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Past Interpretations of the TCPS

Subject Minimal Risk with Children and Inclusion of Vulnerable Persons in Research
Keywords Minimal risk, children, vulnerable persons, competence, harms and benefits, inclusion in research
TCPS Articles 2.5, 5.3, Section 1, part C1
Date December 2007

PDF Minimal Risk with Children and Inclusion of Vulnerable Persons in Research december 2007.pdf

1. This is in response to your question regarding Article 2.5 of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS)1. You seek clarification of TCPS Article 2.5 pertaining to research involving minimal risk with vulnerable persons including children. More specifically, you are interested in whether, if literally interpreted, Article 2.5 would restrict such research in the absence of direct benefit to the individual. You refer to provisions in the American Code of Federal Regulations 45CFR46.407 and other documents concerning biomedical research involving children and provide an example of research in clinical settings to illustrate the issue. Your question has been submitted to the Interagency Advisory Panel on Research Ethics (PRE) for advice2.

2. Based on their collective experience, expertise and knowledge, REB members are expected to make sound ethical judgments and decisions based on the TCPS as a whole rather than on a single TCPS article. In responding to your question, PRE has considered Articles 2.5 and 5.3, and the discussion of minimal risk in Section 1, part C1. The key consideration, as it relates to the focus of your question, is whether the TCPS authorizes research involving children over the threshold of minimal risk when there are no direct benefits to them.

Inclusion of Vulnerable Persons in Research

3. Section 5 of the TCPS focuses on inclusion in research and on fair distribution of the direct and indirect benefits of research. A strict application of the principle that only competent individuals should be permitted to participate in research that would likely be harmful or of no benefit to them, would deny incompetent individuals many of the benefits of research participation, either directly or indirectly. “Subject to the provisions in Articles 2.6 to 2.8, those who are not competent to consent for themselves shall not be automatically excluded from research which is potentially beneficial to them as individuals, or to the group that they represent” (TCPS Article 5.3). Ethical considerations around research involving incompetent subjects must seek a balance of the vulnerability that arises from incompetence with the injustice that would arise from their exclusion from the potential benefits of research.

4. Often, the desire to protect the most vulnerable persons results in a narrow interpretation of the TCPS. This more “restrictive” view is consistent with protective models commonly used in the law and ethics of many countries3 which allow research with vulnerable persons above the threshold of minimal risk under strict conditions. However, this restrictive view does not reflect the flexible nature of the TCPS. The TCPS requires greater protection for vulnerable persons who are unable to consent, such as children. However, it allows flexible interpretation within a Canadian context. Overall, in their deliberations, REBs need to consider if the research will lead to a better outcome for children living with a disease. The fundamental principle is that the welfare of the participant and integrity of the individual remain paramount in human research.

5. TCPS Article 2.5 provides guidance for research conducted with vulnerable persons who are not legally competent to consent, including children. The principle of respect for human dignity, as specified in the commentary above Article 2.5, entails high ethical obligations to vulnerable persons, which often translate into special procedures to promote and protect their dignity. Article 2.5 does not preclude children as research participants, but rather specifies three criteria, as elaborated below, which must be respected for research to be conducted with vulnerable persons.

Research within Identified Groups

6. The first criterion relates to a general requirement in Article 2.5(a) to limit the conduct of research with vulnerable persons to situations where “the research question can only be addressed using individuals within identified groups”. As indicated in the commentary following Article 2.5, this criterion offers to further protect incompetent participants from being recruited or selected by mere convenience, in instances where the research could be conducted with competent subjects. While it provides for extra protection to minimize harms to vulnerable individuals or groups, the TCPS does recognize that research concerning specific situations or conditions may require the recruitment of a select group of children to further advance science and knowledge, for the overall welfare of children.

Free and Informed Consent from Authorized Representatives

7. The second criterion of TCPS Article 2.5(b) specifies that “Free and informed consent will be sought from their authorized representatives”. Subject to Articles 2.6 and 2.7 and to provincial legislative requirements regarding competency and legal age of consent, the provision of free and informed consent by authorized representatives, parents or legal guardians, further protects the dignity, interests and integrity of those who lack the competence to consent to participate in research, such as children. Many factors influence how decisions are made to obtain consent on behalf of children as research participants. These include but are not limited to the nature of the research, the research setting, the level of risk, the capacity to express assent or dissent. Using a subject-centred perspective suggests that parents or legal guardians are often in the best position to “balance 1) the vulnerability that arises from incompetence with the 2) injustice that would arise from their exclusion from the benefits of research” (commentary in E. Competence), to act on behalf of their child’s interests and to not be influenced by conflict of interest.

Minimal Risk and the Potential for Direct Benefit

8. In general, the third condition for conducting research involving individuals who are incompetent to consent, specifies that “the research does not expose them to more than minimal risk without the potential for direct benefits for them” (TCPS Article 2.5(c)). Special attention has been given below to the TCPS concepts of “potential for direct benefits” and “minimal risk”.

1) Defining the Potential for Direct Benefits

9. In its overarching ethics framework, the TCPS recognizes that while research involving humans should primarily benefit research participants and other individuals, most research benefits society as a whole and the advancement of knowledge. In your example you indicate that the research project offered opportunity to understand, prevent, and possibly alleviate a serious problem affecting the welfare of children. Direct benefit to children involved in research is often unknown, however, Article 5.3 refers to the non exclusion of vulnerable persons in research which may be “potentially beneficial to them as individuals, or to the group that they represent”. The TCPS suggests using flexibility in qualifying the “direct benefit”. In several English dictionaries, “potential” is defined as “the existence of possibility4”or the “capacity to develop into something in the future5”, suggesting that in the context of research, it may or not lead to possible beneficial outcomes. In comparison, the American Code of Federal Regulations (US Common rule), Subpart D, Section 45 CFR 46.4066 uses “prospect” of direct benefit, suggesting an “expectation or likelihood or anticipation” that positive outcomes in research will directly benefit the child. The difference in terminology favours a flexible TCPS, which allows the conduct of research with vulnerable persons under some conditions.

2) Determining the Threshold of Minimal Risk

10. The TCPS uses a subject-centered approach for ethical decision-making. It provides guidance to research involving children over the threshold of minimal risk when there is a potential for direct benefits to them and when the risks are no greater than those encountered in their day to day lives. TCPS Section 1, part C1 defines the standard of minimal risk as follows: “if potential subjects can reasonably be expected to regard the probability and magnitude of possible harms implied by participation in the research to be no greater than those encountered by the subject in those aspects of his or her everyday life that relate to the research then the research can be regarded as within the range of minimal risk”. The TCPS offers further clarification regarding potential harms specific to clinical research for therapeutic purposes: “such therapeutic risks may be regarded as within the range of minimal risks for patient-subjects, since they are inherent in the treatment that the patient will be undergoing as a part of his or her current everyday life”. The TCPS considers the assessment of risk in the context of the individual’s everyday experiences and not within the range of day to day experiences of other average, “normal” or healthy children. Your example suggested similar reasoning, where the proposed procedure did not represent a significant increment to the risk associated to the disorder in the research participants’ day to day life.

11. Thus, the TCPS does permit research involving children over the threshold of minimal risk under some conditions, even when there are no direct benefits to them.

We hope you will find this information helpful to your human research ethics deliberations on the TCPS.

Sincerely,

 

Secretariat on Research Ethics
on behalf of
The Interagency Advisory Panel on Research Ethics
pre.ethics.gc.ca


  1. http://www.pre.ethics.gc.ca/eng/archives/tcps-eptc/
  2. PRE provides advice on such interpretation questions to assist the research ethics community in applying the TCPS to the ethical issues it faces. While responses to TCPS interpretation questions may address ethical dimensions of legal issues in research ethics, PRE does not provide legal advice. Nor does it act as an appeal body on REB or institutional decisions.
  3. See, international research ethics perspective of other countries, for example:
    France: http://www.fhf.fr/dossiers/dossiers-fiche.php?id=326&p=10&r=71
    or http://www.recherchebiomedicale.sante.gouv.fr/files/loi/LSP-consolidee.pdf
    Australia: http://www.nhmrc.gov.au/publications/humans/appndix3.htm
    Council of Europe: https://wcd.coe.int/com.instranet.InstraServlet?
    Command=com.instranet.CmdBlobGet&DocId=590272&SecMode
    =1&Admin=0& Usage=4& InstranetImage=43903
  4. Merriam-Webster Online Dictionary: http://www.m-w.com/cgi-bin/mwwod.pl
  5. Concise Oxford English Dictionary: Thumb Index Edition. Toronto: Oxford University Press, Eleventh Edition, 2004.
  6. http://www.hhs.gov/ohrp/children/Guidance_407Process.pdf