Islamic Center of Southern California

International Ethical Guidelines for Biomedical Research Involving Human Subjects

Guideline 8

Benefits and Risks of Study Participation

For all biomedical research involving human subjects, the investigator must ensure that potential benefits and risks are reasonably balanced and risks are minimized.

Interventions or procedures that hold out the prospect of direct diagnostic, therapeutic, or preventive benefit for the individual subject must be justified by the expectation that they will be at least as advantageous to the individual subject, in the light of foreseeable risks and benefits, as any available alternative. Risks of such 'beneficial' interventions or procedures must be justified in relation to expected benefits to the individual subject.

Risks of interventions that do not hold out the prospect of direct diagnostic, therapeutic, or preventive benefit for the individual must be justified in relation to the expected benefits to society (generalizable knowledge). The risks presented by such interventions must be reasonable in relation to the importance of the knowledge to be gained.

Commentary on Guideline 8

The Declaration of Helsinki deals in several paragraphs with the well-being of research subjects and the avoidance of risk. Thus, considerations related to the well-being of the human subject should take precedence over the interests of science and society (Paragraph 5); clinical testing must be preceded by adequate laboratory or animal experimentation to demonstrate a reasonable probability of success without undue risk (Paragraph 11); every project should be preceded by careful assessment of predictable risks and burdens in comparison with foreseeable benefits to the subject or to others (Paragraph 16); physician-researchers must be confident that the risks involved have been adequately assessed and can be satisfactorily managed (Paragraph 17); and the risks and burdens to the subject must be minimized, and reasonable in relation to the importance of the objective or the knowledge to be gained (Paragraph 18).

Biomedical research often employs a variety of interventions of which some hold out the prospect of direct therapeutic benefit (beneficial interventions) and others are administered solely to answer the research question (non-beneficial interventions). Beneficial interventions are justified as they are in medical practice by the expectation that they will be at least as advantageous to the individuals concerned, in the light of both risks and benefits, as any available alternative. Non-beneficial interventions are assessed differently; they may be justified only by appeal to the knowledge to be gained. In assessing the risks and benefits that a protocol presents to a population, it is appropriate to consider the harm that could result from forgoing the research.

Paragraphs 5 and 18 of the Declaration of Helsinki do not preclude well-informed volunteers, capable of fully appreciating risks and benefits of an investigation, from participating in research for altruistic reasons or for modest remuneration.

Minimizing Risk Associated with Participation in a Randomized Controlled Trial. In randomized controlled trials, subjects risk being allocated to receive the treatment that proves inferior. They are allocated by chance to one of two or more intervention arms and followed to a predetermined end-point. (Interventions are understood to include new or established therapies, diagnostic tests, and preventive measures.) An intervention is evaluated by comparing it with another intervention (a control), which is ordinarily the best current method, selected from the safe and effective treatments available globally, unless some other control intervention such as placebo can be justified ethically (See Guideline 11).

To minimize risk when the intervention to be tested in a randomized controlled trial is designed to prevent or postpone a lethal or disabling outcome, the investigator must not, for purposes of conducting the trial, withhold therapy that is known to be superior to the intervention being tested, unless the withholding can be justified by the standards set forth in Guideline 11. Also, the investigator must provide in the research protocol for the monitoring of research data by an independent board (Data and Safety Monitoring Board); one function of such a board is to protect the research subjects from previously unknown adverse reactions or unnecessarily prolonged exposure to an inferior therapy. Normally at the outset of a randomized controlled trial, criteria are established for its premature termination (stopping rules or guidelines).

Risks to Groups of Persons. Research in certain fields, such as epidemiology, genetics or sociology, may present risks to the interests of communities, societies, or racially or ethnically defined groups. Information might be published that could stigmatize a group or expose its members to discrimination. Such information, for example, could indicate, rightly or wrongly, that the group has a higher than average prevalence of alcoholism, mental illness, or sexually transmitted disease, or is particularly susceptible to certain genetic disorders. Plans to conduct such research should be sensitive to such considerations, to the need to maintain confidentiality during and after the study, and to the need to publish the resulting data in a manner that is respectful of the interests of all concerned, or in certain circumstances not to publish them. The ethical review committee should ensure that the interests of all concerned are given due consideration; often it will be advisable to have individual consent supplemented by community consultation. [The ethical basis for the justification of risk is elaborated further in Guideline 9.]

The Islamic Point of View Concerning Guideline 8

Benefits and Risks of Study Participation 1. The need to strike a balance between potential benefits and risks in research involving human subjects - with the prospective benefits being more likely, at least for individual subjects - and the need to minimize risks are both included in a basic principle of Islamic Law, expressed in the following rules of jurisprudence (fiqh): "Harm should be warded off whenever possible;" "if a benefit and a instance of harm are in conflict priority should be given to the weightier of the two;" Ibn Taimiyah says, "The principle of the Law is that if an action involves harm, it is prohibited, unless this harm is in conflict with a weightier benefit, as in the case of permitting a person to eat the flesh of an animal corpse when he has to. The greater of two injuries is warded off by tolerating the lesser one." 2. It is acceptable from a religious perspective to use the expected, significant benefits to society as a justification of the risks of interventions that do not hold out the prospect of direct diagnostic, therapeutic, or preventive benefit for the individual. This is based on the rules of jurisprudence which say: "Public interests take precedence over private ones;" "the concern of the Law for public interests is more comprehensive and complete than its concern for private ones;" and "a public interest is the same as a private necessity," that is in permitting a forbidden thing.

As for the criterion that distinguishes public from private interests, it is that a public, or collective, interest is "everything that involves the realization of a gain or the prevention of an injury that affects the whole nation, a large group, a province, or the like," while a private interest is "everything that involves the realization of a gain or the prevention of an injury or harm that affects a certain individual or few individuals." Islamic Center of Southern California