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Objectives: The non-transfusion-dependent beta-thalassaemia-patient-reported outcome (NTDT-PRO) questionnaire was developed for assessing anaemia-related tiredness/weakness (T/W) and shortness of breath (SoB) among patients with NTDT. Psychometric properties were evaluated using blinded data from the BEYOND trial (NCT03342404)., Design: Analysis of a phase 2, double-blind, randomised, placebo-controlled trial., Setting: USA, Greece, Italy, Lebanon, Thailand and the UK., Participants: Adults (≥18 years) (N=145) with NTDT who had not received a red blood cell transfusion within 8 weeks prior to randomisation, with mean baseline haemoglobin level ≤100 g/L., Measures: NTDT-PRO daily scores from baseline until week 24, and scores at select time points for the 36-Item Short Form Health Survey version 2 (SF-36v2), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Patient Global Impression of Severity (PGI-S)., Results: Cronbach's alpha at weeks 13-24 was 0.95 and 0.84 for the T/W and SoB domains, respectively, indicating acceptable internal consistency reliability. Among participants self-reporting no change in thalassaemia symptoms via the PGI-S between baseline and week 1, intraclass correlation coefficients were 0.94 and 0.92 for the T/W and SoB domains, respectively, indicating excellent test-retest reliability. In a known-groups validity analysis, least-squares mean T/W and SoB scores at weeks 13-24 were worse in participants with worse scores for the FACIT-F Fatigue Subscale (FS), SF-36v2 vitality or PGI-S. Indicating responsiveness, changes in T/W and SoB domain scores were moderately correlated with changes in haemoglobin levels, and strongly correlated with changes in SF-36v2 vitality, FACIT-F FS, select FACIT-F items and the PGI-S. Improvements in least-squares mean T/W and SoB scores were higher in participants with greater improvements in scores on other PROs measuring similar constructs., Conclusions: The NTDT-PRO demonstrated adequate psychometric properties to assess anaemia-related symptoms in adults with NTDT and can be used to evaluate treatment efficacy in clinical trials., Competing Interests: Competing interests: ATT—consulting fees from Agios Pharmaceuticals; research funding and consulting fees from Celgene/Bristol Myers Squibb, Ionis Pharmaceuticals, Novartis Pharmaceuticals and Vifor Pharma. KMM—consulting fees from Agios Pharmaceuticals, Celgene/Bristol Myers Squibb, CRISPR Therapeutics, Novartis, Pharmacosmos and Vifor Pharma. VV—research funding from Bristol Myers Squibb. AK—advisory board fees and consulting fees from Agios Pharmaceuticals, Celgene/Bristol Myers Squibb, Chiesi Farmaceutici, CRISPR Therapeutics/Vertex Pharmaceuticals, Ionis Pharmaceuticals, Novartis and Vifor Pharma; research support from Celgene/Bristol Myers Squibb and Novartis. JL-B, AY, JKS and LMB—employment by and stock/equity holder of Bristol Myers Squibb. SG—employment by Evidera; consultancy fees from Bristol Myers Squibb, Gilead and Janssen. CP—employment by Evidera. ALS—employment by Adelphi Values. DM—employment by Bristol Myers Squibb. MDC—advisory board fees from Celgene/Bristol Myers Squibb, CRISPR Therapeutics, Ionis Pharmaceuticals, Novartis, Novo Nordisk, Sanofi Genzyme and Vifor Pharma., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: General practitioner (GP) training programme involves a complex process. In Italy, unlike in other European countries, there is no national core curriculum for the training of GPs and the three-year specific training course in General Medicine (CSFMG) is not equated as a proper specialty. Furthermore, the quality of the CFSMGs is poorly investigated and data are difficult to find/fragment. The aim of this study is to describe and compare GP tranining from two pilot regions (Lombardy and Lazio)., Methods: The study analysed the white and grey literature. For data collection a descriptive grid was created using the characteristics foreseen by current legislation as comparison indicators; the information came exclusively from official and public written data., Results: The analysis reports indicators: structural-organisational; theoretical activity; practical activity; research/guided study; final thesis., Discussion: The most evident fact that emerges is the lack of available (show the gap), public and official information on the GP training, therefore the description and comparison of the basic indicators in the pilot Regions suffers. A learning model based more on minimum time requirements (time-based learning) than on competences to be acquired (competencies-based learning) is evident. Furthermore, the professional/academic profiles of the lecturers are not available and thus comparable; finally, no information on the training methodologies of the frontal/research sessions can be found., Conclusions: The limitation to only two Regions and the lack of available data do not allow a comprehensive assessment and it would be useful to extend the study on a national scale. However, there is a clear need for improved transparency and evaluation within the GP's training in different Regions through a periodic monitoring system with specific indicators (quantitative and qualitative). The re-establishment/establishment of an independent national observatory on Training in General Practice would be desirable.

Introduction: Plaque psoriasis can significantly impact patients' quality of life. We assessed psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), developed to capture patients' experiences of signs, symptoms and impacts of psoriasis., Methods: Pooled, blinded, 16-week data from 1002 patients in the BE VIVID and BE READY bimekizumab phase 3 trials were analysed. The suitability of the P-SIM missing score rule (weekly scores considered missing if ≥ 4 daily scores were missing) was assessed. Test-retest reliability was evaluated using intraclass correlation coefficients (ICCs). Convergent validity was assessed between P-SIM and relevant patient-reported outcome (PRO) (Dermatology Life Quality Index [DLQI], DLQI item 1 [skin symptoms], Patient Global Assessment of Psoriasis) and clinician-reported outcome (ClinRO) scores (Psoriasis Area and Severity Index [PASI], Investigator's Global Assessment [IGA]) at baseline and week 16. Known-groups validity was assessed, comparing P-SIM scores between patient subgroups predefined using PASI/IGA scores. Sensitivity to change over 16 weeks was evaluated; responder definition (RD) thresholds were explored., Results: The missing score rule used did not impact P-SIM scores. Test-retest reliability analyses demonstrated excellent score reproducibility (ICC 0.91-0.98). Inter-item correlations at baseline and week 16 were strong (> 0.5), apart from "choice of clothing" with "skin pain" and "burning" at baseline (both 0.49). All P-SIM scores were moderately to strongly correlated with other outcomes, demonstrating convergent validity, apart from ClinROs (PASI, IGA) at baseline that had low variability. P-SIM scores discriminated known groups at week 16, confirming known-groups validity. Changes from baseline to week 16 in P-SIM and other clinically relevant outcomes were strongly correlated (> 0.5; weaker with ClinROs), establishing sensitivity to change. Anchor-based RD analyses determined a four-point P-SIM item score decrease as indicative of marked clinically meaningful improvement., Conclusion: P-SIM scores demonstrated good reliability, validity and sensitivity to change. A four-point RD threshold could be used to assess 16-week treatment effects., Trial Registration: BE VIVID: NCT03370133; BE READY: NCT03410992., (© 2021. The Author(s).)

Introduction: This analysis assessed the psychometric properties of the Psoriasis Symptoms and Impacts Measure (P-SIM), a novel patient-reported outcome (PRO) tool designed to capture patient experiences of the signs, symptoms and impacts of psoriasis., Methods: Blinded data from the BE RADIANT phase 3b trial of bimekizumab were analysed. In BE RADIANT, patients were randomised 1:1 to bimekizumab 320 mg every 4 weeks (Q4W) or secukinumab 300 mg (weekly until Week 4, then Q4W). Three items (itching, skin pain and scaling) of the P-SIM were electronically assessed throughout the trial and were scored from 0 to 10 (none to very severe signs/symptoms/impacts). Test-retest reliability was determined using intraclass correlations. Convergent validity was assessed between P-SIM and other relevant PRO and clinician-reported outcome (ClinRO) scores. Known-groups validity was assessed by comparing mean P-SIM item scores between patient subgroups based on the Psoriasis Area and Severity Index (PASI)/Investigator's Global Assessment (IGA) scores. Responsiveness was assessed via correlations between changes from baseline in P-SIM item scores and other relevant PRO and ClinRO scores. Anchor-based responder analyses and empirical cumulative distribution function (eCDF) curves determined responder thresholds., Results: The three P-SIM items yielded high intraclass coefficients (> 0.70). By Week 48, the three P-SIM items had moderate (> 0.30 and ≤ 0.50) to strong (> 0.50) correlations with other PROs and weaker correlations with ClinROs, demonstrating good convergent validity. For almost all known-group comparisons, statistically significant between-subgroup score differences were seen across all three P-SIM items. Changes from baseline in the P-SIM and other relevant outcomes were above the acceptable threshold of ≤ 0.30, demonstrating sensitivity to change. Anchor-based analyses determined a ≥ four-point reduction from baseline to indicate marked clinically meaningful improvement for the P-SIM., Conclusion: These results support the validity, reliability and sensitivity to change of the P-SIM in assessing key symptoms (itching, skin pain and scaling) in patients with moderate to severe plaque psoriasis., Trial Registration: NCT03536884., (© 2021. The Author(s).)

Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR., Methods: This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR. The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry., Results: Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively., Conclusions: Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival.

The growing number of disease-modifying treatments (DMTs) for patients with multiple sclerosis (MS) and the high acquisition costs of these DMTs are likely to increase the demand for information on their cost effectiveness. To improve the comparability and applicability of the findings from future cost-effectiveness analyses, it would be useful to have a clear understanding of the methodological challenges of modelling the cost effectiveness of DMTs in MS and the different approaches taken by such studies to date. In contrast to previous review studies, this review focuses on long-term time horizon (≥10 years) simulation-based cost-effectiveness analyses with homogeneous contexts of analysis (i.e. those with similar study objectives, comparators, and target populations) published over the past decade. By doing so, it provides a clearer picture of how modelling approaches taken in the existing studies truly differ across studies, and reveals major areas for improvement in conducting future cost-effectiveness analyses of DMTs for patients with MS.