Clinical trial register searches for systematic reviews of randomized clinical trials involving interventions
2Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
3Cochrane Netherlands, Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands
Background: Cochrane guidelines recommend broad electronic bibliographic database (EBD) searches and additional clinical trial register (CTR) searches to inform systematic reviews (SRs) of randomized clinical trials (RCTs) involving interventions. This two-step approach limits the number of unidentified RCTs to prevent the synthesis of biased results. Clinical trial registration is performed prospectively for RCTs; thus, the publication status does not interfere with the availability of the CT registration within the register. Performing broad CTR searches by themselves may be a more efficient approach to identify RCTs for SRs of RCTs involving interventions.
Objectives: To evaluate how broad CTR searches compare to broad EBD searches in identifying RCTs for SRs of RCTs involving interventions.
Methods: We performed identical searches in the CTRs of ClinicalTrials.gov and the International Clinical Trials Registry Platform, as well as the EBDs CENTRAL, EMBASE, and MEDLINE, and compared whether we could identify the same RCTs. Our search was based on a subset of RCTs from an SR that studied the underrepresentation of people with chronic kidney disease from cardiovascular trials.
Results: We identified 128 eligible RCTs, of which 68 (49% [95% CI 42 – 58]) were identified by both search approaches. The EBD search missed 54 (43% [95% CI 34 – 51]) of the eligible RCTs. Of these, 37 were still ongoing and 13 were missed although available in the searched EBDs. Three RCTs missed by the EBD search had not been published while having a study completion date before 2020. One RCT had been published in a journal that was not indexed in the EBDs searched in our study. The CTR search missed 11 (8% [95% CI 5 – 15]) of the eligible RCTs. Of these, seven were not identified by the CTR search although available in the included CTRs. We were unable to locate a CT registration for four of the RCTs missed by the CTR search.
Conclusions: Broad CTR searches are suitable to inform SRs of RCTs involving interventions. Patient, public, and/or healthcare consumer involvement: No involvement. Our study has implications for the methodology of SRs of RCTs involving interventions.