Disability Advocates, Inc. 155 Washington Avenue - Suite 300 - Albany - New York -12210 and TDD: 432-7861 950-7861 Fax: (518) 427-6561 Executive Director: Cliff Zucker Staff Attorneys: July 13, 1994 Timothy A. Clune Cailie Currin Simeon Goldman Melanie Shaw Stephen Klaidman Director of Communications Advisory Committee on Human Radiation Experiments 1726 M Street, Suite 600 Washington, D.C. 20036 Dear Mr. Klaidman: Thank you for the invitation to speak to the Advisory Committee on July 25, 1994. 1 am pleased to participate. I am Executive Director of Disability Advocates, Inc (DAI) . DAI provides protection and advocacy services to individuals diagnosed with a mental illness in New York under a contract with the New York State Commission on Quality of Care for the Mentally Disabled. Our legal and advocacy services are performed pursuant to the Protection and Advocacy for Mentally Ill Individuals Amendments Act of 1991 (PAMII), 42 U.S.C. 10801 et A brochure about our office is enclosed for your further information. As advocates for the rights of persons with mental disabilities, we advocate for the rights of psychiatric patients who are research subjects. We are currently litigating (with co-counsel Ruth Lowenkron of New York Lawyers for the Public Interest, Inc.) a case in New York Supreme Court, T.D. v. New York State Office of Mental Health. T.D. challenges certain New York Office of Mental Health experiments upon subjects who are incapable of giving informed consent because of mental disability or because they are children. We are also investigating what we believe are inadequacies in the informed consent process in several other experiments. In several ways, the federal regulations inadequately protect human subjects. Because of these inadequacies, there is a very real risk that subjects will be harmed. The Executive order creating this committee provides that inquiry into experiments conducted after May 30, 1974, may be pursued if the Advisory Committee determines, with the concurrence of the Human Radiation Interagency Working Group, Stephen Klaidman July 15, 1994 that such inquiry is warranted. I urge you to consider how current regulations inadequately protect human subjects. MANY HUMAN SUBJECTS ARE NOT SUBJECT To FEDERAL RESEARCH REGULATIONS, AND ARE THEREFORE UNPROTECTED OR INADEQUATELY PROTECTED. Federal regulations do not protect many human subjects of experimentation.' Experiments that are not federally funded, and do not involve investigational new drugs or devices, may be wholly unregulated by the federal government. Such state or privately funded research may involve drug or electroconvulsive therapy experiments, and may therefore subject subjects to very real risks. Most states do not have laws or regulations governing experimentation on human subjects. Those that do, such as New York, may provide much less protection than do the federal regulations. But in the majority of states that do not regulate human experimentation, there is no regulation or oversight to protect such subjects. Some of the experiments that are not subject to federal regulation are conducted by facilities that have agreed, in a "multiple project assurance" with the Office of Protection from Research Risks (OPRR) , to abide by federal regulations in their non-federally funded research. However, this does not provide sufficient protection for these subjects. The multiple project assurances state that injuries, deaths and other unexpected incidents in non-federally funded research need not be reported to OPRR. OPRR relies on such reports to trigger investigations and remedial action to protect human subjects. Without reporting to OPRR, there is no effective oversight of such experiments. Thus, even in facilities with multiple project assurances, subjects of non-federally funded experiments are inadequately protected. 45 C.F.R. 46.101 limits the applicability of the federal research regulations to research which is "conducted, supported or otherwise subject to regulation by any federal department or. agency.... " The term "research subject to regulation" is "intended to encompass those research activities for which a federal department or agency has specific responsibility for regulating as a research activity, (for example, Investigational New Drug requirements administered by the Food and Drug Administration) . It does not include research activities which are incidentally regulated by a federal agency...'." 45 CFR 46.102(e). 2 Stephen Klaidman July 15, 1994 The remedy is to extend the federal regulations to all experiments involving human subjects. The federal government has broad authority, under the commerce clause and the fourteenth amendment to the United States Constitution, to regulate such experiments. The expanded regulations should specifically require reporting of injuries, deaths and unexpected events in all human experimentation to OPRR and empower OPRR to exercise its remedial and enforcement powers on behalf of all human subjects. The current system, which permits some human subjects to receive little or no regulatory protection, creates an unacceptable threat to the rights of human subjects. Some states, such as New York, have enacted state regulations to govern non-federally regulated experiments. But the 'human subjects who are not protected by federal regulation have substantially inferior protections. For example: 1. The 'federal regulations require that "additional safeguards" be in place to prevent coercion or undue influence of subjects with mental disabilities. 45 C.F.R. 46.111(b). The New York regulations do not require such special safeguards. Under the New York regulations, the subject's consent can be dispensed with altogether if the researchers believe the subject is incapable of providing informed consent. The regulations permit the researchers to seek the consent of a family member or friend in lieu of asking the patient to consent. There is no judicial procedure for determining that the subject is in fact incapable, and that the relative or friend is an appropriate person who will act in the patient's best interest. Subjects can be placed in greater than minimal risk, non-therapeutic experiments under such circumstances. 2. The federal regulations greatly restrict experimentation involving no direct benefit to a child: (1) the experiment can present only a minor increase over minimal risk and (2) the intervention, and procedure must "present experiences to subjects that are reasonably commensurate with those inherent in their actual or expected medical, dental, psychological, social or educational situations." 45 C.F.R. 46.406. Thus, the federal regulations limit non-therapeutic research on children to the least risky experiments and prohibit experiments that will cause additional discomfort or anxiety. The New York regulations do not similarly restrict non-therapeutic research on children. See, 14 N.Y.C.R.R. 527.10(e). 3 Stephen Klaidman July 15, 1994 3. Although the federal regulations permit certain non- therapeutic experimentation on children, 45 C.F.R. 46.406, the federal regulations contain safeguards not in the NY regulations. The federal regulations require the consent of both parents for non-therapeutic experimentation involving greater than minimal risk, unless one parent is dead, unknown, incompetent or not reasonably available, or when only one parent has legal responsibility for the care and custody of the child. 45 C. F.R. 46.408 (b) . The New York regulations do not contain this important safeguard. Under the New York regulations, a child may be experimented upon on the consent of one parent, even when the other parent would refuse to give his or her consent. Therefore, federal regulations should be extended to all human subjects, including subjects in states that regulate such experiments pursuant to state laws or regulations. THE REGULATIONS HAVE BEEN INTERPRETED TO PERMIT EXPERIMENTATION ON INCAPABLE SUBJECTS ON THE CONSENT OF SURROGATES WHO HAVE NOT BEEN AUTHORIZED BY A COURT TO ACT AS GUARDIANS. The federal regulations generally require "the legally effective informed consent of the subject or the subject's legally authorized representative. " 45 CFR 46.116. Although the term "legally authorized representative" is undefined, it should be interpreted to permit surrogate informed consent only by a guardian appointed by a court or by a representative appointed by the subject to make medical decisions. Surrogate consent to non-therapeutic experimentation that involves greater than minimal risk can only be given by a representative appointed by the subject to make decisions about participation in non-therapeutic experimentation. As discussed on page 7, infra, other surrogates, including court appointed guardians, cannot consent to non-therapeutic research that places the subject in greater than minimal risk. This interpretation ensures that the subject retains the right to make decisions about participation unless a court has found the subject to be incapable of doing so and appointed a surrogate. Unfortunately, the regulation is being misinterpreted. New York State has interpreted the regulation to permit an allegedly incapable subject's spouse, parent, adult child, adult sibling, and 4 Stephen Klaidman July 15, 1994 even a "close friend 2 {2 under the New York Regulations a "close friend" is a person who has sworn in an affidavit that he or she is the subject's close friend. Subjects do not get to decide who their close friends are, or if they should make decisions about experiments which may be non-therapeutic and risky.}" to consent to greater than minimal risk research. The surrogate can even consent to risky non-therapeutic research. 14 NYCRR  52 7. 10 (a) . Under New York Is regulations, the researcher may decide that a subject is incapable of informed consent, and there is no requirement of judicial review of that decision, or even notice to the patient. Once designated incapable, the researcher can seek the consent of a relative or close friend. The relative or close friend is not judicially appointed to make such decisions, and there is no procedure to ensure that the surrogate is acting in the patient's best interest or that the subject is really incapable of making his or her own decisions. Allowing relatives or close friends to make such decisions is unlawful.3 {3 The sanctity of choice with respect to one's body has long been established in the common law. Perhaps the earliest articulation of this principle was by the United States Supreme Court in Union Pacific Railway Co. v. Botsford, 141 U.S. 250 (1891) where the court stated that "[n]o right is held more sacred, or is more carefully guarded, by the common law, than the right of every individual to the possession and control of his(/her] own person... " Id. at 251. Similarly, Justice Cardozo in Schloendorff v. Society of New York Hospital, 211 N.Y. 125 (1914) stated that "[e]very human being of adult years and sound mind has a right to determine what should be done with his(/her] own body." Id. at 129. While no case has discussed whether relatives and friends can place subjects in experiments without a judicial finding of incapacity and judicial authorization, such procedures are required for analogous decisions. Except in emergencies, court authorization is generally required to authorize medical decisionmaking for incompetent adults, and the trend is to require more due process to ensure that their rights and needs are respected by a guardian. See for example N.Y. Mental Hygiene Law Article 81. There is no precedent for placing incapable subjects in experiments without a judicial finding of incapacity and judicial appointment of a surrogate. Recent decisions of the U.S. Supreme Court suggest that the liberty interests implicated when an allegedly incapable person is placed in an experiment require a judicial finding of incapacity, judicial appointment of a surrogate decisionmaker, and that surrogate consent to experimentation be limited to experiments offering a prospect of therapeutic benefit. See generally, Zinermon v. Burch, 494 U.S. 113, 110 S.Ct. 975 (1990); Cruzan v. Director. Missouri Dept. of Health, 497 U.S. 261, 110 S.Ct. 2841 (1990); Riggins v. Nevada, _U.S._, 112 S.Ct. 1810 (1992).} 5 Stephen Klaidman July 15, 1994 Being a research subject can involve very significant, and potentially deadly risks. The of death a subject in an experiment at UCLA which was recently cited by the OPRR, and the five deaths of subjects in FDA investigated experiments involving Fialuridine show that, even with the protection of IRBs and regulations, participation in research can be fatal. Incapable patients have a liberty interest in life and health that is implicated when they are placed in experiments without their informed consent. Because of this very great liberty interest, government has a duty to provide procedural safeguards that minimize the risk. See generally, Lassiter v. Department of Social Services, 452 U.S. 18 (1981). Certainly, incapable subjects are entitled to an independent judicial determination of incapacity, not merely a finding by the researcher that they are incapable. And once determined incapable of informed consent, certainly they are entitled, to a surrogate decisionmaker who is judicially appointed and judicially determined to be capable of making decisions that are in the subject's best interest. If a family member wants to manage the finances of an incapable relative, a guardianship proceeding must be brought in court, with elaborate due process. But in New York, the family member can place the incapable relative in an experiment with no review at all. The New York Office of Mental Health believes that this is consistent with federal regulations. I urge you to recommend changes in the federal regulations to clearly outlaw this practice. The New York interpretation of "legally authorized representative" is being challenged in the T.D. litigation, and may ultimately be declared unlawful in New York. But it will take many years for a final judicial resolution of that question, and then the question will only be settled in New York. Meanwhile, the New York Regulations are being promoted as a model for other states. See, Delano, Susan J. and Zucker, J.L., Protecting Mental Health Research Subjects Without Prohibiting Progress, 45 Hospital and Community Psychiatry No. 6, p. 601 (June 1994) The federal regulations should be clarified, by defining the term "legally Stephen Klaidman July 15, 1994 authorized representative" as a "judicially appointed guardian of the person or an individual appointed by a then capable subject to give or withhold informed consent to medical care; or in the case of non-therapeutic research, an individual appointed by a then capable subject to give or withhold informed consent to non- therapeutic research." This will ensure that the right to informed consent is properly protected, and that the only persons placed in experiments are those who consent to research or are placed in research by a person the subject or a court has determined is appropriate to make such a decision. FEDERAL REGULATIONS SHOULD CLEARLY STATE THAT SURROGATES MAY NOT PLACE INCAPABLE SUBJECTS IN RISKY, NON-THERAPEUTIC EXPERIMENTS The federal regulations allow a "legally authorized representative" to consent to both therapeutic and non-therapeutic experiments involving greater than minimal risk.4 {4 If incapable subjects are injured in non-therapeutic experiments to which they did not consent, the federal regulations do not require any compensation for injuries, or even the provision of long term medical care. This is extremely unfair since the subjects did not consent and derived no benefit from the experiments. This is another reason to ban risky non-therapeutic experiments on incapable subjects.} This serious flaw allows surrogates to place incapable subjects in experiments that offer no prospect of benefit to the subject,. and that involve serious risks. As demonstrated by the UCLA and Fialuridine experiments, the risks may unexpectedly prove fatal. This is a departure from the well established principle that surrogate decisionmakers must act in the best interests of the incapable person. As a leading treatise noted, surrogate decision-makers for incompetent adults and minors have a ".narrower range of permissible choices than persons making decisions for themselves because of their duty to act in the best interest of the incompetent adult or minor-" R. Miller, Problems in Hospital Law 268 (1986). Accordingly, "[d]ecision makers cannot authorize two procedures--organ donation or sterilization--for incompetent adults or minors without prior court approval." Id. at 269. Courts only approve such procedures when they are in the best interests of the patient. non-therapeutic research never produces direct benefits for the patient, whereas sterilization and organ transplants may do so in certain circumstances. Therefore, surrogates cannot consent to non-therapeutic research without court approval, and if the research involves significant risks the court will not approve it. 7 Stephen Klaidman July 15, 1994 The federal regulations recognize this principle concerning research involving children. 45 CFR Subpart D concerns research involving children. Section 46.406 limits non-therapeutic research on children involving greater than minimal risk to those experiments that "represent a minor increase over minimal risk" and do not involve new and frightening experiences. The regulations also require the child I s assent. These protections should be extended to incapable adults. THE FEDERAL REGULATIONS VIOLATE THE DUE PROCESS AND STATUTORY RIGHTS OF CHILDREN AND PARENTS BY WAIVING THE CONSENT OF CERTAIN PARENTS TO EXPERIMENTATION ON THEIR CHILDREN Parental consent to experimental treatment for children is one of several safeguards needed to protect children from being used as guinea pigs. Nevertheless, the federal regulations provide that the Institutional Review Board (IRB) may waive the requirement of parental or guardian consent to experimentation on children if the IRB determines that obtaining parental or guardian permission is not a "reasonable requirement." 45 CFR 46.408(c). Parental consent may be waived both for experimental treatment and experimentation offering no benefit to the child. The regulations state that parental. or guardian consent may be found to be unreasonable in the case of "for example, neglected or abused children." Id. Under these circumstances, the IRB may substitute other unspecified procedures, for parental consent. Id. The child, parent or guardian receives no notice or opportunity to be heard. Id. In sum, the regulations empower the IRB, acting ex parte, to determine children to be abused and/or neglected (or that parental and guardian consent is for some other reason unreasonable) and terminate the parents' or guardians' right to decide if their child should be experimented upon. Parents and guardians may never learn that their children are the subject of experiments and therefore have no opportunity to protect their children. Children may never learn that they have been deprived of parental protection regarding experimentation. There is a long history of experimentation on children without sufficient regard for their well-being when -non-parental caretakers and experimenters are permitted to consent to experimentation. See, Katz, Experimentation with Human Beings, 963-964 (1972), citing 1 British Medical Journal 722, 725-726 (1964); Burton v. Brooklyn Doctor's Hospital, 88 A.D.2d 217, 452 N.Y.S.2d 875 (lst Dept. .1982) (a child was intentionally blinded by physicians seeking to demonstrate the efficacy of an alternative treatment for premature infants). The regulations continue the practice of allowing non-parental caretakers to use them for experimentation. 8 Stephen Klaidman July 15, 1994 Because no process at all is substituted when parental consent to research is dispensed with, except an undefined "appropriate mechanism," the regulations deprive the child and parent of liberty without due process of law . They should be modified to require judicial authorization, with parent and child receiving notice and opportunity to be heard before a child may be placed in an experiment without parental consent. HUMAN SUBJECTS NEED ADDITIONAL PROTECTION AND ADVOCACY TO ENSURE THAT THEIR RIGHTS ARE PROTECTED. 5 Annotation, Medical Practitioner's Liability for Treatment Given Child Without Parent's Consent, 67 A.L.R. 4th 511 (1989) reviews all reported state and federal cases which raise a medical practitioner's liability for treatment of a child without parental consent. No case is cited which authorizes medical procedures on children for the benefit of others, without parental consent. The United States Supreme Court held that proof of neglect must be by "clear and convincing evidence, " because freedom of personal choice in matters of family life is "a fundamental liberty interest protected by the Fourteenth Amendment." Santosky v. Kramer, 455 U.S. 745, 753 (1982). Accord, Matter of Marilyn H., 106 Misc. 2d 972, 436 N.Y.S.2d 814, 819 (Family Court, N.Y. Cty. 1981). The Santosky court held: The fundamental liberty interest of natural parents in the care, custody and management of their children does not evaporate simply because they have not been model parents. 455 U.S. at 753 (emphasis added). Without a judicial determination by clear and convincing evidence that parental rights should be terminated, the government "cannot presume that a child and his parents are adversaries." Santosky v. Kramer, 455 U.S. at 760. "The parents and the child share an interest in avoiding erroneous termination." Id. at 756. Yet the regulations permit the IRB to secretly decide that a parent or guardian is unsuitable to make decisions regarding experimentation and to then permit experimentation using some sort of mechanism which the regulations do not bother to describe. When the legal principles of Santosky are applied to the regulations, it is apparent that the regulations deprive fundamental rights without due process. 9 Stephen Klaidman July 15, 1994 The UCLA and Fialuridine experiments make it clear that problems in human experimentation are not a thing of the past. While federal regulation has greatly improved protection, much remains to be done. Some problems flow from deficiencies in the federal regulations, others flow from inadequacies with compliance with the federal regulations. For example at UCLA the researchers failed to obtain informed consent. We believe that the problems at UCLA are not an isolated incident our investigations of protocols also suggest that informed consent documents do not always reveal the significant risks that are discussed in the protocol. Another problem in assuring compliance with federal regulations is that OPRR can not investigate until it receives a complaint or a report of an injury or death that raises concerns. Most research subjects are unaware that OPRR exists. OPRR does not randomly review protocols to ensure compliance with the law. This probably reflects a judgment about how to best use a limited resource. In addition, federal regulation compliance is hampered by problems in IRB oversight; Jay Katz and others argue that the IRB process is not working and have proposed reforms which I endorse. If you expand the scope of the federal regulations to all human subjects, as I propose, the need for oversight will increase. Greater compliance could be achieved by providing a greater role and greater resources to OPRR. In addition, I propose that you create a federally funded "Protection and Advocacy" program to protect and advocate for the rights and safety of human subjects of experimentation. Congress has created" protection and advocacy" programs to protect other groups that are vulnerable to abuse and neglect. See, Protection and Advocacy for Mentally Ill Individuals Act, 42 USC 10801 et. seq. ("Congress finds that individuals with mental illness are vulnerable to abuse and serious injury. ") ; Protection and Advocacy for Individual Rights, 42 USC 6042 et. seq.(Protect and advocate for persons with developmental disabilities) ; Protection and Advocacy for Individual Rights, 29 U.S.C. 794e (Protect and advocate for persons with other disabilities). Each of these programs serves a group that has been identified as vulnerable to abuse or injury. These programs provide grants to an agency in each state, usually a not-for profit corporation, which is authorized to pursue legal, administrative and other appropriate remedies or approaches to protect and advocate for the population at risk. A protection and advocacy (P&A) agency for human subjects 10 Stephen Klaidman July 15, 1994 would complement and work with OPRR. Research institutions would be required to notify all subjects and potential subjects of the existence of the P&A. The P&A would counsel and advise as requested. The P&A would review protocols and consent forms and advocate as needed for adequate informed consent. Where necessary, the P&A would bring matters to the attention of OPRR or seek other remedies. In instances where subjects were harmed as a result of rights violations, the P&A could assist injured subjects in obtaining relief. The P&A model has been found to be effective in serving other vulnerable groups. Because it is largely operated by not-for-profit agencies, it is cost effective. A system of P&As serving every state and territory could be created for $5.5 million dollars-, and provide each jurisdiction with a $100,000 grant to protect human subjects. A pilot program, serving key metropolitan research centers, could be created for much less. The P&A concept is well proven, and I can provide you with additional information about the effectiveness and cost of such a system. Thank you for considering my concerns. Very truly yours, Cliff Zucker, Esq. Executive Director CZ/alt enc. 11