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Venetoclax is a first-in-class targeted therapy option that is an inducer of apoptosis in chronic lymphocytic leukemia (CLL) cells. The open-label phase III CLL14 clinical trial showed that venetoclax combined with obinutuzumab (VEN+O) is superior to obinutuzumab combined with chlorambucil in newly diagnosed patients with CLL. The aim of this study was to assess the health economic value of VEN+O for the frontline treatment of CLL in Canada from a publicly funded healthcare system perspective.A partitioned survival analyses model was developed including three health states: progression free, progressed, and death. A cycle length of 28 days and a time horizon of 10 years was assumed. VEN+O treatment for a fixed duration of 12 months was compared to obinutuzumab combined with chlorambucil, fludarabine plus cyclophosphamide plus rituximab, bendamustine plus rituximab, chlorambucil plus rituximab, ibrutinib, and acalabrutinib. The population in the model included both unfit and overall frontline CLL patients, two subgroups were also assessed (patients with del17p/TP53 mutations and patients without del17p/TP53 mutations). Survival data extrapolated from the CLL14 trial were used to populate the model. Uncertainty was assessed via one-way sensitivity analyses, probabilistic analyses, and scenario analyses.Based on the probabilistic analyses, unfit frontline CLL patients receiving VEN+O were estimated to incur costs of Canadian dollars ($) 217,727 [confidence interval (CI) $170,725, $300,761] (del17p/TP53: $209,102 [CI $159,698, $386,190], non-del17p/TP53: $217,732 [CI $171,232, $299,063]) and accrue 4.96 [CI 4.04, 5.82] quality-adjusted life-years (del17p/TP53: 3.11 [CI 2.00, 4.20], non-del17p/TP53: 5.04 [CI 4.05, 5.92]). Obinutuzumab combined with chlorambucil, bendamustine plus rituximab, chlorambucil plus rituximab, and ibrutinib accrued lower quality-adjusted life-years and higher costs and as such, VEN+O was the dominant treatment option. The full incremental analysis showed that acalabrutinib was more expensive and more efficacious compared with VEN+O with an incremental-cost-effectiveness-ratio of $2,139,180/quality-adjusted life-year versus VEN+O and not a cost-effective option in Canada. Probabilistic analyses show that at a willingness to pay of $50,000/quality-adjusted life-year gained, VEN+O has the greatest probability of being cost effective.VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers.

Summary This study evaluated the cost-effectiveness of 1 year of romosozumab followed by alendronate versus oral bisphosphonates alone in women with postmenopausal osteoporosis at very high risk for fracture in Canada. Results showed that romosozumab sequenced to alendronate is a cost-effective treatment option, dominating both alendronate and risedronate alone. Purpose To demonstrate the value of romosozumab sequenced to alendronate compared to alendronate or risedronate alone, for the treatment of osteoporosis in postmenopausal women with a history of osteoporotic fracture and who are at very high risk for future fracture in Canada. Methods A Markov model followed a hypothetical cohort of postmenopausal osteoporotic women at very high risk for future fractures, to estimate the cost-effectiveness of romosozumab and alendronate compared to oral bisphosphonates alone. A total treatment period of 5 years was assumed. Quality-adjusted life years and costs were estimated for each comparator across health states defined by different types of fragility fractures. Results Romosozumab/alendronate was associated with a lifetime gain of 0.103 and 0.127 QALYs and a cost reduction of $343 and $3805, relative to alendronate and risedronate, respectively. These results were driven by a reduction of the number of fractures (2561 per 1000 patients, versus 2700 for alendronate and 2724 for risedronate over lifetime). Romosozumab/alendronate had the highest probability of being cost-effective, relative to alendronate and risedronate, at any willingness to pay threshold value. Conclusion Romosozumab/alendronate was associated with reduced costs and greater benefit relative to other comparators. Probabilistic, deterministic, and scenario analyses indicate that romosozumab/alendronate represents the best value for money; the uncertainty analyses are robust, and therefore romosozumab should be considered for reimbursement by public drug plans in Canada .

Purpose To assess, from the Canadian public payer perspective, the cost-utility of implanting iStent Inject trabecular bypass stent (TBS) devices in conjunction with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma (OAG) and visually significant cataract. Design Cost-utility analysis using efficacy and safety results of pivotal randomized clinical trial. Participants Modeled cohort of patients with OAG (83.1% with mild disease, 16.9% with moderate disease) and visually significant cataract. Methods Open-angle glaucoma treatment costs and effects were projected over a 15-year time horizon using a Markov model with Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, severe or blind) and death as health states. Patients in the mild or moderate OAG health states received implantation of iStent Inject during cataract surgery versus cataract surgery alone. On worsening of visual field defect and optic disc damage, patients could receive selective laser trabeculoplasty and trabeculectomy. We measured treatment effect as reduction in intraocular pressure (IOP) and mean medication use and estimated transition probabilities based on efficacy-adjusted visual field mean deviation decline per month. Healthcare resource utilization and utility scores were obtained from the literature. Cost inputs (2017 Canadian dollars [C$]) were derived using the Ontario Health Insurance Plan, expert opinion, medication claims datasets, and Ontario Drug Benefit Formulary medication consumption costs. We conducted deterministic and probabilistic sensitivity analyses to examine the impact of alternative model input values on results. Main Outcome Measures Incremental cost per quality-adjusted life year (QALY) gained. Results Compared with cataract surgery alone, TBS plus cataract surgery showed a 99% probability of being more effective (+0.023 QALYs; 95% confidence interval [CI], 0.004 to 0.044) and a 73.7% probability of being cost-saving (net cost, –C$389.00; 95% CI, –C$1712.00 to C$850.70). In 95% of all simulations, TBS plus cataract surgery showed a cost per QALY of C$62 366 or less. Results were robust in additional sensitivity and scenario analyses. Conclusions iStent Inject TBS implantation during cataract surgery seems to be cost effective for reducing IOP in patients with mild to moderate OAG versus cataract surgery alone.

Background: Cardiovascular disease is the second-leading cause of death in Canada. However, limited data are available on the prevalence of atherosclerotic cardiovascular disease (ASCVD) in Canada. The study objective was to describe the incidence and prevalence of ASCVD in adult patients in Ontario, Canada, and to evaluate temporal trends for subsequent ASCVD events among those with new-onset ASCVD. Methods: This retrospective, observational study identified ASCVD incidence and prevalence data from the Institute for Clinical Evaluative Sciences Data Repository for adults from Ontario. Overall prevalence was established for the period from 2002 to 2018. Incident cases from April 1, 2005 to March 2016 were then identified, and followed up to 2018. Primary outcomes were date and type of index event/procedure, patient characteristics/baseline demographics, and comorbidities. Secondary outcomes assessed were time from first to second ASCVD event, subsequent event(s) and/or mortality, and type of subsequent event(s) relative to the type of index/primary event. Results: A total of 1,042,621 eligible prevalent ASCVD cases were identified; of these, 743,309 patients (69%) were newly diagnosed with incident ASCVD. The 10-year prevalence rates for all ASCVD subtypes increased over the study period. Overall event incidence rates per 1000 person-years were mostly stable or increased. Among incident cases, 50% experienced subsequent events over the study period. Conclusions: This observational study demonstrated increasing prevalence and high incidence of new ASCVD diagnoses in adults from Ontario, over the study period. These data, together with the substantial number of subsequent events in ASCVD patients, demonstrate significant clinical burden of this disease in Ontario. Résumé: Contexte: Les maladies cardiovasculaires constituent la deuxième cause de décès au Canada. Toutefois, on dispose de peu de données sur la prévalence de la maladie cardiovasculaire athéroscléreuse (MCVAS) au Canada. L’étude avait pour objectifs de décrire l’incidence et la prévalence de la MCVAS chez les patients adultes en Ontario (Canada) et d’évaluer les tendances temporelles des manifestations subséquentes de MCVAS chez les personnes ayant une MCVAS d’apparition récente. Méthodologie: Cette étude observationnelle rétrospective a permis de colliger les données sur l’incidence et la prévalence de la MCVAS chez les adultes ontariens consignées dans le référentiel de l’Institut des sciences cliniques évaluatives. La prévalence globale a été établie pour la période allant de 2002 à 2018. Les cas incidents survenus du 1er avril 2005 à mars 2016 ont ensuite été recensés et suivis jusqu’en 2018. Les paramètres d’évaluation principaux étaient : date et nature de la manifestation index et de l’intervention; caractéristiques des patients et données démographiques initiales; comorbidités. Les éléments suivants constituaient les paramètres d’évaluation secon-daires : temps écoulé entre la première et la deuxième manifestation de MCVAS, la ou les manifestations subséquentes et/ou le décès; nature de la ou des manifestations subséquentes par rapport à celle de la manifestation index ou primaire. Résultats: En tout, 1 042 621 cas de MCVAS prévalents admissibles ont été dénombrés; parmi ceux-ci, il y avait 743 309 (69 %) cas incidents de MCVAS nouvellement diagnostiqués. Les taux de prévalence à 10 ans de tous les sous-types de MCVAS ont augmenté au cours de la période étudiée. Les taux globaux d’incidence des manifestations par 1000 années-personnes étaient généralement stables ou accrus. Cinquante pour cent des cas incidents ont été associés à des manifestations subséquentes au cours de la période étudiée. Conclusions: Cette étude observationnelle a démontré une prévalence croissante et une incidence élevée de nouveaux diagnostics de MCVAS chez les adultes en Ontario au cours de la période étudiée. Les données à cet égard, ainsi que le grand nombre de manifestations subséquentes de la maladie, démontrent que la MCVAS constitue un fardeau clinique considérable en Ontario.

Objectives: To estimate the cost-utility of two trabecular micro-bypass stents (TBS) implantation vs standard of care (SOC) in patients with mild-to-moderate open-angle glaucoma (OAG) in the Canadian healthcare setting. Methods: The deterioration in visual field (VF) defect over a 15-year time horizon was tracked using a Markov model with Hodapp-Parrish-Anderson stages of glaucoma (mild, moderate, advanced, severe/blind) and death as health states. Meta-analyses of randomized clinical trials were conducted to estimate the pooled reduction in intraocular pressure (IOP) and medication use due to TBS and SOC. The rate of decline in VF loss was adjusted by the extent of IOP reduction to estimate transition probabilities. Healthcare resource utilization, unit costs (2017 CAD), and progression-related utility scores were obtained by literature review, and medication costs with wastage were obtained from IMS Brogan PharmaStat. The impact of parameter and methodological uncertainty on costs and quality-adjusted life years (QALYs) was examined using probabilistic and 1-way sensitivity analyses. Results: The meta-analysis showed an additional reduction of 1.13 medications/patient and an additional decrease in IOP of –1.10 mmHg at 36 months favoring TBS. TBS strongly dominated medication alone, due to higher improvement in quality-of-life (0.068 QALYs), fewer blind eyes (–0.0031), and a decrease in total healthcare costs of C$2,908.3 per patient over the time horizon (C$9,394.1 TBS vs C$12,302.4 medication alone). Sensitivity analyses showed that results were robust to the uncertainties in model inputs and assumptions. Time-to-dominance was 44 months (3.7 years). Conclusions: The TBS procedure was cost-effective over SOC in a 15-year time horizon, with quality-of-life gains.

This chapter begins with a brief introduction to health technology assessment (HTA). HTA is concerned with the systematic evaluation of the consequences of the adoption and use of new health technologies and to improve the evidence on existing technologies. The objective of mainstream HTA is to support evidence-based decision- and policy-making that encourage the uptake of efficient and effective health-care technologies. This chapter provides a basic framework for conducting an HTA, as well as some fundamental concepts and challenges in assessing health technologies. Whether HTA is beneficial-supporting timely access to needed technologies-or detrimental depends on three critical issues: when the assessment is performed; how it is performed; and how the findings are used.

Background/Introduction Limited real-world data are available on attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients with atherosclerotic cardiovascular disease (ASCVD) in Canada. Purpose A retrospective observational study was conducted to describe types of ASCVD events/procedures, time between events and use of lipid lowering treatment (LLT) in patients who did not achieve LDL-C goal. Methods Patients in Ontario ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1-year follow up period for LDL-C goal attainment ( Results Overall, 28% of 143,302 patients ≥65 years on LLT failed to attain LDL-C goal at follow up (Figure). The proportion of patients failing to achieve LDL-C goal decreased from 35% to 22% over the 11-year study period. Mean time between index and follow up LDL-C (based on lowest score >2 weeks and up to 1 year after index LDL-C) was 203±97 days. When analysed by low-, moderate- or high-intensity statin, 57%, 30%, and 22% of patients failed to achieve LDL-C goal at follow up, respectively. Conclusions In this study, more than 1 in 4 patients with ASCVD in Ontario failed to achieve guideline recommended LDL-C goal despite treatment. In particular, ∼1 in 3 patients with cerebral and peripheral arterial disease were not at goal. An opportunity exists to better manage these high risk ASCVD patients with further statin intensification and additional LLTs This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc.

Background/Introduction The prevalence of ischaemic heart disease is lower in women vs men in Canada. Studies have shown that women are more likely to be underdiagnosed and less likely to receive guideline-recommended treatments than men. Women receiving lipid-lowering therapies (LLTs) are also less likely to attain treatment goals vs men. Purpose We analysed use of LLTs and attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in a recent longitudinal cohort of patients with ASCVD with public drug coverage in Ontario to describe differences observed between female and male patients. Methods Patients ≥65 years with a primary ASCVD event/procedure between 1 Apr 2005 and 31 Mar 2016, treated with an LLT and with index and follow up LDL-C values were identified from claims data at the Institute for Clinical Evaluative Sciences data repository. Patients were assessed over a 1 year follow up period for LDL-C goal attainment ( Results 143,302 patients with ASCVD ≥65 years on LLTs were identified of which 41% were female. A higher proportion of female vs male patients were prescribed low (3% vs 2%) and medium intensity statins (51% vs 44%) compared with high intensity statins (43% vs 52%). A higher proportion of women failed to attain LDL-C goal compared to men (33% vs 24%) (Figure). When analysed by low, moderate or high intensity statin, 65%, 35%, and 27% of female patients and 49%, 25% and 19% of male patients failed to attain LDL-C goal at follow up. Conclusions In this retrospective study, women with a diagnosis of ASCVD were more frequently treated with low/moderate intensity statins whereas men were more frequently treated with high intensity statins. Approximately 2 of 3 women and 3 of 4 men receiving statin treatment attained LDL-C goal during the 1-year follow up period. Overall, there appear to be treatment differences between female and male patients with ASCVD, with males receiving higher intensity statin therapy and attaining LDL-C goal more frequently. Further research is needed to determine why these discrepancies exist. This study made use of de-identified data from the ICES Data Repository, which is managed by the Institute for Clinical Evaluative Sciences with support from its funders and partners: Canada's Strategy for Patient-Oriented Research (SPOR), the Ontario SPOR Support Unit, the Canadian Institutes of Health Research and the Government of Ontario. The opinions, results and conclusions reported are those of the authors. No endorsement by ICES or any of its funders or partners is intended or should be inferred. Parts of this material are based on data and/or information compiled and provided by CIHI. However, the analyses, conclusions, opinions and statements expressed in the material are those of the author(s), and not necessarily those of CIHI. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Canada Inc

Background Evidence on the long-term clinical benefits of individual members of angiotensin II receptor blockers is limited given the lack of head-to-head studies. We conducted a network meta-analysis to determine the comparative efficacy of different members within this drug class with respect to outcomes of (i) blood pressure reduction (at 24 and 52 weeks) and (ii) prevention of cardiovascular disease (>104 weeks). Methods A systematic literature review was conducted – Protocol registration: (PROSPERO – CRD42014007067) – to identify relevant literature from the following databases: Cochrane Library, PubMed, MEDLINE and Embase; searched from inception to July 2016. Randomised controlled trials (RCTs) were included if they reported long-term effectiveness relating to blood pressure, mortality, myocardial infarction or stroke. Eligible studies included those with placebo or specific active-treatment comparators (either another angiotensin II receptor blockers or hydrochlorothiazide). A Bayesian random-effects network model was used to combine direct within-trial comparisons between treatment groups with indirect evidence from other trials. Results Thirty-six studies were identified, representing 28 unique trials. Blood pressure reduction, based on 12 studies (n=807) with fixed dosing regimen, was found to be similar amongst members of the angiotensin receptor blocker drug class at both 24 and 52 weeks. A network meta-analysis of five studies (n=16,716) with a treat-to-target approach found that prevention of all-cause mortality, stroke and myocardial infarction was similar across the angiotensin-receptor blockers therapies initiated. Conclusions Current evidence is insufficient to show differences in any members within the angiotensin II receptor blocker drug class with respect to blood pressuring lowering effects or a reduction in cardiovascular diseases.

Background Consideration of cost determinants is crucial to inform delivery of public vaccination programs. Objectives To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs. Methods Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 - 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions. Results Dataset included 2,943 adult admissions to 17 SOS Network hospitals, 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8) and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14,612 CAD (95% CI: $13,852, $15,372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14,031 (95% CI: $13,295, $14,768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days. Conclusion The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per patient cost of influenza-related hospitalization has been underestimated and prevention programs should be evaluated in this context. This article is protected by copyright. All rights reserved.

Objective: The study evaluates the cost-effectiveness of secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A, vs currently licensed biologic treatments in patients with active psoriatic arthritis (PsA) from a Canadian healthcare system perspective. Methods: A decision analytic semi-Markov model evaluated the cost-effectiveness of secukinumab 150 mg and 300 mg compared to subcutaneous biologics adalimumab, certolizumab pegol, etanercept, golimumab, and ustekinumab, and intravenous biologics infliximab and infliximab biosimilar in biologic-naive and biologic-experienced patients over a lifetime horizon. The response to treatments was evaluated after 12 weeks by PsA Response Criteria (PsARC) response rates. Non-responders or patients discontinuing initial-line of biologic treatment were allowed to switch to subsequent-line biologics. Model input parameters (Psoriasis Area Severity Index [PASI], Health Assessment Questionnaire [HAQ], withdrawal rates, costs, and resource use) were collected from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). An annual discount rate of 5% was applied to costs and benefits. The robustness of the study findings were evaluated via sensitivity analyses. Results: Biologic-naive patients treated with secukinumab achieved the highest number of QALYs (8.54) at the lowest cost (CAD 925,387) over a lifetime horizon vs all comparators. Secukinumab dominated all treatments, except for infliximab and its biosimilar, which achieved minimally more QALYs (8.58). However, infliximab and its biosimilar incurred more costs than secukinumab (infliximab: CAD 1,015,437; infliximab biosimilar: CAD 941,004), resulting in higher cost-effectiveness estimates relative to secukinumab. In the biologic-experienced population, secukinumab dominated all treatments as it generated more QALYs (8.89) at lower costs (CAD 954,692). Deterministic sensitivity analyses indicated the results were most sensitive to variation in PsARC response rates, change in HAQ, and utility values in both populations. Conclusions: Secukinumab is either dominant or cost-effective vs all licensed biologics for the treatment of active PsA in biologic-naive and biologic-experienced populations in Canada.

OBJECTIVES: To estimate the cost-effectiveness of venetoclax + obinutuzumab (GAZYVA®, G), (VEN+G) in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL) from a Canadian health care system cost perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival (PFS) and overall survival (OS) over a 10-year time horizon. Cost-effectiveness was estimated comparing 12-month fixed duration of VEN+G versus (vs) G + Chlorambucil (GClb) based on the CLL14 clinical trial (NCT02242942). Other comparators included Bendamustine + rituximab (BR), Chlorambucil + rituximab (Clb+R), Ibrutinib (Ibr), Acalabrutinib (Acala) and Acalabrutinib + GAZYVA (Acala+G). VEN+G was also compared to the combination of fludarabine, cyclophosphamide and rituximab (FCR) in the overall 1L CLL population which included unfit and fit patients. Relative efficacy of VEN+G vs other comparators was estimated using a network meta-analysis. Health state utilities and adverse event disutilities were derived from a systematic literature review and other published sources. Costs included CLL treatment, routine care and monitoring, adverse events, disease progression costs, subsequent treatment costs, and end of life care. Uncertainty was assessed using an underlying probabilistic model (probabilistic analysis of uncertainty generated from 5,000 iterations), through deterministic sensitivity analyses (i.e., one-way sensitivity analyses (OWSA)), and through a series of alternative scenario analyses. RESULTS: For the overall unfit 1L CLL patient population, the probabilistic total discounted costs incurred over a 10-year time horizon were as follows: $217,727 for VEN+G vs $312,287 for GClb, $399,219 for BR, $380,713 for Clb+R, $736,017 for Ibr, $868,797 for Acala and $916,139 for Acala+G. The probabilistic total discounted quality adjusted life years (QALYs) were 4.964 for VEN+G vs 4.750, 4.550, 4.422, 4.709, 5.269, and 5.359, respectively for the comparators. For the overall 1L CLL patient population, the probabilistic total discounted costs were $219,651 for VEN+G vs $312,570 for GClb, $342,195 for FCR, $397,262 for BR, $380,551 for Clb+R, $757,129 for Ibr, $868,388 for Acala, and $916,798 for Acala+G. The probabilistic total discounted QALYs were 5.888 for VEN+G vs 5.519, 5.067, 5.198, 5.073, 5.597, 6.259 and 6.380, respectively for the comparators. VEN+G was found to be less costly and more efficacious (i.e., dominant) compared to GClb, BR, Clb+R, Ibr and FCR. As a result, incremental cost utility ratios (ICERs) were not calculated for these comparators. Acala and Acala+G resulted in ICERs ranging from $1.4-$2.1 million per QALY gained relative to VEN+G, which is not cost-effective. Based on the probabilistic model and 5,000 simulations, VEN+G was found to be at least 97% cost-effective across all decision maker willingness-to-pay thresholds. The results from the deterministic model were found to be similar to the probabilistic model. Using the deterministic model, and in comparison to the most commonly prescribed treatment for 1L CLL in Canada (i.e., Ibr), the OWSA comparing VEN+G to Ibr found that the most influential variables in the model were the PFS and OS hazard ratios for Ibr and the utility values for PFS and post-progression survival. CONCLUSION: VEN+G is an effective novel fixed duration treatment option which leads to deep and durable responses for the treatment of patients with unfit 1L CLL and provides excellent value-for-money compared with existing chemoimmunotherapy and treat to progression novel combinations. Disclosures Chatterjee: Pharmerit: Current Employment. Van de Wetering:Pharmerit: Current Employment. Goeree:AbbVie Inc.: Consultancy. Desbois:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzi:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:AbbVie: Current equity holder in publicly-traded company. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company.

Both public and private insurers provide drug coverage in Canada. All payers are under pressure to contain costs. It has recently been proposed that private plans leverage the public health technology assessment (HTA) evaluation process in their decision-making.The objectives of the current study were to examine use of public health technology assessments (HTAs) for private payer decision-making in the literature, to gather the perspectives of experts from both public and private insurers on this practice, and to summarize which value parameters of public evaluations can be used for private payer decision-making.A targeted literature review was conducted to identify publications on the use of public HTA or cost-effectiveness data for private payer decision-making on pharmaceutical reimbursement. Concurrently, a roundtable meeting was organized with invited panelists, including private payer representatives and health economic consultants (total n = 9). The findings from both were synthesized and expressed in qualitative terms using the PICO framework.The targeted review identified 20 studies meeting the inclusion criteria, primarily originating from the US and Canada. The panelists felt that, despite some similarities, there were substantial differences between both systems. The PICO framework highlighted the issues with transferability between the two systems. Most of the value parameters were either not applicable, needed to be added, needed to be adjusted, or their applicability to private payer systems needed to be confirmed.Some components of public HTA may be relevant for private payers, however there are reservations that still exist on whether the HTA process in Canada, designed for a public system, can address the informational needs of private payers. Private insurers need to use caution in assessing which value parameters from public HTAs can be used and which need to be confirmed, ignored, enhanced, or adjusted. One size HTA does not fit all applications.

Objective To provide a framework for addressing payers' criteria during the development of pharmaceuticals.Methods A conceptual framework was presented to an international health economic expert panel for discussion. A structured literature search (from 2010 to May 2015), using the following databases in Ovid: Medline((R)) and Medline((R)) In-Process (PubMed), Embase (Ovid), EconLit (EBSCOhost) and the National Health Service Economic Evaluation Database (NHS EED), and a 'grey literature' search, were conducted to identify existing criteria from the payer perspective. The criteria assessed by existing frameworks and guidelines were collated; the most commonly reported criteria were considered for inclusion in the framework. A mnemonic was conceived as a memory aide to summarise these criteria.Results Overall, 41 publications were identified as potentially relevant to the objective. Following further screening, 26 were excluded upon full-text review on the basis of no framework presented (n = 13), redundancy (n = 11) or abstract only (n = 2). Frameworks that captured criteria developed for or utilised by the pharmaceutical industry (n = 5) and reimbursement guidance (n = 10) were reviewed. The most commonly identified criteria-unmet need/patient burden, safety, efficacy, quality-of-life outcomes, environment, evidence quality, budget impact and comparator-were incorporated into the summary framework. For ease of communication, the following mnemonic was developed: BEACON (Burden/target population, Environment, Affordability/value, Comparator, Outcomes, Number of studies/quality of evidence).Conclusions The BEACON framework aims to capture the 'essence' of payer requirements by addressing the most commonly described criteria requested by payers regarding the introduction of a new pharmaceutical.

OBJECTIVE Hyperbaric oxygen therapy (HBOT) is used for the treatment of chronic diabetic foot ulcers (DFUs). The controlled evidence for the efficacy of this treatment is limited. The goal of this study was to assess the efficacy of HBOT in reducing the need for major amputation and improving wound healing in patients with diabetes and chronic DFUs. RESEARCH DESIGN AND METHODS Patients with diabetes and foot lesions (Wagner grade 2–4) of at least 4 weeks' duration participated in this study. In addition to comprehensive wound care, participants were randomly assigned to receive 30 daily sessions of 90 min of HBOT (breathing oxygen at 244 kPa) or sham (breathing air at 125 kPa). Patients, physicians, and researchers were blinded to group assignment. At 12 weeks postrandomization, the primary outcome was freedom from meeting the criteria for amputation as assessed by a vascular surgeon. Secondary outcomes were measures of wound healing. RESULTS One hundred fifty-seven patients were assessed for eligibility, with 107 randomly assigned and 103 available for end point adjudication. Criteria for major amputation were met in 13 of 54 patients in the sham group and 11 of 49 in the HBOT group (odds ratio 0.91 [95% CI 0.37, 2.28], P = 0.846). Twelve (22%) patients in the sham group and 10 (20%) in the HBOT group were healed (0.90 [0.35, 2.31], P = 0.823). All other indices of wound healing were also not statistically significantly different between groups. CONCLUSIONS HBOT does not offer an additional advantage to comprehensive wound care in reducing the indication for amputation or facilitating wound healing in patients with chronic DFUs.

Objectives:In 2007, the Ontario Health Technology Advisory Committee (OHTAC) developed a decision framework to guide decision making around nondrug health technologies. In 2012, OHTAC commissioned a revision of this framework to enhance its usability and deepen its conceptual and theoretical foundations.Methods:The committee overseeing this work used several methods: (a) a priori consensus on guiding principles, (b) a scoping review of decision attributes and processes used globally in health technology assessment (HTA), (c) presentations by methods experts and members of review committees, and (d) committee deliberations over a period of 3 years.Results:The committee adopted a multi-criteria decision-making approach, but rejected the formal use of multi-criteria decision analysis. Three broad categories of attributes were identified: (I) context criteria attributes included factors such as stakeholders, adoption pressures from neighboring jurisdictions, and potential conflicts of interest; (II) primary appraisal criteria attributes included (i) benefits and harms, (ii) economics, and (iii) patient-centered care; (III) feasibility criteria attributes included budget impact and organizational feasibility.Conclusion:The revised Ontario Decision Framework is similar in some respects to frameworks used in HTA worldwide. Its distinctive characteristics are that: it is based on an explicit set of social values; HTA paradigms (evidence based medicine, economics, and bioethics/social science) are used to aggregate decision attributes; and that it is rooted in a theoretical framework of optimal decision making, rather than one related to broad social goals, such as health or welfare maximization.

Aim: To assess the cost-effectiveness of interleukin (IL)-17A inhibitor secukinumab vs the currently licensed biologic therapies in ankylosing spondylitis (AS) patients from a Canadian healthcare system perspective. Methods: A decision analytic model (semi-Markov) evaluated the cost-effectiveness of secukinumab 150 mg compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar in a biologic-naïve population, over 60 years of time horizon (lifetime). The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) response rate was used to assess treatment response at week 12. Non-responders or patients discontinuing initial-line of biologic therapy were allowed to switch to subsequent-line biologics. Model input parameters (short-term and long-term changes in BASDAI and Bath Ankylosing Spondylitis Functional Index [BASFI], withdrawal rates, adverse events, costs, resource use, utilities, and disutilities) were obtained from clinical trials, published literature, and other Canadian sources. Benefits were expressed as quality-adjusted life years (QALYs). Cost and benefits were discounted with an annual discount rate of 1.5% for all treatments. Results: In the biologic-naïve population, secukinumab 150 mg dominated all comparators, as patients treated with secukinumab 150 mg achieved the highest QALYs (16.46) at the lowest cost (CAD 533,010) over a lifetime horizon vs comparators. In the deterministic sensitivity analysis, results were most sensitive to changes in baseline BASFI non-responders, BASDAI 50 at 3 months and discount rates. Probabilistic sensitivity analysis showed that secukinumab 150 mg demonstrated higher probability of achieving maximum net monetary benefit vs all comparators at various cost thresholds. Conclusions: This analysis demonstrates that secukinumab 150 mg is the most cost-effective treatment option for biologic-naïve AS patients compared to certolizumab pegol, adalimumab, golimumab, etanercept and etanercept biosimilar, and infliximab and infliximab biosimilar for a lifetime horizon in Canada. Treatment with secukinumab translates into substantial benefits for patients and the healthcare system.

New regimens for the treatment of chronic hepatitis C virus (HCV) genotype 3 have demonstrated substantial improvement in sustained virologic response (SVR) compared with existing therapies, but are considerably more expensive. The objective of this study was to evaluate the cost-effectiveness of two novel all-oral, interferon-free regimens for the treatment of patients with HCV genotype 3: daclatasvir plus sofosbuvir (DCV + SOF) and sofosbuvir plus ribavirin (SOF + RBV), from a Canadian health-system perspective.A decision analytic Markov model was developed to compare the effect of various treatment strategies on the natural history of the disease and their associated costs in treatment-naïve and treatment-experienced patients. Patients were initially distributed across fibrosis stages F0-F4, and may incur disease progression through fibrosis stages and on to end-stage liver disease complications and death; or may achieve SVR. Clinical efficacy, health-related quality-of-life, costs, and transition probabilities were based on published literature. Probabilistic sensitivity analysis was performed to assess parameter uncertainty associated with the analysis.In treatment-naive patients, the expected quality-adjusted life years (QALYs) for interferon-free regimens were higher for DCV + SOF (12.37) and SOF + RBV (12.48) compared to that of pINF + RBV (11.71) over a lifetime horizon, applying their clinical trial treatment durations. The expected costs were higher for DCV + SOF ($170,371) and SOF + RBV ($194,776) vs pINF + RBV regimen ($90,905). Compared to pINF + RBV, the incremental cost-effectiveness ratios (ICER) were $120,671 and $135,398 per QALYs for DCV + SOF and SOF + RBV, respectively. In treatment-experienced patients, DCV + SOF regimen dominated the SOF + RBV regimen. Probabilistic sensitivity analysis indicated a 100% probability that a DCV + SOF regimen was cost saving in treatment-experienced patients.Daclatasvir plus sofosbuvir is a safe and effective option for the treatment of chronic HCV genotype 3 patients. This regimen could be considered a cost-effective option following a first-line treatment of peg-interferon/ribavirin treatment experienced patients with HCV genotype-3 infection.

To investigate the effect of hyperbaric oxygen therapy on health-related quality of life (HRQoL) in participants with diabetes and chronic foot ulcers. Using data from a randomized controlled trial, we included 103 participants (49 in hyperbaric oxygen therapy group and 54 in sham group) for analyses. The primary outcome was HRQoL as measured by the EQ-5D-3L instrument, while secondary outcomes included quality of life evaluated by the Short Form 36 (SF-36) and Diabetic Foot Ulcers Scale-Short Form (DFS-SF). We used the analysis of covariance to assess whether the EQ-5D index values in hyperbaric oxygen therapy group differed from the sham group. Logistic regression was used to assess the relationship between hyperbaric oxygen therapy and the responses of ‘problems’ for the EQ-5D health states. No significant differences in EQ-5D index values were found between the hyperbaric oxygen therapy and sham groups: 0.01 (95% CI −0.25, 0.28; p = 0.93) at week 12; 0.07 (95% CI −0.21, 0.34; p = 0.64) at week 6. Hyperbaric oxygen therapy was found to be associated with fewer participants reporting ‘problems’ in mobility (OR 0.24, 95% CI 0.07, 0.85 at week 12) and pain or discomfort (OR 0.20, 95% CI 0.07, 0.61 at week 6; OR 0.32, 95% CI 0.11, 0.97 at week 12), compared with the sham group. No significant differences in SF-36 or DFS-SF were observed. No significant effect of hyperbaric oxygen therapy on HRQoL measured by EQ-5D index value was found in this study. Due to the potential insufficient power to assess statistical difference, more large-scale research is needed to further evaluate the effect of hyperbaric oxygen therapy on HRQoL in participants with chronic diabetic foot ulcers.

Multi-criteria decision analysis (MCDA), a decision-making tool, has received increasing attention in recent years, notably in the healthcare field. For Canada, it is unclear whether and how MCDA should be incorporated into the existing health technology assessment (HTA) decision-making process. To facilitate debate on improving HTA decision-making in Canada, a workshop was held in conjunction with the 8th World Congress on Health Economics of the International Health Economics Association in Toronto, Canada in July 2011. The objective of the workshop was to discuss the potential benefits and challenges related to the use of MCDA for HTA decision-making in Canada. This paper summarizes and discusses the recommendations of an expert panel convened at the workshop to discuss opportunities and concerns with reference to the implementation of MCDA in Canada.

Anecdotal evidence suggests that functional magnetic resonance imaging (fMRI) studies rarely consider statistical power when setting a sample size. This raises concerns since undersized studies may fail to detect effects of interest and encourage data dredging. Although sample size methodology in this field exists, implementation requires specifications of estimated effect size and variance components. We therefore systematically evaluated how often estimates of effect size and variance components were reported in observational fMRI studies involving clinical human participants published in six leading journals between January 2010 and December 2011. A random sample of 100 eligible articles was included in data extraction and analyses. Two independent reviewers assessed the reporting of sample size calculations and the data components required to perform the calculations in the fMRI literature. One article (1%) reported sample size calculations. The reporting of parameter estimates for effect size (8%), between-subject variance (4%), within-subject variance (1%) and temporal autocorrelation matrix (0%) was uncommon. Three articles (3%) reported Cohen's d or F effect sizes. The majority (83%) reported peak or average t, z or F statistics. The inter-rater agreement was very good, with a prevalence-adjusted bias-adjusted kappa (PABAK) value greater than 0.88. We concluded that sample size calculations were seldom reported in fMRI studies. Moreover, omission of parameter estimates for effect size, between- and within-subject variances, and temporal autocorrelation matrix could limit investigators' ability to perform power analyses for new studies. We suggest routine reporting of these quantities, and recommend strategies for reducing bias in their reported values.

In a climate of escalating demands for new health care services and significant constraints on new resources, the disciplines of health economics and health technology assessment (HTA) have increasingly been turned to as explicit evidence-based frameworks to help make tough health care access and reimbursement decisions. Health economics is the discipline of economics concerned with the efficient allocation of health care resources, essentially trying to maximize health benefits to society contingent upon available resources. HTA is a broader field drawing upon several disciplines, but which relies heavily upon the tools of health economics and economic evaluation. Traditionally, health economics and economic evaluation have been widely used at the political (macro) and local (meso) decision-making levels, and have progressively had an important role even at informing individual clinical decisions (micro level). The aim of this paper is to introduce readers to health economics and discuss its relevance to frontline clinicians. Particularly, the content of the paper will facilitate clinicians' understanding of the link between economics and their medical practice, and how clinical decision-making reflects on health care resource allocation.

Objectives: Approximately 10–15 percent of individuals with diabetes mellitus develop foot ulcers, which precede 85 percent of amputations. Increased oxygen, through the use of hyperbaric oxygen therapy (HBOT), has been suggested to encourage ulcer healing thus reducing the risk of amputation. The objective of this systematic review is to evaluate the efficacy of systemic HBOT for nonhealing ulcers of the lower limb in diabetes patients.Methods: A systematic search, using controlled and keyword terms focusing on “HBOT” and “lower limb diabetic ulcers,” was conducted. Databases searched included Medline, EMBASE, CINAHL, PubMed, Wiley's Cochrane Library, and Biosis. Randomized controlled trials (RCTs) and observational studies were included. Pooled estimates of outcomes were determined when appropriate.Results: Of the 654 citations identified, 157 articles underwent full-text review. Data were abstracted from twelve publications (six RCTs and six comparative observational studies). Pooled analysis of the RCT and observational data showed that treatment with HBOT reduced the risk of major amputation by 60 percent (p = .29) and 61 percent (p = .003) compared with standard wound care, respectively. The RCT data revealed that the relative risk of having an unhealed wound following HBOT was 0.54 (p = .10) and 0.24 (p < .0001) based on observational data.Conclusions: Due to the limited RCT evidence, it is not possible to conclusively establish the benefits and harms of treating diabetic lower limb ulcers with HBOT. No significant effects on amputation rates were found in the RCT evidence and in the high quality studies, no difference was found.

Decision support is a discipline that is becoming increasingly important in health care decision making. Many jurisdictions are exploring the use of multi-criteria decision analysis (MCDA) as a decision support framework. Indeed, health care decision makers still face complex choices while being urged to provide more comprehensiveness, structure, and transparency to the existing decision-making framework. This paper documents MCDA applications in health care and aims at identifying publication patterns as well as the range of topics to which MCDA have been applied. Therefore, a bibliometric analysis was conducted on articles reporting MCDA applications in health care published from 1960 to 2011. Articles identified through a literature search of health databases were categorized by year of publication, research topics, corresponding authors, country of residence of corresponding authors, and journal titles. The analysis of citation data was conducted in Matheo Analyzer 4.062. Over the time horizon of the analysis, the number of MCDA applications in health care has shown a significant and steady increase, with health care resource allocation being the most prevalent research topic. We also found that the top ten corresponding authors were responsible for 28% of the overall articles, with corresponding authors from the United States being the most prolific. The journal ‘Health Economics’ ranked first among the top ten journals. The results of this bibliometric analysis are concordant with the overall publication trends of MCDA methods described in other fields. Further research is needed, within jurisdictions, to select the most appropriate MCDA method to be applied to health care.

Background Cardiovascular disease (CVD) is a leading cause of hospitalizations, death, and health care costs. Although studies have shown that modifying CVD risk factors at the patient level improves patient prognosis, the effect of community-wide interventions at the population level has been uncertain. Objective To evaluate the resource use and cost consequences of a community-wide Cardiovascular Health Awareness Program (CHAP). Methods Thirty-nine medium-sized communities in Ontario, Canada, participated in a community cluster randomized controlled trial stratified by population size and geographic location. All community-dwelling elderly residents (>65 years) in each community were included. Family physicians, pharmacists, community nurses, local organizations, and volunteers in the intervention communities implemented the program. Rates and costs of CVD hospitalizations, all hospitalizations, emergency department visits, physician visits, and prescription medication use in the year before and after the intervention were compared for the 19 control and 20 CHAP communities by using province-wide linked administrative databases. The cost of implementing and administrating CHAP in each community was combined with total community health care cost to determine the net cost effect. Results CHAP was associated with a reduction in CVD hospitalization costs. There were no differences in utilization rates or costs for overall hospitalizations, in visits to emergency rooms, physicians, or specialists, or in the use of prescription medications. Results were robust over a range of cost assumptions. Conclusions A community-wide CVD awareness program can be implemented and can reduce CVD-related hospitalization costs at the level of the community without a corresponding increase in overall health care costs.

We welcome this opportunity to respond to the comments (1–3) regarding our study (4). There are a few common themes that we would like to clarify. The first theme is around the criticism of using “meeting criteria for amputation” instead of “amputation event.” It is ideal to use more final patient outcomes in all research; however, the sample size and time needed to recruit and follow patients of sufficient duration to observe final events is often prohibitive. This is the reason why intermediate markers and outcomes are used in many disease areas, including diabetes. In addition, final events like amputations may be an inappropriate outcome in small, randomized controlled trials (RCTs) where other factors may confound the true treatment effect. For example, patient cultural preferences, psychological trauma, and procedure-booking logistics (among other factors) frequently override medical advice about whether and when the limb should be amputated. This (extrinsic to disease) variability precludes using actual amputation event as a consistent outcome measure unless a very large sample and long follow-up times are used. This is impractical and prohibitively costly in placebo-controlled hyperbaric treatment trials. However, Margolis et al. (5) have done it elegantly in a study of different design. This multicenter observational cohort with propensity score matching methodology showed no amputation-sparing effect or improved wound healing in over 700 patients treated with hyperbaric oxygen therapy (HBOT) matched with over …

Background: New glaucoma diagnostic technologies are penetrating clinical care and are changing rapidly. Having a systematic review of these technologies will help clinicians and decision makers and help identify gaps that need to be addressed. This systematic review studied five glaucoma technologies compared to the gold standard of white on white perimetry for glaucoma detection. Methods: OVID ® interface: MEDLINE ® (In-Process & Other Non-Indexed Citations), EMBASE ® , BIOSIS Previews ® , CINAHL ® , PubMed, and the Cochrane Library were searched. A gray literature search was also performed. A technical expert panel, information specialists, systematic review method experts and biostatisticians were used. A PRISMA flow diagram was created and a random effect meta-analysis was performed. Results: A total of 2,474 articles were screened. The greatest accuracy was found with frequency doubling technology (FDT) (diagnostic odds ratio (DOR): 57.7) followed by blue on yellow perimetry (DOR: 46.7), optical coherence tomography (OCT) (DOR: 41.8), GDx (DOR: 32.4) and Heidelberg retina tomography (HRT) (DOR: 17.8). Of greatest concern is that tests for heterogeneity were all above 50%, indicating that cutoffs used in these newer technologies were all very varied and not uniform across studies. Conclusions: Glaucoma content experts need to establish uniform cutoffs for these newer technologies, so that studies that compare these technologies can be interpreted more uniformly. Nevertheless, synthesized data at this time demonstrate that amongst the newest technologies, OCT has the highest glaucoma diagnostic accuracy followed by GDx and then HRT. J Clin Med Res. 2016;8(9):641-649 doi: http://dx.doi.org/10.14740/jocmr2643w Correction in J Clin Med Res. 2017;9(3):231, doi: https://doi.org/10.14740/jocmr2643wc1

Background: Expenditures on drugs dispensed and administered to patients in Canadian hospitals have been estimated at $2.4 billion per year. Pharmacy and therapeutics (P&T) committees play a key role in the evaluation and management of drug therapies in this setting. Hospitals differ with respect to the composition of these committees, their members’ expertise, and the processes used for making formulary decisions.Objectives: To examine the current processes for formulary drug review from the perspective of P&T committees and their individual members, and to examine the needs and preferences of these stakeholders related to evidence review and potential collaborative drug review processes within a large Local Health Integration Network (LHIN) in Ontario.Methods: Twenty-three sites within 10 hospital corporations in LHIN 4 (Hamilton Niagara Haldimand Brant) were recruited. A 2-part questionnaire was developed and pretested for clarity and comprehensiveness. The institution profile section of the questionnaire was to be completed by pharmacy directors and the P&T section by committee members.Results: Ten pharmacy directors and 28 committee members representing 10 P&T committees responded. A mean of 6.4 new drug requests were reviewed annually by each P&T committee. Across the LHIN, the workload associated with reviewing submissions for new drugs to be added to the formulary represented 0.84 full-time equivalent. The quality of clinical evidence in the drug submissions was rated more favourably than the quality of economic evidence; furthermore, the use of economic evidence was limited by a lack of health economics expertise within the committees. A centralized review process for the LHIN was perceived as beneficial to improve efficiency, the quality of review, and standardization, and also to reduce costs.Conclusions: Across the Hamilton Niagara Haldimand Brant LHIN, considerable time and resources are spent on the review of potential new drugs for addition to the hospitals’ formularies. A standardized formulary review process, with greater use of provincial and national drug reviews, would likely benefit all LHINs.RÉSUMÉContexte : Les dépenses pour les médicaments distribués et administers aux patients dans les hôpitaux canadiens ont été évaluées à 2,4 milliards de dollars par année. Les comités de pharmacologie et de thérapeutique jouent un rôle central dans l’analyse et la prise en charge des pharmacotherapies dans ce milieu. La composition de ces comités et l’expertise de leurs membres varient d’un hôpital à l’autre, tout comme les processus qui y sont employés pour prendre des décisions à propos de la liste des médicaments.Objectifs : Étudier les processus actuels d’ajout de médicaments à la liste locale du point de vue des comités de pharmacologie et de thérapeutique et de leurs membres. Examiner les besoins et préférences de ces parties prenantes quant à l’analyse des données probantes et aux potentiels processus collaboratifs d’évaluation des médicaments au sein d’un important réseau local d’intégration des services de santé (RLISS) ontarien.Méthodes : Vingt-trois établissements dans 10 organisations hospitalières du RLISS 4 (Hamilton Niagara Haldimand Brant) ont été retenus. On a élaboré un questionnaire de deux parties qui a été testé au préalable pour en vérifier la clarté et l’exhaustivité. La section sur le profil de l’établissement devait être remplie par les directeurs de pharmacie et celle sur la pharmacologie et la thérapeutique devait l’être par les membres des comités.Résultats : Dix directeurs de pharmacie et 28 membres représentant 10 comités de pharmacologie et de thérapeutique ont répondu. En moyenne, 6,4 nouvelles demandes d’ajout de médicament étaient analysées annuellement par chaque comité. Dans l’ensemble du RLISS, la charge de travail nécessaire à l’analyse des demandes d’ajout de nouveaux médicaments à la liste locale représentait 0,84 d’un poste équivalent temps plein. La qualité des données cliniques probantes dans les demandes d’ajout était considérée plus favorablement que celle des données économiques. De plus, comme les membres des comités ne possédaient pas l’expertise nécessaire en économie de la santé, l’utilisation des données probantes à ce sujet était limitée. Un processus centralisé d’analyse pour le RLISS était perçu comme avantageux pour améliorer l’efficience, la qualité de l’analyse et la normalization ainsi que pour réduire les coûts.Conclusions : Dans l’ensemble du RLISS de Hamilton Niagara Haldimand Brant, beaucoup de ressources et de temps sont accordés à évaluer l’ajout de médicaments à la liste locale. Tous les RLISS tireraient sûrement profit d’un processus normalisé d’ajout à la liste locale des médicaments ainsi que d’une meilleure utilisation des évaluations réalisées par les organismes provinciaux et national.

Cost-utility models are increasingly used in many countries to establish whether the cost of a new intervention can be justified in terms of health benefits. Health-state utility (HSU) estimates (the preference for a given state of health on a cardinal scale where 0 represents dead and 1 represents full health) are typically among the most important and uncertain data inputs in cost-utility models. Clinical trials represent an important opportunity for the collection of health-utility data. However, trials designed primarily to evaluate efficacy and safety often present challenges to the optimal collection of HSU estimates for economic models. Careful planning is needed to determine which of the HSU estimates may be measured in planned trials; to establish the optimal methodology; and to plan any additional studies needed. This report aimed to provide a framework for researchers to plan the collection of health-utility data in clinical studies to provide high-quality HSU estimates for economic modeling. Recommendations are made for early planning of health-utility data collection within a research and development program; design of health-utility data collection during protocol development for a planned clinical trial; design of prospective and cross-sectional observational studies and alternative study types; and statistical analyses and reporting.

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost, outcomes, and incremental cost-utility.

To systematically review the methods used in economic evaluations (EEs) included in health technology assessments (HTAs) of genetic testing technologies (GTTs).A systematic search using bibliographic databases and gray literature was undertaken to identify HTA reports on GTTs that included EEs in addition to clinical effectiveness results. Studies were reviewed in terms of methodology and reporting.Of 361 identified citations, 15 HTAs consisting of 11 model-based and 4 trial-based EEs were included, more than 50% of which had moderate-to-low-quality scores mainly due to not reporting information on basic elements of a standard EE and inadequate management of uncertainty. Cost-effectiveness analysis accounted for 62% of studies. Approximately 66% of the studies adopted a third-party payer perspective, and 46% used a lifelong time horizon. The majority of studies exclusively included technical costs of testing (100%) and therapeutic or preventive interventions (60%). The most frequent variables tested in sensitivity analysis included costs (66%), effects (50%), and transition probabilities (58%).We found several methodological challenges in the reviewed EEs, including identification of a proper analytical perspective, inclusion of wider range of outcomes and costs, allowing for long-term medical and nonmedical impacts of genetic tests, and sufficient management of uncertainty. These issues should be carefully considered in future EEs of GTTs.

Jean-Eric Tarride,1,2 Natasha Burke,1,2 Camilla Von Keyserlingk,1,2 Daria O'Reilly,1,2 Feng Xie,1,2 Ron Goeree1,21Programs for Assessment of Technology in Health (PATH) Research Institute, St Joseph's Healthcare Hamilton, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Influenza affects all age groups and is common in children. Between 15% and 42% of preschool- and school-aged children experience influenza each season. Recently, intranasal live attenuated influenza vaccine, trivalent (LAIV) has been approved in Canada.Objective: The objective of this study was to determine the cost-effectiveness of LAIV compared with that of the injectable inactivated influenza vaccine, trivalent (TIV) in Canadian children and adolescents from both a payer (eg. Ministry of Health) perspective and a societal perspective.Methods: A cost-effectiveness model comparing LAIV and TIV in children aged 24–59 months old was supplemented by primary (ie, a survey of 144 Canadian physicians) and secondary (eg, literature) data to model children aged 2–17 years old. Parameter uncertainty was addressed through univariate and probability analyses.Results: Although LAIV increased vaccination costs when compared to TIV, LAIV reduced the number of influenza cases and lowered the number of hospitalizations, emergency room visits, outpatient visits, and parents’ days lost from work. The estimated offsets in direct and societal costs saved were CAD$4.20 and CAD$35.34, respectively, per vaccinated child aged 2–17 years old. When costs and outcomes were considered, LAIV when compared to TIV, was the dominant strategy. At a willingness to pay of CAD$50,000 per quality adjusted life year gained, or CAD$100,000 per quality adjusted life year gained, the probabilistic results indicated that the probability of LAIV being cost-effective was almost 1.Conclusions: LAIV reduces the burden of influenza in children and adolescents. Consistent with previously reported results, vaccinating children with LAIV, rather than TIV, is the dominant strategy from both a societal perspective and a Ministry of Health perspective.Keywords: influenza, vaccine, children, cost-effectiveness

Objective The results of two randomized clinical trials (RCTs) demonstrate the clinical effectiveness of alternatives to casting for certain ankle and wrist fractures. We illustrate the use of value of information (VOI) methods for evaluating the evidence provided by these studies with respect to decision making. Study Design and Setting Using cost-effectiveness data from these studies, the expected value of sample information (EVSI) of a future RCT can be determined. If the EVSI exceeds the cost of the future trial for any sample size, then the current evidence is considered insufficient for decision making and a future trial is considered worthwhile. If, on the other hand, there is no sample size for which the EVSI exceeds the cost, then the evidence is considered sufficient, and no future trial is required. Results We found that the evidence from the ankle study was insufficient to support the adoption of the removable device and determined the optimal sample size for a future trial. Conversely, the evidence from the wrist study was sufficient to support the adoption of the removable device. Conclusions VOI methods provide a decision-analytic alternative to the standard hypothesis testing approach for assessing the evidence provided by cost-effectiveness studies and for determining sample sizes for RCTs.

There is a dearth of information about the burden of osteoporosis in Canadian men. To fill this gap, we conducted a burden of illness study aimed at estimating the economic burden attributable to osteoporosis in Canadian men aged 50 years and older. Five national data sources were used to estimate health care resource utilization and costs (in 2010 Canadian dollars) associated with osteoporosis in men. Any information gap was supplemented by using data from provincial and community sources. Direct medical costs included costs associated with hospitalizations, same day surgeries, emergency room visits, rehabilitation, chronic care, long-term care, home care, physician visits, and prescribed medications. The value of lost productivity from patients and informal caregivers was also determined to provide a societal perspective. Sensitivity analyses were conducted to evaluate the impact of key assumptions on the results. In fiscal year 2007/2008, the total economic burden of treating and rehabilitating male osteoporotic fractures was estimated at $570 million per year, where direct medical costs accounted for 86%. Acute care utilization was responsible for 70% of all direct costs. About 51% of all hospitalizations were for hip fractures and hip fractures alone accounted for 54% of the acute care spending. If a proportion of Canadian men were assumed to live in long-term care facilities due to osteoporosis, the overall annual cost of osteoporosis would increase from $570 million to $910 million. Male osteoporosis has a substantial economic burden on the Canadian society. © 2012 American Society for Bone and Mineral Research.

Based on a population age 50+, significant excess costs relative to matched controls exist for patients with incident fractures that are similar in relative magnitude to other chronic diseases such as stroke or heart disease. Prevalent fractures also have significant excess costs that are similar in relative magnitude to asthma/chronic obstructive pulmonary disease. Cost of illness studies for osteoporosis that only include incident fractures may ignore the long-term cost of prevalent fractures and primary preventive care. We estimated the excess costs for patients with incident fractures, prevalent fractures, and nonfracture osteoporosis relative to matched controls. Men and women age 50+ were selected from administrative records in the province of Manitoba, Canada for the fiscal year 2007–2008. Three types of cases were identified: (1) patients with incident fractures in the current year (2007–2008), (2) patients with prevalent fractures in previous years (1995–2007), and (3) nonfracture osteoporosis patients identified by specific pharmacotherapy or low bone mineral density. Excess resource utilization and costs were estimated by subtracting control means from case means. Seventy-three percent of provincial population age 50+ (52 % of all men and 91 % of all women) were included (121,937 cases, 162,171 controls). There were 3,776 cases with incident fracture (1,273 men and 2,503 women), 43,406 cases with prevalent fractures (15,784 men and 27,622 women) and 74,755 nonfracture osteoporosis cases (7,705 men and 67,050 women). All incident fractures had significant excess costs. Incident hip fractures had the highest excess cost: men $44,963 (95 % CI: $38,498–51,428) and women $45,715 (95 % CI: $36,998–54,433). Prevalent fractures (other than miscellaneous or wrist fractures) also had significant excess costs. No significant excess costs existed for nonfracture osteoporosis. Significant excess costs exist for patients with incident fractures and with prevalent hip, vertebral, humerus, multiple, and traumatic fractures. Ignoring prevalent fractures underestimate the true cost of osteoporosis.