A transformational opportunity India requires a better emergency medical service to meet the Despite increasing healthcare costs, healthcare suffers from suboptimal quality and inefficiency. Personalised Healthcare offers the transformational opportunity. This article discusses the science, enabling technologies, opportunities and challenges of moving Personalised Healthcare forward.
Increases in healthcare spending appear to be a global concern. For example, the rising costs in Asia are being driven by many of the same factors that have triggered the spiralling of medical costs in developed countries. Factors include ageing societies with more chronic disease, rising technology costs; high patient expectations of care; and more frequent coverage by third-party payers such as insurers or employers. However, the quality of healthcare does not necessarily correlate with the total spending. Take US as an example, total healthcare costs in the US were US$ 2.2 trillion in 2007, representing 16 per cent of the Gross Domestic Product (GDP), an amount expected to reach US$ 4.2 trillion in 20161. Despite this vast spending, our healthcare system suffers from suboptimal quality and inefficiency, as evidenced by the World Health Organization (WHO) ranking healthcare in the US 37/191 countries in performance2. Furthermore, studies show that prescription drugs are effective in fewer than 60 per cent of treated US patients3. The current trend is unsustainable and ineffective, emphasising the need for transformational change to create value-based, patient-centric healthcare.
Reversal of this trend will require Personalised Healthcare. It incorporates individual genetic, behavioural and environmental information to define individual prescriptions for health maintenance, disease prediction, prevention, and tailored therapy. In addition, it considers individual environments, health-related behaviours, cultures and values. This approach is revolutionary and will fundamentally transition medical practice from illness to wellness. Equally important is patients’ control over their own health by their personal prescription for health, incorporating approaches for their unique risk of disease.
Scientific advances are leading the way to Personalised Healthcare
Rapid advances in platform technologies, such as Single Nucleotide Polymorphism (SNP) analysis, the ‘-omics’ such as genomics, microRNA (miRNA) analysis and systems biology and network analysis, offer the potential for revolutionary change in the practice of medicine. Landmark projects, such as the Human Genome Project completed in 2003, have laid the groundwork for researchers to identify genetic causes and genetic contributions to complex human diseases.
For example, genome-wide association studies have uncovered new genes linked with common diseases, including coronary heart disease, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Crohn’s disease, bipolar disorder and hypertension4. Identification of disease-specific genes could lead to clinical interventions to improve outcome. In addition to genetic research, ‘-omics’ technologies, such as transcriptomics, proteomics and metabolomics have grown rapidly. These powerful tools allow researchers to link phenotype with dynamic protein production, gene-protein and protein-protein interactions to identify markers and molecular targets in health and disease.
Beyond gene and protein activation as disease triggers, underlying regulatory genetic events have drawn significant attention. For instance, miRNAs, small non-coding RNAs of 21-23 nucleotides that bind complementary sequences in target genes and cause mRNA degradation or inhibition of target protein production, are involved in the regulation of gene expression in cell proliferation, differentiation, and apoptosis. miRNAs are implicated in tumorigenesis through regulating the expression of tumour suppressor genes and oncogenes. miRNA expression is abnormal in chronic lymphocytic leukemia, solid organ tumours like lung cancer, and non-tumour diseased tissues.5-11 A recent study suggests miRNAs mediate cancer chemoresistance or sensitivity12. These tools may revolutionise disease classification, diagnosis, monitoring, prognosis, and potential treatments to drive personalised care. Similarly, miRNAs also regulate epigenetic regulation of gene transcription, another actively explored regulatory process in the genetic underpinnings of complex human disease.
Mainstream research focusses on identifying individual gene(s), molecule(s), or pathway(s) that lead to disease. The rise of systems biology tools facilitates dissecting the organisation, regulation and structure of complex systems, such as dynamic gene and protein networks that underlie human health and disease. This approach has great potential in bringing predictive and preventive medicine to reality.
Information technology and biomedical informatics are key enablers of Personalised Healthcare. Electronic and personal health records make complete and current patient information available when and where it is needed. Electronic patient phenotyping provides the opportunity to interface genetic and ‘–omic’ information with patient-specific outcomes to create novel approaches to promote health and prevent disease. These tools support clinical decision-making by clinicians and healthcare providers, thus delivering the best individualised care for each patient. Equally important is that Personalised Healthcare promises to place information technology in the hands of consumers / patients empowering them to take control of their health and managing wellness.
Personalised Healthcare is already happening, but at a slow pace
The rise of personalised medicine is the result of unprecedented advances in biomedical research and technologies, such as DNA sequencing and ultra-high throughput screening. Technological breakthroughs have dropped the price from US$ 3 billion to sequence the entire human genome to US$ 60,00013. Several countries and commercial entities are investing in technology to reduce the cost of sequencing a person’s complete genome to US$ 1,000. Price reduction in this technology will enable each person to obtain a blueprint of their genetic code in the near future.
Moving towards the goal of individualised predictive, preventive and personalised care, researchers have developed genetic tests that can be utilised to diagnose, predict and identify carriers of genetic disease and also determine the risk of adverse medication reaction. Over 1,000 genetic tests are currently available and more are being developed. A current example is testing for BRCA1/2 mutations in women with a family history of breast cancer or ovarian cancer. If a women tests positive for BRCA1/2 mutations, she has an estimated lifetime risk of 36-85 per cent for developing breast cancer, a 16-60 per cent for ovarian cancer14, and should be closely monitored for these diseases.
In addition, companies such as 23andMe, Navigenics, and deCODE Me, continue to develop tools for genetic analysis marketed directly to consumers and physicians. These tests allow consumers to evaluate their genetic risk of disease and genes defining personal traits. Consumers can take control of their own health by understanding their predisposition to disease and modify their lifestyle accordingly, providing potential long-term benefit.
Pharmacogenomics / genetics is a promising area for Personalised Healthcare, translating scientific discovery into clinical application. Pharmacogenetic testing presupposes the availability of validated genetic tests, with data linking the presence or absence of specific variants with a specific outcome, such as improved therapeutic response or reduction in adverse events. A topical example is the genotyping of CYP2C9 and VKORC1 in guiding the titration of the anti-coagulant warfarin towards the optimal maintenance dose.
Despite decades of experience and careful monitoring, the adverse events of warfarin are still among the highest of all commonly prescribed drugs15,16. The challenge of administering warfarin is due to the wide (20-fold) inter-individual variation in dose requirements17,18, the narrow therapeutic range, and the risk of serious bleeding from overtreatment, or risk of repeat thrombosis from under-treatment. Studies show that age, gender, sex, race, body mass index, smoking, diet, and drug interactions, have a significant impact on warfarin sensitivity19,20. Variability in warfarin response can result from polymorphisms in vitamin K epoxide reductase subunit 1 (VKORC1)21, the pharmacologic target of warfarin. In addition, patients with genetic variants of CYP2C922, involved in warfarin metabolism, require lower doses of warfarin because of reduced drug clearance. By applying genotype biomarkers at the beginning of warfarin treatment, one can shorten the time to reach the proper warfarin dosage, thereby reducing adverse drug reactions (ADRs)23,24. Based on these findings, the US Food and Drug Administration changed the labelling information for warfarin to recommend genetic testing of CYP2C9 and / or VKORC1 genes.
Global perspectives on Personalised healthcare
The US Department of Health and Human Services (HHS) plays a leading role in advancing Personalised Healthcare. In particular, the HHS has issued two reports with the first one released in October 2007 and the second in November 2008, demonstrating a strong focus and commitment to delivering the best care possible to each patient. Michael Leavitt, Secretary of HHS, stated that Personalised Healthcare is not a niche concern. Its promise is central to the future of healthcare. Under the HHS leadership, National Institutes of Health and the Food and Drug Administration have both embarked on the journey to Personalised Healthcare. The NIH roadmap and FDA critical path are all part of the efforts for this initiative.
Inspired by the vision, both academia and industry are advancing Personalised Healthcare research, education and clinical practice. Among many of the academic centres, The Ohio State University is committed to developing and creating the future of medicine by improving people’s lives through Personalised Healthcare. Our commitment is to help people maintain healthier, happier, and productive lives. To do so, we are implementing an innovative programme to promote the active participation of individuals in their own ‘personalised’ health maintenance and to use genetic tests and health markers to predict and prevent disease. In addition, Ohio State is developing a general patient informed consent to prospectively collect patient’s biologic specimens and DNA samples for medical research. This biobank will be linked with the patient clinical database to make it highly useful for translational research, such as human cancer genetics, individualised cancer therapy, advanced lung disease and sepsis, cardiovascular diseases, women’s health, pharmacogenomics and diabetes mellitus. The data generated by these research programmes will then be incorporated into the electronic medical record to support clinical decisions.
Personalised Healthcare or Personalised Medicine has become a global initiative. Other countries, such as the UK and Canada, have also embarked on this exciting initiative. Furthermore, countries in Asia, such as China and Japan, have played a critical role in the international HapMap project. The goal of the project is to develop a haplotype map of the human genome, the HapMap, and provide researchers around world with free access to the data to find genes affecting health, disease, and responses to drugs and environmental factors. Combined phase I and phase II projects have identified over 3 million SNPs in 269 individuals, including Han Chinese, Japanese, Nigerian, and European. The data will provide important information to guide genome wide association studies and to identify genetic variations in different ethnic groups. Finally, as part of the 1000 Genomes initiative25, Asian countries, such as China, are playing an increasing role in funding genomic research and technologies. Given the low cost of labour and their intellectual prowess, China and India are on the rise to develop research powerhouses. However, science and technology have always outpaced public policy, regulation and clinical medicine. Integrating genetics / genomics into clinical practice will be at slower pace than we wish, especially in the developing countries, given the disparity of their healthcare system.
Increasing the awareness
As research in Personalised Healthcare advances, educating healthcare providers and consumers is the key to improve healthcare delivery. There is a lack of knowledge and utilisation of clinical genetics, genetic testing and genetic counselling in the medical community and the public. Therefore, it is critical to develop Personalised Healthcare-related educational programmes through continued medical education and integrate this curriculum into medical education for medical students, residents and physicians.
Personalised Healthcare promises to be a predictive, preventive and participatory, and personalised—‘P4’—medicine. To be truly participatory and personalised, seamless and logical information technology interfaces and tools are essential. The development and application of these tools and education targeted to Personalised Healthcare is lacking.
The power of Personalised Healthcare in improving people’s health and saving cost rests on transforming medicine to disease prediction, prevention, and wellness. This will require re-engineering current healthcare reimbursements and delivery to bring healthcare to each home and community on demand. It is not just the right medicine at the right time, but more importantly, a health and wellness intervention strategy that prevents the onset of diseases. This strategy will not work without key public-private partnerships to create the tools to start a social epidemic of change in healthcare delivery.
Issues and challenges
Although Personalised Healthcare offers a transformational opportunity to change the current healthcare system, many issues or challenges must be addressed before it can become a reality, including lack of public policy, regulation, reimbursement, education, standardisation of healthcare information technology such as electronic medical records, clinical validation, adequate funding for research, and privacy concerns.
Each of these challenges must be dealt with by all of the stakeholders, including physicians, scientists, healthcare organisations such as hospitals and health networks, private insurers, public insurance providers such as Medicare and Medicaid, pharmaceutical and diagnostic companies, state governments, the federal government, and, most importantly, patients.
Personalised Healthcare holds the promise of transforming the current healthcare delivery into a value-based and patient-centric healthcare. While advances in science and technology continues at a dramatic pace, other areas such as public policy, regulation, reimbursement, education and clinical validation will continue at a measured pace. This will require all stakeholders in the healthcare arena to work together in years to come to overcome these hurdles and challenges before Personalised Healthcare can become a reality.
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LiHui Xu is currently the program director at the Ohio State University Center for Personalized Healthcare. Prior to that, Xu was the Chief Operating Officer of a biopharmaceutical company. From 1989-2001, she was a postdoctoral fellow and a research assistant professor at University of North Carolina at Chapel Hill.
Henry Zheng is the director of operations at The Ohio State University Center for Personalized Healthcare. Zheng has served in numerous leadership positions since joining OSU in 1997, as senior planning manager, business performance officer, director of Technology and Commercialization Partnerships and director of Data Analysis and Information Services.
Steven Gabbe recently joined the Ohio State University as senior vice president for Health Sciences and Chief Executive Officer of the OSU Medical Center. Prior to that, Gabbe was Dean of the Vanderbilt University School of Medicine. From 1987-1996, he was professor and chair of Obstetrics and Gynecology at OSU.
Clay Marsh came to The Ohio State University in 1985. He is currently professor and vice chair for research of Internal Medicine, director of the Center for Critical Care, and director of Pulmonary, Allergy, Critical Care and Sleep Medicine.