{"doi":"10.1093/aje/kwaf226","title":"Statistical approaches for systematically missing covariates in individual participant data meta-analysis: insights and applications using 5 large cardiovascular trials","abstract":"Abstract Combining multiple studies for evidence synthesis can improve the precision of effect estimates and enable investigation of more granular clinical research questions. However, individual participant data (IPD) meta-analyses are often limited by the presence of systematically missing covariates that are only available in a subset of studies. Common solutions include removing missing covariates from the analyses or excluding studies that have not collected the missing covariates. Both approaches risk losing valuable information and introducing bias. Two additional approaches have been proposed: bivariate meta-analysis and multiple imputation (MI) of systematically missing data. The potential advantages and performances of these approaches, however, have only been discussed using simulation studies. In this analysis, we used data from 5 large cardiovascular clinical trials and illustrate the advantages and applicability of these 2 approaches in retaining missing covariates across various scenarios of increased complexity as compared to the more common approaches of excluding the covariates or the studies. Our results showed that both bivariate meta-analysis and MI of systematically missing data preserve information and improve the precision of the combined estimates. The findings underscore the importance of retaining information that is otherwise lost due to systematically missing values. Trial registration: Trial protocols were approved by the institutional review board at each participating center. All patients provided written informed consent for the study examinations. SOLID-TIMI 52 ClinicalTrials.gov number NCT01000727; SAVOR-TIMI 53 ClinicalTrials.gov number, NCT01107886; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562; DECLARE-TIMI 58 ClinicalTrials.gov number, NCT01730534; and CAMELLIA–TIMI 61 ClinicalTrials.gov number, NCT02019264.","journal":"American Journal of Epidemiology","year":2025,"id":577379,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9371,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":769526,"name":"Paul M. Haller","orcid":"0000-0002-7714-4446","position":1,"is_corresponding":false},{"id":902203,"name":"Siddharth M. Patel","orcid":"0000-0002-4637-4361","position":2,"is_corresponding":false},{"id":380427,"name":"Erin A. Bohula","orcid":"0000-0002-5559-8172","position":3,"is_corresponding":false},{"id":264819,"name":"David A. Morrow","orcid":"0000-0002-9589-5382","position":4,"is_corresponding":false},{"id":2026,"name":"Sabina A. Murphy","orcid":"0000-0002-8231-3611","position":5,"is_corresponding":false},{"id":420378,"name":"Michelle L. O’Donoghue","orcid":"0000-0002-8663-0067","position":6,"is_corresponding":false},{"id":50019,"name":"Marc S. Sabatine","orcid":"0000-0002-0691-3359","position":7,"is_corresponding":false},{"id":1486916,"name":"Benjamin Scirica","orcid":null,"position":8,"is_corresponding":false},{"id":3774,"name":"Deepak L. Bhatt","orcid":"0000-0002-1278-6245","position":9,"is_corresponding":false},{"id":1486508,"name":"Nicola Orsini","orcid":"0000-0002-2210-5634","position":10,"is_corresponding":false},{"id":368527,"name":"Andrea Bellavia","orcid":"0000-0003-4988-4532","position":11,"is_corresponding":false},{"id":1486507,"name":"Robert Thiesmeier","orcid":"0000-0002-4590-5538","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-19T02:58:04.622308Z","pmid":"41067245","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":[]}