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From: TSS ()
##################### Bovine Spongiform Encephalopathy ##################### 1 © SEAC 2006 SEAC 94/2 EVALUATION CRITERIA FOR ANTE MORTEM DIAGNOSTIC TESTS FOR SUBCLINICAL vCJD ISSUE 1. The UK blood services are preparing a systematic process to evaluate rapid ante mortem diagnostic tests for subclinical vCJD. The Department of Health (DH) has requested SEAC advice on general principles to consider for evaluation of such tests, which could be used by the blood services to develop an evaluation strategy. Ante mortem diagnostic tests for subclinical vCJD could also be used to inform on the prevalence of vCJD in the population and be used in the analysis of potential therapies. BACKGROUND 2. Three cases of probable human transmission of prion infection from a blood donor who later developed vCJD have been reported, providing compelling evidence that vCJD infection can be transmitted via blood transfusion1,2,3. Blood donor exclusion criteria and other precautionary safety measures have been introduced since 1998 to reduce the number of potential iatrogenic cases of vCJD. However, the development of an accurate and sensitive ante mortem blood test to identify asymptomatic individuals infected with vCJD could substantially reduce the potential for transmission of vCJD via blood transfusion and other medical interventions. It could be clinically valuable in confirming the diagnosis of symptomatic cases and monitoring the effect of potential therapies. In addition, such a test could provide an important tool to ascertain better the prevalence of vCJD infections. 3. There are ethical and practical issues associated with ante mortem testing for subclinical vCJD. These have been discussed and comparisons made with testing for other blood borne diseases in Duncan et al4 (Annex 1). Ethical 1 Peden et al. (2004) Preclinical vCJD after blood transfusion in a PRNP codon 129 heterozygous patient. Lancet 364, 527-529. 2 Llewelyn et al. (2004) Possible transmission of variant Creutzfeldt-Jakob disease by blood transfusion Lancet. 363, 411-412. 3 http://www.hpa.org.uk/hpa/news/articles/press_releases/2006/060209_cjd.htm 4 Duncan et al.(2005) Ethical considerations in presymptomatic testing for variant CJD. J.Med Ethics 31, 625-30 2 © SEAC 2006 considerations of ante mortem testing for subclinical vCJD have also recently been considered in detail by the Health Protection Agency. A report on this consideration is expected to be released in Autumn 2006 as well as a wider consultation of the recommendations. A report of the consultation is expected in spring 2007. 4. There are a number of rapid post mortem tests validated by the European Food Safety Authority (EFSA) for transmissible spongiform encephalopathies (TSEs) in animals5. A number of commercial organisations have recently claimed to have developed ante mortem tests that can be used on blood or other easily accessible biological material for the identification of asymptomatic individuals infected with vCJD. However, in the absence of a defined standardised system to evaluate and compare the effectiveness of these diagnostic tests, none has undergone formal independent evaluation and validation. Previous scientific committee considerations 5. SEAC has not discussed the evaluation criteria for diagnostic tests for subclicial vCJD. However, this issue has been discussed in recent reports from the World Health Organisation (WHO)6 and the European Commission’s Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR)7. SEAC provided a response to the SCENIHR report consultation in February 2006. This issue has also been considered by a number of advisory groups to DH and an overview will be provided at SEAC 94. WHO report 6. The WHO report states that: The development of reliable diagnostic procedures to detect asymptomatic subjects during the long periods of incubation of CJD and vCJD is of vital importance. However, test methods must be appropriately validated, and validation requires that appropriate blood reference materials be developed, characterized and made available both to qualified test developers and to regulatory authorities. 5 Raeber & Oesch (2006). Diagnostics for TSE agents. Dev.Biol. 123:313-23 and EFSA scientific reports on the evaluation of BSE/TSE tests. http://www.efsa.europa.eu/en/science/tse_assessments/bse_tse.html 6 World Health Organisation (2006) Guidelines on tissue infectivity distribution in transmissible spongiform encephalopathies. http://www.who.int./bloodproducts/TSEREPORT-LoRes.pdf 7 Scientific Committee on Emerging and Newly Identified Health Risks (2006) Opinion on the safety of humanderived products with regard to vCJD. http://ec.europa.eu/health/ph_risk/committees/04_scenihr/scenihr_cons_02_en.htm 3 © SEAC 2006 Attempts to develop, optimize and validate tests to detect infectivity in blood in experimental and natural TSEs, including BSE in ruminants and vCJD in humans, are now in progress. These very important efforts should be encouraged and supported, both financially and by providing test developers with TSE reference materials and panels of replicate coded and randomized samples, including reference materials of human origin when available. SCENIHR report 7. In considering the available data on ante mortem tests for subclinical vCJD, SCENIHR concluded that: Important advances in test methodologies for prion detection have been made in recent years, and the application of these advances in the diagnosis of vCJD has, in particular, been fruitful. However, no diagnostic system has yet emerged with the high level of sensitivity and specificity required for routine screening of blood or urine. It is essential that confirmatory assays are available, and all ethical implications are considered and carefully taken into account before implementing testing. Independent validation of any new methodology should be mandatory prior to implementation, and it is recommended to adopt the EU procedure used for the BSE testing. For validation carefully controlled vCJD reference materials should be used. However, the availability of blood from individuals at increased risk of vCJD or diagnosed with vCJD is very limited. Therefore, ethical collection of such valuable material should be considered a priority. Special strategies are then needed to evaluate potential blood tests in order to conserve material. Collection of urine should be considered which could be tested when more sensitive tests for abnormal prion protein suitable for testing urine become available. The issue of false positives needs careful consideration, as even minute percentages of these may actually involve a large number of individuals. The ethical issues of informing an individual of test results, without providing any certainty as to the likelihood of progression to clinical disease, should be considered seriously. Diagnostic Tests SNIP...FULL TEXT 32 PAGES ; http://www.seac.gov.uk/papers/94-2.pdf RECALLS AND FIELD CORRECTIONS: BIOLOGICS -- CLASS II ______________________________ PRODUCT END OF ENFORCEMENT REPORT FOR SEPTEMBER 13, 2006 ### http://www.fda.gov/bbs/topics/enforce/2006/ENF00969.html PRODUCT END OF ENFORCEMENT REPORT FOR SEPTEMBER 6, 2006 ### http://www.fda.gov/bbs/topics/enforce/2006/ENF00968.html USA mad cow blood for humans are a dime a dozen, the come out just 14 September 2006 - The agenda and meeting papers for the 94th SEAC meeting on Thursday 21st September have been published. http://www.seac.gov.uk/agenda/agen210906.htm TSS #################### https://lists.aegee.org/bse-l.html ####################
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