Indirectness is one of the eight GRADE domains, and one of the five domains that can lead to rating down of the certainty of the evidence. Evaluating indirectness involves considering how closely the population, intervention, comparison, and outcomes (PICO) in the available evidence align with those specified in the question of interest. An additional source of indirectness—indirect comparisons—arises when interventions are not directly compared within the same studies.
Session 5 covered how to rate indirectness in systematic reviews of interventions. It provided an update on the topic, offering a more analytical and structured approach to rating.
Topics included:-
- What is indirectness?
- How to evaluate indirectness in studies about interventions (population, intervention, comparator and outcome indirectness; indirect comparisons)
- Impact of indirectness on the certainty of evidence
- Ways to mitigate indirectness
The webinar was suitable for those wanting to use GRADE to interpret and summarise findings in a systematic review. An understanding of systematic review methods and content covered in the introductory session is assumed.
The session was delivered in September 2026 and below you will find the recording with the accompanying slides to download [PDF].
Presenter Bio
Holger Schünemann is a Professor of Public Health and Preventive Medicine at Humanitas University in Milan, Italy and Professor emeritus in the Departments of Health Research Methods, Evidence, and Impact (formerly “Department of Clinical Epidemiology and Biostatistics”) and of Medicine. He received his MD degree (1993) and a “doctor medicinae” degree (1994) from the Medical School of Hannover where he also began residency training in internal and respiratory medicine before completing his residency and a PhD at SUNY Buffalo (2000). He is director of the Clinical Epidemiology and Research Center (CERC) at Humanitas University. He was Chair of Clinical Epidemiology and Biostatistics from 2009 to 2019, widely considered the birthplace of evidence-based health care and problem-based learning. After completing his second and final term as Chair, he led the Michael G DeGroote Cochrane Canada and McMaster GRADE Centres and was director of Cochrane Canada. Since 2000, he helped reshaping of methodology for guideline development spanning clinical medicine to public health and contributed methodologically and practically to knowledge synthesis research, foremost through his leadership of the GRADE working group that he chairs.
