Detecting deviations from the efficacy and safety results of single-arm trials using real-world data: The case of a CAR-T cell therapy in B-cell lymphoma

Research output: Contribution to journalArticle


Purpose: Personalized therapies are leading to an increasing number of marketing authorizations based on single-arm trials, which increases the demand for better post-authorization monitoring strategies. The aim of the present study was to estimate the power over time as data accrue in population-based registries for detecting deviations from the expected efficacy/safety of chimeric antigen receptor T cell (CAR-T) therapy approved for relapsed/refractory large B-cell lymphoma (RR-LBCL). Methods: The number of real-world RR-LBCL patients was projected over time in a general population of 5, 15, and 25 million citizens using lymphoma registry data. For each scenario, we computed the power over time for detecting significant deviations in efficacy (1-year overall survival [1yOS]) when comparing to historical controls (SCHOLAR-1 study; 1yOS, 28%) and RR-LBCL patients treated with CAR-T cell therapy in a single-arm trial (ZUMA-1; 1yOS, 59%) as well as deviations in selected adverse events (grade ≥3 aphasia) from the ZUMA-1 trial. We assumed a 10% absolute deviation in 1yOS (efficacy) and a relative increase of 50% in grade ≥3 aphasia (safety). Results: Assuming a general population of 5, 15, and 25 million, the accrual time needed to achieve 80% power for detecting a significant increase over the 1yOS reported in SCHOLAR-1 was 9, 4, and 3 years, respectively, while 80% power for detecting a significant decrease in 1yOS compared to ZUMA-1 required 10.5, 4.5, and 3 years of data accrual, respectively. However, corresponding estimates for aphasia were >20, 8, and 5 years, respectively. Conclusions: Projections of the statistical power for detecting important deviations in efficacy/safety from that reported in pivotal clinical trials(s) provide critical information about the expected performance of post-authorization monitoring programs.


  • Lasse Hjort Jakobsen
  • Torbjörn Callréus
  • Maurizio Sessa
  • Mats Jerkeman
  • Morten Andersen
  • Tarec Christoffer El-Galaly
External organisations
  • Aalborg University Hospital
  • Aalborg University
  • University of Copenhagen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Immunology in the medical area


  • CAR-T cell therapy, monitoring, single-arm trial
Original languageEnglish
JournalPharmacoepidemiology and Drug Safety
Publication statusPublished - 2021
Publication categoryResearch

Bibliographic note

Funding Information: Morten Andersen and Maurizio Sessa belongs to the Pharmacovigilance Research Center, Department of Drug Design and Pharmacology, University of Copenhagen, funded by the Novo Nordisk Foundation (NNF15SA0018404). No funding was specifically received for the preparation of this article. Torbjörn Callréus contributed to this report while affiliated with the Center. Lasse Hjort Jakobsen received funding by Aalborg University. Funding Information: Mats Jerkeman has received research grants from Gilead, Abbvie, Janssen and Celgene, and personal fees from Gilead, Janssen, Novartis, Acerta, Roche and Celgene. Tarec Christoffer El‐Galaly is employed by F. Hoffmann‐La Roche, Ltd, Basel. Morten Andersen has participated in research projects funded by AstraZeneca, H. Lundbeck & Mertz, Novartis, Pfizer and Janssen, with grants paid to the institutions where he has been employed, and has personally received fees from Atrium, the Danish Pharmaceutical Industry Association, for leading and teaching pharmacoepidemiology courses. Lasse Hjort Jakobsen, Torbjörn Callréus, and Maurizio Sessa have no conflicts of interest that are directly relevant to the content of this article. Publisher Copyright: © 2021 John Wiley & Sons Ltd Copyright: Copyright 2021 Elsevier B.V., All rights reserved.