The Scientific Foundation for Personal Genomics: Recommendations from the Joint NIH-CDC Workshop

conferenceLast December, some of the true heavyweights in the field of personal genomics convened for a two-day workshop cosponsored by the CDC and NIH to review the science and implementation of personal genomics. Participants included scientific luminaries (e.g., Francis Collins, George Church and Bob Green), personal genomics companies (e.g., 23andMe, Knome, Navigenics, deCODE Genetics and DNA Direct) and policy groups (e.g., Genetic Alliance, Personalized Medicine Coalition and Genetics and Public Policy Center). The workshop and its participants’ recommendations were summarized (pdf) late last month in the journal Genetics in Medicine.

The workshop focused on a review of the “scientific foundation for using personal genomics in risk assessment and disease prevention,” developing five specific recommendations for the future development and use of personal genomics.

1. Develop and implement scientific standards for personal genomics. Of primary importance was the development of scientific benchmarks for evaluating personal genomics testing. Heavily emphasized was the need to establish standards for measuring the clinical validity (how well a genetic variant identifies or predicts an individual’s clinical status) and clinical utility (the health and other benefits of a test balanced against its harms or costs) of personal genomics tests. The importance of voluntary industry guidelines (pdf), randomized clinical trials and economic analysis of personal genomics testing were all discussed.

2. Develop and implement a multidisciplinary research agenda. The workshop recognized that this area is a meeting point for many disciplines, including, in addition to the obvious biological and medical fields, the fields of communication and behavioral and social sciences. There is a need for large-scale research projects to improve risk characterization, “especially of gene-gene and gene-environment interactions.” But there is also a need to study how the results of such research are publicly disseminated and become incorporated into the delivery of health services or the decision-making of individual consumers.

3. Enhance credible knowledge synthesis and dissemination of information to providers and consumers. Continuing with the theme of communicating knowledge to policy makers, health care providers and individuals, workshop participants noted that such communication needs to be timely and capable of “rapid turnaround” (given the pace of developments), based on standardized formats, and subject to agreed standards for what constitutes the “best available data.”

4. Link scientific research on validity and utility to evidence-based recommendations for use of personal genomic tests. One of the key issues for personal genomics, and particularly for direct-to-consumer (DTC) genomics companies, is when and how policymakers, clinicians and healthcare payors (including consumers) will determine that a personalized genomic test has demonstrated sufficient clinical validity and clinical utility to warrant its incorporation “into clinical practice and disease prevention.” Setting the bar for this “evidence threshold” at an appropriate height was another concern of the panel, and it noted that setting the bar too law resulted in the marketing and use of genomic tests without sufficient evidence of their clinical validity and/or utility, a common concern voiced by critics of the DTC genomics industry. Setting the bar too high, on the other hand, “may result in tests with high validity and utility but with lower financial incentive for innovation” which could, paradoxically, “lead to fewer developed tests and potentially diminished health benefits.…” The panel declined to offer its own suggestion for an appropriate evidence threshold, concluding only that the bar must be set by “independent panels that have no conflict of interest and use rigorous systematic evaluations,” such as those employed by EGAPP and USPSTF.

5. Consider the value of personal utility. Finally, the panel went out of its way to highlight the potential “personal utility” of genomic and genetic testing and services. Even in the absence of proven clinical or medical interventions, personal genomics information may have utility for individuals, including promoting improved comprehension of genetic information and the adoption of healthy lifestyle changes. As an example, the participants singled out the recent REVEAL Study conducted by Bob Green et al. that found, in the case of Alzheimer Disease (AD), that “even though there are no proven effective interventions to remediate” the risk of AD, providing participants with genetic information regarding that risk was found “to be useful by allowing them to prepare their families and arrange personal affairs including long-term care.”

DTC genomics companies have long trumpeted the personal utility of their products, often choosing to highlight the educational aspects of their services in the face of doubts about their clinical validity and/or utility. The workshop’s recommendation that these “perceptions of utility” be “scientifically supported” with “objective metrics” and “rigorous multidisciplinary observational studies and [randomized clinical trials],” if carried out, would be an acid test for the personal genomics industry and its claims of personal utility. Some of this work has already begun and, from an industry perspective, the preliminary results are encouraging. A recent study (the NIH Multiplex Initiative) of early adopters of genetic testing services similar to those provided by DTC companies found that such individuals “may be among the most motivated to take steps toward healthier lifestyles.”

Of course, no set of personal genomics recommendations would be complete without the obligatory ELSI nod: “these scientific standards have to be examined in the context of principles of population screening with full consideration of the ethical, legal and social, economic, and policy issues.” Ultimately, however, its encouraging to see such influential individuals in the field of personal genomics continuing to focus their attention on better understanding the science, utilization and effect of personal genomics. This initiative provides a useful counterbalance to calls for the preemptive regulation of a field that remains in its infancy.