{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:58:50Z","timestamp":1787029130623,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,2,2]],"date-time":"2025-02-02T00:00:00Z","timestamp":1738454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>The IPDfromKM method, or Shiny method, is an artificial intelligence tool that enables indirect comparisons between studies by reconstructing individual patient data (IPD) from Kaplan\u2013Meier (KM) curves. The IPDfromKM method is generally used for superiority analyses, but a further application could be represented by non-inferiority analyses. However, there are no studies supporting this methodological hypothesis. The aim of this work was to validate the IPDfromKM method for non-inferiority analyses by \u201cexploiting\u201d the well-described non-inferiority of implantable devices occluding the left atrial appendage compared to oral anticoagulants in patients with atrial fibrillation. We performed a systematic review searching for randomized controlled trials (RCTs) in the PubMed database and found five studies. The R software (version 4.3.3) was used to perform a standard survival analysis comparing Watchman and Amlet devices with warfarin. The hazard ratio (HR), with 95% confidence interval (CI), was the main parameter of our analysis. The results confirmed the non-inferiority of Amlet and Watchman compared to warfarin (HR of Watchman vs. warfarin: 1.23, 95% CI 0.80 to 1.9; HR of Amlet vs. warfarin: 1.05, 95% CI 0.61 to 1.80). Therefore, we proposed a new application of the IPDfromKM method that could be potentially relevant in decision-making for the management of this common cardiac arrhythmia and a wide range of other pathological conditions.<\/jats:p>","DOI":"10.3390\/mps8010013","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T04:36:51Z","timestamp":1738557411000},"page":"13","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The Reconstructed Individual Patient Data from Kaplan\u2013Meier (IPDfromKM) Method for Non-Inferiority Analyses: A New Potential Application"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6558-3065","authenticated-orcid":false,"given":"Eugenia","family":"Piragine","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"},{"name":"School of Specialization in Hospital Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Trippoli","sequence":"additional","affiliation":[{"name":"HTA Unit, Centro Operativo, Regione Toscana, Via Alderotti 26\/N, 50141 Firenze, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0278-9446","authenticated-orcid":false,"given":"Sara","family":"Veneziano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-107X","authenticated-orcid":false,"given":"Andrea","family":"Messori","sequence":"additional","affiliation":[{"name":"HTA Unit, Centro Operativo, Regione Toscana, Via Alderotti 26\/N, 50141 Firenze, Italy"},{"name":"Comitato Scientifico SIFaCT, Societ\u00e0 Italiana di Farmacia Clinica e Terapia, Via Guarini 4, 10123 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Calderone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, Via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Liu, N., Zhou, Y., and Lee, J.J. (2021). IPDfromKM: Reconstruct individual patient data from published Kaplan-Meier survival curves. BMC Med. Res. Methodol., 21.","DOI":"10.1186\/s12874-021-01308-8"},{"key":"ref_2","unstructured":"Messori, A. (2024). Reconstruction of individual-patient data from the analysis of Kaplan-Meier curves: This method is widely used in oncology and cardiology\u2014List of 53 studies in oncology and 61 in cardiology (preprint). Open Sci. Framew."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Zhang, S., Li, S., and Cheng, Y. (2024). The efficacy and safety of immunotherapy as first-line treatment for extensive-stage small cell lung cancer: Evaluating based on reconstructed individual patient data. Front. Oncol., 14.","DOI":"10.3389\/fonc.2024.1371313"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Wang, B.C., Fu, C., and Lin, G.H. (2023). The efficacy of adebrelimab compared with durvalumab and atezolizumab in untreated extensive-stage small-cell lung cancer: A survival analysis of reconstructed patient-level data. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1185577"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Guyot, P., Ades, A.E., Ouwens, M.J., and Welton, N.J. (2012). Enhanced secondary analysis of survival data: Reconstructing the data from published Kaplan-Meier survival curves. BMC Med. Res. Methodol., 12.","DOI":"10.1186\/1471-2288-12-9"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1177\/1536867X1801700402","article-title":"Reconstructing time-to-event data from published Kaplan-Meier curves","volume":"17","author":"Wei","year":"2017","journal-title":"Stata J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"23814683221077643","DOI":"10.1177\/23814683221077643","article-title":"A Method for Reconstructing Individual Patient Data From Kaplan-Meier Survival Curves That Incorporate Marked Censoring Times","volume":"7","author":"Rogula","year":"2022","journal-title":"MDM Policy Pract."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Piragine, E., Veneziano, S., Trippoli, S., Messori, A., and Calderone, V. (2024). Efficacy and Safety of Cardioband in Patients with Tricuspid Regurgitation: Systematic Review and Meta-Analysis of Single-Arm Trials and Observational Studies. J. Clin. Med., 13.","DOI":"10.3390\/jcm13216393"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Ossato, A., Gasperoni, L., Del Bono, L., Messori, A., and Damuzzo, V. (2024). Efficacy of Immune Checkpoint Inhibitors vs. Tyrosine Kinase Inhibitors\/Everolimus in Adjuvant Renal Cell Carcinoma: Indirect Comparison of Disease-Free Survival. Cancers, 16.","DOI":"10.3390\/cancers16030557"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Peng, T.R., Wu, T.W., Yi, T.Y., and Wu, A.J. (2024). Comparative Efficacy of Adagrasib and Sotorasib in KRAS G12C-Mutant NSCLC: Insights from Pivotal Trials. Cancers, 16.","DOI":"10.3390\/cancers16213676"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tcm.2022.04.008","article-title":"Late outcomes of transcatheter aortic valve implantation in bicuspid versus tricuspid valves: Meta-analysis of reconstructed time-to-event data","volume":"33","author":"Jacquemyn","year":"2023","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Wach, J., Vychopen, M., G\u00fcresir, A., Guranda, A., Nestler, U., and G\u00fcresir, E. (2024). A Long-Term Comparative Analysis of Endovascular Coiling and Clipping for Ruptured Cerebral Aneurysms: An Individual Patient-Level Meta-Analysis Assessing Rerupture Rates. J. Clin. Med., 13.","DOI":"10.3390\/jcm13061778"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1186\/s13643-019-1032-6","article-title":"Individual participant data (IPD)-level meta-analysis of randomised controlled trials among dark-skinned populations to estimate the dietary requirement for vitamin D","volume":"8","author":"Cashman","year":"2019","journal-title":"Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e034815","DOI":"10.1161\/JAHA.124.034815","article-title":"Left Atrial Appendage Closure Compared with Oral Anticoagulants for Patients with Atrial Fibrillation: A Systematic Review and Network Meta-Analysis","volume":"13","author":"Oliva","year":"2024","journal-title":"J. Am. Heart Assoc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.7861\/clinmed.2023-23.5.Cardio2","article-title":"Atrial fibrillation: A contemporary update","volume":"23","author":"Saleh","year":"2023","journal-title":"Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"102181","DOI":"10.1016\/j.cpcardiol.2023.102181","article-title":"Atrial fibrillation and stroke: State-of-the-art and future directions","volume":"49","author":"Elsheikh","year":"2024","journal-title":"Curr. Probl. Cardiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.ccep.2020.11.003","article-title":"Atrial Fibrillation and Stroke","volume":"13","author":"Essa","year":"2021","journal-title":"Card. Electrophysiol. Clin."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e034778","DOI":"10.1136\/bmjopen-2019-034778","article-title":"Adherence to oral anticoagulants among patients with atrial fibrillation: A systematic review and meta-analysis of observational studies","volume":"10","author":"Salmasi","year":"2020","journal-title":"BMJ Open"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s40266-024-01138-5","article-title":"Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Decade of Experience","volume":"41","author":"Spruit","year":"2024","journal-title":"Drugs Aging"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1080\/17425255.2021.1965124","article-title":"Strategies for the prevention and treatment of bleeding in patients treated with dabigatran: An update","volume":"17","author":"Xu","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"f20","DOI":"10.1093\/ehjcvp\/pvz073","article-title":"Safety and efficacy of non-vitamin K antagonist oral anticoagulants in elderly patients with atrial fibrillation: Systematic review and meta-analysis of 22 studies and 440\u2009281 patients","volume":"7","author":"Silverio","year":"2021","journal-title":"Eur. Heart J. Cardiovasc. Pharmacother."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12325-022-02333-9","article-title":"Risk and Management of Bleeding Complications with Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Venous Thromboembolism: A Narrative Review","volume":"40","author":"Ballestri","year":"2023","journal-title":"Adv. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/clc.23956","article-title":"Clinical efficacy and safety comparison of Watchman device versus ACP\/Amulet device for percutaneous left atrial appendage closure in patients with nonvalvular atrial fibrillation: A study-level meta-analysis of clinical trials","volume":"46","author":"Bing","year":"2023","journal-title":"Clin. Cardiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.jjcc.2022.11.006","article-title":"Left atrial appendage closure for stroke prevention in nonvalvular atrial fibrillation: A current overview","volume":"81","author":"Ueno","year":"2023","journal-title":"J. Cardiol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Damuzzo, V., Agnoletto, L., Leonardi, L., Chiumente, M., Mengato, D., and Messori, A. (2019). Analysis of Survival Curves: Statistical Methods Accounting for the Presence of Long-Term Survivors. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00453"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1007\/s11606-010-1513-8","article-title":"Understanding equivalence and noninferiority testing","volume":"26","author":"Walker","year":"2011","journal-title":"J. Gen. Intern. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1161\/CIRCULATIONAHA.123.067599","article-title":"One-Year Outcomes After Amulet or Watchman Device for Percutaneous Left Atrial Appendage Closure: A Prespecified Analysis of the SWISS-APERO Randomized Clinical Trial","volume":"149","author":"Galea","year":"2024","journal-title":"Circulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacc.2014.04.029","article-title":"Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: The PREVAIL trial","volume":"64","author":"Holmes","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/j.jcin.2023.06.022","article-title":"3-Year Outcomes From the Amplatzer Amulet Left Atrial Appendage Occluder Randomized Controlled Trial (Amulet IDE)","volume":"16","author":"Lakkireddy","year":"2023","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10840-021-01002-1","article-title":"One year outcome and analysis of peri-device leak of left atrial appendage occlusion devices","volume":"64","author":"Mansour","year":"2022","journal-title":"J. Interv. Card. Electrophysiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1161\/CIRCULATIONAHA.112.114389","article-title":"Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-Year Follow-up of the PROTECT AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) Trial","volume":"127","author":"Reddy","year":"2013","journal-title":"Circulation"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e38","DOI":"10.1016\/j.hlc.2023.12.023","article-title":"Transcatheter Versus Surgical Aortic Valve Replacement in Patients at Low Risk: Long-Term Outcomes From the Three Pivotal Randomised Trials Determined by Reconstruction of Individual Patient Data From Kaplan-Meier Curves","volume":"33","author":"Messori","year":"2024","journal-title":"Heart Lung Circ."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3470","DOI":"10.1093\/eurheartj\/ehw048","article-title":"Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation","volume":"37","author":"Panikker","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1925","DOI":"10.1016\/j.jcin.2015.08.035","article-title":"Bleeding Outcomes After Left Atrial Appendage Closure Compared with Long-Term Warfarin: A Pooled, Patient-Level Analysis of the WATCHMAN Randomized Trial Experience","volume":"8","author":"Price","year":"2015","journal-title":"JACC Cardiovasc. Interv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ahj.2021.08.020","article-title":"Left atrial appendage occlusion vs novel oral anticoagulation for stroke prevention in atrial fibrillation: Rationale and design of the multicenter randomized occlusion-AF trial","volume":"243","author":"Korsholm","year":"2022","journal-title":"Am. Heart J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacc.2021.10.023","article-title":"4-Year Outcomes After Left Atrial Appendage Closure Versus Nonwarfarin Oral Anticoagulation for Atrial Fibrillation","volume":"79","author":"Osmancik","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.ahj.2022.05.003","article-title":"Comparison of anticoagulation with left atrial appendage closure after atrial fibrillation ablation: Rationale and design of the OPTION randomized trial","volume":"251","author":"Wazni","year":"2022","journal-title":"Am. Heart J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1016\/j.jacc.2020.04.067","article-title":"Left Atrial Appendage Closure Versus Direct Oral Anticoagulants in High-Risk Patients with Atrial Fibrillation","volume":"75","author":"Osmancik","year":"2020","journal-title":"J. Am. Coll. Cardiol."}],"container-title":["Methods and Protocols"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-9279\/8\/1\/13\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:25:53Z","timestamp":1760027153000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-9279\/8\/1\/13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,2]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["mps8010013"],"URL":"https:\/\/doi.org\/10.3390\/mps8010013","relation":{},"ISSN":["2409-9279"],"issn-type":[{"value":"2409-9279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,2]]}}}