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Frauke Becker,
Carla G van El, Dolores Ibarreta,
Eleni Zika,
Stuart Hogarth,
Pascal Borry,
Anne Cambon-Thomsen,
Jean Jacques Cassiman,
Gerry Evers-Kiebooms,
Shirley Hodgson, [......],
Victor B Penchaszadeh,
Andrew Read,
Wolf Rogowski,
Jorge Sequeiros,
Lisbeth Tranebjaerg,
Irene M van Langen,
Helen Wallace,
Ron Zimmern,
Jörg Schmidtke,
Martina C Cornel
European journal of human genetics: EJHG 04/2011; 19 Suppl 1:S6-44. · 3.56 Impact Factor
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Frauke Becker,
Carla G van El, Dolores Ibarreta,
Eleni Zika,
Stuart Hogarth,
Pascal Borry,
Anne Cambon-Thomsen,
Jean Jacques Cassiman,
Gerry Evers-Kiebooms,
Shirley Hodgson, [......],
Victor B Penchaszadeh,
Andrew Read,
Wolf Rogowski,
Jorge Sequeiros,
Lisbeth Tranebjaerg,
Irene M van Langen,
Helen Wallace,
Ron Zimmern,
J|[ouml]|rg Schmidtke,
Martina C Cornel
European Journal of HumanGenetics 03/2011; · 4.40 Impact Factor
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ABSTRACT: In order to ascertain data availability and feasibility for conducting cost-effectiveness studies in pharmacogenetics, and as part of a European Commission Joint Research Center, Institute for Prospective Technological Studies (JRC-IPTS) study, data concerning risperidone use and cytochrome P450 (CYP2D6) genotyping in medical care was collected in Germany, Spain and the USA, and are summarized in this perspective. The gene coding for CYP2D6 is highly polymorphic, resulting in a significant part of the population being poor metabolizers and ultrarapid metabolizers. Individuals who are CYP2D6 poor metabolizers, have an increased risk of adverse drug reactions (ADRs) when treated with CYP2D6-metabolized drugs, suggesting that CYP2D6 genotyping might be beneficial for patient care. This might be especially important in psychiatry, where approximately 50% of the patients use at least one drug primarily metabolized by CYP2D6. In particular, ADRs and poor response to treatment are major problems for some antipsychotics, including risperidone. However, there are no published cost-effectiveness studies on CYP2D6 genotyping, and the benefit that pharmacogenetic testing might represent by identifying problematic patients is still unclear. The present European Commission study found that current clinical and economical data concerning the frequency and direct healthcare costs of risperidone-related ADRs, the relation of such ADRs with the patients CYP2D6 genotypes, and costs for CYP2D6 genotyping, are not sufficient for determining if routine CYP2D6 genotyping might be cost beneficial for patients treated with risperidone. Therefore, efforts should be put on performing prospective cost-benefit studies with randomized treatment according to the CYP2D6 genotype to establish the utility of CYP2D6 genotyping for personalizing antipsychotic treatment.
Pharmacogenomics 05/2009; 10(4):685-99. · 3.97 Impact Factor
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Nature 04/2009; 458(7237):407-8. · 36.28 Impact Factor
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ABSTRACT: Thiopurine S-methyltransferase (TPMT) is the rate-limiting step in the conversion of thiopurine drugs including azathioprine (AZA) to inactive metabolites. Heritable deficiency of TPMT activity increases risk for adverse events, most notably, myelosuppression leading to leukopenia and neutropenic sepsis. The reported European Commission study was undertaken to identify current evidence for the clinical utility of testing for TPMT status and extent of uptake, by either genotyping or phenotyping, in the clinical setting. Data presented here for the UK and Spain indicate that there has been a considerable increase in the uptake of TPMT testing in recent years. There are some data that support routine TPMT testing before AZA prescribing for reducing AZA-related adverse events. Key data include evidence in favor of TPMT testing in addition to the current practice of routine monitoring for reducing the number of AZA-related episodes of myelosuppression, averting deaths from neutropenic sepsis and improving health-related quality of life. Further data are needed for determining the cost-effectiveness of routine TPMT testing.
European journal of human genetics: EJHG 03/2009; 17(8):991-8. · 3.56 Impact Factor
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ABSTRACT: The sharing of samples and data stored in biobanks for research has implications for donor privacy, but also raises questions on the regulation of research within Europe. Many legal documents and principles within Europe, with a direct impact on biobanking, have not been developed specifically to support this activity. Moreover, while some new regulations have been set up at national level, there are many variations in the definitions, scope and purpose of these legal instruments. This has resulted in unnecessary hurdles for genome-based research, particularly if samples are shared across national borders. The question is also raised on whether new, specific legislative and governance frameworks designed for biobanking are needed, or whether it is sufficient to modify current general law and to develop specific guidelines, or to accommodate issues raised by biobanking in the current regulation. A workshop with experts from academia and industry, lawyers, national data protection authorities, representatives from the European Commission and the European Data Protection Supervisor was held to review the existing legal bottlenecks and future needs of biobanking, with special regard to the collection, exchange and linkage of samples and data. This report presents highlights of the presentations and discussions from the workshop held in Sevilla, Spain, in March 2007 and the conclusions that followed. The workshop focused on the internal linkage of data and samples stored in a biobank, and the external linkage of biobanks with secondary information resources, such as cancer registries.
Pharmacogenomics 06/2008; 9(6):773-81. · 3.97 Impact Factor
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Anniek Corveleyn,
Michael A Morris,
Elisabeth Dequeker,
Karen Sermon,
James Lawford Davies,
Guillermo Antiñolo,
Andreas Schmutzler,
Jiri Vanecek,
Nick Nagels,
Eleni Zika,
Francesc Palau, Dolores Ibarreta
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ABSTRACT: Preimplantation genetic diagnosis (PGD) is now well established and provided in many European countries. However, regulations, professional standards and accreditation requirements can differ notably. Furthermore, no comprehensive independent data exist either about practice and provision in Europe or about the quality assurance practices and procedures designed to optimize the quality of the results. Consequently, a study was launched to obtain knowledge, currently lacking, of the provision and quality assurance of PGD services and cross-border activities in Europe. An online questionnaire was developed and sent to PGD providers, and expert opinions were obtained through interviews with professionals in specific countries. Information was gathered from 53 centres offering PGD in 17 European countries. There is a diverse array of tests available, with a trend for custom-made services. Although half of the centres have a designated quality manager, just 33% have achieved or are preparing for accreditation or certification. About 66% of the centres responded that they did not participate in external quality assessment, a problem exacerbated by the lack of existing PGD-specific schemes. Approximately 19% of the centres do not keep data on accuracy and 9% do not even follow up until birth. PGD is an expanding activity with an increasing international flow that accounts for approximately one-third of the activity reported. The survey highlights a significant need for improvement in quality assurance in PGD centres. On the positive side, important improvements in the quality management of these services are expected with the European Tissue Directive entering into force.
European Journal of HumanGenetics 04/2008; 16(3):290-9. · 4.40 Impact Factor
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ABSTRACT: The study aims at evaluating the economic evidence related to testing for genetic variants of the drug-metabolizing enzyme, TPMT. Detecting TPMT genetic variants before the administration of azathioprine (AZA) has the potential to prevent serious and costly adverse drug reactions (ADRs), such as neutropenia. In particular, our analysis concentrated on assessing the reliability of data on costs of neutropenia and performing the tests, the two main cost categories that could inform an economic evaluation of TPMT pharmacogenetic testing.
A systematic literature review was performed to gather evidence on the costs of testing and neutropenia. Articles were critically appraised for their comprehensiveness and quality. To better estimate costs of TPMT tests, a small-scale survey of European diagnostic laboratories was conducted.
Only seven articles were retrieved specifying the costs associated with the management and treatment of AZA-induced neutropenia. Most of these studies are based on theoretical modeling reconstructed with key-informants or on very few cases of ADRs, and either the methodology for cost calculation is not specified or costs are based on national cost databases and tariffs. After critical appraisal of these studies, we considered 2,116 euros as the most reliable estimate for the cost of a case of neutropenia. Literature review accompanied by the survey of several diagnostic laboratories also provided an estimate (68 euros) for TPMT testing. Based on these values, the net cost per prevented case of neutropenia equals to 5,300 euros.
Solid economic considerations related to TPMT pharmacogenetic testing are still limited by underreporting of ADRs and high level of approximation related to cost data. Ad hoc observational studies and the ADR recording process embedded in pharmacovigilance systems, established across Europe, should represent more reliable sources of cost data in the future.
International Journal of Technology Assessment in Health Care 02/2008; 24(3):294-302. · 1.37 Impact Factor
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ABSTRACT: This study focuses on the potential impact of genetic screening technologies on healthcare. Genetic screening for asthma in children was chosen as a case study to explore the cost effectiveness of applying early genetic screening to infants, and preventive treatment to the population at risk. Early intervention could prevent progression and facilitate clinical management of the disease. From the elite group of genetic markers that have been associated with asthma-related phenotypes, ADAM33 was the first published candidate gene detected by a positional cloning approach, marking the entry of asthma research into the genomic era. The model was, therefore, initially set for an ex ante analysis of the cost effectiveness of applying the preventive program to an infant population at risk, i.e. infants presenting wheezing episodes during the first year of life, and the ADAM33 ST+7 genetic marker, with the idea of expanding to further markers and their combinations lat a later date.
In accordance with the US National Heart, Lung, and Blood Institute, four categories of asthma were considered. A Markov model was constructed, consisting of six mutually exclusive disease states (including healthy and dead states) with a simulation horizon of 100 years and a cycle length of 1 year. We define a scenario where early genetic screening was applied to infants presenting wheezing episodes during the first year of life and a preventive treatment to those children within this group who tested positive for selected ADAM33 polymorphism (ST+7). The cost-effectiveness analysis was performed from the third-party payer and patient perspective after year 6. We applied our model to a hypothetical cohort of 100 European infants.
The number of quality-adjusted life-years (QALYs) gained during the 6 years was 1.483, and the incremental cost-effectiveness ratio per QALY gained was euro 10,100/QALY. A sensitivity analysis was carried out that varied the discount rate and cost of genetic testing, and considered two different transition matrices for the preventive program. Three main conclusions were drawn from the sensitivity analysis. Firstly, if the discount rate for both cost and health outcomes is increased by 2%, the cost effectiveness of the preventive program does not vary significantly. Discounting costs and benefits at 5%, the preventive program appears cost effective (euro 11,100/QALY). Secondly, if the cost of genetic testing is increased to euro 100, the cost effectiveness of the preventive program remains within the limits of cost effectiveness. Thirdly, the cost of genetic screening, together with transition probabilities between health states, will determine the cost effectiveness of applying a preventive program based on genetic information.
Preventive treatment based on an early genetic screening of those children who present wheezing episodes during the first year of life, with treatment applied to those who test positive for the asthma-associated genetic marker ADAM33 ST+7, is theoretically cost effective. The model is a valuable tool for the ex ante assessment of the cost effectiveness of preventive schemes based on genetic screening. The value of modeling prior to clinical trials lies in informing study design and setting priorities for future research.
Molecular diagnosis & therapy 02/2007; 11(5):313-23. · 1.71 Impact Factor
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ABSTRACT: Only a few studies have addressed the cost-effectiveness of pharmacogenetics interventions in healthcare. Lack of health economics data on aspects of pharmacogenetics is perceived as one of the barriers hindering its implementation for improving drug safety. Thus, a recent Institute for Prospective Technological Studies (IPTS) study, entitled 'Pharmacogenetics and pharmacogenomics: state-of-the-art and potential socio-economic impact in the EU' included an explorative cost-effectiveness review for a pharmacogenetic treatment strategy compared with traditional medical practice. The selected case study examined the cost-effectiveness of thiopurine methyltransferase (TMPT) genotyping prior to thiopurine treatment in children with acute lymphoblastic leukemia (ALL). Information for the cost-effectiveness model parameters was collected from literature surveys and interviews with experts from four European countries (Germany, Ireland, the Netherlands and the UK). The model has established that TPMT testing in ALL patients has a favorable cost-effectiveness ratio. This conclusion was based on parameters collected for TPMT genotyping costs, estimates for frequency of TMPT deficiency, rates of thiopurine-mediated myelosuppression in TPMT-deficient individuals, and myelosuppression-related hospitalization costs in each of the four countries studied. The mean calculated cost per life-year gained by TPMT genotyping in ALL patients in the four study countries was euro 2100 (or euro 4800 after 3% discount) based on genotyping costs of euro 150 per patient. Cost per life-year gained is expected to further improve following the introduction of the wider use of TMPT genotyping and the availability of lower cost genotyping methods. Our analysis indicates that TPMT genotyping should be seriously considered as an integral part of healthcare prior to the initiation of therapy with thiopurine drugs.
Pharmacogenomics 08/2006; 7(5):783-92. · 3.97 Impact Factor
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Sirpa Soini, Dolores Ibarreta,
Violetta Anastasiadou,
Ségolène Aymé,
Suzanne Braga,
Martina Cornel,
Domenico A Coviello,
Gerry Evers-Kiebooms,
Joep Geraedts,
Luca Gianaroli,
Joyce Harper,
György Kosztolanyi,
Kersti Lundin,
Emilio Rodrigues-Cerezo,
Karen Sermon,
Jorge Sequeiros,
Lisbeth Tranebjaerg,
Helena Kääriäinen
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ABSTRACT: The interface between assisted reproductive technologies (ART) and genetics comprises several sensitive and important issues that affect infertile couples, families with severe genetic diseases, potential children, professionals in ART and genetics, health care, researchers and the society in general. Genetic causes have a considerable involvement in infertility. Genetic conditions may also be transmitted to the offspring and hence create transgenerational infertility or other serious health problems. Several studies also suggest a slightly elevated risk of birth defects in children born following ART. Preimplantation genetic diagnosis (PGD) has become widely practiced throughout the world for various medical indications, but its limits are being debated. The attitudes towards ART and PGD vary substantially within Europe. The purpose of the present paper was to outline a framework for development of guidelines to be issued jointly by European Society of Human Genetics and European Society of Human Reproduction and Embryology for the interface between genetics and ART. Technical, social, ethical and legal issues of ART and genetics will be reviewed.
European Journal of HumanGenetics 06/2006; 14(5):588-645. · 4.40 Impact Factor
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Michael M Hopkins, Dolores Ibarreta,
Sibylle Gaisser,
Christien M Enzing,
Jim Ryan,
Paul A Martin,
Graham Lewis,
Symone Detmar,
M Elske van den Akker-van Marle,
Adam M Hedgecoe,
Paul Nightingale,
Marieke Dreiling,
K Juliane Hartig,
Wieneke Vullings,
Tony Forde
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ABSTRACT: Genetics is slowly explaining variations in drug response, but applying this knowledge depends on implementation of a host of policies that provide long-term support to the field, from translational research and regulation to professional education.
Nature Biotechnology 05/2006; 24(4):403-10. · 23.27 Impact Factor
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Nature Biotechnology 11/2004; 22(10):1230-5. · 23.27 Impact Factor
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ABSTRACT: • Genetic testing is an activity which transcends national borders. Rare disease genetics has long involved an international
exchange of human samples and related data and this globalisation is increasing in areas such as cancer diagnostics and consumer
genetics. This international trade takes place in an environment where regulatory and oversight procedures vary significantly
between jurisdictions.
• The last decade has witnessed an international discussion about both technical issues relating to the quality of genetic
testing and broader ethical and social issues such as genetic discrimination. International Organisations such as the Council
of Europe, the Organisation for Economic Cooperation and Development and the World Health Organisation have acted as policy
fora and standard setting bodies.
• Key policy documents are the Council of Europe’s (1997) Convention for the Protection of Human Rights and Dignity of the
Human Being with regard to the Application of Biology (also called The Convention on Human Rights and Biomedicine) and its
2008 Additional Protocol to the Convention on Human Rights and Biomedicine, concerning Genetic Testing for Health Purposes
and the OECD’s (2007) Best Practice Guidelines for Quality Assurance in Molecular Genetic Testing.
• Whilst these documents enshrine broadly accepted international standards it remains to be seen how they will be implemented
and enforced at level of individual nation-states.
KeywordsQuality assurance-Accreditation-Licensing-Council of Europe-Organisation for Economic Cooperation and Development-World Health Organisation
01/1970: pages 243-249;
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ABSTRACT: The final decoding of the human genome has marked the beginning of a new era of biomedical research and both the European Commission (EC) and the Member States try to facilitate this new research direction. In most European countries biobanks are set up to improve the capacities for research. These new research infrastructures require a specific governance framework to ensure public trust and accountability.
Revista de derecho y genoma humano = Law and the human genome review / Cátedra de Derecho y Genoma Humano/Fundación BBV-Diputación Foral de Bizkaia.
