Clinical and Methodological Implications for Research Elements in Systematic Reviews on Covid-19 Treatment Were Often Unstructured and Insufficient – a Meta-Research Study

Objectives: Implications for research (IfR) sections in systematic reviews (SRs) aim to highlight research gaps, guide future research, and reduce unnecessary or uninformative research. The discussion of IfR is part of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist and a required paragraph in the Cochrane Handbook, which suggests considering population, intervention, control, outcome, study design (PICOS) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) domains. We aimed i) to assess whether SRs include an IfR section and, for SRs with an IfR section, ii) to examine which elements informed reporting of IfR.Study Design and Setting: We conducted a meta-research study based on SRs on COVID-19 treatment identified in the L·OVE COVID-19 database by May 2021 in a previous project (CRD42021240423).We defined an IfR section as at least one sentence that contained at least one piece of information that can be helpful in planning future research. We extracted data on predefined IfR variables, specifically PICOS elements and GRADE domains. Three reviewers extracted data independently after piloting the data extraction form. We resolved discrepancies in weekly discussions to ensure a high-quality data extraction.Results: We included 326 SRs. Our analysis focused on the 284 SRs (87.1%) with an IfR section from which 201 (70.8%) referred to the PRISMA guideline and 66 (23.2%) assessed the certainty of evidence using GRADE.The following PICOS elements were commonly addressed in SRs with an IfR section (n=284): ‘intervention’ (242, 85.2%), ‘study design’ (207, 72.9%), ‘population’ (195, 68.7%), and ‘outcome’ (127, 44.7%).GRADE domains were infrequently used to derive IfR recommendations in SRs with an IfR section (n=284): ‘risk of bias’ (14, 4.9%), ‘imprecision’ (8, 2.8%), ‘inconsistency’ (7, 2.5%), ‘publication bias’ (3, 1.1%) and ‘indirectness’ (1, 0.4%).Additional IfR elements mentioned to derive IfR were ‘better reporting’ of future studies (17, 6.0%) and ‘standardization of procedures in clinical trials’ (12, 4.2%).Conclusion: Almost nine out of ten systematic reviews included an IfR section. However, we found that many IfR sections were unstructured and GRADE domains were rarely used to inform IfR. To increase the value of future research, we suggest that IfR sections may consider PICOS elements and methodological concepts underlying the GRADE domains in a more structured format. However, further work is needed to clarify what IfR elements to consider and how to report IfR in SRs of interventions.RegistrationCRD42021240423