Editor's note: This post is part of a series stemming from the Fifth Annual Health Law Year in P/Review event held at Harvard Law School on Monday, January 23rd, 2017. The conference brought together leading experts to review major developments in health law over the previous year, and preview what is to come.
In his 2015 State of the Union address, President Obama launched the Precision Medicine Initiative (PMI), which is intended to help move medicine from the traditional "one-size-fits-all" approach where treatments are designed for the "average" patient, to one that "takes into account individual differences in people's genes, environments, and lifestyles," thereby personalizing treatment. According to the White House, a major goal is to "bring us closer to curing diseases like cancer and diabetes." In December 2016, the 21st Century Cures Act was signed into law, authorizing up to $1.455 billion in funding for the initiative, spread over 10 years (although, importantly, the statute does not guarantee any of the funds, which will be subject to budget negotiations each year).
Central to the PMI is the All of Us Research Program (renamed in October 2016 from the "Precision Medicine Initiative Cohort Program"), which aims to enroll 1 million or more volunteers throughout the United States. If successful, it would be one of the largest longitudinal cohorts ever developed in this country. The All of Us program will, among other things, seek to ascertain the relationships between various environmental exposures, genetic factors, and other biologic determinants of disease. Volunteers will contribute data in various ways, including donating blood samples, completing baseline physical exams and online health surveys, and sharing both existing electronic health records and mobile health data. Enrollment will be possible either directly via smart phone applications developed by a Participant Technologies Center, or through participating medical centers, including community health clinics and medical centers operated by the US Department of Veterans Affairs. A Data and Research Center will acquire, organize, and provide secure access to volunteers' health data, and the Mayo Clinic will manage a biobank of volunteers' biological specimens to support research efforts.
The Cancer Moonshot
In January 2016, one year after the Precision Medicine Initiative was announced, President Obama in his final State of the Union address launched a related national effort, the "Cancer Moonshot." The effort is directed by a Cancer Moonshot Task Force, chaired by the Vice President and comprising the heads of 13 federal agencies, including the Food and Drug Administration, the National Institutes of Health (NIH), and the NIH's National Cancer Institute. The Task Force is charged with leading an effort "to double the rate of progress in the fight against cancer." In addition to the $1.455 billion in funding allocated to the PMI, up to $1.8 billion is authorized by the 21st Century Cures Act to support cancer research over the next seven years, including research aimed at the development of cancer vaccines (this funding is also not guaranteed).
Challenges and Limitations
Despite the clear need for better treatments, commentators in a variety of forums have questioned whether the recent enthusiasm to conquer disease is more accurately viewed as "hope or hype" (e.g., The Wall Street Journal, Harvard Medical School, The New England Journal of Medicine, The Journal of the American Medical Association, The New Yorker, Leukemia Research, Baylor University Medical Center Proceedings, Science-Based Medicine, BioMed Central). While phrases such as "precision medicine" and "ending cancer as we know it" appeal to popular sentiment, they may also lead to hard-to-fulfill expectations. While scientific knowledge relevant to precision medicine has increased substantially in recent years, translating these findings into the clinic to truly transform patient care remains difficult. Considerable time and further research will be necessary to effectively utilize these findings in a clinical setting. In the case of cancer, varying genetic abnormalities within different regions of the same tumor (called "intra-tumor heterogeneity") mean that even a breakthrough therapy that is 100 percent effective in targeting a particular genetic defect may fail to cure the entirety of the condition (see also NEJM). More broadly, the considerable genetic heterogeneity that exists within the US population will also complicate the characterization of patient groups for which new treatment approaches are efficacious.
Others have pointed out that focusing too strongly on technology and research detracts from more basic determinants of population health, such as socioeconomic or geographic disparities, environmental improvements (e.g., clean water), or other factors that have little to do with genetics but may lead to far more measurable improvements in public health. In fact, genetic factors are often not the primary cause of many chronic diseases, including cancers. As policymakers pursue new opportunities in precision medicine, they should therefore consider that the greatest gains may still be more likely to come from public health initiatives related to non-genetic factors such as diet, exercise, smoking cessation, weight loss, or other population-level preventative interventions, than from laboratory breakthroughs or precision medicine.
Where advances in precision medicine occur, the most measurable benefits may be different in kind from what some might expect. It is true that medicines targeted to a molecular defect affecting only a subgroup of people can in some cases (e.g., cystic fibrosis) provide meaningful health benefits. However, as explained by the Food and Drug Administration, medicines that are tailored to a subset of patients go hand in hand with companion diagnostics that can tell health care providers which patients are likely to benefit from particular precision medicine interventions and which are not. Because approved drugs can be offered to all patients whose conditions correspond to the approved indication (or even prescribed for off-label indications), the benefit conferred by companion diagnostics lies not with those who are determined to be likely responders (who would be offered the treatment even if no precision diagnostic were available), but with those patients deemed unlikely to respond who are spared the costs, false hopes, and potential side effects of undergoing an ineffective treatment.
Progress and Opportunities
Despite these challenges and limitations, the social and scientific context of the PMI and Cancer Moonshot are substantially different from when President Nixon declared War on Cancer in 1971. When the National Cancer Act was signed that year, the polymerase chain reaction—a fundamental tool of genetic research—was still more than a decade away. It was not until 2003 that the successful completion of the Human Genome Project provided the molecular backdrop against which scientists can unravel the genetic determinants of disease.
Since the Human Genome Project, the cost of whole genome sequencing has fallen from tens of millions of dollars to around $1,000 per genome today — even more quickly than would be predicted under Moore's law, which in the field of computer science describes a doubling of computing power approximately every two years. CRISPR-Cas9 may perhaps have the greatest effect on precision medicine in the near future by enabling genetic defects to be edited out of the genome and resulting in the elimination of diseases with defined genetic abnormalities.
The rapid development of computer and laboratory technologies has also transformed the context of the PMI. Nearly a half century of advances according to Moore's law means that computers have orders of magnitude more processing power than they did when Nixon was in office, providing the power to analyze the prodigious volumes of data generated from DNA sequence analysis or electronic patient health records.
Today's global communication networks, statistical analysis software, and data sharing platforms bear little resemblance to those of the 1970s. Voluntary data contributions from patients via mobile phone applications or from wearable devices were not practical when Nixon's War on Cancer was announced, but can now be used to help clarify relationships between diseases on the one hand, and environmental, behavioral, and genetic factors on the other. Laboratory technologies, such as next generation sequencing, have also brought us into an "omics" era, where not only genomics, but transcriptomics, epigenomics, proteomics, metabolomics, and microbiomics data can be generated in real time, enabling researchers to study for the first time the effect of multi-omics on disease pathogenesis.
The confluence of advances in genetics, research tools, and data storage and processing technology, among other things, suggests a favorable environment in which to translate these accomplishments into meaningful improvements in clinical care. For all its faults, precision medicine holds more promise now than it ever has — particularly if Congress follows through with the promised funding.
Author's Note
Jessica Lasky-Su is a consultant to Metabolon, Inc.
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