Written by Sneha Bhadti and David Pritchett
Establishing a list of relevant comparators at the protocol development stage is a vital step in the systematic literature review (SLR) process. Scoping research during this stage can help identify comparators to include in the search strategy and eligibility criteria. The Cochrane Handbook for Systematic Reviews of Interventions states that search strategies should “maximize sensitivity whilst striving for reasonable precision”. Adding specific comparators requires careful consideration; on one hand, it can focus the SLR, increase precision, and reduce the screening burden, but on the other hand, it introduces the risk of missing useful evidence if comparators of interest are omitted from the protocol.
The challenge
The SLR team at Source recently completed a global clinical SLR on a specific type of advanced cancer in the first-line setting. An early draft of the Embase search strategy was not restricted by intervention/comparators, and this initial search strategy returned more than 6,000 citations. This number would only increase once other electronic databases (e.g. MEDLINE) were searched, yielding more than 10,000 hits to screen at the title/abstract stage. In consultation with the client, it was decided that screening such a broad literature base to identify a relatively small number of relevant studies would not be an efficient use of time or resources.
The solution
The Source SLR team introduced specific named comparators to the PICOS criteria and electronic database search strategy. Thorough scoping research was performed to identify currently approved competitors to the client’s product, in addition to emerging comparators currently in development. This research involved five key stages, further summarised in Table 1.
Table 1: Summary of methods for comparator scoping research
With the addition of named comparators to the electronic database search strategy, the number of citations to screen at the title/abstract review stage was reduced by approximately 57%. The comprehensive scoping exercise required 6 days of analyst time to complete but focussed the searches to the extent that the title/abstract screening stage was reduced from 40 to 17 days. Overall, the scoping exercise therefore saved 17 days of analyst time.
Scoping the PICOS for the EU JCA
In January 2025, the European Union Joint Clinical Assessment (EU JCA) was implemented for new oncology and advanced therapy medicinal products. Source has previously published a blog post on the implications of the EU JCA for clinical SLRs. Given that manufacturers are given just 100 days between PICOS finalisation and dossier submission, SLRs will often be performed before PICOS consolidation and updated shortly afterwards (JCA guidance states that searches must be no more than 3 months old at dossier submission). From this perspective, SLR protocol development becomes more important than ever, including the careful compilation of potentially relevant comparators across the 27 EU member states. Thorough scoping research, similar to that outlined above, will play an important part in this process. For some disease areas, risk could be mitigated by performing a clinical SLR that is not intervention-specific, but for others, such SLRs may be prohibitively large.
If you would like to learn more about our SLRs, please contact Source Health Economics, an consultancy specialising in evidence generation, health economics, and communication.
