AAAS and the Food and Drug Law Institute present
Colloquium I: Diagnostics and Diagnoses - Paths to Personalized Medicine
Summary: Monday, June 1 – Diagnostic Tools and Their Clinical Utility
Personalized medicine – treatment tailored exclusively for each patient – has a rich past and an even more promising future, according to speakers and panelists at a colloquium held at AAAS on June 1-2. However, the ultimate objective of an individualized medicine fine-tuned to identify subgroups of individuals that share distinctive biomarkers, including genetic ones, remains elusive in the near term because of scientific unknowns and policy issues that must be addressed and resolved. During this meeting, professionals involved in health, medicine, research, law, regulation, patient advocacy and other areas discussed the challenges facing the realization of personalized medicine. Researchers are rapidly sifting through the 23,000 or so human genes and finding thousands of DNA snippets that could be biomarkers for diseases and other medical conditions, colloquium participants said. A biomarker is any physical or chemical variation that can be measured and used to identify something different from the norm. While these biomarkers can be useful in diagnosing or screening some medical conditions, or in developing drugs or predicting their effectiveness, understanding the bigger picture of genomic medicine is in its infancy. Work aimed at identifying medically-related genes is far ahead of research to characterize the proteins they code for that actually affect biological activity, panelists said. Because no disease is strictly genetic, more needs to be learned about linking this new information to social and environmental factors that can play enormous roles in developing or treating medical conditions in patients. The use of new genetic information for developing diagnostic tests or treatments is further complicated by issues of appropriate government regulation and concerns about patient privacy in the use of this information. People want to know their genetic information but many are concerned about who else might obtain it and how it could be used. As obtaining individualized genetic information becomes more common, the issue of interpreting these data becomes critical, experts said. Few physicians and other health providers are trained to explain the relevance of genetic information to patients or to use it in delivering care. There also are relatively few trained genetic specialists available to counsel patients on the meaning of genetic information they might obtain. Although individualized treatment has the potential of reducing health care costs, panelists said, insurers have to decide whether or when to pay for new tests, treatments or procedures involving personalized medicine. Patient advocates and caregivers also cautioned against overly-optimistic projections of the benefits of using genetics in a new era of personalized medicine.
Session 1: A Historical Perspective of Personalized Medicine
Dr. Cowan, the Janice and Julian Bers Professor in the Department of History and Sociology of Science at the University of Pennsylvania, opened the meeting by noting that personalized medicine is not a new field. For most of human history, medicine has been personalized using the knowledge available at the time. Healers and doctors approached ill health by focusing on the patient in front of them and what might be affecting that person. This more personal, subjective approach dominated during most of the history of Western medicine, but began to change in the early 19th Century when medicine became more disease focused, experimental and uniform. This focus on the specific diseases and conditions themselves is more universal and objective, and gained favor as its benefits appeared to apply to more people. By the beginning of the 20th Century, this experimental and more general approach to healing dominated medicine.
Most people are familiar with the story of the origins of genetic medicine in the writings of individuals like Francis Galton, leading to the eugenic belief that the human race could be improved by discouraging or preventing the reproduction of persons with perceived undesirable traits. However, there is another, more positive and humane origin of genetic medicine that preceded the eugenics movement by centuries, Dr. Cowan noted.
In earlier times, forms of Hippocratic medicine with emphasis on the individual dominated in Greece and the Middle East. The basis of humoral medicine, for instance, was the belief that there was a balance in the body of certain substances and qualities. Good health involved maintaining that balance, which was different for each person, and restoring it when it went out of alignment, which resulted in illness. The qualities of hot, dry, cold and moist, for instance, were carried by four humors: blood, black bile, yellow bile and phlegm. Linking factors like these with age, time of day or year, weather conditions and other variables meant that healers had to develop very specific prescriptions for each person’s health and what it took to keep it in balance. Dr. Cowan said this was initially a very naturalistic approach to medicine that later was overlaid with beliefs and mysticism from Christianity and Islam. But the idea that no two persons were alike in their balance, and that any treatment had to be customized, assured individualized medical attention.
Modern genetic medicine originated at the beginning of the 20th century and was personalized from the start. Through observation and experimentation, a number of physicians and scientists recognized hereditary components to certain human conditions and were able to link diseases to genetics.
The work of Britain’s Sir Archibald Garrod was a major force behind the origin of genetic medicine as we know it today. Garrod studied the chemistry of pigments in urine, which led him to study patients with black urine, a condition called alkaptonuria. He found that one patient with the condition had siblings with either black urine or normal urine, but none with a gray urine. In addition, both parents had normal urine. This work coincided with the rediscovery in 1900 of the 19th century plant genetics of Gregor Mendel, and Garrod corresponded with a scientist who had reexamined Mendel’s papers. Garrod identified alkaptonuria as a Mendelian recessive disease and in 1902 published a seminal paper in The Lancet linking four diseases to heredity. In that publication, which Dr. Cowan described as the “most important paper in medical genetics,” Garrod concluded that no two people are the same chemically or metabolically, and went on to say that this physiological diversity was widespread, even if not obvious.
Dr. Cowan said she related the history of personalized medicine and the work of pioneers like Garrod to show that genomic medicine has origins that far precede eugenics and its negative associations. Although eugenics and its belief that the human species could be improved by discouraging reproduction of persons with perceived undesirable inheritable traits are part of the history of genetic research, she said, it is not a cornerstone of genomic medicine. “History shows it is possible to collect individual genetic information for reasons that are humane,” Dr. Cowan said. There are reasons to recognize eugenics and remember its negative pitfalls, she said, but this should not be used to block the progress of genomic medicine.
Session 2: State of the Science: Connecting Biomarkers and Diagnostics
Dr. Hockett, the Chief Medical Officer at Affymetrix, said solving the human genome in 2003 was significant, but did not explain the function of the thousands of genes and other material in the genome. The real challenge for genomic medicine is finding and identifying potentially thousands of biomarkers for diseases, including predisposition to disease and clues to effective treatments, in that genetic material. Biomarkers are proteins and other molecular indicators of activities going on in the body. The “vast ocean of stuff” present in the human genome codes for thousands of proteins and includes millions of small pieces of DNA called single nucleotide polymorphisms, or SNPs, that can be biomarkers. Scientists and policy makers face challenges in linking these genetic materials to specific conditions, understanding how to apply this information to medical care and educating the public and health professionals on how to understand and use results from genetic tests. There are already examples of applications that have worked, Dr. Hockett said, including tests for metabolites of certain drugs to see if they are effective and the identification of genetic perturbations that can increase a patient’s risk of adverse effects from a particular drug. The goals of identifying more biomarkers that are useful for personalized medicine include increasing the benefit-risk ratio for patients by developing clinical aids for precise diagnosis, determining the proper dosing for treatments and assessing the effectiveness of therapy. The rise of personalized medicine, which means moving from one-size-fits-all to targeted therapy, has much promise but should not be oversold or hyped as the solution to all health problems, he said. Individual health is influenced by two major factors – the genetics with which people are born and the environment in which they grow. The genetic side of personalized medicine has yet to be closely correlated with the influential lifestyle portion of the combination. Studying DNA, RNA and other bits of genetic material is only a first step. The products of this genetics, the proteins that affect biology, are where science needs to pay much more attention, he said. An explosion of available genetic information also will cause problems for medical record-keeping, which is already undergoing a transition from paper to electronic form. The current data storage infrastructure is inadequate and information needs to be stored in a form where it is accessible and useful to doctors and other caregivers.
Dr. Anderson, the CEO of Plasma Proteome Institute, noted that there are thousands of proteins in the blood, many of which could be biomarkers, but scientists do not know the clinical significance of most of them, and there are assays for very few of them. These proteins, the products dictated by DNA, carry out the body’s biological functions. Some proteins, like albumin, are very abundant in plasma while others exist only in minute amounts that have yet to be connected to specific clinical indications. A 2006 study found more than 1,200 proteins related to cancer in the literature, but it is still unknown how many might serve as diagnostic indicators of cancer or means to track the effectiveness of treatments, he said. A few plasma proteins have already proved useful, for example in diagnosing heart attacks by measuring heart muscle proteins in the blood. But in general, efforts to verify potential biomarkers and develop assays for them have lagged, Dr. Anderson said, with the number of protein biomarkers approved by the U.S. Food and Drug Administration actually declining in recent years. Inconsistent study methods that make it hard to determine whether a candidate protein is related consistently to a disease in a large number of patient samples poses one barrier to developing more biomarkers. Full biomarker development is going to require, among other things, establishing a database of each of the proteins made by the more than 21,000 genes in the human genome, learning how to make synthetic versions of them and developing antibodies to each of them. There also is a need to develop machines to simplify conducting protein assays. Methods now used are sophisticated, “research quality” technologies that are costly and require highly-trained individuals. Dr. Anderson said there also may be major patent, legal and other business issues in the future related to producing multi-protein assay panels.
Dr. Borsook, Co-Director of the Imaging Consortium for Drug Development, said that rapid advances in imaging are offering another approach to personalizing the diagnosis and treatment of patients. Although imaging does not have the “pedigree” as a biomarker that exists with more traditional genomic-based tests, it allows “seeing the invisible” in the brain to open up diagnosis and treatment, he said. There is a lack of diagnostic tools for central nervous system diseases and imaging can help fill that gap. Biomarkers that can be seen in images and scans will aid in finding problem areas in the brain and other parts of the body, and tracking the progress of therapy. In the brain, for instance, magnetic resonance imaging (MRI) and other types of scans might identify “silent” brain problems that are not obvious and open new ways of looking at anxiety, depression and other mental ills. Imaging also might provide new insights into chronic pain states, which affect more than 50 million Americans, he said. Pain is a major problem that is difficult to treat, partly because the principal way of measuring it, self-reporting, is unreliable. Many treatments do not result in a 100 percent pain-free state, and would be more effective if directed at the particular part of the brain involved. Imaging can be used to monitor pain in the brain and see the effect of specific drugs. Neuro-imaging using MRI or nuclear scans also can be used to study and monitor brain changes associated with Alzheimer’s disease, multiple sclerosis and other conditions.
Session 3: Drug Development, Diagnostics, and Personalized Medicine
Speaking on “Biomarkers in Personalized Health Care: Opportunities, Challenges, Approaches,” Dr. Lindpaintner, the Senior VP of Research, Roche Molecular Medicine Laboratories, said the role of biomarkers in individualized health care involves issues at the cutting edge of science and of society. Genomic medicine involves ethical, legal and societal considerations, including issues of patient privacy and the confidentiality of results. The concept of personalized medicine is not new, but for it to progress in the modern era will require thoughtful consideration of the consequences.
Traditionally, medicine has been about diagnosing what is wrong with the patient and designing therapies to intervene; molecular variants among patients were irrelevant to clinical decision making. Now it is understood that inherited abnormalities or idiosyncrasies affect pharmacokinetics – the effectiveness of drugs — and other aspects of treatment. Therefore, molecular variants are fundamentally important to understanding and treating disease.
Although there are possibly hundreds of molecular biomarkers in various stages of study, he said, the challenge is to find ones that are relevant and useful for patient care. In the past 20 years, advances in microbiology have provided the tools and technology to search for and develop biomarkers. But researchers may have to comb through hundreds of thousands of biomarkers to find the relatively few that will be useful in diagnostic tests. Commercial biomarkers can be validated and developed in parallel with drugs or treatments with which they will be used. However, Dr. Lindpaintner said, biology is not black and white; biomarkers will not make perfect delineations about who should or should not be treated in a specific way. Instead, there will be “likely responders” and “less likely responders” to therapies targeted at certain individuals. In addition, he said, some biomarkers enhance our understanding of disease but are not clinically useful.
Dr. Lindpaintner said regulatory agencies are getting more interested in genetics-based pharmacology, which encourages industry to do research and development in this area. Getting a diagnostic biomarker qualified for approval requires that it has consistent analytical performance, that it have a clinical benefit of showing who should be treated or not, and that the extra benefit justifies the cost of the test. Because it costs about the same to develop a therapy for a small subgroup of patients as for a large one, the realities of the marketplace come into play, he said. The market may be so small that it does not justify the cost of developing a test or therapy. On the other hand, a small market may increase and justify investment if a deadly disease is converted into a chronic one that requires sustained treatment, as with AIDS.
The development of biomarkers is essential to progress in individualized health care, but biomarkers are not a panacea that will help in every disease or condition. There will never be one-on-one custom tailoring of a patient with a disease and treatment developed just for him or her. But having a more differentiated understanding of patients and diseases will produce a better fit for treatments that are available.
One application of advances in biomarkers could be looking at older drugs that may have been withdrawn from general use because of problems with safety or effectiveness to see if they can be used with certain patients. There also may be new life for older drugs that did not pan out in the marketplace that could be licensed to new companies willing to conduct new trials to bring them to market again for certain populations.
Session 4: Taking Research and Development to the Clinic
Dr. Dalton, President and Director of the Moffitt Cancer Center & Research Institute, said that 17 percent of the nation’s gross domestic product is being spent on health care and the percentage is growing so rapidly that it will eventually bankrupt the country. The rise of “precise medicine,” which he said was a better term than personalized medicine, could be beneficial in checking some of the rising costs of health care. Precise medicine encompasses everything about an individual, including family and social needs and circumstances. Personalized medicine is pushing us toward collaboration and inter-disciplinary approaches, he said. To be effective, a new way of delivering treatment should more directly involve patients and their communities in clinical studies to find and evaluate new technologies and approaches. The National Institutes of Health has successfully pushed its “bench-to-bedside” initiative to get laboratory advances into hospitals more quickly, he said. But the majority of patients does not live close to big medical centers and will not get the advantages of personalized or precise medicine if it is not exported to their communities. “The ‘build it, they will come’ approach will not work,” Dr. Dalton said. The usual definition of personalized medicine that embodies delivering the right treatment at the right time to the right patient should also include “the right place,” which means his or her own community, he said. One possibility is to enroll larger numbers of patients into studies and clinical trials. These increased numbers would help speed results of studies of treatment effectiveness while putting patients closer to the latest findings that could apply to them. Involving patients and getting permission to follow them for extended periods would vastly increase data about the long-term ramifications of diseases, as well as improve evidence-based treatment guidelines for all patients. Dr. Dalton said his cancer center had 34,000 patients in its database and was enrolling an additional 100 each day. The Moffitt center also is building a multi-dimensional data warehouse of tissue samples that has grown to more than 9,500 since 2006. Of these samples, 6,500 have been profiled genetically. Increasingly, he said, diseases like cancer will be defined by their molecular profile and not just the origin of tissue or its histological appearance. A consortium of 17 institutions is enrolling patients and contributing tumor samples for study. This network is building an infrastructure for delivering personalized health care through sharing information from individual patients that can point to the best treatment options for others.
According to Dr. Levy, Assistant Professor at Johns Hopkins University School of Medicine, personalized medicine involves customizing all aspects of patient care and not just biomarkers, genetic tests and treatments. No clinical outcome is explained just by genetics, said this physician, who specializes in genetic medicine. Environmental and social factors still are very important. Genetics is not the major predetermining factor in disease for most patients, because genetic aspects can be modified by behavioral and other lifestyle issues. Even biomarkers that have shown some utility in actual practice leave unanswered questions to be answered. Biomarkers for genes that affect a patient’s response to warfarin, a blood-thinning agent, appear effective in helping doctors determine the proper dose more quickly. However, even with this advance, he said, nearly half of the dose variation with the drug remains unexplained, showing that other unknown environmental variables are at play. It is still unclear how to use the results of biomarker tests and what they might ultimately mean to disease inheritability in an individual patient. And no one yet knows how to combine and weigh the effects of multiple biomarkers. If a person finds he or she is at higher risk of a condition, will this knowledge actually change behavior? Does the knowledge that you are at low risk of a medical problem encourage bad behavior? While some biomarker tests on the market appear worthwhile, there still need to be well-controlled, large-scale studies to track their performance and prove their worth. Most studies done so far are big case-controlled, retrospective studies with the power to detect small effects, but they are subject to the same errors as any other epidemiological studies. The validity of a test cannot be assumed just because it is on the market, an assumption most clinicians make, Dr. Levy said. Education remains the biggest challenge, he said, because most physicians are still uncertain how to integrate biomarker results into clinical care.
Ms. Kim, a patient advocate who is the CEO of Translating Research Across Communities, Healthcare Consulting, said personalized medicine promises better individualized treatment with the focus on the patient. But she said there is a difference between hope and hype. Although personalized medicine is moving toward being the norm and not the exception, she urged scientists and health providers to avoid prematurely touting its benefits and availability. “You want to under-promise and over-deliver,” she said. Patients, as the “customers” who must buy this new approach, need to be better informed about personalized medicine. Health professionals must explain the science of genomic medicine to patients and present the information in a way that is relevant and personal. People these days are buried in information from the internet and other sources, but not all of it is good. There needs to be more research on gathering and distributing information to patients.
Summary: Tuesday, June 2 – Looking Out for the Public’s Interest
The coming new era of personalized medicine requires a new, or at least modified, regulatory environment to protect the safety of consumers and patients. More people are getting access to their personal genetic data through increasing numbers of commercial outlets and the trend is expected to increase as the cost of the technology continues to decline. Federal and state regulatory agencies are beginning to address how to protect the public from fraudulent claims while trying to assure the high quality of information, tests and treatments derived from genetic research and development. Consumers want the anticipated benefits of knowing more about their inherited genetic history but are concerned about privacy and how this information might be used. But what is information if patients and caregivers are unsure of what it means? Most health professionals have little training in genetics and its application to patient care, and there are relatively few certified genetic counselors. There is a critical need for better education of both the public and health professionals about genomic medicine if the promises of more personalized care, including better outcomes and reduced costs, are to be realized.
Session 1: Testing in the Open Market
Ms. Avey, co-founder of 23andMe, said people should have access to their genetic data, not as a privilege or an option but as a right. The information about their genetic makeup is empowering. What is available now, some biomarkers and data on some 600,000 small segments of DNA, is tiny compared with what is coming. Whole genome sequencing will be available for each person as the cost of the technology continues to fall and interest in knowing one’s entire genetic makeup increases. “People want to know about their genetic information,” she said. Personal genetic information can be more useful than family histories in determining an individual’s risk for health problems. Using saliva samples, Ms. Avey’s company, 23andMe, is able to provide clients with information on their ancestry and more than 100 traits that may have health implications. This information is bolstered with data from questionnaires. The company is creating online groups of people who share common genetic markers or conditions who can pool information for themselves or researchers. Ms. Avey said the company recently got a grant to sign up 25,000 patients with Parkinson’s disease for genetic testing. It is an obligation of the company doing genetic testing to explain the results clearly to its clients.
Dr. Harper, Acting Director of the Division of Chemistry and Toxicology Devices at the U.S. Food and Drug Administration (FDA) said that regulating molecular diagnostic tests is a complex issue for the FDA and other agencies involved. The FDA is committed to advancing personalized medicine but wants to be rigorous in the process of approving genetic tests. The agency’s 2005 Critical Path Initiative is aimed at moving more products out of the research phase and to the consumer, including medical tests. The FDA is concerned that genetic diagnostic tests be reliable and that both patients and health care professionals understand both the value and the limitations of the tests. Premarket reviews include analyzing the accuracy and reliability of test candidates, checking how well the test might work in clinical situations and making sure labeling includes accurate instructions for use and proper warnings. Results from such tests should be repeatable and reproducible, should be validated within the intended-use population. The agency is working on modifying a long-standing policy that has resulted in a two-tier system for reviewing genetic tests. Test kits developed by commercial companies must be reviewed by the FDA prior to marketing. However, under current regulations, tests developed in a laboratory for use only in that laboratory, for instance at a medical center, do not need to undergo FDA review even if used on patients. Genentech, a biotech company, has petitioned the agency to require pre-market review of laboratory developed genetic tests as it does commercial ones. Even with this disparity, Dr. Harper said, the FDA has the power to take action against laboratory developed tests when it believes patients are at risk. Among the big challenges with regulating biomarkers are what level of clinical evidence is needed for FDA approval, for use by clinicians, and for reimbursement by insurance payers, and how to balance innovation and patient protection.
Ms. Botha, a staff attorney with the Division of Advertising Practices at the Federal Trade Commission (FTC), said that her agency has jurisdiction over advertising claims to consumers that involve health products, including genetic tests. The agency does not pre-approve advertising or products, but monitors and pursues false and deceptive advertising when it arises. “The FTC is basically a law enforcement agency,” she said. Advertising must be true and not misleading, she said, and there must be no deception by omission or presentation. The level of substantiation required for claims varies with the products and the consequences of misuse or abuse. Because the FTC is not a science agency, it consults with other agencies, like the FDA, for scientific validation. The FTC is small with limited resources, so it encourages industry to regulate itself. Therefore, its priorities include monitoring products that claim to treat or cure serious diseases. Ms. Botha said the FTC has been looking at genetic testing advertising claims, but its investigation is ongoing and she could not discuss its current status.
Session 2: Testing in the Open Market – Part 2
Ms. O’Keefe, Acting Chief of Laboratory Field Service at the California Department of Public Health, whose agency is responsible for regulating and licensing laboratories, said that in 2008, regulators started seeing genetic tests offered over the Internet. Looking at what is called a “clinical laboratory test,” regulators decided that tests for determining a person’s genetic profile were diagnostic predictive genetic tests and that laboratories offering them were subject to state jurisdiction and licensing. Genetic testing has been around for a long time, for example, tests for cystic fibrosis. What is new with the latest tests is the use of software algorithms to predict risk, she said. In order to be licensed, a laboratory must be run by a certified expert, in this case a certified geneticist. Last year, California asked 14 companies, including some located outside the United States, to stop offering online genetic tests to its residents. Of these, five laboratories have since been licensed by the state and others have posted disclaimers that their tests are not available in California. Ms. O’Keefe said the state of New York has taken similar action. With an expected 20 percent annual growth in such Internet offers, she said, regulators need to be more active in protecting consumers from direct marketing of personalized medicine products.
Dr. Jacques, Division Director of Items and Devices at the Centers for Medicare and Medicaid Services (CMS) said that CMS requires evidence of a clear benefit before approving a diagnostic test. And even then, Medicare has rules on when a diagnostic test can be ordered and by whom. If a test is not ordered by a physician for a direct health reason, “we will not pay for it,” he said. An advisory panel on coverage guidelines recently recommended that the standards for genetic tests should be “at least as high” as for other diagnostic technology. Before approval, a genetic test must be considered in a clinical context, including how it would be used and the consequences of misguided treatment or of non-treatment stemming from its use. Dr. Jacques noted that his agency would not pay for what he called “recreational testing,” like the general genetic information offered by some companies.
Session 3: You, Biomarkers, and Your Rights. Looking Beyond the Science
Patient advocacy has changed considerably since the 1950s and 1960s, said Ms. Terry, the President and CEO of Genetic Alliance. There are now more than 1,000 organizations pressing the cause of different diseases and health conditions and issues. Patient advocacy used to be just support and information sharing, she said, but it has evolved into research advocacy. At this time, the reaction of advocacy groups to personalized medicine has been mixed, with some expressing high interest and others little at all. With new information technology, Ms. Terry said she sees people developing social networks based on genetics. This approach is illustrated by the Genetic Alliance Biobank, a centralized biological and data repository she helped found, where different groups combine samples and information in one place on rare genetic diseases. There is a sense among the public that privacy is an important issue that must be addressed in genetic medicine. People also expect transparency about genetic testing and openness about individualizing medicine. Proponents of this personalized approach to medicine not only have to educate the public, but they need to send consistent and realistic messages on what it means.
Ms. Davies, a genetic counselor at the Median Clinic in Toronto, said that for the past 20 years, genetic testing has focused on diagnosis of rare diseases that are relevant for only a small percentage of the population. But it is now moving into the areas of genomic tests for common conditions, assessing risk of developing disease and other applications. Personal genome testing has the potential to revolutionize the practice of medicine, enable health care providers to better understand the medical needs of people, design treatments, and customize those treatments based on genetic markers that affect drug metabolism. Although there are many potential benefits of genome testing, there still are limitations to realizing them. These include limited data, how to interpret what is found, and the inability to combine risks associated with genetic markers with family histories. There also are ethical concerns about testing for curiosity’s sake, potential genetic discrimination, and questions of intellectual property when test results are used in research or product development. There are also concerns about education and interpreting results to provide genetic counseling to patients. Once people get genetic test results, how can they be related to specific medical conditions, which in some cases may have multiple factors, and then translated into advice for the patient? Physicians have relatively little training in understanding genetics as it applies to patients and there are a limited number of trained genetic counselors, with only 2,200 currently certified in the United States, she said. Medicare and some other payers do not reimburse for genetic counseling, further limiting access to these services even as there is a growing emphasis in personalized medicine.
Mr. McInerney, the Executive Director of the National Coalition for Health Professional Education in Genetics raised the issue of educating a range of health practitioners in genetics and genomic medicine. In 1991, clinical genetics was the last new medical specialty certified. With the rise of personalized medicine, which involves many specialties and disciplines, training in genetics should be decentralized to some extent and spread more broadly. Generally, many health care professionals, including physicians, are unprepared to deal with genomic medicine, he continued. An advisory panel to the Department of Health and Human Services concluded in 2008 that practitioners had trouble keeping up with the rapid advances in genetic testing and were not adequately prepared to apply this test information to patient care. The challenges to medical education include finding ways to insert more genetics training into already crowded curricula and having enough knowledgeable faculty to teach it. A recent survey of 112 U.S. and Canadian medical schools found that 77 percent of them teach genetics in the first year with basic science courses. This instruction primarily focused on general science rather than medical applications, Mr. McInerney said, and came long before clinical training, creating a disconnect between the science and its. Wider use of individualized medicine also should mean rethinking the relationship between genetics and illness. Health providers should stop using terms like “genetic disorder,” he said, and rephrase the question “Is this a genetic disease?” to ask, “What is the role of genes in this condition?”
Session 4: You, Biomarkers, and Your Rights. Looking Beyond the Science – Part 2
Dr. Sankar, a fellow at the Center for Bioethics at the University of Pennsylvania, said that when looking at ethical issues related to personalized medicine, you have to ask: “Is ethics beyond the science or in the science?” One has to ask if personalized medicine will help U.S. health care with the myriad problems it is facing, she said, while acknowledging that it will not address some of the more pressing issues. It should not be a surprise that the application of genomic medicine is turning out to be more challenging than anticipated. In genomics and genetic research, one size does not fit all. Finding a marker for a disease does not mean everyone with that trait can be treated the same. When genetic information is applied to personalized medicine, patients will still respond differently to disease progression and treatment because of environmental factors that might include other complicating health issues, differences in drug metabolism or even compliance with treatment regimens. The most important thing about treatment is that it be effective, and it is not yet known if individualized treatment will make a difference in outcome, as some envision. Although there is promise in personalized medicine, its benefits have not been proven and advocates should be cautious when touting its promise. “All I am suggesting is that it is not ready for moving into the clinic,” Dr. Sankar said. “It is not ready for prime time.” There is an overload of information from genetic testing that neither patients nor their doctors fully understand at this point. Even if they understood it, who would use it and how? A question people should be asking is whether some of the resources being appropriated to develop personalized medicine might be better spent on other important health issues affecting the country like childhood vaccination, HIV infection and AIDS or chronic obesity. The most important ethical issue in personalized medicine is social justice, access, and resources.
Dr. Hudson, the Director of the Genetics and Public Policy Center at Johns Hopkins University, said that more people want to know what their health risks are, but it is unclear how this knowledge might affect their behavior. Some say this knowledge will help patients change their behavior in order to mitigate risks. This has not proved true in many cases in the past, so the biggest benefit of genetic knowledge in personalized medicine may be in treatment – delivering the right drug to the right patient at the right time. For this to happen, oversight by regulatory agencies and educating patients and health care providers will be critical. Society also has to figure out who wants this whole spectrum of genetic information and what they will do with it. The current regulatory system is ill-equipped to handle the challenge of personal genomics and reform is required, she said. It is important that the regulatory process be transparent and that oversight be based on risk. High risk tests should be subject to independent review before marketing, and not just the data and interpretations supplied by the company that wants to provide the product. Genetic tests should be held to a high standard of accuracy, and claims made about the effectiveness and value of these tests should be closely monitored.
Session 5: Keynote Address
Health care reform is imperative in the United States and personalized medicine could have a role, said Dr. Stephan, the President and CEO of Ignite Institute for Individualized Health. Health care is now consuming more than 16 percent of the gross domestic product and in a few years, that amount will rise to 40 percent. “We are headed for a health care crisis,” he said, citing the changing demographic of an aging population as a major reason. The country has a small window of opportunity to alter this trend, but economics should not be the main driver of reform. Genomic medicine could help potentially by being used to alleviate or delay the onset of chronic disease and decrease the time people stay sick. Personalized medicine will change medicine from reactive and generalized to proactive and personalized, he said. In helping to produce a healthier population through improved disease management and better prevention, it would also cut costs. Key to this is identifying all genetic biomarkers for major diseases such as Alzheimer’s, diabetes and cancer, and using this knowledge to reduce the risks of contracting them or delay their onset through behavioral changes and other preventive strategies, as well as targeted treatment. When people are given genetically-based risk factors, they do change their behavior, unlike with standard risk factors, he said. There is something different about how people relate to genetic information. For Alzheimer’s disease, genetic markers have already been identified that show major predisposition to the condition. In addition, functional MRI brain scans can track increased glucose absorption, an indicator of early onset. This information, coupled with the development of preventive drugs and other strategies to delay onset, could dramatically cut the medical and economic impact of Alzheimer’s, which now costs Americans $148 billion annually in direct and indirect costs. Dr. Stephan said delaying onset even five years throughout the population would improve the quality of life for millions and dramatically reduce prevalence of the disease. We need to shift costs from end-of-life care to wellness programs by starting earlier with genome-based personalized medicine. Developments in health information technology will accelerate personalized medicine. Genetic information would be embedded in electronic health records, allowing new knowledge that affects a patient to be integrated quickly. However, having so much personal information concentrated in electronic records raises sensitive issues of privacy and who has access to it.