“Outcome Reporting In Industry-Sponsored Trials of Gabapentin for Off-Label Use,”

Center for Clinical Trials, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
New England Journal of Medicine (Impact Factor: 55.87). 11/2009; 361(20):1963-71. DOI: 10.1056/NEJMsa0906126
Source: PubMed


There is good evidence of selective outcome reporting in published reports of randomized trials.
We examined reporting practices for trials of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis (hereafter referred to as Pfizer and Parke-Davis) for off-label indications (prophylaxis against migraine and treatment of bipolar disorders, neuropathic pain, and nociceptive pain), comparing internal company documents with published reports.
We identified 20 clinical trials for which internal documents were available from Pfizer and Parke-Davis; of these trials, 12 were reported in publications. For 8 of the 12 reported trials, the primary outcome defined in the published report differed from that described in the protocol. Sources of disagreement included the introduction of a new primary outcome (in the case of 6 trials), failure to distinguish between primary and secondary outcomes (2 trials), relegation of primary outcomes to secondary outcomes (2 trials), and failure to report one or more protocol-defined primary outcomes (5 trials). Trials that presented findings that were not significant (P > or = 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome. The primary outcome was changed in the case of 5 of 8 published trials for which statistically significant differences favoring gabapentin were reported. Of the 21 primary outcomes described in the protocols of the published trials, 6 were not reported at all and 4 were reported as secondary outcomes. Of 28 primary outcomes described in the published reports, 12 were newly introduced.
We identified selective outcome reporting for trials of off-label use of gabapentin. This practice threatens the validity of evidence for the effectiveness of off-label interventions.

Download full-text


Available from: Roberta W Scherer, Oct 10, 2015
28 Reads
  • Source
    • "Trials presenting findings that were not significant (p ! 0.05) for the protocol-defined primary outcome in the internal documents either were not reported in full or were reported with a changed primary outcome [27]. IPD must be provided to drug agencies such as the US Federal Drug Agency (FDA) and the European Medicines Agency (EMA) by pharmaceutical companies when applying for approval of a drug. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Meta-analysis is a statistical procedure that integrates the results of at least two independent studies. The biggest threats to meta-analysis are publication bias due to missing studies with negative results and low-quality evidence due to methodological limitations imposed by included studies. Tools to improve the quality of meta-analysis have been developed by the Cochrane Collaboration and by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Meta-analyses of trials have demonstrated that pain responses in patients with chronic pain, following treatment, are not normally distributed but have a bimodal distribution with the majority of patients having either very little or very good pain relief. The benefit can be detected within 2-4 weeks following drug administration. Further, the efficacy of drug and physical treatments is hampered by high placebo response rates, with modest average benefits with active treatments over placebo in both parallel and crossover design trials. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Bailli&egrave re s Best Practice and Research in Clinical Rheumatology 05/2015; 29(1). DOI:10.1016/j.berh.2015.04.021 · 2.60 Impact Factor
  • Source
    • "Doctors and decision makers cannot depend solely on articles published in medical journals. Articles are often biased [1] [2], and some studies are partially published or not published at all [3]. Drug regulators have access to additional data through the companies' approval applications , for instance individual patient data on harms and analysis of efficacy data for multiple outcomes. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objectives To compare the accessibility, comprehensiveness, and usefulness of data available from the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) drug reports. Study Design and Setting This is a cross-sectional study. All new molecular drugs approved between January 1, 2011 and December 31, 2012 from the FDA and EMA Web sites were eligible. Results We included 27 drug reports. Most were searchable, but the FDA table of contents did not match the file's page numbers. Several FDA documents must be searched compared with a single EMA document, but the FDA reports contain more summary data on harms. Detailed information about harms was reported for 93% of the FDA reports (25 of 27 reports) and 26% of the EMA reports (7 of 27 reports). The reports contained information about trial methodology but did not include trial registry IDs or investigator names. All reports but one contained sufficient information to be used in a meta-analysis. Conclusion Detailed data on efficacy and harms are available at the two agencies. The FDA has more summary data on harms, but the documents are harder to navigate.
    Journal of Clinical Epidemiology 08/2014; 68(1). DOI:10.1016/j.jclinepi.2014.06.019 · 3.42 Impact Factor
  • Source
    • "Die Belege für das strategische Verschweigen von unliebsamen Ergebnissen, egal ob bezogen auf die Wirksamkeit oder bezogen auf das Nebenwirkungsprofil eines Wirkstoffs, sind mannigfaltig. Eine Autorengruppe um Vedula et al. (2009) zweifelte im " New England Journal of Medicine " an den publizierten Ergebnissen für Gabapentin (einem Krampflöser bei Epilepsie). Dessen Indikation sollte auf andere Diagnosen (Migräne, Bipolare Störung, Neuropathischer Schmerz) ausgeweitet werden. "
    Qualität im Gesundheitsjournalismus – Perspektiven aus Wissenschaft und Praxis, Edited by Lilienthal V, Reineck D, Schnedler T., 01/2014: chapter Teil V - Gesundheitsjournalismus und Praxis: Grenzen des Gesundheitsjournalismus: pages 327-348; Springer - Verlag für Sozialwissenschaften., ISBN: 978-3-658-02427-7
Show more