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Motivated by design work in trials of HIV\u20101 curative interventions, we compare the Wilcoxon\u2013Mann\u2013Whitney (WMW) estimand to a difference in medians or means in a two\u2010arm study. First, we define each estimand along with an appropriate estimator. Then, we highlight relevant asymptotic relative efficiency (ARE) results for the estimators under normal distributions (ARE: WMW\/mean = , median\/mean = , median\/WMW = ), as well as normal mixtures. Measurement of outcomes related to HIV\u20101 cure involve laboratory assays with lower limits of quantification giving rise to left\u2010censored data. In our simulation study, we compare the estimators in the presence of left\u2010censored observations and at small sample sizes, illustrating that under a censored normal mixture distribution the WMW approach is unbiased, powerful, and has confidence intervals with nominal coverage. We apply our findings to a randomized trial designed to reduce HIV\u20101 reservoirs. We further expose several extensions of the WMW approach that allows for assessment of interactions between subgroups in a trial, adjustment for covariates, and general ranking methods for clinical outcomes in other disease areas. We end with a discussion summarizing the merits of a WMW based intervention effect estimate versus an estimate summarized on the scale the intervention was originally measured such as the difference in medians or means.<\/jats:p>","DOI":"10.1002\/pst.70036","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T09:53:33Z","timestamp":1754992413000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Wilcoxon\u2013Mann\u2013Whitney Estimand Versus Differences in Medians or Means"],"prefix":"10.1002","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3170-0865","authenticated-orcid":false,"given":"Linda J.","family":"Harrison","sequence":"first","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Department of Biostatistics Harvard TH Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald J.","family":"Bosch","sequence":"additional","affiliation":[{"name":"Center for Biostatistics in AIDS Research, Department of Biostatistics Harvard TH Chan School of Public Health  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,12]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.316.7126.201"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.2886"},{"key":"e_1_2_12_4_1","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2023-076316","article-title":"The Estimands Framework: A Primer on the ICH E9 (R1) Addendum","volume":"384","author":"Kahan B. 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