Biomedical subjects
Publications and source records attributed to M Elske van den Akker-van Marle.
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.
OBJECTIVES: The purpose of this work was to assess the costs of 4 neonatal screening strategies for cystic fibrosis in relation to health effects. In each strategy, the first test was the measurement of serum concentration of immunoreactive trypsin. The second step consisted of either a second immunoreactive trypsin test (strategy 1) or a multiple mutation analysis (strategy 2). In strategies 3 and 4, a third step was added to strategy 2: a second immunoreactive trypsin test (strategy 3) or an extended mutation analysis of the cystic fibrosis gene, that is, a denaturing gradient gel electrophoresis analysis (strategy 4). METHODS: We conducted an economic-modeling exercise in the Netherlands based on published data and expert opinions. Subjects were a hypothetical cohort of 200 000 neonates, the approximate number of children born annually in the Netherlands, and we assessed the costs and number of life-years gained as a result of neonatal screening for cystic fibrosis. The costs and effects of changes in reproductive decisions because of neonatal screening were also assessed. RESULTS: Immunoreactive trypsin + immunoreactive trypsin had the most favorable cost-effectiveness ratio of 24,800 euro per life-year gained. Immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis achieved more health effects than immunoreactive trypsin + DNA + immunoreactive trypsin at lower cost. The incremental costs per life-year gained of the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy compared with the immunoreactive trypsin + immunoreactive trypsin strategy were 130,700 euro, whereas the incremental costs of the immunoreactive trypsin + DNA strategy compared with the immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis strategy were 2,154,300 euro. When changes in reproductive decisions as a result of neonatal screening are also taken into account, neonatal screening for cystic fibrosis may lead to financial savings of approximately 1.8 million euro annually, depending on the screening strategy used. CONCLUSIONS: Cystic fibrosis screening for neonates is a good economic option, and positive health effects can also be expected. Immunoreactive trypsin + immunoreactive trypsin and immunoreactive trypsin + DNA + denaturing gradient gel electrophoresis are the most cost-effective strategies.
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.
BACKGROUND: Recommended screening policies for cervical cancer differ widely among countries with respect to targeted age range, screening interval, and total number of scheduled screening examinations (i.e., Pap smears). We compared the efficiency of cervical cancer-screening programs by performing a cost-effectiveness analysis of cervical cancer-screening policies from high-income countries. METHODS: We used the microsimulation screening analysis (MISCAN) program to model and determine the costs and effects of almost 500 screening policies, some fictitious and some actual (i.e., recommended by national guidelines). The costs (in U.S. dollars) and effects (in years of life gained) were compared for each policy to identify the most efficient policies. RESULTS: There were 15 efficient screening policies (i.e., no alternative policy exists that results in more life-years gained for lower costs). For these policies, which considered two to 40 total scheduled examinations, the age range expanded gradually from 40-52 years to 20-80 years as the screening interval decreased from 12 to 1.5 years. For the efficient policies, the predicted gain in life expectancy ranged from 11.6 to 32.4 days, compared with a gain of 46 days if cervical cancer mortality were eliminated entirely. The average cost-effectiveness ratios increased from $6700 (for the longest screening interval) to $23 900 per life-year gained. For some countries, the recommended screening policies were close to efficient, but the cost-effectiveness could be improved by reducing the number of scheduled examinations, starting them at later ages, or lengthening the screening interval. CONCLUSIONS: The basis for the diversity in the screening policies among high-income countries does not appear to relate to the screening policies' cost-effectiveness ratios, which are highly sensitive to the number of Pap smears offered during a lifetime.
The objective of this article was to evaluate the utility of high-risk human papillomavirus (HR-HPV) testing for triage of women referred for colposcopy because of abnormal smears. We considered women with persistent mild or moderate dyskaryosis and women with severe dyskaryosis who were referred for colposcopy. For both patient groups we evaluated three alternative management policies: (1) conventional management based on histological assessment; (2) HR-HPV-triage with direct treatment without prior histologic assessment for HR-HPV-positive women and conventional management for HR-HPV-negative women; and (3) direct treatment without histologic assessment for all referred women. For each policy the average number of medical procedures, doctor visits, and the costs per referred woman were calculated. Based on a literature review, the results were tested and translated to other patient groups. Per woman with persistent mild or moderate dyskaryosis and compared with conventional policy, HR-HPV-triage will avoid 0.51 colposcopically directed biopsies, but adds 0.05 local treatments of the cervix (i.e., loop excision of the transformation zone) and 0.09 outpatient visits, and will cost $134 US dollars extra. HPV triage is less efficient in women with borderline or mildly dyskaryotic cytology. In women with severe dyskaryosis, direct treatment is more efficient as conventional management or HPV triage. The decision to introduce HPV testing or direct treatment in women with persistent mild or moderate dyskaryosis strongly depends on the relative burden attributed to a colposcopically directed biopsy and an outpatient visit compared to loop excision of the transformation zone treatment of the cervix. For women with severe dyskaryosis, direct treatment should be seriously considered.