Building an innovative model for personalized healthcare
BARRIERS TO THE APPLICATION OF PERSONALIZED HEALTHCARE
The availability and potential of personalized healthcare services and technology is not universally recognized or appreciated by consumers and clinicians. This lack of awareness contributes to a shortage of public support and limited demand for such services. Other barriers include misperceptions regarding the impact of personalized healthcare on disease management, limited incentives to use the available technology, and a knowledge gap among healthcare providers.
Lack of awareness and support
As applications of personalized healthcare advance to the point of clinical relevance, it is important to consider strategies for effective implementation into healthcare practice. Personalized healthcare, when more fully implemented, promises to accelerate the progress that healthcare reform hopes to achieve.
A major challenge to widespread adoption of personalized healthcare is limited recognition by the public and some healthcare providers that personalized healthcare can help to achieve better value. For personalized medicine to be embraced, the concept of “helix to health,” or translation of knowledge to the clinical setting, must resonate with the general public. Despite lack of public and provider awareness, the Personalized Medicine Coalition (PMC) has documented the existence of 56 personalized treatment and diagnostic products. Further, more than 200 product labels now recommend genetic testing prior to use to identify likely responders or inform of the influence of genetic variation on safety and effectiveness.
Consumers’ confidence in the efficacy and safety of medicines they take might contribute to the absence of public support for personalized healthcare. Similarly, despite the availability of genomic tests and tools, many physicians who might be advocates for personalized healthcare do not see the relevance of genomic medicine to their practices in terms of direct benefit to patient care.7
Apart from clinicians and consumers, support is also weak among health insurers and employers, even though the return on investment for personalized healthcare may be profound. Payers await the economic outcomes data that are crucial for their commitment to personalized healthcare. In addition, some have concerns about the ethical implications of personalized healthcare (see “Managing Genomic Information Responsibly”).
Perception of impact on treatment and prevention
A frequent criticism of genomics in medicine is that a genetic diagnosis does not help with patient management. In fact, surveillance and management of patients and family members often changes in response to a genetic diagnosis; knowing which gene is involved personalizes medical management. An example is the management of hereditary nonpolyposis colorectal cancer (HNPCC), or Lynch syndrome, which is the most common form of hereditary colon cancer. For a person with HNPCC, the lifetime risk of developing colorectal cancer is approximately 80%. Lynch syndrome is caused by germline mutations in one of three major mismatch repair (MMR) genes (MLH1, MSH2, and MSH6), and it predisposes to other cancers—uterine, stomach, and ovarian—as well. In women with Lynch syndrome, the lifetime risk for uterine cancer is 40%, compared with 4% in the general population.
At least 90% of patients with Lynch syndrome can be detected through MMR testing via microsatellite instability (MSI) or immunohistochemistry (IHC).8 MSI is a cellular phenotype that indicates a deficiency in at least one DNA MMR protein.
Although 5-fluorouracil–based chemo therapy is the standard of care for treatment of colorectal cancer, it confers no survival advantage in patients with MMR-IHC null (lack of expression of the gene) or MSI-high sporadic colorectal cancer.9,10 Knowing the status of MMR proteins, therefore, would alter the decision regarding neoadjuvant and adjuvant chemotherapy.
Perception of value
Implementation of pharmacogenomics into clinical practice has lagged. One major reason is the lack of an obvious business model for a product that may only be required once in an individual patient’s lifetime.11
A second barrier to integration lies in the limited demand for pharmacogenomics from physicians. This may be related partly to limited expertise in genetics among many physicians and to significant pushback from payers against today’s costs. Without reimbursement, little incentive exists for pharmacogenomics diagnostics. The incentive for physicians is further depressed, perhaps appropriately, when randomized controlled studies fail to demonstrate improved clinical outcomes with the use of pharmacogenomicbased treatment strategies. Two such examples are genotype-guided warfarin dosing, which failed in a randomized controlled trial to improve the proportion of international normalized ratios in the therapeutic range,12 and dosing of clopidogrel based on platelet reactivity, which did not improve outcomes after percutaneous coronary intervention compared with standard dosing in a randomized double-blind clinical trial.13
A significant delay in obtaining the results of pharmacogenomics testing, which also postpones the prescribing encounter, is another major drawback.
A knowledge gap persists
At present, delivery of personalized healthcare is not part of the usual training of physicians and other healthcare providers who are the gatekeepers of medicine. Few medical schools incorporate human and medical genetics, genomics, and pharmacogenomics into their curricula. Genetics is inadequately emphasized in residency curricula outside of pediatrics, family medicine, and obstetrics/gynecology.
The resulting knowledge gap is a fundamental factor in the lack of interest in using genomics in clinical medicine. Educating consumers and physicians at all levels, including specialty societies as well as insurers, will be key to expanding utilization of personalized healthcare. Educating payers and providing them with more data on economic outcomes associated with personalized healthcare will be necessary for adoption into clinical practice; implementation will lag as long as reimbursement decisions do not support personalized approaches to medicine.
As DNA sequencing technology has become less expensive and more powerful, companies have begun to market personal genomic testing. As a result, patients who use these services will increasingly want to discuss the results with their physicians. A significant number of clinicians are unfamiliar with personal genomic testing and emerging genetic testing options. In one survey of physicians who attended educational sessions that discussed recent developments in clinical genetics, only 37% indicated that they were familiar with recent genetic research that affected their patients.14
Targeted education will enhance physicians’ understanding of probabilities and risk estimates from the use of genomic testing; it will also improve recognition of potential causes of patient anxiety, gene variants of unknown significance, and follow-up tests and procedures that can add to expense. Nonphysician healthcare providers (ie, nurses and physician assistants) of direct care also will benefit from education.
