By Turna Ray
Recommendations issued by a government-led panel that convened stakeholders from industry, academia, and patient groups -include some basic guidelines for how to advance the nascent field of personal genomics in a manner that is safe for consumers and useful in terms of medical decision-making and disease prevention.
The recommendations, published in Genetics in Medicine last week, are the result of a December 2008 workshop led by the National Institutes of Health and the Centers for Disease Control and Prevention. Also involved in formulating the recommendations were members of the Personalized Medicine Coalition; the three personal genome firms 23andMe, Navigenics, and Decode Genetics; HHS; Facing Our Risk of Cancer Empowered; Johns Hopkins' Genomics and Public Policy Center; Genetic Alliance; Los Angeles County Department of Public Health; and many others.
The working group issued five recommendations to "enhance the foundation" for using personal genomics in order to improve health: (1) develop and apply scientific standards for assessing personal genomic tests; (2) develop and apply a multi-disciplinary research agenda, including observational and clinical trials, to show the clinical validity and utility of these tests; (3) disseminate "credible" information to doctors and consumers about tests; (4) connect scientific findings to evidence recommendations about personal genomics; and (5) develop metrics on how "personal utility" of genomic risk data can improve health and lower cost.
These recommendations show continued effort by health regulators, business officials, and researchers to develop consensus for advancing the personal genomics field.
Following the December meeting on personal genomics, Navigenics, Decode, and 23andMe issued a white paper outlining the way each company calculated genetic risk and standardized processes in certain areas. In reaction to this white paper, Muin Khoury, director of CDC's Office of Public Health Genomics, said more work needed to be done to align standards in the personal genomics industry, as companies still diverged on clinical validation issues critical to protecting consumer health [see PGx Reporter 04-15-2009].
Khoury is the lead author of the Genetics in Medicine article, which recommends that personal genome firms further align and make transparent criteria for "analytic standards, clinical standards on selection of genetic variants with high credibility, use of appropriate data to interpret reported allelic odds ratios in terms of overall risk compared with appropriate reference populations, and model calibration and evaluation of risk distributions for health conditions included in personal genome tests."
Furthermore, the working group suggests that an independent panel be developed for creating standardized clinical validity and clinical utility measures for personal genomic tests.
In developing a multidisciplinary research agenda, the group advised, researchers should conduct epidemiologic studies that can characterize risk, such as gene/gene and gene/environment studies. According to the group, the research agenda should also assess cost-effectiveness of these interventions and enhance translational research initiatives that join public and private groups.
There was extensive discussion in the article about when randomized-controlled trials are and are not appropriate in the evaluation of personal genome tests. "For most genomic applications (and many other diagnostic tests), direct evidence about the effectiveness and value of testing is rarely available from RCTs," the group wrote.
However, they do outline instances when RCTs are useful, such as developing direct evidence for the clinical utility of personal genetic tests compared to behavioral and pharmacological interventions.
For instance, RCTs could be used to identify subgroups of individuals based on the PG profiles where interventions are most effective and to avoid adverse drug reactions. "Even if no differences in the effects of interventions exist by genotype, RCTs can be used to assess whether genotype-based interventions can be more effective overall if they improve adherence to available interventions that are designed for the general population," the group wrote.
The third recommendation from the group called for improving access and education to doctors and consumers about genetic associations and the utility and validity of tests.
"Such information needs to be translated in an accessible fashion and disseminated to consumers, providers, and policy makers to inform decision making," the group advised.
In this regard, the CDC's Office of Public Health Genomics and NCI's Division of Cancer Control and Population Sciences have launched the Genomic Applications in Practice and Prevention Network, which aims to convene individuals and groups conducting genomics translation research, programs, and policy activities; sponsor new translational research; synthesize and evaluate available research findings; and develop and disseminate "validated, useful genomic knowledge and applications for use in medicine and public health" [see PGx Reporter 07-15-2009].
In developing the standards that will guide the personal genomics industry, independent panels, such as CDC's Evaluation of Genomic Applications in Practice and Prevention group and the US Preventive Services Task Force, should consider the evidence threshold for integrating personal genomic information in clinical practice and disease prevention, the Genetics in Medicine article states.
Setting the bar for evidence too low for clinical utility and clinical validity may allow a diffusion of genomic discoveries into practice, but there may not be adequate information on their effectiveness, the group said. On the other hand, placing the bar for evidence too high could result in tests with high validity and utility but with lower financial incentive for innovation by developers.
For these reasons, the group noted, "extra caution" is needed when determining how much evidence is necessary for clinical utility and validity.
"To achieve an appropriate linkage between evidence and practice, independent panels such as EGAPP and USPSTF should provide rapid and timely assessments to determine in a systematic and transparent fashion whether a personal genomic test and its associated interventions does more good than harm in specific population groups or on a population-wide basis. In preventive services, the USPSTF has had a major role for more than three decades and has conducted formal analyses of hundreds of preventive interventions," the group wrote. "The field of personal genomics will greatly benefit from such independent evaluations."
Finally, the working group advised further exploration and application of "personal utility" in determining cost-effectiveness and usefulness of genomic applications.
In order for personal utility measures to impact the adoption of personal genomics, objective metrics will need to be developed and applied in observational studies and RCTs.
"In conclusion, to make the best use of PG for improved health outcomes, the CV and CU of these tests must be understood by consumers, providers, and policy makers," the working group said. "Scientific standards for evaluating these tests must be established and a mechanism put in place to provide authoritative, unbiased, timely reviews of new discoveries."