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Estimand framework: Are we asking the right questions? A case study in the solid tumor setting.

Publication ,  Journal Article
Casey, M; Degtyarev, E; Lechuga, MJ; Aimone, P; Ravaud, A; Motzer, RJ; Liu, F; Stalbovskaya, V; Tang, R; Butler, E; Sailer, O; Halabi, S; George, D
Published in: Pharm Stat
March 2021

The estimand framework requires a precise definition of the clinical question of interest (the estimand) as different ways of accounting for "intercurrent" events post randomization may result in different scientific questions. The initiation of subsequent therapy is common in oncology clinical trials and is considered an intercurrent event if the start of such therapy occurs prior to a recurrence or progression event. Three possible ways to account for this intercurrent event in the analysis are to censor at initiation, consider recurrence or progression events (including death) that occur before and after the initiation of subsequent therapy, or consider the start of subsequent therapy as an event in and of itself. The new estimand framework clarifies that these analyses address different questions ("does the drug delay recurrence if no patient had received subsequent therapy?" vs "does the drug delay recurrence with or without subsequent therapy?" vs "does the drug delay recurrence or start of subsequent therapy?"). The framework facilitates discussions during clinical trial planning and design to ensure alignment between the key question of interest, the analysis, and interpretation. This article is a result of a cross-industry collaboration to connect the International Council for Harmonisation E9 addendum concepts to applications. Data from previously reported randomized phase 3 studies in the renal cell carcinoma setting are used to consider common intercurrent events in solid tumor studies, and to illustrate different scientific questions and the consequences of the estimand choice for study design, data collection, analysis, and interpretation.

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Published In

Pharm Stat

DOI

EISSN

1539-1612

Publication Date

March 2021

Volume

20

Issue

2

Start / End Page

324 / 334

Location

England

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Neoplasms
  • Humans
  • Data Interpretation, Statistical
  • 4905 Statistics
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0104 Statistics
 

Citation

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Chicago
ICMJE
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Casey, M., Degtyarev, E., Lechuga, M. J., Aimone, P., Ravaud, A., Motzer, R. J., … George, D. (2021). Estimand framework: Are we asking the right questions? A case study in the solid tumor setting. Pharm Stat, 20(2), 324–334. https://doi.org/10.1002/pst.2079
Casey, Michelle, Evgeny Degtyarev, María José Lechuga, Paola Aimone, Alain Ravaud, Robert J. Motzer, Feng Liu, et al. “Estimand framework: Are we asking the right questions? A case study in the solid tumor setting.Pharm Stat 20, no. 2 (March 2021): 324–34. https://doi.org/10.1002/pst.2079.
Casey M, Degtyarev E, Lechuga MJ, Aimone P, Ravaud A, Motzer RJ, et al. Estimand framework: Are we asking the right questions? A case study in the solid tumor setting. Pharm Stat. 2021 Mar;20(2):324–34.
Casey, Michelle, et al. “Estimand framework: Are we asking the right questions? A case study in the solid tumor setting.Pharm Stat, vol. 20, no. 2, Mar. 2021, pp. 324–34. Pubmed, doi:10.1002/pst.2079.
Casey M, Degtyarev E, Lechuga MJ, Aimone P, Ravaud A, Motzer RJ, Liu F, Stalbovskaya V, Tang R, Butler E, Sailer O, Halabi S, George D. Estimand framework: Are we asking the right questions? A case study in the solid tumor setting. Pharm Stat. 2021 Mar;20(2):324–334.
Journal cover image

Published In

Pharm Stat

DOI

EISSN

1539-1612

Publication Date

March 2021

Volume

20

Issue

2

Start / End Page

324 / 334

Location

England

Related Subject Headings

  • Statistics & Probability
  • Research Design
  • Neoplasms
  • Humans
  • Data Interpretation, Statistical
  • 4905 Statistics
  • 3214 Pharmacology and pharmaceutical sciences
  • 1115 Pharmacology and Pharmaceutical Sciences
  • 0104 Statistics