Evidence Generation Throughout the Life Cycle

Duane Schulthess: Thank you for your time, Jacoline. There has been a tremendous amount of discussion that one of the key innovations in MAPPs is that it uses evidence generation throughout the entire product life cycle. Can you explain what that means, and how it differs from our current process for approval?

Jacoline Bouvy: Evidence generation throughout the life cycle means and recognises that there’s not one critical approval point where you’ve learned everything there is to know about a product’s benefit-risk, safety, efficacy, clinical effectiveness, cost-effectiveness, and the kind of real-world impact a product delivers. We are increasingly realising that there’s not one point in time where everything is known.

In the past, assessments that underpin pricing and reimbursement decisions would look at the evidence which was delivered at one point in time, usually directly after regulatory approval. We increasingly recognise that the evidence package matures over the course of a therapy’s use, and that making better use of the evidence as it accumulates throughout the life cycle could support better decision making by the different stakeholders.

DS: If we look at some of the new therapeutics emerging in Immunotherapy, where we have widely different responses with some people effectively cured and others having adverse events, do you see MAPPs as yielding opportunities to change the way reimbursement or effectiveness is determined?

JB: Possibly, yes.  Looking at the evolving and changing nature of some of the products that we see coming to the market now, when compared to five or ten years ago, different products with different types of effects pose new challenges to the way we assess products and make decisions today. So, absolutely. I think that these types of products, especially when they have transformative potential and can have very long-term effects, would be a potential candidate for alternative types of evaluation models such as MAPPs.

DS: You’ve been dealing with various HTA’s in the ADAPT SMART project, particularly EUnetHTA. What are the challenges that you see in implementing MAPPs and putting life cycle management into practice across the various Member States?

JB: I think that there are two main challenges to putting MAPPs into practice. Firstly, not all the stakeholders are equally convinced about the problems that some of the proponents of Adaptive Pathways and the MAPPs approach are addressing, as not everyone is convinced that there is a problem with access and that early access is something that should always be facilitated.

Secondly, some of the ideas and philosophies behind Adaptive Pathways and the MAPPs concept might require the stakeholders in the health ecosystem to make changes to the way they currently work. I think that some of the post-marketing approaches and moving to a model where you would be adapting your decision-making over time as evidence accumulates, which is the key component of the MAPPs concept, does require additional resources as HTAs would need to adapt the way they work.

DS: Is part of that problem legislative?  Are they not legally allowed to change their evaluation methods under the current regulations of their Member States?

JB: Yes. In some of the Member States that’s absolutely the case. We’ve been having lots of discussions about outcomes-based managed entry agreements for example, and some of those concepts are just not implementable in some of the countries but in other countries they could be. Sometimes you find that there are practical limitations.

I think one of the things that we’ve achieved within ADAPT SMART is that, as a platform, we’ve identified that this is a pathway for the more transformative types of products with a substantial added benefit. There is consensus amongst most of the stakeholders that these are the sorts of products – for patients with high unmet needs – where everyone is aligned and where working together to facilitate appropriate patient access is good.

DS: You mentioned briefly the challenges and discussions around managed entry agreements (MEAs). You’ve been very active in the ADAPT SMART project studying how MEAs can facilitate MAPPs, can you provide us with a background on what these are and how they operate from an HTA perspective in the context of MAPPs?

JB: Sure. A managed entry agreement (MEA) is any type of arrangement or contractual agreement between a manufacturer of a product and a payer or provider that puts any conditions on providing access to product. MEAs range from confidential or simple discounts, to price-volume agreements, to more complicated arrangements that can include the collection of additional data or evidence.

The latter we call outcomes-based MEAs, and we’ve been specifically looking at their use in different Member States. So, agreements where coverage is provided, subject to the collection of additional data, will usually focus on the performance or the effectiveness of a certain product.

DS: In the context of MAPPs, how have you been testing the waters practically in ADAPT SMART to lay the groundwork for implementing MEAs?

JB: ADAPT SMART is a ‘coordination and support action’, rather than a primary research project. What we have done is look at the literature to collect and collate experiences with different types of models. We’ve also held a series of workshops and discussions and through rounds of consensus building have drafted a paper to identify what types of models are available and might work in implementing or facilitating managed access to products under an Adaptive Pathway.

We found that there is a lot of room for improvement in coordinating data access. If you’re thinking about an outcomes-based model, you’ll be looking at collecting the same type of data on the performance of a product for different countries. Today, there is very little to no coordination among the various EU member countries with the data they’re collecting as well as making use of that data.

We’ve encountered enthusiasm for exploring how the EU countries could work together in collecting the data.  EUnetHTA is doing work that could also facilitate this process.

DS: One of the key milestones of ADAPT SMART has been putting stakeholders at the centre of decision-making.  Why do you see stakeholders being at the centre of decision-making as such an integral part of MAPPs, and how does that differ from the current way that stakeholders are engaged?  

JB: It is a key concept of the MAPPs approach which offers a huge potential benefit over a more traditional drug development paradigm. For downstream stakeholders, it provides the option to engage early with companies about their development plan and offers the huge potential to improve the evidence of submissions that we will see several years down the line when the product has to go through their regulatory evaluations.

It also offers the option for a company to better align with some of the expectations of both patients and the different healthcare system stakeholders to align their preferences. Ideally, this will bring fewer mismatches between their expectations.

DS: How has this concept of putting other stakeholders at the centre of decision-making been accepted across all of the various EU HTA’s and government bodies? Is this generally seen as a good thing or is there still work to do?

JB: I think it would depend on whom you ask. There is still work to be done, but at the same time you do see some exceptional progress. For example, EUnetHTA now has an established mechanism for early dialogue involving several countries, which is a big step towards a more systematic early engagement with HTA bodies at the European level.

DS: One final thought Jacoline, why has NICE been so adventurous and forward-looking in engaging with a lot of this activity which focuses on changing processes?

JB: I think from the beginning we’ve always had an open mindset regarding MAPPs, and this goes back to before my time at NICE. As you know, Sarah Garner, who’s now left NICE for the World Health Organisation, has been actively involved in developing the Adaptive Pathways concept from the beginning. As an organisation, any concept that could improve timely access for people in the NHS to cost-effective treatments is a concept that might be worth exploring. Why would we not be interested in exploring whether this might actually work?