Medicine 2020: Portable, personalized, informed

Co-chairs:

• The Hon. Arthur T. Porter, Director General and CEO, MUHC
• Dr. Vassilios Papadopoulos, Director, Research Institute of the MUHC
  

Participants:

• Dr. Armen Aprikian, Director, Cancer Care Mission, MUHC
• Dr. Bartha Knoppers, Director, Centre of Genomics and Policy, McGill University
• Mr. Martin Leblanc, President and CEO, Caprion Proteomics
• Ms. Gwen Nacos, Founder, CanSupport, Cedars Cancer Institute
• Dr. Tommy Nilsson, Director, Proteomics and Systems Medicine, Research Institute of the MUHC
• Dr. Louise Pilote, Director, Division of General Internal Medicine, MUHC

Introduction

The Hon. Arthur T. Porter opens the roundtable, putting into context the rationale for the discussion’s timing and the choice of participants.

New technologies continue to be introduced into society at breakneck speed, affecting every sphere of industry including that of the healthcare sector. Whether they are embraced, supported or rejected, there is no question that they are influencing Canadians’ understanding of new knowledge as well as their behaviour, expectations and decision-making. This in turn affects our country’s government programmes, including our healthcare system. Add the omnipresent concern over escalating costs, equitable access and quality as regards the sustainability of our healthcare system and one has the makings of a critical and timely roundtable discussion—Medicine 2020—about how new technologies could transform health care.

As healthcare providers, we try to predict changes to our roles, imagining nascent techniques, physical settings and operational measures that could improve access, delivery and outcomes while optimizing budget allocation. However, a healthcare provider cannot prepare and adapt its role without paying due consideration to that of others. That is why the MUHC-ISAI gathered experts who could represent the roles of provider, researcher, patient and/or healthy person and drug developer.

Dr. Vassilios Papadopoulos then describes the impact of genomics and proteomics on medicine, and presents two scenarios of a hypothetical case to illustrate how these might affect patient care in 2020.

In the 20th century, we learned how lifestyle affects health. We knew, for instance, that smoking and eating habits could predict future outcomes. As a result, we assigned increasing significance to family history as regards risk factors for diseases at all stages of life. In the last decade, however, we’ve experienced a revolution in medicine both in terms of knowledge and accessibility. In 2000, the complete characterization of the human genome got underway. The Map of the Human Genome took twelve years to complete at a cost of $12 billion. In 2007, the full genome sequencing (genotyping) of Dr. James Watson, who discovered DNA, cost $1 million. By 2008, genotyping had dropped to $350,000. Today’s estimates average $65,000 while international competition is further influencing a cost reduction that could lower it to $1,000.

What this has led to is the concept of personalized medicine, which is essentially the use of the information from a person’s genotype to select the most appropriate therapy for a disease or condition. Personalized medicine has started to gain traction in oncology, particularly in breast cancer, where genetic markers allow us to predict quite accurately the type of cancer, its progression and its response to a prescribed therapy. We’re moving away from the era of ‘magic bullets’ where the same drug is administered to everyone, half of whom experience no effect or benefit.

The approach of the future will be much more individualized: every patient will have his/her own prescription for a disease based on his/her genetic profile. In fact, we’re also moving away from care that merely treats disease to care that maintains health—from personalized medicine to personalized health management (PHM). PHM aims to take advantage of the molecular understanding of disease gained by looking at a person’s unique clinical, genomic, genetic and environmental profile. This approach shifts the focus to prevention for those who are still healthy or at the very early stages of disease—from illness to wellness. Some regard prevention as too expensive, but it may well be the solution to controlling spiralling healthcare costs.

While genomics provided the alphabet with which to read individual characteristics, additional information gleaned from proteins, metabolites and detailed imaging allows us to read whole words and put a complete description on a smart card. The patient can bring the card to the physician, who then immediately sees what the problems are and determines what can be done based on the individual’s profile. These technologies exist today, though they’ve yet to be widely applied.

The policy and infrastructure framework within which personalized medicine evolves will have a very significant impact on patient care, indeed personalized health management, in 2020.

Roundtable Discussion

Dr. Papadopoulos and Dr. Porter ask roundtable participants and the audience to think about how we might start to address some of the issues that will make the difference between the optimistic and pessimistic scenarios for medicine in 2020. The following represents some of the topics that emerged and responses.

Will Canadians be protected from discrimination on the basis of their genetic information?

Dr. Bartha Knoppers addressed this issue by stating that legislation to protect people from possible economic harm as a result of knowing their genetic self doesn’t yet exist. “The assurance that our data is secure and won’t be used against us by insurance companies and others isn’t there. Despite that, people display tremendous interest in genetic information for genealogical as well as health reasons. They’re not scared of their genes and their family history. Research ethics committees, however, are very leery of research protocols that involve people learning about diseases they may have and don’t look upon these favourably. They’re fostering what I call genetic ‘exceptionalism’—the idea that genetic information isn’t normal ‘human condition’ information.”

Will personalized medicine change patient care?

Dr. Louise Pilote considers genomic information just one more piece of data physicians will use in the course of treating patients. “First, we need to make the data we currently collect more accessible for consultation. It’s difficult for physicians today to access the results of blood tests, imaging scans and psychosocial assessments in order to make informed decisions about treatment that can help modify disease progression and prognosis. The first challenge is improving access to the information we have today. The second is knowing what to do with the new information that becomes available through genomics.”

Dr. Tommy Nilsson sees a need to reflect on who would interpret the information from a patient’s proteome, genotype, transcriptome and metabolites that will be available within 10 years. “Will the physician become a specialist in all these different techniques? Will we need to create a support level that translates the data into information that’s meaningful to the physician? And what must we do to prepare the next generation of physicians to deal with all these new technologies and the processes around them?”

Dr. Pilote adds that if physicians remain the managers of the information new technology provides, they’ll need to be equipped with the technological knowledge to integrate that information into care. “It boils down to creating models and pathways of care and coordinating care between different professionals. We could also make the MUHC the first place in Canada to train physician assistants, who could extend the expert physician’s ability to integrate new types of information.”

Dr. Nilsson responds that the data becoming available with genotyping and sequencing proteomics is complex enough that it would be impossible for a physician to extract relevant information from the raw data. “There will be hundreds of parameters, some relevant, others not. In the research community right now,” he says, “there is a discipline called systems biology that involves using computers to search all this complex data and extract relevant information. This will become systems medicine as data from genomics is coupled with a patient’s personal traits, such as age, gender and profession, and integrated into computer analysis. Systems expertise will support physicians in their work, but physicians will still make the judgement call. They will simply have another set of results to consult on a PDA to inform treatment decisions. But we need to build the infrastructure to make sure we have that support available.”

Dr. Eugene Bereza, Director of the Biomedical Ethics Unit in McGill’s Faculty of Medicine and Chair of the Research Ethics Bureau at the Montreal Neurological Institute and Hospital, notes that on the clinical side, it isn’t just a matter of acquiring and assembling all the information. “There has to be someone with the knowledge, skills and time to interpret and contextualize it in a meaningful way for a real person. Today, people fall through the cracks because there’s no one person who can put all the information together and interpret it meaningfully. In the pessimistic scenario described above, Betty #2 appears to be a victim of that in 2020.”

Dr. Robert Gagnon, Director of the Obstetrics Division at the MUHC, offers that to have personalized medicine, physicians need to have easy access to personal information. He says: “I have patients with six different paper charts. Trying to get an overview of that patient’s experience is virtually impossible.”

In response, Dr. Arthur Porter notes that electronic records are a priority for the MUHC. “Key to the new practice of medicine and to maintaining standards of care is to have the information you require to treat the patient in front of you, whether it’s just x-rays and blood tests or the entire genomic profile. The MUHC has invested very heavily in information technology because having that backbone is essential. Ideally, we’d have the Quebec Electronic Health Record, the hospital-based Electronic Medical Record and the personal log-book that would enable patients to record their own data and share it with their physician.”

Dr. Bartha Knoppers expresses optimism about the potential for new technologies to improve care. “I see nanotechnology and bioengineering at the point of care simplifying the endless going here for one test and there for another, and getting rid of the endless shuffling of paper records. By 2020, we’ll have electronic medical records organized in a translational sense, all the way from research to the family physician to the hospital.”

Will personalized medicine lead to ‘faceless’ care?

Dr. Armen Aprikian sees a risk that personalized medicine could make health care more impersonal. “If technology continues to improve so we can predict health problems and the effectiveness of particular drugs much better, we can see how personalized medicine could become impersonal, meaning people no longer have doctors but rather a long-term genome-based prescription: At age 20, they should have this test and at 40 they should start taking aspirin and everything will be lined up for them. We would probably need fewer doctors, as their role would be to step in when the algorithm didn’t fit anymore. I don’t know how patients will react to that. Right now, some of them still say they’d like to spend more than five minutes with me, to ask me about my kids and tell me about their vacation.”

Dr. Porter wonders whether this is really a risk or simply a change, much like the shift from record album to iTunes. “With personalized medicine and a more informed consumer, people become more involved in their health care and in some ways drive their own care rather than waiting for their doctor to tell them what to do. That might be something we see in terms of moving from a sickness-dominated society where we, as hospitals, delight in treating illness, to one in which we work to identify, prevent and correct anomalies early on.”

“That doesn’t sync with my personal experience as a clinician,” says Dr. Bereza. “I see people opting out of the medical system to consult alternative medicine specialists. When I ask why they’re going to an aromatherapist and not their family doctor, they say ‘because when I pay him the $60, he’ll spend the hour listening to me. I want his time. You guys don’t have it.’ Good personalized care in the full sense of the word is what patients want: not just a technological recipe on the computer screen, but someone who will listen, interpret, contextualize and respond as a human being. And if physicians don’t provide this, patients will go see their aromatherapist.”

Ms. Gwen Nacos, Founder, Cedars CanSupport, a project of the Cedars Cancer Institute, MUHC, doesn’t believe the need for doctors will decrease. She sees doctors playing increasingly a more consultant-like role. “Patients have access to more information, but I’m not so sure they’re actually better informed. The doctor plays a role in helping the patient muddle through all the information that he or she comes in with.” She adds: “Cedars CanSupport puts on several free public information lectures each year on specific cancers and at every one we ask people why they came. There are always some who saw the ad in the local newspaper and some who saw posters and flyers, but two thirds of those in attendance are there because they received a letter signed by their doctor suggesting they attend. What the doctor tells the patient today is so important and I don’t see that changing. Except that patients will have more information and I think start to challenge the system to respond to their needs.”

Will the tests required to predict a patient’s response to a given drug be developed, validated and reimbursed?

Mr. Martin Leblanc states that the pharmaceutical industry has, until very recently, not really felt the need to find out whether a patient would respond to a given drug. “The average drug reimbursed by our healthcare system only has a positive impact on 40% of people who take it; 60% have no response and some suffer side effects serious enough to require a visit to the ER. That’s changing as approval requirements for new drugs become more stringent. In the U.S., the FDA is demanding that companies study the comparative effectiveness of a new drug against those already on the market before seeking approval. There’s also a push to reduce costs by focusing reimbursement on the 40% of patients in whom a drug can and does have an impact. This requires identifying these patients through some kind of companion diagnostic or early marker of efficacy. One of the early successes in this area is the HER-2 gene in breast cancer,” notes Mr. Leblanc. “We have a test that identifies patients with a much higher chance of responding to the drug Herceptin and we can decide to prescribe it and reimburse it for this group. This is one very isolated case where objective metrics are available, but the world of prescription drugs is begging for a whole lot of new ones.”

This environment is creating a huge opportunity for companies like Caprion Proteomics, which became profitable thanks to the push to discover markers at the protein level in body fluids. Mr. Leblanc feels that similar opportunities exist in genomics, imaging, immunology and other ways of predicting efficacy.

Owen Dyer, an audience participant, asks who would pay for developing the tests required. “I cannot see drug companies paying for something that would reduce their prescriptions by 60%.”

In response, Mr. Leblanc states that pharmaceutical companies are investing in this research, as they need these markers to get their drugs reimbursed. He also sees the public sector funding some of that work, and the appeal of consortia-based approaches. “We have an example now with the Consortium québecois sur la découverte du médicament (CQDM), in which Pfizer, AstraZeneca and Merck Frosst are making investments matched by provincial and federal governments via the Fonds de la recherche en santé du Québec (FRSQ) and the Centres of Excellence of Canada to help discover and bring these tests to market more quickly. It involves collaboration among pharmaceutical companies, but also between them, biotech companies and academic-based researchers. The idea is that more drugs will be reimbursed for fewer identified patients. The CQDM is now in its second year and has worked well so far. Research findings won’t be owned by a particular company, but rather by the institutions that conducts the research, and all members of the consortium will have access to the results and be able to use them.”

“The prospect of reducing waste in the healthcare system by clearly targeting health spending provides enormous incentive for government to partner with the private sector to accomplish this research,” continues Mr. Leblanc. “In prioritizing projects, my sense is that you first have to set a hierarchy of unmet needs that account for the greatest costs and impose the greatest burden on public health. That may be difficult to enact, but it becomes possible if public money participates in the projects.”

How fast will research proceed to create clinically useful tools from ‘omic’ discoveries?

“The simplistic way to develop new metrics,” says Mr. Leblanc, “is by accumulating hundreds or thousands of patient samples and interrogating them in a very systemic fashion using proteomics, genomics and imaging technologies to figure out what measures could actually become a validated test and influence medical practice.” However, he suggests that the pharmaceutical industry cannot afford to undertake independently the parallel programmes to research these companion diagnostics. “Nor should we really want them to. To get the full economic benefit of personalized medicine, we may not want a single company controlling the intellectual property around companion diagnostics. These should ideally serve to create a level playing field where all drugs of a same class would be subject to a same predictive marker of response. That would bring the broadest potential public health benefit out of a companion or predictive marker.”

Dr. Knoppers views the current system for approving research and new technologies as a major impediment. “The regulatory bureaucracy is largely still based on classical divisions between drugs and devices. Researchers involved in new technologies are left wondering which road to go: Is regenerative medicine best suited to a device or drug model? What about nanotechnology? The classification of new technologies at the regulatory level creates incredible hurdles for researchers and the system is no longer responsive.”

The other hurdle on the research side, according to Dr. Knoppers, is the continued difficulty in accessing samples and data to accomplish the large studies needed to identify genetic markers. “The consent forms are still just as complicated and researchers still have to go through clinical ethics committees, university ethics committees, the access commission and the ministry before proceeding with a project. It’s time to build some safe-harbour approaches based on mutual trust and recognition along with multi-centre, single-review processes. What are you supposed to do if your project covers the whole country? Even just in Quebec, I went to 13 ethics committees last year for one project. We need to see systemic approaches to research review.”

Dr. Papadopoulos says this is a vision he has also heard from Canadian Institutes of Health Research (CIHR) President, Dr. Alain Beaudet, who has called for a common pan-Canadian approach where a research protocol developed in a hospital in one province can include patients in another.

Dr. Bereza interjects that in the short time he has been Chair of the Research Ethics Board, the cost of reviewing a research protocol has increased from $700 to $10,000. “A disturbing proportion of that is spent responding to demands of a complex regulatory bureaucracy,” he says. “This is demoralizing for researchers and if the trend continues, we might not get the research innovation anticipated for 2020.”

Dr. Knoppers points to the growing number of U.S. hospitals where patients are notified when they come in that their ‘anonymized’ biological material will be used for research to develop more precise testing and care, unless they opt out. “This may be a way for people to help maintain the universal health system we have in Canada. If an extra contribution is needed, why not have people contribute their leftover samples, assuming that confidentiality and security are assured. It may be one way to keep down the cost of developing the biomarkers that will help control healthcare costs. We need to find out whether people would be willing to share their data and samples in a secure environment.”

Dr. Knoppers hopes that by 2020 the research arena will be international and collaborative, with samples and data shared across borders. “Think of what that would mean to the study of rare diseases, for which you need to share tumour samples across political, legal and jurisdictional borders. Right now this is difficult, even across Canada. We have a real systemic difficulty in sharing samples and data, even when the research participants consent.”

Mr. Leblanc regards the Canadian single-payer reimbursement system as an advantage. “It gives us a greater ability to work together and our track record of collaboration between clinics, researchers, private sector and governments would enable us to take on some of these ambitious projects.”

Dr. Aprikian states that he would like to see the MUHC take a leadership role in the whole field of biomarkers and proteomics. “We have the technology, informatics and minds, but what industry and academia need is actual material from people. I would hope that from now until 2020 every patient who walks through the door at the MUHC provides a blood sample and completes a detailed questionnaire—all highly protected for confidentiality—so that by 2020 we have a longitudinal cohort of people who came through the doors and can use that databank to answer a number of questions. If we cannot get that broad database, we will have newer technology in 10 years, but we will still be asking the same questions.”

Are people interested in obtaining genetic information to predict future health problems?

Ms. Nacos believes that many patients would like to have their genetic information so they could better understand how to make their own choices about elective surgery or other preventive treatments. “Others will choose not to know. The rights of the individual patient must always be respected. In the cases of the BRCA-1 and 2 gene, I’ve seen patients who want to find out because there’s a family history of breast cancer, while others in the same family choose not to know because the information may force them to make a painful decision about undergoing elective preventive surgery. We need to respect individual wishes.”

The audience is asked whether they would want to have their genome sequenced early on in early if this were available to them as it was for the hypothetical ‘Betty 2020.’ While most indicate they would take advantage of the technology, there were some dissenters. One woman feels there are still too many unknowns, regarding confidentiality and possible harms if employers or insurers gain access to the information. She also worries about finding out things she doesn’t want to know.

Dr. Pilote states she wouldn’t have it done. “Aside from a few exceptions like the BRCA gene, there isn’t much I could do today with that information. Most of the disease prevention measures involve common sense prescriptions like exercise, not smoking and avoiding obesity. So it wouldn’t add to what I can actually do to change my prognosis.” She also encourages close consideration of how people would use personalized medicine. “Even after years and years of work in these areas, we have a very hard time changing behaviour, whether lifestyle or adherence to medication. That whole question of how patients integrate the information we provide into their lifestyle needs to be researched as we expand toward personalized medicine.”

Dr. Henry Shibata, Professor Emeritus of Surgery and Oncology at McGill University and Chairman, Cedars Medical Advisory Committee, feels, as a near octogenarian, that preventive personalized medicine reflects a preoccupation with prolonging life that stands to impose a burden on younger generations. “We are trying to make people live longer at a time when 60% of Canadians will soon be over 65 and others will have to look after them. We have to look at the bigger questions. Which is more important: the individual or society? As well, we’re discussing this in a North American context, while people in Africa and India are dying of disease rather than old age. We shouldn’t be selfish.”

There is also concern that the genome can only provide one measure of risk.

Dr. Papadopoulos confirms that this reflects the current situation. “However, systems medicine is more than the genome. It brings proteins, metabolites and everything together to provide a better prediction of disease or response to medication. This is what we’re talking about with the whole personalized health management approach. The genome is the component we already have available. The others are under development. The proteome for individuals is coming soon.”

What impact will personalized medicine have on cost?

Dr. Papadopoulos recognizes concerns about the expense of personalized medicine. “But can it be more expensive than the reactive medicine we use today, where we try drug after drug until something works, with the patient’s condition often growing worse until they require expensive hospital care?”

Dr. Aprikian examines the potential to better target screening efforts using genomic technologies. “In cancer, we’re spending a lot of public funds on mass screening. The return on investment from mammography, PSA or colorectal cancer screening is about a 5 to 7% reduction in mortality from these cancers. If we can develop biomarkers that enable us to identify a smaller target group for screening, the savings could be used on newer cancer treatments that are much more expensive than what we have had in the past. Many of the new drugs based on proteomic discoveries are fine-tuned for one or two targets that not every patient has. You can see how a drug that only applies to 5% of people with a given cancer may be of limited interest to industry unless the price is set quite high. For example, we have a drug for kidney cancer today based on proteomic discovery that will extend life by three months but cost $50,000.”

Mr. Leblanc disputes the idea that personalized medicine will cost more. “The examples of breast- and prostate-cancer screening point to just how non-predictive current tests are, and how not every biomarker is a good biomarker. A biomarker that has very high sensitivity or specificity for detecting disease may be very useful and cost effective for the healthcare system, but there’s increasing evidence that a biomarker like PSA, which produces a great many false positives, is creating more costs than it saves, despite the good intentions at a personal level. The expensive part will be to develop and validate new tools that are far more predictive, but once we have them, they should ultimately reduce costs in the healthcare system if they’re deployed appropriately.”

Dr. Pilote calls for careful assessment of genome-based technologies. “The uptake of some technologies—PSA is one example—occurs before they are proven to be cost effective and useful. It makes sense to have personalized medicine and it makes sense that it will save money. But we have to put these new technologies under the same scrutiny of technology assessment employed with other technologies. The MUHC has a longstanding history of excellence in technology assessment and can play a very important role in conducting these evaluations.”

Conclusion

Dr Porter wraps up the roundtable discussion by looking at the future in the context of ever-evolving medicine and the MUHC’s three-campus Redevelopment Project.

As is evident from history and the dynamic Medicine 2020 roundtable discussion, the future of medicine holds much promise. However, medicine in 2020 clearly depends on what we do today. Many considerations must therefore be addressed sooner than later, not simply by healthcare providers but also by every stakeholder, including healthy Canadians.

Of note: Many people face huge obstacles in trying to change lifestyle behaviour and in adhering to treatment. Will knowing the risk factors years in advance change the outcome? What are the ethical implications of knowing a genetic risk factor for a particular disease when you may be one who may never develop it despite having a predisposition? With the advent of new, costly medications, will we have to make more judgement calls over quantity versus quality of life? Just because a patient today is informed, does it make him better informed? If a new field is systems biology, what else do we need and how are we adjusting our academic programmes to be prepared? How can we manage the ballooning volume of data the most effectively? How can we, as healthy Canadians, become more responsible about our health?

Infrastructures (physical, equipment and medical informatics), cost containment (sustainability), outcomes (value of treatments), ethical frameworks and educational tools (for patients and healthy individuals) should therefore be further explored. On that front, there is a consensus that the MUHC should play a leadership role in the research, development, assessment and integration of the technologies that will shape medicine in 2020.

“When I started working at the MUHC with the goal of rebuilding these hospitals, I looked at some of the concepts that had gone into the building of the Royal Victoria and the Montreal General hospitals, and the relocation of The Children’s Hospital: tuberculosis was rampant, surgeons made large incisions, patients with heart attacks stayed in hospital wards for six weeks. The infrastructure of those hospitals responded to the health challenges and medical knowledge of their time. While we have this unique opportunity to rebuild hospitals, we have the opportunity to look at what has changed— shorter hospital stays, more ambulatory care, keyhole surgeries—but we also need to anticipate where we will be in the next ten, twenty or thirty years. This panel reaffirms my commitment to the Research Institute and its goals, to organizations like the Technology Assessment Unit, founded by Dr. Maurice McGregor to study the benefits of what we do at the MUHC, and also to the MUHC-ISAI, which brings people together to look at the policy frameworks we are working within and how they might be improved.

If we’re not prepared to take the risks to innovate and look to the future, then who will?”

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