Outcomes of interest in evidence-based evaluations of genetic tests

Botkin, Jeffrey R.; Teutsch, Steven M.; Kaye, Celia I.; Hayes, Maxine; Haddow, James E.; Bradley, Linda; Szegda, Kathleen; Dotson, W. David

doi:10.1097/gim.0b013e3181cdde04

Cited by 85 publications

(74 citation statements)

References 51 publications

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“…The European Commission, with its international partners must also ascertain what is required to assemble high-quality research evidence on gene-disease associations-establishing the relative roles of research funder, academia and industry-particularly in generating data on lower penetrance genes by analogy with the Clinical Utility Gene Cards of EuroGentest 25 and as discussed in the ESHG statement. Alongside this research on disease-gene associations, it is also vital to design research studies to collect evidence on the impact of testing on health outcomes 26 and on alternative models for communicating genetic risk. 27 Extending quality control Test quality assurance must cover not only analytical quality but also the professional interpretation of results and the provision of counselling that is appropriate to the disease risk and burden, as discussed in the ESHG statement.…”

Section: Governance Principles For Informing Policy Developmentmentioning

confidence: 99%

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

Fears

Boccia

Cornel³

et al. 2012

Eur J Hum Genet

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Direct-to-consumer (DTC) genetic testing services raise scientific, regulatory and ethical questions. A report was prepared by consultation with an expert Working Group and published by the academies of science (European Academies of Science Advisory Council, EASAC) and medicine (Federation of European Academies of Medicine, FEAM). This report reviews current scientific evidence, ascertains the principles that should underpin the options for action by policy-makers, and discusses the potential for devising proportionate and flexible regulation that enables future innovation, taking account of the work of other expert groups, most notably the European Society of Human Genetics. EASAC-FEAM concluded that DTC genetic testing has little clinical value at present, and expresses especial caution in several specific respects, for example relating to testing for high penetrance, serious disorders, prenatal screening, nutrigenomic and pharmacogenetic testing. It was emphasised that regulation must be on the basis that claims about the link between genetic marker and disease are scientifically valid. Other key issues to address include quality assurance (that includes the professional interpretation of results), transparent supply of accurate information, consideration of the implications for established health services, and clarification of consent procedures for any use of data for research purposes. There are important implications: for the European Commission, in revising the Directive on In Vitro Diagnostic Medical Devices; for professional bodies, in supporting training and guideline development; for the broader research community, in generating the evidence base; and for the public health community, in improving the routine translation of research advances into clinical practice

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Section: Governance Principles For Informing Policy Developmentmentioning

confidence: 99%

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

Fears

Boccia

Cornel³

et al. 2012

Eur J Hum Genet

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“…Determining the clinical significance of genetic information is a complex and evolving process, and as we reported, even within the Colon CFR, there were differences among registries about which results were deemed clinically relevant. Botkin et al (2010) have provided a framework for evaluating genetic tests and list a number of factors that could be considered in making decisions about clinical relevance including clinical validity, clinical utility, and ethical, legal, and social implications. We argue, as suggested by Rothstein (2006), that decisions on how to manage clinically relevant genetic results should be considered and planned at the outset of the research.…”

Section: Discussionmentioning

confidence: 99%

“…We have compiled a set of suggestions for future researchers based on our own experience of returning results to research participants. Our consensus suggestions are designed to be used to supplement guidelines that are currently available (Botkin et al 2010;Fabsitz et al 2010;Bookman et al 2006;Dressler 2009). We have also described the disclosure protocols used by registries in order to increase the information available to research consortia managing clinically relevant genetic results on participants.…”

Section: Discussionmentioning

confidence: 99%

How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry

et al. 2013

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There is consensus internationally that research participants should be offered the opportunity to receive clinically relevant genetic information identified through research, but there is little empirical peer-reviewed work documenting this process. We report the experience of conducting genetic research with nearly 35,000 participants in the Colon Cancer Family Registry, based in the USA, Canada, Australia, and New Zealand. Investigators from six multinational sites provided information about disclosure protocols, implementation, and uptake of genetic results and made suggestions to inform practice. Across 5 of the 6 registry sites, 1,634 participants in families with mismatch repair or MutYH gene muta- Genet (2014) 5:99-108 DOI 10.1007 effort to return results. We offer suggestions in five key areas: (1) planning for the disclosure process, (2) participant information, (3) autonomy of participants, (4) monitoring scientific progress, and (5) involvement of stakeholders. Despite increasing discussion of the importance of returning incidental findings from genetic research, this paper highlights the considerable diversity, challenges, and costs faced in practice when returning expected findings with established utility and validity. We argue that more work is needed to ensure that genetic results in research are optimally managed.

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“…The final EWG recommendation statement was formulated on the basis of magnitude of effect, certainty of evidence, and consideration of contextual factors. 27,28 technology description Direct sequencing and real-time polymerase chain reaction (real-time PCR) are commonly used techniques for KRAS 21 BRAF, NRAS, and PIK3CA mutation analysis. Detection of PTEN and AKT protein expression, or lack thereof, can be accomplished through IHC assays.…”

Section: Methodsmentioning

confidence: 99%

Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

2013

Genetics in Medicine

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EGAPP REcommEndAtion stAtEmEnt summary of recommendations: The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (EWG) found that, for patients with metastatic colorectal cancer (mCRC) who are being considered for treatment with cetuximab or panitumumab, there is convincing evidence to recommend clinical use of KRAS mutation analysis to determine which patients are KRAS mutation positive and therefore unlikely to benefit from these agents before initiation of therapy. The level of certainty of the evidence was deemed high, and the magnitude of net health benefit from avoiding potentially ineffective and harmful treatment, along with promoting more immediate access to what could be the next most effective treatment, is at least moderate.The EWG found insufficient evidence to recommend for or against BRAF V600E testing for the same clinical scenario. The level of certainty for BRAF V600E testing to guide antiepidermal growth factor receptor (EGFR) therapy was deemed low. The EWG encourages further studies of the potential value of testing in patients with mCRC who were found to have tumors that are wild type (mutation negative) for KRAS to predict responsiveness to therapy.The EWG found insufficient evidence to recommend for or against testing for mutations in NRAS, or PIK3CA, and/or loss of expression of PTEN or AKT proteins. The level of certainty for this evidence was low. In the absence of supporting evidence, and with consideration of other contextual issues, the EWG discourages the use of these tests in guiding decisions on initiating anti-EGFR therapy with cetuximab or panitumumab unless further evidence supports improved clinical outcomes.Rationale: It has been suggested that patients with mCRC whose tumors harbor certain mutations affecting EGFR pathway signaling are typically unresponsive to therapy with anti-EGFR antibodies (cetuximab and panitumumab). The EWG identified recent evidence reviews that have addressed this topic, and this recommendation statement is based on results of these reviews. In developing these recommendations the EWG considered evidence in the areas described below. Analytic validity:Although no research syntheses that have formally evaluated analytic validity of these tests were found, the EWG was able to draw the following conclusions from assessments included in the evidence reviews under consideration. There is adequate evidence that KRAS mutation analysis reliably and accurately detects common mutations (codons 12 and 13), whereas evidence was inadequate for less frequent KRAS mutations (e.g., codon 61). There is also adequate evidence that testing for BRAF V600E accurately and reliably detects the mutation. For common mutations in NRAS, PIK3CA, and expression of PTEN AKT, there is adequate evidence of accurate and reliable detection. However, much less data exist in support. Furthermore, in the specific context of mCRC, no evidence was found on the analytic validity of immunohistochemistry (IHC) assays for PTEN or AKT expression.clinical val...

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Outcomes of interest in evidence-based evaluations of genetic tests

Cited by 85 publications

References 51 publications

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

The perspective from EASAC and FEAM on direct-to-consumer genetic testing for health-related purposes

How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry

Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy?

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