Validation strategies for subtypes in psychiatry: A systematic review of research on autism spectrum disorder

Heterogeneity within autism spectrum disorder (ASD) is recognized as a challenge to both biological and psychological research, as well as clinical practice. To reduce unexplained heterogeneity, subtyping techniques are often used to establish more homogeneous subtypes based on metrics of similarity and dissimilarity between people. We review the ASD literature to create a systematic overview of the subtyping procedures and subtype validation techniques that are used in this field. We conducted a systematic review of 156 articles (2001-June 2020) that subtyped participants (range N of studies = 17-20,658), of which some or all had an ASD diagnosis. We found a large diversity in (parametric and non-parametric) methods and (biological, psychological, demographic) variables used to establish subtypes. The majority of studies validated their subtype results using variables that were measured concurrently, but were not included in the subtyping procedure. Other investigations into subtypes' validity were rarer. In order to advance clinical research and the theoretical and clinical usefulness of identified subtypes, we propose a structured approach and present the SUbtyping VAlidation Checklist (SUVAC), a checklist for validating subtyping results.