CONSENSUS STATEMENT Meta-analysis of Observational Studies in Epidemiology A Proposal for Reporting Donna F. Stroup, PhD, MSc Objective Because of the pressure for timely, informed decisions in public health and Jesse A. Berlin, ScD clinical practice and the explosion of information in the scientific literature, research Sally C. Morton, PhD results must be synthesized. Meta-analyses are increasingly used to address this prob- lem, and they often evaluate observational studies. A workshop was held in Atlanta, Ingram Olkin, PhD Ga, in April 1997, to examine the reporting of meta-analyses of observational studies G. David Williamson, PhD and to make recommendations to aid authors, reviewers, editors, and readers. Drummond Rennie, MD Participants Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedi- David Moher, MSc cal editing. Deliberations of the workshop were open to other interested scientists. Fund- Betsy J. Becker, PhD ing for this activity was provided by the Centers for Disease Control and Prevention. Theresa Ann Sipe, PhD Evidence We conducted a systematic review of the published literature on the con- duct and reporting of meta-analyses in observational studies using MEDLINE, Educa- Stephen B. Thacker, MD, MSc tional Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. for the Meta-analysis Of We also examined reference lists of the 32 studies retrieved and contacted experts in Observational Studies in the field. Participants were assigned to small-group discussions on the subjects of bias, Epidemiology (MOOSE) Group searching and abstracting, heterogeneity, study categorization, and statistical methods. Consensus Process From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of ob- ECAUSE OF PRESSURE FOR TIMELY servational studies. The checklist and supporting evidence were circulated to all confer- and informed decisions in pub- ence attendees and additional experts. All suggestions for revisions were addressed. lic health and medicine and the Conclusions The proposed checklist contains specifications for reporting of meta- explosion of information in the analyses of observational studies in epidemiology, including background, search strat- Bscientific literature, research results must egy, methods, results, discussion, and conclusion. Use of the checklist should improve be synthesized to answer urgent ques- the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision tions.1-4 Principles of evidence-based makers. An evaluation plan is suggested and research areas are explored. methods to assess the effectiveness of JAMA. 2000;283:2008-2012 www.jama.com health care interventions and set policy are cited increasingly.5 Meta-analysis, a studies are available.8 Here, we define an Author Affiliations: Centers for Disease Control and systematic approach to identifying, ap- observational study as an etiologic or ef- Prevention, Atlanta, Ga (Drs Stroup, Williamson, and Thacker); University of Pennsylvania School of Medi- praising, synthesizing, and (if appropri- fectiveness study using data from an ex- cine, Philadelphia (Dr Berlin); RAND Corporation, Santa ate) combining the results of relevant isting database, a cross-sectional study, Monica (Dr Morton), University of California, San Fran- cisco (Dr Rennie), Stanford University, Stanford (Dr studies to arrive at conclusions about a a case series, a case-control design, a de- Olkin), Calif; JAMA, Chicago, Ill (Dr Rennie); Thomas body of research, has been applied with sign with historical controls, or a co- C. Chalmers Centre for Systematic Reviews, Chil- 9 dren’s Hospital of Eastern Ontario Research Insti- increasing frequency to randomized con- hort design. Observational designs may tute, Ottawa (Mr Moher); Michigan State Univer- trolled trials (RCTs), which are consid- lack the experimental element of a ran- sity, East Lansing (Dr Becker); and Georgia State ered to provide the strongest evidence dom allocation to an intervention and University, Atlanta (Dr Sipe). 6,7 A complete list of members of the MOOSE Group ap- regarding an intervention. rely on studies of association between pears at the end of this article. However, in many situations random- changes or differences in 1 characteris- Corresponding Author and Reprints: Donna F. Stroup, PhD, MSc, Centers for Disease Control and Preven- ized controlled designs are not fea- tic (eg, an exposure or intervention) and tion, 1600 Clifton Rd NE, Mail Stop C08, Atlanta, GA sible, and only data from observational changes or differences in an outcome of 30333 (e-mail: [email protected]). 2008 JAMA, April 19, 2000—Vol 283, No. 15 ©2000 American Medical Association. All rights reserved. REPORTING META-ANALYSES OF OBSERVATIONAL STUDIES interest. These designs have long been checklist of items for reporting that methods, results, discussion, and con- used in the evaluation of educational builds on similar activities for RCTs22 clusions (TABLE). programs10 and exposures that might and is intended for use by authors, re- cause disease or injury.11 Studies of risk viewers, editors, and readers of meta- Background factors generally cannot be random- analyses of observational studies. Reporting of the background should ized because they relate to inherent hu- include the definition of the problem man characteristics or practices, and ex- METHODS under study, statement of hypothesis, posing subjects to harmful risk factors We conducted a systematic review of description of the study outcome(s) is unethical.12 At times, clinical data may the published literature on the con- considered, type of exposure or inter- be summarized in order to design a ran- duct and reporting of meta-analyses vention used, type of study design used, domized comparison.13 Observational in observational studies. Databases and complete description of the study data may also be needed to assess the searched included MEDLINE, Educa- population. When combining observa- effectiveness of an intervention in a tional Resources Information Center, tional studies, heterogeneity of popu- community as opposed to the special PsycLIT (http://www.wesleyan.edu lations (eg, US vs international stud- setting of a controlled trial.14 Thus, a /libr), and the Current Index to Statis- ies), design (eg, case-control vs cohort clear understanding of the advantages tics. In addition, we examined refer- studies), and outcome (eg, different and limitations of statistical syntheses ence lists and contacted experts in the studies yielding different relative risks of observational data is needed.15 field. We used the 32 articles retrieved that cannot be accounted for by sam- Although meta-analysis restricted to to generate the conference agenda and pling variation) is expected.8 RCTs is usually preferred to meta- set topics of bias, searching and ab- analyses of observational studies,16-18 the stracting, heterogeneity, study catego- Search number of published meta-analyses rization, and statistical methods. We in- Reporting of the search strategy should concerning observational studies in vited experts in meta-analysis from the include qualifications of the search- health has increased substantially dur- fields of clinical practice, trials, statis- ers, specification of databases used, ing the past 4 decades (678 in 1955- tics, epidemiology, social sciences, and search strategy and index terms, use of 1992, 525 in 1992-1995, and more than biomedical editing. any special features (eg, “explosion”), 400 in 1996 alone).19 The workshop included an overview search software used, use of hand While guidelines for meta-analyses of the quality of reporting of meta- searching and contact with authors, use have been proposed, many are written analyses in education and the social of materials in languages other than En- from the meta-analyst’s (author’s) rather sciences. Plenary talks were given on the glish, use of unpublished material, and than from the reviewer’s, editor’s, or topics set by the conference agenda. For exclusion criteria used. Published re- reader’s perspective20 and restrict at- each of 2 sessions, workshop partici- search shows that use of electronic da- tention to reporting of meta-analyses of pants were assigned to 1 of 5 small dis- tabases may find only half of all rel- RCTs.21,22 Meta-analyses of observa- cussion groups, organized around the evant studies, and contacting authors tional studies present particular chal- topic areas. For each group, 1 of the may be useful,27 although this result lenges because of inherent biases and authors served as facilitator, and a may not be true for all topic areas.28 differences in study designs23; yet, they recorder summarized points of discus- For example, a meta-analysis of de- may provide a tool for helping to un- sion for issues to be presented to all pression in elderly medical inpatients29 derstand and quantify sources of vari- participants. Time was provided for the used 2 databases for the search. In ability in results across studies.24 2 recorders and 2 facilitators for each addition, bibliographies of retrieved We describe here the results of a topic to meet and prepare plenary pre- papers were searched. However, the au- workshop held in Atlanta, Ga, in April sentations given to the entire group. thors did not report their search strat- 1997, to examine concerns regarding the We