TY - JOUR
T1 - Discrepancies between registered and published primary outcome specifications in analgesic trials
T2 - ACTTION systematic review and recommendations
AU - Smith, Shannon M.
AU - Wang, Anthony T.
AU - Pereira, Anthony
AU - Chang, R. Daniel
AU - McKeown, Andrew
AU - Greene, Kaitlin
AU - Rowbotham, Michael C.
AU - Burke, Laurie B.
AU - Coplan, Paul
AU - Gilron, Ian
AU - Hertz, Sharon H.
AU - Katz, Nathaniel P.
AU - Lin, Allison H.
AU - McDermott, Michael P.
AU - Papadopoulos, Elektra J.
AU - Rappaport, Bob A.
AU - Sweeney, Michael
AU - Turk, Dennis C.
AU - Dworkin, Robert H.
N1 - Funding Information:
The authors report no conflict of interest. The views expressed in this article are those of the authors and no official endorsement by the U.S. Food and Drug Administration (FDA) or the pharmaceutical companies that provided unrestricted grants to support the activities of the ACTTION public–private partnership should be inferred. Financial support for this project was provided by the ACTTION public–private partnership, which has received research contracts, grants, or other revenue from the FDA, Astellas, Bristol-Myers Squibb, Collegium, Depomed, Eli Lilly, Horizon, Jazz, Johnson & Johnson, Mallinckrodt, Pfizer, Purdue, Zalicus, and other sources.
PY - 2013/12
Y1 - 2013/12
N2 - The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
AB - The National Institutes of Health released the trial registry ClinicalTrials.gov in 2000 to increase public reporting and clinical trial transparency. This systematic review examined whether registered primary outcome specifications (POS; ie, definitions, timing, and analytic plans) in analgesic treatment trials correspond with published POS. Trials with accompanying publications (n = 87) were selected from the Repository of Registered Analgesic Clinical Trials (RReACT) database of all postherpetic neuralgia, diabetic peripheral neuropathy, and fibromyalgia clinical trials registered at ClinicalTrials.gov as of December 1, 2011. POS never matched precisely; discrepancies occurred in 79% of the registry-publication pairs (21% failed to register or publish primary outcomes [PO]). These percentages did not differ significantly between industry and non-industry-sponsored trials. Thirty percent of the trials contained unambiguous POS discrepancies (eg, omitting a registered PO from the publication, "demoting" a registered PO to a published secondary outcome), with a statistically significantly higher percentage of non-industry-sponsored than industry-sponsored trials containing unambiguous POS discrepancies. POS discrepancies due to ambiguous reporting included vaguely worded PO registration; or failing to report the timing of PO assessment, statistical analysis used for the PO, or method to address missing PO data. At best, POS discrepancies may be attributable to insufficient registry requirements, carelessness (eg, failing to report PO assessment timing), or difficulty uploading registry information. At worst, discrepancies could indicate investigator impropriety (eg, registering imprecise PO ["pain"], then publishing whichever pain assessment produced statistically significant results). Improvements in PO registration, as well as journal policies requiring consistency between registered and published PO descriptions, are needed.
KW - Analgesic medications
KW - Clinical trials
KW - Primary outcomes
KW - Registry
KW - Systematic review
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U2 - 10.1016/j.pain.2013.08.011
DO - 10.1016/j.pain.2013.08.011
M3 - Article
C2 - 23962590
AN - SCOPUS:84889101512
SN - 0304-3959
VL - 154
SP - 2769
EP - 2774
JO - Pain
JF - Pain
IS - 12
ER -