coreNASH: Multi-stakeholder Consensus on Core Outcomes for Decision Making About Nonalcoholic Steatohepatitis Treatment

The increasing prevalence and burden of nonalcoholic steatohepatitis (NASH) has spurred the development of new treatments and a need to consider outcomes used for NASH treatment decision making. Development of a NASH core outcome set (COS) can help prioritize outcomes of highest importance by incorporating the perspectives from a variety of decision makers. coreNASH was an initiative to develop a COS for NASH using a modified Delphi consensus process with a multi-stakeholder voting panel. A candidate outcome list was created based on a literature review and key informant interviews. The candidate outcome list was then condensed and prioritized through three rounds of online voting and through discussion at an in-person meeting. Outcomes were retained or eliminated based on predetermined consensus criteria, which included special weighting of patients’ opinions in the first two voting rounds. The coreNASH Delphi panel included 53 participants (7 patients, 10 clinicians and researchers, 7 health technology assessors, 22 industry representatives, 2 regulators, and 5 payers) who considered outcomes for two NASH-related COS: one for NASH without cirrhosis (F2-F3) and one for NASH with cirrhosis (F4). The initial candidate outcome list for both disease stages included 86 outcomes. The panel agreed on including two core outcomes for NASH without cirrhosis and nine core outcomes for NASH with cirrhosis in the COS. Conclusion: A consensus-based COS has been developed that can be used across the life cycle of NASH treatments. Outcomes included can contribute to decision making for regulatory, market access, and on-market decision making. Including the coreNASH COS in clinical development programs will facilitate improved comparisons and help decision makers assess the value of new products

The role of galenic innovation in improving treatment compliance and persistence: three case studies

York Zoellner1, Maria-Magdalena Balp2, Andrea Gili Marco21Hamburg University of Applied Sciences, Hamburg, Germany; 2Novartis Pharma AG, Basel, SwitzerlandBackground: The purpose of this study was to explore whether newer galenic formulations with lower treatment burdens are associated with better patient compliance and persistence compared with older more burdensome modalities.Methods: Data from the IMS Disease Analyzer database were analyzed retrospectively for two pairs of analogs (alendronate sodium once daily vs once weekly and immediate-release vs extended-release methylphenidate) and one pair of drugs with similar indications but important differences in convenience and dosing instructions (desferrioxamine vs deferasirox). Compliance was calculated as the sum of prescription durations for all prescriptions for each patient over 1 year. Persistence was calculated as the time between first and last prescriptions over 2 years (1 year for deferasirox and desferrioxamine). Data from Germany and the UK were available and used for analysis.Results: Incremental improvements in compliance were +30% in the UK and +26% in Germany for alendronate once weekly vs once daily, +14% in the UK and +19% in Germany for extended-release vs immediate-release methylphenidate, and +15% in Germany for desferrioxamine vs deferasirox. Incremental improvements in persistence were +9 months in the UK and +8 months in Germany for alendronate once weekly vs once daily, +4 months in the UK and +3 months in Germany for extended-release vs immediate-release methylphenidate, and +2 months in Germany for deferasirox vs desferrioxamine.Conclusion: The new formulations that we evaluated were associated with better compliance and persistence compared with older formulations. Despite the fact that some sources of bias could not be excluded, it is likely that these improvements can be attributed to the lower treatment burdens of the galenic formulations of the drugs considered. Further investigation is required to confirm these findings and to determine whether new galenic formulations can improve health outcomes in routine clinical practice.Keywords: galenic formulation, immediate-release methylphenidate, alendronate, deferasiro

Psychometric properties of the spanish version of the once-daily urticaria activity score (UAS) in patients with chronic spontaneous urticaria managed in clinical practice (The EVALUAS Study)

BACKGROUND: The daily diary Urticaria Activity Score (UAS) and its weekly score (UAS7) are widely used to assess signs and symptoms in patients with chronic spontaneous urticaria (CSU). The objective of this study was to assess the psychometric properties of a Spanish version of the once-daily UAS. METHODS: Observational study in patients ≥18 years old receiving usual care for CSU (daily or almost daily occurrence of generalized hives or angioedema for ≥6 weeks). Patients were included consecutively and completed the UAS, EQ-5D, and the Chronic Urticaria Quality of Life scale (CU-Q2oL) at two study visits 6 weeks apart. On each occasion, the UAS was completed once-daily for 7 consecutive days to be able to calculate the UAS7 score. Psychometric properties of reliability, construct validity, and responsiveness were assessed. The Minimal Important Difference (MID) was estimated for the UAS7 using anchor- and distribution-based approaches. RESULTS: Data from 166 patients was available for analysis (mean age 49 years, 65.7% female). Floor (5.4% of patients with the lowest possible score) and ceiling (1.2%) effects were low; 15% of patients had missing values. Internal consistency and test-retest reliability were good (Cronbach's alpha of 0.83 and an ICC of 0.84, respectively). Convergent validity was demonstrated through the pattern of correlations with the EQ-5D and CU-Q2oL and known groups' validity was demonstrated by the instrument's ability to discriminate between patients with different overall levels of urticaria severity, with between-group effect-sizes (ES) ranging from 0.36 to 1.19. The UAS7 proved responsive to change with effect sizes ranging from 0.3 to 1.52 in patients reporting improvement or deterioration in overall urticaria status. The MID for the UAS7 score was estimated at 7-8 points, on a scale of 0-42. CONCLUSIONS: The Spanish version of the UAS score has demonstrated a robust psychometric performance in patients with CSU managed in conditions of usual care. It can therefore be considered a suitable instrument to assess disease activity in clinical practice in Spanish-speaking patients. The Spanish version's reliability and validity are similar to those reported for other language versions of the once- and twice-daily variants of the UAS