title: Wasted research when systematic reviews fail to provide a complete and up-to-date evidence synthesis: the example of lung cancer.
abstract: BACKGROUND
  Multiple treatments are frequently available for a given condition, and clinicians and patients need a comprehensive, up-to-date synthesis of evidence for all competing treatments. We aimed to quantify the waste of research related to the failure of systematic reviews to provide a complete and up-to-date evidence synthesis over time.
  
  
  METHODS
  We performed a series of systematic overviews and networks of randomized trials assessing the gap between evidence covered by systematic reviews and available trials of second-line treatments for advanced non-small cell lung cancer. We searched the Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, EMBASE, and other resources sequentially by year from 2009 to March 2, 2015. We sequentially compared the amount of evidence missing from systematic reviews to the randomized evidence available for inclusion each year. We constructed cumulative networks of randomized evidence over time and evaluated the proportion of trials, patients, treatments, and treatment comparisons not covered by systematic reviews on December 31 each year from 2009 to 2015.
  
  
  RESULTS
  We identified 77 trials (28,636 patients) assessing 47 treatments with 54 comparisons and 29 systematic reviews (13 published after 2013). From 2009 to 2015, the evidence covered by existing systematic reviews was consistently incomplete: 45 % to 70 % of trials; 30 % to 58 % of patients; 40 % to 66 % of treatments; and 38 % to 71 % of comparisons were missing. In the cumulative networks of randomized evidence, 10 % to 17 % of treatment comparisons were partially covered by systematic reviews and 55 % to 85 % were partially or not covered.
  
  
  CONCLUSIONS
  We illustrate how systematic reviews of a given condition provide a fragmented, out-of-date panorama of the evidence for all treatments. This waste of research might be reduced by the development of live cumulative network meta-analyses.
authors.affiliation: Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, INSERM U1153, Paris, France. perrine.crequit@aphp.fr.|Université Paris Descartes - Sorbonne Paris Cité, Paris, France. perrine.crequit@aphp.fr.
authors.forename: Perrine
authors.initials: P
authors.lastname: Créquit
authors.affiliation: Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, INSERM U1153, Paris, France. ludovic.trinquart@aphp.fr.|Université Paris Descartes - Sorbonne Paris Cité, Paris, France. ludovic.trinquart@aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Centre d'Epidémiologie Clinique, Paris, France. ludovic.trinquart@aphp.fr.|Cochrane France, Paris, France. ludovic.trinquart@aphp.fr.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Trinquart
authors.affiliation: Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, INSERM U1153, Paris, France. amelie.yavchitz@aphp.fr.|Université Paris Descartes - Sorbonne Paris Cité, Paris, France. amelie.yavchitz@aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Centre d'Epidémiologie Clinique, Paris, France. amelie.yavchitz@aphp.fr.
authors.forename: Amélie
authors.initials: A
authors.lastname: Yavchitz
authors.affiliation: Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, INSERM U1153, Paris, France. philippe.ravaud@aphp.fr.|Université Paris Descartes - Sorbonne Paris Cité, Paris, France. philippe.ravaud@aphp.fr.|Assistance Publique-Hôpitaux de Paris, Hôpital Hôtel-Dieu, Centre d'Epidémiologie Clinique, Paris, France. philippe.ravaud@aphp.fr.|Cochrane France, Paris, France. philippe.ravaud@aphp.fr.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA. philippe.ravaud@aphp.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Ravaud
mesh_terms: D022126:Access to Information; D015982:Bias; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000628:therapy*; D016208:Databases, Factual / Q000592:standards* / Q000706:statistics & numerical data; D055317:Evidence-Based Practice / Q000458:organization & administration / Q000592:standards / Q000706:statistics & numerical data; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000628:therapy*; D015201:Meta-Analysis as Topic; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012196:Review Literature as Topic