An estimated 8,000 rare diseases have been discovered, affecting up to 446m patients around the world. The healthcare industry and research community in recent years have stepped up their efforts to research these conditions and come up with viable treatments.
Contract research organization (CRO) ICON has released “Patient Centricity in Orphan Drug Development: Patient-Reported Outcomes,” a whitepaper outlining trends and developments in rare disease research. The study looks at drug development and examines patient centricity in rare-disease research on three levels:
- Strategic: how patients contribute to study design and interact with regulatory entities
- Endpoints: where patients complete patient-reported outcomes measures in a study or contribute to development and validation
- Participatory: where patients collaborate with researchers to optimize study processes and facilitate patient recruitment and retention in studies
Benoit Arnould, director of patient-centered outcomes with ICON, spoke with Outsourcing-Pharma about the whitepaper, and the importance of elevating the patient voice in improving rare disease research.
OSP: Could you please share why ICON decided to dig into and craft such a comprehensive document about this issue—why is this something that pharma firms and research partners should take a closer look at?
BA: Clinical research in rare disease and orphan drugs is a rapidly growing area and a focus area for ICON. Every aspect of rare disease research, from setting drug development priorities, through funding, regulatory authorization, and reimbursement, to patient advocacy and how rare diseases are communicated in the public media - all of these things are either directly or indirectly influenced by patients and their families.
Also, there is a strong need to put the patient at the center of drug decision-making, as a natural response to the maturity of the evidence-based medicine model and the increasing technicity of care. After decades of patient activism and decades of research on quality of life, the concept of patient centricity has become something of a mantra, with many in pharma centering their communication on patients.
As a scientific company, we at ICON felt the need to question and document objectively how much, how clearly, how explicitly, and how deeply patients are actually at the center of all aspects of clinical research. For me and my team, as outcomes research specialists we paid particular attention to the efforts made in rare disease clinical research to capture the benefits patients experience in this area in terms of outcomes, and how this critical information coming directly from patients is used by regulators to make decisions.
OSP: Patient centricity obviously is an important issue in any study—is it particularly important when the condition at the center of a study is a rare disease patient?
BA: Yes, patient centricity in rare disease research is critically important, for several reasons. By nature, most rare diseases have a remarkable and deleterious impact on the lives of patients and their families.
The heterogeneity of the expression and course of a specific rare disease on the small number of patients concerned make them very complex to assess in a standardized and communicable way. The multiple impacts in terms of symptoms and functions affected necessitate a holistic approach to understand and embrace the reality of the patients.
The dramatic situation of patients and their families and the limitations of the therapeutic options justify an approach of risk-benefit which is not adequately addressed by traditional, well-established public health and ethic paradigms. Altogether, this makes me think that if one area of clinical research needs to be explicitly, totally patient-centric, it is rare disease.
OSP: What do you think are the most interesting, surprising, or otherwise noteworthy, bits of information shared in this whitepaper?
BA: What really surprised me was the limited number of claims based on clinical outcomes assessments (COAs). Not only the limited number of patient reported outcomes (PRO) claims, but even more surprising was the proportion of orphan drugs coming to the market with total absence of clinical measures or even clinical judgment reported in the product labeling and/or its summary of product characteristics (SmPC), both in the US and in the EU.
I was also concerned about the lack of guidance for patient involvement in study protocols. Our team was surprised that there were no standard best practices, guidelines, or metrics for stakeholders to use to select their activities and to assess the success or failure of these activities.
OSP: Avril Daly, vice president of EURODIS, commented, “Listening, and applying patient-centric insight across the life cycle of drug development is critical to better outcomes. This process of patient centricity needs to begin at the earliest stage of clinical development.” Could you share a little more detail and insight about why incorporating patient experience and insight at the outset is helpful?
BA: The ultimate goal of developing a drug is to improve the lives of patients, whether to shorten disease duration, improve the patient’s ability to function, or improve their overall well-being. And the ultimate decision-maker for taking the drug is again, the patient. In its 2003 report on medication adherence, the World Health Organisation (WHO) reported on the incredible waste of energy, time and money due to the lack of prescription adherence in chronic diseases; that is why we need patients to define the priorities in terms of innovation, whether that be around greater efficacy, improved safety, or greater convenience and ease of use.
We also need to hear from them at the outset to understand what has a more detrimental impact on their lives. This could include pain, fatigue, limited mobility, and/or a specific function critical to limit their dependence on caregivers. Only the patient and their families can articulate this information.
OSP: What actions do you hope or expect this whitepaper will inspire drug developers and researchers to take?
BA: First, in the area of endpoints, there are so many unmet needs. I hope that our research will encourage drug developers to develop collaborative approaches to scale development and validation.
This could include defining a core set of COA instruments that would be primarily selected to capture a certain concept of interest in a given rare disease, or group of rare diseases. They can define groups of rare diseases as sharing a significant part of their phenomenology. They can develop multipurpose standardized measures of HRQoL in a specific rare disease for use in public health, observational studies, assessment of activity in clinical care, medical decision making, and clinical research.
Second, I would hope that developers pursue efforts on increased patient participation. The most obvious of this is continuing the major shift toward decentralized trials that we’ve seen over the last year, triggered by the COVID-19 pandemic.
Such activities can lead to less burden on patients and families. I would also like to see more development, validation, and systematic use of a patient experience scale to stimulate awareness among clinicians and researchers, and gain insight from patients on improvements that can be made in the way we conduct clinical research.
Finally, I’d like to see drug developers conduct well-defined, protocoled qualitative research, not only standalone but also embedded in natural history studies and in clinical trials, to document all aspects of the patient experience, improve the relevance of the findings and enhance the validity of decisions.
OSP: Anything to add we didn’t touch on above?
BA: I would like to highlight that the big change for the stakeholders (drug makers, clinical research specialists, regulators, payers) is to first accept that the patient’s subjectivity should no longer be considered a problem: this is the essence of our work to respect each person’s unique experience and values.
Second, we need to recognize the extraordinary power of language to capture and communicate the reality, and third, we need to look to learning from other human science disciplines the theories and methods to integrate subjectivity and language in scientific research, and transfer these into our health research to close the gap and become truly and fully patient-centric.