The role of real world evidence in the cost-effectiveness analyses for pharmacological treatments in overactive bladder

The aim of this thesis is to evaluate the extent to which cost-effectiveness of a recently launched drug in the treatment of overactive bladder is supported by real world evidence. The demand for real world effectiveness data by Payers and decision-makers is increasing to better manage the uncertainty at the time of making reimbursement decisions. Real world data can help to fill the knowledge gap between clinical trials and actual clinical practice. Overactive bladder is one of many chronic conditions likely to impact people as they age. It is a common condition characterised by a group of lower urinary tract storage symptoms, which has a profound and measurable negative effect on patient health-related quality of life (HRQoL). The economic burden of OAB is also considerable. Antimuscarincs have been the mainstay pharmacological treatment for OAB for over 30 years, but adverse events and persistence on medication remain a key issue. Mirabegron, a ß3 adrenoceptor agonist provides an alternative option. The thesis presents and critiques 9 peer-reviewed publications to demonstrate the value evidence generated pre-health-technology assessment (HTA) and that generated post-health -technology assessment in clinical practice. Each publication adds a new building block to the value proposition, and a sophistication of methods that help illustrate the value of the new drug compared to competing alternatives. The impact of OAB on patient HRQoL is explored through analyses of both disease specific and generic validated patient reported outcome (PRO) instruments. Utility values are also derived for the purposes of health economic modelling. The comparison of efficacy and safety of mirabegron with other competing alternatives is assessed using network meta-analysis (NMA), a requirement from most HTA bodies in the absence of head-to-head evidence. The outputs from the NMA and the PRO analyses are then applied to a series of trial based and NMA based HE models to assess the cost-effectiveness of mirabegron. This is followed by an assessment of effectiveness through analysis of a large retrospective database to see if indeed cost-effectiveness is supported in the clinical practice. The thesis concludes that cost-effectiveness of mirabegron is broadly supported by Real world evidence in terms of persistence and adherence while also highlighting the strengths and weaknesses of the current research and making recommendations for future research

Recombinant FVIIIFc Versus BAY 94-9027 for Treatment of Patients with Haemophilia A:Comparative Efficacy Using a Matching Adjusted Indirect Comparison

INTRODUCTION: Prophylaxis with recombinant factor VIII (rFVIII) is the current standard of care for haemophilia A. Several approaches have been used to extend the half-life of rFVIII to improve prophylaxis outcomes. An indirect comparison of pivotal clinical trial data was performed to evaluate the relative efficacy of two extended half-life therapies approved for the prophylactic treatment of haemophilia A: recombinant FVIII-IgG1 Fc domain fusion protein (rFVIIIFc) and pegylated rFVIII (BAY 94-9027). METHODS: Matching-adjusted indirect comparison (MAIC) was conducted to compare the rFVIIIFc individualised prophylaxis arm of the A-LONG phase III clinical trial (n = 117) and the BAY 94-9027 approved dosing regimens of the PROTECT VIII phase II/III study (n = 110). Following matching for baseline characteristics, mean annualised bleeding rate (ABR) and the proportion of patients with zero bleeds were compared for rFVIIIFc and BAY 94-9027. Additional supportive analyses comparing rFVIIIFc individualised prophylaxis and the individual prophylaxis regimens included in the PROTECT VIII group (twice weekly, and every 5 and 7 days [Q5D and Q7D]) were conducted. RESULTS: Mean ABR was lower in the rFVIIIFc individualised prophylaxis group versus the BAY 94-9027 pooled prophylaxis population (3.0 versus 4.9), providing a clinically relevant and statistically significant difference (mean difference [MD] - 1.9; 95% confidence interval [CI] - 3.5 to - 0.4). A statistically significant difference in ABR was also observed for rFVIIIFc compared with BAY 94-9027 Q7D (3.2 versus 6.4; MD - 3.3; 95% CI - 6.4 to - 0.2). The difference in the proportion of patients with zero bleeds between rFVIIIFc (46.5%) and BAY 94-9027 pooled prophylaxis population (38.2%) was not statistically significant (odds ratio 1.4; 95% CI 0.8 to 2.5). CONCLUSIONS: This indirect treatment comparison indicates a statistically significant and clinically relevant difference in ABR favouring individualised prophylaxis with rFVIIIFc versus BAY 94-9027 prophylaxis. The proportion of patients with zero bleeds was numerically greater with rFVIIIFc treatment but did not achieve statistical significance

The Best of Both Worlds : An Example Mixed Methods Approach to Understand Men’s Preferences for the Treatment of Lower Urinary Tract Symptoms

Funded by Astellas Pharma Europe and Chief Scientist Office DI, SH, VW and MR are employed by the University of Aberdeen and performed the research. CM and JN are employees of Astellas Pharma EMEA, which funded the study in an unrestricted contract. All authors were involved in writing or reviewing the manuscript. Ethical approval was obtained from the College Ethics Research Board of the College of Life Science and Medicine, University of Aberdeen (CERB/2013/8/942). The Health Economics Research Unit (HERU) is supported by the Chief Scientist Office (CSO) at the Scottish Government Health and Social Care Directorate.Peer reviewedPostprin

Men’s preferences for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia : a discrete choice experiment

HERU is supported by the Chief Scientist Office (CSO) at the Scottish Government Health and Social Care Directorate. Sebastian Heidenreich acknowledges financial support from the Institute of Applied Health Science, University of Aberdeen. Medical writing support was provided by Tyrone Daniel from Bioscript Medical, and was funded by Astellas Pharma Europe Ltd. Presented in part as a poster at the ISPOR 17th Annual European Congress, November 8–12, 2014, Amsterdam, The Netherlands. The poster’s abstract was published in Value in Health. 2014;17 (7):A472. Open Access JournalPeer reviewedPublisher PD

Health-related quality of life, direct medical and societal costs among children with moderate or severe haemophilia in Europe: multivariable models of the CHESS-PAEDs study.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-04-01, epub 2022-04-04Publication status: PublishedFunder: SanofiBackgroundHaemophilia bears substantial humanistic and economic burden on children and their caregivers. Characterising the differential impact of severe versus moderate paediatric haemophilia is important for clinical and health policy decisions. We analysed health-related quality of life (HRQoL), annual direct medical (excluding factor treatment costs), non-medical and societal costs among children and adolescents with moderate and severe haemophilia A or B without inhibitors from the European CHESS-PAEDs study. Information was reported by physicians and caregivers; patients aged ≥ 8 years self-reported their HRQoL. Descriptive statistics summarised demographic and clinical characteristics, costs, and HRQoL scores (EQ-5D-Y). Regression models estimated differences in HRQoL and costs for moderate versus severe haemophilia adjusting for age, body mass index z-score, country, number of comorbidities, and weight-adjusted annual clotting factor consumption.ResultsThe analytic sample comprised 794 patients with a mean age of 10.5 years; most had haemophilia A (79%) and 58% had severe haemophilia. Mean predicted direct medical costs in moderate patients were two-thirds of the predicted costs for severe disease (€3065 vs. €2047; p ConclusionChildren with haemophilia and their caregivers displayed a significant economic and humanistic burden. While severe patients showed the highest direct medical and societal costs, and worse HRQoL, the burden of moderate haemophilia on its own was substantial and far from negligible

Differential humanistic and economic burden of mild, moderate and severe haemophilia in european adults: a regression analysis of the CHESS II study.

From Europe PMC via Jisc Publications RouterHistory: ppub 2022-04-01, epub 2022-04-04Publication status: PublishedFunder: Sanofi; Grant(s): SanofiBackgroundThe lifelong nature of haemophilia makes patient-centred and societal assessments of its impact important to clinical and policy decisions. Quantifying the humanistic and economic burden by severity is key to assessing the impact on healthcare systems. We analysed the annual direct medical (excluding factor replacement therapy costs) and non-medical costs as well as societal costs and health-related quality of life (HRQoL) of mild, moderate and severe disease among adults with haemophilia A or B without inhibitors in Europe. Participants in the CHESS II study reported their HRQoL, non-medical costs, and work impairment; physicians provided costs and consultation history from the medical chart. Descriptive statistics summarized patient characteristics, costs, and HRQoL scores. Regression models estimated differences in outcomes for moderate and severe versus mild disease, adjusting for age, body mass index, country, comorbidities, weight-adjusted factor consumption and education.ResultsThe analytic sample included 707 patients with a mean age of 38 years; the majority of patients had haemophilia A (81%), and 47% had severe disease, followed by moderate (37%) and mild disease (16%). Patients with severe or moderate disease had on average higher direct costs, €3105 and €2469 respectively, versus mild disease. Societal costs were higher for patients with severe and moderate disease by €11,115 and €2825, respectively (all P ConclusionSeverity of haemophilia is predictive of increasing economic and humanistic burden. The burden of moderate disease, as measured by direct costs and HRQoL, did not appear to be substantially different than that observed among patients with severe haemophilia

Validation of the Patient Perception of Intensity of Urgency Scale in Patients with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia

AbstractObjectiveTo assess the reliability and validity of scores derived from the Patient Perception of Intensity of Urgency Scale (PPIUS) in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).MethodsA post hoc analysis of the phase II Solifenacin and Tamsulosin in Males with Lower Urinary Tract Symptoms Associated with Benign Prostatic Hyperplasia trial (NCT00510406), a 12-week clinical trial in men with LUTS associated with BPH, assessed the measurement properties of six PPIUS-derived scores: mean score; maximum urgency score; total urgency and frequency score (TUFS; average sum of urgency scores over 3 days); and numbers of urgency episodes, urgency episodes of grade 3 or 4, and urgency incontinence episodes. Test-retest reliability, presence of floor/ceiling effects, responsiveness to change, known-group validity, and concurrent validity were assessed for each score.ResultsA total of 901 patients had at least one valid PPIUS assessment after baseline. TUFS demonstrated good test-retest reliability (intraclass correlation coefficient >0.8), discriminated between groups defined based on International Prostate Symptom Score storage score severity (known-groups validity), had high concurrent validity, and had high responsiveness to change (Guyatt’s responsiveness statistic 0.88), with an absence of floor or ceiling effects. The psychometric properties of other PPIUS-derived scores were not as consistently robust and showed either low-to-moderate responsiveness, presence of a floor or ceiling effect, or low-to-moderate test-retest reliability.ConclusionsThis study shows that the PPIUS is reliable and valid in patients with LUTS associated with BPH. TUFS provided the best combination of psychometric properties of the six scores derived from the PPIUS and appeared to be an appropriate measure of urgency and frequency

Exploring Managerial Perspectives of Using Building Management System through TAM: An Empirical Study of Commercial Sector of Pakistan

A cursory review of the Building Management System (BMS) which optimizes building performance as a move towards smart cities has been presented in the present study. The extant study is an effort to distinguish and analyze the circumstances as if the underdeveloped economies are less likely to be benefitted by the contemporary trends of BMS as compare to the developed countries. Moreover, the current study identifies the factors which may cause to render the managerial acceptance for using BMS through the Technology Acceptance Model (TAM). TAM was used to measure four behaviors (latent factors) namely subjective norms, organization support, compatibility, and technology complexity. The data were statistically evaluated via multiple regression analysis using the Statistical Package for Social Sciences (SPSS). Results suggested that organization support and compatibility have a significant influence on managerial intentions to use BMS while subjective norms, technology complexity have no significant influence. The findings of this study may serve as guidelines for improvement in the acceptance process and using building management systems in commercial sectors of developing countries

Discours II.

Median time to discontinuation: sensitivity analyses of treatment-naïve men (no prior combination therapy)* (a); index combination first prescribed on the same date* (b); and men who received an α-blocker and an antimuscarinic as combination therapy within 60 days 635 ‡ (c). (PDF 962 kb