Three Cs for Consideration in Adolescent Alcohol and Other Drug Research

Brenda Heaton, PhD, MPH

Assistant Professor, Department of Health Policy & Health Services Research, Henry M. Goldman School of Dental Medicine, Boston University, Boston, MA, USA

Previous feature articles in this newsletter have focused on general ethical considerations of alcohol and other drug (AOD) research, typically as they apply to adult participants. While many of the same principles apply, the regulatory framework and ethical considerations differ to some degree when the research subject population of interest includes children. The term “children” as defined under the Code of Federal Regulations 45 CFR 46.402 refers to “persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable law of the jurisdiction in which the research will be conducted.”¹ In US jurisdictions, this term most commonly refers to any individual who is less than 18 years of age. Subpart D of 45 CFR 46 sets forth “Additional Protections for Children Involved as Subjects in Research.”²

Despite these additional regulations, researchers and Institutional Review Boards (IRBs) are left with the challenge of interpreting and applying these provisions to all subjects under the age of 18 while maintaining consideration of their varying cognitive and decisional capacities and associated vulnerabilities. Additional challenges for adolescents include their emerging autonomy and the relevance of socially sensitive topics—such as alcohol and drug use—that were primarily absent in childhood, increasing the complexity of ethical considerations under the regulatory framework provided for “children.”³

It is generally accepted that the science of addiction among adolescent populations is different from that of their adult and pediatric counterparts. Developmentally, youth are at higher risk for addiction and addictive behaviors and the social, educational, and family environments of adolescence can lead to rates of alcohol and other drug use that are different from those of adult populations.⁴ These disparities warrant the specific study of addiction among adolescents as a scientific necessity. The Belmont Principle of Justice dictates that the burdens and the benefits of research be distributed fairly and equally.⁵ When the findings of studies in one population cannot be extrapolated to another, the benefits and burdens are similarly maldistributed. Unfortunately, adolescent populations are frequently excluded from research owing to the complexity of the ethical issues related to their involvement, so they may not reap the benefits of some research conducted among adult or younger pediatric populations.⁶

Consent by a Parent: More Harm than Good?

According to the Belmont Report, the Respect for Persons principle mandates that individuals should be considered to be capable of making their own decisions; when they are not, they are deserving of additional protections.⁵ Parental consent for the participation of “children” in research is provided in the regulations as the sine qua non of human subjects protection. However, as stated by the National Health and Medical Research Council of Australia, “an absolute requirement for parental consent is possibly unethical if it denies mature adolescent autonomy and poses a barrier to participation, study validity and improved health outcomes through research findings. This would deny the benefits of research to specific, high-risk groups such as homeless youth, intravenous drug users, or school truants.”⁷ The regulatory and ethical standard of parental consent for participation in research by adolescents is therefore a charged issue that extends beyond the principle of Respect for Persons. For example, the principle of Beneficence cannot be upheld properly if the requirement for parental consent increases the risk to the adolescent participant and, as stated above, the principle of Justice is not upheld if the barriers of parental consent result in the exclusion of adolescent populations from research. For these reasons, parental consent in adolescent research has naturally become a debated issue.⁸ Waivers of parental consent may be considered when research topics are sensitive, the involvement of a parent could potentially increase risk, and when subjects are at a developmental stage at which autonomy in decision-making can reasonably be assumed to be present.

Waivers of Parental Consent

The Code of Federal Regulations supplies provisions for waiving the requirement of parental consent “if the IRB determines that [the] research protocol is designed for conditions or for a subject population for which parental or guardian permission is not a reasonable requirement to protect the subjects (for example, neglected or abused children) […] and that the waiver is not inconsistent with federal, state, or local law” (45 CFR 46.408).⁹ However, uniformity in decision-making with respect to parental waivers or additional guidance on acceptable scenarios does not exist, thereby complicating ethical considerations.

There are numerous reasons why AOD researchers would want to waive the requirement of parental consent. The requisite involvement of a parent could: 1) potentially affect an adolescent’s decision to participate, ultimately biasing the study sample (one consequence being that results may not apply broadly); 2) influence the accuracy with which adolescents report their behaviors; 3) potentially place the subject at greater risk by divulging something about his or her behavior previously unknown to a parent; 4) jeopardize research questions centered on the parent-child relationship; and 5) render the research infeasible if potential subjects are to be identified in such a way that parental involvement is not straightforward (e.g., street youth).

If parental consent is to be justifiably waived, ethics and regulations require that “an appropriate mechanism for protecting [those] who will participate as subjects in the research is substituted” (45 CFR 46.408(b)).⁹ Any necessary protections are determined on a scale of potential risk to the adolescent subjects. The following are possible mechanisms by which adolescent subjects can be additionally protected when a waiver of parental consent is being considered.

• Determination of consent capacity: Previous feature articles in this newsletter have addressed the issues related to capacity to consent in general, and specifically for AOD subject populations.^10,11 In addition to formally determining capacity for reasons related to the content area of addiction, formal determinations may become additionally important if autonomy is going to be protected in this vulnerable population. According to Santelli and colleagues, “With adolescents, respect for persons means balancing respect for the emerging capacity of an adolescent for independent decision-making with the need for continued special protections, where necessary.”⁶ Tools have been developed for formally determining consent capacity that can be applied to adolescent populations.¹¹

• Identification of alternative adult guidance: Although there may be problems associated with the involvement of a parent in adolescent research, the principle of protection through adult decision-making can still be pursued. Depending on the setting, it may be feasible to identify an individual who is uninvolved in the research, reasonably holds the individual’s best interests, and can advocate for the potential subject. For example, a social worker, school staff member, nurse, or physician may be able to fill this role.

• Deference to legal standards on “mature minors”: Many states have dictated circumstances under which non-emancipated minors who have been determined to possess the maturity necessary to make decisions for or against particular health care treatments may be allowed to do so. Individual IRBs may make similar allowances to potential research subjects meeting similar criteria. However, this has rarely been determined as acceptable for those below the age of 15 years. Understanding those situations in which legal jurisdictions have allowed for consent by minors may assist in justification of waivers in research and the adequacy of protections.

Confidentiality

A common barrier to adolescents’ participation in AOD research is their perception of risk associated with the divulging or acknowledgement of illicit or illegal activity. Waivers of parental consent may be argued for in favor of increased confidentiality protections. However, whether or not parental consent is obtained, confidentiality in adolescent research deserves some additional consideration. The confidentiality-related risks associated with AOD research in general are often greater than other health research owing to the involvement of sensitive information, or “information that, if released, might be damaging to an individual’s financial standing, employability, or reputation within the community or might lead to social stigmatization or discrimination” and therefore require greater protections.¹² Strategies for protecting sensitive information in general have been outlined in previous feature articles in this newsletter.¹³ However, by virtue of the regulations, adolescents participating in this type of research face risks beyond those of an adult population and therefore may require additional confidentiality protections. For example, Certificates of Confidentiality¹⁴ may need to be pursued earlier and more frequently for adolescent populations than for adults. Additionally, issues of mandatory reporting are common in AOD research. Consent/assent forms should take special care to provide specific information about when, how, and why mandatory reporting may be required and the possible consequences to the subject, particularly when a waiver of parental consent is being considered.

Compensation

Financial compensation for research participation creates the potential for undue influence. Adolescent participants may be at greater risk of undue influence as a result of financial remuneration compared with their adult counterparts. The principles outlined in a previous feature article entitled “Paying Participants to Take Part in Addiction Research: Ethical Considerations” should be taken into account, bearing in mind that an even more stringent approach may need to be followed if adolescent populations are to be pursued for participation in AOD research.¹⁵

References

1. US Department of Health and Human Services: Code of Federal Regulations no. 45 CFR 46.402. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.402.

2. US Department of Health and Human Services: Code of Federal Regulations no. 45 CFR 46, Subpart D. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#subpartd.

3. Caskey JD, Rosenthal SL. Conducting research on sensitive topics with adolescents: ethical and developmental considerations. J Dev Behav Pediatr. 2005;26(1):61–67.

4. US Department of Health and Human Services. National Institutes of Health: National Institute on Drug Abuse. Drug Facts: High School and Youth Trends. Updated December 2012. Available at: http://www.drugabuse.gov/publications/drugfacts/high-school-youth-trends.

5. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Bethesda, MD: OHSR; 1979. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html.

6. Santelli JS, Smith Rogers A, Rosenfeld WD, et al. Guidelines for adolescent health research. A position paper of the Society for Adolescent Medicine. J Adolesc Health. 2003;33:309–409.

7. National Health and Medical Research Council. Government of Australia. Ethical Issues in Research into Alcohol and Other Drugs: An Issues Paper Exploring the Need for a Guidance Framework. Section 6.6.2, statement ‘c.’ Available at: http://www.nhmrc.gov.au/_files_nhmrc/publications/attachments/ds12_ethical_issues_alcohol_drugs_120625.pd

8. Ruiz-Canela M, Lopez-del Burgo C, Carlos S, et al. Observational research with adolescents: a framework for the management of the parental permission. BMC Med Ethics. 2013;14:2.

9. US Department of Health and Human Services: Code of Federal Regulations no. 45 CFR 46.408. Available at: http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.408.

10. Baedorf Kassis S, Roth MT. Obtaining Informed Consent for Research from People with Alcohol and Other Drug Dependence. AOD Health. March–April. 2012. Available at: http://www.bu.edu/aodhealth/issues/issue_mar12/feature32012.html.

11. Heaton B. Ensuring Subject Competence to Enroll and Participate in Addiction Research. AOD Health. May–June. 2013. Available at: http://www.bu.edu/aodhealth/issues/issue_may13/feature052013.html.

12. National Institutes of Health. Definitions: “sensitive information.” Available at: http://oma.od.nih.gov/public/MS/privacy/Documents/Guide%20for%20Handling%20Sensitive%20Information%20at%20NIH.pdf

13. Baedorf Kassis S. Confidentiality Protections in Research Involving People with Substance Use Disorders. AOD Health. July–Aug. 2013. Available at: http://www.bu.edu/aodhealth/issues/issue_july13/feature072013.html.

14. National Institutes of Health Office of Extramural Research: Certificates of Confidentiality Kiosk. Available at: http://grants.nih.gov/grants/policy/coc/.

15. Roth MT. Paying Participants to Take Part in Addiction Research: Ethical Considerations. AOD Health. Nov–Dec. 2012. Available at: http://www.bu.edu/aodhealth/issues/issue_nov12/feature112012.html.