Critical Review of European Health-Economic Guidelines for the Health Technology Assessment of Medical Devices.

Background: Health-technology assessment (HTA) is a recognized mechanism to determine the relative benefits of innovative medical technologies. One aspect is their health-economic impact. While the process and methodology for pharmaceuticals is well-established, guidance for medical devices is sparse. Aim: To provide an overview of the health-economic aspect in current European HTA guidelines concerning medical devices and identifying issues raised and potential improvements proposed in recent literature. Methodology: Available guidelines by European agencies were each reviewed and summarized. To complement this, a full systematic review of current literature concerning potential improvements to existing HTA practices for medical devices, from PubMed and EMBASE, was conducted; the focus was on health economics. Authors could only review documents in English, French, or German. The systematic review yielded 518 unique articles concerning HTA for medical devices, 32 of which were considered for full-text review after screening of all abstracts. Results: There is very limited consensus in-and mostly a complete lack of-guidance specific to medical devices in official HTA guidelines, for both clinical and economic analyses. Twenty two of 41 European countries had published official HTA guidance in English, French, or German. Among these only 4 (England, France, the Netherlands, and Sweden) dedicated a chapter or separate document to medical devices. In the literature, there is sufficient evidence to suggest medical devices need to be addressed separately from pharmaceuticals. However, mostly challenges are discussed rather than implementable solutions offered. We present the following set of frequently discussed issues and summarize any solutions that pertain to them: a weak evidence base, learning-curve effects, organizational impact, incremental innovation, diversity of devices, dynamic pricing, and transferability. We further combine reviewed information to suggest a set of possible best practices for health-economic assessment of medical devices. Conclusion: For greater efficiency in medical-device innovation, European agencies should look to (re-)address the specific requirements of medical devices in their HTA guidelines. When both the health-economic and data requirements for the HTA of medical devices are defined, the development of practical solutions will likely follow.

The Proteome Analysis database: a tool for the in silico analysis of whole proteomes.

The Proteome Analysis database (http://www.ebi.ac.uk/proteome/) has been developed by the Sequence Database Group at EBI utilizing existing resources and providing comparative analysis of the predicted protein coding sequences of the complete genomes of bacteria, archeae and eukaryotes. Three main projects are used, InterPro, CluSTr and GO Slim, to give an overview on families, domains, sites, and functions of the proteins from each of the complete genomes. Complete proteome analysis is available for a total of 89 proteome sets. A specifically designed application enables InterPro proteome comparisons for any one proteome against any other one or more of the proteomes in the database.

Applications of InterPro in protein annotation and genome analysis.

The applications of InterPro span a range of biologically important areas that includes automatic annotation of protein sequences and genome analysis. In automatic annotation of protein sequences InterPro has been utilised to provide reliable characterisation of sequences, identifying them as candidates for functional annotation. Rules based on the InterPro characterisation are stored and operated through a database called RuleBase. RuleBase is used as the main tool in the sequence database group at the EBI to apply automatic annotation to unknown sequences. The annotated sequences are stored and distributed in the TrEMBL protein sequence database. InterPro also provides a means to carry out statistical and comparative analyses of whole genomes. In the Proteome Analysis Database, InterPro analyses have been combined with other analyses based on CluSTr, the Gene Ontology (GO) and structural information on the proteins.