Subjects’
Rights,
in the
Freedom
of Inquiry,
E. MEYER,
‘
‘ ‘
To THOSE OF US with a humanistic orientation who were educated in the medical schools of the late 1950s and early 1960s, the movement to apply human studies reviews and an ethical brake on research is understandable and justified. To those of us with a concern about the advancement of knowledge and the importance offree inquiry to our profession and our society, the present rush by some to condemn and restrict clinical research (and other scientific studies with human subjects) suggests a dangerous trend that may have moved beyond its initial noble impulse. The scientific community has responded by defending the enterprise on the basis of previous achievements and the continuing need for the struggle against diseases that afflict humankind. The failure of this defense was suggested by a recent editorial in the New York Times (1) equating this position with the defense mustered by our intelligence agencies on behalf of practices that were said to serve the interests of national security. In this context, our political system has seemed to be moving to set up countervailing forces and adversary procedures designed to “equalize” the interaction between research scientists and research subjects. at the 129th annual meeting Miami Beach, Ha., May
of the American 10-14, 1976.
Psychiatric
At the time this work was done, Dr. Meyer was Associate Professor of Psychiatry, Harvard Medical School, Boston, Mass.; Director, Harvard-Boston University Center for Biobehavioral Studies in the Addictions, Boston, Mass.; and Associate Director, Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, Mass. He is now Chairman and Professor, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Conn. 06032.
Future
of Research
M.D.
Since the recent passage ofregulations concerning subjects’ rights andfreedom ofinquiry, opposition by the public and others to some areas ofresearch in the addictions has prevented its implementation or continuation. Research investigators in the biomedical and behavioral sciences have been placed in the position ofdefending their work in an adversary climate. The authorpoints out the importance of transmitting to the public, the scientific community, and legislators the investigators’ concern that ‘subjects rights not be viewed only in a legalistic context, but also in the context ofnot harming the patient.
Presented Association,
the
Addictions
BY ROGER
‘
and
If the concern about research with human subjects were limited to a concern about inadvertent or unavoidable harmful consequences of innovative procedures or research methods, then one could realistically restrict potentially harmful procedures while providing a mechanism to compensate subjects who have participated in research and who have sustained inadvertent complications consequent to their participation in the experiment. This would be consistent with the medical ethic primum non nocere , ‘above all do no harm. We have, however, moved into an area where the ethics of human experimentation are increasingly being defined on the basis of “imperatives” that are more consistent with the principles, practices, and beliefs ofcivil liberties attorneys. It is in the context of these ethical imperatives that individual research investigators have been unable to defend their work and approved research projects have been stopped. To some, this situation is reminiscent of the legitimate anguish of the oppressed against the oppressor elite. To others, the situation is but one more repetition of the classic struggle between scientists and those who hold political power as to whether science shall serve or be independent of political ideology. The distinguished philosopher Charles Frankel has observed that it is not technology per se that threatens mankind or a humanistic view of man; rather, the real threat lies in the tendency of some people to superficially link technological data to support for ideologies and movements (2). Indeed, on the issue of censorship of biomedical reearch, Frankel wrote, ‘
‘ ‘
For while technology is equivocal in its consequences, one thing is not-the damage that ensues, almost always very quickly when a field of inquiry is banned because it is said to subjects
conflict with higher that can come under
The character of the people axe is not reassuring. (2)
moral laws. The number of this axe is indefinitely large.
who have
ever
wielded
this
The future of clinical research seems least secure in areas of experimentation into the causes and treatment of nonlethal conditions, particularly in fields where treatment and prevention programs are polarized and scientific advances “appear” to offer little and may threaten philosophical positions. By these criteria, research into the causes and treatment of substance abuse should be controversial, and it is. There are two general areas of controversy that can be highlighted by Am J Psychiatry
134:8,
August
1977
899
RESEARCH
IN
THE
ADDICTIONS
case examples. A third general and privacy) has been described
FREEDOM
OF
INQUIRY
VERSUS
area (confidentiality by Robins (3).
Narcotic
Study
ofAlcoholic
Mothers
Data from a study by Jones and associates (4) suggest that offspring of alcoholic mothers may have a greater likelihood of premature birth and various 1evels of neonatal distress. The neonatal opiate withdrawal syndrome in the offspring of heroin-addicted mothers was described a number of years ago and has been updated by the work of Finnegan and associates (5). The question of neonatal distress in the offspring of alcoholic mothers is in need of more careful delineation. A team of psychiatrists, obstetricians, and pediatricians at a municipal hospital undertook a study of neonatal behavior and development in the offspring of mothers who were being seen in the prenatal clinic and who were identified as having problems of alcohol abuse. The physicians offered a program of psychotherapy coordinated with the prenatal care to assist the expectant mothers with their drinking problems. Preliminary data suggested that the offspring of mothers who drank heavily were at high risk as compared with the offspring of patients who drank moderately or rarely. On the basis of these preliminary findings, a grant was prepared and submitted to the National Institute on Alcoholism and Alcohol Abuse (NIAAA). Because the protocol also included the support of a treatment and prevention program, the review group included persons who could consider all aspects of the study. One of the reviewers was a community activist on the staff of an agency affiliated with the medical school at which the work was to be done. Despite the fact that this institutional affiliation should have excluded him from the review, he participated in the review of the grant application and a subsequent site visit. The NIAAA staffthen demanded that, in addition to the already obtained institutional reviews, the protocol be considered by a locally constituted group called the Community Research Review Committee. After reviewing the protocol, the committee felt that the research might draw defamatory conclusions regarding the competency of black mothers, since 55% of the clinic population was black. The committee insisted on monitoring the personnel practices and conduct of the research and previewing any formal or informal reports emanating from the project. In order to effectively monitor the work, the committee members stated that they would have to receive a portion of the budget as overhead. The principal investigator was told that since it was already the responsibility of the NIAAA and the institution to monitor the project, federal funding for a third group of monitors could not be budgeted. While it was clear that the NIAAA staff had erred in requiring that the research investigator obtain 900
AmJPsychiat
134:8,
August
group, it was that the fullface of deter-
RESTRICTED
INQUIRY
The
the sanction of this locally constituted also clear to the research investigator scale program was not possible in the mined political opposition.
1977
Antagonist
Project
1
The Community Research Review Committee has made similar budgetary demands upon a number of other nonpolitical research investigators whose research projects involved studies into the causes and treatment ofnonlethal conditions. The committee members have been relatively selective in their approach and apparently have not made these demands upon all research investigators in the geographical area. On one previous occasion they approached a team of research investigators who proposed to study the effects of narcotic blocking drugs in a population of heroin addicts at the same municipal hospital. Their demands at that time included 10% of the budget, 50% of the positions, and the appointment of an associate director of the project from among the membership of their committee. They also demanded censorship of reports. The thrust of the committee’s concern regarding studies of narcotic antagonist treatment of heroin addicts seemed to be that the research investigators were taking a simplistic, biomedical view of a complicated social problem that (in its view) really required a solution to the problems of poverty and other social ills in the community. While the causes of addiction may be multifactorial, the committee was concerned that the biomedical orientation of the research project conflicted with its own view regarding the causes of the problem and its own definition of funding priorities. Faced with powerful opposition that undermined the support by the hospital’s trustees, the research investigators chose to transfer this project to another community. While individual communities will continue to be able to exercise a political veto over research within their midst, the real question concerns the application of this principle on a larger scale. At least one monograph prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (6) proposed to sanction “community consent,” which it defined as “informed consent negotiated with the community in which it is planned to conduct research or from which it is planned to draw prospective subjects.” If this recommendation is adopted in this form, its consequences for the future of research could be extremely restrictive. As the Edelin trial has demonstrated, such political pressure can come from diverse sources and can scapegoat ethical practitioners and scientists. Federal
Opposition
to Behavioral
Research
Political concern about behavioral research with relevance to addictive drugs has not been limited to ad hoc community groups. Comments by Senator Proxmire and the threat by several congressmen to cut off
ROGER
funds from the National Institute on Drug Abuse prevented the implementation of an approved and funded research project at Southern Illinois University on the effects of marijuana on human sexuality. The researcher had previously obtained local lay approval for his study, in addition to required institutional reviews. The penultimate federal document challenging the ethics of behavioral experimentation was a report prepared by the Senate Judiciary Committee on Individual Rights and the Federal Role in Behavioral Modification (7). The report alleged, The behavioral technology being developed in the United States touches upon the most basic sources of individuality, and the core of personal freedom. . . . While psychosurgery under certain forms of electrophysiology is perhaps the most . . . sophisticated method of behavioral control, there are now being tested a number of other techniques based on more traditional, psychological primciples [that] pose similar questions with regard to individual liberties. (7)
The
implications
of this
strict
behavioral
research
report in
suggest the
the
interests
need of
the
to recivil
rights of individuals in the future, as well as the present. It is curious that alcoholism and drug addiction are major behavioral disorders whose alteration will require one or another form of behavioral modification. Indeed, methadone maintenance, narcotic antagonist treatment, and self-help residential programs all seek to modify behavior. The issue would seem to be whether clinical research in these areas can proceed in a variety of voluntary and nonvoluntary settings with appropriate regard for adequate and voluntary informed consent.
SUBJECTS’ TREATMENT;
RIGHTS VERSUS SUBJECTS’
SOCIETY’S
NEEDS
THE RIGHTS
RIGHT VERSUS
TO
There is a recurring notion that research subjects must be protected from researchers by an adversary process (consent committees versus review committees, and patient advocates versus research physicians). The adversary process is a legal construct that works effectively in the courts and the political system. When applied outside this framework to the practice of medicine and research, it may run counter to the medical ethic of “do no harm.” Indeed, as in the field of mental health generally, the arbitrary imposition of “individual rights” in a legal context may impose medical and social risks for individual patients. The following examples highlight the problem in addiction research. Antagonist
Vaillant studies on
Project
(8) has carried heroin addicts
2
out extensive follow-up discharged from the U.S.
MEYER
Public Health Service Hospital in Lexington, Ky. From his work it is clear that patients who are on probation or parole do better in all forms of treatment. Indeed, many of the self-help residential ‘concept houses” have increasingly restricted admission to patients who are court referred because the dropout rate of volunteers in these hierarchical, authoritarian environments was too high. Vaillant’s findings are clear: in the absence of some system of control, the addict is not able to modify his own behavior. As I have described elsewhere (9), that control can be manifested by methadone maintenance; an authoritarian, hierarchical residential community; or the criminal ‘
justice
system.
The recidivism rate of former heroin addicts discharged from prison is quite high. This population presents unique problems in terms of the relatively effective treatments available to narcotics users. Since they have been drug free for a period of time in prison, they are not considered appropriate candidates for a program of opiate substitution (e.g., methadone maintenance). Since they have been living in a prison for a period of time, they are not anxious to volunteer for a 9- to 24-month residence in a “concept house.” While parole or probation support may be helpful to the mdividual in his efforts to seek ajob or obtain some sort of counseling, the presence of many stimuli associated with previous addiction cycles (familiar friends and “drug copping areas”) may encourage relapse. The National Institute on Drug Abuse recognized that this population might be ideal for narcotic antagonist treatment. They funded one such project in one community in association with that city’s drug treatment program. The principal investigator of the project described its course as follows: The project
as approved
and funded
by HEW
proposed
to offer treatment to prison inmates shortly prior to their release from prison and during a parole period subsequent to release. A condition ofthe project . . . stated that under no circumstances could participation in the project be a consideration for parole. Plans were finalized for the conduct of the project in such a way that patients would not be approached to give informed consent until after the parole board had met and voted for parole. Despite the fact that ajoint medical school and hospital based human studies committee approved ofthis project, the study attracted widespread local attention when the research protocol was stolen in a burglary of the office of the principal investigator. [The study was described in the local media in such a way that prison inmates were seen as guinea pigs and parole was described as dependent on participation in
the study.] tion of agencies’
As a consequence
these allegations, human study
the project. resulted
Narcotic
E.
with
In a long series four
of the widespread
community committees
additional
of reviews, human
based requested
circulaand other review of
multiple studies
meetings
committees,
and the project met with final approval shortly before the expiration of the project period. Only two subjects entered the research study and HEW finally made the judgment that extension of the project with refunding was unwise. The principal investigators viewed the episode as Am
J Psychiatry
134:8,
August
1977
901
RESEARCH
IN
THE
ADDICTIONS
one
of continuous harassment by an ill-informed of well-intentioned but unsophisticated times ad hoc human studies committees.
and a series
media and at
When one considers the number of “rehabilitation measures” that are routinely employed in the context of parole, probation, and other aspects of the criminal justice system, one is struck by the fact that these measures are seldom evaluated. Indeed, if informed consent is ruled out for this population in an a priori manner, then the population will be exposed to all sorts of unevaluated interactions with undefined risks while being prevented from participating in rehabiitation programs with a research-oriented design. The
Addiction
Research
Center
Forty years ago the Public Health Service set up the Addiction Research Center at Lexington, Ky., in order to screen new drugs for their potential to cause addiction, to explore the biomedical and behavioral aspects of the addiction process, and to evaluate potentially promising pharmacological approaches to the treatment of addiction. Over the years the mission has evolved consistent with evolving federal priorities. The addiction liability of many new analgesics became known before they could be advertised as “nonaddicting.” The human pharmacology of methadone, 1 -a-acetylmethadol, cyclazocine, naloxone, and naltrexone were all delineated at Lexington. Over its 40year history there have been no deaths or serious disabilities consequent to this research. With the development of locally constituted drug treatment programs in nearly all parts of the country, the need for a “treatment farm” for volunteers in Kentucky became unnecessary. Instead, in 1973 the Federal Bureau of Prisons relocated its facilities for known heroin addicts to Lexington in proximity to the Addiction Research Center. It is now four years later. The staff at the Addiction Research Center was told that they could not begin any new studies using federal prisoners after January 1 1977. The distinguished team of pharmacologists and behavioral scientists has been perplexed. Dr. Wilham Martin testified before the National Commission for the Protection of Human Subjects in March 1976 ,
concerning
the
importance
of
the
work
and
the
safety
of the procedures. Within a month of Dr. Martin’s testimony, the Bureau of Prisons acted independently in response to congressional inquiry and unilaterally ordered the end of research in prisons under its jurisdiction. This order came out before the conclusion of deliberations and the preparation of the final report by the national commission. In his testimony, Dr. Martin wondered how society’s needs for safe analgesics and new pharmacological approaches to the treatment of addiction could be reconciled with the closing of Lexington. He reviewed the safety of the procedures at Lexington, and he argued that the prisoners were capable of giving informed consent. 902
Am J Psychiatry
134:8,
August
1977
COMMENT
Four issues have been raised with regard to informed consent in research involving the mentally disabled, children, and prisoners: 1) the question of the capacity of individuals in each group to give informed consent, 2) the question of coercion, 3) the question of a need for an adversary procedure to defend the rights of research subjects, and 4) the question of community consent. While all four of these questions have been applied to the mentally disabled, only one has been applied to research with prisoners and persons in the criminal justice system-the issue of coercion within an institutional setting. Persons living within institutions are thought to be at risk for coercion. One of the monographs prepared for the commission, which dealt with the mentally disabled, stated, “When proposed research is considered therapeutic, an institutionalized individual may be under more pressure to participate insofar as the possibility exists that the anticipated benefit may relieve the mental illness, and thus increase the likelihood that the patient would be released” (10). So far as research with prisoners is concerned, the problem ofcoercion has been presumed to exist in all phases of the criminal justice system. Regarding research with drug-dependent patients, there may be the presumption of mental disability, and all four issues of informed consent have been raised in different quarters
that
contexts. to assume
coercion
versary
procedures
There
has
been
a tendency
that diminished capacity by the researcher is likely, and and
some
form
in some
exists, that ad-
of community
con-
sent are essential to protect the individual rights of research subjects. The resolution of these issues will be different if primary concern is given to the health and safety of the individual and society’s needs as opposed to individual rights. It is paradoxical that the case for “health and safety,” “society’s needs,” and “individual rights” is usually argued for hypothetical individual patients and subjects by elitists who presume to know more than the patients themselves about what is “good” for them. Indeed, the struggle between objectivism, intellectualism, and the pursuit of knowledge on the one hand and subjectivism anti-intellectualism and equality’ on the other, is a political conflict with implications beyond the limits of biomedical and behavioral research. Daniel Patrick Moynihan has quoted the political philosopher Joseph Schumpeter in words that seem to have some relevance: “It is an error to believe that political attack arises primarily from grievance and that it can be turned by justification. Political criticisms cannot be met effectively by rational argument” (11). ,
,
,
“Equality” has recently come to mean that all points of view are equally valid in any situation involving two or more persons, that the power to veto is distributed widely and across many issues, and that executive power (literally the power to execute, implement, or develop) must be reduced until progress proceeds only by consensus.
ROGER
In the present climate, appeals to the need for scientific advancement will not, and are not, convincing those with power and authority to let the enterprise continue in a number of communities. The research projects that have been stopped were defended (it seems to me) in a characteristic way. The research investigators met repeatedly with their most militant adversaries. They did so at the urging of their colleagues, who let them enter these meetings without significant support. The principal investigators and their colleagues believed that reason would prevail and that they would be able to convince their most ardent opponents. At the least, they expected that they could effect a compromise that would enable them to continue to work and would enable their adversaries to feel that they, too, had accomplished their ends. The institutions that had previously supported the research now supported the mediative process, thereby invalidating the previous support of the project that had been granted by the human studies committee and other relevant structures. Committees were set up to assist in the mediation; the committees usually consisted of the more militant opponents of the research and some individuals who were deemed friendly (although not emotionally committed) to the work of the research investigators. It is untenable for the research investigator to defend his work on his own. It is also probably untenable for the scientific community to defend itself without major support from lay organizations. Previously, lay groups, like some of their scientific counterparts, have been organized to support categorical research. This has increased the risk of “salami tactics” by opponents of research, since attacks on individual projects have not been considered a threat to broader categories of biomedical and behavioral research. A coalition of lay persons and biomedical and behavioral scientists may be essential at this juncture to present to
E.
MEYER
the public, the scientific community, and legislators a concern that includes freedom of inquiry and subjects’ rights. Subjects’ rights should not be stated only in a legalistic context, but also in the traditional context of “do no harm.” Scientists have a major educative role relative to the public and the surface has barely been scratched. The adversaries of science are doing much better. REFERENCES 1. New York Times, March 8, 1976, p24 Frankel C: The specter of eugenics. Commentary Magazine, March 1974, pp 25-33 3. Robins LN: Problems in follow-up studies. Am J Psychiatry 134:904-907, 1977 4. Jones KL, Smith DW, Ulleland CN, et al: Pattern of malformation in offspring of chronic alcoholic mothers. Lancet I: 12671271, 1973 5. Finnegan LP, Connaughtom JF Jr. Schute J: Infants of drug dependent women: practical approaches for management, in Problems of Drug Dependence 1975: Proceedings. Washington, DC, National Academy of Sciences, 1975, pp 489-517 6. Levine Ri: Appropriate Guidelines for the Selection of Human Subjects for Participation in Biomedical and Behavioral Research. Prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Feb 1976 7. Individual Rights and the Federal Role in Behavioral Modification. Prepared by the staffofthe Subcommittee on Constitutional Rights of the Committee on the Judiciary, US Senate, 93rd Congress, second session. Washington, DC, US Government Printing Office, 1974 8. Vaillant GE: A twelve-year follow-up of New York narcotic addicts: I. The relation of treatment to outcome. Am J Psychiatry 122:727-737, 1966 9. Meyer RE: Guide to Drug Rehabilitation. Boston, Beacon Press, 1972 10. Levine R: The Nature and Definition of Informed Consent in Various Research Settings. Prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 11. Schumpeter J, cited in Moynihan DP: An address to the freshman class. Commentary Magazine, Dec 1972, pp 55-60 2.
Am J Psychiatry
134:8,
August
1977
903
Rights,
in the
Freedom
of Inquiry,
E. MEYER,
‘
‘ ‘
To THOSE OF US with a humanistic orientation who were educated in the medical schools of the late 1950s and early 1960s, the movement to apply human studies reviews and an ethical brake on research is understandable and justified. To those of us with a concern about the advancement of knowledge and the importance offree inquiry to our profession and our society, the present rush by some to condemn and restrict clinical research (and other scientific studies with human subjects) suggests a dangerous trend that may have moved beyond its initial noble impulse. The scientific community has responded by defending the enterprise on the basis of previous achievements and the continuing need for the struggle against diseases that afflict humankind. The failure of this defense was suggested by a recent editorial in the New York Times (1) equating this position with the defense mustered by our intelligence agencies on behalf of practices that were said to serve the interests of national security. In this context, our political system has seemed to be moving to set up countervailing forces and adversary procedures designed to “equalize” the interaction between research scientists and research subjects. at the 129th annual meeting Miami Beach, Ha., May
of the American 10-14, 1976.
Psychiatric
At the time this work was done, Dr. Meyer was Associate Professor of Psychiatry, Harvard Medical School, Boston, Mass.; Director, Harvard-Boston University Center for Biobehavioral Studies in the Addictions, Boston, Mass.; and Associate Director, Alcohol and Drug Abuse Research Center, McLean Hospital, Belmont, Mass. He is now Chairman and Professor, Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Conn. 06032.
Future
of Research
M.D.
Since the recent passage ofregulations concerning subjects’ rights andfreedom ofinquiry, opposition by the public and others to some areas ofresearch in the addictions has prevented its implementation or continuation. Research investigators in the biomedical and behavioral sciences have been placed in the position ofdefending their work in an adversary climate. The authorpoints out the importance of transmitting to the public, the scientific community, and legislators the investigators’ concern that ‘subjects rights not be viewed only in a legalistic context, but also in the context ofnot harming the patient.
Presented Association,
the
Addictions
BY ROGER
‘
and
If the concern about research with human subjects were limited to a concern about inadvertent or unavoidable harmful consequences of innovative procedures or research methods, then one could realistically restrict potentially harmful procedures while providing a mechanism to compensate subjects who have participated in research and who have sustained inadvertent complications consequent to their participation in the experiment. This would be consistent with the medical ethic primum non nocere , ‘above all do no harm. We have, however, moved into an area where the ethics of human experimentation are increasingly being defined on the basis of “imperatives” that are more consistent with the principles, practices, and beliefs ofcivil liberties attorneys. It is in the context of these ethical imperatives that individual research investigators have been unable to defend their work and approved research projects have been stopped. To some, this situation is reminiscent of the legitimate anguish of the oppressed against the oppressor elite. To others, the situation is but one more repetition of the classic struggle between scientists and those who hold political power as to whether science shall serve or be independent of political ideology. The distinguished philosopher Charles Frankel has observed that it is not technology per se that threatens mankind or a humanistic view of man; rather, the real threat lies in the tendency of some people to superficially link technological data to support for ideologies and movements (2). Indeed, on the issue of censorship of biomedical reearch, Frankel wrote, ‘
‘ ‘
For while technology is equivocal in its consequences, one thing is not-the damage that ensues, almost always very quickly when a field of inquiry is banned because it is said to subjects
conflict with higher that can come under
The character of the people axe is not reassuring. (2)
moral laws. The number of this axe is indefinitely large.
who have
ever
wielded
this
The future of clinical research seems least secure in areas of experimentation into the causes and treatment of nonlethal conditions, particularly in fields where treatment and prevention programs are polarized and scientific advances “appear” to offer little and may threaten philosophical positions. By these criteria, research into the causes and treatment of substance abuse should be controversial, and it is. There are two general areas of controversy that can be highlighted by Am J Psychiatry
134:8,
August
1977
899
RESEARCH
IN
THE
ADDICTIONS
case examples. A third general and privacy) has been described
FREEDOM
OF
INQUIRY
VERSUS
area (confidentiality by Robins (3).
Narcotic
Study
ofAlcoholic
Mothers
Data from a study by Jones and associates (4) suggest that offspring of alcoholic mothers may have a greater likelihood of premature birth and various 1evels of neonatal distress. The neonatal opiate withdrawal syndrome in the offspring of heroin-addicted mothers was described a number of years ago and has been updated by the work of Finnegan and associates (5). The question of neonatal distress in the offspring of alcoholic mothers is in need of more careful delineation. A team of psychiatrists, obstetricians, and pediatricians at a municipal hospital undertook a study of neonatal behavior and development in the offspring of mothers who were being seen in the prenatal clinic and who were identified as having problems of alcohol abuse. The physicians offered a program of psychotherapy coordinated with the prenatal care to assist the expectant mothers with their drinking problems. Preliminary data suggested that the offspring of mothers who drank heavily were at high risk as compared with the offspring of patients who drank moderately or rarely. On the basis of these preliminary findings, a grant was prepared and submitted to the National Institute on Alcoholism and Alcohol Abuse (NIAAA). Because the protocol also included the support of a treatment and prevention program, the review group included persons who could consider all aspects of the study. One of the reviewers was a community activist on the staff of an agency affiliated with the medical school at which the work was to be done. Despite the fact that this institutional affiliation should have excluded him from the review, he participated in the review of the grant application and a subsequent site visit. The NIAAA staffthen demanded that, in addition to the already obtained institutional reviews, the protocol be considered by a locally constituted group called the Community Research Review Committee. After reviewing the protocol, the committee felt that the research might draw defamatory conclusions regarding the competency of black mothers, since 55% of the clinic population was black. The committee insisted on monitoring the personnel practices and conduct of the research and previewing any formal or informal reports emanating from the project. In order to effectively monitor the work, the committee members stated that they would have to receive a portion of the budget as overhead. The principal investigator was told that since it was already the responsibility of the NIAAA and the institution to monitor the project, federal funding for a third group of monitors could not be budgeted. While it was clear that the NIAAA staff had erred in requiring that the research investigator obtain 900
AmJPsychiat
134:8,
August
group, it was that the fullface of deter-
RESTRICTED
INQUIRY
The
the sanction of this locally constituted also clear to the research investigator scale program was not possible in the mined political opposition.
1977
Antagonist
Project
1
The Community Research Review Committee has made similar budgetary demands upon a number of other nonpolitical research investigators whose research projects involved studies into the causes and treatment ofnonlethal conditions. The committee members have been relatively selective in their approach and apparently have not made these demands upon all research investigators in the geographical area. On one previous occasion they approached a team of research investigators who proposed to study the effects of narcotic blocking drugs in a population of heroin addicts at the same municipal hospital. Their demands at that time included 10% of the budget, 50% of the positions, and the appointment of an associate director of the project from among the membership of their committee. They also demanded censorship of reports. The thrust of the committee’s concern regarding studies of narcotic antagonist treatment of heroin addicts seemed to be that the research investigators were taking a simplistic, biomedical view of a complicated social problem that (in its view) really required a solution to the problems of poverty and other social ills in the community. While the causes of addiction may be multifactorial, the committee was concerned that the biomedical orientation of the research project conflicted with its own view regarding the causes of the problem and its own definition of funding priorities. Faced with powerful opposition that undermined the support by the hospital’s trustees, the research investigators chose to transfer this project to another community. While individual communities will continue to be able to exercise a political veto over research within their midst, the real question concerns the application of this principle on a larger scale. At least one monograph prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (6) proposed to sanction “community consent,” which it defined as “informed consent negotiated with the community in which it is planned to conduct research or from which it is planned to draw prospective subjects.” If this recommendation is adopted in this form, its consequences for the future of research could be extremely restrictive. As the Edelin trial has demonstrated, such political pressure can come from diverse sources and can scapegoat ethical practitioners and scientists. Federal
Opposition
to Behavioral
Research
Political concern about behavioral research with relevance to addictive drugs has not been limited to ad hoc community groups. Comments by Senator Proxmire and the threat by several congressmen to cut off
ROGER
funds from the National Institute on Drug Abuse prevented the implementation of an approved and funded research project at Southern Illinois University on the effects of marijuana on human sexuality. The researcher had previously obtained local lay approval for his study, in addition to required institutional reviews. The penultimate federal document challenging the ethics of behavioral experimentation was a report prepared by the Senate Judiciary Committee on Individual Rights and the Federal Role in Behavioral Modification (7). The report alleged, The behavioral technology being developed in the United States touches upon the most basic sources of individuality, and the core of personal freedom. . . . While psychosurgery under certain forms of electrophysiology is perhaps the most . . . sophisticated method of behavioral control, there are now being tested a number of other techniques based on more traditional, psychological primciples [that] pose similar questions with regard to individual liberties. (7)
The
implications
of this
strict
behavioral
research
report in
suggest the
the
interests
need of
the
to recivil
rights of individuals in the future, as well as the present. It is curious that alcoholism and drug addiction are major behavioral disorders whose alteration will require one or another form of behavioral modification. Indeed, methadone maintenance, narcotic antagonist treatment, and self-help residential programs all seek to modify behavior. The issue would seem to be whether clinical research in these areas can proceed in a variety of voluntary and nonvoluntary settings with appropriate regard for adequate and voluntary informed consent.
SUBJECTS’ TREATMENT;
RIGHTS VERSUS SUBJECTS’
SOCIETY’S
NEEDS
THE RIGHTS
RIGHT VERSUS
TO
There is a recurring notion that research subjects must be protected from researchers by an adversary process (consent committees versus review committees, and patient advocates versus research physicians). The adversary process is a legal construct that works effectively in the courts and the political system. When applied outside this framework to the practice of medicine and research, it may run counter to the medical ethic of “do no harm.” Indeed, as in the field of mental health generally, the arbitrary imposition of “individual rights” in a legal context may impose medical and social risks for individual patients. The following examples highlight the problem in addiction research. Antagonist
Vaillant studies on
Project
(8) has carried heroin addicts
2
out extensive follow-up discharged from the U.S.
MEYER
Public Health Service Hospital in Lexington, Ky. From his work it is clear that patients who are on probation or parole do better in all forms of treatment. Indeed, many of the self-help residential ‘concept houses” have increasingly restricted admission to patients who are court referred because the dropout rate of volunteers in these hierarchical, authoritarian environments was too high. Vaillant’s findings are clear: in the absence of some system of control, the addict is not able to modify his own behavior. As I have described elsewhere (9), that control can be manifested by methadone maintenance; an authoritarian, hierarchical residential community; or the criminal ‘
justice
system.
The recidivism rate of former heroin addicts discharged from prison is quite high. This population presents unique problems in terms of the relatively effective treatments available to narcotics users. Since they have been drug free for a period of time in prison, they are not considered appropriate candidates for a program of opiate substitution (e.g., methadone maintenance). Since they have been living in a prison for a period of time, they are not anxious to volunteer for a 9- to 24-month residence in a “concept house.” While parole or probation support may be helpful to the mdividual in his efforts to seek ajob or obtain some sort of counseling, the presence of many stimuli associated with previous addiction cycles (familiar friends and “drug copping areas”) may encourage relapse. The National Institute on Drug Abuse recognized that this population might be ideal for narcotic antagonist treatment. They funded one such project in one community in association with that city’s drug treatment program. The principal investigator of the project described its course as follows: The project
as approved
and funded
by HEW
proposed
to offer treatment to prison inmates shortly prior to their release from prison and during a parole period subsequent to release. A condition ofthe project . . . stated that under no circumstances could participation in the project be a consideration for parole. Plans were finalized for the conduct of the project in such a way that patients would not be approached to give informed consent until after the parole board had met and voted for parole. Despite the fact that ajoint medical school and hospital based human studies committee approved ofthis project, the study attracted widespread local attention when the research protocol was stolen in a burglary of the office of the principal investigator. [The study was described in the local media in such a way that prison inmates were seen as guinea pigs and parole was described as dependent on participation in
the study.] tion of agencies’
As a consequence
these allegations, human study
the project. resulted
Narcotic
E.
with
In a long series four
of the widespread
community committees
additional
of reviews, human
based requested
circulaand other review of
multiple studies
meetings
committees,
and the project met with final approval shortly before the expiration of the project period. Only two subjects entered the research study and HEW finally made the judgment that extension of the project with refunding was unwise. The principal investigators viewed the episode as Am
J Psychiatry
134:8,
August
1977
901
RESEARCH
IN
THE
ADDICTIONS
one
of continuous harassment by an ill-informed of well-intentioned but unsophisticated times ad hoc human studies committees.
and a series
media and at
When one considers the number of “rehabilitation measures” that are routinely employed in the context of parole, probation, and other aspects of the criminal justice system, one is struck by the fact that these measures are seldom evaluated. Indeed, if informed consent is ruled out for this population in an a priori manner, then the population will be exposed to all sorts of unevaluated interactions with undefined risks while being prevented from participating in rehabiitation programs with a research-oriented design. The
Addiction
Research
Center
Forty years ago the Public Health Service set up the Addiction Research Center at Lexington, Ky., in order to screen new drugs for their potential to cause addiction, to explore the biomedical and behavioral aspects of the addiction process, and to evaluate potentially promising pharmacological approaches to the treatment of addiction. Over the years the mission has evolved consistent with evolving federal priorities. The addiction liability of many new analgesics became known before they could be advertised as “nonaddicting.” The human pharmacology of methadone, 1 -a-acetylmethadol, cyclazocine, naloxone, and naltrexone were all delineated at Lexington. Over its 40year history there have been no deaths or serious disabilities consequent to this research. With the development of locally constituted drug treatment programs in nearly all parts of the country, the need for a “treatment farm” for volunteers in Kentucky became unnecessary. Instead, in 1973 the Federal Bureau of Prisons relocated its facilities for known heroin addicts to Lexington in proximity to the Addiction Research Center. It is now four years later. The staff at the Addiction Research Center was told that they could not begin any new studies using federal prisoners after January 1 1977. The distinguished team of pharmacologists and behavioral scientists has been perplexed. Dr. Wilham Martin testified before the National Commission for the Protection of Human Subjects in March 1976 ,
concerning
the
importance
of
the
work
and
the
safety
of the procedures. Within a month of Dr. Martin’s testimony, the Bureau of Prisons acted independently in response to congressional inquiry and unilaterally ordered the end of research in prisons under its jurisdiction. This order came out before the conclusion of deliberations and the preparation of the final report by the national commission. In his testimony, Dr. Martin wondered how society’s needs for safe analgesics and new pharmacological approaches to the treatment of addiction could be reconciled with the closing of Lexington. He reviewed the safety of the procedures at Lexington, and he argued that the prisoners were capable of giving informed consent. 902
Am J Psychiatry
134:8,
August
1977
COMMENT
Four issues have been raised with regard to informed consent in research involving the mentally disabled, children, and prisoners: 1) the question of the capacity of individuals in each group to give informed consent, 2) the question of coercion, 3) the question of a need for an adversary procedure to defend the rights of research subjects, and 4) the question of community consent. While all four of these questions have been applied to the mentally disabled, only one has been applied to research with prisoners and persons in the criminal justice system-the issue of coercion within an institutional setting. Persons living within institutions are thought to be at risk for coercion. One of the monographs prepared for the commission, which dealt with the mentally disabled, stated, “When proposed research is considered therapeutic, an institutionalized individual may be under more pressure to participate insofar as the possibility exists that the anticipated benefit may relieve the mental illness, and thus increase the likelihood that the patient would be released” (10). So far as research with prisoners is concerned, the problem ofcoercion has been presumed to exist in all phases of the criminal justice system. Regarding research with drug-dependent patients, there may be the presumption of mental disability, and all four issues of informed consent have been raised in different quarters
that
contexts. to assume
coercion
versary
procedures
There
has
been
a tendency
that diminished capacity by the researcher is likely, and and
some
form
in some
exists, that ad-
of community
con-
sent are essential to protect the individual rights of research subjects. The resolution of these issues will be different if primary concern is given to the health and safety of the individual and society’s needs as opposed to individual rights. It is paradoxical that the case for “health and safety,” “society’s needs,” and “individual rights” is usually argued for hypothetical individual patients and subjects by elitists who presume to know more than the patients themselves about what is “good” for them. Indeed, the struggle between objectivism, intellectualism, and the pursuit of knowledge on the one hand and subjectivism anti-intellectualism and equality’ on the other, is a political conflict with implications beyond the limits of biomedical and behavioral research. Daniel Patrick Moynihan has quoted the political philosopher Joseph Schumpeter in words that seem to have some relevance: “It is an error to believe that political attack arises primarily from grievance and that it can be turned by justification. Political criticisms cannot be met effectively by rational argument” (11). ,
,
,
“Equality” has recently come to mean that all points of view are equally valid in any situation involving two or more persons, that the power to veto is distributed widely and across many issues, and that executive power (literally the power to execute, implement, or develop) must be reduced until progress proceeds only by consensus.
ROGER
In the present climate, appeals to the need for scientific advancement will not, and are not, convincing those with power and authority to let the enterprise continue in a number of communities. The research projects that have been stopped were defended (it seems to me) in a characteristic way. The research investigators met repeatedly with their most militant adversaries. They did so at the urging of their colleagues, who let them enter these meetings without significant support. The principal investigators and their colleagues believed that reason would prevail and that they would be able to convince their most ardent opponents. At the least, they expected that they could effect a compromise that would enable them to continue to work and would enable their adversaries to feel that they, too, had accomplished their ends. The institutions that had previously supported the research now supported the mediative process, thereby invalidating the previous support of the project that had been granted by the human studies committee and other relevant structures. Committees were set up to assist in the mediation; the committees usually consisted of the more militant opponents of the research and some individuals who were deemed friendly (although not emotionally committed) to the work of the research investigators. It is untenable for the research investigator to defend his work on his own. It is also probably untenable for the scientific community to defend itself without major support from lay organizations. Previously, lay groups, like some of their scientific counterparts, have been organized to support categorical research. This has increased the risk of “salami tactics” by opponents of research, since attacks on individual projects have not been considered a threat to broader categories of biomedical and behavioral research. A coalition of lay persons and biomedical and behavioral scientists may be essential at this juncture to present to
E.
MEYER
the public, the scientific community, and legislators a concern that includes freedom of inquiry and subjects’ rights. Subjects’ rights should not be stated only in a legalistic context, but also in the traditional context of “do no harm.” Scientists have a major educative role relative to the public and the surface has barely been scratched. The adversaries of science are doing much better. REFERENCES 1. New York Times, March 8, 1976, p24 Frankel C: The specter of eugenics. Commentary Magazine, March 1974, pp 25-33 3. Robins LN: Problems in follow-up studies. Am J Psychiatry 134:904-907, 1977 4. Jones KL, Smith DW, Ulleland CN, et al: Pattern of malformation in offspring of chronic alcoholic mothers. Lancet I: 12671271, 1973 5. Finnegan LP, Connaughtom JF Jr. Schute J: Infants of drug dependent women: practical approaches for management, in Problems of Drug Dependence 1975: Proceedings. Washington, DC, National Academy of Sciences, 1975, pp 489-517 6. Levine Ri: Appropriate Guidelines for the Selection of Human Subjects for Participation in Biomedical and Behavioral Research. Prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Feb 1976 7. Individual Rights and the Federal Role in Behavioral Modification. Prepared by the staffofthe Subcommittee on Constitutional Rights of the Committee on the Judiciary, US Senate, 93rd Congress, second session. Washington, DC, US Government Printing Office, 1974 8. Vaillant GE: A twelve-year follow-up of New York narcotic addicts: I. The relation of treatment to outcome. Am J Psychiatry 122:727-737, 1966 9. Meyer RE: Guide to Drug Rehabilitation. Boston, Beacon Press, 1972 10. Levine R: The Nature and Definition of Informed Consent in Various Research Settings. Prepared for the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research 11. Schumpeter J, cited in Moynihan DP: An address to the freshman class. Commentary Magazine, Dec 1972, pp 55-60 2.
Am J Psychiatry
134:8,
August
1977
903
