Human Subjects Guidelines

The following information is from the Council for International Organizations of Medical Sciences (CIOMS) publication, International Ethical Guidelines for Biomedical Research Involving Human Subjects. This publication is available on this link. The materials below are an extract of relevant points. The original publication includes important details and it should be consulted.

In addition to the information below, please refer to the Human Subjects Protocol.

GENERAL ETHICAL PRINCIPLES

All research involving human subjects should be conducted in accordance with three basic ethical principles, namely respect for persons, beneficence and justice. It is generally agreed that these principles, which in the abstract have equal moral force, guide the conscientious preparation of proposals for scientific studies. In varying circumstances they may be expressed differently and given different moral weight, and their application may lead to different decisions or courses of action. The present guidelines are directed at the application of these principles to research involving human subjects.

Respect for persons incorporates at least two fundamental ethical considerations, namely:

a) respect for autonomy, which requires that those who are capable of deliberation about their personal choices should be treated with respect for their capacity for self-determination; and

b) protection of persons with impaired or diminished autonomy, which requires that those who are dependent or vulnerable be afforded security against harm or abuse.

Beneficence refers to the ethical obligation to maximize benefits and to minimize harms. This principle gives rise to norms requiring that the risks of research be reasonable in the light of the expected benefits, that the research design be sound, and that the investigators be competent both to conduct the research and to safeguard the welfare of the research subjects. Beneficence further proscribes the deliberate infliction of harm on persons; this aspect of beneficence is sometimes expressed as a separate principle, nonmaleficence (do no harm).

Justice refers to the ethical obligation to treat each person in accordance with what is morally right and proper, to give each person what is due to him or her. In the ethics of research involving human subjects the principle refers primarily to distributive justice, which requires the equitable distribution of both the burdens and the benefits of participation in research. Differences in distribution of burdens and benefits are justifiable only if they are based on morally relevant distinctions between persons; one such distinction is vulnerability. "Vulnerability" refers to a substantial incapacity to protect one's own interests owing to such impediments as lack of capability to give informed consent, lack of alternative means of obtaining medical care or other expensive necessities, or being a junior or subordinate member of a hierarchical group. Accordingly, special provision must be made for the protection of the rights and welfare of vulnerable persons.

Sponsors of research or investigators cannot, in general, be held accountable for unjust conditions where the research is conducted, but they must refrain from practices that are likely to worsen unjust conditions or contribute to new inequities. Neither should they take advantage of the relative inability of low-resource countries or vulnerable populations to protect their own interests, by conducting research inexpensively and avoiding complex regulatory systems of industrialized countries in order to develop products for the lucrative markets of those countries.

In general, the research project should leave low-resource countries or communities better off than previously or, at least, no worse off. It should be responsive to their health needs and priorities in that any product developed is made reasonably available to them, and as far as possible leave the population in a better position to obtain effective health care and protect its own health.

Justice requires also that the research be responsive to the health conditions or needs of vulnerable subjects. The subjects selected should be the least vulnerable necessary to accomplish the purposes of the research. Risk to vulnerable subjects is most easily justified when it arises from interventions or procedures that hold out for them the prospect of direct health-related benefit. Risk that does not hold out such prospect must be justified by the anticipated benefit to the population of which the individual research subject is representative.

THE GUIDELINES

Guideline 1: Ethical justification and scientific validity of biomedical research involving human beings

The ethical justification of biomedical research involving human subjects is the prospect of discovering new ways of benefiting people's health. Such research can be ethically justifiable only if it is carried out in ways that respect and protect, and are fair to, the subjects of that research and are morally acceptable within the communities in which the research is carried out. Moreover, because scientifically invalid research is unethical in that it exposes research subjects to risks without possible benefit, investigators and sponsors must ensure that proposed studies involving human subjects conform to generally accepted scientific principles and are based on adequate knowledge of the pertinent scientific literature.

Guideline 2: Ethical review committees

All proposals to conduct research involving human subjects must be submitted for review of their scientific merit and ethical acceptability to one or more scientific review and ethical review committees. The review committees must be independent of the research team, and any direct financial or other material benefit they may derive from the research should not be contingent on the outcome of their review. The investigator must obtain their approval or clearance before undertaking the research. The ethical review committee should conduct further reviews as necessary in the course of the research, including monitoring of the progress of the study.

Guideline 3: Ethical review of externally sponsored research

An external sponsoring organization and individual investigators should submit the research protocol for ethical and scientific review in the country of the sponsoring organization, and the ethical standards applied should be no less stringent than they would be for research carried out in that country. The health authorities of the host country, as well as a national or local ethical review committee, should ensure that the proposed research is responsive to the health needs and priorities of the host country and meets the requisite ethical standards.

Guideline 4: Individual informed consent

For all biomedical research involving humans the investigator must obtain the voluntary informed consent of the prospective subject or, in the case of an individual who is not capable of giving informed consent, the permission of a legally authorized representative in accordance with applicable law. Waiver of informed consent is to be regarded as uncommon and exceptional, and must in all cases be approved by an ethical review committee.

Guideline 5: Obtaining informed consent: Essential information for prospective research subjects

Before requesting an individual's consent to participate in research, the investigator must provide the following information, in language or another form of communication that the individual can understand:

1. that the individual is invited to participate in research, the reasons for considering the individual suitable for the research, and that participation is voluntary;
2. that the individual is free to refuse to participate and will be free to withdraw from the research at any time without penalty or loss of benefits to which he or she would otherwise be entitled;
3. the purpose of the research, the procedures to be carried out by the investigator and the subject, and an explanation of how the research differs from routine medical care;
4. for controlled trials, an explanation of features of the research design (e.g., randomization, double-blinding), and that the subject will not be told of the assigned treatment until the study has been completed and the blind has been broken;
5. the expected duration of the individual's participation (including number and duration of visits to the research centre and the total time involved) and the possibility of early termination of the trial or of the individual’s participation in it;
6. whether money or other forms of material goods will be provided in return for the individual's participation and, if so, the kind and amount;
7. that, after the completion of the study, subjects will be informed of the findings of the research in general, and individual subjects will be informed of any finding that relates to their particular health status;
8. that subjects have the right of access to their data on demand, even if these data lack immediate clinical utility (unless the ethical review committee has approved temporary or permanent non-disclosure of data, in which case the subject should be informed of, and given, the reasons for such non-disclosure);
9. any foreseeable risks, pain or discomfort, or inconvenience to the individual (or others) associated with participation in the research, including risks to the health or well-being of a subject’s spouse or partner;
10. the direct benefits, if any, expected to result to subjects from participating in the research;
11. the expected benefits of the research to the community or to society at large, or contributions to scientific knowledge;
12. whether, when and how any products or interventions proven by the research to be safe and effective will be made available to subjects after they have completed their participation in the research, and whether they will be expected to pay for them;
13. any currently available alternative interventions or courses of treatment;
14. the provisions that will be made to ensure respect for the privacy of subjects and for the confidentiality of records in which subjects are identified;
15. the limits, legal or other, to the investigators' ability to safeguard confidentiality, and the possible consequences of breaches of confidentiality;
16. policy with regard to the use of results of genetic tests and familial genetic information, and the precautions in place to prevent disclosure of the results of a subject's genetic tests to immediate family relatives or to others (e.g., insurance companies or employers) without the consent of the subject;
17. the sponsors of the research, the institutional affiliation of the investigators, and the nature and sources of funding for the research;
18. the possible research uses, direct or secondary, of the subject`s medical records and of biological specimens taken in the course of clinical care;
19. whether it is planned that biological specimens collected in the research will be destroyed at its conclusion, and, if not, details about their storage (where, how, for how long, and final disposition) and possible future use, and that subjects have the right to decide about such future use, to refuse storage, and to have the material destroyed;
20. whether commercial products may be developed from biological specimens, and whether the participant will receive monetary or other benefits from the development of such products;
21. whether the investigator is serving only as an investigator or as both investigator and the subject`s physician; the extent of the investigator's responsibility to provide medical services to the participant;
22. that treatment will be provided free of charge for specified types of research-related injury or for complications associated with the research, the nature and duration of such care, the name of the organization or individual that will provide the treatment, and whether there is any uncertainty regarding funding of such treatment. in what way, and by what organization, the subject or the subject`s family or dependants will be compensated for disability or death resulting from such injury (or, when indicated, that there are no plans to provide such compensation);
23. whether or not, in the country in which the prospective subject is invited to participate in research, the right to compensation is legally guaranteed;
24. that an ethical review committee has approved or cleared the research protocol.

Guideline 6: Obtaining informed consent: Obligations of sponsors and investigators

Sponsors and investigators have a duty to:

1. refrain from unjustified deception, undue influence, or intimidation;
2. 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;
3. 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;
4. 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,
5. 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.