2012 Autumn: Statistical, Clinical, Payor and Regulatory Perspectives on Dimensions That Define the Spectrum of Efficacy and Effectiveness

Co-chairs:  Larry Alphs, MD, PhD; Nina R. Schooler, PhD; Ginger Haynes, PhD

Brief Description

Demands for personalized medicine, comparative effectiveness, and cost control are increasingly driving sponsors to consider both efficacy (explanatory) and effectiveness (pragmatic) trials to be part of a complete drug development program.  Yet, there is much confusion in the field about the differences between these trials including their definition, requirements, design and interpretation.  Further, within each approach, a wide range of clinical trial designs (each with its own strengths and weaknesses) can be used to address these considerations.  Effectiveness trials are particularly poorly understood. Few designs completely address the various types of effectiveness questions that can be raised.  Indeed, essential elements of trials claiming to be ‘effectiveness’ are often not clearly reported and few broadly established standards for qualifying trials as either ‘effectiveness’ or ‘efficacy’ exist.  Not infrequently meta-analyses use results from an explanatory approach and draw conclusions to address questions that require a pragmatic design.  Commonly agreed upon regulatory, provider and publication quality standards for these two approaches are particularly needful.  The lack of clear standards within the field has led to a plethora of generally inadequate local standards that vary by country and by publication. Thus, even when studies are available, a clear, coherent body of work is not being developed and the overall quality of clinical trial programs for effectiveness questions is diminished.  This session will attempt to clarify issues inherent in conducting effectiveness trials and provide initial solutions to address them.

 Goals 

The goals of this session are to:

  1. Increase the understanding of the difference in efficacy (explanatory) and effectiveness (pragmatic) trials, clarifying questions of clinical, regulatory and provider stakeholders that require pragmatic designs
  2. Clarify the criteria that should be addressed when designing effectiveness trials and identify standards to assess whether such trials have been well-designed and well-conducted
  3. Provide initial solutions to address these needs