Isaac Odeyemi

Comparative efficacy and safety of medical treatments for the management of overactive bladder: a systematic literature review and mixed treatment comparison.

CONTEXT Overactive bladder (OAB) treatment guidelines recommend antimuscarinics as first-line pharmacologic therapy. Mirabegron is a first-in-class β3-adrenoceptor agonist licensed for the treatment of OAB and has shown to be well tolerated and effective in the treatment of OAB symptoms. OBJECTIVE To assess the relative efficacy and tolerability of OAB medications, specifically mirabegron 50 mg versus antimuscarinics in patients with OAB. EVIDENCE ACQUISITION A systematic literature search was performed on published peer-reviewed articles from 2000 to 2013. This review included randomised controlled trials (RCTs) studying changes in symptoms (micturition frequency, incontinence, and urgency urinary incontinence [UUI] episodes) and incidence of the most frequently reported adverse events (dry mouth, constipation) associated with current OAB medications. The following drugs were considered in addition to mirabegron: darifenacin, tolterodine immediate release (IR) and extended release (ER), oxybutynin IR/ER, trospium, solifenacin, and fesoterodine. Bayesian mixed treatment comparisons (MTCs) were performed for efficacy (micturition, incontinence, UUI) and tolerability (dry mouth, constipation, blurred vision). EVIDENCE SYNTHESIS Overall, 44 RCTs involving 27,309 patients were included. The MTCs showed that mirabegron 50 mg was as efficacious as antimuscarinics in reducing the frequency of micturition incontinence and UUI episodes, with the exception of solifenacin 10 mg that was more efficacious than mirabegron 50 mg in improving micturition frequency and frequency of UUI. Mirabegron 50 mg had an incidence of dry mouth similar to placebo and significantly lower than all included antimuscarinics. CONCLUSIONS Mirabegron 50 mg had similar efficacy to most antimuscarinics and lower incidence of dry mouth, the most common adverse event reported with antimuscarinics and one of the main causes of discontinuation of treatment. Despite being a powerful tool for evidence-based health care evaluation, the Bayesian MTC method has limitations. Further head-to-head comparisons between mirabegron and antimuscarinics should be conducted to confirm our results.

The impact of the overactive bladder on health-related utility and quality of life

To evaluate the impact of the overactive bladder (OAB) on quality of life and health‐related utility.

Clinical efficacy of fidaxomicin compared with vancomycin and metronidazole in Clostridium difficile infections: a meta-analysis and indirect treatment comparison

OBJECTIVES To evaluate the efficacy of fidaxomicin treatment, which has a limited effect on the normal gut flora, compared with vancomycin and metronidazole treatment in Clostridium difficile infections (CDIs). METHODS A systematic literature review was conducted in July to August 2011 and updated in July 2013. For fidaxomicin versus vancomycin, efficacy was evaluated using meta-analysis of data from two Phase III direct comparative studies (n = 1164). As there were no studies comparing fidaxomicin and metronidazole, an indirect comparison was made using data from three vancomycin versus metronidazole studies (n = 345), using the methodology of Bucher et al. (J Clin Epidemiol 1997; 50: 683-91). This provides an OR for the indirect comparison of fidaxomicin versus metronidazole when direct evidence of fidaxomicin versus vancomycin and vancomycin versus metronidazole is available. RESULTS Clinical cure rates were similar for fidaxomicin and vancomycin; the OR (95% CI) was 1.17 (0.82, 1.66). Recurrence [0.47 (0.34, 0.65)] was significantly lower and sustained cure rates [1.75 (1.35, 2.27)] significantly higher for fidaxomicin than vancomycin. Similar results were obtained in patient subgroups with severe CDI and with non-severe CDI. From the indirect comparison, the likelihood of recurrence [0.42 (0.18, 0.96)] and sustained cure [2.55 (1.44, 4.51)] were significantly improved for fidaxomicin versus metronidazole. Again, similar results were obtained in those with severe and non-severe CDI. CONCLUSIONS Fidaxomicin provides improved sustained cure rates in patients with CDI compared with vancomycin. An indirect comparison indicates that the same is also true for fidaxomicin versus metronidazole. In view of these data, fidaxomicin may be considered as first-line therapy for CDI.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection

Objectives Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. Methods A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20 000/QALY and £30 000/QALY. One-way and probabilistic sensitivity analyses were performed. Results Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14 515 and £14 344, respectively) and in patients with a first recurrence (£16 535 and £16 926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16 529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 60% for severe CDI and 68% in a first recurrence. Conclusions Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin.

Economic analysis of micafungin versus liposomal amphotericin B for treatment of candidaemia and invasive candidiasis in Germany

ABSTRACT Objective: To investigate the economic impact of micafungin (MICA) for treatment of invasive candidiasis and candidaemia (systemic Candida infections), a health economic analysis was conducted comparing MICA with liposomal amphotericin B (L-AMB). Research design and methods: The model was based on a phase III, randomised, double-blind, clinical trial which compared MICA with L-AMB. The model entailed a period of 14–20 weeks starting from initiation of treatment and was analysed from a German hospital perspective. Main outcome measures: The main outcome measures were defined as the percentage of patients achieving clinical and mycological response after initial treatment and who were alive at the end of the study (EOS), and the total treatment-associated costs over the study period. Results: The health economic analysis shows that with MICA, 52.9 % of patients are successfully treated and were alive at EOS compared to 49.1 % for L-AMB. In addition, MICA has, on average, lower treatment-associated costs than L-AMB with [euro]43 243 and [euro]49 216 per patient, respectively. Because the costs are lower and the effectiveness is higher for MICA in comparison with L-AMB, MICA is more cost-effective than L-AMB. However, the results of the probabilistic sensitivity analysis show that the differences cannot be considered significant due to a large variance, although MICA remained the most cost-effective option throughout the one-way sensitivity analyses. Conclusions: The lower costs and higher effectiveness reported for MICA versus L-AMB in this analysis indicate that MICA may be a more cost-effective therapy in the treatment of invasive candidiasis and candidaemia when compared with L-AMB.

A cost-utility analysis of once daily solifenacin compared to tolterodine in the treatment of overactive bladder syndrome

ABSTRACT Objective: To evaluate the cost-utility of solifenacin, a new generation antimuscarinic, compared with tolterodine in the treatment of overactive bladder syndrome (OAB), from the perspective of the UK National Health Service (NHS). Research design and methods: A 1-year Markov model was constructed using data from a 12-week, randomised, double-blind study that compared flexible dosing with solifenacin (5 mg and 10 mg) with tolterodine (IR 2 mg bd/ER 4 mg) in adults with OAB. The model incorporated five discrete health states that were based on disease severity (micturitions/day and incontinence episodes/day). A ‘drop out’ state was also used in the model to account for patients that discontinued treatment in the first year. UK-specific costs for drug treatment and pad use as well as utilities were assigned to each health state. Results: Solifenacin was a less costly and more effective treatment strategy compared with tolterodine. During the course of 1 year, the estimated cost per patient was £509 for patients treated with solifenacin and £526 for those given tolterodine, a cost saving of £17 per patient. Treatment with solifenacin was also associated with a small incremental gain of 0.004 quality-adjusted-life-years (QALYs) over tolterodine. Sensitivity analysis suggests that the incremental cost effectiveness of solifenacin relative to tolterodine does not appear to exceed £30 000/QALY with even large variations in key model parameters. Conclusion: Flexible dosing with solifenacin is likely to be cost-effective versus tolterodine in the treatment of OAB. Further studies are needed to confirm these results.

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

BackgroundThe 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.MethodsPatients 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.ResultsThirty-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.ConclusionsThe 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.

Community-based health insurance programmes and the national health insurance scheme of Nigeria: challenges to uptake and integration

BackgroundNigeria has included a regulated community-based health insurance (CBHI) model within its National Health Insurance Scheme (NHIS). Uptake to date has been disappointing, however. The aim of this study is to review the present status of CBHI in SSA in general to highlight the issues that affect its successful integration within the NHIS of Nigeria and more widely in developing countries.MethodsA literature survey using PubMed and EconLit was carried out to identify and review studies that report factors affecting implementation of CBHI in SSA with a focus on Nigeria.ResultsCBHI schemes with a variety of designs have been introduced across SSA but with generally disappointing results so far. Two exceptions are Ghana and Rwanda, both of which have introduced schemes with effective government control and support coupled with intensive implementation programmes. Poor support for CBHI is repeatedly linked elsewhere with failure to engage and account for the ‘real world’ needs of beneficiaries, lack of clear legislative and regulatory frameworks, inadequate financial support, and unrealistic enrolment requirements. Nigeria’s CBHI-type schemes for the informal sectors of its NHIS have been set up under an appropriate legislative framework, but work is needed to eliminate regressive financing, to involve scheme members in the setting up and management of programmes, to inform and educate more effectively, to eliminate lack of confidence in the schemes, and to address inequity in provision. Targeted subsidies should also be considered.ConclusionsDisappointing uptake of CBHI-type NHIS elements in Nigeria can be addressed through closer integration of informal and formal programmes under the NHIS umbrella, with increasing involvement of beneficiaries in scheme design and management, improved communication and education, and targeted financial assistance.

Modelling the economic impact of recombinant activated Factor VII and activated prothrombin-complex concentrate in the treatment of a mild to moderate bleed in adults with inhibitors to clotting Factors VIII and IX at a comprehensive care centre in the UK

Summary To estimate the costs and consequences of using recombinant activated Factor VII (rFVIIa; NovoSeven (Novo Nordisk)), compared with activated prothrombin-complex concentrate (aPCC; FEIBA (Baxter Healthcare)), to manage a minor (i.e. mild to moderate) bleeding episode at a haemophilia treatment centre (Comprehensive Care Centre; (CCC)) in the UK among adults with high titre, high responding inhibitors (>10 BU). This was a modelling study performed from the perspective of the UKs National Health Service (NHS). Clinical outcomes and resource utilisation attributable to managing a minor bleed were obtained from published literature, supplemented with information about treatment patterns and associated resource utilisation derived from interviews with 22 consultant haematologists experienced in managing inhibitor patients. Using these data sources, a decision tree modelling the management of a minor bleed at a CCC was constructed. Unit resource costs at 1999/2000 prices were applied to the resource utilisation estimates in the model to calculate the expected NHS cost of managing a minor bleeding episode. Consensus on the probabilities and resource utilisation estimates in the model were reached at a meeting comprising seven of the 22 consultant haematologists. The expected NHS cost of managing a minor bleeding episode among adults initially treated with rFVIIa or aPCC was estimated to be £11,794 and £20,467, respectively. Additionally, the expected time to resolving a minor bleeding episode when initially treated with rFVIIa or aPCC was estimated to be 30 hours and 58 hours, respectively. Our model suggests that rFVIIa is a cost effective treatment compared to aPCC for the treatment of a minor bleed at a CCC, since it improves clinical outcome and reduces NHS costs. This finding warrants further investigation in a prospective, comparative, randomised controlled study.

Health economics and outcomes research within drug development: challenges and opportunities for reimbursement and market access within biopharma research.

Healthcare decision makers who determine funding for new medical technologies depend on manufacturers to provide evidence of the technologys efficacy, safety and cost-effectiveness. Constrained budgets and increasing reliance on formal health technology assessment (HTA) have created an abundance of external hurdles that manufacturers must navigate to ensure successful product commercialization. These demands have pushed pharmaceutical companies to adjust their internal structures to coordinate generation of appropriate evidence. In this article we summarize internal and external opportunities for manufacturers to establish a foundation of evidence for successful market access, starting in Phase I of development and continuing throughout the post-approval product lifecycle.