Let's Get Personal

The recommendations suggest that the FDA needs to provide guidance for companies intending to develop drugs and associated diagnostic tools to assess the drugs efficacy for a specific person. In particular it says they need to address the review process for the case where the drug is subject to FDA review but the diagnostic test is not. I have a simpler question: should there ever BE a case where a diagnostic test intended to identify people who will respond to a specific drug? This is a case where I'm not sure how far the regulatory oversight of the FDA extends, and what precisely is covered or not, but one important step in both making PGx effective and ensuring public confidence is extensive and exhaustive validation by an objective body. For drugs and diagnostics this means FDA review. The report also recommends providing incentives to the private sector for developing PGx technologies. To a limited extent I think this is an excellent idea, but it has to be executed properly. Being first into a market is potentially expensive, yes, but there are definite benefits to it. I think that providing some financial incentives is a reasonable way to encourage investment, and I think that expedited FDA review (another suggestion) is an excellent idea. The last suggested way of encouraging investment (and I understand that these are simply ideas for discussion and not concrete recommendations) is increasing intellectual property rights of these early investors. This is a very bad idea, and one that is at odds with another goal - equitable and widespread access to PGx technology. Private industry will be an important driver of the field, but the financial rewards they stand to reap should be enough. Strengthening IP protection will only serve to limit access due to cost.

Analytic validity, clinical validity, clinical utility, and cost-effectiveness are the foundations that clinical practice modifications are based on. Unless a new test or technique sufficiently demonstrates these traits, no physician is going to adopt it. The report recommends that HHS work to assess these for PGx applications and develop ways to improve it, such as better datasets and improvements to study methodologies, as well as quantifying the differing levels of evidence required for different uses of PGx technology. More importantly, pharmaceutical manufacturers should publish the results of studies on the clinical validity and utility of PGx, even (I would say especially) non-significant or negative results) or make the data available to be studied by others. I think a better approach may be to require drug makers to report these results to the FDA as part of the approval and surveillance process. They will still want to publish positive results in peer-review journals, and I think that's a fine thing, but the results from all of their studies should be available to other researchers in some other form.

Data sharing is a potential goldmine for researchers. Right now obtaining datasets can quite difficult, both mechanically (because of their size and format) and politically (because they are well-protected even by government-funded researchers). The report recommends that HHS identify the obstacles to data sharing and encourage companies and academic institutions to participate. It is also important for future research to develop ways to share and use patient data, and again, the report suggests that HHS work in coordination with other agencies and programs to ensure the interoperability of the various electronic health records systems in use and in development.

Of course if this work stays in the basic research phase indefinitely, it doesn't do a lot of good. The report recommends that HHS help to catalog and and disseminate applications of PGx technology, work with professional and licensing organizations to improve physician education, publish systematic reviews of PGx and its applications as they become available to help inform usage guidelines, and ensure that package inserts and labels on both drugs and PGx tests contain all available PGx information. This is especially important, because over 70% of current drugs have some PGx information available about them, but almost none contain this on their labels.

Last is health information technology. HHS needs to both encourage the growth of health IT experts as well as the inclusion of PGx in to current and future electronic health records (EHR). The report recommends working with Office of the National Coordinator for Health Information Technology (did you know there was such a thing?) and other agencies to ensure that both EHR and clinical decision support tools take into account currently available PGx information. Also, for the current time (when EHR are not universal), HHS should develop way for physicians to retrieve and utilize PGx information.

Overall, I think the report strikes the right tone - hopeful for the future applications but realistic both of the current state and the challenges that face the field. A number of the recommendations the report makes will also directly benefit personalized medicine broadly as well. My sense is that this report won't change very extensively before becoming finalized, and when it is, it will be an important roadmap within HHS and the NIH specifically as to what PGx projects should have priority. Anyone who is working in the field should read this both to get a sense for how the wind is blowing as well as for the chance to have some impact through your comments on the direction of PGx in the next decade.