Like so much in life, the concept of precision medicine is simple enough: to make sure the treatments and therapies used with patients match their unique genetic wiring based on the latest science and powerful analytic tools. But it’s not so simple.
According to the National Research Council, precision medicine incorporates genetic, environmental, and lifestyle factors into a patient’s treatment. It encourages the use of the term over “personalized medicine” for clarity, since personalization can convey much beyond the specifics of diagnosing and treating a patient’s medical condition. A key element of precision medicine is pharmacogenomics, a relatively new field that combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to variations in a person’s genes. The early results of precision medicine have taught us a lot about treating cancer and certain maladies in children and there’s promising signs for neurologic and mental health disorders and others. But in precision medicine, the more we know, the less we know. Thus the conundrum.
Years ago, I started the Vanderbilt Center for Evidence-based Medicine working closely with the health system’s biomedical informatists, medical librarians and clinical research teams. The task seemed simple enough: make sure the latest science was the basis for how our patients were treated, and monitor adherence by our care teams to evidence-based algorithms and step therapies. It wasn’t easy then or now. Staying abreast of breakthroughs in precision medicine research was a key element of our task. But then as now, there are challenges in precision medicine that must be addressed:
The Limits of Evidence: When incorporating signs, symptoms, risk factors and co-morbidities into a diagnosis, then adding environmental, lifestyle and patient preferences into the mix, there’s scant evidence upon which to base a definitive conclusion. The databases combining millions of patient records with external data about their lives outside controlled clinical trials are limited. Patient registries for certain chronic and cancer populations are promising, but inadequate. We’re making progress, but not fast enough. And a methodology that’s commonly used across the health system to systematically assess strength of evidence is needed, especially one that can be easily understood by patients and consumers. The bottom line: strength of evidence the efficacy and effectiveness of precision medicines is still a work in process for many biologics in the pipeline.
The Limits of Clinician Acceptance: Physicians are skeptics. They prefer their own tried and true methods if even shown outdated. In the real world, suggestions from genetic counselors, medical librarians, online search tools and even professional society recommendations take a back seat to a clinician’s gut instincts. Though the computational power in the burgeoning field of biomedical informatics is impressive, many clinicians prefer to practice from habits and preferences, rather than proven scientific best practices. And often patients are unaware. The bottom line: precision medicines find their way into routine practice settings slowly, even when evidence of their effectiveness is strong.
The Limits of Funding: Contrary to some views, the healthcare industry is not a money pit. There’s a limit to what can be spent however uncomfortable the concept. Precision medicines that are proven to work help a few at the expense of the many. Investors and clinical researchers see the opportunities for biologics that are efficacious and effective as gold mines; patients see them as clinical salvation; and the rest hope access can be more widely available at lower costs. The lack of a coherent policy about access to and funding for the expansion of precision medicine is a fault line that needs attention. The bottom line: paying for precision medicines is not a payer issue, it’s a systemic issue impacting every sector.
What’s ahead for precision medicine?
There’s no question the future of the health system will be re-shaped by precision medicine: applying genetics to the mix in clinical research opens a world of ways to diagnose more accurately and treat more precisely. The reality is that clinical innovation is progressing at warp speed, while system design, delivery and financing is progressing much more slowly. Precision medicine will not become the standard of care expeditiously in the U.S. because our delivery and financing schemes are change resistant.
In the Affordable Care Act, three mechanisms attempt to mitigate the lethargy:
1-Comparative Effectiveness: The Patient Centered Outcome Research Institute’s (Sections 6301, 6302) aims to bring comparative effectiveness studies into the public domain, but their efforts since 2013 have produced modest results for the $1.4 billion already invested. In all likelihood, private sector efforts led by provider research organizations and clinical analytics organizations will continue to press forward ahead of public efforts.
2-Provider Incentives: The shift of provider incentives from fee for service to value that incorporate outcomes into equations encourage providers to integrate diagnostics and therapeutics that work best the first time in accountable care organizations (Section 3022), bundled payments (Section 3023) and primary care innovations (Section 3021), but the short term methods for defining value and incentives don’t align with the costs associated with their inclusion. Investments in precision medicine are likely to be from strategic investors seeking to combine a promising DNA insight to their current portfolio rather than financial investors looking for a home run. Thus, the continued convergence of large (bio) and small molecule (drugs) companies in the $900 billion global biopharma industry.
3-Care Coordination: The creation of a ‘new healthcare workforce’ (Title V) requires teams of clinicians to apply evidence to care, work as teams and use data and technologies that provide roadmaps for medical management. But in most settings, a new healthcare workforce is prone to debilitating self-defeat. Margin pressures, shortages in key skilled professions and a general sense of hopelessness pervade healthcare workplaces. It’s one thing to pronounce the future is precision medicine; it’s quite another to deliver it consistently in our pluralistic payer world where the workforce is dispirited.
I am hopeful about the promise of precision medicine. I understand the limits of data and allure of mega-bucks for those who take the financial risk in its development. The reality is it will be evolutionary: the development of tools and methodologies necessary to apply it consistently to increasing numbers of discreet populations is a 25-year journey and we’re behind. The government’s efforts will be helpful, but the path to precision medicine is more likely advanced in the private sector. And rationalizing payments for these is a complicated debate few on Capitol Hill seem prepared to tackle.
Precision medicine is our future, but it poses a conundrum for our system of care. After all, assuming we have access to the latest drugs and technologies is as American as baseball and apple pie. But big questions must be addressed: How do we standardize it while addressing smaller populations? How do we deploy capital efficiently toward therapeutics and companion diagnostics where the ROI is not short-term? How do we reward risk takers? How do we restrict gamesmanship and price gouging? How do we expand its evidence-base to include the rich diversity of traits, preferences and treatment methods necessary to being precise? How do we integrate precision medicine into mainstream delivery? How do we integrate precision medicine into national coverage decisions and formulary designs more expeditiously and consistently? How do we obtain funding from other developed systems of care in the world who benefit from our precision medicine advances? How do we engage patients, consumers and voters in these complicated discussions? And how do we pay for all this?
There’s no doubt drug manufacturers and their investors will continue to beat the drum for precision medicine. There’s no question precision medicines will find their way into routine patterns of care in most communities. But the gap between what’s known and what’s practiced remains wide, and the promise of precision medicine compromised as a result.