Ethical and clinical safety considerations in the design of an effectiveness trial: A comparison of buprenorphine versus naltrexone treatment for opioid dependence.
We examine ethical challenges encountered in the design of an effectiveness trial (CTN-0051; X:BOT), comparing sublingual buprenorphine-naloxone (BUP-NX), an established treatment for opioid dependence, to the newer extended-release injectable naltrexone (XR-NTX). Ethical issues surrounded: 1) known poor effectiveness of one possible, commonly used treatment as usual control condition-detoxification followed by counseling without medication; 2) the role of patients' preferences for treatments, given that treatments were clinically approved and available to the population; 3) differences between the optimal "usual treatment" clinical settings for different treatments making it challenging to design a fair comparison; 4) vested interest groups favoring different treatments exerting potential influence on the design process; 5) potentially vulnerable populations of substance users and prisoners; 6) potential therapeutic misconception in the implementation of safety procedures; and 7) high cost of a large trial limiting questions that could be addressed. We examine how the design features underlying these ethical issues are characteristic of effectiveness trials, which are often large trials that compare treatments with varying degrees of existing effectiveness data and familiarity to patients and clinicians, in community-based treatment settings, with minimal exclusion criteria that could involve vulnerable populations. Hence, investigators designing effectiveness trials may wish to remain alert to the possibility of similar ethical issues.
Columbia University Medical Center, New York State Psychiatric Institute, United States. Electronic address: nunesed@nyspi.columbia.edu.
Edward V
EV
Nunes
NYU School of Medicine, Department of Population Health, United States.
Joshua D
JD
Lee
Perelman School of Medicine, University of Pennsylvania, United States.
Dominic
D
Sisti
Perelman School of Medicine, University of Pennsylvania, United States.
Andrea
A
Segal
NYU School of Medicine, Division of Medical Ethics, United States.
Arthur
A
Caplan
Johns Hopkins University School of Medicine, Mountain Manor Treatment Program, United States.
Marc
M
Fishman
Warren Alpert Medical School of Brown University, Stanley Street Treatment and Resources, United States.
Genie
G
Bailey
ADAPT, Roseburg, OR, United States.
Gregory
G
Brigham
NYU School of Medicine, Department of Psychiatry, United States.
Patricia
P
Novo
NYU School of Medicine, Department of Psychiatry, United States.
Sarah
S
Farkas
NYU School of Medicine, Department of Psychiatry, United States.
John
J
Rotrosen
D000286:Administration, Sublingual; D000069479:Buprenorphine, Naloxone Drug Combination / Q000627:therapeutic use*; D057186:Comparative Effectiveness Research / Q000941:ethics / Q000379:methods*; D003376:Counseling; D003692:Delayed-Action Preparations; D032984:Ethics, Research; D006801:Humans; D007258:Informed Consent; D007273:Injections, Intramuscular; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy*; D057240:Patient Preference; D061214:Patient Safety; D011329:Prisoners; D016032:Randomized Controlled Trials as Topic / Q000941:ethics / Q000379:methods*; D035862:Vulnerable Populations
D000069479:Buprenorphine, Naloxone Drug Combination; D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009271:Naltrexone
Buprenorphine; Clinical trial; Effectiveness; Ethics; Naltrexone; Opioid dependence
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