Illustration by Phillip Ortiz
Really Personal Medicine
October / November 2004
Volume 2 Number 5
Much has been written about the promise of personalized medicine, which can be defined as the application of genomic data to better target the delivery of the right medical intervention for each patient or the right choice of patients for clinical trials. Thanks to the growing availability of genomic-based tests for diagnostic testing and for use in clinical trials, personalized medicine has begun to offer new options for patient management.
The concept of personalized medicine has drawn so much attention because it impacts the way researchers and scientists look at disease, the way doctors prescribe treatment, the way reimbursement is defined and the success of clinical trials. In essence, dramatic improvements in patient care are possible with the help of personalized medicine.
Doctors know the reality: patients with the same disease demonstrate individual responses to drugs. This is especially common for cancer treatments, pain-killers, antidepressants, antiarthritics and many blood pressure and asthma drugs, and frequently results in "switching" patients from one drug to another to find the best treatment. But in the future, personalized medicine will enable specific identification of which patients will benefit from a specific treatment, which patients have a "poor prognosis" and require aggressive treatment and alternative drugs for those people most likely to exhibit side effects or who may not respond to a specific drug.
Progress in the adoption of personalized medicine will come from several areas:
—€ Pharmaceutical companies face a growing need to implement a more focused approach to drug development. Clinical trials improve by pre-identifying those patients most likely (and unlikely) to respond to a specific treatment.
—€ Physicians need better information to help them identify which patients have a poor prognosis, which ones may not need treatment, and those who will respond well to a specific drug.
—€ Technology-based companies are rapidly creating new genomic marker (or biomarker) tests for clinical laboratory testing. These genomic tests are being developed by large pharmaceutical companies like Roche, Johnson & Johnson, Bayer and Abbott, and by small startups like Exagen, Arcturus and others.
Early success stories
The primary driver of personalized medicine is the development of genomic markers to create tests that are used to diagnose disease, indicate treatment or define which patients should enter clinical trials. A more detailed scientific understanding of disease and new technologies is enabling the development of new genomic tests for use by clinical testing laboratories and/or by pharmaceutical companies; to date, early successes are many and mounting.
Some genomic tests are already in use by clinical testing laboratories. Patients with invasive breast cancer can be tested to define who should receive Genentech's Herceptin®. One-third of breast cancer patients overexpress Her2/neu, indicating they may benefit from Herceptin. The first FDA-approved test, DakoCytomation's HercepTest®, measures the Her2/neu protein and has been available since 1998. In January 2002, Abbott/Vysis introduced the first genomic test, called PathVysion®, to detect the Her2/neu gene. This genomic test has been shown to be more accurate than the test for Her2/neu protein, which means more of the right patients now receive Herceptin and more of the patients who should not receive the drug are not prescribed it. Sales of Herceptin were $875 million in 2003, demonstrating this drug's success, guided by diagnostic testing.
DakoCytomation recently introduced another genomic test called EGFR pharmaDx® that detects epidermal growth factor receptor (EGFR) in tumor cells from colorectal cancer patients. A new drug from Bristol-Myers Squibb, Erbitux®, binds EGFR; colorectal cancer patients with tumor cells that express EGFR are most likely to benefit from treatment. Both the drug and the diagnostic test were simultaneously approved by the FDA in February. As pharmaceutical companies work to define genomic marker tests for incorporation into clinical trials for new drugs, more drug/test combinations may be launched together.
Meanwhile, other advances are being made to provide definitive genomic tests that more accurately identify patient groups or determine who should receive a specific treatment. One key to a successful clinical trial is identifying and enrolling patients into the study who are most likely to respond to treatment.
One large pharmaceutical company redesigned a $10 million trial to utilize genomic markers to define which patients should enter the study. The result was a clinical trial that cost only $500,000, concluded in a shorter period of time and had a higher patient response rate.
In a similar vein, Amarin recently reported a "failed" clinical trial for Miraxion, a potential treatment for Huntington's disease. When further genomic data analysis was completed, it was determined that a subset of patients with a specific gene variant (e.g., change) clearly benefited from treatment. The next clinical trial will target patients who have this gene variant.
Advances in the development of genomic tests include the definition of combinations of markers that are more powerful than just one marker (like Her2/neu), with each marker adding accuracy due to their combined effect. The challenge is to identify the best combination of markers to create a very small "set" for testing, but only a few commercial companies have shown this capability (Exagen, Arcturus, deCode). Exagen developed platform technology that was used to rapidly define a set of prognostic markers for breast cancer; a four-marker set is currently being validated and holds promise of greater than 80 percent accuracy. Likewise, deCode's marker set of seven genes to predict response to glucocorticoids, a common asthma treatment, may approach 90 percent accuracy [BioWorld, 10/9/02]. In contrast, sets of 20 to 70 genes have a reported accuracy of 60-65 percent.
Enabling adoption
As new genomic tests are developed and introduced, use by physicians for the benefit of patients will generally be driven by physician education and reimbursement levels. Once a new test is available to clinical testing laboratories, its use is heavily dependent on physicians knowing about and ordering the test. This action requires education of physicians so that they change their current practices and is boosted by new testing standards defined by the National Comprehensive Cancer Network (NCCN) and/or the American Society of Clinical Oncology (ASCO). Both groups recommend that Her2/neu testing be performed on all patients with invasive breast cancer.
Broad patient access to genomic marker tests will be determined to a large extent by the availability of adequate coverage and fair levels of reimbursement by public and private payers alike. Coding that precedes reimbursement is also a critical element in ensuring fair payment.
The government entity that oversees reimbursement for Medicare/Medicaid, the Centers for Medicare and Medicaid Services (CMS), covers and pays for genomic tests. But there is still much work to be done to accommodate new technologies that currently have no counterpart in the coding system. The diagnostic industry is working diligently with CMS to ensure that new genomic tests will be coded to reflect the technology and the entire testing process.
While many genomic tests are covered and adequately paid for, there are notable exceptions. Medicare payment for Her2/neu by PathVysion's test has been distinctly undervalued since the test was first FDA approved, placing testing laboratories in a difficult position and placing patient access potentially at risk. CMS has agreed to re-price this test effective January, 2005.
From a legislative and policy standpoint, a "strategic investment" must be made in the reimbursement of new technology so that patients and physicians gain solid access to these life-transforming improvements. Although more expensive, the more definitive genomic marker tests offer targeted treatment, reducing health system costs that occur after the point of treatment, improving patient outcomes and enabling better medical care.
With only a few FDA approvals, genomic marker tests are in the early stages for pricing, reimbursement and payer acceptance. But as with most new opportunities, education is required for all groups involved in making these new tests available to physicians and patients.
To that end, a unique, non-profit group called the Personalized Medicine Coalition (PMC) was founded in 2003 for the purpose of advancing the understanding and adoption of personalized medicine concepts and products. This group, founded by Millennium Pharmaceuticals, includes representatives from universities, patient groups, trade associations, and information technology, pharmaceutical, biotechnology, diagnostic and device companies. By bringing together this multi-disciplinary group of key stakeholders to discuss issues, provide education and develop positions on essential policy changes, PMC aims to help move policy forward as genomic-based science and related pharmaceutical and laboratory test discovery move forward.
Early successes and advances in genomic testing speak to a future time when patients routinely receive tailored treatment based on their individual genetic makeup and discrete disease —€“ as defined by genomic markers. Genomic marker tests and new technologies give pharmaceutical companies the tools to better define disease states at the molecular level and design therapeutics tailored for specific individuals. Tests performed by clinical testing laboratories will support individual treatment as more and more genomic tests become available.
How soon personalized medicine becomes the standard depends on widespread use and rapid adoption of new genomic tests, which depends upon physician education, new testing standards and level of reimbursement. As reflected by the membership of the PMC, multiple stakeholders will help define this future, and each has a significant role.
Suzanne Z. Mattingly, Ph.D., has worked for various diagnostic, pharmaceutical and software companies and is currently a Vice President for Exagen Diagnostics, Inc. and a member of the Personalized Medicine Coalition.
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But Focus on the Patient
New devices, systems programs, diagnostic testing, clinical trials and personalized medicine all help to improve patient management. Still, what's most important to physicians and others involved in patient care is, well, patient care. With all of the technological advances, all of the new smaller, less invasive instruments, face-to-face interaction and the human touch are still central concerns for those on both the clinical and administrative sides of medicine.
The American Medical Association's core purpose, the literature says, is "to promote the science and art of medicine and the betterment of public health." Yet, as stewards of medicine and as advocates for patients and the profession, it would stand to reason that the advancement of technology would only help this cause. Not always. The AMA's policy on the state and development of technology in medicine is that advances must meet requirements of effectiveness and safety followed by cost.
Cecil B. Wilson, M. D. , a prominent AMA trustee, former president of the Florida Medical Association and an internist, acknowledges that we can get enamored with science and neglect to treat the patient. This misdirection is counterproductive, he says. There needs to be an adequate mix of both science and art to facilitate better patient care.
"There is certainly more science available now and the pace of development has accelerated," Dr. Wilson says. He believes that acceleration should be tempered by careful attention to the safety and effectiveness of any innovation.
Though the AMA welcomes technology and embraces innovation, as physicians they are more enthusiastic if that focus is directed toward their interaction with the patient. Toward that end, they are interested in the administration of health care and the advancements in electronic medical records. Additionally, the progress and improvement in technology that is already in practice in the form of the miniaturization of instruments, fiber optics and computer chips have only served to benefit the patient in that the devices decrease the intrusiveness of procedures, hospitalization duration and recovery time.
The American Hospital Association's view is similar. "Technology must support what makes hospitals run—€”people," says Rick Wade, AHA senior vice president. Technological needs grow from what allows health care professionals to take better care of people.
While physicians with their differing specialties might have specific individual needs to best serve a patient Wade says, hospitals must look at the entire operation to better meet the needs in patient care. Their interests lie in the continuity of patient care and the facilitation of what he calls "face time" with the patient. This is evolving with the bedside computer, where the medical staff can stay with the patient as they enter critical information; it also aids in patient education.
So, genomic markers, better patient IT, improvements in medical imaging and biological clues in rational drug design notwithstanding, it seems you can't yet manufacture the ever important bedside manner.
—€”Valerie McKinney
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