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 Journal Article
| Authors: | Mazza, G. L.; Petersen, M. M.; Ginos, B.; Langlais, B. T.; Heon, N.; Gounder, M. M.; Mahoney, M. R.; Zoroufy, A. J.; Schwartz, G. K.; Rogak, L. J.; Thanarajasingam, G.; Basch, E.; Dueck, A. C. |
| Article Title: | 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 |
| 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). © 2021, The Author(s). |
| Keywords: | controlled study; antineoplastic agents; united states; antineoplastic agent; neoplasm; neoplasms; quality of life; randomized controlled trial; psychology; national cancer institute (u.s.); patient reported outcome measures; adverse drug reaction; national health organization; adverse event; patient-reported outcome; multiple imputation; pro-ctcae; missing data; humans; human; drug-related side effects and adverse reactions |
| Journal Title: | Quality of Life Research |
| Volume: | 31 |
| Issue: | 4 |
| ISSN: | 0962-9343 |
| Publisher: | Springer |
| Date Published: | 2022-04-01 |
| Start Page: | 1069 |
| End Page: | 1080 |
| Language: | English |
| DOI: | 10.1007/s11136-021-02968-1 |
| PUBMED: | 34420143 |
| PROVIDER: | scopus |
| PMCID: | PMC8859007 |
| DOI/URL: | |
| Notes: | Erratum issued: see DOI 10.1007/s11136-021-03000-2 -- Article -- Export Date: 25 April 2022 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work