Using the Restricted Mean Survival Time Difference as an Alternative to the Hazard Ratio for Analyzing Clinical Cardiovascular Studies
2019; Lippincott Williams & Wilkins; Volume: 140; Issue: 17 Linguagem: Inglês
10.1161/circulationaha.119.040680
ISSN1524-4539
AutoresZachary R. McCaw, Guosheng Yin, Lee‐Jen Wei,
Tópico(s)Statistical Methods in Clinical Trials
ResumoHomeCirculationVol. 140, No. 17Using the Restricted Mean Survival Time Difference as an Alternative to the Hazard Ratio for Analyzing Clinical Cardiovascular Studies Free AccessArticle CommentaryPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessArticle CommentaryPDF/EPUBUsing the Restricted Mean Survival Time Difference as an Alternative to the Hazard Ratio for Analyzing Clinical Cardiovascular Studies Zachary R. McCaw, PhD, Guosheng Yin, PhD and Lee-Jen Wei, PhD Zachary R. McCawZachary R. McCaw Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (Z.R.M., L.J.W.). , Guosheng YinGuosheng Yin Department of Statistics and Actuarial Science, The University of Hong Kong, China (G.Y.). and Lee-Jen WeiLee-Jen Wei Lee-Jen Wei, PhD, 655 Huntington Ave, Boston, MA 02115. Email E-mail Address: [email protected] Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA (Z.R.M., L.J.W.). Originally published21 Oct 2019https://doi.org/10.1161/CIRCULATIONAHA.119.040680Circulation. 2019;140:1366–1368Cardiovascular trials often use the time to a clinical event as the primary end point when evaluating a new treatment, versus control, via clinical and statistical significance criteria. For the past 50 years, the hazard ratio (HR) has been routinely used for quantifying the treatment effect. However, it is difficult to interpret clinical significance using a ratio measure, such as HR, when there is no reference hazard available from the control arm. Moreover, valid HR analysis requires the proportional hazards (PH) assumption: that the ratio of hazard curves is constant over time. This assumption is hardly plausible in practice. When PH is not met, HR may lack statistical power to detect a true treatment effect. Furthermore, without PH, the estimated HR is not a simple average of HRs over time, and is even more difficult to interpret.1,2 In this article, we discuss the advantages of an alternative analytical procedure based on the restricted mean survival time (RMST)1,2 via 3 examples.The first example comes from the CHARM-Overall (Candesartan in Heart Failure–Assessment of Mortality and Morbidity–Overall) trial, which evaluated the effect of candesartan on all-cause mortality in patients with chronic heart failure.3 The HR (candesartan vs placebo) of 0.91 (95% CI, 0.83–1.00; P=0.055) did not provide strong statistical evidence of a benefit from candesartan. Moreover, it is unclear whether a HR of 0.91 is clinically significant. This does not suggest that candesartan reduced the risk of mortality by 9% versus placebo, because the hazard is not a probability measure like risk. To explore whether HR analysis was appropriate, we reconstructed patient-level survival data from the Kaplan–Meier curves presented in the CHARM-Overall article.3 Here, the reconstructed Kaplan–Meier curves are presented in Figure, A. Because the Kaplan–Meier curves separate initially but remain parallel after 0.5 years, the PH assumption was not met, as was confirmed via the Schoenfeld goodness-of-fit test (P=0.0005).Download figureDownload PowerPointFigure. Reconstructed Kaplan–Meier curves.A, Overall survival comparing candesartan with placebo from the study by Pfeffer and colleagues.3B, RMST as the area under the Kaplan–Meier curve up to 3.5 years of follow-up for patients receiving candesartan. C, MACE-free survival comparing new and early generation stents from the study by Kufner and colleagues.4D, Survival without target vessel failure comparing biodegradable and durable stents from the study by von Birgelen and colleagues.5 MACE indicates major adverse cardiac event.An alternative is to use the difference in RMSTs to quantify the treatment effect. RMST is the average time-to-event over a fixed follow-up period (for example, 3.5-years in Figure, A). Graphically, RMST corresponds to the area under the survival curve. The higher the curve, the greater the RMST. As presented in Figure, B, the area under the curve for candesartan was 3.07 years. That is, across 3.5 years of follow-up, patients treated with candesartan survived for 3.07 years on average. The corresponding RMST for placebo was 3.00 years. The difference of 0.07 years (95% CI, 0.03–0.11; P=0.0016) was highly statistically significant in favor of candesartan. This example demonstrates that RMST can be more statistically efficient than HR when PH is not met. After passing the statistical significance hurdle, the clinical utility of candesartan can be evaluated using individual RMSTs (3.07 and 3.00 years). For the present case, it is debatable whether the 0.07-year (3.6-week) survival gain is clinically significant. A limitation of RMST-based analysis is the need to specify a truncation time. Ideally, this would be prespecified via clinical considerations during study design. Otherwise, one can choose the last observed event or censoring time, which here was at 3.5 years. With this choice, RMST incorporates all available information.For the second example, we show that if HR identifies a statistically significant treatment effect, then so too does RMST. Consider a recent study4 comparing new and early generation sirolimus-eluting stents among patients with coronary artery disease. The primary outcome was time to a major adverse cardiac event. The HR was 0.82 (95% CI, 0.71-0.93), which significantly favored new generation stents. Using the reconstructed time-to-event data in the Figure (C), the 10-year RMSTs were 7.07 years and 6.57 years for new and early generation stents, respectively. The difference of 0.50 years (95% CI, 0.13–0.86; P=0.01) also significantly favored new generation stents. In general, RMST procedures do not result in any power loss versus HR, and beyond the statistical evaluation, provide valuable insight on the clinical utility of the new stents.For the third example, we demonstrate the utility of RMST for noninferiority studies. It is known that the HR's precision depends on the number of observed events, but not on patients' exposure times. Consequently, for noninferiority trials where the event rate is low, HR-based designs may require large numbers of patients. Consider a recent noninferiority study5 comparing 3 types of stents with time to target vessel failure as the primary end point. For evaluating biodegradable everolimus-eluting stents versus durable zotarolimus-eluting stents (n=2345), the HR (biodegradable vs durable) was 0.87 (95% CI, 0.61–1.25). The CI upper bound of 1.25 suggests that biodegradable stents may actually increase the hazard of target vessel failure by 25%. Using the reconstructed Kaplan–Meier curves in the Figure (D), the 12-month RMSTs were 11.41 and 11.36 months for biodegradable and durable stents, respectively. The difference was 1.80 days (95% CI, −3.40 to 6.99). Thus, in the worst case, biodegradable stents may shorten the time-to-failure by 3.40 days. This time-scale quantification is much easier to interpret than HR. For this noninferiority study, the important consideration is whether 12-month follow-up is sufficiently long to evaluate the performance of the stents. In contrast to evaluating superiority, the number of observed events is not crucial for assessing noninferiority.2 To show that RMST may allow one to reduce the study size without losing much precision, we repeatedly drew random subsets with 50% of the data (n=1173) and calculated CIs for the HR and RMST difference. With 100 random subsamples, the average upper bound for the HR increased to 1.49, which seems much higher than 1.25. Thus, a smaller size study may not be justifiable when using HR. On the other hand, with the reduced study size, biodegradable stents would in the worst case shorten the time-to-failure by 5.66 days, which is only slightly higher than 3.40 days. This result suggests that a smaller study may have been justified for assessing noninferiority. When designing a noninferiority study with an appropriate, prespecified exposure time, using RMST to set the noninferiority margin is efficient and heuristically easy to justify.In conclusion, RMST is a powerful, robust, and interpretable tool for the design and analysis of clinical studies. All analyses presented herein can be implemented via the survRM2 package in R, or the RMSTREG proc in SAS.DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.https://www.ahajournals.org/journal/circLee-Jen Wei, PhD, 655 Huntington Ave, Boston, MA 02115. Email [email protected]harvard.eduReferences1. Kim DH, Uno H, Wei LJ. Restricted mean survival time as a measure to interpret clinical trial results.JAMA Cardiol. 2017; 2:1179–1180. doi: 10.1001/jamacardio.2017.2922CrossrefMedlineGoogle Scholar2. Uno H, Wittes J, Fu H, Solomon SD, Claggett B, Tian L, Cai T, Pfeffer MA, Evans SR, Wei LJ. Alternatives to hazard ratios for comparing the efficacy or safety of therapies in noninferiority studies.Ann Intern Med. 2015; 163:127–134. doi: 10.7326/M14-1741CrossrefMedlineGoogle Scholar3. Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Pocock S; CHARM Investigators and Committees. Effects of candesartan on mortality and morbidity in patients with chronic heart failure: the CHARM-Overall programme.Lancet. 2003; 362:759–766. doi: 10.1016/s0140-6736(03)14282-1CrossrefMedlineGoogle Scholar4. Kufner S, Joner M, Thannheimer A, Hoppmann P, Ibrahim T, Mayer K, Cassese S, Laugwitz KL, Schunkert H, Kastrati A, et al; ISAR-TEST 4 (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting Stents) Investigators. Ten-year clinical outcomes from a trial of three limus-eluting stents with different polymer coatings in patients with coronary artery disease.Circulation. 2019; 139:325–333. doi: 10.1161/CIRCULATIONAHA.118.038065LinkGoogle Scholar5. von Birgelen C, Kok MM, van der Heijden LC, Danse PW, Schotborgh CE, Scholte M, Gin RMTJ, Somi S, van Houwelingen KG, Stoel MG, et al. Very thin strut biodegradable polymer everolimus-eluting and sirolimus-eluting stents versus durable polymer zotarolimus-eluting stents in allcomers with coronary artery disease (BIO-RESORT): a three-arm, randomised, noninferiority trial.Lancet. 2016; 388:2607–2617. doi: 10.1016/S0140-6736(16)31920-1CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByMilioglou I, Motairek I, Deo S, Ramani R, Neeland I, Rajagopalan S and Al-Kindi S (2023) Time-Varying Cardiovascular Outcomes of Sodium-Glucose Cotransporter Inhibitors in Patients With Type 2 Diabetes: A Post Hoc Analysis of Pivotal Trials Using Restricted Mean Survival Time, Circulation: Cardiovascular Quality and Outcomes, 16:3, (e009491), Online publication date: 1-Mar-2023. Wang X, Claggett B, Tian L, Malachias M, Pfeffer M and Wei L (2023) Quantifying and Interpreting the Prediction Accuracy of Models for the Time of a Cardiovascular Event—Moving Beyond C Statistic, JAMA Cardiology, 10.1001/jamacardio.2022.5279, 8:3, (290), Online publication date: 1-Mar-2023. Hamaya R, Yonetsu T, Aoyama N, Shiheido‐Watanabe Y, Tashiro A, Niida T, Isobe M, Maejima Y, Iwata T and Sasano T (2023) Contribution of periodontal health in cardiovascular secondary prevention: Analyses on hospitalized patients in cardiology units, Journal of Clinical Periodontology, 10.1111/jcpe.13792 Liu S, Wu Q, Zhang S, Wang Z, Liu H, Teng L, Xiao P, Lu Y, Wang X, Dong C, Xiao J and Zhang J (2022) Serum Galectin-3 levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study, BMC Nephrology, 10.1186/s12882-021-02636-z, 23:1, Online publication date: 1-Dec-2022. Miyagawa S, Kainuma S, Imanishi Y, Shimamoto T, Nitta Y, Matsuo C, Sakata Y, Takeuchi M and Sawa Y (2022) Prognosis of Patients With Heart Failure Receiving Autologous Myoblast Patches ― Comparison of Single-Arm Trial Data to Registry Data ―, Circulation Journal, 10.1253/circj.CJ-22-0319, Online publication date: 15-Nov-2022. Mao L (2022) Power and Sample Size Calculations for the Restricted Mean Time Analysis of Prioritized Composite Endpoints, Statistics in Biopharmaceutical Research, 10.1080/19466315.2022.2110936, (1-9) Hardin C, Claggett B, McCaw Z, Tian L, McMurray J, Jhund P, Uno H, Pfeffer M, Solomon S and Wei L (2022) Quantifying Treatment Effects in Trials with Multiple Event-Time Outcomes, NEJM Evidence, 10.1056/EVIDoa2200047, 1:10, Online publication date: 27-Sep-2022. Apiyasawat S, Thongsri T, Jongpiputvanich K and Krittayaphong R (2022) Outcome disparities in patients with atrial fibrillation based on insurance plan and educational attainment: a nationwide, multicenter and prospective cohort trial, BMJ Open, 10.1136/bmjopen-2021-053166, 12:8, (e053166), Online publication date: 1-Aug-2022. Chew N, Ng C, Kong G, Lee K, Tan D, Lim O, Chin Y, Tai B, Gu T, Park S, Park D, Morice M, Kofidis T, Yip J, Loh P, Chan K, Low A, Lee C, Yeo T, Tan H and Chan M (2022) Meta-Analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Narrowing, The American Journal of Cardiology, 10.1016/j.amjcard.2022.02.044, 173, (39-47), Online publication date: 1-Jun-2022. Jeong D, Lee G, Park J, Chang H, Kim T, Cha W, Yoon H, Hwang S, Shin T, Sim M, Jo I, Lee S, Shin S and Choi J (2022) Extracorporeal Life-support for Out-of-hospital Cardiac Arrest: A Nationwide Multicenter Study, Shock, 10.1097/SHK.0000000000001924, 57:5, (680-686), Online publication date: 1-May-2022. Ye X, Oktay M, Xue X, Rohan T, Ginter P, D'Alfonso T, Kornaga E, Morris D, Entenberg D and Condeelis J (2022) Combining TMEM Doorway Score and MenaCalc Score Improves the Prediction of Distant Recurrence Risk in HR+/HER2− Breast Cancer Patients, Cancers, 10.3390/cancers14092168, 14:9, (2168) Zhang B, Cai Y and Yang J (2022) Liver Transplant for Alcohol-Associated Liver Disease, JAMA Surgery, 10.1001/jamasurg.2021.6550, 157:4, (360), Online publication date: 1-Apr-2022. McCaw Z, Claggett B, Tian L, Solomon S, Berwanger O, Pfeffer M and Wei L (2022) Practical Recommendations on Quantifying and Interpreting Treatment Effects in the Presence of Terminal Competing Risks, JAMA Cardiology, 10.1001/jamacardio.2021.4932, 7:4, (450), Online publication date: 1-Apr-2022. Kitano T, Hori Y, Okazaki S, Shimada Y, Iwamoto T, Kanki H, Sugiyama S, Sasaki T, Nakamura H, Oyama N, Hoshi T, Beck G, Takai H, Matsubara S, Mizuno H, Nishimura H, Tamaki R, Iida J, Iba J, Uno M, Kishima H, Fushimi H, Hattori S, Murayama S, Morii E, Sakaguchi M, Yagita Y, Shimazu T, Mochizuki H and Todo K (2021) An Older Thrombus Delays Reperfusion after Mechanical Thrombectomy for Ischemic Stroke, Thrombosis and Haemostasis, 10.1055/a-1522-4507, 122:03, (415-426), Online publication date: 1-Mar-2022. Duan L, Zhang B, Liao J and Zheng X (2022) Iodized oil CT-guided radiofrequency ablation for hepatocellular carcinoma within Milan criteria, Hepatology International, 10.1007/s12072-021-10274-8, 16:1, (207-208), Online publication date: 1-Feb-2022. Rossello X and González-Del-Hoyo M (2022) Análisis de supervivencia en investigación cardiovascular (II): metodología estadística en situaciones complejas, Revista Española de Cardiología, 10.1016/j.recesp.2021.06.027, 75:1, (77-85), Online publication date: 1-Jan-2022. Rossello X and González-Del-Hoyo M (2022) Survival analyses in cardiovascular research, part II: statistical methods in challenging situations, Revista Española de Cardiología (English Edition), 10.1016/j.rec.2021.07.001, 75:1, (77-85), Online publication date: 1-Jan-2022. Zhou S, Zeng Z, Wei H, Sha T and An S (2021) Early combination of albumin with crystalloids administration might be beneficial for the survival of septic patients: a retrospective analysis from MIMIC-IV database, Annals of Intensive Care, 10.1186/s13613-021-00830-8, 11:1, Online publication date: 1-Dec-2021. Hamaya R, Chang Y, Chewcharat A, Chiu N, Yonetsu T, Kakuta T and Papatheodorou S (2021) Comparison of invasive treatment strategies in patients with non–ST elevation acute coronary syndrome: A systematic review and meta-analysis, JTCVS Open, 10.1016/j.xjon.2021.08.028, 8, (323-335), Online publication date: 1-Dec-2021. Mao L (2021) On restricted mean time in favor of treatment, Biometrics, 10.1111/biom.13570 Liu K, Peng P, Cai F and Huang J (2020) Comparison of the long-term efficacy between tenofovir and entecavir in chronic hepatitis B patients, Gut, 10.1136/gutjnl-2020-322642, 70:8, (1599-1600), Online publication date: 1-Aug-2021. Kuno T, Ikemura N and Kohsaka S (2021) Letter by Kuno et al Regarding Article, "Heart Team/Guidelines Discordance Is Associated With Increased Mortality: Data From a National Survey of Revascularization in Patients With Complex Coronary Artery Disease", Circulation: Cardiovascular Interventions, 14:7, (e010649), Online publication date: 1-Jul-2021. Zhuang B, Li W, Wang W, Li B, Lu M, Kuang M, Xie X and Xie X (2021) Treatment effect of radiofrequency ablation versus liver transplantation and surgical resection for hepatocellular carcinoma within Milan criteria: a population-based study, European Radiology, 10.1007/s00330-020-07551-9, 31:7, (5379-5389), Online publication date: 1-Jul-2021. Messori A, Bartoli L and Trippoli S (2021) The restricted mean survival time as a replacement for the hazard ratio and the number needed to treat in long‐term studies, ESC Heart Failure, 10.1002/ehf2.13306, 8:3, (2345-2348), Online publication date: 1-Jun-2021. Messori A, Bartoli L, Chiumente M, Mengato D and Trippoli S (2020) The Restricted Mean Survival Time as a Tool for Ranking Comparative Outcomes in a Narrative Review that Evaluates a Network of Randomized Trials: An Example Based on PCSK9 Inhibitors, American Journal of Cardiovascular Drugs, 10.1007/s40256-020-00444-8, 21:3, (349-354), Online publication date: 1-May-2021. Freidlin B, Hu C and Korn E (2021) Are restricted mean survival time methods especially useful for noninferiority trials?, Clinical Trials, 10.1177/1740774520976576, 18:2, (188-196), Online publication date: 1-Apr-2021. Hu Z, Li S, Yang A, Li W, Xiong X, Hu J, Jiang J and Song X (2020) Delayed hospital admission and high-dose corticosteroids potentially prolong SARS-CoV-2 RNA detection duration of patients with COVID-19, European Journal of Clinical Microbiology & Infectious Diseases, 10.1007/s10096-020-04085-2, 40:4, (841-848), Online publication date: 1-Apr-2021. Rivano M, Cancanelli L, Spazio L, Chiumente M, Mengato D and Messori A (2021) Restricted mean survival time as outcome measure in advanced urothelial bladder cancer: analysis of 4 clinical studies, Immunotherapy, 10.2217/imt-2020-0160, 13:2, (95-101), Online publication date: 1-Feb-2021. Fu E, Evans M, Clase C, Tomlinson L, van Diepen M, Dekker F and Carrero J (2020) Stopping Renin-Angiotensin System Inhibitors in Patients with Advanced CKD and Risk of Adverse Outcomes: A Nationwide Study, Journal of the American Society of Nephrology, 10.1681/ASN.2020050682, 32:2, (424-435), Online publication date: 1-Feb-2021. Zhou J, Zhang Q and Liu X (2020) Regarding 'moderate to severe hyperphosphataemia as an independent prognostic factor for 28-day mortality in adult patients with sepsis', Emergency Medicine Journal, 10.1136/emermed-2020-210598, 38:2, (166-166), Online publication date: 1-Feb-2021. McCaw Z, Fitzmaurice G and Wei L (2020) Letter by McCaw et al Regarding Article, "The COMPASS Trial: Net Clinical Benefit of Low-Dose Rivaroxaban Plus Aspirin as Compared With Aspirin in Patients With Chronic Vascular Disease", Circulation, 143:1, (e1-e2), Online publication date: 5-Jan-2021. Zhou J, Zhang Q and Liu X (2021) Letter to the editor regarding "the prognostic role of mid-range ejection fraction in ST-segment elevation myocardial infarction", International Journal of Cardiology, 10.1016/j.ijcard.2020.08.082, 322, (53), Online publication date: 1-Jan-2021. Guimarães H, de Barros e Silva P, Liporace I, Sampaio R, Tarasoutchi F, Paixão M, Hoffmann-Filho C, Patriota R, Leiria T, Lamprea D, Precoma D, Atik F, Silveira F, Farias F, Barreto D, Almeida A, Zilli A, de Souza Neto J, Cavalcante M, Figueira F, Junior R, Moisés V, Mesas C, Ardito R, Kalil P, Paiva M, Maldonado J, de Lima C, D'Oliveira Vieira R, Laranjeira L, Kojima F, Damiani L, Nakagawa R, dos Santos J, Sampaio B, Campos V, Saraiva J, Fonseca F, Pinto I, Magalhães C, Ferreira J, Lopes R, Pavanello R, Cavalcanti A and Berwanger O (2021) A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial, American Heart Journal, 10.1016/j.ahj.2020.10.001, 231, (128-136), Online publication date: 1-Jan-2021. Perego C, Sbolli M, Specchia C, Fiuzat M, McCaw Z, Metra M, Oriecuia C, Peveri G, Wei L, O'Connor C and Psotka M (2020) Utility of Restricted Mean Survival Time Analysis for Heart Failure Clinical Trial Evaluation and Interpretation, JACC: Heart Failure, 10.1016/j.jchf.2020.07.005, 8:12, (973-983), Online publication date: 1-Dec-2020. Guimarães H, Lopes R, de Barros e Silva P, Liporace I, Sampaio R, Tarasoutchi F, Hoffmann-Filho C, de Lemos Soares Patriota R, Leiria T, Lamprea D, Precoma D, Atik F, Silveira F, Farias F, Barreto D, Almeida A, Zilli A, de Souza Neto J, Cavalcante M, Figueira F, Kojima F, Damiani L, Santos R, Valeis N, Campos V, Saraiva J, Fonseca F, Pinto I, Magalhães C, Ferreira J, Alexander J, Pavanello R, Cavalcanti A and Berwanger O (2020) Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve, New England Journal of Medicine, 10.1056/NEJMoa2029603, 383:22, (2117-2126), Online publication date: 26-Nov-2020. Kuno T, Takahashi M and Hamaya R (2020) The Randomized TIDES-ACS Trial, JACC: Cardiovascular Interventions, 10.1016/j.jcin.2020.08.004, 13:20, (2444), Online publication date: 1-Oct-2020. (2020) Remdesivir for the Treatment of Covid-19 — Preliminary Report, New England Journal of Medicine, 10.1056/NEJMc2022236, 383:10, (992-994), Online publication date: 3-Sep-2020. Bartoli L and Messori A (2020) Outcomes in patients with spinal muscular atrophy given nusinersen, onasemnogene abeparvovec or no treatment: an analysis based on restricted mean survival time, Expert Opinion on Orphan Drugs, 10.1080/21678707.2020.1802719, 8:8, (303-307), Online publication date: 2-Aug-2020. Messori A, Damuzzo V, Leonardi L, Agnoletto L, Chiumente M and Mengato D (2020) CAR-T Treatment: Determining the Survival Gain in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma, Clinical Lymphoma Myeloma and Leukemia, 10.1016/j.clml.2020.02.007, 20:7, (490-491), Online publication date: 1-Jul-2020. Hasegawa T, Misawa S, Nakagawa S, Tanaka S, Tanase T, Ugai H, Wakana A, Yodo Y, Tsuchiya S and Suganami H (2020) Restricted mean survival time as a summary measure of time‐to‐event outcome, Pharmaceutical Statistics, 10.1002/pst.2004, 19:4, (436-453), Online publication date: 1-Jul-2020. Messori A (2020) CAR‐T treatment: Determining the progression‐free survival gain in patients with heavily pretreated multiple myeloma, eJHaem, 10.1002/jha2.63, 1:1, (371-373), Online publication date: 1-Jul-2020. Messori A, Chiumente M and Mengato D (2020) Axicabtagene ciloleucel in non-Hodgkin lymphoma: the restricted mean survival time as a tool for estimating progression-free life expectancy better than the median, Therapeutic Advances in Medical Oncology, 10.1177/1758835920930643, 12, (175883592093064), Online publication date: 1-Jan-2020. Chiumente M, Mengato D and Messori A (2020) Tisagenlecleucel in Non-Hodgkin Lymphoma: The Restricted Mean Survival Time as a Tool for Estimating Progression-Free Life Expectancy Better than the Median, Acta Haematologica, 10.1159/000505891, 143:6, (598-599), . October 22, 2019Vol 140, Issue 17 Advertisement Article InformationMetrics © 2019 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.119.040680PMID: 31634007 Originally publishedOctober 21, 2019 Keywordsheart failureprobabilityfollow-up studiescoronary artery diseasePDF download Advertisement SubjectsClinical Studies
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