Islamic Center of Southern California

International Ethical Guidelines for Biomedical Research Involving Human Subjects

Guideline 13

Research Involving Vulnerable Persons

Special justification is required for inviting vulnerable individuals to serve as research subjects and, if they are selected, the means of protecting their rights and welfare must be strictly applied.

Commentary on Guideline 13

Vulnerable persons are those who are relatively (or absolutely) incapable of protecting their own interests. More formally, they may have insufficient power, intelligence, education, resources, strength, or other needed attributes to protect their own interests.

General Considerations. The central problem presented by plans to involve vulnerable persons as research subjects is that such plans may entail an inequitable distribution of the burdens and benefits of research participation. Classes of individuals conventionally considered vulnerable are those with limited capacity or freedom to consent or to decline to consent. They are the subject of specific guidelines in this document (Guidelines 14,15) and include children, and persons who because of mental or behavioral disorders are incapable of giving informed consent. Ethical justification of their involvement usually requires that investigators satisfy ethical review committees that:

the research could not be carried out equally well with less vulnerable subjects;

the research is intended to obtain knowledge that will lead to improved diagnosis, prevention, or treatment of diseases or other health problems characteristic of, or unique to, the vulnerable class - either the actual subjects or other similarly situated members of the vulnerable class;

research subjects and other members of the vulnerable class from which subjects are recruited will ordinarily be assured reasonable access to any diagnostic, preventive, or therapeutic products that will become available as a consequence of the research;

the risks attached to interventions or procedures that do not hold out the prospect of direct health-related benefit will not exceed those associated with routine medical or psychological examination of such persons unless an ethical review committee authorizes a slight increase over this level of risk (Guideline 9); and

when the prospective subjects are either incompetent or otherwise substantially unable to give informed consent, their agreement will be supplemented by the permission of their legal guardians or other appropriate representatives.

Other Vulnerable Groups. The quality of the consent of prospective subjects who are junior or subordinate members of a hierarchical group requires careful consideration, as their agreement to volunteer may be unduly influenced, whether justified or not, by the expectation of preferential treatment if they agree or by fear of disapproval or retaliation if they refuse. Examples of such groups are medical and nursing students, subordinate hospital and laboratory personnel, employees of pharmaceutical companies, and members of the armed forces and the police. Because they work in close proximity to investigators, they tend to be called upon more often than others to serve as research subjects, and this could result in inequitable distribution of the burdens and benefits of research.

Elderly persons are commonly regarded as vulnerable. With advancing age, people are increasingly likely to acquire attributes that define them as vulnerable. They may, for example, be institutionalized or develop varying degrees of dementia. If and when they acquire such vulnerability-defining attributes, and not before, it is appropriate to consider them vulnerable and to treat them accordingly.

Other groups or classes may also be considered vulnerable. They include residents of nursing homes, people receiving welfare benefits or social assistance and other poor people and the unemployed, patients in emergency rooms, some ethnic and racial minority groups, homeless persons, nomads, refugees or displaced persons, prisoners, patients with incurable disease, individuals who are politically powerless, and members of communities unfamiliar with modern medical concepts. To the extent that these and other classes of people have attributes resembling those of classes identified as vulnerable, the need for special protection of their rights and welfare should be reviewed and applied, where relevant.

Persons who have serious, potentially disabling or life-threatening diseases are highly vulnerable. Physicians sometimes treat such patients with drugs or other therapies not yet licensed for general availability because studies designed to establish their safety and efficacy have not been completed. This is compatible with the Declaration of Helsinki, which states in Paragraph 32: "In the treatment of a patient, where proven therapeutic methods do not exist or have been ineffective, the physician, with informed consent from the patient, must be free to use unproven or new therapeutic measures, if in the physician's judgment it offers hope of saving life, re-establishing health, or alleviating suffering." Such treatment, commonly called 'compassionate use,' is not properly regarded as research, but it can contribute to ongoing research into the safety and efficacy of the interventions used.

Although, on the whole, investigators must study less vulnerable groups before involving more vulnerable groups, some exceptions are justified. In general, children are not suitable for Phase I drug trials or for Phase I or II vaccine trials, but such trials may be permissible after studies in adults have shown some therapeutic or preventive effect. For example, a Phase II vaccine trial seeking evidence of immunogenicity in infants may be justified when the vaccine has shown evidence of preventing or slowing progression of an infectious disease in adults, or Phase I research with children may be appropriate because the disease to be treated does not occur in adults or is manifested differently in children (Appendix 3: The Phases of Clinical Trials of Vaccines and Drugs).

The Islamic Point of View Concerning Guideline 13

Research Involving Vulnerable Persons

1. The content of and commentary on this guideline are subject to the same rulings as previous guidelines which aim at enforcing the principle of respect for individuals, particularly those considered vulnerable, who might succumb to moral pressure and be open to the influence of the researcher or the sponsor.

2. Therefore, groups and industries that can also considered vulnerable - such as emergency room patients, residents of nursing homes and similar establishments, prisoners, refugees, displaced people, and the like, who all need their rights and interests to be protected - should not be forced, pressured, deceived, or subjected to an exploitation of their psychological condition or financial difficulties in order to make them consent to be research subjects. Such a coercion or exploitation involves injustice that is disapproved by the principles of Islamic Law, which condemns all types and forms of injustice and inequality. In a divine tradition, the Prophet, blessings and peace be upon him, quotes his Lord, the most Glorious and Sublime, as saying, "My worshippers, I have forbidden injustice on my part and made it forbidden among you, so do not be unjust to one another." The Prophet, blessings and peace be upon him, says, "Beware of injustice, for injustice is layers of darkness on the Day of Resurrection."

Thus, a special justification of recruiting vulnerable individuals to serve as research subjects is required in Islamic Law, and, as stipulated in this guideline, strict measures to protect their personal rights and interests should be taken. Islamic Center of Southern California