Searching Clinical Trial Registries in Systematic Literature Reviews (SLR): Which and Why?

OBJECTIVES: The SLR process requires appropriate searching of grey literature (defined as information that is not commercially published). Accordingly, searching trial registries such as clinicaltrials.gov (CTG), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), and the European Union Drug Regulating Authorities Clinical Trials (EudraCT) has become standard practice to identify eligible studies in SLRs of clinical trials, in line with recommendations in the Cochrane Handbook (February 2004). However, it is unclear whether searching the International Standard Randomized Controlled Trial Number (ISRCTN) registry adds value. This comparative analysis therefore aimed to identify similarities and differences in trials recorded for a broad therapeutic area across the four registries.

METHODS: Searches for “diabetes” and “diabetes mellitus” were conducted on June 12, 2024, in WHO, CTG, ISRCTN and EudraCT. Search results were exported to MS Excel® for comparison based on trial identifiers, title, disease condition, phase, and sponsor. Terminated and withdrawn trials were excluded.

RESULTS: A total of 21,623 trials were identified in WHO, 12,347 in CTG, 2134 in EudraCT and 938 in ISRCTN. All the trials from CTG (100%), 87% of EudraCT-registered trials and 85% of ISRCTN-registered trials were found in WHO registry. Comparing CTG with other registries showed little overlap: 6% with ISRCTN and <1% with EudraCT. Also, only 2% of trials from ISRCTN overlapped with the EudraCT-registered trials. When comparing all three registries with ISRCTN, 104 trials were found uniquely in ISRCTN. Geographic distinctions showed ISRCTN and EudraCT focused on European studies, while CTG emphasized on research from North America.

CONCLUSIONS: While searching WHO, CTG and EudraCT can be crucial for SLRs of trials, our findings suggest significant unique trial information in ISRCTN not captured by the other registries. Inclusion of ISRCTN as a data source alongside WHO and CTG enhances the comprehensiveness of such SLRs.