Norm-based comparison of the quality-of-life impact of ravulizumab and eculizumab in paroxysmal nocturnal hemoglobinuria

Aims Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening intravascular hematologic disorder with significant morbidity and premature mortality. Clinical trials (NCT02946463 and NCT03056040) comparing ravulizumab with eculizumab for PNH have supported the non-inferiority of the former and similar safety and tolerability. This secondary analysis compared PNH trial participants after 26 weeks on either treatment (n = 438) to a general-population sample (GenPop) (n = 15,386) and investigated response-shift effects. Methods Multivariate analysis of covariance (MANCOVA) investigated function and symptom scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 of people with PNH as compared to GenPop, after covariate adjustment. Risk-factor groups were created based on clinical indicators known to be associated with worse PNH outcomes, and separate MANCOVAs were computed for lower- and higher-risk-factor groups. Differential item functioning (DIF) analyses examined whether item response varied systematically (1) by treatment, (2) compared to GenPop, and (3) over time, the latter two suggesting and reflecting response-shift effects, respectively. DIF analyses examined 24 items from scales with at least two items. Recalibration response shift was operationalized as uniform DIF over time, reflecting the idea that, for a given group, the difficulty of endorsing an item changes over time, after adjusting for the total subscale score. Reprioritization response shift was operationalized as non-uniform DIF over time, i.e., the relative difficulty of endorsing an item over time changes across the total domain score. Results Across PNH risk-factor levels, people who had been on either treatment for 26 weeks reported better-than-expected functioning and lower symptom burden compared to GenPop. Ravulizumab generally showed larger effect sizes. Results were similar for lower and higher PNH risk factors, with slightly stronger effects in the former. DIF analyses revealed no treatment DIF, but did uncover group DIF (9 items with uniform DIF, and 11 with non-uniform) and DIF over time (7 items with uniform DIF, and 3 with non-uniform). Conclusions This study revealed that people with PNH on ravulizumab or eculizumab for 26 weeks reported QOL levels better than those of the general population. Significant effects of DIF by group and DIF over time support recalibration and reprioritization response-shift effects. These findings suggest that the treatments enabled adaptive changes.

Emotional and Behavioral Problems in Children With a Cleft Lip With or Without Palate or an Infantile Hemangioma

Objective: Life can be challenging for children with a visible difference due to a medical condition, and they might be at risk for emotional and behavioral problems. This study examines emotional and behavioral problems in children with a cleft lip with or without palate (CL ± P) or an infantile hemangioma (IH) in relation to the visibility of the condition, the presence of additional condition-related problems, and parental affect. Setting: This cross-sectional study took place in an academic medical hospital in the Erasmus MC Sophia Children’s Hospital, the Netherlands. Participants: A total of 309 parents (mean age = 40.34, 44.00% male) of 182 children with CL ± P and 48 parents (mean age = 39.21, 37.50% male) of 33 children with an IH completed questionnaires. Children were 1.5 to 12 years old. Results: Parents reported fewer child emotional and behavioral problems compared to normative data. Problems reported were mainly related to learning difficulties and parent gender, while visibility of the condition had no significant influence. Parental negative affect was related to child internalizing problems. Parental positive affect was not related to any of the outcome measures. Conclusions: Parents reported fewer problems for their children compared to normative data. This is inconsistent with previous research, showing similar or worse scores for these children compared to peers. Our findings may be explained by a protective parenting style, a response shift in parents, or problems developing at a later point in life.

Creating idiometric short-form measures of cognitive appraisal: balancing theory and pragmatics

Background The Rapkin and Schwartz appraisal theory and measure provided a path toward documenting response-shift effects and describing individual differences in ways of thinking about quality of life (QOL) that distinguished people in different circumstances. Recent work developed and validated the QOL Appraisal Profileversion 2 (QOLAPv2), an 85-item measure that taps response-shift-detection domains of Frame of Reference, Standards of Comparison, Sampling of Experience, and Combinatory Algorithm. Recent theoretical work proposed that appraisal measurement constitutes a new class of measurement (idiometric), distinct from psychometric and clinimetric. To validate an idiometric measure, one would document that its items reflect different circumstances and population characteristics, and explain variance in QOL. The present work sought to develop idiometric short-forms of the QOLAPv2 item bank by examining which items were most informative, retaining the appraisal-domain structure. Methods This secondary analysis (n = 1481) included chronically-ill patients and their caregivers from a longitudinal web-based survey (mean follow-up 16.6 months). Data included the QOLAPv2, the Center for Disease Control Healthy Days Core Module, the PROMIS-10 Global Health, and demographic/medical variables. Appraisal items were measured at baseline (relevant to understanding cognitive appraisal processes); and with change scores (sensitive to response-shift effects). Multivariate analysis of covariance examined what demographic and health-status change variables were reflected by each of 85 appraisal items (in five sets), as dependent variables, and other demographic/medical variables. Multiple linear regression examined how appraisal items explained variance in global physical- and mental-health change, after covariate adjustment. A tally summarized item performance across all five sets of cross-sectional and longitudinal analyses. Results The vast majority (i.e., 80%) of the QOLAPv2 items performed well across the analyses presented. Using a relatively strict criterion of explaining meaningful variance across 60% of analyses, one would retain 68 items. A more lenient criterion (40%) would retain 71. Conclusions The present study provides heuristics to support investigators’ creating ‘discretionary’ QOLAPv2 short-forms to fit their study aim and amplifying individual differences in the cognitive processes underlying QOL. This approach enables adapting the measure to the study population, as per the expectation that respondent populations differ in the predominant cognitive processes used.

Response shift after coronary revascularization

Purpose The aims of this study were to investigate (1) the extent to which response shift occurs among patients with coronary artery disease (CAD) after coronary revascularization, (2) whether the assessment of changes in health-related quality of life (HRQoL), controlled for response shift, yield more valid estimates of changes in HRQoL, as indicated by stronger associations with criterion measures of change, than without controlling for response shift, and (3) if occurrences of response shift are related to patient characteristics. Methods Patients with CAD completed the SF-36 and the Seattle Angina Questionnaire (SAQ7) at baseline and 3 months after coronary revascularization. Sociodemographic, clinical and psychosocial variables were measured with the patient version of the New York Heart Association-class, Subjective Significance Questionnaire, Reconstruction of Life Events Questionnaire (RE-LIFE), and HEXACO personality inventory. Oort’s Structural Equation Modeling (SEM) approach was used to investigate response shift. Results 191 patient completed questionnaires at baseline and at 3 months after treatment. The SF-36 showed recalibration and reprioritization response shift and the SAQ7 reconceptualization response shift. Controlling for these response shift effects did not result in more valid estimates of change. One significant association was found between reprioritization response shift and complete integration of having CAD into their life story, as indicated by the RE-LIFE. Conclusion Results indicate response shift in HRQoL following coronary revascularization. While we did not find an impact of response shift on the estimates of change, the SEM approach provides a more comprehensive insight into the different types of change in HRQoL following coronary revascularization.