Clinical trialist perspectives on the ethics of adaptive clinical trials: a mixed-methods analysis.
BACKGROUND
In an adaptive clinical trial (ACT), key trial characteristics may be altered during the course of the trial according to predefined rules in response to information that accumulates within the trial itself. In addition to having distinguishing scientific features, adaptive trials also may involve ethical considerations that differ from more traditional randomized trials. Better understanding of clinical trial experts' views about the ethical aspects of adaptive designs could assist those planning ACTs. Our aim was to elucidate the opinions of clinical trial experts regarding their beliefs about ethical aspects of ACTs.


METHODS
We used a convergent, mixed-methods design employing a 22-item ACTs beliefs survey with visual analog scales and open-ended questions and mini-focus groups. We developed a coding scheme to conduct thematic searches of textual data, depicted responses to visual analog scales on box-plot diagrams, and integrated findings thematically. Fifty-three clinical trial experts from four constituent groups participated: academic biostatisticians (n = 5); consultant biostatisticians (n = 6); academic clinicians (n = 22); and other stakeholders including patient advocacy, National Institutes of Health, and U.S. Food and Drug Administration representatives (n = 20).


RESULTS
The respondents recognized potential ethical benefits of ACTs, including a higher probability of receiving an effective intervention for participants, optimizing resource utilization, and accelerating treatment discovery. Ethical challenges voiced include developing procedures so trial participants can make informed decisions about taking part in ACTs and plausible, though unlikely risks of research personnel altering enrollment patterns.


CONCLUSIONS
Clinical trial experts recognize ethical advantages but also pose potential ethical challenges of ACTs. The four constituencies differ in their weighing of ACT ethical considerations based on their professional vantage points. These data suggest further discussion about the ethics of ACTs is needed to facilitate ACT planning, design and conduct, and ultimately better allow planners to weigh ethical implications of competing trial designs.
Department of Family Medicine, University of Michigan, 1018 Fuller Street, Ann Arbor, MI 48109, USA. lauriele@umich.edu.
Laurie J
LJ
Legocki
Departments of Emergency Medicine and Neurology, University of Michigan, Ann Arbor, MI, USA. wmeurer@med.umich.edu.
William J
WJ
Meurer
Department of Emergency Medicine, University of Michigan, Ann Arbor, MI, USA. smfrederiksen@frontier.com.
Shirley
S
Frederiksen
Department of Emergency Medicine, Harbor-UCLA Medical Center, Los Angeles, CA, USA. roger@emedharbor.edu.|Los Angeles Biomedical Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. roger@emedharbor.edu.|Berry Consultants, Austin, TX, USA. roger@emedharbor.edu.
Roger J
RJ
Lewis
Division of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. durkalsv@musc.edu.
Valerie L
VL
Durkalski
Department of Biostatistics, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA. don@berryconsultants.net.|Berry Consultants, Austin, TX, USA. don@berryconsultants.net.
Donald A
DA
Berry
Los Angeles Biomedical Research Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA. wbarsan@med.umich.edu.
William G
WG
Barsan
Department of Family Medicine, University of Michigan, 1018 Fuller Street, Ann Arbor, MI 48109, USA. mfetters@med.umich.edu.
Michael D
MD
Fetters
D001290:Attitude; D035843:Biomedical Research / Q000941:ethics* / Q000379:methods; D002986:Clinical Trials as Topic; D032984:Ethics, Research; D017144:Focus Groups; D006801:Humans; D007258:Informed Consent; D012107:Research Design; D012108:Research Personnel; D016896:Treatment Outcome; D014481:United States