Abstract: Personalized medicine, with the aim of safely, effectively, and cost-effectively targeting treatment to a prespecified patient population, has always been a long-time goal within health care. It is often argued that personalizing treatment will inevitably improve clinical outcomes for patients and help achieve more effective use of health care resources. Demand is increasing for demonstrable evidence of clinical and cost-effectiveness to support the use of personalized medicine in health care. This paper begins with an overview of the existing challenges in conducting economic evaluations of genetics- and genomics-targeted technologies, as an example of personalized medicine. Our paper illustrates the complexity of the challenges faced by these technologies by highlighting the variations in the issues faced by diagnostic tests for somatic variations, generally referring to genetic variation in a tumor, and germline variations, generally referring to inherited genetic variation in enzymes involved in drug metabolic pathways. These tests are typically aimed at stratifying patient populations into subgroups on the basis of clinical effectiveness (response) or safety (avoidance of adverse events). The paper summarizes the data requirements for economic evaluations of genetics and genomics-based technologies while outlining that the main challenges relating to data requirements revolve around the availability and quality of existing data. We conclude by discussing current developments aimed to address the challenges of assessing the cost-effectiveness of genetics and genomics-based technologies, which revolve around two central issues that are interlinked: the need to adapt available evaluation methods and identifying who is responsible for generating evidence for these technologies. Keywords: pharmacogenetics, pharmacogenomics, cost-effectiveness, economic evaluation, somatic variations, germline variations
Objectives To assess the clinical effectiveness and cost-effectiveness of deferasirox for the treatment of iron overload associated with regular blood transfusions in patients with chronic anaemia such as beta-thalassaemia major (beta-TM) and sickle cell disease (SCD). Data sources Electronic databases were searched up to March 2007. Review methods Methods followed accepted procedures for conducting and reporting systematic reviews and economic evaluations. Results A total of 14 randomised controlled trials (RCTs) involving a study population of 1480 (ranging from 13 to 586) met the inclusion criteria. There was a high degree of heterogeneity between trials in terms of trial design and outcome reporting. As such it was only possible to meta-analyse serum ferritin data from six trials making comparisons between deferiprone and DFO and combination therapy and DFO. Only one of the results was statistically significant, favouring combination therapy over DFO alone for serum ferritin at 12 months. How this translates into iron loading in organs such as the heart is unclear, nor was it possible to determine the long-term benefits of chelation therapy. Eight full economic evaluations (one full paper; seven abstracts) were included in the review. The results were generally consistent and appear to demonstrate the cost-effectiveness of deferasirox compared with DFO for the treatment of iron overload in a number of different patient populations and study locations. However, a number of assumptions and, in the case of the long-term studies, extrapolation from short-term RCT data were required, which render the results highly speculative at best. Because of the paucity of long-term data we developed a simple, short-term (1 year) model to assess the costs and benefits of deferasirox, deferiprone and DFO in patients with beta-TM and SCD from an NHS perspective. A number of assumptions were required to generate results and, as such, they should be interpreted as indicative rather than factual. Our model suggests that deferasirox may be a cost-effective strategy compared with DFO, at a cost per quality-adjusted life-year (QALY) below £30,000 per year, for patients with beta-TM and SCD. However, this is highly dependent upon the age of the patient and the use and benefits of balloon infusers to administer DFO. Deferasirox compared with deferiprone is likely to be cost-effective only for young children. Furthermore, if deferiprone is proven to offer the same health benefits as deferasirox, the latter will not be cost-effective for any patient compared with deferiprone. Conclusions In the short term there is little clinical difference between any of the three chelators in terms of removing iron from the blood and liver. Deferasirox may be cost-effective compared with DFO in patients with beta-TM and SCD, but it is unlikely to be cost-effective compared with deferiprone. Elucidating the long-term benefits of chelation therapy, including issues of adverse events and adherence, should be the primary focus for future research. Future work should aim for consistency and transparency in reporting study design and results to aid decision-making when making comparisons across trials.
Objective To determine whether testing for cytochrome P450 (CYP) polymorphisms in adults entering antipsychotic treatment for schizophrenia leads to improvement in outcomes, is useful in medical, personal or public health decision-making, and is a cost-effective use of health-care resources. Data sources The following electronic databases were searched for relevant published literature: Cochrane Controlled Trials Register, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, EMBASE, Health Technology Assessment database, ISI Web of Knowledge, MEDLINE, PsycINFO, NHS Economic Evaluation Database, Health Economic Evaluation Database, Cost-effectiveness Analysis (CEA) Registry and the Centre for Health Economics website. In addition, publicly available information on various genotyping tests was sought from the internet and advisory panel members. Review methods A systematic review of analytical validity, clinical validity and clinical utility of CYP testing was undertaken. Data were extracted into structured tables and narratively discussed, and meta-analysis was undertaken when possible. A review of economic evaluations of CYP testing in psychiatry and a review of economic models related to schizophrenia were also carried out. Results For analytical validity, 46 studies of a range of different genotyping tests for 11 different CYP polymorphisms (most commonly CYP2D6) were included. Sensitivity and specificity were high (99–100%). For clinical validity, 51 studies were found. In patients tested for CYP2D6, an association between genotype and tardive dyskinesia (including Abnormal Involuntary Movement Scale scores) was found. The only other significant finding linked the CYP2D6 genotype to parkinsonism. One small unpublished study met the inclusion criteria for clinical utility. One economic evaluation assessing the costs and benefits of CYP testing for prescribing antidepressants and 28 economic models of schizophrenia were identified; none was suitable for developing a model to examine the cost-effectiveness of CYP testing. Conclusions Tests for determining genotypes appear to be accurate although not all aspects of analytical validity were reported. Given the absence of convincing evidence from clinical validity studies, the lack of clinical utility and economic studies, and the unsuitability of published schizophrenia models, no model was developed; instead key features and data requirements for economic modelling are presented. Recommendations for future research cover both aspects of research quality and data that will be required to inform the development of future economic models.
This review assessed evidence of disparities in benefits of pharmacogenomics related to 'model performance' in subgroups of patients and studies which reported impact on health inequalities. 'Model performance' refers to the ability of algorithms including clinical, environmental and genetic information to guide treatment. A total of 4978 abstracts were screened by one reviewer and 30% (1494) were double screened by a second independent reviewer, after which data extraction was performed. Additional forward and backward citation searching of reference lists was conducted. Investigators independently double rated study quality and applicability of included studies. Only five individual studies were identified which met our inclusion criteria, but were contradictory in their conclusions. While three studies of genotype-guided dosing of warfarin reported that ethnic disparities in healthcare may widen, two other studies (one reporting on warfarin and reporting on clopidogrel) suggested that disparities in healthcare may reduce. There is a paucity of studies which evaluates the impact of pharmacogenomics on health disparities. Further work is required not only to evaluate health disparities between ethnic groups and countries but also within ethnic groups in the same country and solutions need to be identified to overcome these disparities.
Objectives:The authors developed a tool to assess the quality of search filters designed to retrieve records for studies with specific research designs (e.g., diagnostic studies).Methods:The UK InterTASC Information Specialists' Sub-Group (ISSG), a group of experienced health care information specialists, reviewed the literature to evaluate existing search filter appraisal tools and determined that existing tools were inadequate for their needs. The group held consensus meetings to develop a new filter appraisal tool consisting of a search filter appraisal checklist and a structured abstract. ISSG members tested the final checklist using three published search filters.Results:The detailed ISSG Search Filter Appraisal Checklist captures relevance criteria and methods used to develop and test search filters. The checklist includes categorical and descriptive responses and is accompanied by a structured abstract that provides a summary of key quality features of a filter.Discussion:The checklist is a comprehensive appraisal tool that can assist health sciences librarians and others in choosing search filters. The checklist reports filter design methods and search performance measures, such as sensitivity and precision. The checklist can also aid filter developers by indicating information on core methods that should be reported to help assess filter suitability. The generalizability of the checklist for non-methods filters remains to be explored.
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