{"doi":"10.1177/17407745241304065","title":"Evaluating the impact of stratification on the power and cross-arm balance of randomized phase 2 clinical trials","abstract":"Background/aimsRandomized clinical trials often use stratification to ensure balance between arms. Analysis of primary endpoints of these trials typically uses a \"stratified analysis,\" in which analyses are performed separately in each subgroup defined by the stratification factors, and those separate analyses are weighted and combined. In the phase 3 setting, stratified analyses based on a small number of stratification factors can provide a small increase in power. The impact on power and type-1 error of stratification in the setting of smaller sample sizes as in randomized phase 2 trials has not been well characterized.MethodsWe performed computational studies to characterize the power and cross-arm balance of modestly sized clinical trials (less than 170 patients) with varying numbers of stratification factors (0-6), sample sizes, randomization ratios (1:1 vs 2:1), and randomization methods (dynamic balancing vs stratified block).ResultsWe found that the power of unstratified analyses was minimally impacted by the number of stratification factors used in randomization. Analyses stratified by 1-3 factors maintained power over 80%, while power dropped below 80% when four or more stratification factors were used. These trends held regardless of sample size, randomization ratio, and randomization method. For a given randomization ratio and sample size, increasing the number of factors used in randomization had an adverse impact on cross-arm balance. Stratified block randomization performed worse than dynamic balancing with respect to cross-arm balance when three or more stratification factors were used.ConclusionStratified analyses can decrease power in the setting of phase 2 trials when the number of patients in a stratification subgroup is small.","journal":"Clinical Trials","year":2025,"id":527963,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"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":268627,"name":"Michael LeBlanc","orcid":"0000-0001-7192-2860","position":1,"is_corresponding":false},{"id":733492,"name":"Boris Freidlin","orcid":"0000-0002-2359-8063","position":2,"is_corresponding":false},{"id":284242,"name":"Rory M. Shallis","orcid":"0000-0002-8542-2944","position":3,"is_corresponding":false},{"id":280996,"name":"Amer M. Zeidan","orcid":"0000-0001-7017-8160","position":4,"is_corresponding":false},{"id":762311,"name":"David A. Sallman","orcid":"0000-0003-0504-8233","position":5,"is_corresponding":false},{"id":233357,"name":"Harry P. Erba","orcid":"0000-0003-1093-2189","position":6,"is_corresponding":false},{"id":241725,"name":"Richard F. Little","orcid":"0000-0002-4091-1699","position":7,"is_corresponding":false},{"id":383952,"name":"Megan Othus","orcid":"0000-0001-8176-6371","position":8,"is_corresponding":false},{"id":509657,"name":"Anna Moseley","orcid":"0000-0002-7514-7360","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:44.062153Z","pmid":"39815460","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":[]}