gms | German Medical Science

Background/research question: Implications for research (IfR) in systematic reviews are of high importance to indicate research gaps, guide meaningful future research, and to avoid research waste. Besides, IfR is a mandatory chapter in Cochrane Reviews and part of PRISMA [1].

We aimed i) to assess whether review authors state IfR and ii) to identify PICO, GRADE and other factors to which authors refer when stating IfR.

Methods: This meta-research study is based on systematic reviews of interventions in patients with advanced cancer identified in three databases following a systematic review approach (CRD42019134904). Eligible systematic reviews had to include randomized controlled trials as primary studies and at least one statistically significant meta-analysis.

Three reviewers extracted data on predefined IfR variables. We piloted the extraction process using five systematic reviews and validated it in weekly discussions.

Results: We identified 6,234 records and finally assessed 261 systematic reviews. Twenty-nine were Cochrane Reviews (11.1%). GRADE was assessed in 30 systematic reviews (11.5%). The clinical relevance of results was mentioned in 110 (42.1%).

In 51 systematic reviews (19.5%), no IfR were stated.

Common PICO factors addressed in the IfR section were 'intervention' (121, 46.4%), 'patient' (113, 43.3%), 'study design' (107, 41.0%), and 'outcome' (55, 21.1%).

IfR concerning more than one PICO aspect were stated in 71 (27.2%) systematic reviews for 'Patient and intervention', in 56 (21.5%) for 'Patient, intervention and study design', and in 8 (3.1%) for 'Patient, intervention, outcome, study design.'

GRADE factors were rarely used for stating IfR: 'risk of bias' (2, 0.8%), and 'imprecision' (1, 0.4%), 'inconsistency' (1, 0.4%).

Other IfR factors for consideration in future studies were 'adequate sample size / power' (28, 10.7%), 'biomarkers', (21, 8.1%), 'costs' (9, 3.5%), 'reporting' (4, 1.5%), and 'individual patient meta-analysis' (4, 1.5%).

Conclusion: IfR sections were not present in one-fifth. In addition, IfR were unstructured and incomplete regarding PICO factors. GRADE factors played practically no role for IfR statements.

We argue that the IfR section in systematic reviews should be better structured and should address key items (e.g., PICO and GRADE factors) to allow designing meaningful clinical trials to close clinically relevant research gaps.

Competing interests: Waldemar Siemens was employed at Roche Pharma AG, Grenzach-Wyhlen, Germany, from April 2020 to June 2021. Roche Pharma AG was not involved in the project and had no influence at any time on the project. Waldemar Siemens is employed at the Institute for Evidence in Medicine (Medical Center, University of Freiburg, Germany) and Cochrane Germany in Freiburg since September 2021.

The other authors have no conflict of interests.