TY - JOUR
T1 - Consensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials
AU - Mackenzie, Amelia C.L.
AU - Chung, Stephanie
AU - Hoppes, Emily
AU - Miller, Nora
AU - Burke, Anne E.
AU - Achilles, Sharon L.
AU - Allen, C. Leigh
AU - Bahamondes, Luis
AU - Blithe, Diana L.
AU - Brache, Vivian
AU - Callahan, Rebecca L.
AU - Cartwright, Alice F.
AU - Clancy, Kathryn B.H.
AU - Colli, Enrico
AU - Cordova-Gomez, Amanda
AU - Costenbader, Elizabeth C.
AU - Creinin, Mitchell D.
AU - Critchley, Hilary O.D.
AU - Doncel, Gustavo F.
AU - Dorflinger, Laneta J.
AU - Edelman, Alison
AU - Faustmann, Thomas
AU - Gerlinger, Christoph
AU - Haddad, Lisa B.
AU - Hennegan, Julie
AU - Juliato, Cássia Raquel Teatin
AU - Kibira, Simon P.S.
AU - Mansour, Diana
AU - Martinez, Andres
AU - Matteson, Kristen A.
AU - Maybin, Jacqueline A.
AU - Mickler, Alexandria K.
AU - Nanda, Kavita
AU - Nwachukwu, Chukwuemeka E.
AU - OlaOlorun, Funmilola M.
AU - Peine, Kevin J.
AU - Polis, Chelsea B.
AU - Vieira, Carolina Sales
AU - Sitruk-Ware, Regine
AU - Smit, Jennifer A.
AU - Solomon, Marsden
AU - Soule, Lisa M.
AU - Taylor, Douglas
AU - Tolley, Elizabeth E.
AU - Vandeputte, Olivia
N1 - Funding: This expert consultation and consensus-building was made possible by the generous support of the American people through the U.S. Agency for International Development (USAID), provided to FHI 360 through cooperative agreement 7200AA20CA00016. The contents are the responsibility of FHI 360, the views expressed are those of the authors, and contents and views do not necessarily reflect those of any funder, including USAID, the National Institutes of Health, the United States Government, or the Reckitt Global Hygiene Institute Fellowship. ACLM, SC, EH, NM, AEB, RLC, AFC, ECC, LJD, AM, KN, MS, DT, and EET were supported but USAID cooperative agreement 7200AA20CA00016, with SC also supported by the Bill & Melinda Gates Foundation (OPP1200867) and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32 HD52468) and MS also supported by the Bill & Melinda Gates Foundation (INV-045483). EC was supported by Exeltis, and CEN by USAID. LB, VB, KBHC, MDC, HODC (paid to Institution), GFD, AE, LBH, JH, CRTJ, SPSK, DM, KAM, JAM, FMO, CBP, CSV, RSW, JAS, LMS, and OV received an honorarium supported by USAID cooperative agreement 7200AA20CA00016 that was declined by other authors. In addition, GFD was also supported by USAID Cooperative Agreement 7200AA20CA00019 provided to CONRAD/Eastern Virginia Medical School, JH was also supported by a Reckitt Global Hygiene Institute Fellowship, JAM was also supported by Wellcome Fellowship 209589/Z/17/Z, FMO was also supported by EVIHDAF, and RSW was also supported by The Population Council. Funding sources had no role in study design, data collection, analysis and interpretation of data, writing of the report, or decision to submit.
Conflicts of interest: AEB has received research funding mediated through JHU from: Merck, Chemo Pharmaceuticals, Dare Bioscience, and NICHD, and honorarium from Exeltis. LB received honorarium from Bayer and Organon. KBHC received a small honorarium from Pfizer to participate in their Tales From the Uterus podcast series in the summer/fall of 2023. EC is an Exeltis employee. MDC has received speaking honoraria from Gedeon Richter, Mayne, OLIC, and Organon, served on Advisory Boards for Gedeon Richter and Mayne, has stock options with Femasys, and has consulted for Estetra SRL, Medicines360, and Organon. The Department of Obstetrics and Gynecology, University of California, Davis, receives contraceptive research funding for MDC from Chemo Research SL, Evofem, Femasys, Medicines360, Merck, Sebela, and Sumitomo Pharma. HODC has received clinical research support for laboratory consumables and staff from Bayer AG (Paid to Institution) and has provided consultancy advice (Paid to Institution) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc., Myovant Sciences GmbH, and Theramex. HODC has also received royalties from UpToDate for an article on abnormal uterine bleeding. AE has received travel reimbursement from ACOG, WHO, CDC, and honoraria from Gynuity for committee activities. AE also receives royalties from Up to Date, Inc. Oregon Health & Science University receives research funding from OHSU Foundation, Gates, Merck, HRA Pharma, and NIH where AE is the principal investigator. CG is an employee of Bayer AG. KAM has received travel reimbursement from ACOG, ABOG, and Gideon Richter, honoraria from AJOG/Elsevier, and research consulting reimbursement from OHSU Foundation. CSV serves on Medical Advisory Boards and provides lectures for Bayer, Exeltis, and Organon. All other authors have no conflicts of interest to declare.
PY - 2025/6
Y1 - 2025/6
N2 - Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes. Study design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies. Smaller topical working groups drafted and revised recommendations. Results: We developed 44 consensus recommendations, including research approaches to establish the evidence for future improvement in the measurement and analysis of CIMC data and guidance for investigators to implement presently. Priority recommendations call for simplification of terminology to make measurement accessible and patient-centered, accounting for intrinsic and extrinsic factors that may impact outcomes during study design and recruitment, standardized data collection of primary CIMC and acceptability outcomes, and harmonized approaches for analysis of these data, including addressing missing data. Conclusion: By virtually convening a large group of global experts working across disciplines and sectors via a formal methodology, we developed consensus recommendations that will improve the current and future measurement and analysis of CIMC data in contraceptive clinical trials. Using these standardized approaches will permit valid and reliable contraceptive product labeling on CIMC outcomes that matter to users and greater comparability across trials that can inform clinical guidance and contraceptive counseling. Implications: Consensus recommendations on measuring bleeding changes and related outcomes in contraceptive clinical trials can improve reporting of standardized, patient-centered outcomes in future product labeling. These improvements can enable healthcare providers to offer more relevant guidance on contraceptives and users to make more informed decisions about their choice of method.
AB - Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes. Study design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies. Smaller topical working groups drafted and revised recommendations. Results: We developed 44 consensus recommendations, including research approaches to establish the evidence for future improvement in the measurement and analysis of CIMC data and guidance for investigators to implement presently. Priority recommendations call for simplification of terminology to make measurement accessible and patient-centered, accounting for intrinsic and extrinsic factors that may impact outcomes during study design and recruitment, standardized data collection of primary CIMC and acceptability outcomes, and harmonized approaches for analysis of these data, including addressing missing data. Conclusion: By virtually convening a large group of global experts working across disciplines and sectors via a formal methodology, we developed consensus recommendations that will improve the current and future measurement and analysis of CIMC data in contraceptive clinical trials. Using these standardized approaches will permit valid and reliable contraceptive product labeling on CIMC outcomes that matter to users and greater comparability across trials that can inform clinical guidance and contraceptive counseling. Implications: Consensus recommendations on measuring bleeding changes and related outcomes in contraceptive clinical trials can improve reporting of standardized, patient-centered outcomes in future product labeling. These improvements can enable healthcare providers to offer more relevant guidance on contraceptives and users to make more informed decisions about their choice of method.
KW - Bleeding patterns
KW - Consensus
KW - Contraceptive clinical trials
KW - Contraceptive-induced menstrual changes
KW - Menstrual cycle
KW - Patient reported outcome measures
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U2 - 10.1016/j.contraception.2025.110829
DO - 10.1016/j.contraception.2025.110829
M3 - Article
C2 - 39864646
AN - SCOPUS:85219109138
SN - 0010-7824
VL - 146
JO - Contraception
JF - Contraception
M1 - 110829
ER -