Impact of Inclusion of Industry Trial Results Registries as an Information Source for Systematic Reviews

Abstract

BackgroundClinical trial results registries may contain relevant unpublished information. Our main aim was to investigate the potential impact of the inclusion of reports from industry results registries on systematic reviews (SRs).MethodsWe identified a sample of 150 eligible SRs in PubMed via backward selection. Eligible SRs investigated randomized controlled trials of drugs and included at least 2 bibliographic databases (original search date: 11/2009). We checked whether results registries of manufacturers and/or industry associations had also been searched. If not, we searched these registries for additional trials not considered in the SRs, as well as for additional data on trials already considered. We reanalysed the primary outcome and harm outcomes reported in the SRs and determined whether results had changed. A “change” was defined as either a new relevant result or a change in the statistical significance of an existing result. We performed a search update in 8/2013 and identified a sample of 20 eligible SRs to determine whether mandatory results registration from 9/2008 onwards in the public trial and results registry ClinicalTrials.gov had led to its inclusion as a standard information source in SRs, and whether the inclusion rate of industry results registries had changed.Results133 of the 150 SRs (89%) in the original analysis did not search industry results registries. For 23 (17%) of these SRs we found 25 additional trials and additional data on 31 trials already included in the SRs. This additional information was found for more than twice as many SRs of drugs approved from 2000 as approved beforehand. The inclusion of the additional trials and data yielded changes in existing results or the addition of new results for 6 of the 23 SRs. Of the 20 SRs retrieved in the search update, 8 considered ClinicalTrials.gov or a meta-registry linking to ClinicalTrials.gov, and 1 considered an industry results registry.ConclusionThe inclusion of industry and public results registries as an information source in SRs is still insufficient and may result in publication and outcome reporting bias. In addition to an essential search in ClinicalTrials.gov, authors of SRs should consider searching industry results registries.

Reporting of Adverse Events in Published and Unpublished Studies of Health Care Interventions: A Systematic Review

“…The included studies fell into three categories: those which measured the numbers of studies reporting adverse events in published and unpublished sources (9 studies [ 16 , 23 , 25 , 27 , 30 , 34 , 35 , 40 , 43 , 44 ]), those which measured the numbers or types of adverse events in published and unpublished sources (13 studies [ 16 , 18 , 22 , 25 – 28 , 32 , 34 , 36 , 38 , 40 , 46 , 47 ]), and those which measured the difference in effect size of a meta-analysis with and without unpublished sources (11 studies [ 19 – 21 , 24 , 29 , 31 , 33 , 37 , 39 , 41 , 42 , 45 ]). There were 5 studies that contained data for more than one category.…”

“…There were 11 included studies reporting 28 meta-analyses that looked at magnitude of the pooled risk estimate—i.e., odds ratio or risk ratio for adverse events—with unpublished data and published data or a combination of published and unpublished data ( S4 Table ) [ 19 – 21 , 24 , 29 , 31 , 33 , 37 , 39 , 41 , 42 , 45 ]. Of these 28 meta-analyses, there were 20 instances where risk estimates were pooled for all published and unpublished studies as compared to published studies only.…”

“… There were also two systematic reviews identified in Potthast 2014 [ 33 ] in which unpublished additional trial data led to a new comparison not reported in the systematic reviews, which could not be represented here. …”

Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses

“…Our results are consistent with other studies, showing that the search for unpublished trial data is still often lacking in systematic reviews. 24 25 26 29 30 In a random sample of 300 recent systematic reviews indexed in Medline in February 2014, only 19% reported searching trial registries. 31 A previous study by Hart in 2012 aimed to reanalyse meta-analyses by adding unpublished outcome data from trials obtained from the US Food and Drug Administration to published meta-analyses.…”

Einfluss von Registern auf die Versorgungsqualität

“…In einer komplexen Arbeit untersuchten Mitarbeiter des Instituts für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG) 150 systematische Übersichtsarbeiten über 125 verschiedene Pharmaka auf den Einschluss von Daten aus Industrieregistern [13]. Auf den Einschluss von Registern hatten primär 133 Reviews verzichtet.…”