Effectiveness and cost-effectiveness of general immunisation of infants and young children with the heptavalent conjugated pneumococcal vaccine

Background: The European Agency for the Evaluation of Medicinal Products (EMEA) granted market authorisation to the heptavalent pneumococcal vaccine Prevenar (Wyeth) in the year 2001. The indication of Prevenar is the active immunisation of infants and young children under the age of two against invasive disease caused by Streptococcus pneumonia serotypes 4, 6B, 9V, 14, 18C, 19F and 23F. At the time of this study the German vaccination scheme advises the immunisation with Prevenar only for children at high risk. Objectives: The objective of the study is first to determine the efficacy and effectiveness of the immunisation of all children with the heptavalent conjugated pneumococcal vaccine in Germany and second, whether a general recommendation for vaccination of all children would be cost-effective. Methods: A systematic literature search was performed in 29 relevant databases for the period of January 1999 to June 2004. Thus 1,884 articles were identified which were then assessed according to predefined selection criteria. Results: There is evidence for the medical effectiveness of Prevenar against invasive pneumococcal disease caused by the covered serotypes from a major double-blinded RCT undertaken in California. The vaccine shows lower values of effectiveness against otitis media and pneumonia. The values for effectiveness of the vaccine in Germany are below the data for California because of the different incidence of Serotypes. The cost-effectiveness rates for an immunisation of all children with Prevenar vary across different countries. One reason - besides different Health Systems - can be seen in the uncertainty about the duration of protection, another in the assumption on regional serotype coverage of the vaccine. From the healthcare payers' perspective a general vaccination of all children in Germany is not cost-effective, from a societal perspective the benefits from vaccination could prevail the cost. The actual price of the vaccine (if financed by the Healthcare Payer, 2004) has dropped and is lower than the assumed price in the German cost-effectiveness study. This fact could raise the cost-effectiveness-ratio of a general immunisation. Discussion: The low evidence of information on the herd immunity effect of pneumococcal immunisation, the occurrence on serotype-replacement phenomenon and the effects on the prevalence of antibiotic-resistant strains shall be considered when deciding whether the pneumococcal vaccination for all infants and young children should be added to the German vaccination scheme. There is also little information on the duration of vaccine effectiveness and regional effectiveness because of different serotype incidence. The economic models thus incorporate some uncertainties. Conclusion: At present, relatively few pneumococcal strains in Germany show antibiotic resistance. This situation shall further be observed while improving the data evidence for future decisions (epidemiologic data of incidence of pneumococcal diseases and serotyping of pneumococcal bacteria). From the economic perspective no distinct recommendation to add the conjugated vaccination for all children to the German vaccination scheme can be given. This situation may change if the price for the vaccine further decreases. Furthermore a future cost-effectiveness analysis for Germany should incorporate the effects of the replacement phenomenon, the herd immunisation effects and the effects of the vaccination on the antibiotic-resistant pneumococcal strains

Computed tomography for the measurement of coronary calcification in asymptomatic risk patients

Background: In 2003 nearly 20% of deaths in Germany were caused by coronary heart disease (CHD). Risk models are used to estimate the ten-year-risk of a coronary event. Coronary calcification may be seen as an additional risk factor. The amount of calcium is correlated with atherosclerotic lesions, but there is no direct correlation with the probability of a plaque rupture. Coronary calcification may be measured either by electron beam computed tomography (EBCT) or multi-detector computed tomography (MDCT). Objectives: The aim of this HTA report is to investigate the diagnostic validity and cost effectiveness of computed tomography techniques in measuring coronary calcification of asymptomatic risk patients. Ethical aspects are discussed. Methods: A systematic literature research was performed in 35 international databases which yielded 1080 articles. Overall 43 publications were included for assessment, according to predefined selection criteria. Results: Measuring coronary calcification offers additional information compared with traditional risk factors. Yet at present it cannot be said - according to published literature - which population groups gain most. For determining adequate calcium score thresholds standardisation for age and sex is important. When comparing the reference standard EBCT with MDCT results are inconsistent and depend on the calcium-score value as well as on the scoring method. EBCT as a triage instrument in diagnosing CHD appears to be cost-effective. Yet it is rather not cost-effective as a refinement tool for risk stratification. Discussion: Most of the literature was published in the United States and discusses the use of EBCT as well as (traditional) risk stratification by the Framingham Score. Regarding coronary calcification measured by MDCT (which is more widespread in Germany than EBCT) and a risk model applicable for European populations clear recommendations based on published literature cannot be made at present. Conclusion: In conclusion measuring coronary calcification is a promising tool for improving risk stratification with established risk models. Nevertheless many questions remain concerning the targeted use in medical practice, particularly regarding European populations. Therefore also no final conclusions can be drawn with respect to cost-effectiveness. The evaluation of diagnostic procedures measuring other parameters than coronary calcium with regard to CHD risk stratification, compared to EBCT or MDCT, is not part of this report

The use of statins in primary prevention

Background: The use of statins in secondary prevention of cardiovascular events is well established. However, there is ongoing discussion about the use of statins in the context of primary prevention. Moreover statins - besides cholesterol-lowering effects - are assumed to have pleiotropic effects. Positive impacts on diseases like stroke, Alzheimer's disease or osteoporosis are discussed but still have to be proven. Objectives: The aim of this report is first to investigate the efficacy and effectiveness of statins in primary prevention of cardiovascular and non-cardiovascular events and second to examine the economic implications for Germany - particularly in comparison to existing prevention programs. Finally ethical questions are considered. Methods: A systematic literature search was performed for the period between 1998 and 2004 which yielded 3704 abstracts. Overall 43 articles were included for assessment and 167 for background information, according to predefined selection criteria. Results: Most studies within the context of primary prevention describe significant risk reductions with regard to cardiovascular events; yet no significant results according to the reduction of the overall mortality rate can be seen. With respect to stroke, osteoporosis and Alzheimer's disease results are inconsistent. Regarding cost-effectiveness of primary prevention with statins results turn out to be inconsistent as well or even negative for populations with low to moderate risk. For groups with high cardiovascular risk the intervention is mostly assessed to be cost-effective. No cost-effectiveness study for Germany was found. According to a rough estimate of future expenses statin drug expenses of the German legal health insurance might increase at least by 50% in the case of an enlargement of the group of recipients. Discussion: To thoroughly estimate the cost-effectiveness of the use of statins in primary prevention in Germany a model calculation including all relevant parameters has to be done. Moreover - from the economic as well as from the ethic point of view - one of the most important issues in primary prevention therapy is the question of compliance. The amount of risk reduction seen in primary prevention studies can be achieved only if patients as well as doctors follow therapeutic instructions and medical guidelines (as for example the guidelines of the "Adult Treatment Panel III", the "European guidelines on cardiovascular disease prevention in clinical practice" or the guidelines of the German Association of Cardiology and of the "Arzneimittelkommission der deutschen Ärzteschaft für Koronare Herzkrankheit"). Conclusion: For (primary) prevention of cardiovascular diseases the use of statins as suggested in guidelines is recommended - provided that these guidelines are scientifically evaluated at regular intervals. Regarding stroke, osteoporosis and Alzheimer's disease definite conclusions cannot be drawn at present. Particular attention has to be paid to the problem of compliance both in statin-therapy as well as in alternative therapies. The cost-effectiveness of primary prevention with statins mainly depends on the development of statin prices