By Barbara Lopez Kunz, global chief executive, DIA
Patients have an irrefutable role in shaping the care they need. We have come a long way since the days when the idea of involving patients in healthcare product development was controversial, if not unheard of. In recent years, the healthcare ecosystem, and the role patients play in it, has evolved in a promising direction, leading to a much deeper understanding of the impact the patient voice can and should have in healthcare.
Across the entire ecosystem, from industry and academia to regulators and health technology assessments (HTAs), the goal to include patients is now on everyone’s agenda. And patient partnerships have flourished as a direct result of the confidence and sense of autonomy patients have gained. Patients, who are experiencing the illness first-hand, have become an invaluable resource, capable of clarifying their priorities and needs long before we embark on discovery and R&D. But how can we derive the most value from this development?
Numerous initiatives by DIA, the Clinical Trial Transformation Initiative (CTTI), and many other organizations, such as Faster Cures, the European Patients Forum (EPF), and the Patient Centered Outcomes Research Institute (PCORI), to name just a few, are providing us with important insights into patient engagement. They are giving us a sense of the type of metrics, operating models, as well as skills and experiences that are best suited to be effective. For example:
- Over the years, DIA has led and supported several initiatives to provide frameworks for impactful and ethical patient engagement, including CTTI, EUPATI, a PCORI-sponsored patient-engagement workshop, and most recently, the DIA-Tufts Center for the Study of Drug Development (CSDD) patient-engagement research project.
- PARADIGM (Patients Active in Research and Dialogues for an Improved Generation of Medicines), a public-private partnership co-led by the EPF and the European Federation of Pharmaceutical Industries and Associations (EFPIA), is developing processes and tools for three key decision-making points: research priority setting, design of clinical trials, and early dialogue.
- CTTI has put forward recommendations and best practices to support effective patient engagement throughout all stages of the healthcare product development process.
- Faster Cures launched its Patients Count program that gives more extensive opportunities for the perspective of patients to shape how new therapies are discovered, developed, and delivered.
- PCORI’s activities center on building a patient-centered outcomes research community (PCOR), engaging the PCOR community in research, and disseminating PCOR research findings.
In all of these instances we have successfully come together and found common ground. But this is no time to rest on our laurels. We can and must learn from these experiences to tackle areas where we’ve only made modest, if any, progress in providing patients with the active role they deserve.
Patient-Centered Benefit-Risk Assessment
Despite the overall positive development over the past many years and the great advancements we’ve made in patient engagement since the early days, there is still plenty of room for improvement. One area where opinions and interests are still diverging and where we need to come together to focus our efforts is patient-centric benefit-risk assessment.
In benefit-risk assessment, benefits are weighed against the risk of harm when using a specific product as treatment. The benefits, risks, and uncertainties must be appropriately balanced from the patient’s point of view to truly meet the needs of those the product is intended for. But patients may weigh these treatment attributes quite differently compared to physicians, regulators, or sponsors. They may even differ as a group when trading off benefits and risks, or when using the same treatment for different conditions. And, when faced with a life-threatening illness, the patient may be willing to tolerate severe risk and uncertainty for the possibility of a life-saving benefit. In fact, the U.S.-wide Right-to-Try Act (signed into law on May 30, 2018) provides terminally ill patients access to experimental therapies that have passed basic safety testing in Phase 1 trials but are not yet fully approved.
Because patients benefit from effective treatments while also bearing the potential risks, their perspectives and judgements must be at the heart of benefit-risk assessment.
Finding Common Ground: Mission Impossible?
Although industry, regulators, and patient groups are increasingly seeing the value of assessing and incorporating patient preferences in benefit-risk assessment and are exploring ways to do so, there is still no clear consensus on the nature and extent of patient involvement:
- Regulators: Benefit-risk assessment is a keystone in the U.S. FDA’s regulatory review. But the European Medicines Agency (EMA) also acted to better incorporate patients’ values and preferences in regulatory decision making by revising its framework for interacting with patients and consumers. While being receptive to reviewing and using patient preference data, regulators are inherently cautious, though. In their view, the wide adoption of patient-centered value measures will hinge on scientifically validated methods that can reliably quantify patient preferences. Furthermore (and in contrast to clinical trials), any regulatory decision must consider the benefits and risks of a treatment at the population level rather than at the level of a specific group or individual. For example, a common concern is how well patient preference measures capture the diversity of the population at risk.
- Patients: Some patients feel that they have no active role in the healthcare product development process. They may also be unaware of the impact they could have, or they may lack the motivation, skill, and confidence to contribute to the process. Once involved, a patient’s evaluation of the benefit and risk of a treatment will be very much influenced by their goals for health improvement and how they perceive the treatment affects their quality of life. This assessment, on the other hand, may depend on a variety of individually different factors, including what is and is not considered a tolerable side effect and risk or a sufficient health improvement, the level of uncertainty about benefits and/or risks, the severity and stage of the disease, and the available emotional and physical support to manage the disease and treatment.
- Medical Product Sponsors: The goal of sponsors, and the pharmaceutical industry in particular, is to get safe and effective products out to patients quickly and to continuously evaluate the experience of their use in the real world. In industry, the approach to patient engagement is quite fragmented, and some still count patient engagement in the nonessential activities in medical product development. The perceived time and effort of patient involvement is one potential barrier, as is the scarcity of validated methods, the current lack of guidance from regulatory authorities, and the uncertainty whether patient data will be accepted for regulatory decision making. The incentive to involve patients in pre-market benefit-risk assessment may therefore vary widely and be very low among some.
Current Patient Roles In Benefit-Risk Assessment
Despite the issues, patient-centered benefit-risk assessment is emerging as the next key aspiration. Stakeholders are realizing that patient perspectives can indeed make us less uncertain about decisions made during product development, regulatory review, and post-market surveillance.
Various organizations have come together to drive research and policy activities that can provide tangible guidance on how to approach patient-centricity in benefit-risk assessment and to systematically incorporate data on patient perspectives into product approval applications. For example:
- With its Benefit-Risk Bootcamp, Faster Cures tackled the science of eliciting patient preferences, providing a common understanding of methods used to assess patient preferences for benefit expectations and risk tolerance.
- DIA and PCORI addressed the challenge of how and when to best engage patient partners and published their results in Therapeutic Innovation & Regulatory Science. The goal was to raise awareness among all stakeholders of the importance of patients’ perspectives in benefit-risk assessment, to share existing approaches, identify challenges, and recommend next steps for bridging gaps.
- With its Patient-Centered Benefit-Risk Project, the Medical Device Innovation Consortium (MDIC) and its partners provided a framework for incorporating information on patient preferences into benefit-risk assessments, a catalog of methods that can be used to assess patient preferences, and an agenda for further research.
- The goal of the Patient Preferences in Benefit-Risk Assessments during the Drug Life Cycle (or IMI PREFER) project has been to assess when and how patient preferences on benefits and risks should be incorporated into decisions on medicinal products.
- The FDA launched initiatives at CDER and CDRH to incorporate patient perspectives in decision making and to communicate assessments of benefits and risks consistently across divisions in each center. The FDA has also made several commitments in PDUFA VI for continued implementation of structured benefit-risk assessment during FY 2018–2022 (see “Benefit-Risk Assessment in Drug Regulatory Decision-Making”).
For patients to be truly integrated into the healthcare product development process and life cycle management, it will require consensus and conscious commitment from all stakeholders to work together to develop shared solutions and map a common path forward. It’s imperative to advance the dialogue, particularly among those who might address the issue from different perspectives. Only then are we able to overcome current barriers.
Some first initiatives have shown that this is possible, despite the cultural changes that need to take place among patients, sponsors, and regulators alike. At DIA we realize that, because each approach will be unique, we need to share our knowledge and experiences to make consistent progress in understanding how patients, regulators, and research sponsors can best work together to improve the medical development process — a topic that will be explored extensively at the upcoming DIA Global Annual Meeting in Boston in June.
We are committed to working with all stakeholders to find scientifically valid metrics to reliably assess patient preferences, establish frameworks for incorporating that information into product development, and examine how patient experience data can be incorporated into structured benefit-risk assessment frameworks in regulatory decision-making.
It won’t be easy, but with the right amount of commitment and passion, I’m confident we will make great strides toward benefit-risk assessment in healthcare product development that is truly patient-centric.
Note: Since the publication of this article, the FDA released a Patient-Focused Drug Development (or PFDD) draft guidance that provides methodological recommendations for collecting and submitting comprehensive and representative input from patients and caregivers. The guidance provides a framework for the inclusion of patient preference data in drug development and regulatory decision making and addresses commonly raised concerns, such as the lack of scientifically validated methods and their application to well-defined patient groups. This draft is the first of four guidances required by the 21st Century Cures Act.
About The Author:
Barbara Lopez Kunz, M.S., is global chief executive of DIA. She is leading the transformation of DIA through developing and implementing a strategy that focuses on engaging the global healthcare community in DIA’s neutral platform, to drive thought leadership and innovation in the development of therapeutics to improve the health of people worldwide.