Psychometrics of patient-reported bother from side effects of treatment single-items in industry-sponsored oncology trials

Purpose The Functional Assessment of Cancer Therapy item (FACT-GP5) has the potential to provide an understanding of global treatment tolerability from the patient perspective. Longitudinal evaluations of the FACT-GP5 and challenges posed by data missing-not-at-random (MNAR) have not been explored. Robustness of the FACT-GP5 to missing data assumptions and the responsiveness of the FACT-GP5 to key side-effects are evaluated. Methods In a randomized, double-blind study (NCT00065325), postmenopausal women (n = 618) with hormone receptor-positive (HR+), advanced breast cancer received either fulvestrant or exemestane and completed FACT measures monthly for seven months. Cumulative link mixed models (CLMM) were fit to evaluate: (1) the trajectory of the FACT-GP5 and (2) the responsiveness of the FACT-GP5 to CTCAE grade, Eastern Cooperative Oncology Group (ECOG) Performance Status scale, and key side-effects from the FACT. Sensitivity analyses of the missing-at-random (MAR) assumption were conducted. Results Odds of reporting worse side-effect bother increased over time. There were positive within-person relationships between level of side-effect bother (FACT-GP5) and severity of other FACT items, as well as ECOG performance status and Common Terminology Criteria for Adverse Events (CTCAE) grade. The number of missing FACT-GP5 assessments impacted the trajectory of the FACT-GP5 but did not impact the relationships between the FACT-GP5 and other items (except for nausea [FACT-GP2]). Conclusions Results support the responsiveness of the FACT-GP5. Generally speaking, the responsiveness of the FACT-GP5 is robust to missing assessments. Missingness should be considered, however, when evaluating change over time of the FACT-GP5. Trial Registration NCT00065325. Trial Registration Year 2003.

show abstract

Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer

Regnault,

Bunod,

Loubert

et al. 2024

J Patient Rep Outcomes

View full text Add to dashboard Cite

Background This psychometric analysis generated evidence to support the use of the Functional Assessment of Cancer Therapy item GP5 (GP5) as a measure of tolerability and confirms the appropriateness of categorizing “high side-effect burden” using a rating of 3 or 4 (score ranges 0–4) in patients with advanced/metastatic RET-mutant medullary thyroid cancer (MTC). Methodology Blinded, pooled interim data from the safety population (n=290) enrolled in the phase 3 LIBRETTO-531 trial (NCT04211337) were used. Intraclass correlation coefficients (ICC) were calculated for test-retest reliability using data from cycles 1-2 post-baseline. Construct validity was evaluated by examining the correlations of GP5 ratings with (a) symptomatic adverse events (AEs; measured by the PRO-CTCAE), and (b) functioning scores of EORTC QLQ-C30. The ability to detect change over time was examined by Cochrane-Mantel-Haenszel tests for GP5 ratings and PRO-CTCAE. The relationship of “high side-effect burden” categories with QLQ-C30 functioning scores was examined. Results ICCs for the GP5 ratings after cycle 1 ranged between 0.80 and 0.85, indicating good reliability. Correlations between GP5 and PRO-CTCAE items ranged from 0.18 to 0.62 and ranged from -0.37 to -0.50 for QLQ-C30 functioning scores, consistent with study assumptions. Post-baseline GP5 ratings showed significant associations with PRO-CTCAE scores (p<0.001). Participants with GP5 ratings of 3 or 4 had worse physical function than those with GP5 ratings of 0 to 2 (p<0.0001). Conclusions This analysis generated evidence supportive of the psychometric properties of the GP5 as a fit-for-purpose measure to assess treatment tolerability in patients with advanced/metastatic MTC. The definition of “high side-effect burden” was associated with the clinical feature of tolerability.

show abstract

Psychometrics of patient-reported bother from side effects of treatment single-items in industry-sponsored oncology trials

Cited by 3 publications

References 36 publications

Patient-Reported Tolerability in Oncology Drug Development

Patient-Reported Tolerability in Oncology Drug Development

The FACT-GP5 as a global tolerability measure: responsiveness and robustness to missing assessments

Assessing tolerability with the Functional Assessment of Cancer Therapy item GP5: psychometric evidence from LIBRETTO-531, a phase 3 trial of selpercatinib in medullary thyroid cancer

Contact Info

Product

Resources

About