{"doi":"10.1001/jama.286.7.821","title":"Comparison of Evidence of Treatment Effects in Randomized and Nonrandomized Studies","abstract":"<h4>Context</h4>There is substantial debate about whether the results of nonrandomized studies are consistent with the results of randomized controlled trials on the same topic.<h4>Objectives</h4>To compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between randomized and nonrandomized studies.<h4>Data sources</h4>MEDLINE (1966-March 2000), the Cochrane Library (Issue 3, 2000), and major journals were searched.<h4>Study selection</h4>Forty-five diverse topics were identified for which both randomized trials (n = 240) and nonrandomized studies (n = 168) had been performed and had been considered in meta-analyses of binary outcomes.<h4>Data extraction</h4>Data on events per patient in each study arm and design and characteristics of each study considered in each meta-analysis were extracted and synthesized separately for randomized and nonrandomized studies.<h4>Data synthesis</h4>Very good correlation was observed between the summary odds ratios of randomized and nonrandomized studies (r = 0.75; P<.001); however, nonrandomized studies tended to show larger treatment effects (28 vs 11; P =.009). Between-study heterogeneity was frequent among randomized trials alone (23%) and very frequent among nonrandomized studies alone (41%). The summary results of the 2 types of designs differed beyond chance in 7 cases (16%). Discrepancies beyond chance were less common when only prospective studies were considered (8%). Occasional differences in sample size and timing of publication were also noted between discrepant randomized and nonrandomized studies. In 28 cases (62%), the natural logarithm of the odds ratio differed by at least 50%, and in 15 cases (33%), the odds ratio varied at least 2-fold between nonrandomized studies and randomized trials.<h4>Conclusions</h4>Despite good correlation between randomized trials and nonrandomized studies-in particular, prospective studies-discrepancies beyond chance do occur and differences in estimated magnitude of treatment effect are very common.","journal":"JAMA","year":2001,"id":5039,"datarank":1.0239817835334892,"base_score":6.826545223556594,"endowment":6.826545223556594,"self_citation_contribution":1.0239817835334892,"citation_network_contribution":0.0,"self_endowment_contribution":1.0239817835334892,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":921,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.3868,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2001-08-15","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":148,"name":"John P. A. Ioannidis","orcid":"0000-0003-3118-6859","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}