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. 2024;20(22):1601-1615.
doi: 10.1080/14796694.2024.2357537. Epub 2024 Jun 18.

End points in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

Evgeny Degtyarev  1 , Natacha Bolaños  2 , Joshua D Brody  3 , Aby Buchbinder  4 , Marc Buyse  5   6 , Miriam Fuchs  1 , Susan Halabi  7   8 , Robert Hemmings  9 , Aisha Masood  4 , Simon Newsome  1 , Claire Saxton  10 , Lorna Warwick  11 , Nigel A Yateman  1 , Emmanuel Zuber  1
Affiliations

End points in clinical trials in diffuse large B-cell lymphoma: time for more dialogue?

Evgeny Degtyarev et al. Future Oncol. 2024.

Abstract

We observed lack of clarity and consistency in end point definitions of large randomized clinical trials in diffuse large B-cell lymphoma. These inconsistencies are such that trials might, in fact, address different clinical questions. They complicate interpretation of results, including comparisons across studies. Problems arise from different ways to account for events occurring after randomization including absence of improvement in disease status, treatment discontinuation or the initiation of new therapy. We call for more dialogue between stakeholders to define with clarity the questions of interest and corresponding end points. We illustrate that assessing different end point rules across a range of plausible patient journeys can be a powerful tool to facilitate such a discussion and contribute to better understanding of patient-relevant end points.

Keywords: estimand framework; event-free survival; non-Hodgkin lymphoma; overall survival; patient journeys; patient-reported outcomes; progression-free survival; treatment effects.

Plain language summary

What is this article about? This article talks about the lack of clarity and consistency in the definitions of outcomes used in clinical trials that investigate new treatments for diffuse large B-cell lymphoma. This is mainly due to how these different outcome definitions handle events such as absence of improvement in disease status, treatment discontinuation or initiation of new treatment. The authors discuss how these inconsistencies make it hard to interpret the results of individual clinical trials and to compare results across clinical trials.Why is it important? Defining the above events and consequently defining outcomes affects what we can learn from the trials and can lead to different results. Some approaches may not reflect good and bad outcomes for patients appropriately. This makes it challenging for patients, physicians, health authorities and payors to understand the true benefit of treatments under investigation and which one is better.What are the key take-aways? This article serves as a call-to-action for more dialogue among all stakeholders involved in drug development and the decision-making process related to drug evaluations. There is an urgent need for clinical trials to be designed with more clarity and consistency on what is being measured so that relevant questions for patients and prescribing physicians are addressed. Understanding patient journeys will be key to successfully understand what truly matters to patients and how to measure the benefit of new treatments. Such discussions will contribute toward more clarity and consistency in the evaluation of new treatments.

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Conflict of interest statement

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Examples of patient journeys in diffuse large B-cell lymphoma trials. PD: Progressive disease; R: Randomization; SD: Stable disease; CR: Complete Response.
Figure 2.
Figure 2.
Scheme of CAR-T and transplant treatment strategies.
Figure 3.
Figure 3.
Patient journeys and assessment of quality of life at 6 months. CR: Complete Response; SD: Stable Disease; PRO: Patient-reported outcomes.
See this image and copyright information in PMC

References

    1. Richardson NC, Kasamon Y, Pazdur R, et al. . The saga of PI3K inhibitors in haematological malignancies: survival is the ultimate safety endpoint. Lancet Oncol. 2022;23(5):563–566. doi:10.1016/S1470-2045(22)00200-5 - DOI - PubMed
    1. FDA Guidance for Industry . Clinical trial endpoints for the approval of cancer drugs and biologics. December 2018. Available from: www.fda.gov/media/71195/download
    1. Dabisch I, Dethling J, Dintsios CM, et al. . Patient relevant endpoints in oncology: current issues in the context of early benefit assessment in Germany. Health Econ Rev. 2014;4(1):2. doi:10.1186/2191-1991-4-2 - DOI - PMC - PubMed
    1. ICH Harmonised Guideline . E8(R1) General considerations for clinical studies. [updated 2021 Oct 06]. Available from: www.ema.europa.eu/en/documents/regulatory-procedural-guideline/ich-guide...
    1. ICH Harmonised Guideline . E9(R1) Addendum on estimands and sensitivity analysis in clinical trials. [updated 2019 Nov 20]. Available from: https://database.ich.org/sites/default/files/E9-R1_Step4_Guideline_2019_...

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