Eine klinisch experimentelle Querschnittstudie zur Charakterisierung des subbasalen Nervenplexus der Kornea: Untersuchung von gesunden Kindern und Jugendlichen sowie von pädiatrischen Patienten mit einem Typ 1 Diabetes mellitus oder einer chronischen Niereninsuffizienz

Die diabetische und urämische Polyneuropathie sind häufige und schwer therapierbare Folgeerkrankungen eines Diabetes mellitus bzw. einer chronischen Nierenerkrankung. Die Konfokale-Laser-Scanning-Mikroskopie ist ein objektives und nichtinvasives Messverfahren, welches es ermöglicht den subbasalen Nervenplexus der Kornea darzustellen. Bereits bei Kindern und Jugendlichen mit einem Diabetes mellitus Typ I oder einer chronischen Nierenerkrankung ohne polyneuropathischen Symptomen sind mit dieser Methode Veränderungen des kornealen Nervenplexus zu erfassen

Lapatinib for HER2 overexpressing breast cancer

This paper presents a summary of the evidencereview group (ERG) report into the clinicaleffectiveness and cost-effectiveness of lapatinib forthe treatment of advanced or metastatic HER2-overexpressing breast cancer based upon a reviewof the manufacturer’s submission to the NationalInstitute for Health and Clinical Excellence (NICE)as part of the single technology appraisal (STA)process. The scope included women with advanced,metastatic or recurrent HER2-overexpressingbreast cancer who have had previous therapy thatincludes trastuzumab. Outcomes were time toprogression, progression-free survival, responserates, overall survival, health-related qualityof life and adverse effects. The submission’sevidence came from one randomised controlledtrial (RCT) of reasonable methodologicalquality, although it was not powered to detect astatistically significant difference in mean overallsurvival. Median time to progression was longerin the lapatinib plus capecitabine arm than inthe capecitabine monotherapy arm {27.1 [95%confidence interval (CI) 17.4 to 49.4] versus 18.6[95% CI 9.1 to 36.9] weeks; hazard ratio 0.57 [95%CI 0.43 to 0.77; p = 0.00013]}. Median overallsurvival was very similar between the groups [67.7(95% CI 58.9 to 91.6) versus 66.6 (95% CI 49.1to 75.0) weeks; hazard ratio 0.78 (95% CI 0.55to 1.12; p = 0.177)]. Median progression-freesurvival was statistically significantly longer inthe lapatinib plus capecitabine group than in thecapecitabine monotherapy group [27.1 (95% CI24.1 to 36.9) versus 17.6 (95% CI 13.3 to 20.1)weeks; hazard ratio 0.55 (95% CI 0.41 to 0.74);p = 0.000033]. The manufacturer’s economicmodel to estimate progression-free and overallHTA 07/10/01Date of ERG submission:June 2007TAR Centre(s):Southampton Health Technology Assessments CentreList of authors:J Jones, A Takeda, J Picot, C von Keyserlingk and A CleggContact details:Andrea Takeda, Southampton Health TechnologyAssessments Centre, Wessex Institute for HealthResearch and Development, University of Southampton,Mailpoint 728, Boldrewood, Southampton SO16 7PX,UKE-mail: [email protected] research reported in this article of the journalsupplement was commissioned and funded by theHTA programme on behalf of NICE as project number07/10/01. The assessment report began editorial reviewin May 2008 and was accepted for publication in May2009. See the HTA programme web site for furtherproject information (www.hta.ac.uk). This summaryof the ERG report was compiled after the AppraisalCommittee’s review.The views and opinions expressed therein are those ofthe authors and do not necessarily reflect those of theDepartment of Health.Discussion of ERG reports is invited. Visit the HTAwebsite correspondence forum (www.hta.ac.uk/correspond).Lapatinib for the treatment of HER2-overexpressing breast cancer2survival for patients with HER2-positive advanced/metastatic breast cancer who had relapsedfollowing treatment with an anthracycline, a taxaneand trastuzumab was appropriate for the diseasearea. The base-case incremental cost-effectivenessratios (ICERs) for lapatinib plus capecitabinecompared with capecitabine monotherapy orvinorelbine monotherapy were higher than wouldconventionally be considered cost-effective.When compared with trastuzumab-containingregimes, lapatinib plus capecitabine dominated.In sensitivity analyses the ICER for lapatinibplus capecitabine compared with capecitabinemonotherapy or vinorelbine monotherapy wasrobust to variation in assumptions. In all sensitivityanalyses the ICERs remained higher than wouldconventionally be considered cost-effective.ICERs for trastuzumab-containing regimes wereparticularly sensitive to assumptions over thefrequency of treatment, which had a large effect onthe cost-effectiveness of lapatinib plus capecitabine.In conclusion, there was a general lack of evidenceon the effectiveness of comparators included inthe model and on key parameters such as doseadjustments and the model outputs need to beinterpreted in the light of this uncertainty. At thetime of writing, NICE were still considering theavailable evidence for this appraisal

A Review of Methods Used in Long-Term Cost-Effectiveness Models of Diabetes Mellitus Treatment

Diabetes mellitus is a major healthcare concern from both a treatment and a funding perspective. Although decision makers frequently rely on models to evaluate the long-term costs and consequences associated with diabetes interventions, no recent article has reviewed the methods used in long-term cost-effectiveness models of diabetes treatment. The following databases were searched up to April 2008 to identify published economic models evaluating treatments for diabetes mellitus: OVID MEDLINE, EMBASE and the Thomson's Biosis Previews, NHS EED via Wiley's Cochrane Library, and Wiley's HEED database. Identified articles were reviewed and grouped according to unique models. When a model was applied in different settings (e.g. country) or compared different treatment alternatives, only the original publication describing the model was included. In some cases, subsequent articles were included if they provided methodological advances from the original model. The following data were captured for each study: (i) study characteristics; (ii) model structure; (iii) long-term complications, data sources, methods reporting and model validity; (iv) utilities, data sources and methods reporting; (v) costs, data sources and methods reporting; (vi) model data requirements; and (vii) economic results including methods to deal with uncertainty. A total of 17 studies were identified, 12 of which allowed for the conduct of a cost-effectiveness analysis and a cost-utility analysis. Although most models were Markov-based microsimulations, models differed with respect to the number of diabetes-related complications included. The majority of the studies used a lifetime time horizon and a payer perspective. The DCCT for type 1 diabetes and the UKPDS for type 2 diabetes were the trial data sources most commonly cited for the efficacy data, although several non-randomized data sources were used. While the methods used to derive the efficacy data were commonly reported, less information was given regarding the derivation of the utilities or the costs. New interventions were generally deemed cost effective based on ten studies presenting results. Authors relied mostly on univariate sensitivity analyses to test the robustness of their models. Although diabetes is a complex disease, several models have been developed to predict the long-term costs and consequences associated with diabetes treatment. Combined with previous findings, this review supports the development of a reference case that could be used for any new diabetes models. Models could be enhanced if they had the capacity to deal with both first- and second-order uncertainty. Future research should continue to compare economic models for diabetes treatment in terms of clinical outcomes, costs and QALYs when applicable.Cost-effectiveness, Diabetes-mellitus, treatment, Modelling