Islamic Center of Southern California

International Ethical Guidelines for Biomedical Research Involving Human Subjects

Guideline 6

Obtaining Informed Consent

Obligations of Sponsors and Investigators

Sponsors and investigators have a duty to:

refrain from unjustified deception, undue influence, or intimidation;

seek consent only after ascertaining that the prospective subject has adequate understanding of the relevant facts and of the consequences of participation and has had sufficient opportunity to consider whether to participate;

as a general rule, obtain from each prospective subject a signed form as evidence of informed consent - investigators should justify any exceptions to this general rule and obtain the approval of the ethical review committee (See Guideline 4 Commentary, Documentation of Consent);

renew the informed consent of each subject if there are significant changes in the conditions or procedures of the research or if new information becomes available that could affect the willingness of subjects to continue to participate; and

renew the informed consent of each subject in long-term studies at pre-determined intervals, even if there are no changes in the design or objectives of the research.

Commentary on Guideline 6

The investigator is responsible for ensuring the adequacy of informed consent from each subject. The person obtaining informed consent should be knowledgeable about the research and capable of answering questions from prospective subjects. Investigators in charge of the study must make themselves available to answer questions at the request of subjects. Any restrictions on the subject's opportunity to ask questions and receive answers before or during the research undermines the validity of the informed consent.

In some types of research, potential subjects should receive counseling about risks of acquiring a disease unless they take precautions. This is especially true of HIV/AIDS vaccine research (UNAIDS Guidance Document Ethical Considerations in HIV Preventive Vaccine Research, Guidance Point 14).

Withholding Information and Deception. Sometimes, to ensure the validity of research, investigators withhold certain information in the consent process. In biomedical research, this typically takes the form of withholding information about the purpose of specific procedures. For example, subjects in clinical trials are often not told the purpose of tests performed to monitor their compliance with the protocol, since if they knew their compliance was being monitored they might modify their behavior and hence invalidate results. In most such cases, the prospective subjects are asked to consent to remain uninformed of the purpose of some procedures until the research is completed; after the conclusion of the study they are given the omitted information. In other cases, because a request for permission to withhold some information would jeopardize the validity of the research, subjects are not told that some information has been withheld until the research has been completed. Any such procedure must receive the explicit approval of the ethical review committee.

Active deception of subjects is considerably more controversial than simply withholding certain information. Lying to subjects is a tactic not commonly employed in biomedical research. Social and behavioral scientists, however, sometimes deliberately misinform subjects to study their attitudes and behavior. For example, scientists have pretended to be patients to study the behavior of health-care professionals and patients in their natural settings.

Some people maintain that active deception is never permissible. Others would permit it in certain circumstances. Deception is not permissible, however, in cases in which the deception itself would disguise the possibility of the subject being exposed to more than minimal risk. When deception is deemed indispensable to the methods of a study, the investigators must demonstrate to an ethical review committee that no other research method would suffice; that significant advances could result from the research; and that nothing has been withheld that, if divulged, would cause a reasonable person to refuse to participate. The ethical review committee should determine the consequences for the subject of being deceived, and whether and how deceived subjects should be informed of the deception upon completion of the research. Such informing, commonly called "debriefing", ordinarily entails explaining the reasons for the deception. A subject who disapproves of having been deceived should be offered an opportunity to refuse to allow the investigator to use information thus obtained. Investigators and ethical review committees should be aware that deceiving research subjects may wrong them as well as harm them; subjects may resent not having been informed when they learn that they have participated in a study under false pretences. In some studies there may be justification for deceiving persons other than the subjects by either withholding or disguising elements of information. Such tactics are often proposed, for example, for studies of the abuse of spouses or children. An ethical review committee must review and approve all proposals to deceive persons other than the subjects. Subjects are entitled to prompt and honest answers to their questions; the ethical review committee must determine for each study whether others who are to be deceived are similarly entitled.

Intimidation and Undue Influence. Intimidation in any form invalidates informed consent. Prospective subjects who are patients often depend for medical care upon the physician/investigator, who consequently has a certain credibility in their eyes, and whose influence over them may be considerable, particularly if the study protocol has a therapeutic component. They may fear, for example, that refusal to participate would damage the therapeutic relationship or result in the withholding of health services. The physician/investigator must assure them that their decision on whether to participate will not affect the therapeutic relationship or other benefits to which they are entitled. In this situation the ethical review committee should consider whether a neutral third party should seek informed consent.

The prospective subject must not be exposed to undue influence. The borderline between justifiable persuasion and undue influence is imprecise, however. The researcher should give no unjustifiable assurances about the benefits, risks, or inconveniences of the research, for example, or induce a close relative or a community leader to influence a prospective subject's decision. (See also Guideline 4: Individual Informed Consent.)

Risks. Investigators should be completely objective in discussing the details of the experimental intervention, the pain and discomfort that it may entail, and known risks and possible hazards. In complex research projects it may be neither feasible nor desirable to inform prospective participants fully about every possible risk. They must, however, be informed of all risks that a 'reasonable person' would consider material to making a decision about whether to participate, including risks to a spouse or partner associated with trials of, for example, psychotropic or genital-tract medicaments. (See also the Commentary on Guideline 8, Risks to Groups of Persons.)

Exception to the Requirement for Informed Consent in Studies of emergency Situations in Which the Researcher Anticipates That Many Subjects Will Be Unable to Consent. Research protocols are sometimes designed to address conditions occurring suddenly and rendering the patients/subjects incapable of giving informed consent. Examples are head trauma, cardiopulmonary arrest and stroke. The investigation cannot be done with patients who can give informed consent in time and there may not be time to locate a person having the authority to give permission. In such circumstances it is often necessary to proceed with the research interventions very soon after the onset of the condition in order to evaluate an investigational treatment or develop the desired knowledge. As this class of emergency exception can be anticipated, the researcher must secure the review and approval of an ethical review committee before initiating the study. This can be done readily, for example, if the condition is one that recurs periodically in individuals; examples include grand mal seizures and alcohol binges. In such cases, prospective subjects should be contacted while fully capable of informed consent, and invited to consent to their involvement as research subjects during future periods of incapacitation. If they are patients of an independent physician who is also the physician-researcher, the physician should likewise seek their consent while they are fully capable of informed consent. In all cases in which approved research has begun without prior consent of patients/subjects incapable of giving informed consent because of suddenly occurring conditions, they should be given all relevant information as soon as they are in a state to receive it, and their consent to continued participation should be obtained as soon as is reasonably possible.

Before proceeding without prior informed consent, the investigator must make reasonable efforts to locate an individual who has the authority to give permission on behalf of an incapacitated patient. If such a person can be located and refuses to give permission, the patient may not be enrolled as a subject. The risks of all interventions and procedures will be justified as required by Guideline 9 (Special limitations on risks when research involves individuals who are not capable of giving consent). The researcher and the ethical review committee should agree to a maximum time of involvement of an individual without obtaining either the individual's informed consent or authorization according to the applicable legal system if the person is not able to give consent. If by that time the researcher has not obtained either consent or permission - owing either to a failure to contact a representative or to a refusal of either the patient or the person or body authorized to give permission - the participation of the patient as a subject must be discontinued. The patient or the person or body providing authorization should be offered an opportunity to forbid the use of data derived from participation of the patient as a subject without consent or permission.

Plans to conduct emergency research without prior consent of the subjects should be publicized within the community in which it will be carried out. In the design and conduct of the research, the ethical review committee, the investigators and the sponsors should be responsive to the concerns of the community. If there is cause for concern about the acceptability of the research in the community, there should be a formal consultation with representatives designated by the community. The research should not be carried out if it does not have substantial support in the community concerned. (See the Commentary on Guideline 8, Risks to Groups of Persons.)

Exception to the Requirement of Informed Consent for Inclusion in Clinical Trials of Persons Rendered Incapable of Informed Consent by an Acute Condition. Certain patients with an acute condition that renders them incapable of giving informed consent may be eligible for inclusion in a clinical trial in which the majority of prospective subjects will be capable of informed consent. Such a trial would relate to a new treatment for an acute condition such as sepsis, stroke or myocardial infarction. The investigational treatment would hold out the prospect of direct benefit and would be justified accordingly, though the investigation might involve certain procedures or interventions that were not of direct benefit but carried no more than minimal risk; an example would be the process of randomization or the collection of additional blood for research purposes. For such cases the initial protocol submitted for approval to the ethical review committee should anticipate that some patients may be incapable of consent, and should propose for such patients a form of proxy consent, such as permission of the responsible relative. When the ethical review committee has approved or cleared such a protocol, an investigator may seek the permission of the responsible relative and enroll such a patient

The Islamic Point of View Concerning Guideline 6

Obtaining Informed Consent

Obligations of Sponsors and Investigators

The obligations of research and researcher sponsors cited in this guideline are, in general, in agreement with the principles of Islamic Law, for actually, they explain and elaborate on what Guidelines 4 and 5 mention in a more concise form. The basis in Islamic Law for endorsement of the basic idea of those guidelines, as well as their amplification and details, has already been specified, and it is sufficient and clear enough to render any repetition here unnecessary. Islamic Center of Southern California