Personalized Medicine: A Patient Primer On Best Practice
Personalized medicine is focused on meeting patients’ needs, but it also has the potential to transform the delivery and financing of health care. In Vivo probes the path toward meeting both goals in an in-depth interview with Eleanor Perfetto, SVP for strategic initiatives at the National Health Council, the DC-based patient advocacy organization whose members include groups representing 133 million patients nationwide.
- Tracking the patient perspective on personalized medicine is critical to pharma’s success in commercializing new products.
- Patient advocacy groups have knowledge, access and expertise to surmount drug development process hurdles.
- Such groups can provide essential third-party validation of clinical outcomes relevant to the real-world standard of care.
- As interest grows in evidence-based “value frameworks” to guide actions on drug access and reimbursement, the addition of a broadly distinctive patient point of view will counter reliance on narrow economic criteria as the driver in decision-making.
Every missive, every map and model, on the evolving landscape of personalized medicine puts the patient at the center. Yet it’s surprising that many patient advocates don’t feel their perspective is adequately captured as this new treatment paradigm matures from a conceptual vision in the medical literature to an institutional reality at the point of care. One word defines what patient groups want from a system that promises the right medicine, for the right person, at the right time. That word is clarity – about the patient role in the way science and regulation are applied to develop new medicines and how commerce intervenes to set their value and access in the marketplace.
The stake for patients in the process around both is self-evident – but will more clarity bring more clout in delivering the health outcomes that patients want most?
Certainly, the science on precision targeting of medicines to address a patient’s unique genetic expression of disease has advanced faster than the institutions responsible for regulating approval, access and the administration of care. The first reliable scientific measure of personalization arrived back in the 1960s, with the introduction of the Kirby-Bauer test on individual patient susceptibility to different antibiotic drugs. Testing with genetic biomarkers emerged later, in the 1990s. Of the 22 novel drugs and biologics approved by the FDA in 2016, two – Clovis Oncology Inc.'s Rubraca (rucaparib) and Roche's Tecentriq (atezolizumab)for cancers of the ovaries and bladder, respectively – carry mandates for such tests prior to use in patients. Several other approvals, including Sarepta Therapeutics Inc.'s Exondys 51 (eteplirsen) for Duchenne MD and Biogen Inc.'s Spinraza (nusinersen) for spinal muscular atrophy, also rely on a genetic ID of patients most likely to benefit. The FDA approved two additional diagnostic imaging agents designed to establish a specific treatment pathway in patients with rare neuroendocrine disorders and recurrent prostate cancer.
Nevertheless, the FDA has only recently moved to establish a mechanism for patient input in evaluating potential curative advances from targeted therapies. A series of pilot consultations with patient groups covering some two dozen disease areas led, in 2016, to the creation of a formal FDA Patient Engagement Advisory Committee. For the first time, the “patient interest” emerged as a certified stakeholder in the FDA institutional process. The DC-based National Health Council (NHC), which represents disease advocacy groups with a collective membership of 133 million patients with chronic diseases, is spearheading a coordinated effort to draft a series of draft FDA guidances to structure engagement by patients throughout the drug R&D life cycle. The objective is to encourage more cooperation between patients, industry and the FDA in defining what is most useful and appropriate in advancing timely drug evaluations.
Patient Pain Points
Some aspects of the push toward engagement are likely to be challenging for the NHC and other patient groups seeking a more prominent position at the institutional level. One is the growing desire of payers for hard evidence in proving a medicine actually works. Does this negatively impact the authenticity and passion of the individual patient’s subjective experience of disease? Many patient advocates cite the disease experience as the defining characteristic of what it means to be a patient. Will payers and regulators bend to allow use of real-world qualitative measures such as patient reported outcomes (PROs) in clinical trials? While there is movement in this direction at the FDA, payers and the professional medical community remain skeptical of PROs as a benchmark of efficacy and value. Failure to resolve the ambiguity will continue to disincentivize the drug industry from investing additional resources to generate evidence beyond the randomized clinical trial (RCT).
At the same time, are patient groups ready to support what payers desire most in assessing a drug’s value: head-to-head trials against competitor products relying on the same patient population? For most of industry, it’s a bridge still too far to cross. Likewise, patients, payers and the industry face a discussion around the patient interest in having a vector of individual financial burden included when value is assessed on the basis of economic factors like price and cost.
As volume yields to value as the key criterion for determining access for a new drug in the marketplace, detailed, prescriptive frameworks are being developed under the sponsorship of a wide variety of stakeholders, from academia to insurers, professional associations and even industry – PhRMA itself is quietly constructing pilot value frameworks on drugs for rheumatoid arthritis and multiple sclerosis. Again, groups such as NHC contest being left out of the decision matrix and are pushing their own ideas on how value determination can be refocused more toward outcomes that deliver to patients.
Parsing The Value Question
But it’s a fine line that has to be drawn between patient engagement and even tacit endorsement of access decisions that might make patient advocates culpable in limiting drug choices for the very patients they represent. The risk is considerable as these frameworks start making tough choices about value, like justifying a high-tier, high-cost formulary listing or even barring access to a new medicine entirely. Peter Bach, MD, director of the Memorial Sloan Kettering Cancer Center's Center for Health Policy Outcomes, cited this dilemma in a March 8 talk at the annual Cancer Progress summit in New York, noting that if organized patient groups want “skin in the access game” it shouldn’t be done by putting individual patients in the position of having to live with the consequences – like forgoing a child’s future college tuition to pay for a medicine that offers one shot at saving a life. “Acting in this manner would be unconscionable for any organization purporting to represent the patient interest," he said.
To shed more light on the issues around a patient-centric agenda on personalized medicine, In Vivo spoke recently with Eleanor Perfetto, PhD, senior vice president for strategic initiatives at NHC and professor of pharmaceutical health services at the University of Maryland School of Pharmacy. Her assessment of the prospects for a truly patient-centered system of care? It’s still a work in progress – but it's progress nonetheless.
The most important aspect here is the outcome of treatment relates directly to what is important to the patient, including factors like quality of life, well-being and functional physical and mental capacities. Patients are partners in care, not study subjects. And personalized means personal. It means having a conversation with the provider that directs treatment toward answering the question: what does health mean to me, the patient? What are the results I want to obtain from treatment? The answer does not necessarily relate to the state of the science. A therapy might be tailored precisely to an individual’s genetic profile but that does not make it the exemplar of personalized medicine. To call it patient-centered, there must be a connection to the patient experience and what the patient desires as the outcome of treatment.
For other stakeholders, there is a similar understanding of how personalized medicine is supposed to work in the practice of medicine. But in our fragmented delivery system, perception is not always in synch with reality. For example, physicians see themselves as prime advocates for the patient, yet are often reluctant to yield their professional autonomy in return for higher levels of patient engagement. Nevertheless, I believe a broad societal consensus on the importance of personalized approaches to treatment is at hand. Science is moving in that direction and so too is the growing emphasis on value in the financing of care. You can’t prioritize value without making the patient – the ultimate consumer of care – central to the process.
"Until recently, the industry did little to incorporate the patient view during drug development, especially at the early stages when crucial decisions are made in bringing compounds forward for human trials. Conversation on the benefit-risk calculation focused entirely on the science." – Eleanor Perfetto, PhD
The NHC is particularly excited about the changes at the FDA, where patient-centered drug development has an unstoppable momentum. The 2012 Prescription Drug User Fee Act [PDUFA V] for the first time required the FDA to solicit patient input in the drug development and approval process. The attitude at the time was that the provision to convene a series of “voice of the patient” meetings was a check-the-box exercise; nothing would change. Gradually, however, opinions began to shift and today we can say these encounters have proved their merit to FDA staff.
This raises another issue: methodology. It’s important to identify the specific information that patients can and should provide to drug developers to ensure the FDA has what it needs to make a “patient-centric” approval decision. We need a framework that makes the process more consistent. Technology gives us new ways to achieve this without barring creative approaches to what stakeholders can bring to the table. A few weeks ago we released the first in a series of proposed language “mini-guidance” documents covering topics that we recommend be included in a comprehensive FDA guidance on the patient role in drug development. We are using this list to start a conversation for the FDA with our members and other stakeholders which we hope will inform the progress of the required PDUFA VI guidance documents.
"Companies have come around to the view that engaging patients is not just an expenditure that drives up development costs but a test run to guide the direction of everything from the trial protocol to the final market launch plan." – Eleanor Perfetto, PhD
The creation of patient advisory and focus groups in many companies has had a positive effect on what researchers thought they knew about the diseases they study. Instead of addressing it from a purely theoretical point of view, discussions with patients offer insightful details on how physical symptoms affect daily life, especially on functional capabilities that usually escape the scrutiny of clinicians. Slowly companies have come around to the view that engaging patients is not just an expenditure that drives up development costs but a test run to guide the direction of everything from the trial protocol to the final market launch plan.
Biopharma’s heightened interest has increased the time and resource demands on patient organizations. Drug developers want patient input, whether it be joining a KOL advisory board or helping in trial subject recruitment. Our groups also collect significant amounts of data, which companies find desirable, such as in building customized patient registries to support their medicines. While the interest is welcome, there is a drawback in that it may deflect from the mission of these groups to serve their own patient population. Patient groups have to find a balance around that.
It should also be noted that some payers are trying new programs that focus on patient-centric care. However, once again, the definition of patient centric isn’t the one we’d like to see, with the patient treated as a partner rather than a recipient.
To us, what matters is the breadth and quality of patient engagement with framework sponsors. We are, for example, not for just a survey of a population with the patient as a study subject. That is confining. Instead, patients want to be full negotiating partners and to have a seat at the table before decisions on value for products are made. The NHC has prepared a “Patient- Centered Value Model Rubric” that sets criteria for patient centricity and engagement in the design and execution of a value framework. (See sidebar, "Drug Value: It's Personal, Patients Say.") One of its key points, for example, is that assessment methodologies must be flexible to account for the heterogeneity of the patient population, in which disease affects each individual patient differently over time, throughout the course of treatment, and from initial diagnosis to recovery to long-term survival.
To capture this, the evidence base used for evaluation must allow for more diversity in sources of data. We need to move beyond just the RCT as the sole benchmark of performance because it fares poorly in measuring outcomes like quality of life, which provides significant insight when examined through the prism of the patient.
A third priority is transparency. Everyone should know the constituent elements of each framework, the assumptions that buttress the methodology, and how the model actually works in practice. To a patient, transparency is simple: where did the data come from and how did you apply it in making the decision as to the value of the product? And, most important, how can I apply it to my own situation, with my physician and caregivers?
It remains to us to debunk the persistent myth that personalized medicine is a cost driver, not a cost saver. We know that when patients are involved and have the best knowledge available about their own condition and options, they make the right choices. In many cases, the right choices are the least expensive.
"I am concerned that attention to pricing could slow the progress we’ve achieved. If we lose our focus on patient-centered care, innovations that improve actual clinical outcomes will suffer." – Eleanor Perfetto, PhD
I am concerned that attention to pricing could slow the progress we’ve achieved. If we lose our focus on patient-centered care, innovations that improve actual clinical outcomes will suffer. There will be fewer options for patients, particularly those with rare diseases. We should be creating a health care system that drives patients to higher value care and discouraging lower value care. Solving this requires a conversation more honest than what we as a society have conducted to date. And the critique must extend to other health interventions – a larger conversation than targeting a single new drug for scrutiny while other cost drivers in the overall system go untouched. It’s easy to single out one factor. It’s hard to solve the bigger problem. But the onus is on the industry to take more initiative.