How will the normal timelines be impacted by MAPPs given there is no hard starting point?

Duane Schulthess: Can you describe CASMI’s role and contribution in the ADAPT SMART project?

Stuart Falkner: Yes, CASMI has been very busy with its involvement, both in the consortium as a whole and in the work packages, and that’s really been on two levels. First of all, we have been co-lead of Work Package 3 with Sanofi/Genzyme, and that’s been a large and diverse work package that covers decision-making sustainability and their implications for Medicines Adaptive Pathways to Patients (MAPPs). On the second level, CASMI has been leading a number of work streams within Work Package 3 and joint actions with Work Package 2. These cover themes such as the enabling of decision-making and resource requirements of stakeholders, intellectual property (IP), regulatory data protection, and some of the broader ethical and legal considerations around adaptive decision-making.

DS: Do you see this as synergistic with the academic work CASMI is doing day-to-day?

SF: Oh, very much so. As you rightly pointed out, CASMI has been one of the leaders in adaptive licensing and new models of regulation and medicines development so this is really being very much at the forefront of what we’re trying to address as a group.

DS: There are many questions on the practicality of MAPPs from the standpoint of IP and market exclusivity. How will the normal timelines be impacted by MAPPs given there is no hard starting point, i.e., no magic moment? Does it matter at all?

SF: I think to answer that question we have to take a step back and understand that MAPPs is not a new designation, nor is it a new type of marketing authorisation. MAPPs seek to operate within the existing legal and regulatory frameworks. So, as such, when we consider patent exclusivity, regulatory data exclusivity, market exclusivity, and related supplementary and paediatric rewards, they will all exist and operate as they do today both independently and complementarily to encourage medicine development.

One of the key considerations, as you pointed out, is when the marketing authorisation for a new product triggers the start of an exclusivity clock which is finite. Whether we consider the scenario under MAPPs or not, there might be a conditional marketing authorisation with a less comprehensive data package that requires subsequent post authorisation data collection. There are extra considerations as to the benefits and incentives of being early to market, and how that impacts patent exclusivity balanced against regulatory and other incentives that will be ‘running down’, as it were, whilst the additional data required is being collected.

But from a company perspective, things like conditional marketing authorisation have been around for a number of years. So, companies have a fairly good understanding of those incentives, benefits, and risks of coming earlier to market versus any remaining incentives.

Yes, the exclusivity periods, whether patent, regulatory data protection, or other incentives are important, but they form only part of a much more complex and multifaceted economic case for each product. That includes other incentives like the commercial incentives and pricing/reimbursement considerations.

DS: Would the fact that we’re getting those therapies to patients sooner also be an overriding concern?  

SF: It would be indeed. Companies will have their own processes to map and understand what the patent benefits will be when coming earlier to market versus subsequent exclusivity benefits during data collection and possible indication expansion.

DS: And one assumes, using MAPPs to change the process for data collection and coming earlier to market will influence the overall way you engage stakeholders in the process?

SF: The importance of having that early input from all stakeholders during those early dialogues will really be very beneficial to all, but particularly to companies. They need to understand things like the disease populations, the potential mapping of indication expansion, as well as some early estimates from payers as to what might be their return on investment. So, under MAPPs those daily dialogues will be extremely beneficial.

DS: One of the core missions of ADAPT SMART has been ‘putting patients at the centre’. Is the previous example an extension of that philosophy?

SF: Yes, indeed. Putting patients at the centre comes a bit from some historical approaches that have been somewhat fragmented and superficial, where patient input has been perhaps a one-off event or based on patients’ choice and satisfaction. Putting patients at the centre really means moving away from a tokenistic approach to a more participatory engagement, which is what we have tried to do in the ADAPT SMART consortium.

Practically it means utilising the patient’s implicit knowledge of the disease in everyday life and translating that into explicit knowledge that can be used by other stakeholders. For that to happen, we’ve explored with patients how that process can be inclusive, continuous, and sustainable.

DS: When you say ‘other stakeholders’, are we talking the regulators and the payers; those sitting at the wheel of the decision-making apparatus that would make those therapies available and funded?

SF: That is correct, yes.

DS: One of the key ideas of MAPPs is that rather than having a single test of efficacy and then moving into the market for effectiveness measuring, we can join those two through an earlier release with much more aggressive data capture. How has ADAPT SMART been addressing the many questions that exist around this new approach?

SF: The consortium has tried to understand and listen to what are some of those ethical concerns coming from stakeholders, but particularly from patients and healthcare professions. Are these concerns MAPPs specific? How do those concerns appear to be impacting the decisions of stakeholders? I think it’s important to remember that we have been presented with an educational opportunity for all stakeholders, and particularly patients and healthcare professionals, as to what the MAPPs concept is and, consequently, what it is not.

We have to remember that MAPPs operates within the current legal and regulatory frameworks, that being any new product authorised under an adaptive approach will have met the same rigorous standards of safety, efficacy, and the demonstration of a positive benefit-risk. Our education efforts have been quite important and that should continue after the programme of work is finished, so that stakeholders, but particularly the patients and healthcare professionals, have that information and the tools in place to have those bilateral conversations as to what MAPPs is, what it is not, when a product is prescribed, any need for extra data collection, the impact of MAPPs on the patient and the healthcare professional, the impact of a change in benefit-risk assessment, etc. It’s these upfront discussions that will really help reduce some of the ethical concerns, so there aren’t any big surprises later on.

DS: You’ve highlighted many questions that MAPPs needs to address through early dialogue amongst stakeholders. What tools and processes have the ADAPT SMART consortium put in place to facilitate that early interaction, and what still needs to be addressed?

SF: In terms of the tools that need to be in place, the big thing is education, and that can be done at several levels. There is the education that we’ve done within the consortium, but also through utilising some of the larger patient organisations as brokers of information and some of the professional healthcare networks. Also, by tapping into resources from either companies or regulators to make sure that the information about MAPPs and the products that would be prescribed under MAPPs is accurate, relevant and timely.

There are also a number of traditional European tools that MAPPs can use, such as the summary of product characteristics and direct healthcare professional communications. These provide vital information to regulators and professionals. There are also a variety of other Member State level tools able to provide support for driving appropriate information both to healthcare professionals and patients alike.

DS: So, those are the tools, what still needs to be addressed to put MAPPs into practice for real?

SF: We still need to understand a lot more about the practical application of MAPPs outside of the countries that have been involved in the consortium. There has been very good work that has gone on in Work Package 3 trying to understand the broader context of how Managed Entry Agreements (MEAs) would be implementable in some of the other Member States, and I think the same applies here when we look at some of the ethical and legal considerations as well. What works in one Member State might not necessarily work in another, and we need to address those constraints in the context of the societal issues locally. That may require further empirical research.