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We evaluated trial design features associated with registry\u2010defined trial completion and phase transition, and synthesized end\u2010of\u2010treatment hepatitis B surface antigen (HBsAg) decline as an on\u2010treatment antiviral signal.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically reviewed clinical trial registries and bibliographic databases for CHB cure trials. Associations between trial design characteristics and trial performance were analyzed using Cox regression (time to registry\u2010defined completion), logistic regression (phase I to phase II transition), and random\u2010effects meta\u2010analysis of end\u2010of\u2010treatment HBsAg decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Larger sample size (HR = 0.819, 95% CI = 0.710\u20130.945) and longer treatment duration (HR = 0.897, 95% CI = 0.816\u20130.987) were associated with a lower likelihood of registry\u2010defined completion in phase I trials. In phase II trials, larger sample size was associated with a lower likelihood of registry\u2010defined completion (HR = 0.936, 95% CI = 0.879\u20130.997). Novel trial designs were not associated with faster completion. Among phase I trials with a definitive status, trials enrolling healthy volunteers were more often followed by phase II registration (adjusted OR = 2.82, 95% CI = 1.16\u20137.08). Meta\u2010analysis showed that direct\u2010acting antivirals were associated with marked end\u2010of\u2010treatment HBsAg decline (SMD = 1.28, 95% CI = 0.47\u20132.08).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Smaller and shorter early\u2010phase trials were more likely to complete, whereas novel trial designs were not associated with faster completion. Direct\u2010acting antivirals showed marked end\u2010of\u2010treatment HBsAg decline, an on\u2010treatment signal rather than durable functional cure.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70346","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:24:58Z","timestamp":1773465898000},"page":"1389-1402","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Trials for Curing Chronic Hepatitis B: A Comprehensive Analysis of Trial Design Considerations and Their Association With Trial Performance"],"prefix":"10.1111","volume":"41","author":[{"given":"Lichen","family":"Shi","sequence":"first","affiliation":[{"name":"Clinical Epidemiology and EBM Unit, Beijing Clinical Research Institute, Beijing Friendship Hospital Capital Medical University  Beijing China"},{"name":"Department of Clinical Epidemiology and Clinical Trial Capital Medical University  Beijing 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