Alternative Analysis Methods for Time to Event Endpoints Under Nonproportional Hazards: A Comparative Analysis
Ray S. Lin,Ji Lin,Satrajit Roychoudhury,Keaven M. Anderson,Tianle Hu,Bo Huang,Larry Leon,Jason J. Z. Liao,Rong Liu,Xiaodong Luo,Pralay Mukhopadhyay,Rui Qin,Kay Tatsuoka,Xuejing Wang,Yang Wang,Jian Zhu,Tai-Tsang Chen,Renee Iacona +17 more
TLDR
The log-rank test is most powerful under proportional hazards (PH) as mentioned in this paper, however, non-PH patterns are often observed in clinical trials, such as in immuno-oncology; therefore, alternative methods ar...Abstract:
The log-rank test is most powerful under proportional hazards (PH). In practice, non-PH patterns are often observed in clinical trials, such as in immuno-oncology; therefore, alternative methods ar...read more
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Journal ArticleDOI
Durvalumab alone and durvalumab plus tremelimumab versus chemotherapy in previously untreated patients with unresectable, locally advanced or metastatic urothelial carcinoma (DANUBE): a randomised, open-label, multicentre, phase 3 trial
Thomas Powles,Michiel S. van der Heijden,Daniel Castellano,Matthew D. Galsky,Yohann Loriot,Daniel P. Petrylak,Osamu Ogawa,Se Hoon Park,Jae-Lyun Lee,Ugo De Giorgi,Martin Bögemann,Aristotelis Bamias,Bernhard J. Eigl,Howard Gurney,Som D. Mukherjee,Yves Fradet,Iwona Skoneczna,Marinos Tsiatas,Andrey Novikov,Cristina Suarez,Andre P. Fay,Ignacio Duran,Andrea Necchi,Sophie Wildsmith,Philip He,Natasha Angra,Ashok K. Gupta,Wendy Levin,Joaquim Bellmunt,Jae-Lyun Lee,Hans Westgeest,Aude Flechon,Yen-Chuan Ou,Inkeun Park,Vsevolod Matveev,Begoña Perez-Valderrama,Susanna Cheng,Stephen Jay Frank,Urbano Anido,Alketa Hamzaj,Margitta Retz,Srikala S. Sridhar,Giorgio V. Scagliotti,Jens Voortman,Boris Alekseev,Anna Alyasova,Boris Komyakov,Herlinde Dumez,Michel Pavic,Go Kimura,Atsushi Mizokami,Susanne Osanto,Jose Angel Arranz,Djura Piersma,Sang Joon Shin,Oleg Karyakin,Ignacio Delgado,Jose Luis Gonzalez,See-Tong Pang,Anna Tran,Oleg Lipatov,Wen Pin Su,Thomas W. Flaig,Ajjai Alva,Hwa Park Kyong,Evgeny Kopyltsov,Elena Almagro,Monserrat Domenech,Yen-Hwa Chang,Brieuc Sautois,Andre Ravaux,Gerasimos Aravantinos,Vasileios Georgoulias,Sasja Mulder,Yu Jung Kim,Fabio Kater,Christine Chevreau,Scott T. Tagawa,Pawel Zalewski,Florence Joly,Gencay Hatiboglu,Luca Gianni,Franco Morelli,Rosa Tambaro,Yasuhiro Hashimoto,Alexander Nosov,Albert Font,Alejo Rodriguez-Vida,Robert Jones,Naveen S. Vasudev,Sandhya Srinivas,Jingsong Zhang,Thierry Gil,Daygen Finch,Marc-Oliver Grimm,Yu-Li Su,Simon Chowdhury,Christopher Hocking,Eugen Plas,Scott North,Niels Viggo Jensen,Christine Theodore,Florian Imkamp,Avivit Peer,Takashi Kobayashi,Hideki Sakai,Naoto Sassa,Kazuhiro Yoshimura,Maureen J.B. Aarts,Ana Ferreira Castro,Marlen Topuzov,Juan Francisco Rodriguez,Federico Vazquez,Yu-Chieh Tsai,Simon J. Crabb,Syed A. Hussain,Johanna C. Bendell,Marine Gross-Goupil,Gravis Gwenaelle,Raanan Berger,Galina Statsenko,Linda Evans,Alexandra Drakaki,Bradley Somer,Ian D. Davis,James Lynam,Giuliano Santos Borges,Aldo Dettino,Graziella Martins,Luis Eduardo Zucca,Mads Agerbæk,Haralambos Kalofonos,Eli Rosenbaum,Hideki Enokida,Hiroaki Kikukawa,Kazuo Nishimura,Satoshi Tamada,Motohide Uemura,Yamil Lopez,Jourik A. Gietema,Marcin Slojewski,Isabel Fernandes,Alexey Smolin,Danish Mazhar,Arash Rezazadeh Kalebasty,Bradley Carthon,Wolfgang Loidl,Fabio Franke,Gustavo Girotto,Nimira S. Alimohamed,Robyn Macfarlane,Helle Pappot,Guenter Niegisch,Dimitrios Mavroudis,Avishay Sella,Camillo Porta,Shin Ebara,Motonobu Nakamura,Wataru Obara,Norihiko Okuno,Nobuo Shinohara,Mikio Sugimoto,Akitaka Suzuki,Noriaki Tokuda,Hiroji Uemura,Akito Yamaguchi,Francisco Ramirez,Pawel Rozanowski,Paweł Wiechno,Bhumsuk Keam,Nikolay Kislov,Denis Plaksin,Irfan Cicin,Satish Kumar,Joseph Rosales,Ulka N. Vaishampayan,Stéphane Culine,Christos Papandreou,Taketoshi Nara,Mustafa Erman,Laurence Kreiger,Juliana Janoski,Diogo Rosa,Mariana Siqueira,Christina Canil,Lisa Sengeløv,Jean-Marc Tourani,Gaku Arai,Katsuyoshi Hashine,Mutsushi Kawakita,Noboru Nakaigawa,Hayahito Nomi,Hiroaki Shiina,Hiroyoshi Suzuki,Junji Yonese,Roberto Kuri,Eleazar Macedo,Samuel Rivera,Alberto Villalobos Prieto,Anna Polakiewicz-Gilowska,Renata Zaucha,Fabio Lopes,Roman Ponomarev,Mark Pomerantz,Shahrokh F. Shariat,Cynthia Luk,Krzysztof Lesniewski-Kmak +206 more
TL;DR: The overall survival of patients who received durvalumab (a PD-L1 inhibitor), with or without tremelimumab ( a CTLA-4 inhibitor), as a first-line treatment for metastatic urothelial carcinoma was assessed.
Journal ArticleDOI
Robust Design and Analysis of Clinical Trials With Nonproportional Hazards: A Straw Man Guidance From a Cross-Pharma Working Group
TL;DR: In this article, a log-rank test was used to evaluate the risk of nonproportional hazard in a clinical trial where NPH is a possibility and loss of power and clear description of treatment differences are key issues in designing and analyzing clinical trials.
Posted Content
Robust Design and Analysis of Clinical Trials With Non-proportional Hazards: A Straw Man Guidance from a Cross-pharma Working Group
TL;DR: Design and analysis considerations based on a combination test under different non-proportional hazard types and a straw man proposal for practitioners are provided.
Journal ArticleDOI
Assessing the Impact of COVID-19 on the Clinical Trial Objective and Analysis of Oncology Clinical Trials—Application of the Estimand Framework
Evgeny Degtyarev,Kaspar Rufibach,Yue Shentu,Godwin Yung,Michelle Casey,Stefan Englert,Feng Liu,Yi Liu,Oliver Sailer,Jonathan Siegel,Steven Sun,Rui Tang,Jiangxiu Zhou +12 more
TL;DR: It is argued that the clinical trial objective from a world without COVID-19 pandemic remains valid and the applicability of the estimand framework may even go beyond what it was initially intended for.
Journal ArticleDOI
The hazards of period specific and weighted hazard ratios
Jonathan W. Bartlett,Tim P. Morris,Mats Julius Stensrud,Rhian Daniel,Stijn Vansteelandt,Carl-Fredrik Burman +5 more
TL;DR: How to adequately handle nonproportional hazards (NPH) in clinical trials is an important and timely question, particularly given recent advances in immuno-oncology treatments.
References
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Edward L. Kaplan,Paul Meier +1 more
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Proportional hazards tests and diagnostics based on weighted residuals
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Linear rank tests with right censored data
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