Approximately 21% of new HIV diagnoses occurred in young people aged 13–24.1 87% of youth diagnosed with HIV were young men, and the vast majority of these infections were attributed to male-to-male sexual contact (93%).2 Creating a shared understanding of how to legally and ethically conduct research with adolescents is a key step to reducing the incidence of HIV in youth. While the ethics of including minors, without parental consent, in HIV prevention research is a very important consideration, IRBs have to first decide what is possible under the law. Different regulations apply to the type of research contemplated. Research studies regulated by the Federal Policy for the Protection of Human Subjects (the “Common Rule”) typically require parental permission for studies of minors, but allow waiver of parental permission if certain conditions are met.3 The Department of Health and Human Service (HHS) research regulations comply with the Common Rule and are codified in 45 CFR § 46.4 The Food, Drug and Cosmetic Act regulates all clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration (FDA), including drugs and medical devices, and is more restrictive than the Common Rule.5 It is important to note that when research studies are regulated by both the FDA and the Common Rule — as is the case for most clinical pharmacological studies — the more stringent regulations govern. Other types of research, such as behavioral or educational interventions, would not be regulated by the FDA.
The FDA does not permit waiver of parental permission for research involving children.6 The FDA regulation defines children as, “persons who have not attained the legal age for consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted.”7 Thus, adolescents could only participate in FDA-regulated research if: 1) parental permission was obtained; or 2) the adolescent could legally consent to the intervention under the law of the state where research is being conducted, and therefore would not be considered a child (parental permission would not be required).
In this issue of JLME, Bauman et al. recognize that there are several reasons why parental permission is important in protecting the rights of adolescents in research.Reference Bauman, Mellins and Klitzman8 However, there are a variety of justified rationales for not wanting to obtain parental permission as part of an FDA-regulated trial. For example, there could be public health justifications for not desiring parental permission.Reference Moore, Paul, Mcguire and Majumder9 High-risk adolescents may avoid seeking services if parental permission is required or experience negative consequences from parents. Access to pharmacological therapies as part of a comprehensive HIV prevention strategy may be the key to protecting young men who have sex with men (MSM) and other high-risk adolescents from acquiring HIV,10 and not requiring parental permission may be an important component of ensuring equitable access to research for at-risk populations and optimizing research results.
However, ethical and public health justifications must be considered within the constraints of federal and state law. Because FDA does not permit waiver of parental permission for children, adolescents can only participate in FDA-regulated research if parental permission would not otherwise be required under state law. All 50 states and DC have statutes or regulations that explicitly authorize minors' access to sexually transmitted infection diagnosis and treatment.11 As noted by the study authors, 32 states explicitly authorize minors to independently consent to HIV testing and treatment.12 Sixteen states explicitly authorize minors to access HIV prevention without parental consent.13 Thus, only 16 states have clear statutory guidance that would allow adolescents to participate in FDA-regulated HIV prevention research without parental permission. In the remaining states, legal counsel should be sought to determine if the statute would permit minors to consent to the research. However, not all IRBs seek legal guidance or when sought, institutional counsel's advice is aimed at protecting organizational priorities and therefore may yield a narrower interpretation of the law. For instance, there are important challenges with obtaining legal clarity on whether the IRB could approve a phase II clinical trial for oral pre-exposure prophylaxis (PrEP) in adolescents age 15-17 years old,14 in which parental permission was not permitted by the funding agency.Reference Gilbert, Knopf, Fortenberry, Hosek, Kapogiannis and Zimet15 PrEP involves a prophylactic usage of antiretroviral medication to prevent transmission of the virus to HIV-negative individuals16 and was a critical study to advance HIV prevention in at-risk youth.
Creating a shared understanding of how to legally and ethically conduct research with adolescents is a key step to reducing the incidence of HIV in youth. While the ethics of including minors, without parental consent, in HIV prevention research is a very important consideration, IRBs have to first decide what is possible under the law. Different regulations apply to the type of research contemplated.
Only after consulting the institutional ethics consult service was the IRB able to render a decision. However, not all IRBs have access to ethics consult services and the delay in receiving IRB approval can lead to loss of funding for investigators. The delays in Texas did not ultimately hinder FDA approval of PrEP for older adolescents (aged 15–17),17 but adolescents in Texas were not represented in the sample. Southern states account for more than half of new HIV cases.18 Rates of diagnosis, treatment, and viral suppression are also significantly lower in this geographic region, while mortality rates are much higher compared to other areas of the country.19 Cultural, structural and socioeconomic factors drive disparities in HIV rates in the South.20 Without inclusion in clinical trials, PrEP access and uptake may be especially challenging for youth living in this region.
Ensuring equitable access to HIV prevention research for at-risk youth is an important goal in advancing HIV prevention. However, disparate state laws and IRB interpretation can hinder equitable access to research and perpetuate health disparities because those who may be most at-risk for HIV acquisition are not included in the research needed to show efficacy. Bauman et al.'s ethical guidance and road-map can contribute to uniformity in IRB decision-making, but it is important to clarify that those guidelines can only apply when not obtaining parental permission is allowed under state and federal law. Thus, any guidance regarding IRB consideration of waiver of parental permission is only applicable in the following instances: 1) when FDA regulations do not apply to the research (thus waiver allowed under Common Rule); 2) FDA regulations do apply, but state law allows the adolescent to consent to the intervention, so the adolescent is not considered a child under FDA regulations; 3) or FDA regulations do apply, but state law is ambiguous on whether the adolescent can consent to the intervention and legal canons of interpretation are applied, which support adolescent being able to consent, and therefore not considered a child under FDA regulations. Once it is determined that parental permission is not required under state law, IRBs can weigh the ethical considerations for not including parental permission in the research and Bauman et al.'s decision tree can lead to more consistent determinations among IRBs.
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Access
Approximately 21% of new HIV diagnoses occurred in young people aged 13–24.1 87% of youth diagnosed with HIV were young men, and the vast majority of these infections were attributed to male-to-male sexual contact (93%).2 Creating a shared understanding of how to legally and ethically conduct research with adolescents is a key step to reducing the incidence of HIV in youth. While the ethics of including minors, without parental consent, in HIV prevention research is a very important consideration, IRBs have to first decide what is possible under the law. Different regulations apply to the type of research contemplated. Research studies regulated by the Federal Policy for the Protection of Human Subjects (the “Common Rule”) typically require parental permission for studies of minors, but allow waiver of parental permission if certain conditions are met.3 The Department of Health and Human Service (HHS) research regulations comply with the Common Rule and are codified in 45 CFR § 46.4 The Food, Drug and Cosmetic Act regulates all clinical investigations that support applications for research or marketing permits for products regulated by the Food and Drug Administration (FDA), including drugs and medical devices, and is more restrictive than the Common Rule.5 It is important to note that when research studies are regulated by both the FDA and the Common Rule — as is the case for most clinical pharmacological studies — the more stringent regulations govern. Other types of research, such as behavioral or educational interventions, would not be regulated by the FDA.
The FDA does not permit waiver of parental permission for research involving children.6 The FDA regulation defines children as, “persons who have not attained the legal age for consent to treatments or procedures involved in clinical investigations, under the applicable law of the jurisdiction in which the clinical investigation will be conducted.”7 Thus, adolescents could only participate in FDA-regulated research if: 1) parental permission was obtained; or 2) the adolescent could legally consent to the intervention under the law of the state where research is being conducted, and therefore would not be considered a child (parental permission would not be required).
In this issue of JLME, Bauman et al. recognize that there are several reasons why parental permission is important in protecting the rights of adolescents in research.Reference Bauman, Mellins and Klitzman8 However, there are a variety of justified rationales for not wanting to obtain parental permission as part of an FDA-regulated trial. For example, there could be public health justifications for not desiring parental permission.Reference Moore, Paul, Mcguire and Majumder9 High-risk adolescents may avoid seeking services if parental permission is required or experience negative consequences from parents. Access to pharmacological therapies as part of a comprehensive HIV prevention strategy may be the key to protecting young men who have sex with men (MSM) and other high-risk adolescents from acquiring HIV,10 and not requiring parental permission may be an important component of ensuring equitable access to research for at-risk populations and optimizing research results.
However, ethical and public health justifications must be considered within the constraints of federal and state law. Because FDA does not permit waiver of parental permission for children, adolescents can only participate in FDA-regulated research if parental permission would not otherwise be required under state law. All 50 states and DC have statutes or regulations that explicitly authorize minors' access to sexually transmitted infection diagnosis and treatment.11 As noted by the study authors, 32 states explicitly authorize minors to independently consent to HIV testing and treatment.12 Sixteen states explicitly authorize minors to access HIV prevention without parental consent.13 Thus, only 16 states have clear statutory guidance that would allow adolescents to participate in FDA-regulated HIV prevention research without parental permission. In the remaining states, legal counsel should be sought to determine if the statute would permit minors to consent to the research. However, not all IRBs seek legal guidance or when sought, institutional counsel's advice is aimed at protecting organizational priorities and therefore may yield a narrower interpretation of the law. For instance, there are important challenges with obtaining legal clarity on whether the IRB could approve a phase II clinical trial for oral pre-exposure prophylaxis (PrEP) in adolescents age 15-17 years old,14 in which parental permission was not permitted by the funding agency.Reference Gilbert, Knopf, Fortenberry, Hosek, Kapogiannis and Zimet15 PrEP involves a prophylactic usage of antiretroviral medication to prevent transmission of the virus to HIV-negative individuals16 and was a critical study to advance HIV prevention in at-risk youth.
Creating a shared understanding of how to legally and ethically conduct research with adolescents is a key step to reducing the incidence of HIV in youth. While the ethics of including minors, without parental consent, in HIV prevention research is a very important consideration, IRBs have to first decide what is possible under the law. Different regulations apply to the type of research contemplated.
Only after consulting the institutional ethics consult service was the IRB able to render a decision. However, not all IRBs have access to ethics consult services and the delay in receiving IRB approval can lead to loss of funding for investigators. The delays in Texas did not ultimately hinder FDA approval of PrEP for older adolescents (aged 15–17),17 but adolescents in Texas were not represented in the sample. Southern states account for more than half of new HIV cases.18 Rates of diagnosis, treatment, and viral suppression are also significantly lower in this geographic region, while mortality rates are much higher compared to other areas of the country.19 Cultural, structural and socioeconomic factors drive disparities in HIV rates in the South.20 Without inclusion in clinical trials, PrEP access and uptake may be especially challenging for youth living in this region.
Ensuring equitable access to HIV prevention research for at-risk youth is an important goal in advancing HIV prevention. However, disparate state laws and IRB interpretation can hinder equitable access to research and perpetuate health disparities because those who may be most at-risk for HIV acquisition are not included in the research needed to show efficacy. Bauman et al.'s ethical guidance and road-map can contribute to uniformity in IRB decision-making, but it is important to clarify that those guidelines can only apply when not obtaining parental permission is allowed under state and federal law. Thus, any guidance regarding IRB consideration of waiver of parental permission is only applicable in the following instances: 1) when FDA regulations do not apply to the research (thus waiver allowed under Common Rule); 2) FDA regulations do apply, but state law allows the adolescent to consent to the intervention, so the adolescent is not considered a child under FDA regulations; 3) or FDA regulations do apply, but state law is ambiguous on whether the adolescent can consent to the intervention and legal canons of interpretation are applied, which support adolescent being able to consent, and therefore not considered a child under FDA regulations. Once it is determined that parental permission is not required under state law, IRBs can weigh the ethical considerations for not including parental permission in the research and Bauman et al.'s decision tree can lead to more consistent determinations among IRBs.