Research designs for proof-of-concept chronic pain clinical trials: IMMPACT recommendations

Jennifer S. Gewandter, Robert H. Dworkin, Dennis C. Turk, Michael P. McDermott, Ralf Baron, Marc R. Gastonguay, Ian Gilron, Nathaniel P. Katz, Cyrus Mehta, Srinivasa N. Raja, Stephen Senn, Charles Taylor, Penney Cowan, Paul Desjardins, Rozalina Dimitrova, Raymond Dionne, John T. Farrar, David J. Hewitt, Smriti Iyengar, Gary W. JayEija Kalso, Robert D. Kerns, Richard Leff, Michael Leong, Karin L. Petersen, Bernard M. Ravina, Christine Rauschkolb, Andrew S.C. Rice, Michael C. Rowbotham, Cristina Sampaio, Søren H. Sindrup, Joseph W. Stauffer, Ilona Steigerwald, Jonathan Stewart, Jeffrey Tobias, Rolf Detlef Treede, Mark Wallace, Richard E. White

Research output: Contribution to journalReview articlepeer-review

Abstract

Proof-of-concept (POC) clinical trials play an important role in developing novel treatments and determining whether existing treatments may be efficacious in broader populations of patients. The goal of most POC trials is to determine whether a treatment is likely to be efficacious for a given indication and thus whether it is worth investing the financial resources and participant exposure necessary for a confirmatory trial of that intervention. A challenge in designing POC trials is obtaining sufficient information to make this important go/no-go decision in a cost-effective manner. An IMMPACT consensus meeting was convened to discuss design considerations for POC trials in analgesia, with a focus on maximizing power with limited resources and participants. We present general design aspects to consider including patient population, active comparators and placebos, study power, pharmacokinetic-pharmacodynamic relationships, and minimization of missing data. Efficiency of single-dose studies for treatments with rapid onset is discussed. The trade-off between parallel-group and crossover designs with respect to overall sample sizes, trial duration, and applicability is summarized. The advantages and disadvantages of more recent trial designs, including N-of-1 designs, enriched designs, adaptive designs, and sequential parallel comparison designs, are summarized, and recommendations for consideration are provided. More attention to identifying efficient yet powerful designs for POC clinical trials of chronic pain treatments may increase the percentage of truly efficacious pain treatments that are advanced to confirmatory trials while decreasing the percentage of ineffective treatments that continue to be evaluated rather than abandoned.

Original languageEnglish (US)
Pages (from-to)1683-1695
Number of pages13
JournalPain
Volume155
Issue number9
DOIs
StatePublished - 2014

Keywords

  • Clinical trials
  • IMMPACT
  • Methodology
  • Proof of concept

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Anesthesiology and Pain Medicine

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