Modelling costs and outcomes of newborn hearing screening: The economic part of a German health technology assessment project

The prevalence of newborn hearing disorders is 1-3 per 1000. Crucial for later outcome are correct diagnosis and effective treatment in the first year of life. With BERA and TEOAE low-risk techniques for early detection are available. Universal screening is recommended but not realised in most European health care systems. Objective of the study was to examine the scientific evidence of newborn hearing screening, thus to compare cost-effectiveness of different programmes, differentiated by type of strategy (risk screening, universal screening, no screening). Methods: In an interdisciplinary health technology assessment project all relevant studies on newborn hearing screening were identified and data on medical outcome, costs and cost-effectiveness extracted. A Markov model was designed to calculate cost-effectiveness ratios. Results: Economic data were extracted from 20 relevant publications. In the model total costs for screening of 100.000 newborns with a time horizon of ten years were calculated: 2.0 Mio . for universal screening (U), 1.0 Mio. for risk screening (R) and 0.6 Mio. for no screening (N). The costs per child detected: 13,395 (U) respectively 6,715 (R) and 4,125 (N). Conclusions: A remarkable small number of economic publications mainly of low methodo-logical quality was found. In our own model we found reasonable cost-effectiveness ratios also for universal screening. Considering the outcome advantages of higher numbers of cases detected a universal newborn hearing screening is recommended. --

Ein Health-Technology-Assessment

Fragestellung: In einem Health Technology Assessment-Bericht wurde die medizinische Wirksamkeit von Medikamente-freisetzenden Koronarstents (DES) im Vergleich zu konventionellen Metallstents (BMS) und zur Bypasschirurgie untersucht: Methodik: Es wurde ein systematischer Literaturreview mit a priori festgelegten Ein- und Ausschlusskriterien für die Publikationen durchgeführt. Alle Schritte der Informationsrecherche und –selektion wurden dokumentiert. Die identifizierten Publikationen wurden anhand von in nationalen oder internationalen Leitlinien konsentierten Checklisten für die methodische Qualität bewertet und selektiert. Für die eingeschlossenen randomisierten klinischen Studien wurde eine Metaanalyse durchgeführt. Für eingeschlossene nichtrandomisierte Primärstudien wurde eine Informationssynthese in Form einer tabellarischer Synopsis und Beschreibung vorgenommen. Ergebnisse: Mit Ausnahme einer Studie zum Vergleich DES gegenüber Bypass, wurden nur Publikationen identifiziert, die die Sicherheit und Wirksamkeit von DES im Vergleich zu BMS untersuchten. Hierzu wurden zehn RCT bei Patienten mit einer de novo-Läsion identifiziert, für die eine Metaanalyse hinsichtlich Mortalität, des Auftretens von Stentthrombosen, Myokardinfarkten, der Zielläsionsrevaskularisierung (TLR), der Zielgefäßrevaskularisierung (TVR) und der kombinierten Ereignisrate sowie der binären Restenoserate und des späten Lumenverlusts durchgeführt wurde. Insgesamt umfasste die ­Analyse 5036 Patienten in beiden Behandlungsarmen. Statistisch signifikante Unterschiede zwischen DES und BMS konnten bei den klinischen Parametern nur für erneute Revaskularisierungen, sowohl TLR als auch TVR, und für die durch die Unterschiede durch erneute Revaskularisierungen bedingten kombinierten Ereignisraten nach einem Jahr und zwei Jahren festgestellt werden. Nach einem Jahr und zwei Jahren betrug das relative Risiko (RR) des DES-Arms gegenüber dem BMS-Arm für eine TLR in der Metaanalyse 0,3 (95%-KI: 0,20-0,44 bzw. 0,23-0,38) für eine TVR betrug das RR 0,39 (95%-KI: 0,27-0,56) nach einem Jahr und 0,42 (95%-KI: 0,34-0,51) nach zwei Jahren, was einer Risikoreduktion zwischen 58 bis 70% entspricht. Bei Analyse der Subgruppen der DES wiesen nichtpolymerbeschichtete Paclitaxelstents eine geringere Wirksamkeit mit RR =0,66 (95%-KI:0,38-1,16) und keine statistische Signifikanz des Effekts auf. Bei Stentthrombosen war nach zwei Jahren ein statistisch nicht signifikanter Trend zu einem höheren Risiko für Stentthrombosen im zweiten Jahr bei DES feststellbar (RR=1,68, 95%-KI: 0,73-3,87). Die Ergebnisse aus nichtrandomisierten Studien zu weiteren Indikationen lassen noch keine gesicherten Aussagen zu, stehen jedoch nicht in Widerspruch zu den Ergebnissen der Metaanalyse

Key Recommendations from the MedtecHTA Project

There are particular characteristics ofMedical Devices, such as the device–user interaction, the incremental nature of innovation and the broader organizational impact that lead to additional challenges for health technology assessment (HTA). The project explored key aspects of the conduct andmethods ofHTAforMDs. Systematic reviews and original research studieswere conducted todetermine improvements inprocesses andmethods that could enhance the potential forHTAand optimize the diffusion ofMDs. Regulatory processes for MDs should be more closely aligned, the HTA evaluative framework should be harmonized and processes for conditional coverage and evidence development should be used. The methods for HTA should consider MDs as complex interventions, require the establishment of high quality registries, consider an iterative approach to the evaluation over time, recognize and allow for the particular characteristics of devices and use appropriate approaches for confounder adjustment in comparative effectiveness studies. To optimize the diffusion, a common classification should be developed across countries in order to facilitate international comparisons, factors driving diffusion should be explored in HTA reports and physiciansˈ personal goals and motivation should be better understood. The key recommendations of the MedtecHTA project should improve the conduct and use of HTA for MDs

Health Technology Assessment zur medizinischen Wirksamkeit und Kosten-Effektivität der Phototherapeutischen Keratektomiemit dem Excimerlaser bei rezidivierenden Erosionen, Hornhautdystrophien, Hornhautdegenerationen und oberflächlichen Hornhautnarben

Hintergrund und Fragestellung: Die phototherapeutische Keratektomie mit dem Excimer-Laser (PTK) wird bei rezidivierenden Hornhauterosionen, oberflächlichen Hornhautdystrophien, zentralen Hornhautdegenerationen, oberflächlichen Hornhautnarben und -irregularitäten mittlerweile weit verbreitet als Therapie eingesetzt. Beim Großteil der Indikationen gibt es nach Ausschöpfung konservativer Maßnahmen, abgesehen von der Hornhautstichelung bei rezidivierenden Erosionen und der Keratoplastik bei Hornhautdystrophien und Hornhautnarben, keine therapeutischen Alternativen. Bisher wurde die PTK bei diesen Indikationen noch nicht in den Leistungskatalog der GKV aufgenommen. Der vorliegende HTA-Bericht sollte die wissenschaftliche Evidenz zusammentragen, inwiefern der medizinischen Nutzen, die medizinischen Notwendigkeit und die Wirtschaftlichkeit der PTK bei den genannten Indikationen nachgewiesen werden können. --

Antioxidative vitamines for prevention of cardiovascular disease for patients after renal transplantation and patients with chronic renal failure

Introduction: The mortality from cardiovascular disease in patients with chronic renal failure is much higher than in the general population. In particular, patients with chronic renal failure with replacement therapies (dialysis patients and patients with renal transplantation) show both increased traditional risk factors and risk factors due to the dysfunction of the renal system. In combination with necessary medication for renal insufficiency oxidative stress is elevated. Progression of atherosclerosis is promoted due to increased oxidation of lipids and endothelium damage. This link between lipid oxidation and artherogenesis provides the rationale for the supposed beneficial effect of supplementation with antioxidative vitamins (vitamin A, C and E). Such an effect could not be demonstrated for patients with a history of cardiovascular disease and without kidney diseases. However, in high risk patients with chronic renal failure and renal replacement therapies this could be different. Objectives: The objective of this systematic literature review was to assess the clinical effectiveness and cost-effectiveness of supplementation with antioxidative vitamins A, C or E to reduce cardiovascular events in patients with chronic kidney diseases, dialysis-requiring patients and patients after a renal transplantation with or without cardiovascular diseases. Methods: A systematic literature review was conducted with documented search and selection of the literature, using a priori defined inclusion and exclusion criteria as well as a documented extraction and assessment of the literature according to the methods of evidence-based medicine. Results: 21 publications met the inclusion criteria for the evaluation of clinical effectiveness. No study could be identified for the economic evaluation. Two studies (four publications) analysed the effect of oral supplementation on the secondary prevention of clinical cardiovascular endpoints. Studies analysing the effect on patients without a history of cardiovascular disease could not be identified. 17 studies analysed the effect of oral supplementation or infusion with antioxidative vitamins or the supplementation with dialysis membranes coated with vitamin E on intermediate outcomes like oxidative stress or vessel parameters. The two randomized clinical trials analysing the effect of orally supplemented vitamin E on clinical endpoints in patients with mild-to-moderate renal insufficiency and for haemodialysis patients respectively reported different results. After 4.5 years supplementation with a daily dose of 400 IU vitamin E renal insufficiency patients showed neither a beneficial nor a harmful effect on a combined event rate of myocardial infarction, stroke or death by cardiovascular causes. The second study reported a 50% risk reduction (RR=0.46, 95%-KI: 0.27-0.78, p=0.014) on the combined event rate of fatal myocardial infarction, nonfatal myocardial infarction, stroke, peripheral vascular disease or unstable angina pectoris in the study arm with vitamin E-Supplementation of 800 IU daily. In 16 of 17 studies with intermediate endpoints the supplementation with vitamins was associated with a change of one or several of the examined endpoints in the expected direction. This means that the concentrations of the markers for oxidative stress decreased in the Vitamin E-group, the progression of aortic calcification (only one study) was reduced, the intima media thickness decreased and the lipid profile improved. No studies regarding costs or cost-effectiveness were identified. Discussion: A possible explanation for the different results in the two studies with clinical endpoints may be due to the different study populations with different risk profiles, to different dosage during the intervention or to variation by chance. Due to the absence of clinically meaningful endpoints, the relevance of studies analysing the effect of antioxidative vitamins on intermediate endpoints like oxidative stress markers is basically limited to show single intermediate steps of the postulated biological effect mechanisms by which a potentially preventive effect could possibly be mediated. The mainly unsatisfactory planning and reporting quality of the 17 identified studies and a possible "publication bias" are further limitations. Conclusion: The available evidence is not sufficient to support or to reject an effect of antioxidative vitamins on secondary prevention for cardiovascular disease for patients with chronic renal insufficiency or renal replacement therapy. There is a lack of randomized, placebo-controlled studies with a sufficient number of cases and clinical endpoints of cardiovascular disease, on the effect of antioxidative vitamins either orally applied or given by vitamin E-modified dialysers.No data are available about supplementation with antioxidative vitamins for primary prevention of cardiovascular disease. Therefore the current evidence does not allow to draw conclusions concerning this subject either. As opposed to patients with a history of cardiovascular disease without kidney diseases where there is enough evidence to exclude a beneficial effect on secondary prevention of cardiovascular disease for patients with chronic renal insufficiency and renal replacement therapy this question remains unanswered. Conclusions about costs and cost-effectiveness also cannot be drawn

A universal outcome measure for headache treatments, care-delivery systems and economic analysis

Background The first manuscript in this series delineated a model of structured headache services, potentially cost-effective but requiring formal cost-effectiveness analysis (CEA). We envisaged a need for a new outcome measure for this purpose, applicable to all forms of treatment, care and care-delivery systems as opposed to comparisons of single-modality treatments. Conception and delineation A literature review confirmed the lack of any suitable established measure. We prioritised construct validity, simplicity, comprehensiveness and expression in intuitive units. We noted that pain was the key burdensome symptom of migraine and episodic tension-type headache (TTH), that pain above a certain level was disabling, that it was difficult to put economic value to pain but relatively easy to do this for time, a casualty of headache leading to lost productivity. Alleviation of pain to a non-disabling level would be expected to bring restoration of function. We therefore based the measure on time spent in the ictal state (TIS) of migraine or TTH, either as total TIS or proportion of all time. We expressed impact on health, in units of time, as TIS*DW, where DW was the disability weight for the ictal state supplied by the Global Burden of Disease (GBD) studies. If the time unit was hours, TIS*DW yielded hours lived with (or lost to) disability (HLDs), in analogy with GBD’s years lived with disability (YLDs). Utility assessment Acute treatments would reduce TIS by shortening attack duration, preventative treatments by reducing attack frequency; health-care systems such as structured headache services would have these effects by delivering these treatments. These benefits were all measurable as HLDs-averted. Population-level estimates would be derived by factoring in prevalence, but also taking treatment coverage and adherence into account. For health-care systems, additional gains from provider-training (promoting adherence to guidelines and, therefore, enhancing coverage) and consumer-education (improving adherence to care plans), increasing numbers within populations gaining the benefits of treatments, would be measurable by the same metric. Conclusions The new outcome measure expressed in intuitive units of time is applicable to treatments of all modalities and to system-level interventions for multiple headache types, with utility for CEA and for informing health policy

Systematic review of the clinical effectiveness of biomarkers as cancer screening test offered as self-pay service in Austria and Germany [Abstract]

Background: Individual health services (IGeL) are medical self-pay services that are not under the liability of the German statutory health insurance. Up to 14% of IGeL are blood or laboratory and cancer screening tests, which are offered to asymptomatic individuals [1]. The aim was to investigate the clinical effectiveness of eleven biomarkers that are the most often offered biomarkers for cancer screening by physicians and laboratories on the internet in Germany (i.e., AFP, CA125, CA15-3, CA19-9, CEA, Cyfra21-1, β-HCG, NMP22, M2-PK, NSE and PCA3). Research Question: What is the benefit-harm-balance regarding patient relevant outcomes (mortality, morbidity, quality of life) for using these biomarkers as cancer screening test in comparison to usual care? Methods: Firstly, searches for Health Technology Assessment (HTA) reports and systematic reviews (SR) were performed in three different databases in spring 2012. Secondly, randomized controlled trials (RCT) that were published after the end of the research period of the most recent included secondary study were searched. We included publications in English or German which compared cancer screening with one of these biomarkers in asymptomatic persons to unscreened controls. References were independently screened by two reviewers. One reviewer extracted relevant characteristics from full text and evaluated the quality of included studies. Results: Five HTA or SR dealing with CA125 (4) or NMP22 (1) and 2 RCTs (CA125) were included. For ten biomarkers, incl. NMP22, no direct evidence on patient relevant outcomes was available. One RCT combining CA125 and vaginal ultrasound for ovarian cancer screening provided results of interest [2]. Screening compared with usual care did not reduce ovarian cancer mortality (RR, 1.18; 95% CI, 0.82-1.71) [2]. Harms occurred through overdiagnosis and false-positive results, e.g., 20.6 complications occurred per 100 surgical procedures in women who underwent surgery after a false-positive result [2]. About 4.5 surgeries were performed per one case of invasive cancer identified through CA125 screening [3]. Conclusion: While ovarian cancer screening with CA125 showed no survival benefit, false-positive tests, overdiagnosis and -treatment resulted in harm. For ten biomarkers no sufficient evidence was available. When IGeL are offered, patients should get comprehensive information about the lack of evidence on patient-relevant outcomes and potential harm caused by biomarker screening

Extracorporal hemodialysis with acute or decompensated chronical hepatic failure

Background: Conventional diagnostic procedures and therapy of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus), because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. Objectives: To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? Methods: An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Results: Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed advantages of the technology compared with standard conventional therapy concerning survival, clinical scores or clinical surrogate parameter like laboratory tests of liver function. Some studies reported complications and side effects of BioLogic-DT. All studies were methodologically insufficient. Concerning the use of MARS overall five studies - three of them randomised - were identified. Two studies reported a significant higher 30d-survival after MARS compared to controls, one study showed a non-significant trend to a better survival probability after one year. The studies showed statistically significant advantages in severity of hepatic encephalopathy, routine lab tests and hemodynamic parameter of the MARS group. None of the studies reported relevant complications or side effects. Although the methodological quality of the studies is seen as slightly better than in the studies on BioLogic-DT, there are methodological limitations: The largest sample size of the randomised trials was twelve patients per group and the study population was highly selected. Because of the methodological limitations the results can hardly be generalised. Only two economic publications presenting analyses of MARS could be de-tected. One publication shows major methodological mistakes which make a further interpretation of the results impossible. The other publication presents an incremental cost-effectiveness of MARS of 29,719 EUR per life year gained after one year from a payer's perspective (German statutory sickness fund, neglecting the intervention costs because of lacking reimbursement at this time), respectively 79,075 EUR per life year gained from a societal perspective. Including health related quality of life aspects the incremental costs per QALY (Quality adjusted life years) gained were calculated to be 44,784 EUR from a payer's perspective respectively 119,162 EUR from a societal perspective. The authors state that prolonging the time horizon of the calculations would improve cost-effectiveness ratios. The limitations of the study design also limit the scientific evidence of the results. Conclusion: The results of the detected publications do not give any evidence for a positive medical efficacy of BioLogic-DT. Concerning MARS there is some evidence for positive effects on 30d-survival, clinical parameter, and some lab tests, although the evidence is limited by the small number of studies and their methodological weakness. The currently strongly limited evidence shows a trend to an acceptable cost-effectiveness of MARS, although the results are based on only one non-randomised trial. To give valid recommendations concerning the medical efficacy as well as the cost-effectiveness of artificial liver support systems further studies are necessary