Environmental Health Perspectives • VOLUME 122 | NUMBER 7 | July 2014 711 Research All EHP content is accessible to individuals with disabilities. A fully accessible (Section 508–compliant) HTML version of this article is available at http://dx.doi.org/10.1289/ehp.1307972. Introduction Systematic-review methodologies increase the objectivity and transparency in the process of collecting and synthesizing scientific evi- dence on speciic questions. he product of a systematic review can then be used to inform decisions, reach conclusions, or identify research needs. here is increasing interest in applying the principles of systematic review to questions in environmental health [European Food Safety Authority (EFSA) 2010; National Research Council (NRC) 2011, 2013a; Rhomberg et al. 2013; Woodruf and Sutton 2011]. Although systematic-review methodol- ogies are well established in clinical medi- cine to assess data for reaching health care recommendations [Agency for Healthcare Research and Quality (AHRQ) 2013; Guyatt et al. 2011a; Higgins and Green 2011; Viswanathan et al. 2012], these approaches are most developed for human clinical trials, and therefore, typically consider small data sets of similar study design in develop- ing conclusions. Questions in environmental health require the evaluation of a broader range of relevant data including experimental animal and mechanistic studies as well as observational human studies. Also, there is a need to integrate data from multiple evidence streams (human, animal, and “other rele- vant data” including mechanistic or in vitro studies) in order to reach conclusions regard- ing potential health efects from exposure to substances in our environment. The National Toxicology Program (NTP) Office of Health Assessment and Translation (OHAT) conducts literature- based evaluations to assess the evidence that environmental chemicals, physical sub- stances, or mixtures (collectively referred to as “substances”) cause adverse health efects and provides opinions on whether these substances may be of concern given levels of current human exposure (Bucher et al. 2011). Building on a history of rigorous and objective scientiic review, OHAT has been working to incorporate systematic-review procedures in its evaluations since 2011 through a process that has included adop- tion of current practice, as well as methods development (Birnbaum et al. 2013; NTP 2012a, 2012b, 2013e). Here we explain the framework developed by OHAT that uses procedures to integrate multiple evidence streams including observational human study findings, experimental animal toxicology results, and other relevant data in developing hazard identification conclusions or state- of-the-science evaluations regarding health effects from exposure to environmental substances. The seven-step framework out- lines methods to increase transparency and consistency in the process, but it also presents opportunities to increase eiciencies in data management and data display that facilitate the process of reaching and communicating hazard identiication conclusions. Methods In 2011, OHAT began exploring systematic- review methodology as a means to enhance transparency and increase efficiency in summarizing and synthesizing findings from studies in its literature-based health assessments. OHAT used a multipronged strategy to develop the OHAT Approach, working with advisors to adapt and extend existing methods from clinical medicine and obtaining input from technical experts and the public on early drafts (see Supplemental Material, Table S1). The methods- development process is described in detail in Supplemental Material (“Process for develop- ing the OHAT Approach,” pp. 2–7). In brief, OHAT reviewed guidance from authorita- tive systematic-review groups (AHRQ 2013; Guyatt et al. 2011a; Higgins and Green 2011) in developing an initial draft and sought additional advice through web-based discussions and consultation with techni- cal experts, the NTP Executive Committee, the NTP Board of Scientific Counselors, and the public (NTP 2012a, 2012b, 2013b, 2013c, 2013d, 2013e). he resulting OHAT Approach has been refined based on the input received and through application to case studies. Address correspondence to A.A. Rooney, NIEHS, P.O. Box 12233, Mail Drop K2-04, Research Triangle Park, NC 27709 USA. Telephone: (919) 541-2999. E-mail: andrew.rooney@nih.gov Supplemental Material is available online (http:// dx.doi.org/10.1289/ehp.1307972). We appreciate the valuable advice and comments on the development of this systematic-review frame- work from a number of technical experts, the public, the National Toxicology Program (NTP) Executive Committee, and the NTP Board of Scientific Counselors. he authors declare they have no actual or potential competing inancial interests. Received: 6 December 2013; Accepted: 18 April 2014; Advance Publication: 22 April 2014; Final Publication: 1 July 2014. Systematic Review and Evidence Integration for Literature-Based Environmental Health Science Assessments Andrew A. Rooney, Abee L. Boyles, Mary S. Wolfe, John R. Bucher, and Kristina A. Thayer Office of Health Assessment and Translation, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA BACKGROUND: Systematic-review methodologies provide objectivity and transparency to the process of collecting and synthesizing scientiic evidence in reaching conclusions on speciic research questions. There is increasing interest in applying these procedures to address environmental health questions. OBJECTIVES: he goal was to develop a systematic-review framework to address environmental health questions by extending approaches developed for clinical medicine to handle the breadth of data relevant to environmental health sciences (e.g., human, animal, and mechanistic studies). METHODS: he Oice of Health Assessment and Translation (OHAT) adapted guidance from authorities on systematic-review and sought advice during development of the OHAT Approach through consultation with technical experts in systematic review and human health assessments, as well as scientiic advisory groups and the public. he method was reined by considering expert and public comments and through application to case studies. RESULTS AND DISCUSSION: Here we present a seven-step framework for systematic review and evidence integration for reaching hazard identiication conclusions: 1) problem formulation and protocol development, 2) search for and select studies for inclusion, 3) extract data from studies, 4) assess the quality or risk of bias of individual studies, 5) rate the confidence in the body of evidence, 6) translate the conidence ratings into levels of evidence, and 7) integrate the information from diferent evidence streams (human, animal, and “other relevant data” including mechanistic or in vitro studies) to develop hazard identiication conclusions. CONCLUSION: he principles of systematic review can be successfully applied to environmental health questions to provide greater objectivity and transparency to the process of developing conclusions. CITATION: Rooney AA, Boyles AL, Wolfe MS, Bucher JR, hayer KA. 2014. Systematic review and evidence integration for literature-based environmental health science assessments. Environ Health Perspect 122:711–718; http://dx.doi.org/10.1289/ehp.1307972