Assessment of health-related quality of life and patient preferences for treatments of overactive bladder

Overactive bladder (OAB) is a highly prevalent symptomatic condition characterised by urinary symptoms: urgency and urinary frequency, and is often accompanied by incontinence and nocturia. Although it has no impact on mortality, OAB is a debilitating condition and has a significant impact on health-related quality of life (HRQoL). The patient perspective is becoming increasingly important in the assessment of the value of new treatments by Health Technology Assessment (HTA) bodies as it informs the burden of disease, the clinical relevance of the treatment benefit and can be a predictor of the persistence with treatment which is often an important factor in health economic evaluations. Therefore, it is important to ensure that a robust assessment of the patient perspective is included during the HTA process for OAB therapies. The aim of this thesis was to provide an understanding and a critical assessment of HRQoL for treatments of OAB in relation to HTA. The thesis presented and critically assessed eight peer reviewed publications by the researcher that examined several aspects of patient perspective by applying different methodologies. The studies that were included in this thesis provide a coherent body of evidence that has been used by HTA bodies to assess the value of OAB treatments and has had an influence on reimbursement guidelines for mirabegron, a first in class treatment for overactive bladder. Patient burden was assessed using concept elicitation interviews allowing a comprehensive evaluation of the quality of life dimensions affected by OAB. The patient preferences influencing patients and physician treatment choices were investigated through two discrete choice experiments conducted in three European countries. The clinical relevance of the treatment benefit on OAB symptoms was examined in three large clinical trials by conducting single and double responder analyses involving a response based on both objectively assessed symptoms and PRO instruments. Finally, the estimation of utility values and a robust economic evaluation that were integral part of the single technology appraisal of mirabegron in the United Kingdom were discussed. The thesis concluded that performing a robust and comprehensive assessment of the patient perspective is a critical component of the value demonstration in OAB and has been a critical element informing HTA decisions in OAB. Limitations were discussed and the thesis provides recommendations for future research to further examine the generalisability of this work in other setting

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

Development of Quality Assessment Tool for Systematic Reviews and Meta-analyses of Real-world Studies: A Delphi Consensus Survey

Background: The increasing adoption of real-world studies in healthcare for decision making and planning has further necessitated the need for a specific quality assessment tool for evidence synthesis. This study aimed to develop a quality assessment tool for systematic reviews (SR) and meta-analysis (MA) involving real-world studies (QATSM-RWS) using a formal consensus method. Methods: Based on scoping review, the authors identified a list of items for possible inclusion in the quality assessment tool. A Delphi survey was formulated based on the identified items. A total of 89 experts, purposively recruited, with research experience in real-world data were invited to participate in the first round of Delphi survey. The participants who responded in the first Delphi round were invited to participate (n = 15) in the phrasing of the items. Results: Strong level of agreement was found on the proposed list of items after the first round of Delphi. A rate of agreement ≥ 0.70 was used to define which items to keep in the tool. A list of 14 items emerged as suitable for QATSM-RWS. The items were structured under five domains: introduction, methods, results, discussions, and others. All participants agreed with the proposed phrasing of the items. Conclusion: This is the first study that has developed a specific tool that can be used to appraise the quality of SR and MA involving real-world studies. QATSM-RWS may be used by policymakers, clinicians, and practitioners when evaluating and generating real-world evidence. This tool is now undergoing validation process

Improvement in pain-related quality of life in patients with hemophilia A treated with rFVIIIFc individualized prophylaxis: post hoc analysis from the A-LONG study

Background: Pain, a common symptom of hemophilia, begins early in life primarily due to joint bleeding. Recurrent bleeding adversely affects patients’ pain-related physical functioning, which can negatively impact their quality of life (QoL). Objective: Post hoc analysis of data from the A-LONG study (NCT01181128), to assess change over time in pain-related QoL in patients with severe hemophilia A treated prophylactically with recombinant factor VIII Fc fusion protein (rFVIIIFc). Methods: Patients who completed Haem-A-QoL (17–65 years) and EQ-5D-3L (⩾12–65 years) questionnaires at baseline (BL) and end of study (EoS). Individual-level changes were assessed using three pain-related items of the Haem-A-QoL ‘Physical Health’ domain and the pain/discomfort item of EQ-5D-3L. Distributions of responses (EoS versus BL) were compared using McNemar’s test. Results: A significantly greater proportion of patients reported they did not experience painful swellings (n = 87; 66% versus 46%, p < 0.01) or pain in their joints (n = 89; 42% versus 27%; p < 0.05) at EoS versus BL. The proportion of patients who did not find it painful to move numerically increased at EoS versus BL (n = 86; 47% versus 38%; p = NS). A significantly greater proportion of patients reported no pain/discomfort at EoS versus BL (n = 116; 45% versus 34%; p < 0.05). Conclusion: This study reports the effect of FVIII prophylaxis on patient-reported measures of pain over time in patients with severe hemophilia A. The results of this post hoc analysis showed improvements in pain from BL to EoS in patients receiving rFVIIIFc individualized prophylaxis indicating effective pain management, a key component of patient care

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

Content validity and test-retest reliability of patient perception of intensity of urgency scale (PPIUS) for overactive bladder

BACKGROUND: The Patient Perception of Intensity of Urgency Scale (PPIUS) is a patient-reported outcome instrument intended to measure the intensity of urgency associated with each urinary or incontinence episode. The objectives of this study were to assess the content validity, test-retest reliability, and acclimation effect of the PPIUS in overactive bladder (OAB) patients. METHODS: Patients undergoing treatment for OAB were recruited to participate in a non-interventional study by completing a three-day micturition diary including the PPIUS for three consecutive weeks. Following completion of the three-week study, participants from two select sites also completed a cognitive interview to assess their comprehension of the PPIUS. RESULTS: Thirty-nine participants successfully completed the three-week test-retest study; twelve of these participants completed the cognitive interview. Test-retest reliability was high based on intra-class correlation coefficient of 0.95. Among stable patients, the difference between the mean ratings of any two weeks was non-significant. Among the twelve interview participants, nine found it simple to choose a PPIUS rating for each of their micturition episodes and most found the urgency rating definitions consistent with their urgency experiences. CONCLUSIONS: The results demonstrated content validity based on qualitative interviews, and excellent test-retest reliability among stable patients. In addition, no acclimation effect was observed among stable patients. These findings support the use of the PPIUS as a reliable measure of urgency in both clinical trial and real life settings. The validity of PPIUS could be further established with future studies investigating the relationship between discretely graded urgency and incontinence continuum

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

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

From Springer Nature via Jisc Publications RouterHistory: received 2021-12-01, accepted 2022-03-22, registration 2022-03-23, pub-electronic 2022-04-04, online 2022-04-04, collection 2022-12Publication status: PublishedFunder: Sanofi; doi: http://dx.doi.org/10.13039/100004339; Grant(s): SanofiAbstract: Background: The 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. Results: The 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 < 0.01). HRQoL scores were also significantly worse for severe and moderate patients versus those with mild disease. Conclusion: Severity 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