Adelphi Group (United Kingdom)

For patients with advanced breast cancer (ABC), standard-of-care (SOC) treatment in first line (1L) with CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) is well established. However, data on treatment patterns in second line (2L), where the treatment landscape is evolving, are lacking. This large real-world study investigated treatment sequencing from 1L to 2L in patients with HR+/HER2- ABC in the post-CDK4/6i era. Data leveraged the Adelphi ABC Disease Specific Programme (DSP)™, a cross-sectional survey conducted in Europe and the United States between July 2022 and March 2023. Physicians provided data for consecutively consulting patients, including current and historic clinical status, treatment sequencing and biomarker testing history. All analyses were descriptive. Data for 767 patients with HR+/HER2- ABC receiving 2L treatment at data collection were analyzed. In 2L, 31.6% received chemotherapy-based regimens, 17.7% received ET monotherapy, 21.5% received CDK4/6i+ET, and 26.3% received a targeted therapy (mTOR/PARP/PI3K inhibitors). Of those receiving 2L, 58% previously received a CDK4/6i regimen in 1L, in line with treatment guidance, while 21% received chemotherapy. Use of targeted therapies in 2L was driven by biomarker testing. Country/region-specific variation in biomarker testing and treatments were likely due to differences in local guidance and practice. This study provides insights into treatment sequencing in patients with HR+/HER2- ABC who progress to 2L in the post-CDK4/6i era. For patients without targetable mutations, there is no clear SOC at 2L and treatment options are limited. New treatments may further shape this developing landscape.

Hereditary angioedema (HAE) is a rare, genetic condition characterized by recurrent, unpredictable tissue swelling attacks. Using patient-reported outcome (PRO) instruments, we evaluated the patient experience of HAE attack manifestations and what constitutes a meaningful change in those manifestations to support development of key endpoints in clinical trials for on-demand treatment (ODT) of HAE attacks. This non-interventional, mixed methods study included participants with HAE in the United States. During the quantitative phase, participants completed electronic PRO assessments including Angioedema syMptom Rating scAle (AMRA) and Patient Global Impression of Severity (PGI-S) and Change (PGI-C) for ≥ 1 HAE attack in real time. A subset participated in a qualitative interview within 1–2 weeks of attack resolution. The quantitative phase included 35 participants (74.3% female; 85.7% White), 20 of whom participated in the qualitative phase. Data collected from 98 non-upper-airway attacks and 35 upper-airway attacks, including laryngeal attacks (total = 133), indicated associations between PGI-S/-C scores and AMRA composite scores, change from baseline (CFB), and percentage CFB. When comparing different definitions of time to onset of symptom relief, PGI-C had greater sensitivity in detecting early symptom relief yet remained comparable to AMRA symptom relief endpoints. Interviews confirmed most participants understood the PROs and considered them relevant. By characterizing the patient experience with approved ODTs on HAE manifestations using various PROs (AMRA, PGI-C/S), these mixed methods findings may inform the inclusion of suitable PRO instruments, and selection and hierarchical structuring of PRO-based clinical endpoints, in future trials of ODTs for HAE attacks.

To develop and validate an owner-reported health-related quality-of-life (HRQoL) questionnaire in cats with chronic kidney disease (CKD). This was a noninterventional, international study. Initial draft items were identified through qualitative literature and social media reviews. Concept elicitation and cognitive debriefing interviews were conducted with owners of cats with International Renal Interest Society-staged CKD in the US and United Kingdom to further inform item development. A 2-time point observational study was then conducted in a Greek sample of owners of cats with stable CKD to allow for psychometric analysis. Expert veterinarian input was incorporated throughout. Participants were recruited using purposive convenience sampling. Owners of 10 cats participated in interviews, and owners of 208 cats were included in the psychometric evaluation. An initial 20-item questionnaire was debriefed and refined across 2 rounds of interviews, resulting in a 21-item version for psychometric evaluation. The final questionnaire comprised 13 items assessing observable HRQoL impacts of feline CKD. Psychometric analyses confirmed a unidimensional structure, with high internal consistency (Cronbach α coefficient = 0.92; McDonald ω coefficient = 0.93), moderate to good test-retest reliability (≥ 0.72), and strong convergent validity. Questionnaire responses discriminated between early and late International Renal Interest Society stages and varying levels of overall HRQoL as reported by owners and veterinarians. This research presents a novel, disease-specific, psychometrically validated questionnaire assessing HRQoL in feline CKD. The questionnaire is fit for purpose for use in feline CKD both in clinical trials and veterinary practice.

Background: Hereditary angioedema (HAE) is a rare, potentially fatal genetic disorder characterized by unpredictable attacks of bodily swelling that substantially impair patients' quality of life (QoL). Lanadelumab is approved for long-term prophylaxis (LTP) in patients with HAE; however, there are limited real-world data that compare lanadelumab with other treatments to guide patient care. Objective: The objective was to describe real-world QoL and related outcomes of patients with HAE who received lanadelumab versus other LTP. Methods: Data were drawn from a real-world, cross-sectional survey of physicians and their consulting patients with HAE in the United States from January 2023 to January 2024. Physician-reported attack and disease severity, pain, fatigue, QoL, and patient-reported outcomes were compared among patients receiving lanadelumab or other LTP. Results: Physicians reported data on 86 patients treated with lanadelumab and 84 treated with other LTP. A statistically significantly higher proportion of patients receiving lanadelumab had no chronic pain (58.1%) and no chronic fatigue (51.2%) at the time of the survey than those receiving other LTP (38.1% [p = 0.0023] and 34.9% [p = 0.0037], respectively). More patients receiving lanadelumab had "very good" physician-reported QoL and less patient-reported QoL impairment at the time of the survey compared with those receiving other LTP (p = 0.0102). A higher proportion of patients receiving lanadelumab compared with other LTP reported complete satisfaction overall with their treatment (30.2% versus 17.9%, respectively; p = 0.0144) and complete satisfaction with the efficacy of their treatment (44.2% versus 11.9%, respectively; p < 0.0001). Conclusion: In this real-world study, physicians reported a higher proportion of patients receiving lanadelumab had no chronic pain or fatigue compared with those receiving other LTP. Both physicians and patients reported higher QoL in those receiving lanadelumab. Continued real-world research in patients with HAE to further assess the effect of lanadelumab on QoL will help guide patient care.

Small-cell lung cancer (SCLC) is associated with poor survival and is accompanied by symptoms that impact patients' quality of life. Although quality of life can be assessed by the EORTC 30-item core questionnaire (QLQ-C30) and 13-item lung cancer (QLQ-LC13) module, interpretation of meaningful improvement or deterioration within and between individuals is challenging. The objective of this study was to derive thresholds for interpretation of changes over time for the key scales of Coughing, Chest Pain, Dyspnea, Physical Functioning, and Global Health Status (GHS). Anchor- and distribution-based analyses were used to derive meaningful within-patient change (MWPC) and meaningful between-group difference (MBGD) thresholds using data from the phase II DeLLphi-301 trial in patients with previously treated SCLC. Methods included estimating mean change scores, mixed models for repeated measures, classification statistics, receiver operating characteristic curves, alongside calculating half standard deviation and standard error of measurement. MWPC recommendations were ±33.3 for single-item scales QLQ-LC13 Chest Pain and Coughing, ±16.7 for both QLQ-LC13 Dyspnea and QLQ-C30 GHS, and ±20.0 for QLQ-C30 Physical Functioning. Estimated MBGD thresholds ranged from ±6 for GHS to ±22 for Coughing. To our knowledge, this study is the first to estimate MWPC and MBGD thresholds specifically in patients with relapsed SCLC. Estimated threshold ranges are considered robust given the comprehensive considerations and triangulation of various methods and can help clinicians, researchers, and healthcare decision makers to evaluate the clinical meaningfulness to patients of changes in key SCLC scales over time.

Objective To identify relevant concepts of measurement for people with amyotrophic lateral sclerosis (ALS) and to evaluate the face and content validity of clinical outcome assessments (COAs) that can be used to measure treatment benefits in ALS clinical trials. Methods A targeted literature review was conducted to explore patient experience (stage 1) and COAs used in ALS research (stage 2). s were screened against predefined eligibility criteria; full-text articles were reviewed for eligible abstracts and relevant data were extracted. Face and content validity of the identified COAs were assessed. Results Stage 1 searches identified 3,527 abstracts, of which 12 full-text articles, two summary reports, and one conference poster were included in this review. Twenty-five symptoms and 35 health-related quality of life (HRQoL) impacts were identified. Frequently reported symptoms included breathing and speech difficulties and muscle/limb weakness, each associated with a diverse range of impacts, including those related to emotional wellbeing, physical function, social and leisure activities, and activities of daily living. Stage 2 searches identified 119 COAs, of which 28 were reviewed. Many had acceptable face (13/28) and content validity (15/28), but 13 had not involved patients during development; only 10 were clearly worded and seven were lengthy, increasing patient burden risk. Conclusions This review identified wide-ranging symptoms and HRQoL impacts experienced by people with ALS, but detailed qualitative evidence is sparse. Multiple COAs were identified as potential measures in ALS clinical trials.

ObjectiveThis study aimed to develop a consensus of expert opinion on the quality standards of care and outline management best practices for pulmonary arterial hypertension (PAH) in SSc and other CTDs.MethodsTwenty physicians and four nurse practitioners (NPs) managing patients with CTD-PAH (including SSc-PAH) from six European countries participated in a modified Delphi panel. Consensus was defined as ≥80% agreement among the physicians.ResultsThe importance of a multimodal approach to screening and early detection of PAH through combining echocardiography, biomarker tests and symptom evaluation was emphasised. Consensus agreement was also reached on the usefulness and increased access of echocardiography for optimising screening and early detection processes, noting the importance of cardiology expertise for accurate assessment of right-heart variables. Panellists reached consensus agreement on the importance of a multidisciplinary approach to managing SSc- and other CTD-PAHs through collaboration between rheumatologists and pulmonary hypertension (PH) specialists, NPs and patients. Rheumatologists aligned on the usefulness of the DETECT screening algorithm, whereas cardiologists and pulmonologists remained divided, with consensus not being reached, thus highlighting the lack of agreement regarding the relevance of a stepwise approach. Similarly, no consensus was reached on the impact of the new haemodynamic definition of PH in CTD-PAH management, where greater evidence is required.ConclusionsConsensus was reached on key recommendations for optimising CTD-PAH management, including the standardisation of multimodal screening and promotion of closer collaboration between healthcare specialties and patients.