Originally Published IVD Technology November/December 2005
COMMENTARY
Realizing the potential of molecular diagnosticsHenry L. Nordhoff
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| Henry L. Nordhoff is chairman, president, and chief executive officer at Gen-Probe Inc. (San Diego). He can be reached at hankn@gen-probe.com. |
The IVD industry plays an indispensable and increasingly important role in providing high-quality, cost-effective medical care. According to a study conducted by the Lewin Group (Falls Church, VA) for AdvaMed (Washington, DC), even though diagnostics influence 60-70% of healthcare decision making, they make up less than 5% of hospital costs and 1.6% of Medicare costs. During the next decade, the IVD industry could play an even more prominent role in healthcare decision making, primarily due to the potential of molecular diagnostics.
Molecular diagnostics are expected to be the fastest growing segment of the IVD industry, based on their ability to provide rapid, vital, and actionable information for making appropriate healthcare decisions. According to Forbes, while the $30 billion U.S. clinical diagnostics market is growing at a 4% annual rate, the $2.5 billion molecular diagnostics segment of the market is expanding 15% annually.1
Molecular diagnostic technologies have been used primarily to test for infectious diseases. For example, Gen-Probe Inc. (San Diego) and Chiron Corp. (Emeryville, CA) have developed amplified nucleic acid assays that screen for HIV-1, hepatitis B and C, and the West Nile virus. These tests detect viral RNA or DNA directly, rather than the body's immune response to an infection. Roche Diagnostics (Indianapolis) has also developed technologies that enable physicians to monitor disease progression, not just detect the presence of an infectious agent. HIV infection can now be managed as a chronic condition thanks in part to viral-load tests that guide decisions about when to modify therapeutic regimens.
Despite such significant advances in molecular diagnostics, IVD manufacturers have only scratched the surface of the technology's potential. So what are the next areas of potential growth? Two potential applications include pharmacogenomics and cancer diagnostics.
Advantages of Pharmacogenomics
When the human genome was sequenced several years ago, many industry observers, physicians, and Wall Street analysts believed that this incredible scientific achievement would immediately usher in a new era of personalized medicine. Clearly, that has not happened. While there have been some successes in this area, they have been few and far between. However, recent events, along with a series of innovative products and business deals, have begun to accelerate the trend toward personalized medicine.
The very public struggles of the world's leading pharmaceutical companies suggest that the traditional model of drug development is broken. Success can no longer be achieved by plowing hundreds of millions of dollars into the search for blockbuster drugs, and then spending even more to market such products to wide swaths of presumably homogeneous consumers. One problem with this model is that patients are not genetically identical. A cover story in Business Week said that "the biggest problem with most major drugs today is that they don't work in anywhere from 25% to 60% of patients."2
In addition, drugs cause side effects that vary in intensity among individuals and populations treated, as demonstrated by the voluntary market withdrawals of two COX-2 inhibitors. While some of these side effects result from improper prescribing, many others emerge because clinical trials, no matter how large, cannot fully predict the fantastic diversity of real-world use. In the trade journal Advance for Administrators of the Laboratory, Gregory Tsongalis, PhD, director of molecular pathology at Hartford Hospital (Hartford, CT), wrote that "therapeutic response is highly variable between individuals and can be associated with serious adverse reactions, which rank as one of the leading causes of morbidity and mortality in the developed world."3 According to FDA, more than 100,000 Americans die each year from adverse drug reactions, while the annual cost to treat the misuse of medicines exceeds $130 billion.
Despite such risks, drugs such as the cox-2 inhibitors offer the only hope for some patients with chronic pain. Patients with other serious conditions such as cancer, AIDS, and multiple sclerosis face similar dilemmas. So how do physicians and patients, not to mention insurers and global healthcare systems, determine which products are worth using or paying for?
Molecular diagnostics can answer this question by shedding light on how individuals react to and process specific drug therapies. For example, Roche received FDA clearance for its AmpliChip CYP450 test, which detects mutations in two genes that contribute to the metabolism of about a quarter of all prescription drugs. According to Roche, the test is "intended to be an aid for physicians in individualizing treatment doses for patients on therapeutics metabolized through these genes." Similarly, an article in the New England Journal of Medicine found that variations in a gene called VKORC1 can determine patients' responses to warfarin, a drug that is commonly prescribed to prevent blood clots, but is difficult to dose correctly.4
The Diagnostics-Therapeutics Fusion
Such new technologies and discoveries demonstrate that broader use of innovative IVD products can make healthcare delivery safer, more precise, and more cost-effective. Although current reimbursement and insurance policies focus on short-term cost reductions, the value of comprehensive diagnostic testing will be better understood in the future as a means to reduce overall healthcare costs by guiding earlier and more-effective interventions. The Lewin report found that in some cases, proper diagnostics use enabled 30–50% reductions in direct hospital and outpatient charges by detecting key changes in health status, which led to adjustments in treatment. This is especially important for certain new, targeted cancer therapies that can cost tens of thousands of dollars. For example, companion diagnostics for the cancer drugs Herceptin and Gleevec have illustrated the potential of combining molecular diagnostics with therapy.
This model suggests that IVD companies could play a more influential role in healthcare delivery. Today, the IVD paradigm includes early detection, early intervention, and statistically better outcomes. In the future, IVD manufacturers will provide genotyping, monitoring, and customizing that ensures individual patient benefits, with a greater positive effect on healthcare practice. In the process, the line between diagnostics and treatment will blur. An article in Intelligent Life quoted Leroy Hood, who helped to develop the DNA sequencer, as saying, "In the future, diagnostics and therapeutics and prevention will all fuse into a continuum."5
Cancer is a good example of this fusion, and an attractive area for future growth in molecular diagnostics. The Intelligent Life story said that diagnostic tools based on biomarkers "aim to catch cancer in its early stage before it has spread and when the chance for cure is high. Biomarkers can also be used to monitor and classify a disease, identify the best treatment, and catch early signs of a recurrence."
This article also highlighted Gen-Probe's investigational PCA3 test, which may improve the diagnosis of prostate cancer. While the prostate specific antigen (PSA) test is the current standard for prostate cancer screening and monitoring, levels of the antigen are often elevated even though prostate cancer is not present. As a result, PSA screening yields many false positive results. In fact, about three-quarters of biopsies that are conducted based on an elevated PSA score come back negative or inconclusive. This is especially alarming since such biopsies are invasive, can cause infections, and are expensive to the healthcare system. In contrast, the PCA3 gene is highly overexpressed only in cancerous prostate tissue. As a result, it has the potential to exhibit a higher positive predictive value than PSA.
Potential Challenges
Based on such opportunities in oncology, pharmacogenomics, and many other areas, the future is bright for molecular diagnostics and better patient care. However, with such great opportunities come great challenges for the IVD industry. Two of the most important challenges are the way IVD manufacturers communicate, and the way they interact with their colleagues in the pharmaceutical industry.
IVD manufacturers must do a better job of communicating the value of their technologies to healthcare regulators, payers, providers, and even patients. Even though AdvaMed has made important strides in this area, manufacturers can and must do more. For example, IVD manufacturers must capitalize on the Lewin Group's report on the value of diagnostics. AdvaMed has received positive feedback on the study from key constituencies on Capitol Hill. Similarly, the IVD industry's work with FDA has paid off with the release of the final guidance on pharmacogenomic data submissions. By describing a regulatory path for new drugs that are developed along with biomarkers, this guidance was developed to "facilitate the use of pharmacogenomic tests during drug development and encourage open and public sharing of data and information on pharmacogenomic test results."
While regulators are an important audience, so too are consumers. A research report by PricewaterhouseCoopers (London) stated that "patient demand could have a significant effect on the acceptance or rejection of pharmacogenomics. If a new product captures the public's attention and patients push their doctors and insurers for the genetic test to determine if it is right for them, the mainstreaming of pharmacogenomics products could be accelerated."6 However, the adoption of new molecular diagnostic technologies will be hampered if IVD manufacturers are not able to implement privacy safeguards that protect against discrimination based on genetic information.
In addition to communicating more effectively with their various constituencies, IVD manufacturers must find creative ways to partner with pharmaceutical firms. Some of these firms will be threatened by the potential of pharmacogenomics to fragment their target markets. An article in IVD Technology said that "the question remains whether IVD manufacturers and their counterparts in the pharmaceutical industry can work together to develop the necessary technologies for personalized medicine."7 This question could be answered by emphasizing that pharmacogenomics has the potential to do the following.
Resurrect failed drugs. Drug makers have libraries of compounds that they mothballed in development due to potential toxicities. But what if these toxicities only affected patients with a certain genetic make-up? According to an article in Diagnostic Testing and Technology Report, Ed Ashwood, MD, chief medical officer at ARUP Laboratories (Salt Lake City), said, "I'd be surprised if drug companies weren't dusting off the shelves to find drugs that had been killed in clinical trials because of dangerous side effects. Pharmacogenomics could help bring some of these drugs to the market after all."8
Reduce development costs and risks. Pharmaceutical companies could design clinical trials that enroll only those patients who are most likely to benefit from treatment, presumably reducing the size and length of costly development programs.
Increase profitability. Capturing a large portion of a small market rather than a small percentage of a large market may prove to be more profitable. Pricing is likely to be competitive when patients have a strong chance of benefiting, and clinical trial and marketing costs probably will be lower.
Conclusion
These are a few of the ways in which the IVD and pharmaceutical industries can find common ground to simultaneously improve patient care and financial performance. And progress is being made. For example, Roche Diagnostics and Eli Lilly (Indianapolis) are working together to validate biomarkers that may help to determine which patients are most likely to benefit from certain cancer drugs such as Gemzar. Other similar collaborations will help the molecular diagnostics industry branch out beyond infectious-disease testing into new fields such as oncology and predictive medicine. In turn, growth in these areas will provide excellent opportunities to communicate the value of molecular diagnostic technologies to key audiences.
IVD manufacturers have a compelling story to tell, as the potential of the IVD industry is practically limitless. Manufacturers should look forward to the challenges of making diagnostics a more integral part of better, more cost-effective medical care for patients around the world.
References
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