National Alliance on Mental Illness
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MAY 8, 1997


Chairman Shays, Congressman Towns and Members of the SubCommittee, my name is Laurie M. Flynn and I am the Executive Director of the National Alliance for the Mentally Ill (NAMI). I very much appreciate the opportunity to appear before this Subcommittee today. In addition to my role as NAMIís Executive Director, I am a member of President Clintonís National Bioethics Advisory Council (NBAC).


NAMI is the nationís largest grassroots organization dedicated to improving the lives of persons with severe mental illnesses, including schizophrenia, bipolar disorder (manic-depressive illness), major depression, obsessive-compulsive disorder, and anxiety disorders. NAMIís membership includes more than people with severe mental illnesses and their families, and 1,100 state and local affiliates in all 50 states, the District of Columbia, Puerto Rico and Canada. NAMIís mission includes advocacy for nondiscriminatory and effective federal and state policies, research into the causes, symptoms and treatments for severe mental illnesses and education to eliminate the pervasive stigma toward those who suffer from these serious brain disorders.


NAMI has been and will continue to be a strong advocate for biomedical research on severe mental illnesses. Biomedical research has yielded remarkable breakthroughs in the understanding and treatment of severe mental illnesses. The development of promising new medications for the treatment of schizophrenia and other debilitating brain disorders have occurred as a result of biomedical research. So too have advances in understanding the causes and etiology of these brain disorders, advances which may ultimately result in the ability to control and even cure the symptoms of these illnesses. These remarkable advances would not have occurred without the participation of individuals with severe mental illnesses as human subjects in research. These individuals, many of whom are NAMI members, are heroes in the struggle to overcome these devastating brain disorders.


Because of these remarkable advances, it is critically important to maintain a climate conducive to biomedical research on severe mental illnesses. It is equally important to address the complex ethical questions concerning the use of human subjects in research of this nature. The use of human subjects in biomedical research presumes that individuals who participate are capable of comprehending the nature and scope of the research and can therefore consent on an informed basis to such participation. However, the nature of severe illnesses render individuals who suffer from these disorders sometimes incapable of providing such consent. I believe that scientists, bioethicists, and advocates are committed to balancing the importance of maintaining a healthy climate for research with protecting vulnerable subjects who may lack capacity to fully understand the nature, risks and benefits of the research they are participating in. We welcome this dialogue as vital to fostering our partnership with science.


Recently, these issues have received renewed attention since revelations, a few years ago, that a specific psychiatric research protocol at the UCLA Neuropsychiatric Research Institute (one of the nationís largest psychiatric research programs) may not have included adequate informed consent and other procedures for fully informing research participants or their families about the potential risks and benefits of this protocol. We have discussed our concerns about this study with officials at the National Institute of Mental Health (NIMH) and the Office for Protection from Research Risks (OPRR). In 1995, in response to the concerns engendered by the UCLA case, the NAMI Board of Directors, after extensive consultation with outside experts, adopted comprehensive policies addressing protections of individuals who participate as human subjects in research. (These policies are attached to this testimony as Appendix I).


Since adoption of these policies, I have worked actively within the psychiatric research community to promote adoption of practices reflecting the principles embedded in these policies. While the time allotted to me will not allow me to present all of these policy recommendations at this hearing, I would like to use this opportunity to submit those which I believe to be most important to this Subcommittee for its consideration.


First, it is important to distinguish between research and treatment for persons with severe mental illnesses. Due to the inadequacies of many treatment systems and pervasive discrimination in health insurance coverage of severe mental illnesses, many individuals with schizophrenia, manic-depressive illness and other serious brain disorders do not have access to treatments which could benefit them. Most of these individuals are reliant on underfunded public mental health systems for their care and treatment. Most are Medicaid recipients, due to their extreme poverty and disability. Because of the failures of public mental health systems, many individuals with severe mental illnesses must turn to research protocols for access to promising new medications. Consequently, the boundary lines between clinical treatment and research have been somewhat blurred.


Nevertheless, there are significant distinctions between clinical treatment and research. While clinical treatment programs are designed solely to benefit individuals who participate in them, this is frequently not the case with research. Some research protocols are designed to produce basic information about characteristics or patterns of specific brain disorders, with no expectation that the research will yield specific benefits for individuals who participate in these protocols. Other protocols are designed to assess the progression and course of specific disorders, without focus on treatments to alleviate the symptoms of these disorders. For example, the UCLA study in question involved a relapse protocol: research subjects were withdrawn from their medications specifically to study relapse patterns.


Even research protocols which are designed to study potentially beneficial treatments of severe mental illnesses may not prove beneficial to individual participants. Many new medication protocols are designed as placebo controlled studies, i.e. some participants are administered the medication being studied and some are administered placebo. In studies of this nature, there is no guarantee that individual participants will ever be administered the new medication under study.


Finally, biomedical research on the causes and treatments of severe mental illnesses involve varying degrees of risk for individual participants. Some protocols involve minimal risks to individual participants, e.g. studies which involve no more than a blood test, whereas other protocols involve risks which are potentially quite significant, e.g. early trials of new medications with unknown potential benefits or side effects.

These multiple factors, i.e. the cognitive impairments of individuals who participate as human subjects in psychiatric research, the unknown clinical benefits of such research, and the potential risks of research together mitigate strongly in favor of the need for comprehensive, strengthened procedures for protecting the best interests of these vulnerable individuals. The remainder of my presentation will focus on certain steps which can be taken, in accordance with NAMIís policies, to improve these protections.


(1) National standards to govern voluntary consent, comprehensive exchange of information, and related protections of persons with cognitive impairments who become research subjects must be developed and they must include the interests of persons who become human subjects, families, and other caregivers.


Two national Commissions - The National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research (1979) and the Presidentís Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research (1981) identified persons with mental illnesses as a particularly vulnerable group and therefore recommended special protections for these individuals in future Federal regulations governing biomedical research. Despite this, the Federal Regulations which were adopted did not include persons with severe mental illnesses among the vulnerable populations listed as needing special protections.

These regulations set forth specific elements required for the provision of informed consent for all research involving greater than minimal risks for individual subjects. However, these regulations are silent concerning special factors which must be considered concerning the provision of information about specific research and the process of obtaining fully informed consent from individuals who have cognitive impairments.


For example, the capacity of an individual with a cognitive impairment may fluctuate over periods of time. While an individual may be capable of comprehending the nature of a specific research protocol at the beginning of the process (the time when informed consent is typically provided), his/her capacity to comprehend may be impaired at some point during the research process. Nevertheless, the regulations do not address the importance of the ongoing provision of information to the research subject throughout the research process (which, in the case of some protocols, may be rather lengthy).


Similarly, the regulations do not address the importance of providing information to family members or others who function as caregivers in the lives of persons with cognitive impairments. There is a presumption implicit in the regulations that if an individual does not have a legal guardian or representative, there is no obligation to communicate information about the research to anyone other than the individual, including members of his/her family. Finally, the regulations do not provide guidance concerning surrogate consent and other procedures which should be utilized when individuals are determined to lack capacity to provide informed consent. Scientists involved in research on Alzheimerís Disease and other neurological disorders impacting primarily on senior citizens have done important work in developing mechanisms for (a) considering when surrogate consent may be appropriate in biomedical research, and (b) determining who may appropriately provide surrogate consent in specific types of biomedical research. These guidelines have been incorporated, in part, into draft legislation in Maryland addressing informed consent and other protections for decisionally incapacitated subjects in research.


The lack of guidance specific to research on subjects with cognitive impairments speaks to the need to develop general, national standards governing research of this nature. Since the National Institute of Mental Health (NIMH) funds more than 75% of all biomedical research on severe mental illness, NAMI believes that it should take the lead, in concert with other federal agencies funding research conducted on individuals with cognitive impairments, to promulgate such standards. Persons with severe mental illnesses, family members, and other stakeholders should be integrally involved in this process. NAMI is pleased that NIMH Director Steven Hyman, M.D., has begun such a process.


The development of national standards governing research on individuals with cognitive impairments must emphasize that informed consent is an ongoing process and that individual research subjects should be provided with comprehensive information, orally and in writing, throughout the research process. This should include information about the purposes and scale of the research, the objectives of the research, the likely research process, the potential benefits and risks of the research, and treatment options available to the research subject, in lieu of research. Specific information should also be provided about the role and functions of the Institutional Review Board (IRB) and who to contact in the event that the research subject or his/her family have questions or concerns about the research. NAMI believes that the development of model and policies and practices would be extremely useful to IRBs and the research community.


(2) Research participants should be carefully evaluated before and throughout the research for their capacity to comprehend information and their capacity to consent to continued participation in the research. The determination of competence shall be made by someone other than the principal investigator or others involved in the research. Except for research protocols approved by the Institutional Review Board (IRB) as minimal risk, whenever it is determined that the subject is not able to continue to provide consent, consent to continued participation shall be sought from families or others legally entrusted to act in the participantís best interests.


There are three important principals embedded in this policy. First, since persons suffering from severe mental illnesses such as schizophrenia frequently experience fluctuations in decisional capacity, the capacity of all individuals with these disorders who participate as human subjects in research should be monitored on an ongoing basis. Research on those persons most impaired by severe mental illnesses is critical, as these brain disorders are often devastating. But research of this type must be conducted with special attention to the cognitive impairments which characterize these diseases.


Second, if questions arise concerning an individualís capacity to provide initial or ongoing informed consent, an immediate, thorough assessment of capacity should occur. Since the ability of the principal investigator or his/her staff to conduct objective assessments may be compromised, the assessment should be conducted by a qualified individual who is not directly involved in the research.


Finally, if it is determined that an individual lacks decisional capacity, substitute consent should be sought. Unless there are indications to the contrary, family members should be asked to provide substitute consent. If no family members are willing or able to function in this capacity, substitute consent should be permitted only from one who has been legally entrusted to function in this capacity, e.g. an individual assigned durable power of attorney pursuant to a properly executed advance directive or an alternative legal mechanism for assigning a proxy.


(3) Institutional Review Boards that regularly review research proposals for severe mental illnesses must include consumers and family members who have direct and personal experience with these brain disorders.


At many universities and research facilities, one Institutional Review Board (IRB) has responsibility for reviewing and approving all research conducted at these facilities. There are no assurances that anyone serving on these IRBs has specific knowledge about severe mental illnesses or research conducted on these illnesses.


NAMI strongly believes that all IRBs approving research on severe mental illnesses must include (a) at least one person, and preferably more, with knowledge of severe mental illnesses, and (b) a person with a severe mental illness or a family member of someone with an illness. If this is not possible, then IRBs considering research protocols on severe mental illnesses should be required to consult with individuals who have direct experience with these illnesses before approving a specific protocol.


Additionally, IRBs approving research on individuals with severe mental illnesses must receive specialized training about these disorders and issues pertinent to the participation of individuals with these disorders in research protocols. Persons with severe mental illnesses and their families should be involved in designing and conducting this training.


(4) Investigators must ensure that individuals who participate in research as outpatients are linked to appropriate care, treatment and supports for the entire duration of the research protocol.


Today, most biomedical research on severe mental illnesses is conducted on an outpatient basis. Individuals with these illnesses who participate in research may be particularly vulnerable to relapse or decompensation due to exacerbation of their psychiatric symptoms. This is especially, but not uniquely true, when the protocol involves "drug washouts" (i.e. withdrawal from psychotropic medications).


The potential implications of relapse or decompensation can be devastating for individuals with severe mental illnesses and their families. These consequences can include broken relationships, loss of housing and supports, homelessness, petty crimes, victimization, violence, or arrest and incarceration. Consequently, researchers have an important ethical and moral obligation to ensure that all vulnerable research participants are linked to treatment which can be accessed on a timely basis for as long as needed. Since families are generally the first to recognize signs of relapse, investigators and their staff must also be prepared to respond to family questions and concerns on a timely and appropriate basis.


5. All participants in research protocols involving the assessment of new medications must be provided with opportunities by the investigator for a trial on the medication being studied, so long as other research on the new medication has demonstrated potential safety and efficacy.


Many research protocols evaluating the efficacy and safety of experimental medications for the treatment of severe mental illnesses are designed as placebo controlled studies. These studies typically include one group of subjects who receive the experimental treatment and one group of subjects who are administered placebo or an older psychotropic medication. In these studies, researchers are precluded from informing subjects of the group they are in. Consequently, individuals in desperate need of treatment may think that they are receiving an experimental treatment, when in fact they are being administered a placebo.


NAMI has serious questions about whether "double blind" studies are still necessary in this era. We urge that the Food and Drug Administration (FDA), the National Institute of Mental Health (NIMH) and other involved federal agencies be charged with evaluating the need for this approach and reporting back to the Subcommittee on a timely basis.


Additionally, NAMI strongly believes that all individuals participating in protocols involving the evaluation of experimental medications should be afforded the opportunity for a trial on the experimental treatment. Therefore, if individuals receive placebo as part of the study design, they should receive a trial on the new medication following completion of the placebo phase.


(6) All individuals who have benefited from the administration of experimental medications in research should be provided with continual access to the medication by the investigator without cost until a source of third-party payment is found.


Recently, I received a call from an old friend who suffers from schizophrenia. She informed me that after two successful years on an experimental medication for schizophrenia, she had been taken off the medication because the drug company funding the research would no longer pay for her to receive the medication. Consequently, she is now desperately searching for a new protocol which she can participate in to receive the medication until it is approved by the FDA.


Unfortunately, sad stories like these are all too common for persons with severe mental illnesses. While drug companies frequently try to make experimental medications available free of charge to people who have successfully completed trials for fixed periods of time, the time limits established by these companies, coupled with the lengthy drug approval process, result in many people suffering relapses after being terminated from these drugs for lack of funding.


In view of the sacrifices made by people who voluntary participate in trials of experimental medications, NAMI believes that all individuals should have continuing access to medications they have benefited from until alternative sources of funding are found. We believe that drug companies have a moral responsibility to those who participate in their protocols.




I have very much appreciated the opportunity to testify before you on informed consent and other protections for individuals who participate as human subjects in research on severe mental illnesses. The complete NAMI policies are attached as an appendix to our written testimony. I look forward to any questions you may have.