biostudies-literatureUnknown8(9)Sia J<h4>Importance</h4>Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking.<h4>Objective</h4>To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements.<h4>Design, setting, and participants</h4>In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohorJAMA network opene2532195https://www.ebi.ac.uk/biostudies/studies/S-EPMC12441877biostudies-literatureEstimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.PMC12441877Ray ICrosbie ETaylor SPovolotskaya NHamed HAhmed MBaxter KChattopadhyay SOxley SDuncan TElboraei RMackintosh MMatthews NLane EFHanson HNewton CWillett MKhaing TTReig GDevaja OChalhoub TDalton JSundar SGurumurthy MPROTECTOR teamBryson GOhwo VLegood RWei XHarley IBorley JGhaem-Maghami SRagupathy KCasey LDe Souza BKalra ASingh AFaruqi AVan Seters MEdey KIdahl ASideris MSide LKamran ARao SPiletska NIyer RPrasad MSaridogan EMcDermott JMisiura HBrady AFraser HArora RSasieni PSharma AGanesan RKaushik SGanesan SEvans DGSingh NBarker VManchanda RKohut KFierheller CTKodiathodi SFegan SHutson ROktaba MPark CBolton HSnape KTryczynska MTailor AAlazzani HRyan NMcArdle GBalega JGnanachandran CMehra GMenon UAbdelaziz MMcCluggage WGSia JRowlands GPhillips ASengupta PAbdul BWilliamson KO'Donnell RPeevor RRosenthal AMarks MSassarini JBrentnall ACameron IPilkington TDoh HMansour LTrevisan GZulfiqar NDeshmukh PfalseEstimands for Clinical Effectiveness of Risk-Reducing Early Salpingectomy in Women With High Risk of Ovarian Cancer.<h4>Importance</h4>Risk-reducing early-salpingectomy (RRES) and delayed oophorectomy (DO) is a novel 2-stage alternative prevention strategy to risk-reducing salpingo-oophorectomy (RRSO) that avoids detrimental consequences of premature menopause. However, direct data on the clinical effectiveness for ovarian cancer (OC) risk reduction are lacking.<h4>Objective</h4>To explore how to define clinical effectiveness from prospective cohort studies using the estimand framework and sample size requirements.<h4>Design, setting, and participants</h4>In this comparative effectiveness research study, estimand and analysis options were considered to evaluate the clinical effectiveness of RRES with DO by extending the UK PROTECTOR cohort study, a multicenter, prospective, observational, national cohor2025-01-01T00:00:00Z2025 Sep2026-07-15T06:51:33.026Z2026-06-30T03:27:09.062ZS-EPMC124418774095657710.1001/jamanetworkopen.2025.32195