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Abstract
This article examines the critical role of endpoints as a benchmark for data reliability in both real-world clinical practice (RWP) and traditional oncological research. We provide a contemporary classification of oncology-specific endpoints (outcomes), detailing their definitions, key characteristics, and comparative strengths and limitations. A central focus is the methodological adaptation of these endpoints for RWP applications to better capture clinical realities. For practical purposes, the article outlines the types of data (attribute composition) required for a comprehensive assessment of each outcome. The discussion encompasses commonly accepted endpoints in oncological research that involve time-to-event analysis, such as overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Additionally, the article thoroughly examines the potential use of complementary and alternative endpoints, including disease-specific survival (DSS), time to treatment failure, time to next treatment, and other relevant outcomes.
References
I International conference on harmonisation; guidance on statistical principles for clinical trials; availability--FDA. Notice. Fed. Regist. 1998; 63(179): 49583-49598.-URL: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e9-statistical-principles-clinical-trials.
Schulz K.F., Altman D.G., Moher D. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. BMJ. 2010; 340: 332.-DOI: 10.1186/1741-7015-8-18.
Aiyegbusi O.L., di Ruffano L.F., Retzer A., et al. Outcome selection for tissue-agnostic drug trials for immune-mediated inflammatory diseases: a systematic review of core outcome sets and regulatory guidance. Trials. 2022; 23(1): 42.-DOI: 10.1186/s13063-022-06000-w.
Pinquart M. Experimental Studies and observational studies. Encyclopedia of gerontology and population aging. Ed. by Gu D., Dupre M.E. Cham: Springer International Publishing. 2021: 1748-1756.-DOI: 10.1007/978-3-030-22009-9_573.
Christensen R., Ciani O., Manyara A.M., et al. Surrogate endpoints: a key concept in clinical epidemiology. J Clin Epidemiol. 2024; 167: 111242.-DOI: 10.1016/j.jclinepi.2023.111242.
NIH, NCI dictionary of cancer terms.-URL: https://www.cancer.gov/publications/dictionaries/cancer-terms.
Mercieca-Bebber R., King M.T., Calvert M.J., et al. The importance of patient-reported outcomes in clinical trials and strategies for future optimization. Patient Relat Outcome Meas. 2018; 9: 353-367.-DOI: 10.2147/PROM.S156279.
Goldacre B., Drysdale H., Marston C., et al. COMPare: Qualitative analysis of researchers’ responses to critical correspondence on a cohort of 58 misreported trials. Trials. 2019; 20(1): 124.-DOI: 10.1186/s13063-019-3172-3.
Florez M.A. Jaoude J.A., Patel R.R., et al. Incidence of primary end point changes among active cancer phase 3 randomized clinical trials. JAMA Netw Open. 2023; 6(5): e2313819.-DOI: 10.1001/jamanetworkopen.2023.13819.
Mathoulin-Pelissier S., Gourgou-Bourgade S., Bonnetain F., Kramar A. Survival end point reporting in randomized cancer clinical trials: a review of major journals. J Clin Oncol. 2008; 26(22): 3721-6.-DOI: 10.1200/JCO.2007.14.1192.
Wilson M.K., Karakasis K., Oza A.M. Outcomes and endpoints in trials of cancer treatment: the past, present, and future. Lancet Oncol. 2015; 16(1): e32-42.-DOI: 10.1016/S1470-2045(14)70375-4.
Tang M. Pearson S.A., Simes R.J., Chua B.H. Harnessing real-world evidence to advance cancer research. Curr Oncol. 2023; 30(2): 1844-1859.-DOI: 10.3390/curroncol30020143.
Ramsey S.D., Onar-Thomas A., Wheeler S.B. Real-world database studies in oncology: A call for standards. J Clin Oncol. 2024; 42(9): 977-980.-DOI: 10.1200/JCO.23.02399.
Исследования реальной клинической практики: оценка технологий здравоохранения и клинические рекомендации. Под ред. В.В. Омельяновского. М.: Наука. 2024: 179.-ISBN 978-5-02-041101-2.-URL: https://rosmedex.ru/pub. [Real-world evidence studies: Health technology assessment and clinical guidelines. Ed. by Omelyanovskiy V.V. Moscow: Nauka. 2024: 179.-ISBN 978-5-02-041101-2.-URL: https://rosmedex.ru/pub (In Rus)].
Castelo-Branco L., Pellat A., Martins-Branco D. et al. ESMO guidance for reporting oncology real-world evidence (GROW). Ann Oncol. 2023; 34(12): 1097-1112.-DOI: 10.1016/j.annonc.2023.10.001.
Clinical trial endpoints for the approval of cancer drugs and biologics. Guidance for industry. 2018.-URL: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/clinical-trial-endpoints-approval-cancer-drugs-and-biologics.
McLeod C., Norman R., Litton E., et al. Choosing primary endpoints for clinical trials of health care interventions. Contemp Clin Trials Commun. 2019; 16: 100486.-DOI: 10.1016/j.conctc.2019.100486.
Delgado A., Guddati A.K. Clinical endpoints in oncology - a primer. Am J Cancer Res. 2021; 11(4): 1121-1131.-URL: https://pmc.ncbi.nlm.nih.gov/articles/PMC8085844/pdf/ajcr0011-1121.pdf.
Kemp R., Prasad V. Surrogate endpoints in oncology: when are they acceptable for regulatory and clinical decisions, and are they currently overused? BMC Med. 2017; 15(1): 134.-DOI: 10.1186/s12916-017-0902-9.
Feigin A. Evidence from biomarkers and surrogate endpoints. NeuroRx. 2004; 1(3): 323-30.-DOI: 10.1602/neurorx.1.3.323.
Gharzai L.A., Jiang R., Wallington D., et al. Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis. Lancet Oncol. 2021; 22(3): 402-410.-DOI: 10.1016/S1470-2045(20)30730-0.
Zichi C., Paratore C., Gargiulo P., et al. Adoption of multiple primary endpoints in phase III trials of systemic treatments in patients with advanced solid tumours. A systematic review. Eur J Cancer. 2021; 149: 49-60.-DOI: 10.1016/j.ejca.2021.03.007.
Fiteni F., Pam A., Anota A., et al. Health-related quality-of-life as co-primary endpoint in randomized clinical trials in oncology. Expert Rev Anticancer Ther. 2015; 15(8): 885-91.-DOI: 10.1586/14737140.2015.1047768.
Fiteni F., Westeel V., Pivot X., et al. Endpoints in cancer clinical trials. J Visc Surg. 2014; 151(1): 17-22.-DOI: 10.1016/j.jviscsurg.2013.10.001.
Тихомирова А.В. Критерии оценки клинической эффективности противоопухолевых лекарственных препаратов. Ведомости Научного центра экспертизы средств медицинского применения. 2019; 9(1): 34-40.-DOI: 10.30895/1991-2919-2019-9-1-34-40. [Tikhomirova A.V. Criteria for evaluation of clinical efficacy of anticancer medicines. The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products. 2019; 9(1): 34-40.-DOI: 10.30895/1991-2919-2019-9-1-34-40 (In Rus)].
IQVIA report, Evolving oncology endpoints – a new horizon for health outcomes. 2021.-URL: https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/evolving-oncology-endpoints.
Eisenhauer E.A., Therasse P., Bogaerts J., et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45(2): 228-47.-DOI: 10.1016/j.ejca.2008.10.026.
Seymour L., Bogaerts J., Perrone A., et al. iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics. Lancet Oncol. 2017; 18(3): e143-e152.-DOI: 10.1016/S1470-2045(19)30240-2.
Kapetanakis V., Prawitz T., Schlichting M., et al. Assessment-schedule matching in unanchored indirect treatment comparisons of progression-free survival in cancer studies. Pharmacoeconomics. 2019; 37(12): 1537-1551.-DOI: 10.1007/s40273-019-00831-3.
Kapetanakis V., Prawitz T., Schlichting M., et al. How Assessment-schedule matching limits bias when comparing progression-free survival in single-arm studies: An application in second-line urothelial carcinoma treatments. Value Health. 2021; 24(8): 1137-1144.-DOI: 10.1016/j.jval.2021.03.004.
Cimen А., Nelsen L.M., Fameli А., et al. Shifting perspectives on the value of non-OS endpoints and PROs: Considerations across stakeholder groups to support oncology HTA decision-making. J Clin Oncol. 2023; 41: e13646-e13646.-DOI: 10.1200/JCO.2023.41.16_suppl.e13646
Schuurhuis G.J., Heuser M., Freeman S., et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018; 131(12): 1275-1291.-DOI: 10.1182/blood-2017-09-801498.
Менделеева Л.П., Соловьев М.В., Рехтина И.Г., et al. Множественная миелома. Клинические рекомендации. Рубрикатор клинических рекомендаций: Минздрав России. 2024: 89-URL: https://cr.minzdrav.gov.ru/view-cr/144_2 (10.03.2025). [Mendeleeva L.P., Solov'ev M.V., Rekhtina I.G., et al. Multiple myeloma: Clinical guidelines. Clinical Guidelines Directory: Ministry of Health of the Russian Federation. 2024: 89.-URL: https://cr.minzdrav.gov.ru/view-cr/144_2 (10.03.2024) (in Rus)].
Аль-Ради Л.С., Виноградова О.Ю., Кузьмина Л.А., et al. Хронический миелоидный лейкоз. Клинические рекомендации. Рубрикатор клинических рекомендаций: Минздрав России. 2024: 89.-URL: https://cr.minzdrav.gov.ru/view-cr/889_1 (10.03.2025). [Al'-Radi L.S., Vinogradova O.Yu., Kuz'mina L.A., et al. Chronic Myeloid Leukemia. Clinical Guidelines. Clinical Guidelines Directory: Ministry of Health of the Russian Federation. 2024: 89.-URL: https://cr.minzdrav.gov.ru/view-cr/889_1 (10.03.2025) (in Rus)].
Bellera C.A., Pulido M., Gourgou S., et al. Protocol of the Definition for the Assessment of Time-to-event Endpoints in CANcer trials (DATECAN) project: formal consensus method for the development of guidelines for standardised time-to-event endpoints’ definitions in cancer clinical trials. Eur J Cancer. 2013; 49(4): 769-81.-DOI: 10.1016/j.ejca.2012.09.035.
Galvin A., Soubeyran P., Brain E., et al. Assessing patient-reported outcomes (PROs) and patient-related outcomes in randomized cancer clinical trials for older adults: Results of DATECAN-ELDERLY initiative. J Geriatr Oncol. 2024; 15(1): 101611.-DOI: 10.1016/j.jgo.2023.101611.
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