Reforming Informed Consent to Genetic Research

Examination of the current system of protecting human subjects has highlighted concerns about its overall effectiveness.^{1 - 4} It is infused with conflicts of interest, and research is increasingly financed and promoted by for-profit entities.^{1 ,4} Institutional review boards (IRBs) review "too much, too quickly, and with too little expertise," with many IRBs spending "only 1 or 2 minutes of review per study."^{2 - 3} This inadequate system of protection of the rights and welfare of human subjects in medical research requires extensive reform. As part of the change process, efforts should focus on taking the entire consent process seriously. In this issue of THE JOURNAL, Beskow et al⁵ suggest elements that may be helpful in preparing a consent form for population-based research involving genetics.

As a lawyer, I certainly understand the value of specific forms for documentation and cannot fault Beskow et al⁵ for trying to improve them. Nonetheless, initiatives to better safeguard the rights and welfare of research subjects require a broader vision. Research volunteers should be accurately and effectively educated about what they are getting into. Improving consent forms is only a part of this educational process.

Informed consent is a process, not a form.^{6 - 7} This point is simple, yet it continues to elude many researchers. At least since the Nuremberg Code was enunciated in 1947, it has been understood that the voluntary, competent, informed, and understanding consent of the research subject is a necessary (but not sufficient) condition for ethical and lawful experimentation involving humans.^{6 - 7} Consent forms are not mentioned in the Nuremberg Code; it is the substance of the consent process that matters.

The current system of protecting human subjects unfortunately often focuses almost exclusively on the consent form, treating it more like a legal contract than a useful document for education and explanation. Angell⁸ has complained that consent forms are written "by lawyers for other lawyers." My own view is that most often, consent forms are written by researchers for other researchers, who make up the majority of IRB members.⁹ As arguably illustrated in the article by Beskow et al,⁵ even when written by both lawyers and researchers, the resulting consent form may be more likely to protect researchers and their institutions than research subjects.

Informed consent forms should be designed to document the process that occurred with the research subject, not to serve as a substitute for it. Focusing on documents and the words in them is a legalistic and bureaucratic approach to the complex and nuanced ethical issues involved in research. When IRBs devote most of their time to the wording of the consent document, investigators may lose respect for the entire IRB review system, which may be viewed simply as red tape and a waste of time and energy. This lack of respect can then translate quickly into developing methods to circumvent or restructure IRB review that may lead to research programs in universities being temporarily shut down by federal regulators.¹⁰ Johns Hopkins University, for example, has recently and constructively announced 14 specific steps it is taking to strengthen research oversight.¹¹ One of them mentions the consent form.

The National Bioethics Advisory Commission has highlighted the general problem of placing the importance of the consent form above that of substance. In their report, Ethical and Policy Issues in Research Involving Human Participants,⁹ the commission notes that IRBs and investigators "have tended to focus on the disclosures found in the consent form" rather than on "the ethical standard of informed consent and what is entailed in the process of obtaining informed consent." In a specific recommendation, the commission is unequivocal: "Federal policy should emphasize the process of informed consent rather than the form of its documentation and should ensure that competent participants have given their voluntary informed consent. Guidance should be issued about how to provide appropriate information to prospective research participants, how to promote prospective participants' comprehension of such information, and how to ensure that participants continue to make informed and voluntary decisions throughout their involvement in the research."⁹

Consent forms can be used to protect or exploit research subjects. Lawyers who draft consent documents may view the institution or researcher as their client, and the research subject as an adversary. Thus, consent forms may not serve as the shield they were intended to be. For example, Beskow et al⁵ suggest language that can be used to preclude research subjects from sharing in financial benefits that may accrue to the researchers should a patented product be developed using the research participants' DNA. In population studies, benefit to the population has become one of the critical issues in determining the ethical justification for the study itself, and sharing benefits with the population is critical in preventing exploitation.¹² An analysis of what benefits may accrue and how they can be fairly shared would be useful to research subjects. Most consent forms also indicate that if subjects are injured in the research, neither the researcher nor the institution is responsible for providing compensation for their injury. This clause, of course, is against the interests of the subject.

One element that is commonly found in consent forms is not suggested by Beskow et al, and they are to be commended for rejecting it. Many consent forms require a subject to certify that he or she "understands" all of the information contained in the form and has been given the opportunity to ask questions. If self-determination is the goal, the researcher is responsible for determining that the subject actually understands what is at stake in the research. An untested certification of understanding is no substitute for asking the subject questions (eg, about the nature of the research project, the risks involved, and the alternatives available to the subject) and requiring answers that confirm understanding.¹³

Additional educational approaches might also be helpful to subjects, such as brochures and videotapes about the research,¹⁴ and conversations with others who have agreed or declined to participate in the research. It may also be useful for the consent process to be monitored by an independent person, such as a physician not involved with the study or with the patient's care, who may be able to suggest ways to improve the communication process. As Katz,¹⁵ a respected authority on informed consent, has suggested, however, the most difficult task is for physician-investigators to "acknowledge that their patient-subjects view them as physicians and not investigators, and that they, the doctors themselves, have the responsibility to challenge that trust in research settings. Patient-subjects must be told that their own and their physician-investigators' agendas are not the same. Research is not therapy."

Many consent issues are generic, but some are unique to population-based genetics studies and have been usefully outlined by the National Research Council's Committee on Human Genome Diversity: community objections to the research must be understood by potential subjects; measures must be taken to "protect individual research participants from stigmatization and discrimination"; consent must be limited to the specific proposed uses of DNA samples in the research protocol; and individuals must have the right to withdraw their DNA samples from the research at any time.¹²

Central to population-based genetics research is the risk that finding patterns of genes in a community could stigmatize the entire community as being predisposed to specific diseases, thus affecting how the individuals in the entire community are seen by others and how they see themselves. Prior consultation is not optional when the community itself can be seen as the subject of research.¹² But how and by whom should this consultation be conducted? Who should be consulted? What information should be communicated, and how? Who speaks for the community, and what weight should be given to their views?¹⁶ Only after a detailed method for obtaining community consultation is devised and the results of this consultation determined can it be decided whether the research should be attempted. Furthermore, if such research is attempted, what information about the community's views must be presented to the individual research subject in the consent process?¹²

The misuse of genetic data is a concern with population-based genetics research.^{12 ,17} At least some of the studies contemplated by Beskow et al⁵ seek to categorize genetic data by race. This categorization is accepted even though the Human Genome Project has confirmed prior scientific opinion that race has no genetic basis and is a social construct.¹⁸ It is possible that using an arbitrary social construct as a scientific variable in a genetics study may reinforce it by providing an unscientific genetic basis for it.¹⁹ In this way, racism could be replaced or supplemented by "genism."²⁰ This fundamental issue must be faced with all proposed population-based genetics studies, but is easy to ignore by concentrating primarily on the content of consent forms.

The goal of informed consent is to provide protection by making sure that potential research subjects understand the research they are being asked to volunteer for, its risks, its benefits, and its alternatives. Informed consent is a process, and only after that process occurs is documenting it with a form such as that suggested by Beskow et al⁵ useful. To protect the rights of research subjects, the first question about every aspect of the consent process should be "how will this help the subject?" and not "how will this help the researcher?"