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Cost-effectiveness analysis for statin therapies in the primary prevention of coronary heart disease in Italy |
Berto P, Munro V, Gaddi A, Negrini C, Hutton J, Mast O |
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Record Status This is a critical abstract of an economic evaluation that meets the criteria for inclusion on NHS EED. Each abstract contains a brief summary of the methods, the results and conclusions followed by a detailed critical assessment on the reliability of the study and the conclusions drawn. Health technology The study compared two dosage regimens (0.2 and 0.4 mg/day) of cerivastatin against two other statins, simvastatin and pravastatin, in the primary prevention of coronary heart disease (CHD).
Economic study type Cost-effectiveness analysis.
Study population The study population comprised a hypothetical cohort of Italian men aged 35 to 69. The cohort was subdivided into seven 5-year age groups. The study was based on patients enrolled onto the Lipid Research Clinics Primary Prevention Trial, adjusted to reflect demographic and disease data for the Italian male population.
Setting The setting was secondary care. The economic study was carried out in Italy.
Dates to which data relate The effectiveness and resource data were taken from studies published between 1987 and 1995. The price year was 1998.
Source of effectiveness data The effectiveness data were taken from a synthesis of completed studies and published data. This was supplemented by expert opinion.
Modelling The study used a Markov decision-analysis model: the Coronary Heart Disease Risk Assessment Model (CHD-RAM) developed by Glick et al. (1990). This was used to estimate the lifetime risks of CHD, probability of CHD-free survival, life expectancy lost due to CHD, CHD-free life expectancy, life-time costs of cholesterol lowering measures and treating CHD, cost-effectiveness of alternative programmes for cholesterol lowering, and savings realised by preventing CHD through reduction of cholesterol levels.
Outcomes assessed in the review The outcomes used as input parameters to the model were divided into four categories, as follows:
Italian demographic variables: the mean systolic blood pressure (SBP) of the population, the mean body mass index (BMI) of the population, and the percentage of smokers.
Italian disease variables: all-cause death rate, sudden death as a percentage of CHD death, the percentage of CHD excluding CHD death and acute myocardial infarction (AMI) that is uncomplicated angina pectoris (UAP), and the life expectancy of healthy individuals and those with CHD.
Efficacy parameters: the efficacy/effectiveness of cerivastatin and the competitor statins (simvastatin and pravastatin) measured as the percentage reduction in lipoprotein cholesterol (LDL-C).
Pharmacological variables: the adverse effects of cholesterol lowering therapies, and the compliance of the population with the drug therapies (%).
Study designs and other criteria for inclusion in the review The authors reported that clinical trials, cohort and prospective epidemiological studies and other sources of data were included in the review. The authors did not report the type of study used to derive each input parameter and did not report whether inclusion and exclusion criteria were specified.
Sources searched to identify primary studies The authors did not report the sources searched or search methods used to identify the primary studies included in the review.
Criteria used to ensure the validity of primary studies The authors did not report the criteria used to ensure the validity of primary studies.
Methods used to judge relevance and validity, and for extracting data The criteria used to judge the relevance and validity of the studies and the methods to extract data were not reported.
Number of primary studies included The authors referenced 7 primary studies or datasets that were included in the review.
Methods of combining primary studies The authors did not report the method of combination of primary studies to generate estimates for individual parameters.
Investigation of differences between primary studies The difference between primary data sources, in terms of participants, intervention or outcome measures, were not investigated or explained by the authors.
Results of the review The results of the outcomes assessed in the review were as follows:
ITALIAN DEMOGRAPHIC VARIABLES:
Mean SBP (mm Hg) for each of the male average age groups: 37.5 years = 126.4 mm Hg; 42.5 years = 129.6 mm Hg; 47.5 years = 132.6 mm Hg; 52.5 years = 137.6 mm Hg; 57.5 years = 142.7 mm Hg; 62.5 years = 146.4 mm Hg; 67.5 years = 150.8 mm Hg.
Mean BMI for each of the male average age groups: 37.5 years = 26.0 BMI; 42.5 years = 26.3; 47.5 years = 28.6; 52.5 years = 26.7; 57.5 years = 26.8; 62.5 years = 26.9; 67.5 years = 27.1.
The percentage of smokers in each of the male average age groups: 37.5 years = 53.6%; 42.5 years = 52.6%; 47.5 years = 50.0%; 52.5 years = 51.3%; 57.5 years = 48.2%; 62.5 years = 42.5%; 67.5 years = 34.5%.
ITALIAN DISEASE VARIABLES:
All-cause death rate for each of the male average age groups: 37.5 years = 0.0151; 42.5 years = 0,0201; 47.5 years = 0.0317; 52.5 years = 0.0545; 57.5 years = 0.0907; 62.5 years 0.1556; 67.5 years = 0.2550.
Sudden deaths as a percentage of CHD deaths for each of the male average age groups: 37.5 years = 49.1%; 42.5 years = 21.2%; 47.5 years = 0.0%; 52.5 years = 20.9%; 57.5 years = 21.3%; 62.5 years = 10.3%; 67.5years = 8.7%.
Percentage of CHD excluding CHD death and AMI that is UAP for each of the male average age groups: 37.5 years = 80.80%; 42.5 years = 80.80%; 47.5 years = 80.80%; 52.5 years = 76.90%; 57.5 years = 76.90%; 62.5 years = 87.80%; 67.5 years = 80.40%.
MEAN ITALIAN LIFE EXPECTANCIES BY AGE OF ONSET:
No complications: 37.5 years = 38.7 years; 42.5 years = 34.0 years; 47.5 years = 29.4 years; 52.5 years = 25.0 years; 57.5 years = 20.9 years; 62.5 years = 16.2 years; 67.5 years = 12.9 years.
AMI: 37.5 years = 23.8 years; 42.5 years = 21.3 years; 47.5 years = 18.6 years; 52.5 years = 14.4 years; 57.5 years = 12.4 years; 62.5 years = 8.8 years; 67.5 years 7.4 years.
Sudden death: life expectancy = 0 for each of the male age groups.
Non-sudden death: life expectancy = 0 for each of the male age groups.
UAP: 37.5years = 33.3 years; 42.5 years = 29.3 years; 47.5 years = 25.5 years; 52.5 years = 21.8 years; 57.5 years = 18.3 years; 62.5 years = 15.0 years; 67.5 years = 12.1 years.
Complicated angina pectoris (CAP): 37.5 years = 23.8 years; 42.5 years = 21.3 years; 47.5 years = 18.6 years; 52.5 years = 14.4 years 57.5 years = 12.4 years; 62.5 years = 8.8 years; 67.5 years = 7.4 years.
EFFICACY PARAMETERS (the effectiveness/efficacy of each of the drugs (measured as % reduction in LDL-C levels):
Cerivastatin 0.2 mg/ per day = 29%.
Cerivastatin 0.4 mg/ per day = 36%.
Simvastatin 20 mg/ per day = 35%.
Simvastatin 49 mg/ per day = 40%.
Pravastatin 20 mg/ per day = 25%.
PHARMACOLOGICAL VARIABLES:
The percentage chance of adverse effects = 1.5% for each of the drugs and dosage regimens.
The non-compliance of patients with drug therapies = 30% for each of the drugs and dosage regimens.
Methods used to derive estimates of effectiveness The authors reported that expert opinion was used to estimate the adverse effects of cholesterol lowering therapy and compliance with drug therapy.
Estimates of effectiveness and key assumptions The incidence of adverse effects was estimated at 1.5% and the rate of non-compliance with drug therapy was estimated at 30%.
Measure of benefits used in the economic analysis The measure of health benefit used in the economic analysis was life-years gained.
Direct costs The authors did not report costs and quantities separately. The authors used the approved prices of drugs in the Italian market, and a price estimate for the increased dosage of cerivastatin 0.4 mg/day of L 3,090 per tablet.
Clinical experts estimated the cost of:
Initiating the intervention (L 162,050 per patient), with the costs assumed to be the same for different drugs and dosage regimens.
The annual non-drug costs of therapy, which were also assumed to be the same for the different drugs and dosage regimens (L 239,200 per patient).
Initiation of therapy for adverse events (L 27,000 per patient). However, it was assumed that there were no annual drug costs incurred for active patient management of adverse effects, as Italian clinical experts estimated that patients who experienced adverse effects would not receive any additional medication for their treatment.
The initiation of therapy for non-compliant individuals (L 173,000 per non-compliant individual). The cost of drug therapy for non-compliant individuals was assumed to be equal to the costs associated with 3 months of drug therapy, a figure that was assumed to be the same for each of the drugs and dosage regimens.
The authors also estimated the direct costs of the following coronary heart disease events: acute myocardial infarction (AMI); sudden death; non-sudden death; uncomplicated angina pectoris (UAP) and complicated angina pectoris (CAP). The authors did not report the sources of data for these estimates. The costs were reported for the first 6 months after the event, for the 6th to 12th month after the event, and for subsequent years. The costs (in thousands of Italian Lire) were as follows:
AMI cost for the first 6 months = 14,793;
AMI cost for the 6th to 12th month = 1,062;
AMI cost for subsequent years = 1,062 (per year);
Sudden death for the first 6 months = 3,550 (costs for the 6th to 12th months and subsequent years are not applicable);
Non-sudden death for the first 6 months = 3,550 (the costs for the 6th to 12th months and subsequent years are not applicable);
UAP cost for the first 6 months = 4,730;
UAP cost for the 6th to 12th month = 4,453;
UAP cost for subsequent years = 475 (per year);
CAP cost for the first 6 months = 6,082;
CAP cost for the 6th to 12th month = 502;
CAP cost for subsequent years = 386 (per year).
Also estimated were the lifetime direct costs of coronary heart disease events for seven 5-year age groups, with average age groups represented by the midpoint of each interval e.g. 35 to 39 years = 37.5 years. The costs (in thousands of Italian Lira - L) were as follows:
AMI, 37.5 years = 26,770; 42.5 years = 26,153; 47.5 years = 25,399; 52.5 years = 23,993; 57.5 years = 23,197; 62.5 years = 21,493; 67.5 years = 20,172.
Sudden death, 37.5years = 3,550; 42.5 years = 3,550; 47.5 years = 3,550; 52.5 years = 3,550; 57.5 years = 3,550; 62.5 years = 3,550; 67.5years = 3,550.
Non-sudden death, 37.5 years = 3,550; 42.5 years = 3,550; 47.5 years = 3,550; 52.5 years = 3,550; 57.5 years = 3,550; 62.5 years = 3,550; 67.5 years = 3,550.
UAP, 37.5years = 10,881; 42.5 years = 10,576; 47.5 years = 10,237; 52.5 years = 9,849; 57.5 years = 9,413; 62.5 years = 8,926; 67.5 years = 8,412.
CAP, 37.5 years = 10,547; 42.5 years = 10,323; 47.5 years = 10,048; 52.5 years 9,537; 57.5 years = 9,248; 62.5 years = 8,626; 67.5 years = 8,341.
Costs were discounted at 5% per annum, and the price year was 1998.
Statistical analysis of costs No statistical analysis of costs was conducted.
Indirect Costs The authors reported that life expectancy data were used to calculate social productivity (earnings up to the retirement age of 65 years) for the Italian male population. An average annual salary of L 44,000,000 was assumed, with a discount rate of 5% per annum.
Currency Italian lira (L) and EUROS. The currency conversion rate reported by the authors was Eur1 = L 1,936.27.
Sensitivity analysis The authors reported that sensitivity analysis of the data was performed. The sensitivity analysis was only performed for one of the seven age groups, (Italian men aged 50-54 years old beginning therapy for the primary prevention of coronary heart disease). A one-way economic sensitivity analysis was conducted on the following parameters: the discount rate, non-compliance, smoking behaviour, mean SBP, and mean BMI.
Estimated benefits used in the economic analysis The authors reported the incremental lifetime benefit/effect in terms of life-years gained (LYG) of simvastatin 20 and 40 mg/day compared with cerivastatin 0.2 and 0.4 mg/day for three age groups under analysis; these were 30-35 years, 50-54 years, and 65-69 years. The results were as follows:
Cerivastatin 0.2 mg/day versus simvastatin 20 mg /day: age 30-35 years = 0.019 (LYG); 50-54 years = 0.028 (LYG); 65-69 years = 0.018 (LYG).
Cerivastatin 0.4 mg/day versus simvastatin 40 mg/day: age 30-35 years = 0.012 (LYG); age 50-54 years = 0.018 (LYG); 65-69 years = 0.011 (LYG).
The authors also reported the lifetime incremental benefit/effect of cerivastatin 0.2 and 0.4 mg/day compared with pravastatin 20 mg/day for the three age groups under analysis: 30-35 years, 50-54 years, 65-69 years. The results were as follows:
Cerivastatin 0.2 mg/day versus pravastatin 20 mg/day: age 30-35 years = -0.013 (LYG); 50-54 years = -0.019 (LYG); 65-69 years = -0.012 (LYG).
Pravastatin 20 mg/day versus cerivastatin 0.4 mg/day: age 30-35 years = 0.035 (LYG); 50-54 years = 0.052 (LYG); 65-69 years = 0.033 (LYG).
Cost results The authors reported the incremental lifetime costs (in thousands of Lira - L) of cerivastatin 0.2 and 0.4 mg/day compared with simvastatin 20 and 40 mg/day for the three age groups under analysis: 30-35 years, 50.54 years, and 65-69 years. The incremental costs were reported from both the Italian NHS and the societal perspective and the results were as follows:
Cerivastatin 0.2 mg/day versus simvastatin 20 mg/day:
Italian NHS perspective: age 30- 35 years = 1,758; age 50-54 years = 1,264; age 65-69 years = 732.
Societal perspective: age 30-35 years = 1,715; age 50-54 years = 1,292; age 65-69 years = 732.
Cerivastatin 0.4 mg/day versus simvastatin 40 mg/day:
Italian NHS perspective: age 30-35 years = 7,833; age 50-54 years = 5,795; 65-69 years = 3,494.
Societal perspective: age 30-35 years = 7,807; age 50-54 years = 5,813; 64-69 years = 3,494.
The authors also reported the lifetime incremental costs (in thousands of Lira - L) of cerivastatin 0.2 and 0.4 mg/day compared with pravastatin 20 mg/day for the three age groups under analysis: age 30-35 years, 50-54 years; and 65-69 years. The incremental costs were reported from both the NHS and societal perspective and the results were as follows:
Cerivastatin 0.2 mg/day versus pravastatin 20 mg/day:
Italian NHS perspective: age 30-35 years = 1,489; age 50-54 years = 1,131; age 65-69 years = 736.
Societal perspective: age 30-35 years = 1,521; age 50-54 years = 1,112, age 64-69 years = 736.
Pravastatin 20 mg/day versus cerivastatin 0.4 mg/day:
Italian NHS perspective: age 30-35 years = 1,113; age 50-54 years = 753; age 65-69 years = 368.
Societal perspective: age 30-35 years = 1,031; age 50-54 years = 805; 65-69 years = 368.
Synthesis of costs and benefits The authors reported the incremental cost effectiveness (the additional cost per LYG) of cerivastatin 0.2 and 0.4 mg/day compared with simvastatin 20 and 40 mg/day for the three age groups under analysis: age 30-35 years, 50-54 years, and 65-69 years. The incremental cost-effectiveness was reported in thousands of Lira (L), from both the Italian NHS and societal perspective. The results were as follows:
Cerivastatin 0.2 mg/day versus simvastatin 20 mg/day:
Italian NHS perspective: age 30-35 years = 92,256; age 50-54 years = 45,143; age 65-69 years = 40,667.
Societal perspective: age 30-35 years = 90,623; age 50-54 years = 46,143; age 65-69 years = 40,667.
Cerivastatin 0.4 mg/day versus simvastatin 40 mg/day:
Italian NHS perspective: age 30-35 years = 652,750; age 50-54 years = 321,944; age 65-69 years = 317,636.
Societal perspective: age 30-35 years = 650,583; age 50-54 years = 322,944; 65-69 years = 317,636.
The authors also reported the incremental cost-effectiveness (the additional cost per LYG of cerivastatin 0.2 and 0.4 mg/day compared with pravastatin 20 mg/day for the three age groups under analysis: age 30-35 years, 50-54 years, and 65-69 years. The incremental cost-effectiveness was reported in thousands of Lira (L), from both the NHS and societal perspective. The results were as follows:
Cerivastatin 0.2 mg/day versus pravastatin 20 mg/day:
Italian NHS perspective: age 30-35 years = cerivastatin dominant (CD); age 50-54 years = CD; age 65-69 years = CD.
Societal perspective: age 30-35 years = cerivastatin dominant (CD); age 50-54 = CD; age 65-69 = CD.
Pravastatin 20 mg/day versus cerivastatin 0.4 mg/day:
Italian NHS perspective: age 30-35 years = 31,800; age 50-54 years = 14,481; age 65-69 years = 11,152.
Societal perspective: age 30-35 years = 29457; age 50-54 years = 15481; age 65-69 years = 11152.
In relation to the sensitivity analysis the authors reported that the changes in the discount rate caused significant shifts in the cost per LYG ratios, but reported that the rankings of cerivastatin 0.2 and 0.4 mg/day, and the comparative statins did not change. Consequently the authors stated that the main result of the changes in the discount rate was in terms of the cost-effectiveness of statin therapy as a whole. The authors reported that changes in the values used for the mean SBP, mean BMI, and the rate of patient non-compliance do impact on the results of treatment. The results of this analysis were not reported.
Authors' conclusions In conclusion the authors stated that the results of the study showed that the average cost-effectiveness of cerivastatin compared favourably with those of the other pharmacological interventions available in the Italian market (simvastatin and pravastatin).
CRD COMMENTARY - Selection of comparators A justification was given for the choice of comparator, namely that it represented current practice in the authors setting. You, as a user of the database should decide if this is a widely used health technology in your own setting.
Validity of estimate of measure of effectiveness The authors did not report whether a systematic or selective search and review of the literature had been undertaken. The authors appeared to use data from the reviewed studies selectively, and did not consider the impact of differences between the primary studies when estimating effectiveness. The authors did not report the validity of the studies used to derive data from, or the impact of using expert opinion. The authors noted a number of limitations with using modelling techniques to generate estimates of effectiveness. These include the use of CHD risk equations that were developed for a different purpose, the use of epidemiological data collected for a specific population and time period, incomplete specification of CHD risk factors, incomplete specification of the factors that modify cholesterol levels, the use of intervention data from a resin rather than statin trial, and the use of short term efficacy data. The authors reported a limited sensitivity analysis of the demographic and clinical characteristics of the hypothetical cohort. The authors did not report whether a sensitivity analysis had been conducted on the safety, efficacy and compliance data used for each of the interventions evaluated.
Validity of estimate of measure of benefit The effectiveness data were used to model the expected life years gained, the measure of health benefit. The validity of the estimates of life years gained is dependent on the validity of the effectiveness data and the structure of the model used. There was insufficient data to assess these factors. The authors noted that they did not adjust the life years gained by a quality or utility weight to reflect the value of health states gained by each intervention. The authors also noted that no a priori judgement about the impact of including health related quality of life could be made.
Validity of estimate of costs The authors included all categories of cost relevant to the two perspectives adopted (NHS and societal) in the analysis. Although some costs such as the additional costs of medication for adverse events were not included, these are unlikely to affect the authors' conclusions. The authors performed no statistical analysis of quantities or prices. A sensitivity analysis of prices was performed, and the ranges used appeared appropriate. The authors performed appropriate currency conversions, and discounting was undertaken at a rate of 5% per annum. The sensitivity analysis of costs only considered changes in the discount rate. The authors did not report whether any other cost variables were tested or the impact on the results, thus it is not possible to assess the robustness of the cost results to variation in the values of cost or effect parameters.
Other issues The authors made appropriate comparisons of their findings with those from other studies and the issue of generalisability to other settings was addressed. The authors reported a number of limitations to their study, as noted above. A further limitation reported by the authors was that the study was limited to a subset of the population, male patients with type IIa lipid abnormalities and no evidence of CHD, and consequently it is not applicable to women or men with type IIb lipid abnormalities.
Implications of the study In conclusion, the authors state that the results of the study show that the average cost-effectiveness of cerivastatin compared favourably with those of the other pharmacological interventions available in the Italian market (simvastatin and pravastatin).
Source of funding Supported by Bayer Medical Affairs HEOR Europe and Overseas.
Bibliographic details Berto P, Munro V, Gaddi A, Negrini C, Hutton J, Mast O. Cost-effectiveness analysis for statin therapies in the primary prevention of coronary heart disease in Italy. Clinical Drug Investigation 2000; 20(2): 109-121 Other publications of related interest Glick H, Heyse J F, Thompson D, et al. A model for evaluating the cost-effectiveness of cholesterol-lowering treatment. Leonard Davis Institute of Health Economics (discussion paper no.73). University of Pennsylvania, 1990.
Indexing Status Subject indexing assigned by CRD MeSH Anticholesteremic Agents /drug therapy /economics; Cardiovascular Diseases /prevention & Cost-Benefit Analysis; Costs and Cost Analysis; Drug Costs; Humans; Italy; Myocardial Ischemia /prevention & Pravastatin /drug therapy /economics; Primary Prevention; Probability; Risk Assessment; Risk Factors; Simvastatin /drug therapy /economics; Treatment Outcome; control /drug therapy /epidemiology; control /economics AccessionNumber 22000001490 Date bibliographic record published 30/04/2002 Date abstract record published 30/04/2002 |
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