Antti Malmivaara
Performance Assessment of the Health and Social Service System, Finnish Institute for Health and Welfare , Helsinki, Finland. E-mail: antti.malmivaara@thl.fi
DOI: 10.2340/16501977-2843

Background: The value of randomized controlled trials is dependent on the applicability of their findings to clinical decision-making. The aim of this study is to determine a definition and principles for the applicability of evidence from randomized controlled trials and systematic reviews.
Methods: This narrative review searched studies from PubMed and Web of Science databases using Cochrane Collaboration’s Qualitative Evidence Syntheses guidance. Empirical studies were excluded. Based on the included studies, a definition for the concept and propositions for principles of applicability were formulated.
Results: A definition and 11 propositions are presented, 6 propositions having additional sub-propositions. Low risk of bias, ability to answer to specific questions, documentation of the details of how randomized controlled trials turned out, reporting of favourable and adverse outcomes, and systematic comparison of randomized controlled trials and clinical data were considered important. Biomedical randomized controlled trials have the widest applicability, while heterogeneity in study characteristics, human perception, behaviour, environmental, equity factors, and health economic issues lessen applicability. Obtaining applicable evidence is a gradual process. Methodological and substance expertise is necessary for assessing applicability.
Discussion: A definition of applicability and requirements for applicable evidence from randomized controlled trials to real-world contexts are presented. Propositions are suggested for any assessment of applicability of findings from randomized controlled trials, systematic reviews and meta-analyses.

Clinicians’ need for knowledge about a specific patient (or group of patients) is the underlying principle for applicability. Consequently, randomized controlled trials and systematic reviews should document all essential factors needed for clinical decision-making. Documentation of the study protocol (inclusion and exclusion criteria of patients, description of content of interventions and the outcome measures) is not sufficient. The documentation must also cover what actually happened in the randomized controlled trial, i.e. the characteristics of patients, the adherence to the index and control interventions, and the amount of co-interventions. Clinical registers using uniform documentation with randomized controlled trials increase the applicability of the research findings to clinical practice. The broadest applicability of findings comes from randomized controlled trials that assess the effectiveness of a single biological intervention for a well-defined disease using a valid biological outcome measure. Heterogeneity in study characteristics (patients, interventions and outcomes), and the presence of human perception (diagnosis, interventions and outcomes based on patient perception), and behaviour, environmental and equity factors, lessen the applicability of evidence. Randomized controlled trials must also report probabilities for favourable and adverse outcomes in order to increase the applicability of evidence.