Cost effectiveness analysis of heptavalent pneumococcal conjugate vaccine in Germany considering herd immunity effects.

BACKGROUND: In Germany the heptavalent pneumococcal conjugate vaccine (PCV7) has been recommended as a general infant vaccination since 2006. Data from similar programmes in the USA have reported a reduction of pneumococcal diseases in both vaccinated and unvaccinated populations, suggesting herd immunity effects. This study analyses the cost-effectiveness of a general vaccination with PCV7 in Germany based on these findings. METHODS: A Markov model adapts efficacy and herd immunity data to the German population. Further main model inputs are incidence, vaccination uptake, serotype distribution, case fatality rates, and vaccination and health-care costs. RESULTS: A general vaccination with PCV7 would avoid about 232,000 pneumococcal infections and 1,879 premature deaths per year in Germany. From the health-care payer's perspective, direct cost savings would outweigh vaccination expenditures by a ratio of 1:1.16. The sensitivity analysis shows that these estimates are quite conservative. CONCLUSION: Based on the health-economic evaluation, the authors recommend the continuation of the general recommendation of PCV7 according to the 3 + 1 schedule within the German Statutory Health Insurance.

Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects.

In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease. Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating (1) children at high risk, (2) all children when considering only benefits for vaccinated individuals and (3) all children when also considering herd immunity benefits. Costs in the model included vaccination, management of meningitis, bacteraemia, pneumonia and acute otitis media, insurance payments to parents and the costs of care for long-term disabilities. The model estimated that the cost-effectiveness of vaccination would be 38,222 euros per life year gained in children at high risk and 100,636 euros per life year gained in all children when not considering herd immunity. When considering herd immunity effects, the model estimated that offering vaccination for all children would reduce adult deaths by 3,027 per year, and vaccination would be broadly cost neutral. The findings are sensitive to the effect of conjugate vaccine on the rates of pneumonia and invasive disease in the elderly. If the herd immunity effect of conjugate vaccination in Germany is similar to that observed elsewhere, offering vaccine to all children will be more attractive than the current policy of restricting vaccination to children at high risk of pneumococcal disease.

[Incremental cost-effectiveness of dipyridamole + acetylsalicylic acid in secondary prevention of ischemic noncardioembolic stroke]. / Inkrementelle Kosteneffektivität von Dipyridamol + Acetylsalicylsäure in der Sekundärprävention bei ischämischem nichtkardioembolischem Schlaganfall.

BACKGROUND AND PURPOSE: The aim of secondary prevention in stroke is to avoid restrokes. The current standard treatment in Germany is a lifelong therapy with low-dose acetylsalicylic acid (ASA). As the incidence of restrokes remains relatively high from a health-care payer's perspective, the question arises, whether the combination of dipyridamole + acetylsalicylic acid (Dip + ASA) is cost-effective in comparison with a therapy based on ASA only. METHODS: A decision-analytic cross-sectional epidemiologic steady-state model of the German population compares the effects of two strategies of secondary prevention with Dip + ASA (12 months vs. open end) and with ASA monotherapy. RESULTS: The model predicts the following estimates: the annual incidence of initial ischemic strokes in Germany is estimated at 130,000 plus an extra 34,000 restrokes (base year 2005). Additionally, there are 580,000 people that experienced a stroke > 12 months earlier, of whom 135,000 had a restroke. Every year, nearly 89,000 Germans die of the consequences of an ischemic stroke. If Dip + ASA would have been the standard therapy in secondary prevention of ischemic stroke, an additional 7,500 persons could have been saved in 2005. Statutory health insurance would have to spend 33,000 Euro for every additional life year gained with Dip + ASA as secondary prevention strategy. If secondary prevention with Dip + ASA would be limited to the first 12 months after an initial stroke, which is the time of the highest risk for a restroke, the incremental cost-effectiveness ratio is about 7,000 Euro per life year gained. The results proved to be robust in sensitivity analyses. CONCLUSION: Secondary prevention with Dip + ASA is cost-effective in comparison to treatment with ASA in monotherapy, because its incremental cost-effectiveness ratio is within common ranges of social willingness to pay. From the standpoint of the patient as well as the health-care payer, focusing on the first 12 months after the initial incident for intensified preventive drug treatment with Dip + ASA should be valuable from a medical as well as a health-economic perspective.

Cost effectiveness of pneumococcal vaccination for infants and children with the conjugate vaccine PnC-7 in Germany.

BACKGROUND: The introduction of the conjugate vaccine PnC-7 implies that a pneumococcal vaccine is available, for the first time, which also gives children under the age of 2 years reliable protection against invasive pneumococcal infections and offers some protection against non-invasive pneumococcal infections. OBJECTIVE AND PERSPECTIVE: In the context of a multiple-period Markov model, a cost-effectiveness analysis of a recommendation for general pneumococcal vaccination in Germany for infants and children under the age of 2 years was performed from the healthcare payer, public authority and societal perspectives. DESIGN: Various published data on age-specific incidence rates, mortality rates, efficacy of the conjugate vaccine PnC-7 and treatment costs of pneumococcal infections were incorporated into a Markov model to quantify the consequences of vaccinating versus not vaccinating. RESULTS: From a German healthcare payers' perspective, general vaccination with the conjugate vaccine would redeem 51.1% of the vaccination costs due to avoidable treatment costs, whereas, from a broader point of view, the benefits, expressed in monetary terms, would exceed the cost of vaccination. The conjugate vaccine would require an investment of euro72 866 per life-year saved (discounted, healthcare payers' viewpoint). Besides this benchmark, there are further outcome measures which cannot be ignored by those deciding on a general vaccination recommendation: 450 000 preventable episodes of illness and 134 cases of sequelae which can be prevented. CONCLUSIONS: The vaccination with the conjugate vaccine PnC-7 is cost saving from a broader perspective and the results should not be ignored by policy makers in regard to a general vaccination recommendation.

[Persistence and frequency of prescriptions of subcutaneous allergen-specific immunotherapy (SCIT) prescribed within the German statutory health insurance]. / Persistenz und Frequenz von Verordnungen im Bereich der subkutanen allergenspezifischen Immuntherapie (SCIT) bei GKV-Patienten in Deutschland.

BACKGROUND AND PURPOSE: In accordance with guidelines subcutaneous allergen-specific immunotherapy (SCIT) should be continued for at least 3 consecutive years, which makes compliance to an issue of special importance. Measuring this compliance poses a methodological challenge. The aim of this study is to analyze persistence (reuptake of SCIT in the following years) and frequency (mean number of prescriptions) with the help of secondary data. METHODS: The sample, which was taken from a regional prescription database, includes all members of the German statutory health insurance, who received at least one prescription of selected allergen extracts between January 1, 2003 and June 30, 2006. In addition to persistence, average prescriptions for each year of therapy were used to compare long-term SCIT and short-term SCIT. Based on mean number of prescriptions per year, it was examined whether persistence is higher in short-term than in long-term SCIT. RESULTS: Mean number of prescriptions is significantly different in the 1st (2nd; 3rd) year of therapy: 1.50 (1.31; 1.28) prescriptions for long-term SCIT, 1.30 (1.42; 1.42) prescriptions for short-term SCIT, and 1.10 (1.12; 1.14) prescriptions for a shortened therapy regimen with an adjuvant-supported allergoid. As presented, persistence is decreasing. Altogether 45% of SCIT patients continue therapy in the 2nd year. In the 3rd year of therapy, there are only 24% of patients remaining. Persistence rates to a certain degree seem to be dependent on the application form. CONCLUSION: The analysis of this secondary dataset has found that nonpersistence may jeopardize the therapy according to guidelines to a greater extent than expected from the literature. Except for one allergen extract the differentiation between long-term and short-term SCIT seems diffuse. Packages for consecutive treatment are used not only in long-term SCIT, but also in short-term SCIT regimens, if they are available. The analysis provides first hints that a shorter therapy regimen supports persistence of SCIT during the 2nd and 3rd year of therapy.

Therapy of moderate and severe psoriasis.

OBJECTIVE AND METHODS: This health technology assessment (HTA) report synthesises systematically randomized controlled studies (RCT) on the therapy of moderate and severe psoriasis vulgaris which were published between 1999 and 2004; it includes some important clinical studies which have been published after 2004 and thus updates the English HTA report by Griffiths et al. [1]. The major objective is the evaluation of the medical effectiveness of different therapeutical approaches and the cost effectiveness with relevance for Germany. RESULTS: The major conclusions from the results of medical RCT on moderate and severe psoriasis vulgaris are: Oral fumarates are effective in the treatment of moderate to severe psoriasis vulgaris. However, fumarates quiet frequently cause moderate side effects. Cyclosporine and methotrexate are both effective in the treatment of severe psoriasis vulgaris. Both substances have a different spectrum of side effects which may limit the individual applicability. Acetritin is only moderately effective in the treatment of severe psoriasis of the plaque type. Calcipotriol or UV-radiation used at the same time can increase the clinical effectiveness of acetritin. Systemic PUVA, balneo-PUVA and UVB therapy are all effective for the treatment of severe psoriasis. The combination of UV therapy with vitamin D3 analogues or with topical steroids is more effective than the treatment with UV radiation alone. Saltwater baths increase the effectiveness of UVB therapy. No RCT on the therapeutical effects of topical tar or of dithranol in combination with UV therapy have been published so far. A continuous therapy with PUVA should not be applied due to its proven photocarcinogenicity. Three substances from the group of biologicals (Efalizumab, Etanercept, and Infliximab) are now available in Europe and a further substance (Alefacept) is available in the USA for the treatment of moderate to severe psoriasis. All biologicals have been effective in placebo controlled studies. The substances differ in the times until a clinical effect is observable, in the spectrum of side effects and in their efficiency on psoriasis arthritis. From health-economic studies considering both costs and clinical efficiency oral fumarates appear to be superior to acitretin or cyclosporine (although cyclosporine appears to be more effective in severe psoriasis). From the health economic view methotrexate is equivalent with UVB or PUVA and superior to cyclosporine. The therapy options UVB, UVB plus calcipotriol and PUVA are equivalent and superior to balneo-phototherapy. Biologicals are cost intensive and should be used when other approaches are not sufficient or are not applicable due to their side effects. The HTA report summarizes some health-economic studies on dithranol, on calcipotriol and on the combination with tar and UV light. No RCT have been published for the treatment of severe psoriasis with these agents alone but it appears to be certain that these substances are effective in severe psoriasis as well. DISCUSSION: The spectrum of therapeutical options has fortunately increased during the last years. It must be emphasized that a number of therapeutical procedures exist which are not discussed in detail in this HTA. This is due to the search strategy of literature: Only RCT performed with patients with moderate and/or severe psoriasis vulgaris were included into this evaluation. This led to the exclusion of a number of substances which are traditionally used alone or in combination for the treatment of moderate or severe psoriasis vulgaris (e.g. dithranol, salicyc acid, tar, corticosteroids and topical retinoids). Moreover, other approaches which include neither drugs nor UV light are not discussed in this HTA although the authors believe in the importance of psychotherapeutical interventions, educational approaches and combined medical and non-medical approaches in rehabilitational medicine in the management of psoriasis vulgaris. The transferability of the health economic evaluations is strongly limited by the fact that all included health economic evaluations except one were not aligned to a German setting. A future research question will be the evaluation of the duration of remission and relapse ratios in the context of different therapy options of moderate and severe psoriasis. Moreover, the consideration of combined outcomes such as the improvement of psoriatic symptoms and the decrease of symptoms in accompanying psoriasis arthritis represents a future requirement of health assessment. CONCLUSIONS: From the clinical point of view it is positive that the spectrum of therapeutic procedures for a chronic severe skin disease has increased continuously during the last years. In cases of individual contraindications or individual inefficacies it is now possible to try alternative approaches. Moreover the risk of long-term side effects can be reduced by changing the therapeutical procedure after some time (so-called rotation therapy). The therapeutical algorithm for severe psoriasis vulgaris now includes photo(chemo-)therapy in combination with topical substances, oral fumaric acid esters, retinoids (in combination with phototherapy or topical substances), methotrexate, cylosporine and the new biologics. Future studies should address therapeutical approaches which can not easily be studied by RCT, e.g. physical, balneological, climate approaches, educational programs and complex rehabilitation therapy which all may have positive effects on individuals with severe psoriasis. As in medical therapy management of moderate and severe psoriasis the economic evaluation also points out the way of a strategic therapy concept which corresponds to a large extent to the algorithm in medical practice.

Therapy of atopic eczema.

OBJECTIVES: Major objective is the evaluation of the medical effectiveness of different therapeutical approaches and the cost effectiveness with relevance for Germany. METHODS: This health technology assessment (HTA) evaluates systemically randomized controlled studies (RCT) on the therapy of atopic dermatitis which were published between 1999 and 2004. Further it includes some important clinical studies which have been published after 2004 and other updates the English HTA report by Hoare et al. [1]. RESULTS: Topical corticosteroids and topical calcineurin-inhibitors are the principal substances which are currently used for anti-inflammatory therapy in atopic dermatitis. These substances have shown a significant therapeutic efficacy in controlled studies. In newer controlled studies no difference was observable when corticosteroids were applied once or more than once daily onto the skin. Moreover, there is now one controlled study available which points to the fact that an interval therapy with a stronger topical corticosteroid over a limited time (some weeks) may lower the risk of recurrent flares of atopic dermatitis. Both topical calcineurin-inhibitors pimecrolimus and tacrolimus have shown a significant therapeutical efficacy in a number of placebo-controlled prospective studies. The wealth of data is high for these substances. Both substances have been shown to be efficient in infants, children and adult patients with atopic dermatitis. The importance of a so-called basic therapy with emollients which have to be adapted to the current status of skin is generally accepted in clinical practice. Controlled studies show the efficacy of "basic therapy" - although the level of evidence is quite low for this approach. The skin of patients with atopic dermatitis is colonized in the majority with Staphylococcus aureus, a gram-positive bacterium. Therefore, a therapeutical approach for the treatment of atopic dermatitis is the anti-bacterial or anti-septic treatment of the skin. Due to the lack of randomized controlled studies there is still not certain proof that antimicrobial or anti-septic treatment of non-infected eczematous skin is efficient for the treatment of atopic dermatitis. A reduction of Staphylococcus aureus is observable during an anti-inflammatory treatment of the skin with topical corticosteroids and/or the topical calcineurin-inhibitor tacrolimus. Antihistaminic drugs which are orally applied in atopic dermatitis may support the therapy of the itching skin disease. One controlled study showed a rapid reduction of itch during the use of a non-sedating antihistaminic drug. There are, however, no controlled studies which show the efficacy of antihistaminic drugs on the skin condition in atopic dermatitis. Dietetic restrictions should be applied only after a specific allergological diagnostic clarification. The "gold standard" is still a (blinded) oral provocation test which has to show an influence of a given food on the skin condition. There is sufficient evidence that there is no general dietetic approach which shows efficacy in atopic dermatitis. The treatment of patients with lactobacillae is still controversially discussed. Available studies which showed an efficacy show methodological weaknesses so that this approach can not be generally recommended for clinical practice at the time now. Approaches reducing house dust mite in the surroundings of patients with atopic dermatitis can have an effect on the skin condition so that at least in mite sensitized patients this approach appears to be reasonable. The specific immunotherapy with house dust mite showed clinical efficacy in a controlled study and in some open studies. The education of patients with atopic dermatitis or their parents is a further efficient approach in the management of this chronic skin disease. Interdisciplinary approaches in patients' education containing also psychological elements appear to be an attractive new approach for the treatment of atopic dermatitis. Phototherapy is a further possibility of intervention in atopic dermatitis in adolescent or adult patients. The available evidence points to the fact that UVB radiation (both small and broad spectrum), UVA-1 radiation and balneo-phototherapy are efficient therapeutical options for atopic dermatitis. The systemic treatment with the immunosuppressive substance cyclosporine A is efficient in the treatment of severe atopic dermatitis. Cyclosoprine A is approved for the treatment of adult patients with this skin disease. The immunosuppressive substance azathioprine showed a high clinical efficacy in two controlled studies for severe atopic dermatitis in adults. There are still controversial results for the application of antagonists to leucotriens in the treatment of atopic dermatitis: in some open studies a therapeutical efficacy was described which was, however, not reproducible in a newer controlled study. The phosphodiesterase-4-inhibitor cipamphyllin was efficient in the treatment of atopic dermatitis in a controlled study but weaker than a topical class II (i. e. moderate strength) corticosteroide. The HTA assessment further describes so-called complementary therapeutical approaches which have either not properly been studied in controlled clinical trials or which have been shown to be of no value for the treatment of atopic dermatitis. Altogether six full health-economic evaluations were found which did not cover the whole therapy spectrum of atopic dermatitis. The choice of the most cost effective treatment option of topic corticosteroids depends less on application frequency, but rather on the drug price and more used or unused quantity of the standard packages, so even smallest improvements justify a more frequent application. The results from health economic evaluations of calcineurin-inhibitors are not reliable. The therapy of severe atopic dermatitis in adults with ciclosporin shows comparable cost effectiveness in comparison to UVA/UVB therapy. DISCUSSION: The spectrum of therapeutical procedures has increased for atopic dermatitis but is still not sufficient. The spectrum of established substances is much smaller compared to psoriasis, another chronic and common inflammatory skin disease. There is need for the development new substances which can be applied topically and which are aimed to treat atopic dermatitis in early childhood. Another need for new developments can be found for the treatment of severe atopic dermatitis in adults. CONCLUSIONS: The spectrum of therapeutical procedures has increased for atopic dermatitis but is still not sufficient. The spectrum of established substances is much smaller compared to psoriasis, another chronic and common inflammatory skin disease. There is need for the development new substances which can be applied topically and which are aimed to treat atopic dermatitis in early childhood. Another need for new developments can be found for the treatment of severe atopic dermatitis in adults. Due to lack of health economic evaluations therapy decisions in the treatment of atopic dermatitis must take place on the basis of clinical decision criteria. The prescription of topic corticosteroids should prefer low priced drugs. Reliable statements about the cost effectiveness of the new calcineurin-inhibitors tacrolimus and pimecrolimus.

Cost-effectiveness of managing HIV infection.

The worldwide spread of HIV infection continues, particularly in economically vulnerable, developing and emerging countries. There is a lack of resources to supply effective prevention measures and apply highly active antiretroviral therapies. In the regions concerned, economical effects of morbidity- and mortality-associated productivity losses in those of a working age remain serious. Thus, the United Nations Program on HIV/AIDS and the World Health Organization have predicted a dramatic decrease of South Africa's and other African states' domestic product in the coming years. Therefore, with the world economical consequences from the HIV pandemic, a large political challenge in the next 10 years will arise.