title: The ethics and regulatory landscape of including vulnerable populations in pragmatic clinical trials.
abstract: Policies have been developed to protect vulnerable populations in clinical research, including the US federal research regulations (45 Code of Federal Regulations 46 Subparts B, C, and D). These policies generally recognize vulnerable populations to include pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons. The aim has been to protect these populations from harm, often by creating regulatory and ethical checks that may limit their participation in many clinical trials. The recent increase in pragmatic clinical trials raises at least two questions about this approach. First, is exclusion itself a harm to vulnerable populations, as these groups may be denied access to understanding how health interventions work for them in clinical settings? Second, are groups considered vulnerable in traditional clinical trials also vulnerable in pragmatic clinical trials? We argue first that excluding vulnerable subjects from participation in pragmatic clinical trials can be harmful by preventing acquisition of data to meaningfully inform clinical decision-making in the future. Second, we argue that protections for vulnerable subjects in traditional clinical trial settings may not be translatable, feasible, or even ethical to apply in pragmatic clinical trials. We conclude by offering specific recommendations for appropriately protecting vulnerable research subjects in pragmatic clinical trials, focusing on pregnant women, fetuses, neonates, children, prisoners, persons with physical handicaps or mental disabilities, and disadvantaged persons.
authors.affiliation: Human Subjects' Protection, College of Nursing, Rush University Medical Center, Chicago, IL, USA Mary_Jane_Welch@rush.edu.
authors.forename: Mary Jane
authors.initials: MJ
authors.lastname: Welch
authors.affiliation: Columbia University Medical Center, New York, NY, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Lally
authors.affiliation: Kenan Institute for Ethics, Duke University, Durham, NC, USA Edmond J. Safra Center for Ethics, Harvard University, Cambridge, MA, USA Division of Medical Ethics, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Miller
authors.affiliation: Human Subjects' Protection, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pittman
authors.affiliation: Cook County Health & Hospitals System, Chicago, IL, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Brodsky
authors.affiliation: Division of Medical Ethics, NYU Langone Medical Center, New York, NY, USA.
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Caplan
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Uhlenbrauck
authors.affiliation: Duke Clinical Research Institute, Duke University, Durham, NC, USA.
authors.forename: Darcy M
authors.initials: DM
authors.lastname: Louzao
authors.affiliation: University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Fischer
authors.affiliation: Treuman Katz Center for Pediatric Bioethics, Seattle Children's Hospital, Seattle, WA, USA Division of Bioethics, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wilfond
mesh_terms: D035843:Biomedical Research / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic / Q000941:ethics* / Q000331:legislation & jurisprudence / Q000592:standards; D006233:Persons with Disabilities; D005260:Female; D005333:Fetus; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007258:Informed Consent / Q000941:ethics* / Q000331:legislation & jurisprudence* / Q000592:standards; D008297:Male; D011247:Pregnancy; D011329:Prisoners / Q000331:legislation & jurisprudence; D035842:Research Subjects / Q000331:legislation & jurisprudence*; D035862:Vulnerable Populations / Q000331:legislation & jurisprudence*
keywords: Vulnerable subjects; cluster randomized trials; pragmatic clinical trials; regulation; research ethics; research with children; research with disadvantaged populations; research with persons with diminished capacity; research with pregnant women; research with prisoners