OBJECTIVES : The requirements from health technology assessment (HTA) agencies for systematic literature reviews (SLRs) within submission vary. The objective of this study was to assimilate SLR methodological guidance issued by HTA agencies in Europe, North America, and Asia; and to compare these requirements to the methods of SLRs in HTA submissions.

METHODS : Requirements for SLRs as issued within guidance for HTA submissions in Australia (PBAC), Canada (CADTH), England and Wales (NICE), France (HAS), Germany (IQWiG/G-BA), Ireland (NCPE), Scotland (SMC), Sweden (TLV), Wales (AWMSG) and Europe (EUnetHTA) were examined in May 2019. Additionally, submitted SLRs were studied from selected submissions to NICE, IQWiG, and EUnetHTA.

RESULTS : NICE and IQWiG requirements for SLRs are the most prescriptive, whereas the others have few explicit requirements. All agencies require a clinical SLR (except AMCP and ICER) and critical assessment of clinical studies (except CADTH), although recommended appraisal tools vary. Clinical reviews should generally be conducted with two reviewers; searches should cover Medline, Embase and Cochrane Library, and be supplemented with trial registries. HTA guidance recommends following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Reviews of economic evidence (economic evaluations, model inputs, utilities) are often not compulsory. Where required (NICE, HAS, NCPE, SMC) methodological requirements are generally less comprehensive than clinical SLR.

Submitted SLR evidence usually adhered to the requested sources. Searches were conducted between 3mo – 1yr before submission. Details on search string and results are provided per database; screening results are provided with reasons for inclusion/exclusion. When relevant head-to-head clinical trial evidence can be provided for the drug under assessment, the SLR evidence becomes dispensable.

CONCLUSIONS : Requirements from HTA agencies vary but overlap to a large extent. For all reviews, besides comprehensiveness, transparency in the methodology and the minimization of bias is key to the provision of relevant evidence for national HTAs.