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Prevention of coronary heart disease through treatment of infection with Chlamydia pneumoniae? Estimation of possible effectiveness and costs |
Sanderson C, Kubin M |
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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 screening for Chlamydia pneumoniae (C. pneumoniae) and the use of antichlamydial antibiotics in the treatment of coronary heart disease (CHD).
Economic study type Cost-effectiveness analysis.
Study population The patient population comprised males aged 25 to 84 years in England and Wales.
Setting The setting was primary and secondary care. The economic study was carried out in the United Kingdom.
Dates to which data relate The effectiveness evidence came from studies published between 1988 and 1996. The resource use data were derived from studies reported between 1995 and 1999. The price year was 2000.
Source of effectiveness data The effectiveness data were derived from a synthesis of completed studies and from the authors' assumptions.
Modelling A decision analysis spreadsheet model was used. This was used to establish the likely costs and life-years enjoyed by a cohort of 1,000 males under a screening and treatment programme, and to compare that with the no screening option.
Outcomes assessed in the review The outcomes were the numbers of persons in each of the four states, one year after intervention. The four states were death from CHD, death from non-cardiac causes, nonfatal myocardial infarction (MI), and survival without MI.
Study designs and other criteria for inclusion in the review There were no specific inclusion criteria relating to the study design.
Sources searched to identify primary studies MEDLINE and Excerpta Medica were searched for all articles on Chlamydia pneumoniae published between 1985 and 1998. The search was updated for major journals to December 1999.
Criteria used to ensure the validity of primary studies No specific criteria were used to ensure the validity of the primary studies.
Methods used to judge relevance and validity, and for extracting data No specific methods were used to assess the validity of the primary studies.
Number of primary studies included Three studies were included for the effectiveness of antibiotic treatment in reducing the risk of MI and cardiac mortality.
Methods of combining primary studies The results of the effectiveness studies were not combined, instead the results from one of the studies were used.
Investigation of differences between primary studies Differences between the primary studies were not investigated.
Results of the review The results were only reported for study 1. Study 2 was said to give comparable results, while study 3 showed no effects of antibiotic treatment on reducing the risk of MI and cardiac mortality. After a mean follow-up of 18 months, the reported study showed reductions in the risk of death (50% lower), the risk of MI (75% lower), and the total risk of cardiovascular events (71% lower).
Methods used to derive estimates of effectiveness Apart from the risk reduction estimates obtained from the review, it was necessary to make a range of assumptions around other parameters of the model.
Estimates of effectiveness and key assumptions The population structure and life expectancy in 10-year age bands were taken from official publications for England and Wales. The age-specific CHD prevalence rates were taken from the Health Survey for England (1993). The number of people with heart disease but no history of angina was assumed to be equal to the number with angina.
The base probabilities of cardiac death for post-MI and CHD patients were derived from clinical studies. The probabilities of cardiac death for those with at least three cardiac risk factors were established using Framlington equations with conservative assumptions about individual risk components.
The probabilities of acute C. pneumoniae infection were assumed to be higher than the known general seropositive status among the whole population.
A single parameter of 50% was assumed to represent the proportion willing to attend a second screening, the proportion having chronic infection, and the proportion willing to start treatment.
The true positive rate of the test for chronic infection was taken from pilot trials of microimmunofluorescence. It was assumed to be 90% for those judged to have a chronic infection after the two screening stages.
Measure of benefits used in the economic analysis The outcome measures included deaths avoided and MIs avoided. These translated into life-years gained and had implications for the lifetime costs of treating people with CHD whose deaths were postponed. No valuation of health states was applied.
Direct costs The costs were discounted at a rate of 6%. The quantities and the unit costs were reported separately in terms of the time for visits and antibiotic treatment. Other cost categories were the cost of treating CHD and of cardiac death. The costs were estimated from 5 published studies and 1 unpublished study. The reported costs from the studies were converted to the year 2000 using an annual inflation factor of 3%.
The cost categories included first and second screening, preventive treatment per month for 3 months for general practitioner visit and antibiotics, the cost of treating CHD in the first year after MI, the cost of cardiac death, and the long-term treatment costs per year for CHD.
Statistical analysis of costs No statistical analysis of the costs was undertaken.
Indirect Costs The indirect costs were not estimated. They were not thought to be relevant, as most affected patients would be retired and no loss of earnings would, therefore, be incurred.
Sensitivity analysis Two sensitivity analyses were performed. The first to investigate the variability of the data by reducing the value of all key parameters by 10%. The second to include "plausible variant assumptions". A one-way analysis was performed in both cases.
Estimated benefits used in the economic analysis Incremental benefits were assumed for three groups in terms of the reduced risk of MI and cardiac death:
for the post-MI group, it was assumed there was a 50% reduction in the risk of cardiac death and a 75% reduction in the risk of non-fatal MI;
for the CHD and CHD-risk groups, the assumptions were stated to be "progressively lower than above".
The benefits were given in terms of the MIs and deaths avoided, and the years of life saved per 1,000 screened in each age group.
The MIs avoided for post-MI patients ranged from 2.3 in the 25 to 34 age group, to 45 in the 75 to 84 age group.
The range of cardiac deaths avoided for equivalent groups was 0.1 to 27.
The resulting years of life saved for post-MI patients ranged from 2.3 for the 25 to 34 age group, to 151 for the 75 to 84 age group.
Cost results The net costs (000s per 1,000 screened) for MI patients ranged from 177 for the 25 to 34 age group, to 230 for the 75 to 84 age group. For CHD patients, the range was 178 to 333 for the same age groups. For CHD-risk patients, the equivalent net costs were 166 and 191.
Synthesis of costs and benefits The incremental costs and benefits were combined by calculating the cost per MI avoided, death avoided and the resulting years of life saved.
For post-MI patients, the costs (1,000) per year of life saved ranged from 75.8 for the 25 to 34 age group, to 1.5 for the 75 to 84 age group.
For CHD patients, the costs (1,000) per year of life saved ranged from 18.4 for the 35 to 44 age group, to 2 for the 75 to 84 age group.
For CHD-risk patients, the costs (1,000) per year of life saved ranged from 689.1 for the 25 to 34 age group, to 11.9 for the 75 to 84 age group.
The one-way sensitivity analysis investigating reductions in parameter values by 10%, led to changes of between 1 and just under 10% in cost-effectiveness. In general, the results were more sensitive to factors related to the screening results, which influence the numbers of people in the treatment programme, than to the treatment effectiveness or costs.
Authors' conclusions If the link between Chlamydia pneumoniae and coronary heart disease (CHD) were to prove causal, and if the assumptions of the model were acceptable, then the cost of screening for those who have had myocardial infarction (MI; 2,000 per life saved) would compare favourably with other screening and treatment programmes. For example, statins for the treatment of hypercholesterolaemia.
CRD COMMENTARY - Selection of comparators The comparator was no screening for C. pneumoniae antibodies, which is standard practice in the UK general practice setting.
Validity of estimate of measure of effectiveness The literature was searched for measures of effectiveness. No information was provided on how the studies were retrieved or on the quality of the studies used. The estimates of effectiveness from primary studies were not combined. Instead, the results from one of the three studies found in the literature search were used. This use of a single study is a weakness. In addition, several assumptions on the prevalence of CHD and MIs were made. The authors examined "plausible" variations in the assumptions about effectiveness in their sensitivity analysis. However, the validity of these "plausible' variations was not fully supported.
Validity of estimate of measure of benefit The measures of benefit were the life-years gained as a result of a reduction in MIs and coronary deaths. The validity of these measures might not be strongly supported given the above reservations about the validity of the effectiveness, and the additional assumptions made about the life expectancy of different groups of patients.
Validity of estimate of costs The costs were taken from published UK studies. The costs and benefits were discounted using reasonable rates. Alternative rates were used in the sensitivity analysis. The direct cost categories appeared satisfactory. References were given for some of the cost derivations, while the unit costs were provided for others. The price year was 2000 and the costs were converted to be consistent with this. The costs included in the analysis were the costs incremental to standard treatment of CHD, without screening and treatment for C. pneumoniae. All relevant incremental costs were included. The costs were reported separately from the quantities. A sensitivity analysis was performed to investigate the effect of variability of the data and to vary the assumptions made. However, the results reported were limited to a one-way sensitivity analysis.
Other issues The authors acknowledged that the effectiveness of treatment for C. pneumoniae was based on a simple extrapolation from a single pilot study of one group of patients (post-MI patients). The reductions in mortality (50%) were large compared with other cardiovascular treatments such as statins (34%). Further, the pilot studies conducted so far either show no effects of C. pneumoniae treatment on CHD mortality, or effects that are not statistically significant.
The authors also acknowledged some shortcomings of the model. For example, each member of the target group entered the programme only once. This did not allow for the situation where some patients become reinfected. Other shortcomings identified were the use of standard annual costs of treating CHD. Also, the fact that the impact and costs of adverse events following treatment were not considered due to the lack of data. The results were reported in full. The issue of generalisability was addressed partially through the sensitivity analysis.
Implications of the study The results suggest that screening for C. pneumoniae could be a cost-effective way of reducing deaths from CHD for patients who have had a MI. In addition, for these patients, it could be comparable with the cost of other CHD prevention programmes. The authors suggest that the model indicates which parameters are likely to have a major impact on the cost-effectiveness of the programme, thus highlighting areas that need attention during future research and development of antichlamydial treatment.
Source of funding Supported by a grant from Bayer Plc (UK).
Bibliographic details Sanderson C, Kubin M. Prevention of coronary heart disease through treatment of infection with Chlamydia pneumoniae? Estimation of possible effectiveness and costs. Health Care Management Science 2001; 4: 269-279 Indexing Status Subject indexing assigned by NLM MeSH Adult; Aged; Anti-Bacterial Agents /economics /therapeutic use; Chlamydia Infections /complications /drug therapy /microbiology; Chlamydophila pneumoniae /isolation & Coronary Disease /complications /epidemiology /prevention & Cost-Benefit Analysis; Great Britain /epidemiology; Humans; Male; Middle Aged; Prevalence; Treatment Outcome; control; purification AccessionNumber 22001008280 Date bibliographic record published 28/02/2003 Date abstract record published 28/02/2003 |
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