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. --

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

The contribution of a 9p21.3 variant, a KIF6 variant, and C-reactive protein to predicting risk of myocardial infarction in a prospective study

<p>Abstract</p> <p>Background</p> <p>Genetic risk factors might improve prediction of coronary events. Several variants at chromosome 9p21.3 have been widely reported to be associated with coronary heart disease (CHD) in prospective and case-control studies. A variant of <it>KIF6 </it>(719Arg) has also been reported to be associated with increased risk of CHD in large prospective studies, but not in case-control studies. We asked whether the addition of genetic information (the 9p21.3 or <it>KIF6 </it>variants) or a well-established non-genetic risk factor (C-reactive protein [CRP]) can improve risk prediction by the Framingham Risk Score (FRS) in the Cardiovascular Health Study (CHS)--a prospective observational study of risk factors for cardiovascular disease among > 5,000 participants aged 65 or older.</p> <p>Methods</p> <p>Improvement of risk prediction was assessed by change in the area under the receiver-operator characteristic curve (AUC) and by net reclassification improvement (NRI).</p> <p>Results</p> <p>Among white participants the FRS was improved by addition of <it>KIF6 </it>719Arg carrier status among men as assessed by the AUC (from 0.581 to 0.596, P = 0.03) but not by NRI (NRI = 0.027, P = 0.32). Adding both CRP and 719Arg carrier status to the FRS improved risk prediction by the AUC (0.608, P = 0.02) and NRI (0.093, P = 0.008) in men, but not women (P ≥ 0.24).</p> <p>Conclusions</p> <p>While none of these risk markers individually or in combination improved risk prediction among women, a combination of <it>KIF6 </it>719Arg carrier status and CRP levels modestly improved risk prediction among white men; although this improvement is not significant after multiple-testing correction. These observations should be investigated in other prospective studies.</p

Improved clinical investigation and evaluation of high-risk medical devices: the rationale and objectives of CORE-MD (Coordinating Research and Evidence for Medical Devices)

: In the European Union (EU) the delivery of health services is a national responsibility but there are concerted actions between member states to protect public health. Approval of pharmaceutical products is the responsibility of the European Medicines Agency, whereas authorizing the placing on the market of medical devices is decentralized to independent 'conformity assessment' organizations called notified bodies. The first legal basis for an EU system of evaluating medical devices and approving their market access was the medical device directives, from the 1990s. Uncertainties about clinical evidence requirements, among other reasons, led to the EU Medical Device Regulation (2017/745) that has applied since May 2021. It provides general principles for clinical investigations but few methodological details-which challenges responsible authorities to set appropriate balances between regulation and innovation, pre- and post-market studies, and clinical trials and real-world evidence. Scientific experts should advise on methods and standards for assessing and approving new high-risk devices, and safety, efficacy, and transparency of evidence should be paramount. The European Commission recently awarded a Horizon 2020 grant to a consortium led by the European Society of Cardiology and the European Federation of National Associations of Orthopaedics and Traumatology, that will review methodologies of clinical investigations, advise on study designs, and develop recommendations for aggregating clinical data from registries and other real-world sources. The CORE-MD project (Coordinating Research and Evidence for Medical Devices) will run until March 2024; here we describe how it may contribute to the development of regulatory science in Europe