Incorporating patients’ voices in the drug development process

Published on: Sep 23rd, 2020

Our Senior Director, Mike Day recently interviewed Robyn Bent, Director, CDER PFDD Program, Center for Drug Evaluation and Research, US FDA, on behalf of TOPRA. In this interview, Robyn Bent talked about the Patient-Focused Drug Development Program, patient engagement and the lessons learnt so far from the COVID-19 pandemic. She also shared some advice on the preferred or most successful methodologies to engage with patient groups, as well as highlighting the risks today for the companies who have not engaged with patients groups before interacting with the FDA.

Q: Could you tell our readers a bit about your background and how you came to join the FDA/Center for Drug Evaluation and Research (CDER) Patient-Focused Drug Development (PFDD) Program? 

I’ve been a nurse for over 20 years, and have had the opportunity to be involved in a lot of the clinical trials process, including design, conduct, and oversight. But throughout my career I’ve continued to practise as a nurse and work with patients and their families. I feel like advocating for patients is a key part of being a nurse. I wasn’t looking for a new position, but when the opportunity to work with a great group of people to move the science of patient input forward became available, I leapt at it.

Q: What does your current role involve, and what current therapeutic areas are most active in PFDD?

In my current role I oversee the FDA-led PFDD Meetings, our externally led (EL) PFDD Program, and the development of the PFDD methodological guidance documents that will outline how stakeholders can collect and submit patient experience data and other relevant information from patients and caregivers for medical product development and regulatory decision making. I am also the Program Officer for our Standard Core Clinical Outcome Assessment (COA) Grant Program.

We are really impressed with the level of uptake we’ve seen for PFDD. It really looks like industry and patient groups are coming together to move PFDD forward across therapeutic areas. It can be hard to measure which therapeutic areas are most active in PFDD because the idea behind PFDD is that the patient voice is incorporated throughout the drug development process. But one very rough metric is that about 80% of applications approved by CDER in 2018 and 2019 contained patient experience data.

This includes almost all recently approved oncology products and neurology products. We are also seeing an increasing number of EL-PFDD meetings being focused on rare diseases.

Q: Have you seen outcomes of the PFDD Office initiatives implemented in pharmaceutical development programmes in practice, or in labels of newly approved products?

Absolutely. As I mentioned above, we are seeing an increase in the percentage of applications that contain patient experience data. We’ve seen a number of reviews reference PFDD meetings as a source of evidence that has been used in regulatory decision making, and we’ve seen an increasing number of applications submitting COAs as trial endpoints. A lot of these endpoints are discussed in labelling.

Q: Do you have recommendations or advice on the preferred or most successful methodologies to engage with patient groups?

We’ve just finalised our first PFDD methodological guidance, “Patient-focused drug development: collecting comprehensive and representative input”. This guidance discusses sampling methods that could be used when planning a study to collect patient input. It also provides a general overview of the relationship between potential research question(s) and method(s) when deciding from whom to get input (including defining the target population and development of the sampling strategy). The FDA recommends engaging patients and patient groups early in the drug development process and continuing to involve them throughout.

Q: Does PFDD primarily interact with patients? Are these interactions initiated at the FDA’s request or proactively by other stakeholders?

The FDA has a large number of efforts that allow us to interact directly with patients. Selected examples include the FDA Patient Representative Program and our FDA listening sessions. We also interact directly with patient groups during PFDD and other public meetings. However, it is important to note that while FDA plays a critical role in drug development, we are only one part of the process. It is one of the missions of the FDA to protect and promote the public health by evaluating the safety and effectiveness of new drugs. The FDA does not develop drugs, nor do we conduct clinical trials. It is not our role to lead much of the development work on specific tools or for specific drug development programme.

However, we play a role in guiding, helping, and evaluating. These interactions can be initiated by patients or patient groups, such as submitting a Letter of Intent for an EL-PFDD meeting or reaching out to our patient engagement staff to request a smaller, more directed patient listening session.

Q: What are the risks today for a company to have not begun engagement with patient groups before interacting with the FDA?

The answer can differ depending on therapeutic area. If a disease is well characterised and there is already a lot of publicly available patient engagement information, and the sponsor makes good use of these resources to inform their development programme, then the risk of proposing something that the FDA does not believe is reflective of what is important to patients may be less than in a disease that is not well characterised, and where patients may not have been involved previously. It is important to note that the FDA is not asking every drug developer in every disease area to continue to repeat work that has already been done. If there is high quality, representative patient information available, then it makes sense to use that information.

Q: What are the most important issues of the drug product development to address with patient experts?

I think it is important to include patients throughout the drug development process, but if I had to pick a few discrete points, I would say it is important to ensure that trial endpoints reflect outcomes and clinical changes that are meaningful to patients. I would also say that patients should be involved as trials are planned and developed so that they can provide feedback on aspects of the trial that may cause problems with recruitment and retention. But again, patient-centricity cannot be measured at a single point in time.

Q: Will patient engagement become mandatory in the future?

I don’t have an answer if you mean “Is the FDA going to require patient engagement?”. I do think that patient engagement is becoming a norm, and that patient groups can decide who they want to collaborate with, perhaps choosing drug development programmes that are more patient-centered over those that are less patient-centric.

Q: What have been the FDA’s key successes to date? Did the Agency take any important lessons from the COVID-19 pandemic with regard to PFDD and, if so, how will these be applied in the future?

Our key successes have been changing face of drug development where we see an increasing involvement of patients and patient groups throughout the process and the number of patient-centred endpoints that are being included in clinical trials. I think we will be learning lessons from the COVID-19 pandemic for a long time. Regarding our PFDD meetings, we have seen both the FDA-led and EL meetings pivot to a virtual format. Previously we had really focused on faceto-face meetings, but we have now seen some very well done PFDD meetings that have the ability to reach an even broader population because of the interactive nature of the virtual meetings. We have also found that some COA measures need to be completed in a virtual setting. We have provided some guidance within the FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency, Question 13 (https://www.fda.gov/media/136238/download).

Q: What are your aims for future changes within the organisation?

We are continuing to work on the methodological guidance series. We hope that the guidance series will provide more clarity to our stakeholders about what the FDA considers methodologically sound data. We have received patient experience data as part of applications that, for various reasons, was not considered to be developed or collected in a methodologically sound manner and, therefore, we were unable to use it for regulatory decision making. We are also working on expanding the Standard Core COA(s) and their Endpoint(s) Grant Program as a method of making inclusion of the patient voice a sustainable part of regulatory decision making.