{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T20:34:52Z","timestamp":1740170092426,"version":"3.37.3"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006483","name":"AbbVie","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006483","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006396","name":"Alexion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006396","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Caelum"},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Amyloidosis Research Consortium"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ther Innov Regul Sci"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunoglobin light chain (AL) amyloidosis is a rare disease in which a plasma cell dyscrasia leads to deposition of insoluble amyloid fibrils in multiple organs. To facilitate development of new therapies for this heterogenous disease, a public\u2013private partnership was formed between the nonprofit Amyloidosis Research Consortium and the US Food and Drug Administration Center for Drug Evaluation and Research. In 2020, the Amyloidosis Forum launched an initiative to identify clinical trial endpoints and analytic strategies across affected organ systems and life impacts via specialized working groups. This review summarizes the proceedings of the Statistical Group and proposes a pathway for development and validation of multi-domain endpoints (MDEs) for potential use in AL amyloidosis clinical trials. Specifically, drawing on candidate domain-specific endpoints recommended by each organ-specific working group, different approaches to constructing MDEs were considered. Future studies were identified to assess the validity, meaningfulness and performance of MDEs through use of natural history and clinical trial data. Ultimately, for drug development, the context of use in a regulatory evaluation, the specific patient population, and the investigational therapeutic mechanism should drive selection of appropriate endpoints. MDEs for AL amyloidosis, once developed and validated, will provide important options for advancing patient-focused drug development in this multi-system disease.<\/jats:p>","DOI":"10.1007\/s43441-024-00641-6","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T19:01:53Z","timestamp":1713380513000},"page":"600-609","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pathway for Development and Validation of Multi-domain Endpoints for Amyloid Light Chain (AL) Amyloidosis"],"prefix":"10.1007","volume":"58","author":[{"given":"James","family":"Signorovitch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jialu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Brown","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Preston","family":"Dunnmon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Xiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicolae","family":"Done","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yolanda","family":"Barbachano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabelle","family":"Lousada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,4,17]]},"reference":[{"issue":"1","key":"641_CR1","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41572-018-0034-3","volume":"4","author":"G Merlini","year":"2018","unstructured":"Merlini G, Dispenzieri A, Sanchorawala V, Sch\u00f6nland SO, Palladini G, Hawkins PN, et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018;4(1):38.","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"641_CR2","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1182\/bloodadvances.2018016402","volume":"2","author":"TP Quock","year":"2018","unstructured":"Quock TP, Yan T, Chang E, Guthrie S, Broder MS. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018;2(10):1046\u201353.","journal-title":"Blood Adv"},{"key":"641_CR3","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1750-1172-7-54","volume":"7","author":"E Desport","year":"2012","unstructured":"Desport E, Bridoux F, Sirac C, Delbes S, Bender S, Fernandez B, et al. Al amyloidosis. Orphanet J Rare Dis. 2012;7:54.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"641_CR4","first-page":"472","volume":"94","author":"E Muchtar","year":"2019","unstructured":"Muchtar E, Gertz MA, Kyle RA, Lacy MQ, Dingli D, Leung N, et al. A modern primer on light chain amyloidosis in 592 patients with mass spectrometry-verified typing. Mayo Clin Proc. 2019;94(3):472\u201383.","journal-title":"Mayo Clin Proc"},{"issue":"1","key":"641_CR5","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1001\/jama.2020.5493","volume":"324","author":"MA Gertz","year":"2020","unstructured":"Gertz MA, Dispenzieri A. Systemic amyloidosis recognition, prognosis, and therapy: a systematic review. JAMA. 2020;324(1):79\u201389.","journal-title":"JAMA"},{"issue":"9","key":"641_CR6","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1200\/JCO.2011.38.5724","volume":"30","author":"S Kumar","year":"2012","unstructured":"Kumar S, Dispenzieri A, Lacy MQ, Hayman SR, Buadi FK, Colby C, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol. 2012;30(9):989\u201395.","journal-title":"J Clin Oncol"},{"issue":"1","key":"641_CR7","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1182\/blood.V68.1.220.220","volume":"68","author":"RA Kyle","year":"1986","unstructured":"Kyle RA, Greipp PR, O\u2019Fallon WM. Primary systemic amyloidosis: multivariate analysis for prognostic factors in 168 cases. Blood. 1986;68(1):220\u20134.","journal-title":"Blood"},{"issue":"10","key":"641_CR8","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1007\/s12325-015-0250-0","volume":"32","author":"I Lousada","year":"2015","unstructured":"Lousada I, Comenzo RL, Landau H, Guthrie S, Merlini G. Light chain amyloidosis: patient experience survey from the amyloidosis research consortium. Adv Ther. 2015;32(10):920\u20138.","journal-title":"Adv Ther"},{"key":"641_CR9","unstructured":"Multiple Endpoints in Clinical Trials. Guidance for Industry [Internet]. 2022 17 Jan 2024. Available from: https:\/\/www.fda.gov\/media\/162416\/download."},{"key":"641_CR10","unstructured":"Patient-Focused Drug Development: Incorporating Clinical Outcome Assessments Into Endpoints For Regulatory Decision-Making. Guidance for Industry [Internet]. 2023. Available from: https:\/\/www.fda.gov\/drugs\/development-approval-process-drugs\/fda-patient-focused-drug-development-guidance-series-enhancing-incorporation-patients-voice-medical."},{"key":"641_CR11","unstructured":"Rare Diseases: Considerations for the Development of Drugs and Biological Products. Guidance for Industry [Internet]. 2023 1\/17\/2024. Available from: https:\/\/www.fda.gov\/media\/119757\/download."},{"key":"641_CR12","unstructured":"Patient-Focused Drug Development: Methods to Identify What is Important to Patients. Guidance for Industry [Internet]. 2022 17 Feb 2023. Available from: https:\/\/www.fda.gov\/media\/131230\/download."},{"key":"641_CR13","unstructured":"Patient-Focused Drug Development: Collecting Comprehensive and Representative Input. Guidance for Industry [Internet]. 2022 17 Feb 2023. Available from: https:\/\/www.fda.gov\/media\/131230\/download."},{"key":"641_CR14","unstructured":"Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. Guidance for Industry [Internet]. 2009 14 Mar 2022. Available from: https:\/\/www.fda.gov\/media\/77832\/download."},{"key":"641_CR15","doi-asserted-by":"crossref","unstructured":"Inaugural Amyloidosis Forum Panelists, Lousada I. The Amyloidosis Forum: a public private partnership to advance drug development in AL amyloidosis. Orphanet J Rare Dis. 2020;15(1):268.","DOI":"10.1186\/s13023-020-01525-2"},{"issue":"3","key":"641_CR16","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.ymgme.2020.01.003","volume":"129","author":"RY Wang","year":"2020","unstructured":"Wang RY, da Silva Franco JF, Lopez-Valdez J, Martins E, Sutton VR, Whitley CB, et al. The long-term safety and efficacy of vestronidase alfa, rhGUS enzyme replacement therapy, in subjects with mucopolysaccharidosis VII. Mol Genet Metab. 2020;129(3):219\u201327.","journal-title":"Mol Genet Metab"},{"issue":"2","key":"641_CR17","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.ymgme.2014.08.012","volume":"114","author":"CJ Hendriksz","year":"2015","unstructured":"Hendriksz CJ, Giugliani R, Harmatz P, Mengel E, Guffon N, Valayannopoulos V, et al. Multi-domain impact of elosufase alfa in Morquio A syndrome in the pivotal phase III trial. Mol Genet Metab. 2015;114(2):178\u201385.","journal-title":"Mol Genet Metab"},{"key":"641_CR18","unstructured":"Points to Consider on Multiplicity Issues in Clinical Trials. Committee for Proprietary Medicinal Products [Internet]. 2002. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/scientific-guideline\/points-consider-multiplicity-issues-clinical-trials_en.pdf."},{"key":"641_CR19","unstructured":"Endpoints Used for Relative Effectiveness Assessment of Pharmaceuticals. Guideline [Internet]. 2013. Available from: https:\/\/www.eunethta.eu\/wp-content\/uploads\/2018\/01\/Composite-endpoints.pdf."},{"issue":"Suppl 6","key":"641_CR20","doi-asserted-by":"publisher","first-page":"vi5","DOI":"10.1093\/rheumatology\/kes279","volume":"51","author":"J Kay","year":"2012","unstructured":"Kay J, Upchurch KS. ACR\/EULAR 2010 rheumatoid arthritis classification criteria. Rheumatology (Oxford). 2012;51(Suppl 6):vi5-9.","journal-title":"Rheumatology (Oxford)"},{"issue":"1","key":"641_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13506129.2020.1868810","volume":"28","author":"G Palladini","year":"2021","unstructured":"Palladini G, Schonland SO, Sanchorawala V, Kumar S, Wechalekar A, Hegenbart U, et al. Clarification on the definition of complete haematologic response in light-chain (AL) amyloidosis. Amyloid. 2021;28(1):1\u20132.","journal-title":"Amyloid"},{"issue":"10","key":"641_CR22","doi-asserted-by":"publisher","first-page":"2240","DOI":"10.1038\/s41375-018-0060-x","volume":"32","author":"E Muchtar","year":"2018","unstructured":"Muchtar E, Dispenzieri A, Leung N, Lacy MQ, Buadi FK, Dingli D, et al. Depth of organ response in AL amyloidosis is associated with improved survival: grading the organ response criteria. Leukemia. 2018;32(10):2240\u201349.","journal-title":"Leukemia"},{"issue":"12","key":"641_CR23","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1001\/jamainternmed.2018.4710","volume":"178","author":"B Kovic","year":"2018","unstructured":"Kovic B, Jin X, Kennedy SA, Hylands M, Pedziwiatr M, Kuriyama A, et al. Evaluating progression-free survival as a surrogate outcome for health-related quality of life in oncology: a systematic review and quantitative analysis. JAMA Intern Med. 2018;178(12):1586\u201396.","journal-title":"JAMA Intern Med"},{"issue":"25","key":"641_CR24","doi-asserted-by":"publisher","first-page":"2631","DOI":"10.1056\/NEJMoa055373","volume":"355","author":"TJ Wang","year":"2006","unstructured":"Wang TJ, Gona P, Larson MG, Tofler GH, Levy D, Newton-Cheh C, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355(25):2631\u20139.","journal-title":"N Engl J Med"},{"issue":"1","key":"641_CR25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1056\/NEJMoa2028631","volume":"385","author":"E Kastritis","year":"2021","unstructured":"Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, Lee HC, et al. Daratumumab-based treatment for immunoglobulin light-chain amyloidosis. N Engl J Med. 2021;385(1):46\u201358.","journal-title":"N Engl J Med"},{"key":"641_CR26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.116.003815","author":"MS Maurer","year":"2017","unstructured":"Maurer MS, Elliott P, Merlini G, Shah SJ, Cruz MW, Flynn A, et al. Design and rationale of the phase 3 ATTR-ACT clinical trial (Tafamidis in transthyretin cardiomyopathy clinical trial). Circ Heart Fail. 2017. https:\/\/doi.org\/10.1161\/CIRCHEARTFAILURE.116.003815.","journal-title":"Circ Heart Fail"},{"issue":"4","key":"641_CR27","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.ymgme.2018.02.006","volume":"123","author":"P Harmatz","year":"2018","unstructured":"Harmatz P, Whitley CB, Wang RY, Bauer M, Song W, Haller C, et al. A novel Blind Start study design to investigate vestronidase alfa for mucopolysaccharidosis VII, an ultra-rare genetic disease. Mol Genet Metab. 2018;123(4):488\u201394.","journal-title":"Mol Genet Metab"},{"issue":"9","key":"641_CR28","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO 3rd, et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum. 2010;62(9):2569\u201381.","journal-title":"Arthritis Rheum"},{"issue":"Supplement 1","key":"641_CR29","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1182\/blood-2020-137582","volume":"136","author":"RL Comenzo","year":"2020","unstructured":"Comenzo RL, Kastritis E, Palladini G, Minnema MC, Wechalekar AD, Jaccard A, et al. Reduction in absolute involved free light chain and difference between involved and uninvolved free light chain is associated with prolonged major organ deterioration progression-free survival in patients with newly diagnosed AL amyloidosis receiving bortezomib, cyclophosphamide, and dexamethasone with or without daratumumab: results from Andromeda. Blood. 2020;136(Supplement 1):48\u201350.","journal-title":"Blood"},{"issue":"11","key":"641_CR30","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1002\/(SICI)1097-0258(19990615)18:11<1341::AID-SIM129>3.0.CO;2-7","volume":"18","author":"DM Finkelstein","year":"1999","unstructured":"Finkelstein DM, Schoenfeld DA. Combining mortality and longitudinal measures in clinical trials. Stat Med. 1999;18(11):1341\u201354.","journal-title":"Stat Med"},{"issue":"2","key":"641_CR31","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1093\/eurheartj\/ehr352","volume":"33","author":"SJ Pocock","year":"2012","unstructured":"Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012;33(2):176\u201382.","journal-title":"Eur Heart J"},{"issue":"11","key":"641_CR32","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","volume":"379","author":"MS Maurer","year":"2018","unstructured":"Maurer MS, Schwartz JH, Gundapaneni B, Elliott PM, Merlini G, Waddington-Cruz M, et al. Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy. N Engl J Med. 2018;379(11):1007\u201316.","journal-title":"N Engl J Med"},{"issue":"3","key":"641_CR33","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1111\/biom.12475","volume":"72","author":"R Ramchandani","year":"2016","unstructured":"Ramchandani R, Schoenfeld DA, Finkelstein DM. Global rank tests for multiple, possibly censored, outcomes. Biometrics. 2016;72(3):926\u201335.","journal-title":"Biometrics"},{"issue":"1","key":"641_CR34","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1186\/s13023-021-01805-5","volume":"16","author":"PK Tandon","year":"2021","unstructured":"Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021;16(1):183.","journal-title":"Orphanet J Rare Dis"},{"issue":"4","key":"641_CR35","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1002\/ajmg.a.38629","volume":"176","author":"GF Cox","year":"2018","unstructured":"Cox GF. The art and science of choosing efficacy endpoints for rare disease clinical trials. Am J Med Genet A. 2018;176(4):759\u201372.","journal-title":"Am J Med Genet A"},{"issue":"5","key":"641_CR36","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/j.jpeds.2004.01.046","volume":"144","author":"JE Wraith","year":"2004","unstructured":"Wraith JE, Clarke LA, Beck M, Kolodny EH, Pastores GM, Muenzer J, et al. Enzyme replacement therapy for mucopolysaccharidosis I: a randomized, double-blinded, placebo-controlled, multinational study of recombinant human alpha-L-iduronidase (laronidase). J Pediatr. 2004;144(5):581\u20138.","journal-title":"J Pediatr"},{"issue":"4","key":"641_CR37","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.2307\/2531158","volume":"40","author":"PC O'Brien","year":"1984","unstructured":"O\u2019Brien PC. Procedures for comparing samples with multiple endpoints. Biometrics. 1984;40(4):1079\u201387.","journal-title":"Biometrics"},{"issue":"2","key":"641_CR38","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1093\/biomet\/72.2.359","volume":"72","author":"LJ Wei","year":"1985","unstructured":"Wei LJ, Johnson WE. Combining dependent tests with incomplete repeated measurements. Biometrika. 1985;72(2):359\u201364.","journal-title":"Biometrika"},{"key":"641_CR39","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-023-02637-4","author":"ML Mauermann","year":"2023","unstructured":"Mauermann ML, Clarke JO, Litchy WJ, Obici L, Lousada I, Gertz MA, et al. Peripheral nervous, hepatic, and gastrointestinal endpoints for AL amyloidosis clinical trials: report from the amyloidosis forum multi-organ system working group. Adv Ther. 2023. https:\/\/doi.org\/10.1007\/s12325-023-02637-4.","journal-title":"Adv Ther"},{"issue":"6","key":"641_CR40","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.121.009038","volume":"15","author":"MS Maurer","year":"2022","unstructured":"Maurer MS, Dunnmon P, Fontana M, Quarta CC, Prasad K, Witteles RM, et al. Proposed cardiac end points for clinical trials in immunoglobulin light chain amyloidosis: report from the amyloidosis forum cardiac working group. Circ Heart Fail. 2022;15(6): e009038.","journal-title":"Circ Heart Fail"},{"key":"641_CR41","doi-asserted-by":"publisher","first-page":"153","DOI":"10.2147\/PROM.S399658","volume":"14","author":"AAWM Rizio","year":"2023","unstructured":"Rizio AAWM, D\u2019Souza A, Hsu K, Schmitt P, Quock TP, Signorovitch J, Lousada I, Sanchorawala V. Health-related quality of life instruments for clinical trials in AL amyloidosis: report from the amyloidosis forum HRQOL working group. Patient Relat Outcome Meas. 2023;14:153\u201369.","journal-title":"Patient Relat Outcome Meas"},{"issue":"1","key":"641_CR42","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/bimj.201400049","volume":"58","author":"M Buyse","year":"2016","unstructured":"Buyse M, Molenberghs G, Paoletti X, Oba K, Alonso A, Van der Elst W, et al. Statistical evaluation of surrogate endpoints with examples from cancer clinical trials. Biom J. 2016;58(1):104\u201332.","journal-title":"Biom J"},{"issue":"7","key":"641_CR43","doi-asserted-by":"publisher","first-page":"605","DOI":"10.7326\/0003-4819-125-7-199610010-00011","volume":"125","author":"TR Fleming","year":"1996","unstructured":"Fleming TR, DeMets DL. Surrogate end points in clinical trials: are we being misled? Ann Intern Med. 1996;125(7):605\u201313.","journal-title":"Ann Intern Med"},{"issue":"25","key":"641_CR44","doi-asserted-by":"publisher","first-page":"2973","DOI":"10.1002\/sim.5403","volume":"31","author":"TR Fleming","year":"2012","unstructured":"Fleming TR, Powers JH. Biomarkers and surrogate endpoints in clinical trials. Stat Med. 2012;31(25):2973\u201384.","journal-title":"Stat Med"},{"issue":"2","key":"641_CR45","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1111\/j.1541-0420.2008.01109.x","volume":"65","author":"D Ghosh","year":"2009","unstructured":"Ghosh D. On assessing surrogacy in a single trial setting using a semicompeting risks paradigm. Biometrics. 2009;65(2):521\u20139.","journal-title":"Biometrics"},{"issue":"4","key":"641_CR46","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1002\/sim.4780080407","volume":"8","author":"RL Prentice","year":"1989","unstructured":"Prentice RL. Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med. 1989;8(4):431\u201340.","journal-title":"Stat Med"},{"issue":"3","key":"641_CR47","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.2307\/2533853","volume":"54","author":"M Buyse","year":"1998","unstructured":"Buyse M, Molenberghs G. Criteria for the validation of surrogate endpoints in randomized experiments. Biometrics. 1998;54(3):1014\u201329.","journal-title":"Biometrics"},{"issue":"10","key":"641_CR48","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1002\/sim.1780","volume":"23","author":"VW Berger","year":"2004","unstructured":"Berger VW. Does the Prentice criterion validate surrogate endpoints? Stat Med. 2004;23(10):1571\u20138.","journal-title":"Stat Med"},{"issue":"1","key":"641_CR49","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1093\/biostatistics\/1.1.49","volume":"1","author":"M Buyse","year":"2000","unstructured":"Buyse M, Molenberghs G, Burzykowski T, Renard D, Geys H. The validation of surrogate endpoints in meta-analyses of randomized experiments. Biostatistics. 2000;1(1):49\u201367.","journal-title":"Biostatistics"},{"key":"641_CR50","unstructured":"Methods to Identify What is Important to Patients & Select, Develop or Modify Fit-for-Purpose Clinical Outcomes Assessments. Patient-focused Drug Development Guidance Public Workshop [Internet]. 2018. Available from: https:\/\/www.fda.gov\/media\/116277\/download."}],"container-title":["Therapeutic Innovation &amp; Regulatory Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-024-00641-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s43441-024-00641-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s43441-024-00641-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T19:07:56Z","timestamp":1718219276000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s43441-024-00641-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,17]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["641"],"URL":"https:\/\/doi.org\/10.1007\/s43441-024-00641-6","relation":{},"ISSN":["2168-4790","2168-4804"],"issn-type":[{"type":"print","value":"2168-4790"},{"type":"electronic","value":"2168-4804"}],"subject":[],"published":{"date-parts":[[2024,4,17]]},"assertion":[{"value":"28 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 March 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"James Signorovitch is an employee of Analysis Group, Inc., which has received consulting fees from ARC. Nicolae Done is an employee of Analysis Group, Inc., which has received consulting fees from ARC and all other authors have no conflict of interest to declare.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interests"}}]}}