Principles of Early Stopping of Randomized Trials for Efficacy: A Critique of Equipoise and an Alternative Nonexploitation Ethical Framework
Miller, Franklin G.
Kennedy Institute of Ethics Journal 2005 June; 15(2): 161-178
Recent controversial decisions to terminate several large clinical trials have called attention to the need for developing a sound ethical framework to determine when trials should be stopped in light of emerging efficacy data. Currently, the fundamental rationale for stopping trials early is based on the principle that equipoise has been disturbed. We present an analysis of the ethical and practical problems with the "equipoise disturbed" position and describe an alternative ethical framework based on the principle of nonexploitation. This framework acknowledges the need for balancing the dual ethical obligations of clinical research, the protection of human subjects and the generation of new medical knowledge. Based on this framework, we put forward a proposal to make early stopping guidelines more stringent under specified conditions. The temporary withholding of apparent benefits in certain circumstances is justified by achieving a fair contract with the research participants, one that protects them from undue harm and exploitation while reducing the many uncertainties surrounding new investigational treatments that arise when trials are stopped prematurely.
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Miller, Franklin G.; Brody, Howard (2003-05)A predominant ethical view holds that physician-investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second-rate treatments, the experimental ...
Stopping Randomized Trials Early for Benefit and Estimation of Treatment Effects: Systematic Review and Meta-Regression Analysis Bassler, Dirk; Briel, Matthias; Montori, Victor M; Lane, Melanie; Glasziou, Paul; Zhou, Qi; Heels-Ansdell, Diane; Walter, Stephen D.; Guyatt, Gordon H.; Flynn, David N.; Elamin, Mohamed B.; Murad, Mohammad Hassan; Abu Elnour, Nisrin O.; Lampropulos, Julianna F.; Sood, Amit; Mullan, Rebecca J.; Erwin, Patricia J.; Bankhead, Clare R.; Perera, Rafael; Ruiz Culebro, Carolina; You, John J.; Mulla, Sohail M.; Kaur, Jagdeep; Nerenberg, Kara A.; Schünemann, Holger; Cook, Deborah J.; Lutz, Kristina; Ribic, Christine M.; Vale, Noah; Malaga, German; Akl, Elie A.; Ferreira-Gonzalez, Ignacio; Alonso-Coello, Pablo; Urrutia, Gerard; Kunz, Regina; Bucher, Heiner C.; Nordmann, Alain J.; Raatz, Heike; da Silva, Suzana Alves; Tuche, Fabio; Strahm, Brigitte; Djulbegovic, Benjamin; Adhikari, Neill K.J.; Mills, Edward J.; Gwadry-Sridhar, Femida; Kirpalani, Haresh; Soares, Heloisa P.; Karanicolas, Paul J.; Burns, Karen E.A.; Vandvik, Per Olav; Coto-Yglesias, Fernando; Chrispim, Pedro Paulo M.; Ramsay, Tim (2010-03-24)CONTEXT: Theory and simulation suggest that randomized controlled trials (RCTs) stopped early for benefit (truncated RCTs) systematically overestimate treatment effects for the outcome that precipitated early stopping. ...