J. J. Cassiman Genetic testing services in is Professor in Human Genetics and Developmental Biology, Europe: Quality assurance and heads the Laboratory for Human Mutations and and policy issues Polymorphisms ± Center of Human Date received "in revised form): 12th October, 2001 Genetics at the University of Leuven. He is also coordinator of the EU "FP5) Jean-Jacques Cassiman, Alastair Kent, Glenn Miller, Peter Miny supported Thematic Network on Cystic and Erik Tambuyzer Fibrosis, and the RTD project CF-Pronet.His research mainly focuses on genetic testing, cystic ®brosis and Abstract The popular press is painting a picture of a future in which everyone has a tumour biology. detailed DNA pro®le of themselves drawn up.Such a vision of the future, however, is more science ®ction than science practice.Predictive tests for complex diseases and Alastair Kent cancer, eg colon cancer and breast cancer, are increasingly being used, and the related, is the Director of the and important, genetic counselling may become complex and comprehensive. Genetic Interest Group "GIG) Ð the UK alliance Quality assurance in genetic testing for both cytogenetics and molecular genetic of charities and support testing in Europe is also described.The quality of genetic testing in Europe could be groups for people affected by genetic substantially improved, and before a genetic test is accepted as a routine diagnostic or disorders.GIG's mission prognostic procedure it should have proven clinical utility.Pharmacogenetic testing is to promote the looks at the ef®cacy of medicines and their side effects on patients and patient groups, development of the scienti®c understanding and is increasingly being used to develop better targeted medicines. of genetics and the part Genetic testing services and genetic counselling are structured in different ways in that genetic factors Europe, and organisation and reimbursement differ among European countries. play in health and disease, and to see the Quality and non-directive genetic counselling must be made an integral part of quality speedy transfer of this genetic testing services, and be suf®ciently reimbursed.European networking and new knowledge into identi®cation of reference centres for quality-based diagnostic testing of genetic improved services and support for the diseases should be encouraged.Reimbursement within Europe for sample forwarding treatment of currently should be adapted to allow samples to be tested in countries other than the country of incurable conditions. Prior to joining GIG, origin of the patient. Alastair worked for a number of voluntary Keywords: genetic testing, quality assurance, counselling, pharmocogenetics, patients, society organisations on issues concerning policy, service development and disabled people. Introduction it is mapped and understood will allow such a deterministic vision of our future to The popular press is painting a picture of a materialise), the complexity of the future in which everyone has a detailed technology and the sophistication of Erik Tambuyzer Genzyme Corporate Affairs DNA pro®le of themselves drawn up, useful healthcare systems that would need to Europe, for disease prediction and treatment handle the sheer volume of information Interleuvenlaan 5, selection now and throughout their lives. generated for each of the 350 million citizens B-3001 Leuven, Quite apart from the scienti®c improbability of the , put such a vision of

Tel: ‡32 16 40 15 50 of this scenario it is extremely unlikely that the future ®rmly into the realm of science Fax: ‡32 16 40 03 91 genetic information no matter how carefully ®ction, not science practice.

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Glenn A. Miller On the other hand, genetic testing has becoming available and only a limited is Associate Scienti®c been used since the 1960s for both prenatal number of diagnostic kits are commercially Director of Genetics and postnatal applications. Genetic tests can available, mainly for well-characterised Applications at Genzyme.His be performed on clinical samples diseases with well-studied mutations which laboratory carries out originating from a foetus prenatal testing), have been identi®ed years ago. In addition, genotype/phenotype on early embryos pre-implantation testing) many different DNA defects can be correlation studies for or on children and adults postnatal testing). responsible for the same or similar clinical internal therapeutic programmes, genetic Cytogenetic testing, ie chromosome analysis symptoms, and these defects may even have analysis for the on dividing cells from amniotic ¯uid or different regional frequencies in Europe. selection of appropriate other clinical samples, visualises This further complicates standardisation of protein replacement therapies as well as chromosome abnormalities such as procedures or kits. Diagnostic methods for contract research in trisomies ± three chromosomes of the same genetic testing are no longer used collaboration with type instead of two ± translocations or exclusively in genetic laboratories. The biotechnology and deletions. Cytogenetics is also being used in identi®cation of changes in DNA, RNA and pharmaceutical partners. the diagnosis or con®rmation of cancer and proteins relevant for the diagnosis and can be complemented by newer molecular therapy of somatic diseases, such as cancer cytogenetic techniques, including FISH and infections, has created a large number Peter Miny ¯uorescent in situ hybridisation) or CGH of additional applications of these is Associate Professor of comparative genome hybridisation) for methodologies in practically all medical Human Genetics at the University of Basel.He more subtle changes in the chromosome specialties. As a result, they have also is Vice Head of the structure or for studies on non-dividing become basic tools for most clinical Division of Medical cells. chemistry and clinical biology laboratories. Genetics at the Since the 1990s, molecular genetic testing, Another area that is growing rapidly is University Children's Hospital Basel and looking for deleterious changes in human pharmacogenetic testing. This technology responsible for the genes, has increasingly been used to detect tests the ef®cacy of medicines and their side cytogenetic laboratory gene defects. Such molecular testing studies effects on patients and patient groups, and and the prenatal diagnosis programme. changes in the composition or structure of is increasingly being used to develop better Dr Miny is also Medical DNA, RNA or even proteins using targeted medicines. The potential Director of Aristogen molecular techniques, such as polymerase consequences of pharmacogenetics on the GmbH, Ingelheim, chain reaction PCR), quantitative PCR, development of medicines from a research, Germany. mass spectrometry or sequencing. These clinical trial, regulatory process and methods are all different ways of detecting marketing point of view are staggering. Erik Tambuyzer changes in the composition of genetic is Genzyme material. Single gene disorders, caused by Corporation's Vice defects in a single gene resulting in the President, Corporate Clinical use, counselling, Affairs Europe, and a absence of a critical protein or the presence regulation for genetic testing and member of the of an abnormal protein, are being searched accessibility European Board of for and diagnosed with the help of such Genzyme.He started his techniques. Cystic ®brosis, for example, is a professional career at Before a genetic test is accepted as a routine Baxter Health Care, rather rare condition, but presents itself diagnostic or prognostic procedure it should followed by Innovi NV. through more than 900 mutations, most of have clear clinical utility, meaning that the He co-founded the them very rare, with a frequency of much test should help the medical staff in biotechnology company Innogenetics less than 0.1 per cent of all diagnosed cases diagnosing and treating or counselling a NV in 1985, of which he in the population. Many other so-called patient. Providing diagnostic or predictive remained General multifactorial disorders also have a genetic genetic testing is not just the provision of a Manager until 1992.In component, which may involve several test result to a doctor or a patient, but October 2000, Dr Tambuyzer was elected genes interacting with an individual's should also include, depending on the Chairman of the Board lifestyle or living environment. disease being looked at, the provision of of EuropaBio, of which Some of the methods used in genetic non-directive and professional genetic he is also the Founder testing have been or are being automated, counselling to the patient and sometimes and Chairman of the Ethics Committee. but many must still be performed manually. family members. For genetic testing, the Indeed, automation is only gradually decision to test and the evaluation of its

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results should always occur in the context of ESHG) is currently calling for this a genetic counselling session. recognition. Predictive tests for complex diseases and cancer, eg colon cancer, breast cancer, are increasingly being used, and the related counselling may become complex and Organisation and reimbursement comprehensive. The correct meaning and of genetic testing consequence of the test will have to be explained in detail to the individual if they Samples to be analysed can be referred to a are to understand its precise meaning or testing laboratory, when available. limitations. The knowledge of genetics in Depending on the expertise and the the general population and even in the equipment of the laboratory, some medical profession is still very limited. Over laboratories will test for all possible the counter testing or testing on the request variations and mutations a particular gene of a physician who does not grasp the full while others will only test for a limited set of signi®cance of a test result could have mutations. For many rare diseases, serious consequences for a patient. however, the prevalence is so low that no Therefore, counselling is an extremely expertise can be found in the immediate important part of the process of explaining a geographical vicinity, or the equipment and test result to a patient, determining the way expertise may not allow a local laboratory to they may cope with a test result, and should provide a full investigation. In that case, the be valued as such in the healthcare system clinical sample must be forwarded to of tomorrow. Since these counselling another laboratory. In view of the many sessions are essential but also expensive, in inherited and somatic diseases that are view of the time spent with the counsellee, it being identi®ed more than 1,000 at present is becoming very important to provide and 11,000 more to come1), based on suf®cient and appropriately trained intensive research efforts and on the recent counsellors and ®nancial support. publication of the Human Genome Genetic services and molecular genetic Sequence, it has become almost impossible testing laboratories in particular are for any single laboratory to provide testing structured in different ways in Europe. In for all identi®ed diseases. Samples are some European countries, eg in Benelux, the therefore being sent to specialised services, including genetic counselling, are laboratories in Europe or in the USA. For restricted to genetic centres that offer `total' diagnostic samples, such networking is very care to the patients and their families. dif®cult, because of the different legislation Access to these facilities is either through and related reimbursement in each the family physician or directly via the European country. Some countries, such as geneticist. In other European countries, such France and the Netherlands, forbid as Germany, only speci®c aspects of the diagnostic testing of patient samples outside services are regulated, eg genetic their borders, or do not reimburse such counselling or some aspects of prenatal testing services. diagnosis, while all other services are The lackof reimbursement for genetic provided by whomever wants to provide it. testing, when done in a country other than Finally, many European countries have no the country of residence or social security regulations and as a consequence, `self- subscription of the patient, based on made' geneticists, with or without geography, hampers equal availability of experience or training, with or without good genetic testing services to all citizens quality control, provide services. The even within the EU. In some European majority of the European countries do also countries, such as the UK and the not recognise the specialty of human Netherlands, genetic testing when done genetics as a separate medical specialty, so within the national healthcare system is the European Society for Human Genetics fully reimbursed as part of the overall

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health services to the regional population. In assures consistent evaluation of genetic test other countries each type of test is information before it is provided to the reimbursed at a speci®c rate by the national patient. health insurance system. This may or may The quality control programme installed not include a restriction to have the testing in the UK is probably the best known in done in a genetic laboratory and to have the Europe. In this paper, Germany is used as patient pay a rather symbolic personal an example of a country where quality contribution. Also of increasing importance assurance and quality control QA/QC) are efforts to determine reasonable measures in genetic testing services are reimbursement rates for adequate genetic required by law and implemented by the counselling, because in Europe, counselling scienti®c societies or professional is not always part of what is reimbursed organisations. A formal quali®cation while it is an extremely important part of specialisation in human genetics) is the package. required for medical doctors as well as for Some private insurance systems will PhDs in the provision of genetic testing cover public or private testing while others services in Germany. This is a direct will not, and some will cover testing in a consequence of the inclusion in German foreign country while others will not. It is social legislation book5) of QA/QC as a clear that there are about as many systems permanent commitment to genetic testing as countries in Europe and that depending service providers. According to on where one lives a service can be recommendations of the Federal Medical available, partially or fully covered or not at Council, an external quality assessment all. In other countries, outside the EU, the scheme for cytogenetics was established as a USA and Japan, major problems may either pilot project in the late 1980s and introduced be the cost of the testing, incomplete or total nationwide in 1993. The quality of the lackof reimbursement, or the availability of chromosome preparation is assessed by a a counselling centre located suf®ciently commission using a scoring system close to the families in need. developed by the British Association of Clinical Cytogeneticists.2 In addition, the turn-around time TAT) for cytogenetic Quality assurance in genetic analysis of a sample is recorded. At present testing there are more than 80 participating laboratories. Cytogenetics In accordance with activities to harmonise Cytogenetic testing, although existing since standards and guidelines within Europe3 an the 1960s, demonstrates no uniform quality exchange of ideas and/or collaborations in Europe. The number of cells being looked with several countries including at per sample, the banding quality and the Switzerland and Austria is beginning. turn-around time are not standardised, and Observations based on the past ten years no minimum European quality norms are following the introduction of the German set. In addition, many small laboratories QA/QC scheme for service cytogenetics performing cytogenetic testing all over include increased quality of pre- and Europe only see a few abnormal cases per postnatal chromosome preparations and no year, which raises concerns about the apparent difference in quality between experience level of the personnel academic and private laboratories, while performing the testing. Quality turn-around time for private laboratories is improvement is possible at the laboratory somewhat shorter. level, by quality testing of reagents, by installing standard laboratory operating Molecular genetic testing procedures and appropriate quality assurance protocols. Additionally, the The limited number of studies performed to clinical genetic training of physicians date have clearly shown that the quality of

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molecular genetic testing in Europe could be disease type and by year, not correlating substantially improved. The lackof stable with the technical dif®culty of a particular positions and training of academic test. For cystic ®brosis for example, in the personnel due to vagaries of funding, and year 2000 there were eight diagnosis errors the lackof standard laboratory operating and one report error in 288 cases. In general, procedures in academic settings contribute for all diseases, some of the errors appeared to the issue. Two initiatives have been to result from inadequate internal quality funded by the European Union to organise management, while other errors originated quality assessments. The European from the application of non-validated Molecular Quality NetworkEMQN), a methods or inadequate reporting. Errors project funded by the EU to set up pilot were not found to cluster in a small number studies for external quality assessments of of `incompetent labs' but also affect facilities laboratories involved in genetic testing as considered experienced. There is a tendency well as to draft best practice guidelines for towards improvement in quality of these tests, has shown in its three year molecular genetic testing, although this is existence that molecular testing for not easy to quantify. The development of Huntington disease, fragile X, breast cancer guidelines in addition to those already in and a series of other diseases is subject to existence and good laboratory practices unacceptable error rates with dramatic GLP) workshops were helpful in improving consequences for the tested individual, and the quality of genetic testing. Horsthemke4 can be improved with appropriate quality raised concerns about the performance of assurance programs. As a further example, the participating German laboratories the Cystic Fibrosis Thematic Network, speci®cally with respect to methylation ®nanced by the FrameworkV programme assays and microsatellite analysis, reporting of Directorate General Research of the an overall error rate of approximately 8 per , has organised cent since 1998. external quality assessments for close to 200 To our knowledge, comparable ®gures do laboratories in Europe over the past ®ve not exist for other regions. From these years. Initially, more than 30 per cent of the European assessments it has become clear laboratories made technical errors in the that there is also an international need for assessments. Through training and testing standards. Indeed the absence of information, this error rate has dropped in standards prevents unequivocal validation the past two years to approximately 6 per of commercial or home-brew diagnostic cent. tests. For this reason, the EU has decided to Within Germany, national quality fund a four-year project to develop such assessment schemes for molecular genetic standards the CRMGEN project), planned testing were introduced in 1994. At present to start late in 2001. In addition, further there are 11 disease-speci®c programmes training and systematic external quality chaired by individuals with proven assessments will be required to bring expertise acting in collaboration with a genetic testing services up to an acceptable commission of the Professional level. It will undoubtedly be necessary to Organisation for Medical Genetics covering install some form of laboratory accreditation the most important laboratory methods. at the national and preferably at the DNA samples are sent to the participating European or even international level. This laboratories and testing as well as reporting was also recognised during a workshop performance is assessed using a numerical organised by the Organisation for Economic scoring system. The experience of the past Collaboration and Development OECD) in ®ve years shows a number of common Vienna, Austria in February 2000.5 factors. These common factors include at Accreditation, if designed speci®cally for least one misdiagnosis in all schemes, with genetic testing laboratories, will clearly the exception of myotonic dystrophy, and, identify laboratories that can provide a unexpectedly, an error rate, different by reliable diagnosis, and an acceptable and

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reasonable turn-around time. Staff affect the ultimate utility of the information competency testing, incident tracking being derived. systems, performance measures, quality The introduction of testing intimately tied control monitoring and a follow-up to therapeutic administration is already a programme comparing laboratory results to reality with testing for Her2 determining patient outcomes will help assure accurate HerceptinTM administration in the treatment testing. Accreditation and accurate testing of breast cancer, and bcr/abl analysis may also help to solve the matter of playing an important role in the selection of reimbursement and networking between GleevecTM therapy for chronic myelogenous accredited laboratories, since the different leukaemia. The number of these types of countries would not be able to invoke tests will inevitably increase over time, quality as a reason not to allow testing in while the range of test types will include another country. Moreover, regional immunohistochemistry, single nucleotide reference centres with proven expertise for polymorphism analysis, standard the identi®cation of particular genetic cytogenetic analysis and in situ defects could be identi®ed in such a system. hybridisation. The identi®cation and announcement of markers linked to therapeutic selection, diagnosis, prognosis or predisposition will outstrip the current Pharmacogenetics:potential and ability of the medical community to consequences critically evaluate the clinical utility of each marker. Without appropriate quality Mechanisms of disease, individual genetic assurance methods, test validation variation, therapeutic response and genetic procedures and guidelines, the genetic predisposition will all be the bene®ciaries of assays of real value will be mixed with those the knowledge developed as the result of that have little or no value. Such an outcome the Human Genome Project HGP). The use will be contrary to the goals society put to which this information is ultimately put forward for the Human Genome Project. will decide the true value of this huge The role that broad population-based project. The impact of this information ¯ow genetic testing for the purpose of providing on drug development will signi®cantly a DNA pro®le will play in the future is change how new drugs are registered and unclear. The position taken by genetic how existing therapies are used. It is testing laboratories concerning the provision unlikely, at least in the foreseeable future, of genetic information has traditionally been that one's entire genetic makeup will be to test only for speci®c conditions or recorded for clinical use. As discussed markers as requested by a quali®ed medical earlier, the use of genetic information to professional. This limits the inadvertent provide better care has been in regular discovery of genetic information that may practice for decades. The fact that impact an individual in ways not individuals respond differently to drugs, anticipated when the decision to have even to the extent that people may die as a testing performed was made. Current consequence of drug side effects, has been medical practice is unlikely to support the part of common medical practice for over provision of unsolicited information when half a century. Using the new information, there is no available treatment or prevention the pharmaceutical industry routinely tests plan beyond counselling lifestyle changes. clinical trial populations for variants in drug In addition to the dif®culties inherent in metabolism genes that augur severe adverse performing testing without a speci®c reactions. The increase in information outcome, the current level of technology provided by the genomic revolution is does not support this type of testing. If one resulting in a greater number of genetic tests postulates a hypothetical US$200m drug valuable in predicting individual response and links a genetic test to the administration to therapy. The quality of such testing will of that drug, the number of tests required

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for new prescriptions per year could be in The pressure on the medical community to the range of 200,000. This would be nearly incorporate genetic information in their double, for example, the current number of selection of treatment options will come cystic ®brosis tests performed annually in from scienti®c advances, the pharmaceutical the USA prior to population screening. If industry, regulatory agencies and the this pattern were repeated for a number of public. The incorporation of genetic tests drugs, the ability of the genetic testing and genetic information in clinical trials and community to perform such testing would treatment provision will have a signi®cant be rapidly exceeded. The incorporation of and long-lasting impact on the practice of this type of genetic testing into routine medicine. clinical practice will require the development of novel technologies having the accuracy and reliability assumed as a Bene®ts and risks, industry standard for other routine clinical laboratory involvement and societal issues tests. The propagation of such testing will require clinical trials to validate the Genetic tests are undoubtedly of major accuracy and reliability of the markers as value in the medical diagnosis of genetic well as the laboratory procedures that are disorders, especially since many disorders involved. seem to have a genetic component. Prenatal Appropriate quality assurance methods testing provides valuable information to will also be necessary for the effective assist women in making an informed development of pharmacogenetic testing decision about their pregnancy. The procedures in the future, thereby again provision of rapid, accurate information is pointing to the needs identi®ed for of crucial importance for these women, diagnostic genetic testing. The identi®cation making turn-around time one of the of a marker thought to be clinically relevant performance indicators for prenatal testing. is but the ®rst step in a process. Postnatal diagnosis provides con®rmation Establishment of relevant clinical data of diagnosis, or may be used in a predictive demonstrating the value of the marker and way. The provision of predictive genetic peer-reviewed publication of that testing when insuf®cient clinical data are information is essential prior to the available for a test, or for a disease for which acceptance of the marker. The evaluation of no cure yet exists, may raise ethical issues. the marker by a peer-reviewed publication Another ethical issue may be related to the method is a valuable part of the process in issue of informed consent: indeed a patient the widespread adoption of a clinical should be fully informed about the test and genetic test. This process avoids endless its consequences before consenting to it, and repetition of clinical trials by each provider has the right to refuse to undergo testing. In and allows the widest possible review of the addition, society should use genetic test data. Once the value of a marker has been results con®dentially and at the least with established, each laboratory considering the same care as other medical information. provision of such a testing must consider This means that one has to avoid negative the design and implementation of the assay discrimination based on genetic test data, eg in the context of appropriate quality and for insurance or employment. design control. The development of In some European countries, such as standard procedures within each laboratory Germany, Switzerland, Italy and Spain, for assay selection and design control will genetic testing is increasingly being be essential as the number of tests being performed by private organisations. introduced increases. Responsible private providers are also While the level of genetics expertise in the concerned about the issues of privacy, medical community needs to improve con®dentiality and negative discrimination, dramatically, genetic testing is beyond any and have been participating, and will doubt an area of signi®cant future growth. continue to participate, in the dialogue to

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create policy for these issues. In recognising predisposition to frequent societal diseases, the sensitivity of the area, responsible such as diabetes, osteoporosis, asthma, industry players involved in genetic testing rheumatic disease, psychiatric diseases, as a whole have been fairly cautious in Alzheimer's and Parkinson's, among others. introducing new genetic tests. In addition, Clearly, the available facilities for genetic informed consent and education of patients testing will soon drown under the requests. and physicians have been and will continue If at that time no European consensus has to be taken seriously by them. Responsible been reached about how all this testing will industry also understands the need for high- be done and how it will be ®nanced, the quality counselling services as part of the rights of patients are at serious riskand total service package.6 negative discrimination will ¯ourish. The One unusual feature of the genetic testing has created a services is that the few industry players ®nd Temporary Committee on Human Genetics themselves competing with non-pro®t and other New Technologies in Modern organisations. Still, industry believes that, Medicine, to lookat these issues, and is because of its organisational expertise and organising hearings with experts and with standard operating methods, it is well the civil society to discuss them.7 placed to provide high-quality genetic Indeed, following the decision in the UK testing services, which are rigorously to extend the Human Fertilisation and quality controlled. In order to do so, Embryology Act 1990) to allow the use of partnerships with academia, with patient human embryos in tightly de®ned research, groups and with healthcare systems may the European Parliament passed a emerge in the future. resolution that sought to deny access to EU It is clear that genetic testing and related funding to those institutions where workon issues may have an impact on the human embryos was undertaken. In the fundamental rights of any individual. Full debate around this proposal a decision was access to genetic tests when these are of the taken to set up a special committee of utmost importance to obtain a correct Parliament members to examine the ethical diagnosis, to determine the riskto develop a and social consequences of development in particular disease, to determine a carrier human genetics and modern medicine, status or to be able to start an appropriate which were perceived to be potentially treatment, should indeed be considered as a problematic. This committee is due to report basic right. Poor quality of test results will to the plenary session of the Parliament in have dramatic consequences for individuals, November 2001. who are erroneously identi®ed or not Like all European Parliament committees identi®ed as carriers of gene defects that are the temporary committee on genetics life-threatening, or who make the decision includes members from across the political to stop a pregnancy. Inaccessibility of the spectrum. Its terms of reference give it service because of ®nancial reasons is almost complete freedom of action to pick discriminatory, while refusal to send a and choose the issues that it deems to be of sample to a foreign laboratory for regulatory signi®cance and that it chooses to address. or ®nancial reasons is irresponsible. These In order to produce a draft resolution, issues will become gradually more members of the committee held a series of important as the number of inherited open meetings at which they heard evidence diseases that can be tested increases. Also, from a range of interested parties, the rapidly increasing applications of the representatives of whom were invited to same methodology in sporadic or acquired make written and oral presentations to the somatic diseases, such as cancer, leukaemia committee. Among those invited were and infectious diseases, will necessitate a academic scientists, doctors, representatives better organised laboratory service than in of the biotechnology and pharmaceutical the past. Moreover, the not-too-distant industries and delegates from patient future will bring testing for the genetic support groups, disability organisations,

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religious bodies, women's groups and they will not be the last word on this others. Those selected were inevitably important subject. determined by reference either to contacts known to the committee members and or its secretariat or those suf®ciently `on the ball' The patients to make their presence and their wish to contribute known. Given the task facing the Try to put yourself in the position of committee, the time-scale allowed it by the someone receiving genetic information. European Parliament and the resources People do not decide to go to get tested on available for it to undertake its task, it may the spur of the moment. It is not a `What be easy for critics of its workto pickholes in shall we do today ± go shopping or get my both the process and the outcome which at DNA analysed?' type of decision. Rather the the time of writing is still to be determined). need to know what might be in your genes However, it is clear that the robust approach arises because some external event creates of the chair, Robert Goebbels will go a long anxiety about your current or future health way towards preventing the Committee's or that of your unborn) child. procedures being hijacked by vested It may be that someone knows of a interests either uncritically in favour of disease such as cystic ®brosis in her family science or unreasonably opposed to the new and wishes to ®nd out if the baby she is knowledge arising from genetic research going to have will be affected. It may be that and its application for the resolution of her mother and her mother's sister both complex medical, social and ethical issues. died of breast cancer in their 40s or it may Among the dif®culties facing the be for some other serious reason that a members of the Committee is the need to person ®nds himself in the situation where beware of seeking unity when diversity is the need to know exerts itself. Whatever the more legitimate, particularly with regard to precipitating event it is likely that the ethical questions. There is no general circumstances that create the need to seek European ethic on genetics and attempts to genetic testing will be seen by the patient develop one are likely to result in with a certain degree of stress and a high statements that are either so bland as to be degree of concern. This being the case worthless or so rigid as to be unacceptable. people are likely to approach the acquisition The members of the committee will, it is to of genetic information with feelings of be hoped, recognise that there has been a anxiety ± possibly even fear about what due process undertaken in some of the they may be going to ®nd out ± uppermost. member states and that decisions taken have Coupled with the fact that most people have a validity in that member state. little understanding of genetics and where The report of the Committee's the limits on genetic prediction may deliberation and the resolutions that it realistically be drawn and a situation is passes will eventually form a background to created where stress and uncertainty considerations by the Parliament and the predominate. So what do people expect of Commission for decisions to be taken in the test procedure? What helps them to respect of, for example, the Sixth make the best of the situation in which they FrameworkProgramme. In a fast-changing ®nd themselves and empowers rather than ®eld such as genetics it must be recognised disables them? They need to be able to make that any report and recommendations will informed choices, rather than being pushed have a limited shelf-life and that new along by chance ± even if this means knowledge may alter perceptions choosing the least worst outcome, rather signi®cantly. Hopefully the wisdom of the than a good one. In such a situation patients members of the committee and of the need reliability of test results and honesty: European Parliament as a whole will ensure clear and unambiguous information. They that no matter how helpful or otherwise the want an accurate test and precise committee's resolution in the short term, communication of information in a way that

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is appropriate and usable, not clouded by professionals. What patients do care about is too much jargon. the context in which the outcome of testing The language of DNA is commonplace in is to be delivered and the access to society, yet investigation often reveals that information advice and support from a this apparent genetic literacy conceals a diverse range of sources if they wish to deep well of confusion and access them) that is facilitated for them. If misunderstanding about genetics. The this goes well then information, even if it is apparent precision of DNA-derived results, fundamentally bad news ± `I'm very sorry rightly or wrongly ± often fuelled by media Mrs Smith, but the test results are positive images of the accuracy of forensic uses of and you do have the mutation' ± can be DNA evidence in serious crimes ± may dealt with and assimilated in such a manner mean that many place a higher value on the that people can make good decisions that predictive value of the result than is they feel to be right for them. A quality warranted. After all, if DNA analysis can genetic testing service will be set up in such tell that there is only a one in a million a way as to ensure that this happens to the chance that a person whose DNA matches fullest possible extent. that at a crime scene is not guilty, then surely it can tell me whether I'm going to Conclusions get breast cancer or not? Communicating uncertainty is dif®cult and there is no With the progress of the Human Genome absolutely guaranteed method that will Project, more and more pre- and postnatal workevery time. As a consequence a variety genetic tests are being developed with of different strategies must be employed to diagnostic or predictive impact. These tests ensure mutual comprehension. are likely to play an increasing role in the Yet it is important to be clear in the provision of healthcare and related services. message given or people will not be able to Genetic testing therefore comes under the use this new knowledge and make spotlight of society through press coverage decisions. It is also important to be clear on the patenting of genes, the relationship about what test results do not tell you. between genetic test results and life Knowing what inferences you cannot draw insurance or employment, and by the can be as useful as knowing those you can. relationship with the development of Giving reasons that explain why things are medicines of the future. The main question as they are can also help patients to is and will be how to use these new contextualise and to accept or reject the developments to the bene®t of patients, service being offered. As a general rule it is without negative discrimination or easier to accept reasons for an inability to be stigmatisation, and by providing suf®cient precise that are `real' ± such as the fact that and honest information for the patient to research has not yet discovered a gene that understand what they have learned. causes XYZ condition or the biology does Medical doctors and patients choosing to not workthat way so we cannot tell you ± take advantage of these genetic tests will be rather than those that are `systems driven'. able to make more informed decisions about For patients waiting for a result, the need to health and lifestyle. collect a batch of samples to make analysis It is up to our society and its leaders to `economic' or the fact that a test used to be make sure that the bene®ts offered by available as part of the research programme, technological progress in this ®eld are used but now the project has concluded, is deeply in a positive way and that the quality of the frustrating. genetic tests offered is high. To fail to do so By and large patients do not have strong would open genetic testing to an views about where and how genetic tests environment fuelled by unjusti®ed fears and are done. Organising the service and using misinformation, thus depriving the public of the best available technologies are usually medical knowledge increasingly valuable to thought to be the responsibilities of their health. Therefore, quality assurance of

122 Journal of Commercial Biotechnology Henry Stewart Publications 1462-8732 "2001) Vol. 8, 2, 113±123 Genetic testing services in Europe

genetic testing, and accreditation of genetic tempcom/genetics/intro_en.htm testing laboratories should be organised on # Cassiman, Kent, Miller, Miny and a European or even international level Tambuyzer 2001 before the con®dence of society in genetic testing is badly undermined. Efforts should be increased to ensure that quality and non-directive genetic Bibliography counselling is made an integral part of quality genetic testing services, and is Dequeker, E., Cuppens, H., Doge, J., Stivill, X., Gossens, M., Pignatti, P. F., Scheffer, H., Schwartz, M., reimbursed as part of the package. Schwarz, M., Tummler, B. and Cassiman, J.-J. 2000), European networking and identi®cation of `Recommendations for quality improvement in reference centres for quality-based genetic testing for cystic ®brosis', Eur. J. Hum. Genet., diagnostic testing of genetic diseases should Vol. 8, suppl. 2, pp. 1±23. be encouraged. Reimbursement within Dequeker, E. and Cassiman, J.-J. 2000), `Genetic testing and quality control in diagnostic laboratories', Europe for sample forwarding should be Nature Genetics, Vol. 25, pp. 259±260. adapted to allow samples to be tested in Harris, R. 1997), `Genetic services in Europe', Eur. J. countries other than the country of origin of Hum. Genet., Vol. 5, pp. 1±220. the patient. Finally, participation in national, Loosekoot, M., Bakker, B., Laccone, F., Stenhouse, S. European EMQN) or other quality and Elles, R. 1999), `A European pilot quality assessment scheme for molecular diagnosis of assurance programmes should be Huntington's disease', Eur. J. Hum. Genet., Vol. 7, pp. encouraged for all laboratories involved in 217±222. providing any kind of medical genetic Yan, H., Kinzler, K. and Vogelstein, B. 2000), `Genetic testing services. testing ± present and future', Science, Vol. 289, pp. 1890±1892. Propping, P. 1998), `Genetische PraÈnataldiagnostik± References Brauchen wire eine QualitaÈtskontrolle?', Deutsches 1. URL: http://www.ncbi.nlm.nih.gov/Omim/ AÈ rzteblatt, Vol. 95, pp. 21±22. 2. UK NEQAS 1988), `United Kingdom External XXVIIIth meeting of the European Group on Ethics in Quality Assessment Scheme: Slide assessment Science and New Technologies 2000), `Round table: scoring guide', ACC Clin. Cytogenet. Bull., Vol. 2, Genetic testing in the workplace', , 6th pp. 26±35. March. 3. EUCROMIC quality assessment group 1997), Medizinische Genetik2001), `Of®cial publication of the `Quality guidelines and standards for genetic German and Austrian Societies of Human Genetics laboratories/clinics in prenatal diagnosis on fetal and the German Professional Organisation for samples obtained by invasive procedures. An Medical Genetics', January. attempt to establish a common European framework Held, K. R., Eiben, B. and Miny, P. 2000), `The long- for quality assessment', Europ. J. Human Genet., Vol. term effect of external quality assessment on 5, pp. 342±350. performance in service cytogenetics', Cytogenet. Cell 4. Horsthemke, B. 2001), `Bericht uÈ ber den Genet., Vol. 91, pp. 124±127. Ringversuch 2000 zur molekulargenetischen Held, K. R., Eiben, B. and Miny, P. 2001), `10 Jahre Diagnostikvon Prader-Willi-Syndrom PWS) und QualitaÈtssicherung in der Cytogenetik', Vol. 13, pp. Angelman-Syndrom AS)', Vol. 13, p. 81. 75±77 in German). 5. OECD News Release 2000), `Genetic testing: health MuÈ ller-Reible, C. R. 2001), `Ringversuche zur care of the future?', OECD, Paris, 1st March. molekulargenetischen Diagnostik: Ein 6. URL: http://www.europabio.org Erfahrungsbericht nach 5 Jahren', Vol. 13, pp. 78±80 7. URL: http://www.europarl.eu.int/comparl/ in German).

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