Building a Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology Added Value Framework for Hematologic Malignancies: A Comparative Analysis of Existing Tools.

OBJECTIVES: The Innovative Medicines Initiative-funded, multistakeholders project Healthcare Alliance for Resourceful Medicine Offensive Against Neoplasms in Hematology (HARMONY) created a task force involving patient organizations, medical associations, pharmaceutical companies, and health technology assessment/regulator agencies' representatives to evaluate the suitability of previously established value frameworks (VFs) for assessing the clinical and societal impact of new interventions for hematologic malignancies (HMs). METHODS: Since the HARMONY stakeholders identified the inclusion of patients' points of view on evaluating VFs as a priority, surveys were conducted with the patient organizations active in HMs and part of the HARMONY network, together with key opinion leaders, pharmaceutical companies, and regulators, to establish which outcomes were important for each HM. Next, to evaluate VFs against the sources of information taken into account (randomized clinical trials, registries, real-world data), structured questionnaires were created and filled by HARMONY health professionals to specify preferred data sources per malignancy. Finally, a framework evaluation module was built to analyze existing clinical VFs (American Society of Clinical Oncology, European Society of Medical Oncology, Magnitude of Clinical Benefit Scale, Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen, Institute for Clinical and Economic Review, National Comprehensive Cancer Network Evidence Blocks, and patient-perspective VF). RESULTS: The comparative analysis describes challenges and opportunities for the use of each framework in the context of HMs and drafts possible lines of action for creating or integrating a more specific, patient-focused clinical VF for HMs. CONCLUSIONS: None of the frameworks meets the HARMONY goals for a tool that applies to HMs and assesses in a transparent, reproducible, and systematic way the therapeutic value of innovative health technologies versus available alternatives, taking a patient-centered approach and using real-world evidence.

Value assessment of oncology drugs using a weighted criterion-based approach.

BACKGROUND: Globally, the rising cost of anticancer therapy has motivated efforts to quantify the overall value of new cancer treatments. Multicriteria decision analysis offers a novel approach to incorporate multiple criteria and perspectives into value assessment. METHODS: The authors recruited a diverse, multistakeholder group who identified and weighted key criteria to establish the drug assessment framework (DAF). Construct validity assessed the degree to which DAF scores were associated with past pan-Canadian Oncology Drug Review (pCODR) funding recommendations and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS; version 1.1) scores. RESULTS: The final DAF included 10 criteria: overall survival, progression-free survival, response rate, quality of life, toxicity, unmet need, equity, feasibility, disease severity, and caregiver well-being. The first 5 clinical benefit criteria represent approximately 64% of the total weight. DAF scores ranged from 0 to 300, reflecting both the expected impact of the drug and the quality of supporting evidence. When the DAF was applied to the last 60 drugs (with reviewers blinded) reviewed by pCODR (2015-2018), those drugs with positive pCODR funding recommendations were found to have higher DAF scores compared with drugs not recommended (103 vs 63; Student t test P = .0007). DAF clinical benefit criteria mildly correlated with ESMO-MCBS scores (correlation coefficient, 0.33; 95% CI, 0.009-0.59). Sensitivity analyses that varied the criteria scores did not change the results. CONCLUSIONS: Using a structured and explicit approach, a criterion-based valuation framework was designed to provide a transparent and consistent method with which to value and prioritize cancer drugs to facilitate the delivery of affordable cancer care.

Changes in mortality associated with cancer drug approvals in the United States from 2000 to 2016.

AIMS: To estimate the extent to which the approvals of new pharmacological therapies were associated with cancer mortality in the USA between 2000 and 2016. MATERIALS AND METHODS: The analysis quantified cancer drug approvals across the 15 tumor types with the highest incidence. Number of approvals in a given time period for each tumor was translated into a treatment stock measure, defined as a weighted sum of new indication approvals since 1976. The primary outcome was the annual tumor-specific cancer mortality, defined as the number of deaths per 100,000 U.S. population. The analysis used a multivariable ordinary least squares and a fixed effects model, controlling for incidence (new cases per 100,000 U.S. population) and the primary exposure, the treatment stock measure by year. RESULTS: Between 2000 and 2016, deaths per 100,000 population across the 15 most common tumor types declined by 24%. Additionally, 10.2 new indications were approved per year across the 15 most common tumor types. Cancer drug approvals were associated with statistically significant deaths averted in 2016 for colorectal cancer (4,991, p = 0.004), lung cancer (33,825, p < 0.001), breast cancer (11,502, p < 0.001), non-Hodgkin's lymphoma (6,636, p < 0.001), leukemia (4,011, p < 0.001), melanoma (1,714, p < 0.001), gastric cancer (758, p = 0.019), and renal cancer (739, p < 0.001). Between 2000 and 2016, new cancer treatments were correlated with 1,291,769 (p < 0.001) total deaths prevented across the 15 most common tumor types. LIMITATIONS AND CONCLUSIONS: Cancer drug approvals between 2000 and 2016 were associated with significant reduction in deaths from the most common cancers in the USA. Mortality changes were largest in prevalent tumor types with relatively more approvals, i.e. lung cancer, breast cancer, melanoma, lymphoma and leukemia. Future research evaluating the relationship between drug approvals and cancer mortality post 2016 is needed.

The Impact of Recent Generic Drug Price Policies on Pharmaceutical Innovation: A Theoretical Rationale and Proposal of a Method Supporting Innovation in Areas of Unmet Medical Need.

New discoveries are a critical priority for the pharmaceutical industry. However, the use of fixed incremental cost-effectiveness (ICER) thresholds for health technology assessment (HTA) may compromise incentives to innovate and affect future treatment options. This paper highlights the impact of generic drug price policies on pharmaceutical innovation in the context of fixed ICER thresholds and proposes a new consideration for the cost-effectiveness analysis (CEA). There is a direct causal relationship between HTA and the market price of a drug; in jurisdictions where HTA agencies apply fixed ICER thresholds as an important reimbursement listing criterion, the incremental cost of a new drug is expected to be proportional to its incremental benefit over the comparator. However, the comparator price is subject to market forces or sudden policies and may change markedly affecting the cost-effectiveness assessment (e.g. where the comparator patent has expired). Since recent generic price regulations increased the price gap between drugs' generic and patented versions, it is harder to achieve a sufficient level of incremental benefits in order to offset incremental prices of new treatments. Consequently, even promising drugs may have challenges to show attractive ICERs and research and development (R&D) investments may become unattractive in certain disease area. In order to promote innovation in therapeutic fields with unmet medical needs, a compromise would be to include the comparator's patented price in the CEA instead of the generic drug. By identifying the relevant disease areas, decision makers and HTA authorities could therefore convey the importance of investing in these therapeutic areas to manufacturers.

Bias within economic evaluations - the impact of considering the future entry of lower-cost generics on currently estimated incremental cost-effectiveness ratios of a new drug.

BACKGROUND: Most economic evaluation models compare a new patented drug (NPRx) to a generic comparator. Drug costs within these models are usually limited to the retail cost of both drugs at the time of model conception. However, the retail cost of the NPRx is expected to drop once generic versions of this molecule are introduced following the expiration of the NPRx's patent. The objective of this study was to examine the impact on the incremental cost-effectiveness ratio (ICER) of the future introduction of lower-cost generic versions of the NPRx within the model's time horizon. METHODS: We examined the impact of this parameter with the use of two approaches: 1) a mathematical proof identifying its impact on the NPRx's ICER; and 2) applying this parameter to a previously published economic model comparing a NPRx to a generic comparator and identifying what would have been the NPRx's ICER had this model considered this parameter. RESULTS: As expected, both the mathematical proof and the application to the previously published economic model showed that considering the future introduction of lower-cost generic versions of the NPRx within the model's time horizon lowers the NPRx's ICER. The timing of the future entry of lower-cost generic molecules, their relative price compared to that of the patented version, and the discount rate applied to future costs all influenced the results. CONCLUSION: An ICER estimated within economic evaluations comparing NPRx to generic comparators which ignore the future introduction of lower-cost generic versions of the NPRx within the model's time horizon will tend to be overestimated. Inclusion of this parameter should be considered within future economic evaluations.

The effect of pharmacist intervention and patient education on lipid-lowering medication compliance and plasma cholesterol levels.

BACKGROUND: Dyslipidemias are a modifiable risk factor for coronary heart disease. The benefits of cholesterol reduction drug therapies are limited by poor patient compliance with drug regimens. OBJECTIVES: To determine the impact of a community pharmacist pilot disease-management program on patient compliance with lipid-lowering drug therapy and on serum cholesterol levels. METHODS: One hundred forty-nine patients who were nonadherent to prescribed hypolipidemic drug regimens were recruited for this six-month prospective study. Each subject served as their own control. Pharmacists educated these patients on lipid disorders, the benefit of medication compliance and lifestyle modifications that reduce the risk for coronary heart disease. Pharmacists followed up participants by telephone at two-month intervals. Drug renewal rates were monitored throughout the study and plasma lipid levels were measured at study outset and study end. RESULTS: Pharmacist intervention and patient-education programs significantly increased medication compliance, as shown by a 15.3% increase (P<0.05) in the number of compliant patients and an 11 day (P<0.001) reduction in the average number of days to prescription renewal. Concurrently, levels of total cholesterol, triglycerides and low-density lipoprotein (LDL) cholesterol, were reduced by 6%, 16.2%, and 8.5% (P<0.001, 0.01, 0.01), respectively. High density lipoprotein (HDL) cholesterol remained relatively unchanged (+0.7%) so that the LDL to HDL ratio was improved by 17.2% overall (P<0.01). Almost all of the patients (99.2%) were satisfied with the program and expressed a willingness to pay an average $34.50 per 30 min consultation for the pharmacist services offered. CONCLUSION: Pharmacists can contribute significantly to disease management of dyslipidemic individuals.

An economic evaluation of voriconazole versus amphotericin B for the treatment of invasive aspergillosis in Canada.

BACKGROUND: Invasive aspergillosis (IA) is a serious fungal infection that affects immunocompromised patients. The Global Comparative Aspergillosis study demonstrated that voriconazole, a new broad-spectrum triazole, had better responses and improved survival compared with conventional amphotericin B deoxycholate (CAB) and other licensed antifungal therapy (OLAT) for the treatment of definite or probable aspergillosis. OBJECTIVES: To compare costs and outcomes of voriconazole and CAB for the treatment of definite or probable aspergillosis in Canada. METHODS: A cost-consequence decision tree model was designed to reflect the treatment pathways used in clinical practice when using voriconazole or CAB as primary therapy for IA. Therapy included initial treatment with either voriconazole or CAB and then switched to an OLAT in the event of an inadequate response, severe toxicity or intolerance. The principal data source used was the Global Comparative Aspergillosis study. RESULTS: The total cost of voriconazole when compared with CAB as initial therapy for IA was $38,319 versus $42,495 per patient, respectively, representing a 9.8% cost reduction for each patient treated with voriconazole. The higher mean cost in the CAB arm was primarily due to the high proportion of patients (73.7%) who were switched to an OLAT due to severe side effects or an inadequate response. Treating with voriconazole was a dominant strategy. The number of patients that had to be treated with voriconazole instead of CAB to save one additional life was eight. CONCLUSIONS: Voriconazole as primary treatment for IA increased the chances of successful treatment, improved survival and may represent a potential cost saving strategy in Canada.

Choices, persistence and adherence to antihypertensive agents: evidence from RAMQ data.

BACKGROUND: Most treatment recommendations for hypertension are based on criteria that consider efficacy, safety and cost. Given the need for long-term use of antihypertensive agents, treatment compliance should also be taken into consideration in the selection process. OBJECTIVE: The purpose of the present study was to estimate persistence and adherence to antihypertensive agents in a real-life setting. METHODS: Persistence and adherence to treatment were estimated using data from the Regie de l'assurance maladie du Quebec. RESULTS: Data from a random sample of 4561 subjects with a diagnosis of hypertension covered by the Regie de l'assurance maladie du Quebec drug plan and using one of the antihypertensive agents reimbursed by the drug plan for the first time between January 2000 and December 2001 were analyzed. The persistence rate observed after a two-year period with diuretics was significantly lower (52.8%) than with any other classes of antihypertensive agent (P<0.01). Persistence rates for beta-blockers, calcium channel blockers, angiotensin-II receptor blockers and angiotensin-I converting enzyme inhibitors were 69.3%, 64.3%, 60.9% and 58.9%, respectively. After two years, the proportion of patients who were 80% adherent to their treatment was 64.9% for angiotensin-I converting enzyme inhibitors, 65.0% for angiotensin-II receptor blockers, 64.2% for calcium channel blockers, 60.3% for beta-blockers and 50.9% for diuretics. The proportion of patients who were 80% adherent to their treatment was significantly lower for diuretics than with any other antihypertensive agents (P<0.01). CONCLUSION: Persistence and adherence to treatment are essential to treatment success. Results of the present study indicate that, in a real-life setting, patients are significantly less compliant to diuretics than to any other antihypertensive agents.