Establishing content-validity of a disease-specific health-related quality of life instrument for patients with chronic hypersensitivity pneumonitis

Background Chronic Hypersensitivity Pneumonitis (CHP) is caused by an immune mediated response in the lung tissue after exposure to an inhaled environmental antigenic stimulant. We previously documented the ways in which CHP impacts patients’ lives and have now developed a disease-specific instrument, the CHP-HRQOL instrument, to measure health-related quality of life (HRQOL). The objective of this study was to assess content validity for the CHP-HRQOL. Methods Cognitive interviews were conducted among adults with CHP. The instrument was revised and refined between each round of interviews. Feedback was obtained on the instructions, items, response options, and recall period. Items where participants had difficulty with comprehension, wording, or misinterpretation were marked by the interviewer and participant feedback was reviewed to make revisions, add or delete items when appropriate. Readability statistics were calculated using Flesch-Kincaid grade level and reading ease scores. Results Ten participants were interviewed over three rounds, with revisions made to the questionnaire in an iterative process. In the initial 39 item instrument, we identified 7 items where two or more participants reported difficulty. Participants preferred a four-week recall period (compared to a two-week recall period) and response options with a 5-point response scale. The final version of the CHP-HRQOL includes 40 items with a median reading level between 6th and 7th grade. Conclusion The CHP-HRQOL instrument demonstrated high content validity and is ready for psychometric testing in further validation studies.

The impact of chronic orofacial pain on health-related quality of life

Background and aimsHealth-related quality of life (HRQoL) assessments have been widely used in pain medicine as they are able to reflect the subjective and multidimensional nature of chronic pain. Studies have shown a consistent impairment in HRQoL in different chronic pain conditions. However, it is not known whether HRQoL is impaired in chronic orofacial pain (OFP). The generic 15D HRQoL instrument has been shown to fare as well as or better than other generic HRQoL instruments in the study of chronic pain. The aim was to investigate HRQoL in patients with chronic OFP using the generic 15D HRQoL instrument. The validity of the instrument was tested by studying the association of the 15D data with pain interference.MethodsOne hundred fifty-one patients (mean age 50 years, SD 15 years, 119 females) were recruited from three tertiary facial pain clinics. HRQoL data of the participants were contrasted with that of an age- and gender- standardized sample of general population by comparing the mean 15D scores and profiles. The data for the general population came from the National Health 2011 Survey representing Finnish population aged 18 years and older. Pain interference was assessed using Brief Pain Inventory. Based on pain interference distribution the participants were divided into tertiles. Statistical comparison between patient and population HRQoL values were performed using Monte-Carlo-type simulations. Statistical significance for the hypothesis of linearity was evaluated by using generalized linear models.ResultsThe mean 15D score of OFP patients (0.824, SD 0.113) was statistically significantly lower than that of the age- and gender-standardized general population (0.929, SD 0.019) (p < 0.001). The difference between the patients and the general population was also clinically important, i.e. over the minimum clinically important difference in the 15D score. All mean 15D dimension values were significantly lower compared with the general population values (p < 0.001 for all dimensions). The largest differences were seen in the dimensions of discomfort and symptoms (0.418, SD 0.222 vs. 0.816, SD 0.027), sleeping (0.693, SD 0.258 vs. 0.838, SD 0.029), and vitality (0.702, SD 0.221 vs. 0.884 SD 0.026). There was a statistically significant linear decrease in the 15D dimension values (p < 0.001) with increasing pain interference. The greatest differences were found on the dimensions of discomfort and symptoms, sleeping and vitality.ConclusionsHRQoL is significantly impaired in patients with chronic OFP. A decrease in the 15D dimension values with increasing pain interference indicated convergent validity between 15D and pain interference.ImplicationsThe findings suggest that 15D is an appropriate instrument for use in the assessment of HRQoL in OFP patients. By showing the usefulness of the 15D, the present study may encourage further use of generic HRQoL assessments in the study of chronic OFP, and contribute e.g. to the implementation of HRQoL as one of the core outcome measures in future treatment studies on chronic OFP.

Health-related quality of life (HRQoL) of pembrolizumab (pembro) vs chemotherapy (chemo) for previously treated advanced urothelial cancer (UC) in KEYNOTE-045.

4530 Background: In KEYNOTE-045 (NCT02256436) (N = 542), pembro 200 mg Q3W significantly improved OS over investigator’s choice of paclitaxel, docetaxel, or vinflunine as second-line therapy for advanced UC following platinum-based chemo (HR 0.73; P = 0.0022). Fewer treatment-related AEs were reported with pembro. We present results of the prespecified HRQoL analysis of KEYNOTE-045. Methods: The EORTC QLQ-C30 HRQoL instrument was administered electronically at cycles 1–4, then every 2 cycles for up to 1 y and 30 d after discontinuation. The key HRQoL end points were 1) change from baseline to wk 15 and 2) time to deterioration (TTD) (defined as ≥10-point decrease from baseline) in the QLQ-C30 global health status/QoL score. HRQoL was assessed in patients (pts) who received ≥1 dose of assigned study treatment and completed ≥1 HRQoL instrument (N = 520). Score change from baseline was compared using a constrained longitudinal data analysis model. TTD was compared using a stratified log-rank test and Cox proportional hazards model. Results: Baseline global health status/QoL scores were similar between arms. HRQoL compliance at wk 15 was 88% for both arms. From baseline to wk 15, scores were stable for pembro (n = 266) (least squares [LS] mean +0.75 [95% CI –2.34 to +3.83]) but worsened for chemo (n = 254) (LS mean –8.30 [95% CI –11.76 to –4.83]); the difference in LS means between arms was 9.05 (95% CI 4.61-13.48; nominal 2-sided P < 0.001). At wk 15, pts without PD had improved scores with pembro but worsened scores with chemo (LS mean +5.97 vs –4.31), while pts with PD had less worsening with pembro (LS mean –3.54 vs –13.95). TTD was prolonged with pembro (HR 0.70; 95% CI 0.55-0.90; nominal 1-sided P = 0.002; median 3.5 mo vs 2.2 mo). Rates of improvement (defined as ≥10-point increase from baseline) at wk 15 were 31.2% with pembro and 22.0% with chemo; rates of deterioration were 28.9% and 40.6%, respectively. Conclusions: Pembro was associated with substantially better HRQoL for a longer duration than investigator-choice chemo in pts with previously treated advanced UC. Along with superior OS, these data support pembro as a new standard-of-care in this population. Clinical trial information: NCT02256436.

Health-related quality of life (HRQoL) in the KEYNOTE-045 study of pembrolizumab versus investigator-choice chemotherapy for previously treated advanced urothelial cancer.

282 Background: In KEYNOTE-045 (NCT02256436) (N = 542), pembro 200 mg Q3W significantly improved OS over investigator’s choice of paclitaxel, docetaxel, or vinflunine as second-line therapy for advanced UC following platinum-based chemo (HR 0.73; P = 0.0022). Fewer treatment-related AEs were reported with pembro. We present results of the prespecified HRQoL analysis of KEYNOTE-045. Methods: The EORTC QLQ-C30 HRQoL instrument was administered electronically at cycles 1–4, then every 2 cycles for up to 1 y and 30 d after discontinuation. The key HRQoL end points were 1) change from baseline to wk 15 and 2) time to deterioration (TTD) (defined as ≥ 10-point decrease from baseline) in the QLQ-C30 global health status/QoL score. HRQoL was assessed in patients (pts) who received ≥ 1 dose of assigned study treatment and completed ≥ 1 HRQoL instrument (N = 520). Score change from baseline was compared using a constrained longitudinal data analysis model. TTD was compared using a stratified log-rank test and Cox proportional hazards model. Results: Baseline global health status/QoL scores were similar between arms. HRQoL compliance at wk 15 was 88% for both arms. From baseline to wk 15, scores were stable for pembro (n = 266) (least squares [LS] mean +0.75 [95% CI –2.34 to +3.83]) but worsened for chemo (n = 254) (LS mean –8.30 [95% CI –11.76 to –4.83]); the difference in LS means between arms was 9.05 (95% CI 4.61-13.48; nominal 2-sided P < 0.001). At wk 15, pts without PD had improved scores with pembro but worsened scores with chemo (LS mean +5.97 vs –4.31), while pts with PD had less worsening with pembro (LS mean –3.54 vs –13.95). TTD was prolonged with pembro (HR 0.70; 95% CI 0.55-0.90; nominal 1-sided P = 0.002; median 3.5 mo vs 2.2 mo). Rates of improvement (defined as ≥ 10-point increase from baseline) at wk 15 were 31.2% with pembro and 22.0% with chemo; rates of deterioration were 28.9% and 40.6%, respectively. Conclusions: Pembro was associated with substantially better HRQoL for a longer duration than investigator-choice chemo in pts with previously treated advanced UC. Along with superior OS, these data support pembro as a new standard-of-care in this population. Clinical trial information: NCT02256436.

Health-related quality of life in pediatric Chiari Type I malformation: the Chiari Health Index for Pediatrics

OBJECT The purpose of this study was to design and validate a patient-reported health-related quality of life (HRQOL) instrument for pediatric Chiari Type I malformation (CM-I), the Chiari Health Index for Pediatrics (CHIP). METHODS The CHIP has 45 items with 4 components making up 2 domain scores, physical (pain frequency, pain severity, nonpain symptoms) and psychosocial; physical and psychosocial scores are combined to create an overall HRQOL score. Increasing scores (0 to 1) represent increasing HRQOL. Fifty-five patients with CM-I (mean age 12 ± 4 years, 53% male) were enrolled and completed the CHIP and Health Utilities Index Mark 3 (HUI3). Twenty-five healthy controls (mean age 11.9 ± 4 years, 40% male) also completed the CHIP. CHIP scores were compared between these groups via the Mann-Whitney U-test. For CHIP discriminative function, subscore versus presence of CM-I was compared via receiver operating characteristic curve analysis. CHIP scores in the CM-I group were stratified by symptomatology (asymptomatic, headaches, and paresthesias) and compared via Kruskal-Wallis test with Mann-Whitney U-test with Bonferroni correction (p < 0.0167). CHIP was compared with HUI3 (Health Utilities Index Mark 3) via univariate and multivariate linear regression. RESULTS CHIP physical and psychosocial subscores were, respectively, 24% and 18% lower in CM-I patients than in controls (p < 0.001); the overall HRQOL score was 23% lower as well (p < 0.001). The area under the curve (AUC) for CHIP physical subscore versus presence of CM-I was 0.809. CHIP physical subscore varied significantly with symptomatology (p = 0.001) and HUI3 pain-related quality of life (R2 = 0.311, p < 0.001). The AUC for CHIP psychosocial subscore versus presence of CM-I was 0.754. CHIP psychosocial subscore varied significantly with HUI3 cognitive- (R2 = 0.324, p < 0.001) and emotion-related (R2 = 0.155, p = 0.003) quality of life. The AUC for CHIP HRQOL versus presence of CM-I was 0.820. Overall CHIP HRQOL score varied significantly with symptomatology (p = 0.001) and HUI3 multiattribute composite HRQOL score (R2 = 0.440, p < 0.001). CONCLUSIONS The CHIP is a patient-reported, CM-I-specific HRQOL instrument, with construct validity in assessing pain-, cognitive-, and emotion-related quality of life, as well as symptomatic features unique to CM-I. It holds promise as a discriminative HRQOL index in CM-I outcomes assessment.