Articulating and Responding to Uncertainties in Clinical Research

Abstract

This paper introduces taxonomy of clinical uncertaintes and argues that the choice of scientific method should match the underlying level of uncertainty. Clinical trial is one of these methods aiming to resolve clinical uncertainties. Whenever possible these uncertainties should be quantified.

The paper further shows that the still ongoing debate about the usage of “equipoise” vs. “uncertainty principle” vs. “indifference” as an entry criterion to clinical trials actually refers to the question “whose uncertainty counts”. This question is intimately linked to the control of research agenda, which is not quantifiable and hence is not solvable to equal acceptability to all interested parties. The author finally shows that there is a predictable relation between [acknowledgement of] uncertainty (the moral principle) on which trials are based and the ultimate outcomes of clinical trials. That is, [acknowledgement of] uncertainty determines a pattern of success in medicine and drives clinical discoveries.

Keywords:

• clinical trials
• equipoise
• ethics
• uncertainty

ACKNOWLEDGMENTS

I wish to thank Howard Mann, Iztok Hozo, Mike Clarke, Stan Shapiro, Alex London, and Sir Iain Chalmers for their important feedback to the ideas expressed in this article. I also want to thank Robert Veatch, Frank Miller, Charles Weijer, Paul Miller, Howard Brody, and Fred Gifford for the stimulating exchange of ideas and the opportunity to read their articles which in turn influenced the final draft of this article. Although they may not necessarily agree with the final content of this text, many discussions I have had with most of them over the years had been invaluable in my own advancement of the ideas expressed herein.

This work was supported by the Research Program on Research Integrity, Office of Research Integrity/National Institute of Health collaboration, grants No: 1 R01 NS044417-01 and 1 R01 NS052956-01.