Differences in reporting of analyses in internal company documents versus published trial reports: comparisons in industry-sponsored trials in off-label uses of gabapentin

PLoS Med. 2013;10(1):e1001378. doi: 10.1371/journal.pmed.1001378. Epub 2013 Jan 29.

Abstract

Background: Details about the type of analysis (e.g., intent to treat [ITT]) and definitions (i.e., criteria for including participants in the analysis) are necessary for interpreting a clinical trial's findings. Our objective was to compare the description of types of analyses and criteria for including participants in the publication (i.e., what was reported) with descriptions in the corresponding internal company documents (i.e., what was planned and what was done). Trials were for off-label uses of gabapentin sponsored by Pfizer and Parke-Davis, and documents were obtained through litigation.

Methods and findings: For each trial, we compared internal company documents (protocols, statistical analysis plans, and research reports, all unpublished), with publications. One author extracted data and another verified, with a third person verifying discordant items and a sample of the rest. Extracted data included the number of participants randomized and analyzed for efficacy, and types of analyses for efficacy and safety and their definitions (i.e., criteria for including participants in each type of analysis). We identified 21 trials, 11 of which were published randomized controlled trials, and that provided the documents needed for planned comparisons. For three trials, there was disagreement on the number of randomized participants between the research report and publication. Seven types of efficacy analyses were described in the protocols, statistical analysis plans, and publications, including ITT and six others. The protocol or publication described ITT using six different definitions, resulting in frequent disagreements between the two documents (i.e., different numbers of participants were included in the analyses).

Conclusions: Descriptions of analyses conducted did not agree between internal company documents and what was publicly reported. Internal company documents provide extensive documentation of methods planned and used, and trial findings, and should be publicly accessible. Reporting standards for randomized controlled trials should recommend transparent descriptions and definitions of analyses performed and which study participants are excluded.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / adverse effects
  • Amines / therapeutic use*
  • Cyclohexanecarboxylic Acids / adverse effects
  • Cyclohexanecarboxylic Acids / therapeutic use*
  • Documentation*
  • Drug Industry* / ethics
  • Gabapentin
  • Humans
  • Off-Label Use*
  • Publishing* / standards
  • Randomized Controlled Trials as Topic*
  • Research Report* / standards
  • Treatment Outcome
  • Truth Disclosure / ethics
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / therapeutic use*

Substances

  • Amines
  • Cyclohexanecarboxylic Acids
  • gamma-Aminobutyric Acid
  • Gabapentin

Grants and funding

SSV's effort related to this manuscript was supported by funds, which would have been paid to KD for serving as an expert witness in litigation against Pfizer, deposited in an account at Johns Hopkins to support scholarship in reporting biases. KD and TL did not receive any funding for working on this manuscript. No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.