A proposal for integrated efficacy-to-effectiveness (E2E) clinical trials.
We propose an "efficacy-to-effectiveness" (E2E) clinical trial design, in which an effectiveness trial would commence seamlessly upon completion of the efficacy trial. Efficacy trials use inclusion/exclusion criteria to produce relatively homogeneous samples of participants with the target condition, conducted in settings that foster adherence to rigorous clinical protocols. Effectiveness trials use inclusion/exclusion criteria that generate heterogeneous samples that are more similar to the general patient spectrum, conducted in more varied settings, with protocols that approximate typical clinical care. In E2E trials, results from the efficacy trial component would be used to design the effectiveness trial component, to confirm and/or discern associations between clinical characteristics and treatment effects in typical care, and potentially to test new hypotheses. An E2E approach may improve the evidentiary basis for selecting treatments, expand understanding of the effectiveness of treatments in subgroups with particular clinical features, and foster incorporation of effectiveness information into regulatory processes.
1] Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts, USA [2] Institute for Clinical Research and Health Policy Studies, Tufts Medical Center, Boston, Massachusetts, USA.
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Selker
Massachusetts Institute of Technology Political Science and Engineering Systems, Cambridge, Massachusetts, USA.
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Oye
European Medicines Agency, London, UK.
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Eichler
US Food and Drug Administration Center for Drug Evaluation and Research, Silver Spring, Maryland, USA.
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Stockbridge
Harvard School of Public Health, Boston, Massachusetts, USA.
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Mehta
1] Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts, USA [2] Tufts Center for the Study of Drug Development, Boston, Massachusetts, USA.
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Kaitin
Merck & Co., Whitehouse Station, New Jersey, USA.
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McElwee
Collegeville, Pennsylvania, USA.
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Honig
1] Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts, USA [2] Tufts Cancer Center, Boston, Massachusetts, USA.
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Erban
1] Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA [2] Harvard Clinical Research Institute, Boston, Massachusetts, USA.
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D'Agostino
D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004358:Drug Therapy / Q000379:methods; D006801:Humans; D018579:Patient Selection; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D016896:Treatment Outcome