By Karen P. Alexander, MD, FACC, chair of ACC’s Geriatric Section, and Timothy F. Feltes, MD, FACC, chair of ACC's Adult Congenital and Pediatric Cardiology Section.

We recently attended a National Institutes of Health (NIH)-sponsored workshop titled, Inclusion Across the Lifespan, on behalf of the ACC. The 21st Century Cures Act, signed by Former President Barack Obama in December 2016, mandated that the NIH convene a workshop of experts to provide input on appropriate age groups to be included in research studies involving human subjects and acceptable justifications for excluding participants from a range of age groups from human research studies. The Act also required a review of NIH policies on the inclusion of relevant age groups to determine if these should be updated. The workshop brought together researchers, clinicians, biostatisticians and patient and professional organizations.

Opening remarks from Francis Collins, MD, director of the NIH, emphasized the need to consider health care research across the lifespan. He acknowledged that the NIH is aware that studies claiming to include children are typically between 18 and 21 years of age, and studies claiming to include older adults were largely conducted on younger elderly without comorbid conditions. According to Collins, the NIH previously lacked time and funding, but the 21st Century Cures Act provides the necessary motivation to perform a review of these issues. He concluded by noting the potential promise of pragmatic trials, the need to make trial designs more powerful and assessment of enrolled populations more nuanced, the need to improve rapid access to trial data through ClinicalTrials.gov and other mechanisms to make trials more representative.

A workshop following the opening remarks featured speakers from various institutes and offices at NIH and the U.S. Food and Drug Administration (FDA), including the National Institute on Aging, the National Institute on Child Health and Human Development, the Office of Research on Women's Health and the FDA Center for Drug Evaluation and Review. Additionally, the workshop merged pediatric and geriatric perspectives highlighting similarities and differences in vulnerability, drug safety and inclusion in clinical studies across the lifespan. It dismissed "conveniently" held reasons for inability to include young and old in clinical studies and questioned the use of any unilateral age-based exclusions. Discussions expanded into strategies for inclusion of sex-gender and race-ethnicity in research subjects. The importance of clear enumeration of age groups at both ends of the spectrum with more transparency and accountability was encouraged. The workshop provided a unique opportunity to discuss strategies to the ethical issues pertaining to the inclusion of representative populations to improve our knowledge on human health.

Individual workgroups, which met prior to and during the conference, focused on patient inclusion, study design, ethical challenges of research based on age, sex/gender and race/ethnicity, and data collection and reporting. The groups specifically addressed and provided recommendations on the various issues described in NIH's Request for Information, including best study designs, strategies for all-age inclusion, ethical justification for excluding vulnerable populations, standardized approaches to reporting of age-related enrollment and potential barriers to age inclusion in trials. Workgroup activity and discussion prompted the emergence of common themes such as the need to harmonize reporting structure across agencies and journals, the need to utilize purposeful recruitment to better represent pediatric and elderly cohorts, expectations for investigators to have an explicit recruitment plan and minimize "acceptable" exclusion criteria, and consideration for adaptive trials to optimize enrollment and age subgroup analysis.

Moving forward, the College plans to collect input from appropriate member councils and submit public comments to inform and shape inclusion in NIH clinical trials and studies. Visit the conference website and view recordings of sessions here.

Keywords: Health Services Research, National Institute on Aging (U.S.), National Institutes of Health (U.S.), Research Design, Research Personnel, Research Subjects, Social Responsibility, United States Food and Drug Administration, Vulnerable Populations, Geriatrics, Heart Defects, Congenital

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