriateness of the proposed research design and methods, requir-
ing only that IRBs determine that risks to subjects are minimized "by
using procedures which are consistent with sound research design."
One observer concluded that "most social research is now exempt
from the regulations either because it is specifically exempted or be-
cause it is not federally supported, thoweverl, the extent to which IRBs
thin backing off from this position, which had been a recommendation of the na-
tional commission, DHHS responded to concerns of the SEES community, a growing
opposition to federal regulation in general, and a specific conclusion of the 1980 Presi-
dent's Commission for the Study of Ethical Problems in Medicine and Biomedical and
Behavioral Research that the National Research Act of 1974 could not be used to justify
extension of DHHS regulations to non-DHHS-funded research.
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REGULA TORY HISTORY
73
will actually continue to review such research remains to be seen"
(Gray, 1982:3441.
FROM 1981 TO 1991
With the adoption of the 1981 regulations, a period of relative calm
ensued. A handful of studies of IRB operations were carried out. One
study, which surveyed 341 IRB chairs soon after the passage of the
regulations, found that almost all IRBs at that time had decided not
to use the option to exempt protocols from review that fell under one
of the four eligible categories of educational, social, and behavioral
research (Grundner, 19831.
A somewhat later study examined how IRBs were functioning from
the perspective of political scientists; it queried 115 chairs of political
science departments that offered Ph.D. programs and chairs of IRBs at
those institutions (Cleary, 1987; see also Appendix D). Generally, most
chairs were supportive of the IRB system, reporting that most political
science protocols (88 percent) cleared without change. Problems iden-
tified included uncertainty and lack of information regarding infold ailed
consent and confidentiality protection; confusion at some institutions
as to whether unfunded student research was covered; and variability
in IRB procedures with regard to exemptions and infold consent.
In 1981 the President's Commission for the Study of Ethical Prob-
lems in Medicine and Biomedical and Behavioral Research (which met
from 1980 to 1983) recommended that a Common Rule be developed
that would apply to all federally supported research involving human
participants. In response, in 1982 the President's Science Adviser, Of-
fice of Science and Technology Policy, appointed an interagency com-
mittee to develop a common framework on the basis of the DHHS regu-
lations. The committee published a proposed common policy in 1986.
Its work culminated on June 18, 1991, when 45 CFR 46, subpart A,
was adopted in the regulations of 15 departments and agencies and by
the Central Intelligence Agency by legislation (see Box 1-1 in Chapter
11. The Food and Drug Administration also modified its regulations to
agree in large part with 45 CFR 46, subpart A.
In addition to making the Common Rule regulations applicable
to research conducted, supported, or regulated by any of the federal
agency signatories, the 1991 regulations incorporated several other
changes from the 1981 DHHS version (see Appendix A). First, the defi-
nition of research was expanded to include research development, test-
ing, and evaluation. Second, two categories of research that could be
exempted were added: research and demonstration projects involving
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74 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
public benefit or service programs and taste and food quality evalu-
ation and consumer acceptance studies. Third, the requirements for
exempting survey and observational research were modified so that
IRBs could more readily decide not to exempt as much research as
before (see Box A-4 in Appendix A). The list of types of research that
were eligible for expedited review, provided they were deemed to be of
minimal risk, was not changed at that time, but it was later amended
in a Federal Register notice in 1998: many more categories of SBES
research were added to the list than had been included in the original
(1981) list (see Box A-5 in Appendix A).
DEVELOPMENTS SINCE 1991
Raising the Alarm
Even as the federal regulatory system for protection of human re-
search participants was strengthened by the widespread adoption of
the Common Rule, a spate of reports in the mid- to late 1990s con-
cluded that IRBs were less and less able to meet their responsibili-
ties. These reports dealt almost exclusively with concerns arising from
biomedical, particularly clinical, research.
The first such report emerged from the Advisory Committee on Hu-
man Radiation Experiments, convened in 1994 to follow up media re-
ports of federally sponsored radiation research with human partici-
pants conducted between 1944 and 1974 that violated ethical no~s.~2
The committee also investigated the current state of human partici-
pant protection by reviewing the regulatory system, examining a sam-
ple of recent research proposals, and interviewing past, current, and
prospective research participants. While concluding that "significant
advances" had occurred in human participant protection since the
1940s and 1950s (Advisory Committee on Human Radiation Experi-
ments,1996:510), the committee found "evidence of serious deficien-
cies in some parts of the current system." These included substantial
variability in the performance of IRBs and inattention to problems of
informed consent for people with diminished decision-making capabil-
ity, as well as confusion among participants as to whether they were
involved in experimentation or treatment.
The U.S. General Accounting Office (GAO) in 1996 found that the
ability of IRBs to operate effectively was impaired by heavy IRB work-
loads, lack of expertise on IRBs to review complex research, failure
pouch experiments included injecting hospitalized patients with plutonium, likely
without their knowledge or consent, and intentional release of radiation into the envi-
ronment without public notice.
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REGULATORY HISTORY
75
of IRBs to exercise continuing review over research projects, and lack
of adequate facilities and support for IRB operations. The GAO also
found that OPRR lacked time and funding to conduct site visits to re-
view IRB operations, even though the value of such visits in identifying
IRB compliance problems was known.~3
Beginning in 1998 the DHHS Office of Inspector General issued a
series of reports warning that IRBs were being overwhelmed by the
complexity and volume of research they had to review. The first report
(Office of Inspector General, 1998b:ii-iii) concluded that "the effective-
ness of IRBs is in jeopardy" because "they face major changes in the
research environment," "they review too much, too quickly, with too
little expertise," "they conduct minimal continuing review of approved
research," "they face conflicts that threaten their independence," "they
provide little training for investigators and board members," and "nei-
ther IRBs nor HEIS devote much attention to evaluating IRB effec-
tiveness." Furthermore, the report claimed that IRBs lacked adequate
resources to do their job and were being pushed by regulations to focus
on paperwork requirements more than on basic ethical issues.
The National Bioethics Advisory Commission, established by pres-
idential appointment in 1995, concluded in its final report (2001:4-8)
that several factors underlay these gloomy assessments of the IRB sys-
tem. They included:
· a large increase between 1985 and 1996 in the volume of research
resulting from a two-fold increase in federally funded research
and a three-fold increase in industry-funded research (particu-
larly by pharmaceutical firms);
a growing propensity for academic medical centers to develop
ties with industry for research funding;
· an increase in industry-sponsored research conducted through
nonacademic organizations;
· the emergence of stand-alone IRBs that operate on a fee-for-service
basis;
a growing number of clinical studies conducted at multiple, some-
times hundreds, of sites;
i3Between 1990 and 1995, OPRR conducted only 15 site visits during the course of
over 200 compliance investigations triggered by charges of misconduct. No site visits
were conducted randomly, nor were any visits conducted as part of assurance negotia-
tions, when OPRR first reviewed an institution's written procedures for conformity with
the Common Rule (U.S. General Accounting Office, 1996:19).
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76 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
.
and new technologies, such as research on genetic links to dis-
eases and new gene therapies for medical treatment, and changes
in public attitudesi4 that pose new ethical challenges.
All of these factors overloaded IRBs with no offsetting increases in
the resources available for their work.
Federal Response
In response to these reports and to media attention on tragic events
in biomedical studies (see below), the federal government stepped up
its regulator efforts. In June 2000, the Office for Human Research
Protections (OHRP) was established in the Once of the Secretary of
DHHS, taking over responsibilities from OPRR and acquiring new
responsibilities (see http://ohrp.osophs.dhhs.gov t4/10/031; 67 Federal
Register 10217, March 6, 20021. OHRP was given a broad mandate,
not only to monitor the operations of IRBs that review DHlIS-funded
research, but also to provide guidance on human research participant
protection for the federal and nonfederal sectors, develop educational
programs, and exercise leadership for human participant protection
in cooperation with other federal agencies. A standing committee of
outside experts, the National Human Research Protections Advisory
Committee (NHRPAC), was established to provide continuing advice
to OHRP.
Prior to the establishment of OHRP, OPRR had become somewhat
more active in enforcement: from one on-site inspection in 1997, OPRR
conducted ten on-site inspections in 1998-2000 (all at medical research
centers). Several of these reviews resulted in temporary suspension
of all or some research at the visited institutions (Office of Inspector
General, 2000:2~.~5 OHRP emphasized working cooperatively with re-
search institutions and associations to develop training programs for
IRBs and investigators and to improve IRB operations, but it, too, on
occasion took drastic action. In July 2001 OHRP suspended nearly all
research at Johns Hopkins University when a healthy young woman
participating in a study about asthma medications died from an over-
~4Examples are research that is conducted with the assistance of community organi-
zations and initiatives by some very ill patient groups to obtain greater access to clinical
trials, seeing participation as a benefit, not a burden.
Din May 1999, OPRR suspended all research at the Duke University Medical Cen-
ter for 5 days and required several corrective actions, including re-review of DHHS-
funded research approved by the IRB, establishment of a second IRB, and development
of educational programs for IRB staff and members and researchers (National Bioethics
Advisory Commission, 2 00 1: 5 6).
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REGULATORY HISTORY
77
dose of an asthma-inducing substance (see Keiger and De Pasquale,
2002~.16
In these and other widely publicized incidents, such as the death
of Jesse Gelsinger in 1999 in a University of Pennsylvania gene trans-
fer experiment, it appeared that the researchers failed in one or more
respects to follow the protocol approved by the IR:B. Nevertheless, the
events increased calls for reform of the IRB system, such as recommen-
dations by the National Bioethics Advisory Commission (2001:xi-xxi)
for legislation to establish human participant protection for all pub-
licly and privately funded research and a single independent federal
office to lead and coordinate the oversight system; a single set of fed-
eral regulations and guidance; accreditation of IRBs; and certification
of IRB members.
In fall 2001 DHHS commissioned the Institute of Medicine to un-
dertake a thorough review of the IRB system, including proposed
schemes for voluntary accreditation of IRBs by nonprofit organiza-
tions (Institute of Medicine, 2001, 2002~. Congressional committees
held hearings, and Representatives DeGette (D-CO) and Greenwood
(R-PA) introduced a bill in May 2002 that would extend federal human
participant protection to all federally funded research and require the
harmonization of the Common Rule and Food and Drug Administra-
tion regulations. Senator Kennedy (D-MA) introduced a bill in October
2002 that would expand protections to all research involving human
participants. It would also strengthen OHRP, providing for a 6-year
term for the director.
SBES Involvement
During this same period, researchers involved in SBES studies in-
creasingly raised concerns that IRBs were overreacting to the increased
scrutiny of their operations by putting minimal-risk studies through as
time-consuming a review as clinical trials and other higher risk stud-
ies and by rigidly adhering to the main provisions of the regulations
rather than taking advantage of their options for flexibility. Some ar-
gued (although less strongly than in earlier debates about IRBs and
SBES research) that the IRB system infringed on academic freedom to
conduct research (see, e.g., Shea, 20001. Many argued that IRBs were
unnecessarily impeding research and sometimes increasing the risk to
participants by their bureaucratic stance for example, by requiring
written consent even when such consent could endanger participants
thin all, work on 2,400 protocols was halted, some for 5 days and some for longer pe-
riods. Research at Johns Hopkins' Homewood campus, which operated under a different
federal assurance, was not affected.
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78 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
by linking them to the study (see, e.g., American Association of Uni-
versity Professors, 2001; Brainard, 2001; Moreno, 2001; Shea, 20001.
In 1998, at the behest of the SBES community, additional categories
of minimal-risk SBES research were added to the list of research cat-
egories that IRBs could review under expedited procedures (see Box
A-5, Appendix A).
SBES researchers also fought to become involved in key groups
that were part of the debate and that often initially excluded SBES
disciplines. In January 2001, NHRPAC (the advisory body to OHRP)
was expanded from 11 to 17 members in order to include SBES re-
searchers. In June 2001, NHRPAC established an ad hoc Behavioral
and Social Science Working Group, which is currently operating as
a separate entity with private foundation funding. In September 2002,
DHHS declined to renew NHRPAC's 2-year charter. A new Secretary's
Advisor Committee on Human Research Protections was chartered
in October 2002 with 11 members. The membership of the commit-
tee was announced in January 2003; it includes only two SBES re-
searchers, both psychologists.~7
The National Science Foundation (NSF), a principal funder of SBES
research, established an ad hoc Social, Behavioral, and Economic Sub-
committee for Human Subjects. The subcommittee developed a guide
for SBES researchers, which was put up on the NSF Policy Office web-
site as "Frequently Asked Questions and Vignettes: Interpreting the
Common Rule for the Protection of Human Subjects for Behavioral
and Social Science Research" (National Science Foundation, 20021.
A new Association for the Accreditation of Human Research Protec-
tion Programs (AAHRPP) added 3 seats for SBES researchers to its
21-member board and involved SBES researchers in pilot tests of ac-
creditation procedures at several dozen research institutions. (See
Appendix B for information about groups active in and resources for
human research participant protection.)
i7See http://www.hhs.gov/news/press/2003press/20030 ~ 1 3a.html [2/23/03]. In De-
cember 2002 the presidents of the National Academy of Sciences, the National Academy
of Engineering, and the Institute of Medicine wrote a letter to DHHS Secretary Thomp-
son stating that "it is critical for this important body to represent all of the scientific
disciplines engaged in research with human participants that is, the biological, clini-
cal, social, behavioral, and economic sciences."
i8AAHRPP was established in May 2001 as the national accrediting arm of Public Re-
sponsibility in Medicine and Research. It is developing a voluntary, peer-driven human
research accreditation program, using a site visit model; see Appendix B.
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REGULATORY HISTORY
79
CONCLUSION
This brief history makes clear that the concerns of the SBES re-
search community about the IRB system are not new. In fact, the
lists of concerns voiced in 1974 (see Box 3-2) are remarkably similar
to those being voiced today. Moreover, both today and three decades
ago, some researchers believe that the regulations need to be changed,
while others maintain that the regulations have sufficient flexibility and
the real concern is with their interpretation.
fine conclude that the current focus for improvement of participant
protection and facilitation of research in SBES should be on the devel-
opment of guidance and other means to encourage IRBs to avail them-
selves appropriately of the flexibility in the regulations rather than on
further changes in the regulations themselves. A primary reason for
our conclusion is the past successes of the SBES research community
with respect to regulatory change. Thus, in the late 1970s, SBES re-
searchers successfully participated in a process that resulted in the cur-
rent provisions for exemption and expedited review. In the late 1990s,
SBES researchers influenced the process that resulted in an expanded
list of types of research that, if minimal risk, could be reviewed with
an expedited procedure. The regulations also provide for flexibility in
procedures for obtaining and documenting informed consent.
As we discuss in subsequent chapters, OHRP and other actors in
the protection system, such as accreditation organizations and pro-
fessional associations, must assert leadership in providing guidance
that can help IRBs use the flexibility in the Common Rule to carry out
their responsibilities more effectively. To assure the development of ap-
propriate guidance, SBES researchers must actively continue to seek
formal and informal channels for input to OHRP and other relevant
agencies and organizations. The SBES research community must also
actively seek to develop a knowledge base that can inform OHRP, IRBs,
and researchers about appropriate procedures for informed consent,
balancing of risks and benefits, and other aspects of ethically responsi-
ble research.
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80 PROTECTING PARTICIPANTS AND FACILITATING SOCIAL AND BEHAVIORAL SCIENCES RESEARCH
decided not to use the option to exempt protocols from review that
fell uncler one of the four eligible categories of eclucational, social,
and behavioral research (Grundner, 1983~.
A somewhat later stucly examined how IRBs were functioning
from the perspective of political scientists; it queried 115 chairs
of political science departments that offered Ph.D. programs and
chairs of IRBs at those institutions (Cleary, 1987; see also Appendix
D). Generally, most chairs were supportive of the IRE system, re-
porting that most political science protocols (who) cleared without
change. Problems identified included uncertainty ant] lack of infor-
mation regarding informed consent and confidentiality protection;
confusion at some institutions as to whether unfuncled student re-
search was covered; and variability in IRB procedures with regard
.
to exemptions en cl informed consent.
In 1981 the Presiclent's Commission for the Study of Ethical
Problems in Medicine and Biomedical and Behavioral Research
(which met from 1980 to 1983) recommended that a Common Rule
be ~leveloped that wouic! apply to all federally supported research
involving human participants. In response, in 1982 the Presiclent's
Science Adviser, Office of Science and Technology Policy, appointed
an interagency committee to develop a common framework on the
basis of the DHHS regulations. The committee published a pro-
posed common policy in 1986. Its work culminated on June 18,
1991, when 45 CFR 46, subpart A, was adopter! in the regulations of
15 departments and agencies and by the Central Intelligence Agency
by legislation (see Box 1-1 in Chapter 11. The Food ant! Drug Acimin-
istration also mortified its regulations to agree in large part with 45
CFR 46, subpart A.
In addition to making the Common Rule regulations applicable
to research conducted, supported, or regulated by any of the fecI-
eral agency signatories, the 1991 regulations incorporated several
other changes from the 1981 DHHS version (see Appendix A). First,
the definition of research was expanded to include research clevel-
opment, testing, anct evaluation. Second, two categories of research
that could be exempted were addecI: research and demonstration
projects involving public benefit or service programs and taste and
food quality evaluation and consumer acceptance studies. Third,
the requirements for exempting survey ant! observational research
were mollified so that IRBs could more readily decide not to ex-
empt as much research as before (see Box A-4 in Appendix A). The
list of types of research that were eligible for expedited review, pro-
5
Representative terms from entire chapter:
informed consent
