The aim of this assessment was to analyse the current scientific knowledge and the situation of genetic counselling on predictive genetic testing for hereditary breast and colorectal cancer.
Predictive genetic testing will be available for several common diseases in the near future and questions related to reimbursement and quality assurance will be raised.
This report is based on non-systematic literature research using several databases (e.g. EmBase, Medline, Cochrane Library) and on a CCOHTA-assessment or US-review (American Gastroenterological Ass.). In addition to the scientific basis on genetic testing, the different diagnostic test methods, the benefit of early detection methods and prophylactic interventions are described and analysed in the context of individual/familial and social consequences.
Breast and colorectal cancer are among the most frequent cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gen is responsible for the increased cancer risk. In these families high tumour frequency, young age at diagnosis and multiple primary tumours are striking.
von hereditären Krebssyndromen stellen auf Grund der raschen neuen Informationsgewinne eine Herausforderung dar. Die Beweislage ist oft unvollständig und von begrenzter Qualität. Zur objektiven Ergebnispräsentation sind u. a. Angaben zu Sensitivität, Spezifität sowie positiv prädiktivem Wert (PPW) der jeweiligen Labortestmethode bzw. Früherkennungsuntersuchung sowie die Angabe der „Number Needed to Treat“ (NNT) für chirurgische Interventionen erforderlich.
Weitere Mutationsidentifizierungen und Assoziationen mit bestimmten Erkrankungen sowie auch der Trend zur Bedarfsweckung wird in den nächsten Jahren zu einer Ausweitung der prädiktiven genetischen Beratung und Diagnostik führen. Problematisch erweist sich die größer werdende Kluft zwischen möglicher genetischer Diagnostik und den begrenzten Vorhersage, -Präventions-, Früherkennungs- bzw. Therapieoptionen. Dies erfordert eine vorausschauende Strategieplanung mit einem Konzept und klaren Rahmenbedingungen. Denn den besonderen Chancen, die durch die prädiktive Diagnostik realisiert werden können, stehen hohe Qualitätsanforderungen und die Gefahr von Missbrauch gegenüber. Das Aufzeigen von unterschiedlichen Interessen und deren Konsequenzen erscheint wichtig.
Auch Journalisten tragen wesentlich zur Information und Stellenwertbesetzung der prädiktiven genetischen Diagnostik in der Gesellschaft bei. Die (heutige) Betonung der genetischen Testung beruht auf falschen Metaphern über die Rolle, die der DNA und den Genen zukommt. Mitbestimmen setzt ein gewisses Maß an Mitwissen voraus! Eine aktive Beteiligung der Bevölkerung an gesellschaftspolitischen Entscheidungen wäre in Österreich ein weiterer Schritt auf dem Weg zu einer differenzierten Ausseinandersetzung mit den Konsequenzen der Gentechnologieforschung.
This project has been co-funded by the 'Fonds Gesundes Österreich'.
Predictive Genetic Testing for Hereditary Breast and Colorectal Cancer An Assessment Aim and Methods • The aim of this health technology assessment was to analyse the current scientific and genetic counselling situation about predictive genetic testing for hereditary breast and colorectal cancer. Predictive genetic testing will be possible for several common diseases in the future and questions related to financial issues and quality standards will be raised. • This report is based on a systematic literature research using several databases (e.g. EmBase, Medline, Cochrane Library) and on a specific health technology assessment (CCOHTA) resp. review (American Gastroenterological Ass.). Laboratory test methods, early detection methods and the benefit from prophylactic interventions were well directed analysed and social consequences were interpreted. Background • Breast and colorectal cancer are counted among the most frequently cancer diseases. Most of them are based on random accumulation of risk factors, 5-10% show a familial determination. A hereditary modified gene is responsible for the increased cancer risk. In this families high tumour frequency, young age at diagnosis and multiple primary tumours are remarkable. Results and Reflection • Genetic diagnosis: The sequence analysis is the gold standard. Denaturing high performance liquid chromatography is a quick alternative method. The identification of the responsible gene defect in an affected family member is important. If the test result is positive there is an uncertainty about if the disease will occur, when and in which degree founded in the geno-/phenotype correlation. The individual risk estimation is based upon empirical evidences. The test results have effects on the whole family. • Prevention/early detection: At the moment primary prevention is possible for familial adenomatous polyposis (celecoxib, prophylactic colectomy) and for hereditary mamma carcinoma (prophylacti
Immunoglobulins in Transplant Medicine Prevention and Therapy of Cytomegalovirus Infections An Assessment Background Cytomegalovirus (CMV) infections are one of the most common infection complications of transplant recipients. In immune competent persons CMV infections are usually asymptomatic but in immune compromised patients there can be fatal consequences. CMV infections are linked to graft dysfunction and graft loss. The most favourable prophylactic treatment/therapy regime and the starting point of the intervention are under long lasting discussion. Aim and Methods The aim of this health technology assessment (HTA) was to analyse the clinical effectiveness of immunoglobulins (IG) for prevention/therapy of CMV infections in transplant recipients and to compare IG with other prevention/therapy regimes (virustatica, e.g. Ganciclovir) with regard to clinical effectiveness and cost efficiency. This assessment is based on a systematic review and a meta analysis. Additionally basic knowledge on CMV infection, frequency of transplantations and cost issues are analysed. Results • With IG there is a significant reduction of CMV infections and diseases in comparison with placebo or no prophylactic treatment/therapy. • A comparison of effectiveness based on a systematic review and meta analysis gives no evidence that IG are more effective than virustatica. There is also no evidence for additional effects of IG in antiviral therapy. • A review of cost-efficieny/clinical effectiveness studies shows that virustatica are the most cost efficient option for prophylactic treatment/therapy of CMV infections. Conclusio Before clinical symptoms appear the avtive CMV infection can already be diagnosed by laboratory tests. This allows for a combined CMV management consisting of risk adapted prophylactic treatment in high risk groups and the start of preemptive therapy. For risk evaluation the most important citeria are: CMV an
10/2001 - 03/2002