Skip to main content
Top
Gepubliceerd in: Quality of Life Research 4/2022

Open Access 21-08-2021

Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2

Auteurs: Gina L. Mazza, Molly M. Petersen, Brenda Ginos, Blake T. Langlais, Narre Heon, Mrinal M. Gounder, Michelle R. Mahoney, Alexander J. Zoroufy, Gary K. Schwartz, Lauren J. Rogak, Gita Thanarajasingam, Ethan Basch, Amylou C. Dueck

Gepubliceerd in: Quality of Life Research | Uitgave 4/2022

Log in om toegang te krijgen
share
DELEN

Deel dit onderdeel of sectie (kopieer de link)

  • Optie A:
    Klik op de rechtermuisknop op de link en selecteer de optie “linkadres kopiëren”
  • Optie B:
    Deel de link per e-mail

Abstract

Purpose

Missing scores complicate analysis of the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) because patients with and without missing scores may systematically differ. We focus on optimal analysis methods for incomplete PRO-CTCAE items, with application to two randomized, double-blind, placebo-controlled, phase III trials.

Methods

In Alliance A091105 and COMET-2, patients completed PRO-CTCAE items before randomization and several times post-randomization (N = 64 and 107, respectively). For each trial, we conducted between-arm comparisons on the PRO-CTCAE via complete-case two-sample t-tests, mixed modeling with contrast, and multiple imputation followed by two-sample t-tests. Because interest lies in whether CTCAE grades can inform missing PRO-CTCAE scores, we performed multiple imputation with and without CTCAE grades as auxiliary variables to assess the added benefit of including them in the imputation model relative to only including PRO-CTCAE scores across all cycles.

Results

PRO-CTCAE completion rates ranged from 100.0 to 71.4% and 100.0 to 77.1% across time in A091105 and COMET-2, respectively. In both trials, mixed modeling and multiple imputation provided the most similar estimates of the average treatment effects. Including CTCAE grades in the imputation model did not consistently narrow confidence intervals of the average treatment effects because correlations for the same PRO-CTCAE item between different cycles were generally stronger than correlations between each PRO-CTCAE item and its corresponding CTCAE grade at the same cycle.

Conclusion

For between-arm comparisons, mixed modeling and multiple imputation are informative techniques for handling missing PRO-CTCAE scores. CTCAE grades do not provide added benefit for informing missing PRO-CTCAE scores. ClinicalTrials.gov Identifiers: NCT02066181 (Alliance A091105); NCT01522443 (COMET-2).
Voetnoten
1
The PRO-CTCAE does not include an item on interference of hand-foot syndrome with usual or daily activities. However, this item was written to mimic other PRO-CTCAE items.
 
2
In A091105, we conducted between-arm comparisons on the PRO-CTCAE at week 12 because week 12 was a time point of interest for evaluating patient-reported pain palliation. In COMET-2, we conducted between-arm comparisons on the PRO-CTCAE at week 12 because the primary endpoint was pain response at week 6 confirmed at week 12. However, the analyses and results presented here are intended to illustrate different missing data strategies and not to replace results reported in other A091105 and COMET-2 publications.
 
Literatuur
3.
go back to reference Basch, E. (2010). The missing voice of patients in drug-safety reporting. The New England Journal of Medicine, 362(10), 865–869.CrossRef Basch, E. (2010). The missing voice of patients in drug-safety reporting. The New England Journal of Medicine, 362(10), 865–869.CrossRef
4.
go back to reference Basch, E., et al. (2017). Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. Journal of the American Medical Association, 318(2), 197–198.CrossRef Basch, E., et al. (2017). Overall survival results of a trial assessing patient-reported outcomes for symptom monitoring during routine cancer treatment. Journal of the American Medical Association, 318(2), 197–198.CrossRef
5.
go back to reference Gounder, M. M., et al. (2018). Sorafenib for advanced and refractory desmoid tumors. New England Journal of Medicine, 379(25), 2417–2428.CrossRef Gounder, M. M., et al. (2018). Sorafenib for advanced and refractory desmoid tumors. New England Journal of Medicine, 379(25), 2417–2428.CrossRef
6.
go back to reference Basch, E. M., et al. (2019). Cabozantinib versus mitoxantrone-prednisone in symptomatic metastatic castration-resistant prostate cancer: A randomized phase 3 trial with a primary pain endpoint. European Urology, 75(6), 929–937.CrossRef Basch, E. M., et al. (2019). Cabozantinib versus mitoxantrone-prednisone in symptomatic metastatic castration-resistant prostate cancer: A randomized phase 3 trial with a primary pain endpoint. European Urology, 75(6), 929–937.CrossRef
7.
go back to reference Coens, C., et al. (2020). International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: Recommendations of the SISAQOL Consortium. The Lancet Oncology, 21(2), e83–e96.CrossRef Coens, C., et al. (2020). International standards for the analysis of quality-of-life and patient-reported outcome endpoints in cancer randomised controlled trials: Recommendations of the SISAQOL Consortium. The Lancet Oncology, 21(2), e83–e96.CrossRef
8.
go back to reference Collins, L. M., Schafer, J. L., & Kam, C.-M. (2001). A comparison of inclusive and restrictive strategies in modern missing data procedures. Psychological Methods, 6(4), 330–351.CrossRef Collins, L. M., Schafer, J. L., & Kam, C.-M. (2001). A comparison of inclusive and restrictive strategies in modern missing data procedures. Psychological Methods, 6(4), 330–351.CrossRef
9.
go back to reference Enders, C. K. (2001). The impact of nonnormality on full information m aximum-likelihood estimation for structural equation models with missing data. Psychological Methods, 6(4), 352–370.CrossRef Enders, C. K. (2001). The impact of nonnormality on full information m aximum-likelihood estimation for structural equation models with missing data. Psychological Methods, 6(4), 352–370.CrossRef
10.
go back to reference Enders, C. K. (2010). Applied missing data analysis. Guilford Press. Enders, C. K. (2010). Applied missing data analysis. Guilford Press.
11.
go back to reference Graham, J. W., & Collins, L. M. (2012). Using modern missing data methods with auxiliary variables to mitigate the effects of attrition on statistical power. In J. W. Graham (Ed.), Missing data: Analysis and design (pp. 253–275). Springer.CrossRef Graham, J. W., & Collins, L. M. (2012). Using modern missing data methods with auxiliary variables to mitigate the effects of attrition on statistical power. In J. W. Graham (Ed.), Missing data: Analysis and design (pp. 253–275). Springer.CrossRef
12.
go back to reference Enders, C. K. (2008). A note on the use of missing auxiliary variables in full information maximum likelihood-based structural equation models. Structural Equation Modeling, 15(3), 434–448.CrossRef Enders, C. K. (2008). A note on the use of missing auxiliary variables in full information maximum likelihood-based structural equation models. Structural Equation Modeling, 15(3), 434–448.CrossRef
Metagegevens
Titel
Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2
Auteurs
Gina L. Mazza
Molly M. Petersen
Brenda Ginos
Blake T. Langlais
Narre Heon
Mrinal M. Gounder
Michelle R. Mahoney
Alexander J. Zoroufy
Gary K. Schwartz
Lauren J. Rogak
Gita Thanarajasingam
Ethan Basch
Amylou C. Dueck
Publicatiedatum
21-08-2021
Uitgeverij
Springer International Publishing
Gepubliceerd in
Quality of Life Research / Uitgave 4/2022
Print ISSN: 0962-9343
Elektronisch ISSN: 1573-2649
DOI
https://doi.org/10.1007/s11136-021-02968-1

Andere artikelen Uitgave 4/2022

Quality of Life Research 4/2022 Naar de uitgave