Traditional approaches to cost-effectiveness analysis have not considered the downstream possibility of a new standard of care coming out of the research and development pipeline. However, the treatment landscape for patients may change significantly over the course of their lifetimes.
To present a Markov modeling framework that incorporates the possibility of treatment evolution into the incremental cost-effectiveness ratio (ICER) that compares treatments available at the present time.
. Markov model evaluated by matrix algebra. Measurements. The author evaluates the difference between the new and traditional ICER calculations for patients with chronic diseases facing a lifetime of treatment.
The bias of the traditional ICER calculation may be substantial, with further testing revealing that it may be either positive or negative depending on the model parameters. The author also performs probabilistic sensitivity analyses with respect to the possible timing of a new treatment discovery and notes the increase in the magnitude of the bias when the new treatment is likely to appear sooner rather than later. Limitations. The modeling framework is intended as a proof of concept and therefore makes simplifying assumptions such as time stationarity of model parameters and consideration of a single new drug discovery.
For diseases with a more active research and development pipeline, the possibility of a new treatment paradigm may be at least as important to consider in sensitivity analysis as other parameters that are often considered.
Tamoxifen is a prototypic cancer chemopreventive agent, yet clinical trials have not evaluated its effect on mortality or the impact of drug pricing on its cost-effectiveness.
A state-transition Markov model for a hypothetical cohort of women age 50 years was used to evaluate the effects of tamoxifen on mortality and tamoxifen price on cost-effectiveness. Incidence and mortality rates for breast and endometrial cancers were derived from Surveillance, Epidemiology and End Results statistics, and noncancer outcomes were obtained from published studies. Relative risks of outcomes were derived from the National Surgical Adjuvant Breast and Bowel Project P-1 trial. Costs were based on Medicare reimbursements.
Projected overall mortality for women at 1.67% 5-year breast cancer risk showed little difference with or without tamoxifen, resulting in a cost-effectiveness ratio of $1,335,690 per life-year saved as a result of tamoxifen use. Adjusting for the differential impact of estrogen receptor-negative cancers, tamoxifen increased mortality for women with a uterus until the 5-year breast cancer risk reached > or =2.1%. Assigning the Canadian price for tamoxifen dramatically reduced the incremental cost (to $123,780 per life-year saved). At that price, the use of tamoxifen was less costly and more effective for women with 5-year breast cancer risks >4%.
Tamoxifen may increase mortality in women at the lower end of the "high-risk" range for breast cancer. If prices in the U.S. approximated Canadian prices, then tamoxifen use for breast cancer risk reduction in women with a 5-year risk >3% could be a reasonable strategy to reduce the incidence of breast cancer. Because they are used by many unaffected individuals, the price of chemopreventive agents has a major influence on their cost-effectiveness.
During the years following menopause, estrogen levels decline leading to accelerated bone loss and an increased risk of osteoporosis and osteoporosis-related fractures.
Using a Markov model and decision analytic techniques, the long-term costs and outcomes of five treatment and secondary prevention strategies for osteoporosis were compared: 'no intervention', alendronate, etidronate, risedronate, and raloxifene. The base case analysis examined postmenopausal (65 year old) osteoporotic women without prior fracture. Probabilistic sensitivity analysis (PSA) was used to incorporate the impact of parameter uncertainty, and deterministic sensitivity analysis (DSA) was used to compare alternative patient populations and modeling assumptions. Life years and Quality Adjusted Life Years (QALYs) were used as measures of effectiveness.
In the base case analysis, risedronate was dominated by etidronate and alendronate. Alendronate and etidronate were projected to have similar costs and QALYs, and the efficiency frontier was represented by 'no intervention', etidronate, alendronate, and raloxifene (Can$32 571, Can$38 623 and Can$114 070 per QALY respectively). Alternative assumptions of raloxifene's impact on CHD and breast cancer, alternative discount rates and alternative patient risk factors (e.g., starting age of therapy, CHD risk, and prior fracture risk) had significant impacts on the overall cost-effectiveness results for both the bisphosphonates and raloxifene.
Using conventionally quoted benchmarks and compared to no therapy, alendronate, etidronate, and raloxifene would all be considered cost-effective alternatives for treating women with osteoporosis. Potential limitations of this study include the usual caveats and cautions associated with long-term projection models and the fact that not all inputs into the model are Canadian data sources.
Patient self-management of long-term oral anticoagulation therapy is an effective strategy in a number of clinical situations, but it is currently not a funded option in the Canadian health care system. We sought to compare the incremental cost and health benefits of self-management with those of physician management from the perspective of the Canadian health care payer over a 5-year period.
We developed a Bayesian Markov model comparing the costs and quality-adjusted life years (QALYs) accrued to patients receiving oral anticoagulation therapy through self-management or physician management for atrial fibrillation or for a mechanical heart valve. Five health states were defined: no events, minor hemorrhagic events, major hemorrhagic events, thrombotic events and death. Data from published literature were used for transition probabilities. Canadian 2003 costs were used, and utility estimates were obtained from various published sources.
Self-management resulted in 3.50 fewer thrombotic events, 0.78 fewer major hemorrhagic events and 0.12 fewer deaths per 100 patients than physician management. The average discounted incremental cost of self-management over physician management was found to be 989 dollars (95% confidence interval [CI] 310 dollars-1655 dollars) per patient and the incremental QALYs gained was 0.07 (95% CI 0.06-0.08). The cost-effectiveness of self-management was 14,129 dollars per QALY gained. There was a 95% chance that self-management would be cost-effective at a willingness to pay of 23,800 dollars per QALY. Results were robust in probabilistic and deterministic sensitivity analyses.
This model suggests that self-management is a cost-effective strategy for those receiving long-term oral anticoagulation therapy for atrial fibrillation or for a mechanical heart valve.
OBJECTIVE: To estimate the costs and health outcomes of C-Leg and non-microprocessor-controlled (NMC) knees using a decision-analytic model. DESIGN: Data on costs, rates and duration of problems, knee survival, and health-related quality of life were obtained from interviews with patients and prosthetists with experience of both C-Leg and NMC knees. Interview data were assessed in a decision-analytic Markov model to estimate cost-effectiveness from a health care perspective. SETTING: Outpatient. PARTICIPANTS: A population sample of 20 patients currently using the C-Leg and prior experience of nonmicroprocessor knees, and 5 prosthetists. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Incremental cost per quality-adjusted life year (QALY). RESULTS: The mean incremental cost (in 2006 Euros) and QALYs for the C-Leg was 7657 euros and 2.38, respectively, yielding a cost per QALY gained of 3218 euros. CONCLUSIONS: It is important to provide decision-makers with relevant information on costs and health outcomes of different treatment strategies on actual decision problems despite limited evidence. The results of the study, taking into account both costs and a broadly defined health outcome in terms of QALY, show that given existing albeit limited evidence the C-Leg appears to yield positive health outcomes at an acceptable cost.
This study evaluated the costs and cost-effectiveness of a school-based grade 6 universal vaccination program against hepatitis B.
We performed a descriptive cost study and cost-effectiveness analysis of British Columbia's vaccination program for 1994 and 1995. Since 1992, public health nurses have administered hepatitis B vaccine to grade 6 students in schools. We measured costs of vaccine, vaccine administration, and net program costs and used a validated Markov model to calculate the cost-effectiveness of the program.
Vaccinating each student cost $44, $24 of which was the cost of vaccine administration. The net cost was $9 per person; considering productivity costs, net savings were $75 per person. Marginal cost per life year gained was $2100. Universal adolescent vaccination is also economically attractive in the United States but less attractive in regions with incidence rates below 3 cases per 100,000 per year.
Hepatitis B vaccine can be delivered in North American schools at a reasonable cost. Adolescent vaccination is economically attractive in North American regions of high and average incidence rates. Our analysis supports vaccination in adolescents who remain at risk for hepatitis B virus infection.
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OBJECTIVES: The purpose of this study was to evaluate the long-term cost-effectiveness of clopidogrel on top of standard therapy (including ASA) in patients with acute coronary syndromes without ST-segment elevation in Sweden. METHODS AND RESULTS: Incremental cost-effectiveness ratios (ICER) were assessed using a Markov model with transition probabilities estimated from the Swedish hospital discharge and cause of death registers. Patients were assumed to be treated for 1 year, with treatment effects (RR = 0.8) and costs taken from the Clopidogrel in Unstable Angina to prevent Recurrent ischaemic Events Trial. Two scenarios were analysed: with patients similar to those in the trial and with patients similar to those from the register. In the first scenario, the predicted net direct cost was 160 euro and the net total cost -54 euro, which with an incremental survival of 0.12 years give the ICER of 1365 euro per life-year gained from the health care payer perspective (including direct costs) and cost savings from the societal perspective (also including indirect costs). The net costs in the second scenario were 149 euro, giving an ICER of 1009 euro for both perspectives. CONCLUSIONS: Adding clopidogrel to standard therapy including ASA is cost-effective in the studied setting and compares favourably with other cardiovascular treatment and prevention strategies.
The objective of this analysis was to calculate the cost-effectiveness of amlodipine therapy in patients with coronary artery disease in Sweden. It is hypothesised that treatment with amlodipine will have an impact on overall cardiovascular disease treatment costs, resulting in a positive cost-effectiveness profile. A Markov cohort simulation model was constructed to simulate event-related and procedure-related health economic outcomes of coronary artery disease populations on amlodipine versus those on placebo. Patient level data from the Prospective Evaluation of the Vascular Effects of Norvasc Trial was used to populate the model. The total number of adverse cardiovascular clinical outcomes experienced over a three-year period was lower for patient on amlodipine than for those on placebo. The rate of hospitalisation per patient due to angina, coronary artery bypass graft, percutaneous transluminal coronary angioplasty, congestive heart failure, and myocardial infarction in the placebo cohort was 64.7%, while the rate in the amlodipine cohort was 46.9%. The cost per patient was Swedish kroner (SEK)26,600 for amlodipine patients and SEK27,400 for placebo patients. The use of amlodipine resulted in improved clinical outcomes as well as a slight savings in cost over a three-year period.
Although tuberculosis (TB) screening of immigrants has been conducted for over 50 yr in many industrialized countries, its cost- effectiveness has never been evaluated. We prospectively compared the yield and cost-effectiveness of two immigrant TB screening programs, using close-contact investigation and passive case detection. Study subjects included all immigration applicants undergoing radiographic screening, already arrived immigrants requiring surveillance for inactive TB, and close contacts of active cases resident in Montreal, Quebec, Canada, who were referred from June 1996 to June 1997 to the Montreal Chest Institute (MCI), a referral center specializing in respiratory diseases. For all subjects seen, demographic data, investigations, diagnoses, and therapy were abstracted from administrative data bases and medical charts. Estimated costs of detecting and treating each prevalent active case and preventing future active cases, based on federal and provincial health reimbursement schedules, were compared with the costs for passively diagnosed cases of active TB. Over a period of 1 yr, the three programs detected 27 cases of prevalent active TB and prevented 14 future cases. As compared with passive case detection, close-contact investigation resulted in net savings of $815 for each prevalent active case detected and treated and of $2,186 for each future active case prevented. The incremental cost to treat each case of prevalent active TB was $39,409 for applicant screening and $24,225 for surveillance, and the cost of preventing each case was $33,275 for applicants and $65,126 for surveillance. Close-contact investigation was highly cost effective and resulted in net savings. Immigrant applicant screening and surveillance programs had a significant impact but were much less cost effective, in large part because of substantial operational problems.
Comment In: Am J Respir Crit Care Med. 2001 Jan;163(1):1-211208612
Current hypertension guidelines differ in their recommendations for first-line antihypertensive therapy.
To evaluate the cost effectiveness of ACE inhibitor therapy as antihypertensive first-line therapy as compared with conventional antihypertensive therapy with beta-adrenoceptor antagonists or diuretics.
Cost-effectiveness analysis based on data from randomised trials and observational studies comparing the effectiveness of ACE inhibitor and conventional antihypertensive therapy, we constructed a Markov model to compare four strategies in the management of uncomplicated hypertension: (i) prescribing ACE inhibitor therapy to all patients; (ii) prescribing conventional therapy to all patients; (iii) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on electrocardiography (ECG); or (iv) individualised antihypertensive therapy based on the presence or absence of left ventricular hypertrophy on echocardiography.
Cost data were derived from the medical literature and focus groups, and utility values were derived from patients on antihypertensive monotherapy. All costs were calculated in 1999 Canadian dollars, but are reported in US dollars according to the 1999 purchasing power parity rate for medical and healthcare. The effectiveness of ACE inhibitor therapy in the presence of left ventricular hypertrophy was derived from observational studies. The time horizon was over a lifetime.
A cohort of men aged 40 years without cardiovascular comorbidity requiring antihypertensive drug therapy.
In the baseline analysis, all four strategies resulted in expected discounted QALYs that differed from each other only at the third decimal point (i.e. less than 0.003). Given the uncertainties in the variable estimates and the small size of the differences, these differences are extremely small and unlikely to represent real differences. Even accepting the small gains as real, the resulting cost-effectiveness ratios are unattractively high: $US 200,000 per QALY gained for the echocardiography strategy (compared with ECG), and $US 700,000 for the "ACE inhibitor for all" strategy (compared with ECG). The incremental cost effectiveness of prescribing ACE inhibitor therapy to everybody was never less than $US 100,000/QALY in the sensitivity analysis.
Prescribing ACE inhibitors as antihypertensive first-line therapy in patients without cardiovascular morbidity cannot be recommended at the present time unless the acquisition costs of ACE inhibitors become substantially more attractive.