Are diseases burdens or opportunities?
We are all too aware of the immense global burden of heart, lung and kidney failure, and the challenges they pose to communities, health systems, care providers, and patients and families. The impact of ischemic heart disease alone outstrips all other socioeconomic burdens in health, while not including diseases of the valves, cardiomyopathies, and developmental abnormalities. Chronic obstructive pulmonary disease, third in the world as a cause of death, is now second in the U.S. Other common conditions like asthma, pneumonias and various forms of environmental lung disease still plague people of our planet. The epidemic of dysmetabolism and obesity that now enwraps almost all societies is associated with a progressive frequency of renal disease and failure. Old-age associated dementias, ischemic brain diseases and cognitive impairment evoke fear for patients and great concern by architects of health care for the emerging 21st century.
Many of the risks and illnesses we face are termed “chronic” diseases. They do cast a shadow on health for years and in many instances for nearly a lifetime. Indeed, the roots of these “organ-based” conditions reside in the prenatal and perinatal periods and then evolve under the influence of environments, behaviours and genes over a lifetime. Yet, these chronic diseases are punctuated by episodes of acuteness and precipitant decline which lead to urgent care utilization and to cost-centre incursions underlying our painfully bloated healthcare budgets.
The enormity of the challenges in healthcare delivery cannot be overstated, but neither can the opportunities to make changes that alter the cost curve while improving quality of care and patient experiences. Tools to identify people at risk with early disease, susceptible to rapid decline or unresponsiveness to various therapies are emerging. Better predictive, diagnostic and prognostic tests are now possible through the alignment and interrogation of multi-marker data sets that can represent the “system of health, risk or disease.”
The PROOF Centre of Excellence resides at the eye of the storm in enabling a new era of laboratory medicine that supports better care for the many patients suffering from chronic diseases.
Can medicine really be more personal?
Personalized medicine shines before us like the Holy Grail. The term (or a poor variant like precision medicine) is used more and more – the right drug, for the right patient, at the right time, in the right dose, at the right frequency – in a very pharmaco therapy constrained context. However, there is much speculation on the promise of the molecular genetic approach alone to render widespread, person-specific prevention and care. The essential inclusion of high quality data and information regarding environmental influences (physical, ethnic, social, economic, educational, therapeutic, etc.) and behaviours (diet, physical activity, stress reduction, substance abuse, medication compliance, etc.) is often taken for granted or ignored in the rush to think about genes. Humans are not locked in cages, do not have standardized light-dark cycles, did not come from the same genetic stock, and have widely variant journeys that modify their gene expression, their regulatory systems and their responses to stimulation or injury. With these caveats, and while truly personalized medicine is currently less rather than more common, even in the most advanced societies, we are seeing great strides, especially in areas such as biomarker development, pharmacogenomics,and oncogenomics—inching towards a more tailored approach to health care.
Personalized medicine will not be achieved in a basic laboratory, by a government, through a private corporation or as individuals alone. If there is anything we have learned on this first leg of the journey, it is that we must build on the potential of diverse teams, knowledge and resources to truly achieve anything of pervasive and lasting value. Humans and their societies are complex, so we know that the solutions will not be immediately simple in production or implementation. Tapping the value that resides in a full range of sectors has become a maxim for success. Others like Drs. Federica Raia and Mario Deng would say that we need to consider the entire interface between new technologies and human beings, what they define as Relational Medicine in order to be truly effective in an era when technology appears to dominate our lives as patients or caregivers.
What has the PROOF Centre learned that we bring to the table?
In the Centre of Excellence for Prevention of Organ Failure (PROOF Centre), teams are developing high-value biomarker-based blood tests for improved patient management, especially those with heart, lung or kidney failure. A world-leading analytics team in the PROOF Centre is harnessing the power of clinical, molecular and computational data and nuances to move laboratory medicine into a new dimension of impact for patients and their caregivers. Health economists are providing essential and rigorous guidance on questions of value and in the development of decision support tools that can help to assure better tests and make them more useful. Similarly, outcome collaborators are poised to assess the impact of new tests along the life cycle of organ failure on patients, their families, caregiving and the healthcare system itself.
PROOF Centre’s core strengths relate to critical guidance by expert clinicians regarding unmet needs in clinical management that could be addressed by a new generation of sensitive and specific blood tests. The multimarker tests are reflective molecular science of human biology and its systems, are generated by a layered data analytics strategy, and draw scientists, practitioners, and trainees to the challenge that extends across all disciplines, sectors and geographies. Together this team harnesses all relevant perspectives necessary to mature and implement new blood tests. Such tests are driven by the desire to prevent disease or catch it early in an accurate fashion, and to enable physicians and their teams, whether they practice in primary or quaternary care settings. Such a thrust is also influenced greatly by patient needs and comforts. Tools to accelerate and make drug discovery programs of the pharmaceutical industry more efficient are also front and centre. Thus, the development of companion diagnostics or providing support for more efficient drug development pipelines, including cohort enrichment and patient population stratification, are among our day-to-day objectives.
By brief examples, the team, in strong collaboration with physicians and scientists of Alberta Heart and Dr. Ignaszewski locally, is working on new tests to correctly and more quickly identify patients as having chronic heart failure than possible now without imaging at regional or quaternary centres. Such blood tests, as well as those to identify different subtypes of chronic heart failure and to monitor patients for recovery of heart function from drug therapy, will improve care. For acute heart failure patients, teams including Dr. Anson Cheung have identified biomarkers that predict outcomes such as survival and response to mechanical circulatory assist device therapy. These tools are expected to lead to better patient care through appropriate targeted therapies.
With many collaborators, especially Dr. Don Sin, the PROOF Centre is also committed to develop new blood tests to manage COPD patients, hopefully reducing their need to access urgent care through early recognition of their individual risks of acute exacerbation (lung attacks). We are similarly intent on helping to forecast the rate of decline in lung function in COPD patients, which will improve patient management directly and in hastening drug development by industry. In another example, the most advanced, the decade-mature Biomarkers in Transplantation program will render tests to be implemented at the St. Paul’s Hospital clinical laboratory for validation and real-time studies this year. This critical implementation step occurs through the expertise of Drs. Dan Holmes and Mari DeMarco, and with the collaboration of HTG Molecular Diagnostics, Inc. A majority of heart transplant patients could thereby ultimately forego the need from so many invasive heart biopsies during the first year post-transplant.
The PROOF Centre currently has developed blood test content for more than 15 indications in acute and chronic heart failure, chronic obstructive lung disease, asthma, chronic kidney disease, and heart and kidney transplantation. They also have major biomarker collaborations related to spinal cord injury and muscular dystrophy.
It is worth emphasizing once again that each biomarker program begins with understanding patients and their pressing clinical needs. The team works to develop clinically relevant diagnostic, prognostic and monitoring tests for earlier diagnosis and more effective and patient-friendly care of patients as well as guidance tools for the pharmaceutical industry. Blood tests are tailored to maximize patient benefit while reducing healthcare costs. The diversity and depth of the team mirrors the degree of difficulty in getting across the goal line with products. It is easy to get to the “red zone” with partially validated biomarker solutions, but it requires everyone on the field to score the touchdown.
Why is the future all about systems?
From molecule to population, biomarker development, for whatever end purpose, demands a systems attitude. In fact, it is a systems within systems within systems within systems philosophy that is required. From DNA to protein, to metabolite, to cell, to tissue, to organ, to whole organism, to community, to health system – all must be under consideration. Then, the fine art is taking that complexity and reducing it to signatures that define or relate to patient phenotypes and physiology in precise and accurate ways for given risks and diseases.
To achieve this complete view, we need to embrace new tools and technologies; we need to not only think of the gene for example, but also the epigene; we need to think about biological networks, social networks, linkages among medical disciplines, policy networks, engineering innovation, community designs, and as Dr. Mark FitzGerald would remind us, about “humanomics”, the artful core of health care. We need a truly systems approach to developing new, powerful solutions to improve health and meet, face on, the towering shadow of chronic diseases.
Can BC and Canada harvest their great opportunity in personalization of care?
Personalized medicine requires collaboration. It especially requires enabling frameworks for data management. While there is understandable emphasis on “Big Data”, since there is SO much data within various resources, generated from such platforms as “Next Generation” sequencing technologies, yet there is simply a need to share data of all types and sizes in order for value to be realized in a timely fashion. We are fortunate in Canada to have many data resources of direct pertinence to the efforts to improve health care. A number of these resources are national in scope. In BC alone, we host expert clusters and rich data sources. The Ministries are home to immense and potentially useful resources. While there are tools like Privacy by Design, a made-in-Canada solution for the challenges of data access and linkage, these are cumbersome, slow and still shrouded in fear. The future of healthcare innovation will be we can master data, locally, nationally and internationally. Fortunately, patients are well on their way to generating and immediately acting on their own data, recorded on wearable, mobile devices. Many will soon have their genomes and what such at their electronic fingertips. As data is democratized, we must be nimble or innovation will pass by bureaucratically hampered health sciences innovators like a roadrunner passes a stone.
About the Author
Bruce M. McManus MD, PhD, FRSC, FCAHS is a Professor, Department of Pathology and Laboratory Medicine, UBC, Co-Director, Institute for Heart + Lung Health, CEO, Centre of Excellence for Prevention of Organ Failure (PROOF Centre) and Board Member, Personalized Medicine Initiative (British Columbia). He can be reached by email at firstname.lastname@example.org