Have Stakeholders Been More Involved at the Centre of Decision Making?

Yann Le Cam from Eurordis and Mathieu Boudes from the European Patients’ Forum, two of Europe’s leading patient representatives participating in ADAPT SMART, discussed adaptive pathways from the patient perspective. EURORDIS is a non-governmental patient-driven alliance of patient organisations representing 792 rare disease patient organisations in 69 countries. They are the voice of 30 million people affected by rare diseases throughout Europe. And the European Patients’ Forum (EPF) is an umbrella organisation that works with patients’ groups in public health and health advocacy across Europe. Our members represent specific chronic disease groups at EU level or are national coalitions of patients.

Duane Schulthess: When the ADAPT SMART project started two years ago, there was an overall desire to have stakeholders more involved at the centre of decision making. How has this process evolved over the past 24 months for ADAPT SMART specifically, and regulation for medicines more broadly?

Yann Le Cam: I would love to have an easy answer and say, “Yes, that’s fantastic! It’s great we are much more involved!” But for me, in terms of delivering on the project and how we involve all stakeholders, I think we need to gain more experience. If we look at some of the parallel projects inspired by Medicines Adaptive Pathways to Patients (MAPPs), such as the European Medicines Agency’s (EMA’s) PRIority MEdicines (PRIME), yes, we’re very much involved in the process and that’s been satisfactory.

Regarding ADAPT SMART, we’ve tried to harmonise procedures and be much more systematic, but it’s not about bringing one patient into a discussion to ‘tick-the-box’ that patient engagement is in place. We need to make sure that this engagement is meaningful, and that may require us to have more than one patient representative present. It’s a big responsibility on their shoulders when they come into the discussions.

We see some difficulties today in the scientific committees, the system seems to work well with scientific advice, but in many other places we see challenges. Where this is relevant to ADAPT SMART is that we have the desire to put patients at the centre to contribute to the process, but we need to figure out how this is best done systematically.

If we take the example of the European Network for Health Technology Assessment (EUnetHTA) under the new legislation, patient participation is clearly identified for scientific advice but also for the common assessment. In practice, that is far from easy as you may have a budget divided between sixty partners with zero budget allocated for patient engagement.

DS: So, you’d say that we have patient engagement, but that contribution is not yet organically incorporated into the processes, there is still work to do?

YLC: Yes, partly. It’s about ensuring that the contribution is meaningful and supportive, and that it is supported by compensating the patient’s time, or support of staff, or whatever. It’s also about the patients providing the scientific and medical information on time. It’s also making sure there are enough patients physically in the room participating, enabling several to attend, not just one lone patient voice.

We are at the moment where there is a lot of excitement for patient engagement; EMA sees that it has an impact on scientific advice, HTAs see that it has an impact on scientific opinion. There is satisfaction from both the developers and assessors. This is good, and the patients are satisfied.

But it’s not ‘real’ yet. We’re still lacking recognition that this is really useful and meaningful. It’s better than a token involvement, but it’s still below the level of engagement that’s needed.

Mathieu Boudes: I have the feeling that patient engagement within MAPPs is the ‘low hanging fruit’. There is the parallel scientific advice of HTA/EMA which is one of the parts, and patient engagement is there. It’s happening, it’s not perfect, it’s not systematic, but it is happening at the EMA, it is happening in EUnetHTA, and it is happening in the Mechanism of Coordinated Access to orphan medicinal products (MoCA). So, it’s in place in the three main stakeholder groups participating in MAPPs.

One thing that MAPPs could build on is the engagement with patients within the adaptive system. I think we, the patients, will be the community with whom it will be the easiest to engage, because we’re already engaged in MAPPs.

DS: So, the both of you feel there’s progress, but there’s still a need to better establish the foundations for putting patients at the centre of decision making and we still need to work on those processes?

YLC: Yes. I really think so.

DS: Moving on from patient engagement, there’s a push in Europe to speed up access of needed new medicines to patients. This has led to much debate on the impact on benefits and risks of faster approvals. How have you two worked in ADAPT SMART to address these concerns?

YLC: What I observe is that progress is slow because the adaptive approach is very transformative and disruptive to the status quo.  It’s faced a lot of conservatism within the sector. The industry taken as a whole is very diverse, some companies are very innovative, and others are very conservative, in a company some of their senior staff ready to innovate when others are conservative.  There is a lot of focus on product or technology innovation, but ironically, there is often little appetite to take risks in the design of clinical trials or post-market utilisation schemes.

EURORDIS is fortunate in the field of rare diseases; we have more companies or leaders in these companies who are keen to take risks and to try to find new ways of doing things. But I see a lot of resistance from their regulatory affairs staff  because MAPPs is new science.

We have a regulatory system that was shaped by science in the seventies and eighties. There are hundreds of thousands of people trained in these techniques, and they think, “That’s that”. This is dogma, very much like focusing on the ritual of the church rather than faith!

Our clinical practices have become dogmatic, there are many people who are saying that the way we do clinical trials now is the only way to do it. That’s one of the major challenge which ADAPT SMART and MAPPs are facing.

Adaptive approaches can help to go faster, and act as a bridge between research and access based on evidence from the real-life use of the medicines. This will help define the correct use of medicines based on the collection of post-marketing data, integrating the heterogeneity of the targeted population. It will also contribute to the better implementation of precision medicines.

The major difficulty we have here is with the engagement of payers. There’s been a lot of misunderstanding as many have said Adaptive Pathways are just as a way to bring products to market with a lower level of evidence. In the view of the patients, it’s the exact opposite!

From our perspective, when there is a product which fits the criteria of ADAPT SMART, a transformative product for an unmet medical need, not only are you providing earlier access but you’re also moving away from a clinical trial to collect evidence on the effectiveness of the drug in the real-world that better reflects patients’ heterogeneity and how patients respond. For us, this generation of knowledge from clinical use is just as important as going earlier to the patients as it improves medical practices and patients’ health outcomes.

In adaptive pathways, the disconnection between value, evidence, and effectiveness are reduced. After marketing authorisation the payer will have better control of the prescriptions, and the ability to regularly assess the product’s benefits based on effectiveness data that is collected.

DS: That’s a very important point. Do you think there’s a better understanding now amongst regulators and payers regarding the value of them moving from a system based on efficacy to effectiveness? Do you think patients are helping to make that point?

YLC: This is certainly a role that the patients have been playing, trying to bridge that gap between the two. It seems to have some impact, we see an appropriation of these ideas far beyond ADAPT SMART, but we’re still far from a perfect solution.

Adaptive pathways is not only about being adaptive, it’s about the pathway! There is a lack of attention on the pathway, and the fact this evaluation occurs over time. It’s the different stakeholders, after marketing authorisation, working together to manage the evaluation, including the economic evaluation, which is key. This needs to work for the company, but also the payers and patients.

MB: In ADAPT SMART we’ve been really good at starting to move the needle towards more innovation. We’ve moved from conservative, to innovative, and that’s a really important point. We’ve started to change the process.

YLC: I fully agree.

DS: ADAPT SMART’s been trying to break down the barriers to change. It’s a first step.

YLC: Baby Steps. Yes.  And that was really the intent of the project.

DS: ADAPT SMART will hold its final even on March 21st and 22nd in Budapest. From the patient’s perspective, what do you think the project succeeded in accomplishing?

MB: One of the key findings of the project is that it made clear to all that none of the stakeholders are there to strong-arm the others. At the beginning, there was a lot of uncertainty to engage, as everyone was concerned that somebody was going to take advantage. At the end of the project, I’m pleased to say, that we’ve arrived as a kindred spirit within ADAPT SMART discussions. For me, that’s a clear point of progress.

We still have the problem of the stewardship of the programme after the final event; who should take the lead? Who will make things operational? And that’s one lingering question that ADAPT SMART didn’t answer.

YLC: ADAPT SMART succeeded in focusing the attention on innovation, particularly transformative products. That sends a very strong signal to the healthcare system to focus on what’s transformative in the lives of patients and addresses unmet medical needs.

Also, it has focused on bringing innovations faster to patients and society. We’re trying to re-engineer the regulatory process through an adaptive pathway, not only through a new trial process, but also by better data collection and harnessing new technologies. It has already established a culture of the various stakeholders working together. I think it has created real value in breaking down some of the regulatory silos that existed before the project was started.

We need to remember where we were eight years ago in these very defensive discussions between HTAs, regulators, and payers.  Patient groups such as EURORDIS have been advocating for years that payers should take part as observers to the meetings of HTA early dialogues or EMA scientific advice in order to hear what is being said about the disease, product, development plan, etc. That was considered unacceptable..

Because of the incorporation of payers into ADAPT SMART, that opinion has changed a lot. EMA hosted a meeting last year between the payers, EMA, and EUnetHTA, it became very easy to say, “Oh yes, the payer should attend very early discussions on the scientific advice.” ADAPT SMART has succeeded in making that obvious, and I think that’s a huge benefit of the project. I hope this will happen right now in PRIME pilots, particularly in rare diseases.

To implement the strategic approach on adaptive pathways developed thanks to ADAPT-SMART, someone will have to take ownership to support the process in a responsible way: for us, it should be the European Commission, as part of the EU agenda on internal market, innovation, attractiveness and competitiveness.