Appendix I: History of Regulatory Efforts in This Area
History
of Regulatory Efforts in This Area
When the National Commission was created in 1974, the
decisionally impaired were among the special populations that
it intended to consider, partly because of the controversy
about lobotomy. In its 1978 Report and Recommendations on
Research Involving Those Institutionalized as Mentally
Infirm,263 which came at the very end of its tenure,
the National Commission rejected both the Nuremberg
Code’s complete ban and the 1964 Declaration of
Helsinki’s limitation on the involvement of incapable
subjects in research. The members of the National Commission
believed a less restrictive approach was justified to avoid
indirect harm to incapable persons by crippling research
efforts designed to yield potential treatment for these
persons’ conditions. They introduced this idea as
follows:
[S]ince some research involving the mentally infirm cannot
be undertaken with any other group, and since this research
may yield significant knowledge about the causes and
treatment of mental disabilities, it is necessary to
consider the consequences of prohibiting such research.
Some argue that prohibiting such research might harm the
class of mentally infirm persons as a whole by depriving
them of benefits they could have received if the research
had proceeded.264
This concept marked an important turning point in the
social philosophy underlying the regulation of human subjects
research; benefits to others (particularly those who now or
someday may suffer from the same disorder) could now be given
more weight. The National Commission concluded that the dual
goals of benefiting mentally infirm persons and protecting
individual subjects from undue harm could be met by a third
approach: incapable subjects could be involved in studies
offering them potential direct benefit, as well as studies
that did not offer potential direct benefit, as long as the
burdens and risks of research participation did not exceed a
certain level.
Based on this general approach, the National Commission
created a framework for evaluating research involving
incapable subjects. Its proposals regarding children and
institutionalized persons with mental impairments were
similar, though with some variation. Their common elements
included a requirement to justify the involvement of these
subject groups rather than alternative but less vulnerable
subject populations; a hierarchy of research categories
establishing more rigorous substantive and procedural
standards for proposals presenting more than minimal risk to
incapable subjects; and a mechanism for incapable subjects to
provide input in the form of "assent" or objection to study
participation—that is, a simple yes or no when
questioned about willingness to be in a study.
Differences in the recommendations on children and
institutionalized persons were based on the National
Commission’s recognition that some adults
institutionalized as mentally infirm retain the ability to
give an informed and voluntary decision. Because of concerns
about the vulnerability of institutionalized persons,
however, the National Commission recommended that IRBs be
given discretion to appoint "an auditor to observe and assure
the adequacy of the consent process for research" that
presents greater than minimal risk. Moreover, the National
Commission believed that such auditors should be required in
projects presenting no prospect of direct benefit and more
than minimal risk to subjects. Their proposals also gave
incapable adults more authority than children to refuse study
participation.265 Finally, because incapable adults usually
lack the legal guardian that most children have, the National
Commission noted that in some cases a court-appointed
guardian would be required to authorize research
participation.
In response to the National Commission’s work, DHEW
proposed regulations to govern research on the two
populations. Those affecting children were adopted by DHHS in
June 1983,266 but those affecting persons
institutionalized as mentally infirmed were not.267 In explaining
why the latter were not adopted, the Secretary of DHHS
pointed to a lack of consensus on the proposed regulatory
provisions and a judgment that the general regulations
governing human subjects’ participation sufficiently
incorporated the National Commission’s
recommendations.268 Robert Levine blames the reported lack of
consensus on DHEW’s earlier failure to adhere to the
National Commission’s recommendations.269 In particular,
DHEW’s proposed regulations indicated that consent
auditors might be mandatory for all research involving
institutionalized mentally disabled persons, and suggested
that the authorization of an additional person assigned the
role of independent advocate might be necessary before an
incapable person could become a research subject. During the
public comment period, many respondents objected to these
additional procedural requirements, presumably on the belief
that they were unnecessary and overly burdensome to
research.270
The 1981 DHHS rules largely followed from the National
Commission’s work. In 1991, these rules were codified
for 16 federal agencies that conduct or sponsor research with
human subjects and are now known as the "Common Rule."271 In
the United States today, research involving adults diagnosed
with a condition characterized by mental impairment is
governed by no special regulations, but falls instead under
the Common Rule, in which a few provisions address research
involving persons with mental disabilities. First, the Common
Rule identifies "mentally disabled persons" as a vulnerable
population, and directs IRBs to include "additional
[unspecified] safeguards . . . to protect the rights and
welfare" of mentally disabled research subjects. These
safeguards could involve consultation with specialists
concerning the risks and benefits of a procedure for this
population, or special monitoring of consent processes to
ensure voluntariness. It is not known how frequently IRBs
actually implement such measures.272
The Common Rule also advises IRBs to ensure that "subject
selection is equitable."273 In particular, "[i]f an IRB
regularly reviews research that involves a vulnerable
category of subjects, such as . . . mentally disabled
persons, consideration should be given to the inclusion of
one or more individuals who are knowledgeable about and
experienced in working with these subjects."274 The Common
Rule allows an incapable individual’s "legally
authorized representative" to give valid consent to the
individual’s research participation,275 but provides
no definition of incapacity, no guidance on the identity or
qualifications of a subject representative beyond "legally
authorized," and no guidance on what ratio of risks to
potential benefits is acceptable.
In the 1980s and 1990s, numerous groups and individuals
expressed dissatisfaction with gaps in the existing
regulations. After the ACHRE reviewed eight studies conducted
in the early 1990s involving adult subjects with uncertain
decisionmaking capacity, and found that four of the studies
required subjects to undergo diagnostic imaging that offered
them no prospect of direct benefit and that two appeared to
present greater than minimal risk to the subjects, it noted,
"there was no discussion in the documents or consent form of
the implications for the subjects of these potentially
anxiety-provoking conditions. Nor was there discussion of the
subjects’ capacity to consent or evidence that
appropriate surrogate decision makers had given permission
for their participation."276 Inquiries into studies
involving rapid medication withdrawal from persons diagnosed
with schizophrenia have also raised questions about the
adequacy of current federal policy and the ethical
acceptability of certain research protocols.277
NBAC is not aware of strong evidence that IRBs are
actively using, or not using, their existing discretionary
authority when reviewing protocols involving individuals with
mental disorders. In addition, although IRBs currently have
authority to monitor research in progress, including research
involving persons with mental disorders, it does not appear
that such monitoring routinely occurs, possibly because
institutional and other resources have not been devoted to
this critical activity. Observers of the review process agree
that although the workload of many IRBs at some of the
largest research centers has greatly increased in recent
years, the institutional support for IRB activities has often
not kept pace.278 While some institutions have responded to
this increase by establishing more than one board, the
practice may not be widespread enough. According to the
report of the DHHS Office of the Inspector General,
monitoring of a protocol’s progress after its initial
approval is practically nonexistent apart from
investigators’ routine filing of annual progress
reports. After the initial stages, local review has only
minimal impact on actual research practices.279
The lack of more specific federal guidance on research
involving persons with mental disorders has also meant that
research not under federal jurisdiction has been subject to
widely divergent state laws and regulations; most states have
no rules that specifically apply to research involving this
population while some states have quite restrictive
regulations. Several states currently prohibit certain types
of research on persons with mental disorders, such as
research that presents greater than minimal risk without the
prospect of direct benefit to subjects.280 This suggests
that both IRBs and researchers may have trouble identifying
(and thus following) the procedures required for ethical and
legal investigations involving persons with mental disorders,
even in states that have attempted to provide the badly
needed guidance.
Uncertainty about legal and ethical norms can contribute
to an adversarial tone in public discourse about this kind of
research. Indeed, as events in New York State illustrate,
advocacy of sharply differing ethical perspectives can result
in litigation. In T.D. v. New York State Office of Mental
Health, several individuals and organizations challenged
regulations of the New York State Office of Mental Health
with respect to participation in greater than minimal risk
research by minors and persons who lacked the capacity to
give informed consent. In 1995, the trial court invalidated
the regulations on the grounds that the Office of Mental
Health lacked statutory authority to adopt them.281 The next year,
the intermediate appellate court in New York agreed with the
trial court’s conclusion but added a far more
wide-ranging critique of the regulations, indicating that
they violated both constitutional due process rights and
substantive protections granted these research subjects under
New York’s statutory and common law.282 Finally,
however, New York’s highest court narrowed the judicial
holding to the original decision of the trial court.283
Cognizant of the tensions revealed in the New York case,
officials in Maryland have undertaken a cooperative process
of policy formulation. A working group under the auspices of
the Maryland Attorney General has, over more than 2 years,
produced a series of reports culminating in a proposed state
statute that would govern the substantive and procedural
aspects of research involving "decisionally incapacitated
individuals."284
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Footnotes