GMS health technology assessment最新文献

Introduction: Sepsis is defined as an invasion of microorganisms and/or their toxins into the blood associated the reaction of the organism to this invasion. Severe sepsis is a major cost driver in intensive care medicine. In Germany, prevalence data was assessed in the context of the German Prevalence Study. Severe sepsis has a prevalence of 35% in German intensive care units.

Research questions: THE FOLLOWING QUESTIONS WERE ANALYSED: is Drotrecogin alfa (activated) (DAA) effective in the treatment of patients with severe sepsis and a mixed risk of death, both in all patients and in different subgroups? Is DAA effective in the treatment of patients with severe sepsis and low risk of death? Is DAA cost effective in the treatment of patients with severe sepsis compared to placebo?

Methods: Only studies with adult patients are included. There are no other exclusion criteria. A systematic literature search is performed by the German Institute of Medical Documentation and Information (DIMDI). The literature search yielded as a total of 847 hits. After screening of the abstracts, 165 medical and 101 economic publications were chosen for full text appraisal.

Results: Therapy with DAA appears to be cost effective in reducing 28-day-mortality in patients with severe sepsis and a high risk of death. A high risk of death is indicated by the presence of multiorgan failure (≥2) and/or an APACHE-II-Score ≥25. Therapy with DAA is not associated with a long-term reduction of mortality at later follow-up assessments. Therapy with DAA is not associated with a long-term reduction of mortality at later follow-up assessments. Therapy with DAA is cost-effective in patients with multiorgan failure and/or an APACHE II Score (≥25). In patients with a lower risk of death, DAA is not cost-effective. Costs associated with bleeding events have been rarely included in cost calculations.

Discussion: DAA appears to reduce mortality in patients with severe sepsis and a high risk of death, but not in patients with a low risk of death. Bleeding events and mortality are considerable higher in studies in the usual care setting compared to clinical trials. In a number of subgroup analyses, both retrospectively and prospectively performed, DAA was not significantly associated with improved survival. The role of concurrent therapy with heparin is unclear, as DAA was only effective in reducing mortality in patients without heparin. There was no significant long-term survival benefit associated with DAA beyond the initial 28 days. Also, there is a lack of studies assessing prospectively functional ability, health-related quality of life, and morbidity in the long-term. In the subgroup of patients with a high risk of death, therapy with DAA ranges at the top level of generally accepted costs per LYG or QALY, in the subgroup of patients with low risk of death, cost effectiveness

Health political background: Methadone substitution treatment in Germany is introduced in 1988 in the framework of a scientific pilot study in North Rhein Westphalia. Recent statistics show that by now a broad offer of substitution treatment exists. From 1 June 2002 to 31 December 2003 113,000 substitution treatments have been recorded as being started of which around 56,000 have been recorded as ongoing treatments by 1 December 2003.

Scientific background: Substitution treatment (treatment of opioid-dependent persons using substitution substances) is one part of addiction treatment. Its goals are harm reduction and the stabilisation of opioid dependent persons. Integration of opioid-dependent persons in a treatment-setting, reduction of consumption of psychoactive substances, reduction of risk behaviour (primarily related to infectious diseases), decrease of mortality and improvements concerning the social, psychic and physic situation are seen as a success of substitution treatment as maintenance therapy.

Research questions: The aim of this HTA report is to investigate which indicators can be used to evaluate the effectiveness of substitution treatment. Based on these indicators an evaluation of the medical, social and economical benefit of substitution treatment - also in relation to abstinence oriented treatment - is carried out.

Methods: A systematic literature search was performed in 31 international databases which yielded 2451 articles with publication date between 1995 and February 2005.

Results: After a twofold selection process 32 publications were included for assessment and 276 publications were used as background literature. Despite serious restrictions due to selection bias and dropout in most studies focusing on substitution treatment, reduction of consumption of illegal opioids, reduction of risk behaviour, criminal behaviour, mortality and incidence of HIV can be seen as an empirically proven success of substitution treatment. Concerning the improvement of life and health situation the results of the studies are contradictory. The results show that retention rate of substitution treatment is higher than retention rate of abstinence oriented treatment. Regarding economical aspects substitution treatment is efficient in avoiding secondary illnesses (infections) and decreasing criminality. From the perspective of medical ethics substitution treatment as well as medical prescription of heroin is in principle acceptable.

Discussion and conclusions: Based on these results, it can be recommended that substitution treatment in principle should be made available for all opioid dependent persons. The decision whether substitution treatment or another treatment (e. g. abstinence oriented treatment) is more promising has to take into account the individual situation of the client. In addition a combination o

Background: In Western countries hormone replacement therapy (HT) is widely used in the treatment of climacteric women who are affected with hot flashes and night sweats. Besides, long-term HT was frequently used to manage the higher risks for osteoporosis and heart attack in postmenopause. Estrogens alone or combined with progestin feature most frequently in HT.

Objectives: This HTA report addresses the questions on medical efficacy and cost-effectiveness of HT as a treatment of hot flashes and night sweats as well as in the primary prevention of osteoporosis and cardiovascular disease in postmenopause in general healthy women.

Methods: The literature search for articles published after 1998 was conducted in March 2004 in standard medical and economic databases. The analysis included randomised controlled trials, systematic reviews, meta-analysis and economic evaluations considering relevant clinical endpoints in English or German language. The quality of the studies was assessed using checklists corresponding to the study type.

Results: HT is highly effective in treating hot flashes in climacteric women. The question of economical efficiency cannot be answered due to the scarce database. As the positive effects (lower risk for fractures and endometrial cancer) do not outweigh the negative effects (higher risk for breast cancer and general cardiovascular risk) estrogen-progestin combination HT cannot be recommended for primary prevention of osteoporosis and cardiovascular disease in postmenopausal women.

Discussion: The observation period of most of the studies regarding therapy of hot flashes and night sweats were too short to evaluate possible risks of long-term HT. The economic publications assessing HT for this indication varied vastly in terms of applied methods and were not carried out with respect to the German health care system.

Conclusions: HT can be recommended in the short-term treatment of hot flashes and night sweats in climacteric women. To explore the economic effects of HT for this indication for Germany, studies constructed with respect to the German health care system are desirable.

Background: In industrialised nations age-related macular degeneration (AMD) is the most common cause of blindness and severe visual impairment. AMD is a disease of the retina characterized by the accumulation of metabolic products in the macula. In early stages drusen and pigment disorders occur, in late stages a dry form is distinguished from the exsudative form with choroidal neovascularisation. AMD causes vision disorders such as blurred vision of the central part of the visual field, leading finally to a dark spot. Several therapies are available for the exsudative form, however an exact diagnosis is partially essential. The gold standard for the diagnosis of AMD is fluorescein angiography (FA), an invasive investigation with intravenous application of a dye. Optical coherence tomography (OCT) is a more recent non-invasive procedure.

Objectives: The aim of this HTA report is to investigate the efficacy and efficiency of OCT compared to FA. Ethical, societal and legal aspects are also considered.

Methods: A systematic literature search was performed in 34 international databases which yielded 2324 articles. Eight publications were included for assessment, according to predefined selection criteria.

Results: The number of studies investigating OCT compared to FA in patients with AMD is presently very limited and the quality of the studies is generally low. The number of investigated patients is below 35 in four publications and in only one publication it is above 100. Moreover in most of the articles very selected patient groups are studied. Economic studies concerning the efficiency of OCT compared to FA cannot be identified.

Discussion: Even though the patient groups investigated and the objectives of the studies are very heterogenous, all publications uniformly show that OCT cannot replace FA. However, OCT yields additional diagnostic findings and may verify unclear findings of FA. Therefore the application of OCT in addition to FA is useful in many cases. With regard to costs German patients on average currently have to pay more for performing OCT than for performing FA.

Conclusion: Future studies have to show whether OCT may give diagnostic information essential for therapeutic decisions in addition to FA and whether it can replace FA in selected cases. The number of patients included in these studies should be high enough to answer relevant questions with sufficient statistical power. An economic model calculation can be built upon the resulting findings.

Health political background: About 950,000 people are affected by glaucoma in Germany, about 50% of which are undiagnosed. The German Ophthalmological Society and the German Association of Ophthalmologists recommend a screening for glaucoma according to their guidelines. The Federal Joint Committee disapproved a glaucoma-screening program on expense of the compulsory health insurance in 2004.

Scientific background: Primary open angle glaucoma is diagnosed by evaluation of the optic disc, the retinal fibre layer and the visual field. The main examinations are ophthalmoscopy, scanning laser polarimetry, confocal scanning laser ophthalmoscopy, retinal thickness analysis and optical coherence tomography. Scotomas are diagnosed by perimetry (standard automated perimetry, short wavelength automated perimetry and frequency doubling perimetry). The intraocular pressure is the most important treatable risk factor and is measured by (contact or non-contact) tonometry.

Research questions: The aim of this HTA-report is to investigate the diagnostic validity and cost effectiveness of diagnostic techniques or combinations of these methods with respect to the use in a screening setting in Germany.

Methods: A systematic literature research was performed in 35 international databases and yielded 2602 articles. Overall 57 publications were included for assessment, according to predefined selection criteria.

Results: The 55 medical articles deal mainly with frequency doubling perimetry, confocal scanning laser ophthalmoscopy and scanning laser polarimetry. Few articles cover short wavelength automated perimetry, tonometry and ophalmocopic evaluations by ophthalmologists. The quality of the papers is generally low, as far as the evidence in respect of screening is concerned. No single method exists with both, high sensitivity and high specificity for screening purpose. Data are also not sufficient to recommend combinations of methods. Only two economic models on cost-effectivenes of screening investigations could be identified. No economic evaluations of the most recent methods can be found in the published literature. A British cost-effectiveness analysis calculates cost per true positives and favours a combination of ophthalmoscopy, tonometry and perimetry either for people at high risk for glaucoma or for the total population as an initial examination. A Canadian HTA-report models the cost per year of blindness avoided. The report concludes that because of a high degree of uncertainty with respect to the benefits and the high costs involved, the setting-up of a glaucoma-screening program cannot be supported.

Discussion: The literature shows that combinations of methods have to be used for screening of glaucoma in order to get reasonable values of sensitivity and specificity. Presently no combination of methods and no algorithm can

Scientific background: Appendicitis is an inflammation of the appendix of the blind intestine. Appendicitis remains the most frequent cause for an acute abdomen. Both interventions, the open surgical (through opening of the abdominal cavity) as well as the laparoscopic approach (via insertion of an optic system and instruments into the abdominal cavity through three small incisions), are used for the excision of the inflamed appendix (appendectomy).

Research questions: The performed evaluation addresses questions on the medical effectiveness of the use of laparoscopic appendectomy in comparison with the classical open appendix excision as well as on its cost-effectiveness based on the German health system.

Methods: A literature search was conducted in October 2005 in the most important medical electronic databases. The medical analysis was performed on the basis of the most up to date systematic review (basic review) of randomized controlled studies (RCT), newly published RCT and on our own quantitative information synthesis of all studies as well as of selected methodologically high-value RCT. In the health economic analysis, relevant publications were evaluated and cost differences of both interventions were calculated.

Results: One systematic review and 56 primary studies were included in the medical evaluation, 24 of these studies were included in the conducted subanalysis on the basis of methodologically high-value studies. In total, a relation of three avoided wound infections per one additional intraabdominal abscess has to be expected by the use of laparoscopic appendectomy in com-parison with the open operation. Diagnostic laparoscopy reduces the rate of unclear diagnoses within the scope of planned appendectomy in fertile women. By routine, leaving the macroscopically bland appendix in situ, the rate of negative appendectomy is reduced significantly and profound. The results speak for a small advantage of the laparoscopic appendec-tomy with regard to pain intensity, the time until reintroduction of liquid and solid diet, time until first stool as well as for a slightly better cosmetic result and slightly better quality of life. In the contemporary practice in Germany, a longer operation time, a reduced length of hospital stay and a similar time to return to work have to be expected by the use of laparoscopic appendectomy in comparison with open appendectomy. In the current health care situation in Germany, the use of laparoscopic appendectomy is associated with additional operation costs of approximately 150 to 200 Euro compared with the open appendectomy. By approximately 200 Euro costs savings due to the shorter length of hospital stay, the total (direct and indirect) costs of in-patient care of both interventions seem to be similar. Due to similar indirect costs, the total costs of both interventions lie also in the same range and the incremental

Background: The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology - can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other.

Objectives: The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD). It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD.

Methods: The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983.

Results: The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical significance despite a large number of participants. Only one out of two clinical studies looked at further impairment in late stages of AMD and could not find an interrelation with cataract extraction. Thus the available evidence was not sufficient to come to a conclusion on the contribution of cataract extractions to the first manifestation of AMD and to the further impairment in late stages.

Discussion: The presentation of the evaluated literature made clear that only a small number of publications dealt with the development of age related macula degeneration in consequence of a cataract extraction. The overall scientific level of evidence of these articles was not very high. Therefore it was not possible to obtain a well-defined conclusion on the effect of a cataract extraction on the development or progression of an age related macula degeneration.

Conclusion: Additional

Introduction: Permanent congenital bilateral hearing loss (CHL) of moderate or greater degree (≥40 dB HL) is a rare disease, with a prevalence of about 1 to 3 per 1000 births. However, it is one of the most frequent congenital diseases. Reliance on physician observation and parental recognition has not been successful in the past in detecting significant hearing loss in the first year of life. With this strategy significant hearing losses have been detected in the second year of life. With two objective technologies based on physiologic response to sound, otoacoustic emissions (OAE) and auditory brainstem response (ABR) hearing screening in the first days of life is made possible.

Objectives: The objective of this health technology assessment report is to update the evaluation on clinical effectiveness and cost-effectiveness of newborn hearing screening programs. Universal newborn hearing screening (UHNS) (i), selective screening of high risk newborns (ii), and the absence of a systematic screening program are compared for age at identification and age at hearing aid fitting of children with hearing loss. Secondly the potential benefits of early intervention are analysed. Costs and cost-effectiveness of newborn hearing screening programs are determined. This report is intended to make a contribution to the decision making whether and under which conditions a newborn hearing screening program should be reimbursed by the statutory sickness funds in Germany.

Methods: This health technology assessment report updates a former health technology assessment (Kunze et al. 2004 [1]). A systematic review of the literature was conducted, based on a documented search and selection of the literature using predefined inclusion and exclusion criteria and a documented extraction and appraisal of the included studies. To assess the cost-effectiveness of the different screening strategies in Germany the decision analytic Markov state model which had been developed in our former health technology assessment report was updated.

Results: Universal newborn hearing screening programs are able to substantially reduce the age at identification and the age at intervention of children with CHL to six months of age in the German health care setting. High coverage rates, low fail rates and - if tracking systems are implemented - high follow-up-rates to diagnostic evaluation for test positives were achieved. New publications on potential benefits of early intervention could not be retrieved. For a final assessment of cost-effectiveness of newborn hearing screening evidence based long-term data are lacking. Decision analytic models with lifelong time horizon assuming that early detection results in improved language abilities and lower educational costs and higher life time productivity showed a potential of UNHS for long term cost savings compared to selective screening and no screening. F