title: Meta-analyses including non-randomized studies of therapeutic interventions: a methodological review.
abstract: BACKGROUND
  There is an increasing number of meta-analyses including data from non-randomized studies for therapeutic evaluation. We aimed to systematically assess the methods used in meta-analyses including non-randomized studies evaluating therapeutic interventions.
  
  
  METHODS
  For this methodological review, we searched MEDLINE via PubMed, from January 1, 2013 to December 31, 2013 for meta-analyses including at least one non-randomized study evaluating therapeutic interventions. Etiological assessments and meta-analyses with no comparison group were excluded. Two reviewers independently assessed the general characteristics and key methodological components of the systematic review process and meta-analysis methods.
  
  
  RESULTS
  One hundred eighty eight meta-analyses were selected: 119 included both randomized controlled trials (RCTs) and non-randomized studies of interventions (NRSI) and 69 only NRSI. Half of the meta-analyses (n = 92, 49%) evaluated non-pharmacological interventions. "Grey literature" was searched for 72 meta-analyses (38%). An assessment of methodological quality or risk of bias was reported in 135 meta-analyses (72%) but this assessment considered the risk of confounding bias in only 33 meta-analyses (18%). In 130 meta-analyses (69%), the design of each NRSI was not clearly specified. In 131 (70%), whether crude or adjusted estimates of treatment effect for NRSI were combined was unclear or not reported. Heterogeneity across studies was assessed in 182 meta-analyses (97%) and further explored in 157 (84%). Reporting bias was assessed in 127 (68%).
  
  
  CONCLUSIONS
  Some key methodological components of the systematic review process-search for grey literature, description of the type of NRSI included, assessment of risk of confounding bias and reporting of whether crude or adjusted estimates were combined-are not adequately carried out or reported in meta-analyses including NRSI.
authors.affiliation: Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.
authors.forename: Timor
authors.initials: T
authors.lastname: Faber
authors.affiliation: Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Cochrane France, Paris, France.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
authors.affiliation: Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.
authors.forename: Carolina
authors.initials: C
authors.lastname: Riveros
authors.affiliation: Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris, France.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Perrodeau
authors.affiliation: Centre d'Epidémiologie Clinique, Hôpital Hôtel-Dieu, APHP, Paris, France. agnes.dechartres@aphp.fr.|Centre de Recherche Epidémiologie et Statistique, INSERM U1153, Paris, France. agnes.dechartres@aphp.fr.|Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. agnes.dechartres@aphp.fr.|Cochrane France, Paris, France. agnes.dechartres@aphp.fr.
authors.forename: Agnes
authors.initials: A
authors.lastname: Dechartres
mesh_terms: D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D008297:Male; D063868:Patient Outcome Assessment; D011786:Quality Control; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D058028:Research Report
keywords: Meta-analyses; Non-randomized studies; Reporting; Therapeutic evaluation