Stacie Hudgens

Background: X-linked retinitis pigmentosa (XLRP) is a rare inherited eye disease that has negative impacts on patients’ health-related quality of life and increased lifetime burden. The Low Luminance Questionnaire (LLQ) was modified to enhance clarity and relevance for use in XLRP. This study evaluated the psychometric measurement properties of the 30-item modified Low Luminance Questionnaire (mLLQ) in adults with XLRP. Methodology: Data from 2 clinical studies of participants with XLRP underwent psychometric and statistical analyses. Validation analyses included: item-level (missingness, distribution, correlations, discrimination), Rasch, confirmatory factor (CFA), and tests of reliability (internal consistency, test-retest), validity (convergent/divergent, known groups), and responsiveness. Results: Data from 141 adult participants in the EXPLORE XLRP-2 study were included, of which 115 (81.6%) were male, mean age was 42.6 years (range 18–88 years), and 49 (35.0%), 36 (25.7%) and 55 (39.3%) had mild, moderate or severe disease, respectively. mLLQ domains demonstrated excellent internal reliability (Cronbach’s alpha: 0.843 to 0.957). Convergent validity was supported by moderate-to-strong correlations with reference measures ( r > 0.60 in expected domains). The mLLQ domains demonstrated acceptable to good capacity to discriminate between groups of participants known to differ on XLRP disease stage. Item-level rates of missing responses were very low across all items (range 0.0% to 2.1%) and each mLLQ response option was used for all items. Floor effects were identified for 22/30 items (73.%). Items within the same domain correlated well with one another and with their respective domain. 63% (19/30) of items had a discrimination index > 0.40. The hypothesized 6-factor CFA model provided relatively good fit to the data. Assigning 2 Extreme Lighting items to the Driving domain also demonstrated an improved model-data agreement. Rasch analysis suggested a lack of items to assess participants that are more severe, consistent with the observed floor effects for most items. Strong evidence of responsiveness was observed for all mLLQ domains except Driving and Peripheral vision domains, where observed evidence was weaker. Conclusions: Psychometric analyses indicate the mLLQ has acceptable measurement properties to assess self-reported task difficulty under low luminance and at night experienced by adult patients with XLRP.

Background: Rejoyn (CT-152) is a prescription digital therapeutic (DTx) adjunct to antidepressive medication authorized for patients with major depressive disorder. To better understand the patient benefit of DTx and other treatment modalities, current regulatory standards support the use of modern psychometric methods to interpret the clinical meaningfulness of treatment effects for patients. In the primary analysis of Rejoyn from the pivotal phase 3 Mirai trial (NCT04770285), Rejoyn showed a broad risk-to-benefit profile as demonstrated on multiple clinician- and patient-rated scales, including the primary efficacy outcome measure, the Montgomery-Åsberg Depression Rating Scale (MADRS). These findings supported US Food and Drug Administration authorization of Rejoyn as a prescription DTx. However, the clinical relevance of these changes in the MADRS score is not immediately interpretable in clinical practice. Here, we present the results from several post hoc analyses of the Mirai trial data to support the interpretation of clinically meaningful treatment differences on clinician- and patient-reported change in depressive symptoms. Objective: This study had two main objectives: (1) establish threshold parameters that allow for clinically meaningful interpretation of the Mirai results in clinical practice, based on the clinical trial end points of change from baseline in depressive symptoms, and (2) apply this threshold in a responder and sensitivity analysis in the intent-to-treat (ITT) population (which is more frequently reported in pharmacological trials) to further support the interpretation of change in unblinded analysis of the Mirai results. Methods: For the Mirai meaningful within-patient change (MWPC) analysis, anchor-based methods were used to define an MWPC threshold by exploring the associations between the MADRS and the clinician-rated Clinical Global Impression-Severity Scale (CGI-S) and the patient-reported Patient Health Questionnaire 9-Item Scale (PHQ-9). Additional post hoc efficacy analyses (including that of responders) are reported for the ITT population. Results: Using the MWPC thresholds of 8 and 10 points (derived with the CGI-S and PHQ-9 as anchor measures, respectively), the distribution of MADRS responders favored the Rejoyn group over the sham group, and the Rejoyn group had 24%‐47% higher odds of meaningful improvement on the MADRS. Post hoc ITT analyses also favored the Rejoyn group over the sham group for response rates and PHQ-9 and CGI-S score change from baseline. Conclusions: Results are consistent with the primary findings of the Mirai trial, supporting the efficacy of Rejoyn as an adjunctive treatment to antidepressive medication monotherapy for adults with major depressive disorder. The MWPC analyses offered a measure of meaningful change on the MADRS, providing a framework of clinical meaningfulness for the Mirai trial findings.

Introduction Deucravacitinib, a novel, oral, selective allosteric tyrosine kinase 2 inhibitor, demonstrated superiority versus placebo and apremilast in the POETYK PSO-1 and PSO-2 studies. We describe patient-reported outcomes with deucravacitinib treatment versus placebo and apremilast in these studies. Methods Two multicenter, global, double-blind, placebo- and active comparator-controlled studies randomized patients with moderate-to-severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Score changes from baseline and meaningful within-patient change responses for Psoriasis Symptoms and Signs Diary (PSSD) and Dermatology Life Quality Index (DLQI) were assessed. Results In POETYK PSO-1 (n = 666) and PSO-2 (n = 1020), respectively, improvement from baseline in PSSD total score was greater with deucravacitinib (− 27.8 and − 30.1) versus placebo (− 4.4 and − 5.9) and apremilast (− 18.9 and − 22.5) at Week 16 and versus apremilast at Week 24 (deucravacitinib: − 32.8 and − 30.7; apremilast: − 21.6 and − 22.8) (nominal p < 0.0001). Improvement from baseline in DLQI score was also greater with deucravacitinib (− 8.5 and − 7.6) versus placebo (− 3.3 and − 3.0) and apremilast (− 5.9 and − 5.8) at Week 16 and versus apremilast at Week 24 (deucravacitinib: − 8.6 and − 7.5; apremilast: − 5.6 and − 5.5) (nominal p < 0.0001). Achievement of meaningful within-patient change in PSSD total score and in DLQI score occurred more frequently with deucravacitinib than placebo and apremilast at Week 16 and versus apremilast at Week 24. Conclusions Deucravacitinib demonstrated meaningful improvements in patient-reported outcomes in patients with moderate-to-severe plaque psoriasis compared with apremilast and placebo. Clinical Trial Registration NCT03624127, NCT03611751.

Introduction This qualitative research study was conducted to develop a novel, comprehensive, patient-reported outcome measure (PRO), the “Symptoms and Impacts of Androgen Deprivation Therapy (ADT) for Prostate Cancer” (SIADT-PC), assessing hormonal therapy-related symptoms and their impacts on men with advanced prostate cancer. Methods Concept elicitation (CE) interviews were conducted among adult men with prostate cancer to evaluate their experiences with ADT. Based on key symptom and impact concepts mentioned, an initial PRO measure was developed. The draft measure was further assessed in cognitive debriefing (CD) interviews with men with prostate cancer, in which participants reviewed items, response options, and recall periods. Initial item-based psychometric analyses were conducted using interview data. The draft questionnaire was revised on the basis of participant feedback, quantitative psychometric results, and consultation with clinical experts. Results A total of 21 participants were interviewed (CE concept elicitation, n = 12; CD cognitive debriefing, n = 17; n = 8 completed both). Mean participant age (SD) was 59.7 (8.7) years and 76.2% were white. The de novo SIADT-PC measure consists of 27 items: 11 symptoms (e.g., fatigue, hot flashes, and erectile dysfunction), 2 long-term symptoms (e.g., weight gain), 10 impacts (e.g., impacts on physical activities and relationships), and 4 related to mode of administration (i.e., injection-site reactions). Items were assessed with a 5-point verbal rating scale, with answer choices that capture frequency or severity. Conclusions Once fully validated, this de novo measure may be used in clinical studies and clinical practice to assess hormone therapy-related symptoms and impacts, enabling physicians to identify timely and appropriate interventions.

Background: Psoriasis is a common autoimmune dermatologic condition which has a pronounced negative impact on patient quality of life and disease burden. Currently, there are a number of treatments available for psoriasis, with differences in efficacy, mechanism of action, mode of administration, adverse effects, and tolerability. However, a reliable, validated patient-reported instrument to address patient expectations and of psoriasis treatment has not been developed. This project was undertaken with the aim of developing a fit-for-purpose self-reported instrument to inform patient expectations and preferences of psoriasis treatments. Methods: Two studies, both utilizing qualitative and quantitative methods, were conducted in patients within the entire spectrum of psoriasis severity. In Study 1, a group concept mapping (GCM) exercise was conducted with dermatologists and moderate-to-severe psoriasis patients to identify concepts important in the treatment of psoriasis. In Study 2, a preliminary Treatment Acceptability Questionnaire (TAQ) was developed using GCM-derived concepts from Studies 1 and 2, followed by cognitive debriefing (CD) telephone interviews of the preliminary TAQ. In Study 2, another GCM exercise was conducted with mild and newly diagnosed psoriasis patients. Psychometric analyses were performed on the TAQ to evaluate validity and reliability. Results: The Study 1 GCM exercise generated 43 concepts from moderate-to-severe psoriasis patients (n = 20) and dermatologists (n = 10). In Study 2, 37 GCM concepts were generated from mild and newly diagnosed psoriasis patients (n = 20). From the 2 GCM exercises, 28 concepts were selected to form the preliminary TAQ; CD interviews indicated strong understanding and relevance of TAQ items among patients with disease ranging from mild to severe. The final TAQ consisted of 20 items; psychometric analysis demonstrated strong validity and reliability of the TAQ. Conclusions: The TAQ is a novel psychometrically validated patient-reported instrument to inform healthcare providers of patients’ expectations of and preferences for treatment of their psoriasis and can help in shared decision making between patients and physicians.

Objective: To quantitatively compare equivalence and compliance of patient-reported outcome (PRO) data collected via provisioned device (PD) versus bring your own device (BYOD). Methods: Participants with stable chronic obstructive pulmonary disease (COPD) completed the EXAcerbations of Chronic Pulmonary Disease Tool (EXACT^®) daily and COPD Assessment Test™ (CAT) and Patient Global Impression of Severity (PGIS) of COPD weekly on either PD or BYOD for 15 days, then switched device types for 15 days. EXACT was scored using the Evaluating Respiratory Symptoms in COPD (E-RS^®: COPD) algorithm and equivalence assessed using intraclass correlation coefficients (ICCs) adjusting for cross-over sequence, period, and time. Two one-sided tests (TOSTs) used ICC adjusted means with 10%, 20%, and 40% of total score tested as equivalence margins. Compliance and comfort with technology were assessed. Equivalence across 3 device screen sizes was assessed following the second completion period. Results: Participants (N = 64) reported high comfort with technology, with 79.7% reporting being “quite a bit” or “very” comfortable. Weekly compliance was high (BYOD = 89.7–100%; PD = 76.9–100%). CAT and E-RS: COPD scores correlated well with PGIS (r > 0.50) and demonstrated equivalence between PD and BYOD completion (ICC = 0.863–0.908). TOST equivalence was achieved within 10% of the total score (p > 0.05). PRO measure scores were equivalent across 3 different screen sizes (ICC = 0.972–0.989). Conclusions: Measure completion was high and scores equivalent between PD and BYOD, supporting use of BYOD in addition to PD for collecting PRO data in COPD studies and in demographically diverse patient populations.