High-dose inactivated influenza vaccine is associated with cost savings and better outcomes compared to standard-dose inactivated influenza vaccine in Canadian seniors.

Seasonal influenza infects approximately 10-20% of Canadians each year, causing an estimated 12,200 hospitalizations and 3,500 deaths annually, mostly occurring in adults ≥65 years old (seniors). A 32,000-participant, randomized controlled clinical trial (FIM12; Clinicaltrials.gov NCT01427309) showed that high-dose inactivated influenza vaccine (IIV-HD) is superior to standard-dose vaccine (SD) in preventing laboratory-confirmed influenza illness in seniors. In this study, we performed a cost-utility analysis (CUA) of IIV-HD versus SD in FIM12 participants from a Canadian perspective. Healthcare resource utilization data collected in FIM12 included: medications, non-routine/urgent care and emergency room visits, and hospitalizations. Unit costs were applied using standard Canadian cost sources to estimate the mean direct medical and societal costs associated with each vaccine (2014 CAD). Clinical illness data from the trial were mapped to quality-of-life data from the literature to estimate differences in effectiveness between vaccines. Time horizon was one influenza season, however, quality-adjusted life-years (QALYs) lost due to death during the study were captured over a lifetime. A probabilistic sensitivity analysis (PSA) was also performed. Average per-participant medical costs were $47 lower and societal costs $60 lower in the IIV-HD arm. Hospitalizations contributed 91% of the total cost and were less frequent in the IIV-HD arm. IIV-HD provided a gain in QALYs and, due to cost savings, dominated SD in the CUA. The PSA indicated that IIV-HD is 89% likely to be cost saving. In Canada, IIV-HD is expected to be a less costly and more effective alternative to SD, driven by a reduction in hospitalizations.

Clinical Guidelines: A NICE Way to Introduce Cost-Effectiveness Considerations?

The National Institute for Health and Care Excellence (NICE) in the United Kingdom initiated its clinical guidelines program in 2001 and more than 200 guidelines have been produced to date. As with most of NICE's other programs, the clinical guidelines program also must take into account the relative costs and benefits of interventions when deciding whether to recommend them. The three main advantages of the program are that 1) it represents an important collaboration with the medical profession, thereby increasing the likelihood of recommendations being adopted; 2) the guidelines provide an opportunity to review all aspects of the clinical pathway, rather than focusing on only the adoption of a new technology; and 3) the guidelines offer the potential to discuss disinvestment as well as new investment. All the guidelines contain a systematic review of the relevant economic evaluation literature, and the 12 guidelines published from January 1 to August 31, 2015, contain 28 de novo economic analyses. The main challenges encountered in the guidelines program are that 1) there is an inevitable tension in advising on the quality of care that individual patients could expect while recognizing the broader public health objectives of equity, fairness, and efficiency; 2) the impact of economics is sometimes lessened because of the lack of time to conduct de novo analyses; and 3) unlike NICE's technology appraisal program, the adoption of recommendations is not mandatory for the UK National Health Service.

Applying health economics for policy decision making: do devices differ from drugs?

Medical devices pose unique challenges for economic evaluation and associated decision-making processes that differ from pharmaceuticals. We highlight and discuss these challenges in the context of cardiac device therapy, based on a systematic review of relevant economic evaluations. Key challenges include practical difficulties in conducting randomized clinical trials, allowing for a 'learning curve' and user characteristics, accounting for the wider organizational impacts of introducing new devices, and allowing for variations in product characteristics and prices over time.

Evidence and values: requirements for public reimbursement of drugs for rare diseases--a case study in oncology.

INTRODUCTION: Doubts have been expressed about whether standard methods of health technology assessment are suitable for the evaluation of drugs for rare diseases. Under conditions of rarity, it may be more difficult to conduct large randomized trials in order to gather adequate evidence on efficacy, and the standard methods of economic evaluation may not adequately reflect societal preferences for the treatment of serious and/or life-threatening rare diseases. METHODS: A roundtable was held at the University of Toronto Joint Centre for Bioethics on February 18, 2008 to address these issues. While the focus was on evaluation and reimbursement decision-making for rare cancers, the discussion was broadened to consider the place of evidence and values in considering public reimbursement of drugs prescribed for rare disorders more generally. DISCUSSION: This paper explores the relevant issues in more detail, using the example of a new drug for treatment of renal cell carcinoma. CONCLUSION: There should be a greater commitment by reimbursement agencies to a fair and transparent decision-making process with appropriate community input. Criteria should be developed to validate surrogate markers for rare diseases. It should also be acknowledged that the traditional measures of benefit in economic studies do not incorporate all elements of social value. The need should be recognized to balance equity with an efficient use of resources.

The cost-effectiveness of influenza vaccination for people aged 50 to 64 years: an international model.

OBJECTIVES: Routine influenza vaccination is currently recommended in several countries for people aged more than 60 or 65 years or with high risk of complications. A lower age threshold of 50 years has been recommended in the United States since 1999. To help policymakers consider whether such a policy should be adopted more widely, we conducted an economic evaluation of lowering the age limit for routine influenza vaccination to 50 years in Brazil, France, Germany, and Italy. METHODS: The probabilistic model was designed to compare in a single season the costs and clinical outcomes associated with two alternative vaccination policies for persons aged 50 to 64 years: reimbursement only for people at high risk of complications (current policy), and reimbursement for all individuals in this age group (proposed policy). Two perspectives were considered: third-party payer (TPP) and societal. Model inputs were obtained primarily from the published literature and validated through expert opinion. The historical distribution of annual influenza-like illness (ILI) incidence was used to simulate the uncertain incidence in any given season. We estimated gains in unadjusted and quality-adjusted life expectancy, and the cost per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Comparing the proposed to the current policy, the estimated mean costs per QALY gained were R$4,100, EURO 13,200, EURO 31,400 and EURO 15,700 for Brazil, France, Germany, and Italy, respectively, from a TPP perspective. From the societal perspective, the age-based policy is predicted to yield net cost savings in Germany and Italy, whereas the cost per QALY decreased to R$2800 for Brazil and EURO 8000 for France. The results were particularly sensitive to the ILI incidence rate, vaccine uptake, influenza fatality rate, and the costs of administering vaccination. Assuming a cost-effectiveness threshold ratio of EURO 50,000 per QALY gained, the probabilities of the new policy being cost-effective were 94% and 95% for France, 72% and near 100% for Germany, and 89% and 99% for Italy, from the TPP and societal perspectives, respectively. CONCLUSIONS: Extending routine influenza vaccination to people more than 50 years of age is likely to be cost-effective in all four countries studied.

Cost-effectiveness analysis of oxaliplatin compared with 5-fluorouracil/leucovorin in adjuvant treatment of stage III colon cancer in the US.

BACKGROUND: The MOSAIC trial demonstrated that oxaliplatin/5-fluorouracil/leucovorin (FU/LV) (FOLFOX4) as adjuvant treatment of TNM stage II and III colon cancer significantly improves disease-free survival compared with 5-FU/LV alone. For stage III patients the 4-year disease-free survival (DFS) was 69% in the FOLFOX4 arm vs 61% in the LV5FU2 arm, P = .002). The cost-effectiveness of FOLFOX4 in stage III patients was evaluated from a US Medicare perspective. METHODS: By using individual patient-level data from the MOSAIC trial (median follow-up: 44.2 months), DFS and overall survival (OS) were estimated up to 4 years from randomization. DFS was extrapolated from 4 to 5 years by fitting a Weibull model and subsequent survival was estimated from life tables. OS beyond 4 years was predicted from the extrapolated DFS estimates and observed survival after recurrence. Costs were calculated from trial data and external estimates of resources to manage recurrence. RESULTS: Patients on FOLFOX4 were predicted to gain 2.00 (95% confidence interval [CI]: 0.63, 3.37) years of DFS over those on 5-FU/LV. The predicted life expectancy of stage III patients on FOLFOX4 and 5-FU/LV was 17.61 and 16.26 years, respectively. Mean total lifetime disease-related costs were $56,300 with oxaliplatin and $39,300 with 5-FU/LV. Compared with 5-FU/LV, FOLFOX4 was estimated to cost $20,600 per life-year gained and $22,800 per quality-adjusted life-year (QALY) gained, discounting costs and outcomes at 3% per annum. CONCLUSIONS: FOLFOX4 is likely to be cost-effective compared with 5-FU/LV in the adjuvant treatment of stage III colon cancer. The incremental cost-effectiveness ratio compares favorably with other funded interventions in oncology.

European perspective on the costs and cost-effectiveness of cancer therapies.

In Europe, the vast majority of the costs of cancer therapy fall on third-party payers, normally the government, or sickness funds. Therefore, the main focus of cost-effectiveness studies is to assist payers in deciding whether new therapies are worthwhile, despite their high cost. Drug budgets are regulated in most European countries. The main form of central control is price setting, with some form of reference pricing being the most common approach. This sets the price of drugs, either to an international standard, or to a common price for drugs in the same group or cluster. At the hospital level, the main control over cancer drugs is the hospital formulary. Studies have shown a wide variation among European countries in access to cancer drugs. Explanations for these variations include differences in research funding, the drug approval process, the role of health economics in decision making, and budgetary issues. Several countries in Europe now require economic data in making decisions about the reimbursement of new drugs. An examination of decisions made by the National Institute for Health and Clinical Excellence in the United Kingdom suggests that cancer drugs have fared quite well, with most recommendations being positive. This could be because of the seriousness of the health condition and the lack of alternative therapies for some cancer patients. If the policy of requesting cost-effectiveness evidence for pricing and reimbursement decisions becomes more popular, a major implication for the pharmaceutical industry is that studies should be conducted during phase III of clinical development to generate the required data.

An economic evaluation of sequential i.v./po moxifloxacin therapy compared to i.v./po co-amoxiclav with or without clarithromycin in the treatment of community-acquired pneumonia.

STUDY OBJECTIVE: To evaluate costs, clinical consequences, and cost-effectiveness from a German and French health-care system perspective of sequential i.v./po moxifloxacin monotherapy compared to co-amoxiclav with or without clarithromycin (AMC +/- CLA) in patients with community-acquired pneumonia (CAP) who required parenteral treatment. METHODS: Costs and consequences over 21 days were evaluated based on clinical cure rates 5 to 7 days after treatment and health resource use reported for the TARGET multinational, prospective, randomized, open-label trial. This trial compared sequential i.v./po monotherapy with moxifloxacin (400 mg qd) to i.v./po co-amoxiclav (1.2 g i.v./625 mg po tid) with or without clarithromycin (500 mg bid) for 7 to 14 days in hospitalized patients with CAP. Since no country-by-treatment interaction was found in spite of some country differences for length of hospital stays, resource data (antimicrobial treatment, hospitalization, and out-of-hospital care) from all centers were pooled and valued using German and French unit prices to estimate CAP-related cost to the German Sickness Funds and French public health-care sector, respectively. RESULTS: Compared to AMC +/- CLA, treatment with moxifloxacin resulted in 5.3% more patients achieving clinical cure 5 to 7 days after therapy (95% confidence interval [CI], 1.2 to 11.8%), increased speed of response (1 day sooner for median time to first return to apyrexia, p = 0.008), and a reduction in hospital stay by 0.81 days (95% CI, - 0.01 to 1.63) within the 21-day time frame. Treatment with moxifloxacin resulted in savings of 266 euro and 381 euro for Germany and France respectively, primarily due to the shorter length of hospital stay. Cost-effectiveness acceptability curves show moxifloxacin has a > or = 95% chance of being cost saving from French and German health-care perspectives, and higher probability of being cost-effective at acceptability thresholds up to 2,000 euro per additional patient cured. CONCLUSION: i.v./po monotherapy with moxifloxacin shows clinical benefits including increased speed of response and is cost-effective compared to i.v./po AMC +/- CLA in the treatment of CAP.