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Table 4 Recommendations for managing external validity issues made by included studies

From: A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results

Patient populations
Broadening of RCT inclusion and exclusion criteria [19, 20, 29, 3133, 36, 38, 40, 42, 44, 47, 49]
Selection of patients from more appropriate settings/populations to achieve a more representative sample (for example, prospective use of registry data; a priori estimation of patient eligibility by application of trial exclusion criteria to the target population) [15, 17, 18, 31, 44, 54]
Conduct of RCTs in specific patient subgroups [20, 28, 30, 31, 46]
Standardization of inclusion/exclusion criteria and diagnostic and screening assessments across RCTs in a given medical condition [51]
Broader range of RCT treatments (that is, different and realistic dosing regimens, use of concurrent therapy, and appropriate duration of treatment); comparison of new treatments with treatments as usual rather than to a prescribed dose of a particular medicine [49]
Improved reporting of populations and results (that is, greater transparency in the reporting of how exclusion criteria are operationalized and how this influences eligibility, and of the rate and major characteristics of excluded patients) [28, 38, 51]
Collection, reporting, and comparison of data from patients within and outside of the trial [24, 28, 63]
Development of statistical analysis plans and power calculation adjustment to ensure adequate powering for subgroup analyses [20, 37]
Generation of supportive data
Conduct of observational studies after the demonstration of treatment efficacy at the RCT level [15, 23, 36]
Development of large patient registries in specific disease areas [19]
Adoption of pragmatic studies [48, 49]
Clinical practice recommendations
Prospective auditing of drug efficacy and safety in everyday practice settings and comparison of these data with RCT results [25]
Provision of more detailed product information to include the criteria by which patients were selected in pivotal RCTs [20]
  1. RCT randomized controlled trial