title: An approach to addressing subpopulation considerations in systematic reviews: the experience of reviewers supporting the U.S. Preventive Services Task Force.
abstract: Guideline developers and other users of systematic reviews need information about whether a medical or preventive intervention is likely to benefit or harm some patients more (or less) than the average in order to make clinical practice recommendations tailored to these populations. However, guidance is lacking on how to include patient subpopulation considerations into the systematic reviews upon which guidelines are often based. In this article, we describe methods developed to consistently consider the evidence for relevant subpopulations in systematic reviews conducted to support primary care clinical preventive service recommendations made by the U.S. Preventive Services Task Force (USPSTF).
  
  
  
  Our approach is grounded in our experience conducting systematic reviews for the USPSTF and informed by a review of existing guidance on subgroup analysis and subpopulation issues. We developed and refined our approach based on feedback from the Subpopulation Workgroup of the USPSTF and pilot testing on reviews being conducted for the USPSTF. This paper provides processes and tools for incorporating evidence-based identification of important sources of potential heterogeneity of intervention effects into all phases of systematic reviews. Key components of our proposed approach include targeted literature searches and key informant interviews to identify the most important subpopulations a priori during topic scoping, a framework for assessing the credibility of subgroup analyses reported in studies, and structured investigation of sources of heterogeneity of intervention effects.
  
  
  
  Further testing and evaluation are necessary to refine this proposed approach and demonstrate its utility to the producers and users of systematic reviews beyond the context of the USPSTF. Gaps in the evidence on important subpopulations identified by routinely applying this process in systematic reviews will also inform future research needs.
authors.affiliation: Patient-Centered Outcomes Research Institute, 1919 M Street NW 2nd Floor, Washington DC, 20036, USA.
authors.forename: Evelyn P
authors.initials: EP
authors.lastname: Whitlock
authors.affiliation: Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave, Portland, OR, 97227, USA. Michelle.l.eder@kpchr.org.
authors.forename: Michelle
authors.identifier: 0000-0003-4417-3731
authors.initials: M
authors.lastname: Eder
authors.affiliation: Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave, Portland, OR, 97227, USA.
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Thompson
authors.affiliation: Department of Medicine, University of North Carolina Chapel Hill, 5034 Old Clinic Building, Chapel Hill, NC 27599, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Jonas
authors.affiliation: Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave, Portland, OR, 97227, USA.
authors.forename: Corinne V
authors.initials: CV
authors.lastname: Evans
authors.affiliation: Department of Family Medicine, Tacoma Family Medicine Residency Program, University of Washington, 521 Martin Luther King Jr. Way, Tacoma, WA 98405, USA.
authors.forename: Janelle M
authors.initials: JM
authors.lastname: Guirguis-Blake
authors.affiliation: Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente Northwest, 3800 N. Interstate Ave, Portland, OR, 97227, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lin
mesh_terms: D026683:Advisory Committees; D019317:Evidence-Based Medicine / Q000592:standards; D006801:Humans; D007407:Interviews as Topic; D017410:Practice Guidelines as Topic; D011314:Preventive Health Services / Q000592:standards*; D011320:Primary Health Care; D012196:Review Literature as Topic; D014481:United States; D016270:United States Agency for Healthcare Research and Quality
keywords: Heterogeneity; Patient subpopulation; Subgroup; Systematic review