Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations

Jennifer S Gewandter; Shannon M Smith; Andrew McKeown; Laurie B Burke; Sharon H Hertz; Matthew Hunsinger; Nathaniel P Katz; Allison H Lin; Michael P McDermott; Bob A Rappaport; Mark R Williams; Dennis C Turk; Robert H Dworkin

doi:10.1016/j.pain.2013.11.009

Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations

Pain. 2014 Mar;155(3):461-466. doi: 10.1016/j.pain.2013.11.009. Epub 2013 Nov 23.

Authors

Jennifer S Gewandter¹, Shannon M Smith, Andrew McKeown, Laurie B Burke, Sharon H Hertz, Matthew Hunsinger, Nathaniel P Katz, Allison H Lin, Michael P McDermott, Bob A Rappaport, Mark R Williams, Dennis C Turk, Robert H Dworkin

Affiliation

¹ Department of Anesthesiology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA United States Food and Drug Administration, Silver Spring, MD, USA School of Professional Psychology, Pacific University, Hillsboro, OR, USA Analgesic Solutions, Natick, MA, USA Tufts University, Boston, MA, USA Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA.

PMID: 24275257
DOI: 10.1016/j.pain.2013.11.009

Abstract

Performing multiple analyses in clinical trials can inflate the probability of a type I error, or the chance of falsely concluding a significant effect of the treatment. Strategies to minimize type I error probability include prespecification of primary analyses and statistical adjustment for multiple comparisons, when applicable. The objective of this study was to assess the quality of primary analysis reporting and frequency of multiplicity adjustment in 3 major pain journals (ie, European Journal of Pain, Journal of Pain, and PAIN®). A total of 161 randomized controlled trials investigating noninvasive pharmacological treatments or interventional treatments for pain, published between 2006 and 2012, were included. Only 52% of trials identified a primary analysis, and only 10% of trials reported prespecification of that analysis. Among the 33 articles that identified a primary analysis with multiple testing, 15 (45%) adjusted for multiplicity; of those 15, only 2 (13%) reported prespecification of the adjustment methodology. Trials in clinical pain conditions and industry-sponsored trials identified a primary analysis more often than trials in experimental pain models and non-industry-sponsored trials, respectively. The results of this systematic review demonstrate deficiencies in the reporting and possibly the execution of primary analyses in published analgesic trials. These deficiencies can be rectified by changes in, or better enforcement of, journal policies pertaining to requirements for the reporting of analyses of clinical trial data.

Keywords: Multiplicity; Primary analysis reporting; Systematic review.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review
Systematic Review

MeSH terms

Analgesics / therapeutic use*
Humans
Randomized Controlled Trials as Topic / methods
Research Design / standards*
Statistics as Topic / methods
Statistics as Topic / standards*
Treatment Outcome

Substances

Analgesics