DEVELOPMENT OF THE ONTARIO DECISION FRAMEWORK: A VALUES BASED FRAMEWORK FOR HEALTH TECHNOLOGY ASSESSMENT.

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.

Comparative Efficacy of Angiotensin II Antagonists in Essential Hypertension: Systematic Review and Network Meta-Analysis of Randomised Controlled Trials.

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.

Estimating Health-State Utility for Economic Models in Clinical Studies: An ISPOR Good Research Practices Task Force Report.

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.

Cost Consequence Analysis of Implementing the Low Risk Ankle Rule in Emergency Departments.

STUDY OBJECTIVE: Implementation of the Low Risk Ankle Rule can safely reduce radiographs for children with acute ankle injuries. The main objective of this study is to examine the costs and consequences of implementing the rule. METHODS: For children aged 3 to 16 years and with an acute ankle injury, we collected data on health care provider visits, imaging, and treatment at the index emergency department (ED) visit and days 7 and 28 post-ED discharge. This was done during 3 consecutive 6-month phases at 6 EDs. After the baseline phase 1, the Low Risk Ankle Rule was introduced in phases 2 and 3 in 3 intervention EDs, but not in the 3 pair-matched control EDs. We compared the effect of the Low Risk Ankle Rule on health care and patient-paid costs, the proportion of radiographs ordered, the proportion of missed clinically important fractures, and the follow-up use of health care resources. RESULTS: We enrolled 2,151 children with ankle injuries, 1,055 at the intervention and 1,096 at the control EDs. Health care costs were $36.93 less per patient at intervention compared with control sites (P=.02). Out-of-pocket costs to the patients were $2.09 more per patient at intervention sites (P=.30). In intervention versus control sites, the main contributor to cost reduction was the 22.9% reduction in ankle radiography. Furthermore, there were no significant differences in the frequency of missed clinically important fractures (0.1% versus 0.9%) or follow-up use of health care resources. CONCLUSION: Widespread implementation of the Low Risk Ankle Rule may lead to reduction of unnecessary radiographs for children and result in cost savings.

Economic burden of illness associated with diabetic foot ulcers in Canada.

BACKGROUND: The primary objective was to estimate the national burden of illness in Canada for diabetic foot ulcer (DFU) for 2011. Secondary objectives included estimating the national incidence and prevalence of DFU, and the 3-year average cost for DFU incident cases. METHODS: Analyses were conducted using four national databases for the period April 1, 2006 to March 31, 2011, with cases being identified by ICD-10 CA codes. Resource utilization and costs, expressed in 2011 Canadian dollars, were estimated for DFU-related hospitalizations, emergency care (ER), same day surgeries, home care, long term care, physician visits and caregiver time losses. RESULTS: In Canada in the year 2011, DFU was associated with 16,883 hospital admissions (327,140 days), 31,095 ER or clinic visits, 41,367 rehabilitation clinic visits, and 26,493 interventions, including 6,036 amputations and 5,796 surgical debridements. This acute institution care represented $320.5 M, and with an additional $125.4 M for home care and $63.1 M for long term care, the annual cost associated with DFU-related care was $547.0 M, or $21,371 annual cost per prevalent case. In 2011, the national prevalence of DFU was 25,597 cases (75.1 per 100,000 population), consisting of 16,161 men (63.1%) and 9,436 women (36.9%), and an estimated 14,449 incident cases. For an incident case of DFU, the average 3-year cumulative cost was $52,360. CONCLUSION: The annual burden for DFU cases that have at least one admission or ER/clinic visit over a 5 year period is higher than previously reported.

Barriers and facilitators influencing ethical evaluation in health technology assessment.

OBJECTIVES: The objective of this study was to explore barriers and facilitators influencing the integration of ethical considerations in health technology assessment (HTA). METHODS: The study consisted of two complementary approaches: (a) a systematic review of the literature; and (b) an eighteen-item online survey that was distributed to fifty-six HTA agencies affiliated with the International Network of Agencies for Health Technology Assessment. RESULTS: The review identified twenty-six relevant articles. The most often cited barriers in the literature were: scarcity, heterogeneity and complexity of ethical analysis methods; challenges in translating ethical analysis results into knowledge that is useful for decision makers; and lack of organizational support in terms of required expertise, time and financial resources. The most frequently cited facilitators included: usage of value-based appraisal methods, stakeholder and public engagement, enhancement of practice guidelines, ethical expertise, and educational interventions. Representatives of twenty-six (46.5 percent) agencies from nineteen countries completed the survey. A median of 10 percent (interquartile range, 5 percent to 50 percent) of the HTA products produced by the agencies was reported to include an assessment of ethical aspects. The most commonly perceived barriers were: limited ethical knowledge and expertise, insufficient time and resources, and difficulties in finding ethical evidence or using ethical guidelines. Educational interventions, demand by policy makers, and involvement of ethicists in HTA were the most commonly perceived facilitators. CONCLUSIONS: Our results emphasize the importance of simplification of ethics methodology and development of good practice guidelines in HTA, as well as capacity building for engaging HTA practitioners in ethical analyses.

Cost-effectiveness of ventricular assist device therapy as a bridge to transplantation compared with nonbridged cardiac recipients.

BACKGROUND: Current available treatment options for advanced heart failure include heart transplantation and ventricular assist device (VAD) therapy. This project aimed to evaluate the cost-effectiveness of a bridge-to-transplantation (BTT)-VAD approach relative to direct heart transplantation in transplant-eligible patients. METHODS AND RESULTS: A Markov model was used to evaluate survival benefits and costs for BTT-VAD versus nonbridged heart transplant recipients. Three different scenarios were considered according to severity of patients' baseline hemodynamic status (high, medium, and low risk). Results are presented in terms of survival, costs, and cost-effectiveness ratio. Sensitivity analyses were used to analyze uncertainty in model estimates. Over a 20-year time horizon, BTT-VAD therapy increased survival at an increased cost relative to nonbridged heart transplant recipients: $100 841more in costs and 1.19 increased life years (LYs) in high-risk patients ($84 964/LY), $112 779 more in costs and 1.14 more LYs ($99 039/LY) in medium-risk patients, and an additional cost of $144 334 and incremental clinical benefit of 1.21 more LYs ($119 574/LY) in low-risk patients. The sensitivity analysis estimated a 59%, 54%, and 43% chance of BTT-VAD therapy being cost-effective for high-, medium-, and low-risk patients at a willingness-to-pay level of $100 000/LY. Subgroup analyses indicated that risk of post-VAD and transplantation complications, waiting time, renal dysfunction, and patient age substantially affected the cost-effectiveness ratio. CONCLUSIONS: BTT-VAD therapy is associated with improved survival and increased costs. On the basis of commonly accepted willingness-to-pay thresholds, BTT-VAD therapy is likely to be cost-effective relative to nonbridged heart transplantation in specific circumstances.

A systematic review of the reporting of sample size calculations and corresponding data components in observational functional magnetic resonance imaging studies.

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.

Economic evaluation of an influenza immunization strategy of healthy children.

OBJECTIVES: Vaccinating healthy children is proposed as a strategy to produce a herd effect and protect vulnerable groups. The Hutterite Influenza Prevention Study investigated this strategy, comparing communities with or without childhood influenza immunization programs. There are costs associated with vaccination therefore there may be a trade-off between these costs and the benefits of avoiding influenza cases. This evaluation estimates the cost-effectiveness of immunizing only healthy children in preventing cases of influenza within entire communities. METHODS: Effect data and resource utilization were collected during the trial. Cost data were collected from payer, literature and Internet sources. A two-stage bootstrap (TSB) with shrinkage correction was used to estimate average costs and effects. The incremental cost effectiveness ratio (ICER) and sample uncertainty around this estimate were calculated from the TSB results. RESULTS: Mean costs per patient for the treatment and control arms were $69.07 and $32.66 (difference $36.41). Mean number of influenza cases for the treatment and control arms were 0.04 and 0.27 (difference 0.23). ICER was $164.12 ($28.38, $2767.75) per case of influenza averted. CONCLUSIONS: Immunizing healthy children for influenza is more costly, yet more effective than no immunization in preventing cases in the sample. At a cost of $164.12 to prevent a case of influenza, immunizing healthy children to protect all community members may be considered costeffective. Estimated results are conservative as the influenza season was mild and the sample population was healthy. In a more severe season with a less healthy population the ICER is expected to decrease.

Active surveillance, radiofrequency ablation, or cryoablation for the nonsurgical management of a small renal mass: a cost-utility analysis.

BACKGROUND: Patients with a cortical small (≤4 cm) renal mass often are not candidates for or choose not to undergo surgery. The optimal management strategy for such patients is unclear. METHODS: A decision-analytic Markov model was developed from the perspective of a third party payer to compare the quality-adjusted life expectancy and lifetime costs for 67-year-old patients with a small renal mass undergoing premanagement decision biopsy, immediate percutaneous radiofrequency ablation or percutaneous cryoablation (without premanagement biopsy), or active surveillance with serial imaging and subsequent ablation if needed. RESULTS: The dominant strategy (most effective and least costly) was active surveillance with subsequent cryoablation if needed. On a quality-adjusted and discounted basis, immediate cryoablation resulted in a similar life expectancy (3 days fewer) but cost $3,010 more. This result was sensitive to the relative rate of progression to metastatic disease. Strategies that employed radiofrequency ablation had decreased quality-adjusted life expectancies (82-87 days fewer than the dominant strategy) and higher costs ($3,231-$6,398 more). CONCLUSIONS: Active surveillance with delayed percutaneous cryoablation, if needed, may be a safe and cost-effective alternative to immediate cryoablation. The uncertainty in the relative long-term rate of progression to metastatic disease in patients managed with active surveillance versus immediate cryoablation needs to be weighed against the higher cost of immediate cryoablation. A randomized trial is needed directly to evaluate the nonsurgical management of patients with a small renal mass, and could be limited to the most promising strategies identified in this analysis.

Economic appraisal of a community-wide cardiovascular health awareness program.

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.

The excess burden of rheumatoid arthritis in Ontario, Canada.

OBJECTIVES: The purpose of this study was to estimate the excess burden of RA in Ontario, the largest province in Canada. METHODS: The records of all adult Ontarians who participated in the Canadian Community Health Survey (CCHS) cycle 1.1 (2000/2001) and provided consent to data linkage were linked to the Ontario Health Insurance Program (OHIP) physician claims database and the Discharge Abstract Database (DAD) In-Patient (i.e. hospitalisation) and Day-Procedure databases. RA individuals (n=233) were identified using CCHS 1.1 and the physician claims database. A control group matched by age, gender and rural/urban status was created with three controls for one case (n=699). Socio-demographic variables, medical characteristics, health-related quality of life (HRQoL) and one-year physician services, hospitalizations and day procedures costs were determined for the RA and non-RA groups. Regression techniques were used to identify predictors of medical characteristics, utility and cost data. RESULTS: The mean age of the population was 59 years and 76% were female. Compared to the matched control group, individuals with RA were statistically more likely to be obese, less educated, physically inactive and have a lower income. RA individuals also reported a statistically higher number of comorbidities and a lower HRQoL. Although no statistical differences were observed between the RA and non-RA groups for the costs associated with hospitalisations, the physician ($1,015 vs. $624, respectively) and day procedure ($102 vs. $51, respectively) costs were statistically higher among RA individuals. CONCLUSIONS: These results indicate that the human and economic burden of RA in Ontario is considerable.

The excess burden of osteoarthritis in the province of Ontario, Canada.

OBJECTIVE: Little is known about the burden of osteoarthritis (OA) in Canada. This study was undertaken to estimate the excess burden of OA in Ontario, the largest province in Canada. METHODS: The records of Ontarian respondents to the Canadian Community Health Survey (CCHS) who provided consent to data linkage were linked to the Ontario Health Insurance Program physician claims database and the Discharge Abstract Database Inpatient and Day Procedure databases. Patients with OA (n = 1,474) were identified using CCHS 1.1 and the physician claims database. To determine the excess burden of OA, a control group matched by age, sex, and rural/urban status was created, with 3 controls per case (n = 4,422). Sociodemographic and medical characteristics, health-related quality of life, and 1-year physician, day (outpatient) procedure, and hospitalization costs were compared between the 2 groups. Regression analyses were performed to identify predictors of medical characteristics, health utility, and cost. RESULTS: The mean age of the OA patients and the control subjects was 66 years, and 74% of all study subjects were women. Several differences were observed between patients with OA and subjects without OA in terms of socioeconomic and medical characteristics. On a scale of 0-1, the mean utility value associated with OA was 0.68, compared to 0.84 for the control group (P < 0.0001), representing a utility decrement of 0.16. The 1-year physician, outpatient procedure, and hospitalization costs were significantly higher in the OA group than in the non-OA group ($2,233 Canadian versus $1,033 Canadian, respectively; P < 0.0001). CONCLUSION: These results indicate that the excess burden of OA in Ontario is considerable.

Surrogate outcomes: experiences at the Common Drug Review.

BACKGROUND: Surrogate outcomes are a significant challenge in drug evaluation for health technology assessment (HTA) agencies. The research objectives were to: identify factors associated with surrogate use and acceptability in Canada's Common Drug Review (CDR) recommendations, and compare the CDR with other HTA or regulatory agencies regarding surrogate concerns. METHODS: Final recommendations were identified from CDR inception (September 2003) to December 31, 2010. Recommendations were classified by type of outcome (surrogate, final, other) and acceptability of surrogates (determined by the presence/absence of statements of concern regarding surrogates). Descriptive and statistical analyses examined factors related to surrogate use and acceptability. For thirteen surrogate-based submissions, recommendations from international HTA and regulatory agencies were reviewed for statements about surrogate acceptability. RESULTS: Of 156 final recommendations, 68 (44%) involved surrogates. The overall 'do not list' (DNL) rate was 48%; the DNL rate for surrogates was 41% (p = 0.175). The DNL rate was 64% for non-accepted surrogates (n = 28) versus 25% for accepted surrogates (odds ratio 5.4, p = 0.002). Clinical uncertainty, use of economic evidence over price alone, and a premium price were significantly associated with non-accepted surrogates. Surrogates were used most commonly for HIV, diabetes, rare diseases, cardiovascular disease and cancer. For the subset of drugs studied, other HTA agencies did not express concerns for most recommendations, while regulatory agencies frequently stated surrogate acceptance. CONCLUSIONS: The majority of surrogates were accepted at the CDR. Non-accepted surrogates were significantly associated with clinical uncertainty and a DNL recommendation. There was inconsistency of surrogate acceptability across several international agencies. Stakeholders should consider collaboratively establishing guidelines on the use, validation, and acceptability of surrogates.

Hyperbaric oxygen therapy for diabetic ulcers: systematic review and meta-analysis.

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.

Simulating an emergency department: the importance of modeling the interactions between physicians and delegates in a discrete event simulation.

BACKGROUND: Computer simulation studies of the emergency department (ED) are often patient driven and consider the physician as a human resource whose primary activity is interacting directly with the patient. In many EDs, physicians supervise delegates such as residents, physician assistants and nurse practitioners each with different skill sets and levels of independence. The purpose of this study is to present an alternative approach where physicians and their delegates in the ED are modeled as interacting pseudo-agents in a discrete event simulation (DES) and to compare it with the traditional approach ignoring such interactions. METHODS: The new approach models a hierarchy of heterogeneous interacting pseudo-agents in a DES, where pseudo-agents are entities with embedded decision logic. The pseudo-agents represent a physician and delegate, where the physician plays a senior role to the delegate (i.e. treats high acuity patients and acts as a consult for the delegate). A simple model without the complexity of the ED is first created in order to validate the building blocks (programming) used to create the pseudo-agents and their interaction (i.e. consultation). Following validation, the new approach is implemented in an ED model using data from an Ontario hospital. Outputs from this model are compared with outputs from the ED model without the interacting pseudo-agents. They are compared based on physician and delegate utilization, patient waiting time for treatment, and average length of stay. Additionally, we conduct sensitivity analyses on key parameters in the model. RESULTS: In the hospital ED model, comparisons between the approach with interaction and without showed physician utilization increase from 23% to 41% and delegate utilization increase from 56% to 71%. Results show statistically significant mean time differences for low acuity patients between models. Interaction time between physician and delegate results in increased ED length of stay and longer waits for beds. CONCLUSION: This example shows the importance of accurately modeling physician relationships and the roles in which they treat patients. Neglecting these relationships could lead to inefficient resource allocation due to inaccurate estimates of physician and delegate time spent on patient related activities and length of stay.

Effect of provider and patient reminders, deployment of nurse practitioners, and financial incentives on cervical and breast cancer screening rates.

OBJECTIVE: To evaluate the effect of the Provider and Patient Reminders in Ontario: Multi-Strategy Prevention Tools (P-PROMPT) reminder and recall system and pay-for-performance incentives on the delivery rates of cervical and breast cancer screening in primary care practices in Ontario, with or without deployment of nurse practitioners (NPs). DESIGN: Before-and-after comparisons of the time-appropriate delivery rates of cervical and breast cancer screening using the automated and NP-augmented strategies of the P-PROMPT reminder and recall system. SETTING: Southwestern Ontario. PARTICIPANTS: A total of 232 physicians from 24 primary care network or family health network groups across 110 different sites eligible for pay-for-performance incentives. INTERVENTIONS: The P-PROMPT project combined pay-for-performance incentives with provider and patient reminders and deployment of NPs to enhance the delivery of preventive care services. MAIN OUTCOME MEASURES: The mean delivery rates at the practice level of time-appropriate mammograms and Papanicolaou tests completed within the previous 30 months. RESULTS: Before-and-after comparisons of time-appropriate delivery rates (< 30 months) of cancer screening showed the rates of Pap tests and mammograms for eligible women significantly increased over a 1-year period by 6.3% (P < .001) and 5.3% (P < .001), respectively. The NP-augmented strategy achieved comparable rate increases to the automated strategy alone in the delivery rates of both services. CONCLUSION: The use of provider and patient reminders and pay-for-performance incentives resulted in increases in the uptake of Pap tests and mammograms among eligible primary care patients over a 1-year period in family practices in Ontario.

A Probabilistic Cost-Effectiveness Analysis of Venetoclax and Obinutuzumab as a First-Line Therapy in Chronic Lymphocytic Leukemia in Canada.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: VEN+O is a cost-effective treatment option for unfit frontline CLL patients and provides value for money to healthcare payers.

Cost-effectiveness analysis of antiviral treatments for HBeAg-positive chronic hepatitis B in Canada.

OBJECTIVE: To conduct a cost-effectiveness analysis of currently available nucleos(t)ide antiviral treatments (lamivudine, telbivudine, entecavir, and tenofovir) for chronic hepatitis B in Canada. METHODS: Markov modeling was used to project the lifetime health benefits and costs associated with the antiviral treatments. The hypothetical patient population was hepatitis B e antigen-positive chronic hepatitis B-infected patients aged 34 years. Quality-adjusted life-years were used as a measure of effectiveness. Long-term cumulative incidence of liver complications was also projected. Treatment effectiveness data were derived from the literature; meta-analysis was conducted when there was a large variance in reported effectiveness data. Costs were obtained from a cost analysis of treating chronic hepatitis B-related complications in Canada. Stochastic parameter uncertainty was examined in probabilistic sensitivity analysis by using second-order Monte Carlo simulation. Alternative modeling assumptions were assessed in scenario analysis. One-way sensitivity analysis was used to explore each parameter's impact on the uncertainty of the results. RESULTS: In the base-case analysis, telbivudine was dominated by entecavir and tenofovir. Tenofovir strictly dominated lamivudine, telbivudine, and entecavir. Over the 72-year period of the model, the expected life expectancy (undiscounted) of lamivudine, telbivudine, entecavir, and tenofovir was 35.71, 36.94, 37.65, and 37.99 years, respectively. Tenofovir had the highest expected quality-adjusted life-years at 11.86 (discounted) in all comparisons. Scenario and sensitivity analyses proved the robustness of the base-case results. The projected 10-year cumulative incidence of cirrhosis and hepatocellular carcinoma was 11.40% and 3.05%, respectively, for tenofovir, which is significantly lower than that for lamivudine. CONCLUSION: Tenofovir generated the best results compared with all other therapies under evaluation.

Cost-effectiveness of romosozumab for the treatment of postmenopausal women at very high risk of fracture in Canada.

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 .