title: Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses.
abstract: ObjectiveTo evaluate the impact of searching clinical trial registries in systematic reviews.DesignMethodological systematic review and reanalyses of meta-analyses.Data sourcesMedline was searched to identify systematic reviews of randomised controlled trials (RCTs) assessing pharmaceutical treatments published between June 2014 and January 2015. For all systematic reviews that did not report a trial registry search but reported the information to perform it, the World Health Organization International Trials Registry Platform (WHO ICTRP search portal) was searched for completed or terminated RCTs not originally included in the systematic review.Data extractionFor each systematic review, two researchers independently extracted the outcomes analysed, the number of patients included, and the treatment effect estimated. For each RCT identified, two researchers independently determined whether the results were available (ie, posted, published, or available on the sponsor website) and extracted the data. When additional data were retrieved, we reanalysed meta-analyses and calculated the weight of the additional RCTs and the change in summary statistics by comparison with the original meta-analysis.ResultsAmong 223 selected systematic reviews, 116 (52%) did not report a search of trial registries; 21 of these did not report the information to perform the search (key words, search date). A search was performed for 95 systematic reviews; for 54 (57%), no additional RCTs were found and for 41 (43%) 122 additional RCTs were identified. The search allowed for increasing the number of patients by more than 10% in 19 systematic reviews, 20% in 10, 30% in seven, and 50% in four. Moreover, 63 RCTs had results available; the results for 45 could be included in a meta-analysis. 14 systematic reviews including 45 RCTs were reanalysed. The weight of the additional RCTs in the recalculated meta-analyses ranged from 0% to 58% and was greater than 10% in five of 14 systematic reviews, 20% in three, and 50% in one. The change in summary statistics ranged from 0% to 29% and was greater than 10% for five of 14 systematic reviews and greater than 20% for two. However, none of the changes to summary effect estimates led to a qualitative change in the interpretation of the results once the new trials were added.ConclusionsTrial registries are an important source for identifying additional RCTs. The additional number of RCTs and patients included if a search were performed varied across systematic reviews.
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Baudard
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France amelie.yavchitz@aphp.fr.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.|Cochrane France, Paris, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Yavchitz
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.|Cochrane France, Paris, France.|Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, 75004 Paris, France.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.|Cochrane France, Paris, France.|Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, 75004 Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Perrodeau
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.|Cochrane France, Paris, France.|Centre d'Épidémiologie Clinique, Hôpital Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, 75004 Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boutron
mesh_terms: D062313:Databases, Pharmaceutical; D006801:Humans; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D012196:Review Literature as Topic