Benefit–harm analysis of azithromycin for the prevention of acute exacerbations of chronic obstructive pulmonary disease

BackgroundLow-dose oral azithromycin therapy is recommended as a preventive treatment for acute exacerbations of COPD. However, the overall benefit–harm balance of this treatment has not been well studied.MethodsA probabilistic Markov model of COPD was created to simulate the course of COPD over 20 years. The model was populated with evidence from the literature and dedicated data analysis. The benefit of azithromycin was modelled as a reduction in exacerbation rates. Adverse events, including cardiovascular events, hearing loss, gastrointestinal symptoms and antimicrobial resistance (leading to a gradual decline in the effectiveness of azithromycin), were considered. All outcomes were assigned a health-related utility weight to estimate the overall net change in the quality-adjusted life year (QALY) associated with the use of azithromycin.ResultsIn patients with a positive exacerbation history, azithromycin resulted in a net QALY gain of 17.9 per 100 patients (99.8% probability of expected QALY gain) over 20 years. The net benefit increased to 21.8 QALYs per 100 patients (99.9% probability of expected QALY gain) among the ‘frequent exacerbator’ subgroup. Azithromycin was not net beneficial among those without any moderate/severe exacerbations in the previous year. Findings were robust against series of sensitivity, scenario and threshold analyses.ConclusionsLong-term therapy with azithromycin confers a net benefit to ex-smoker patients with COPD with a recent history of exacerbations and an even larger benefit to those who are frequent exacerbators.

Comparative Effectiveness of Implantable Defibrillators for Asymptomatic Brugada Syndrome: A Decision‐Analytic Model

Background Optimal management of asymptomatic Brugada syndrome (BrS) with spontaneous type I electrocardiographic pattern is uncertain. Methods and Results We developed an individual‐level simulation comprising 2 000 000 average‐risk individuals with asymptomatic BrS and spontaneous type I electrocardiographic pattern. We compared (1) observation, (2) electrophysiologic study (EPS)‐guided implantable cardioverter‐defibrillator (ICD), and (3) upfront ICD, each using either subcutaneous or transvenous ICD, resulting in 6 strategies tested. The primary outcome was quality‐adjusted life years (QALYs), with cardiac deaths (arrest or procedural‐related) as a secondary outcome. We varied BrS diagnosis age and underlying arrest rate. We assessed cost‐effectiveness at $100 000/QALY. Compared with observation, EPS‐guided subcutaneous ICD resulted in 0.35 QALY gain/individual and 4130 cardiac deaths avoided/100 000 individuals, and EPS‐guided transvenous ICD resulted in 0.26 QALY gain and 3390 cardiac deaths avoided. Compared with observation, upfront ICD reduced cardiac deaths by a greater margin (subcutaneous ICD, 8950; transvenous ICD, 6050), but only subcutaneous ICD improved QALYs (subcutaneous ICD, 0.25 QALY gain; transvenous ICD, 0.01 QALY loss), and complications were higher. ICD‐based strategies were more effective at younger ages and higher arrest rates (eg, using subcutaneous devices, upfront ICD was the most effective strategy at ages 20–39.4 years and arrest rates >1.37%/year; EPS‐guided ICD was the most effective strategy at ages 39.5–51.3 years and arrest rates 0.47%–1.37%/year, and observation was the most effective strategy at ages >51.3 years and arrest rates <0.47%/year). EPS‐guided subcutaneous ICD was cost‐effective ($80 508/QALY). Conclusions Device‐based approaches (with or without EPS risk stratification) can be more effective than observation among selected patients with asymptomatic BrS. BrS management should be tailored to patient characteristics.

Economic Evaluation of a Mobile Diary App versus Paper-based Diary Cards for Patients with Borderline Personality Disorder (Preprint)

BACKGROUND The use of mobile diary applications (apps) in dialectical behaviour therapy (DBT) could entail several positive consequences, such as allowing therapists to follow their patients during treatment. OBJECTIVE The objective of this study was to examine the costs and consequences of using a mobile diary app compared to paper-based diary cards in DBT treatment for patients with borderline personality disorder (BPD) in a psychiatric outpatient facility to develop the current knowledge. METHODS The study was conducted alongside a pragmatic, multicentre randomized controlled trial. Participants were recruited at five Danish psychiatric outpatient facilities and were randomized to register emotions, urges, and skills use in a mobile diary app or on paper-based diary cards. Participants in both groups received DBT delivered by therapists. A cost-consequence analysis with a time horizon of 12 months was undertaken. Consequences included quality-adjusted life years (QALY), depression severity, borderline severity, suicidal behaviour, healthcare use, and treatment compliance. Moreover, advantages and disadvantages of using a mobile diary app were studied. All relevant costs were included. RESULTS In total, 78 participants were included in the analysis. Participants in both groups had a QALY gain, and a decrease in depression severity, borderline severity, and suicidal behaviour. Significant differences were found between the app group and the paper group for both QALY gain (adjusted difference -0.054, SE 0.03) and depression severity (adjusted difference -1.11, SE 1.57). The use of services in the healthcare sector was similar across both time points and groups (difference: psychiatric hospitalization <5 and <5, general practice -1.32, SE 3.68 and 2.02, SE 3.19). An insignificantly higher number of participants in the paper group dropped out before treatment start (P value .07). Of those starting treatment, participants in the app group had an average of 37.1 (SE 27.55) more days of treatment and registered an average of 3.16 (SE 5.10) more skills per week than participants in the paper group. The mobile diary app was considered timesaving as it was expected to be 1 minute faster to complete. Advantages of the app were the opportunity to choose between different methods of registering; comparative ease of use; increased self-insight; and a new type of data collection. Disadvantages were a negative influence on the therapist-patient interaction; worries about performance goals; reduced flexibility in data collection; and implementation issues. The between-group difference in total costs ranged from £78.15-234.44 per participant during the 12-months. CONCLUSIONS A mobile diary app can potentially entail several positive consequences for patients suffering from BPD although at a higher cost than paper-based diary cards. A mobile diary app might contribute with new information on the patients, which is not available from the paper diary. Further research is encouraged, as this is still a new field. CLINICALTRIAL ClinicalTrials.gov NCT03191565 INTERNATIONAL REGISTERED REPORT RR2-

A Decision Analytical Model Investigating Cost-Effectiveness of Erlotinib

Background: A decision analytical model investigating cost-effectiveness of Erlotinib was submitted to the UK NICE (National Institute for Health and Care Excellence), which was not based on actual health-state transition probabilities, leading to structural uncertainty in the model. The study adopted a Markov state-transition model for investigating the cost-effectiveness of Erlotinib versus Best Supportive Care (BSC) as a maintenance therapy for patients with non-small cell lung cancer (NSCLC). Methods: Unlike manufacturer submission (MS), the Markov model was governed by transition probabilities, and allowed a negative post-progression survival (PPS) estimate to appear in later cycle. Using published summary survival data, the study employs three fixed- and time-varying approaches to estimate state transition probabilities that are used in a restructured model. Results: Post-progression probabilities and probabilities of death for Erlotinib were different than fixed-transition approaches. The best fitting curves are achieved for both PPS and probability of death across the time for which data were available, but the curves start diverging towards the end of this period. The Markov model which extrapolates the curves forward in time suggests that this difference between a time-varying and fixed-transition becomes even greater. Our models produce an ICER of £54k -£66k per QALY gain, which is comparable to an ICER presented in the MS (£55k/QALY gain). Conclusions: Results from restructured Markov models show robust cost-effectiveness results for Erlotinib vs BSC. Although these are comparable to manufacturer submissions, in terms of magnitude, they vary, and which are crucial for interventions falling near a threshold value. The study will further explore the cost-effectiveness of therapies for NSCLC in Qatar.

Cost-effectiveness of offering an area-level financial incentive on breast feeding: a within-cluster randomised controlled trial analysis

ObjectiveTo provide the first estimate of the cost-effectiveness of financial incentive for breastfeeding intervention compared with usual care.DesignWithin-cluster (‘ward’-level) randomised controlled trial cost-effectiveness analysis (trial registration number ISRCTN44898617).SettingFive local authority districts in the North of England.Participants5398 mother-infant dyads (intervention arm), 4612 mother-infant dyads (control arm).InterventionsOffering a financial incentive (over a 6-month period) on breast feeding to women living in areas with low breastfeeding prevalence (<40% at 6–8 weeks).Main outcome measuresBabies breast fed (receiving breastmilk) at 6–8 weeks, and cost per additional baby breast fed.MethodsCosts were compared with differences in area-level data on babies’ breast fed in order to estimate a cost per additional baby breast fed and the quality-adjusted life year (QALY) gains required over the lifetime of babies to justify intervention cost.ResultsIn the trial, the total cost of providing the intervention in 46 wards was £462 600, with an average cost per ward of £9989 and per baby of £91. At follow-up, area-level breastfeeding prevalence at 6–8 weeks was 31.7% (95% CI 29.4 to 34.0) in control areas and 37.9% (95% CI 35.0 to 40.8) in intervention areas. The adjusted difference between intervention and control was 5.7 percentage points (95% CI 2.7 to 8.6; p<0.001), resulting in 10 (95% CI 6 to 14) more additional babies breast fed in the intervention wards (39 vs 29). The cost per additional baby breast fed at 6–8 weeks was £974. At a cost per QALY threshold of £20 000 (recommended in England), an additional breastfed baby would need to show a QALY gain of 0.05 over their lifetime to justify the intervention cost. If decision makers are willing to pay £974 (or more) per additional baby breast fed at a QALY gain of 0.05, then this intervention could be cost-effective. Results were robust to sensitivity analyses.ConclusionThis study provides information to help inform public health guidance on breast feeding. To make the economic case unequivocal, evidence on the varied and long-term health benefits of breast feeding to both the baby and mother and the effectiveness of financial incentives for breastfeeding beyond 6–8 weeks is required.

Drug funding price negotiations: Towards achieving a balance between individual and population gains in health benefits.

6641 Background: Drug price negotiation to lower cost to a cost-effectiveness threshold (λ) is a recognized approach to improve health care opportunities for the greater benefit of the population. Critics have raised concerns for this approach given the additional time required and speculated loss of quality-adjusted life-years (QALY) for patients. The current study aimed to quantify the incremental net health benefit (INHB) of publicly funded oncology drugs, if funding occurred at list prices without (w/o) negotiations. Methods: Pan-Canadian Oncology Drug Review submissions were reviewed to identify funded drugs with unique indications. For included drug indications economic guidance panel (EGP) reports were reviewed for incremental costs (ΔC) and ΔQALY from manufacturer’s base case cost-effectiveness analyses, EGP lower (LL) and upper limit (UL) re-analyzed estimates (based on list prices). Number of new cases in Ontario (most populous province in Canada) per indication (2017-18) was obtained from provincial databases. Annual QALY gain for each indication was determined by: (ΔQALY×cases). Provincial QALY gain/loss w/o price negotiations to reference λ was estimated by: (INHB= [ΔQALY− (ΔC/λ)] ×cases). Incremental net monetary benefit demonstrated annual monetary gain/loss w/o price negotiations to reference λ: (INMB= [(ΔQALY×λ) −ΔC] ×cases). Results: 34 drug indications including 4,629 new cases were identified. Annual QALY gain for funded indications using manufacturer, LL and UL estimates was 1,851, 1,617 and 1,301, respectively. At reference λ CAD$100,000/QALY, funding w/o negotiations resulted in loss of 2,176, 2,368, 2,451 QALY, representing budgetary diversions away from other health care interventions. This would result in a provincial net annual loss of 325, 751 and 1,150 QALY, respectively. INMB demonstrated provincial net monetary loss of CAD$32,472,389, $75,113,684 and $115,022,331, respectively. Conclusions: Despite an annual gain in QALY for funded drug indications, a net provincial loss in QALY w/o price negotiations was demonstrated. Thus, supportive evidence exists for drug price negotiations towards the promotion of health benefits for the population.

OP65 Pharmacoeconomic Evaluation Of Orphan Drugs: Impact Of Extra Criteria?

IntroductionThere is ongoing debate as to whether conventional pharmacoeconomic evaluation (PE) methods are appropriate for orphan medicinal products (OMPs). The National Centre for Pharmacoeconomics (NCPE) in Ireland has a well-defined process for conducting pharmacoeconomic evaluations of pharmaceuticals, which is the same for OMPs and non-OMPs. The objective of this study was to identify whether supplementary criteria considered in the pharmacoeconomic evaluation of OMPs would affect final reimbursement recommendations.MethodsA literature search was conducted to identify criteria. Orphan drug pharmacoeconomic evaluations completed by the NCPE between January 2015 and December 2017 were identified and supplementary criteria, where feasible, were applied.ResultsFourteen pharmacoeconomic evaluations were included in the study. Three criteria that could feasibly be applied to the NCPE evaluation process were identified, all three of which essentially broadened the economic perspective of the pharmacoeconomic evaluation. Higher cost-effectiveness threshold: Despite being arbitrarily raised from EUR 45,000/QALY to EUR 100,000/QALY, only one orphan drug demonstrated cost-effectiveness at this higher threshold. Weighted QALY gain: here, a weighted gain of between one and three is applied to drugs demonstrating QALY gains between 10 and 30, respectively. No OMPs included in the study showed a QALY gain of more than 10. Thirteen demonstrated QALY gains less than 10 and one could not be evaluated. Societal perspective: six submissions incorporated societal perspective as a scenario analysis. Despite incremental cost-effectiveness ratios (ICERs) being reduced between 4 percent and 58 percent, only two OMPs demonstrated cost-effectiveness at the higher threshold (EUR 100,000/QALY).ConclusionsApplication of supplementary criteria to the pharmacoeconomic evaluation of OMPs had a minor effect on three products assessed. However, for the majority, the final cost-effectiveness outcomes remained the same. The study highlights that other criteria are being considered in the decision to reimburse.

OP20 Has The New HST Process Improved The Recommendation Chance In England?

IntroductionThe National Institute for Health and Care Excellence (NICE) in England has a separate appraisal process for drugs for very rare conditions, i.e. Highly Specialised Therapies (HST). In April 2017, the HST process has been changed to incorporate a quantitative approach: automatically fund treatments with incremental cost-effectiveness ratio (ICERs) up to GBP 100,000 (EUR 113,008 based on the 2018 average GBP / EUR exchange rate) per quality-adjusted life year (QALY). For treatments with an ICER above GBP 100,000 per QALY, NICE will consider treatments that offer a substantial magnitude of improvement, with additional QALY weighting. We investigated the impact of this more quantitative approach on the likelihood of a HST receiving a positive recommendation.MethodsAll HST appraisals and draft guidance documents were reviewed (up to November 2018) and data were extracted on ICERs, incremental QALY gain, budget impact, and recommendations. The extracted data from each HST were assessed based on the interim HST guidance.ResultsEighteen products have been or are currently going through the NICE HST process. Of these, 8/18 (44%) have received a positive recommendation, while 5/18 (28%) have received a draft negative guidance, and for 5/18 (28%) products, no recommendations have been published. For the products with a positive outcome, 5/8 (63%) had incremental QALY gain of at least 10, qualifying these products for additional QALY weighting. For the products that received a draft negative recommendation, the negative decision was related to the cost-effectiveness estimates being higher than GBP 100,000 per QALY (5/5 reported) in all cases, while none of these products were eligible to receive a ‘QALY modifier’.ConclusionsIt has become more difficult for HSTs to get recommended by NICE under the new guidance, which requires cost-effectiveness analyses, whereas previously there was no official ICER threshold. The additional weighting of QALYs may be insufficient to meet an ICER threshold of GBP 100,000 per QALY for many products.