CWWeekly presents this biweekly feature as a spotlight on issues that executives in clinical research face. This week, writer Suz Redfearn spoke with Dr. Stella Blackburn, vice president and global head of risk management for real-world evidence solutions at QuintilesIMS. As part of her efforts, Blackburn has been focused on the EMA’s adaptive pathways pilot program.

Q: Please explain the EMA’s adaptive pathways. How does it work?

A: Adaptive pathways (AP) is a proactively planned, iterative approach to bringing medicines to market for patients with an unmet medical need. The aim is to balance access to medicines for patients with life-limiting condi­tions who have few or no treatment options, with the need to provide comprehensive information on the medicine as it’s being developed. The program is, essentially, trying to move the initial authorization point to allow earlier market access, while at the same time ensuring that evidence continues to be devel­oped. One of the key parts is the involvement of all stakeholders—patients, regulators, health technology assessment (HTA) bodies, payers and doctors—during the development program.

The AP concept is: you do your initial drug development using a very well-defined group of patients who have the most clinical need for this drug. If the studies show a significant benefit and the overall benefit/risk balance is positive, then the medicine gets an initial authorization in that niche indication with a condition that those pa­tients who receive the marketed medicine would have to be in some form of an observational study or monitoring program. What you’ve got is the patients with the most immediate need getting access, while ensuring that evidence about the benefits and risks continues to be generated.

At the same time, as real world evidence is generated from the medicine being marketed, clinical trials continue to gain additional informa­tion about the expanded and original indications. Using evidence generated from both real world studies and clinical trials means that a more complete picture of the drug can be generated to satisfy the needs of all stakeholders. But compa­nies need to be prepared—if the initial promise on the drug doesn't hold forth, there has to be a plan for removing the drug from the market.

Thus far, this is all theoretical as no medi­cine has gone through the whole pathway and received an initial authorization. The pilot program started in 2014, and out of 62 submitted proposals, seven products have made it through the initial stages and are being developed using this approach.

Q: Why is the program important? Why has it been controversial?

A: Patients with an unmet medical need may not have time on their side. Remember the HIV/AIDS epidemic? Patients were absolutely desperate to have any sort of treatment and couldn't wait for the years-long clinical research and development programs required to achieve regulatory approval and access.

The adaptive pathways program gives pa­tients the choice; if they are willing to take the risk of much greater uncertainty with a drug earlier on in development, they can. Adaptive pathways isn't new legislation—it’s a concept that uses the existing conditional marketing authorization. Some critics feel it would lead to a reduction in the amount of evidence required to bring drugs to market and they say it’s just pandering to the industry. Others worry that patient safety will be compromised. But still others feel the very controlled access actually offers more safety, es­pecially regarding the time just after a drug goes to market when potentially a massive number of patients could begin using the new treatment.

I was at the EMA when Viagra was licensed. In its first week on the market, rumor has it that close to 100,000 patients used it. In a situation like that, you go from a controlled trial environ­ment to maybe hundreds of thousands of people using it in a very short space of time. It is arguably safer to have a more staggered introduction to the market like the adaptive pathways program offers.

Q: What’s the future of adaptive pathways and what will the impact be on the industry?

A: I think many EU regulators are supportive of this. The HTA bodies and the payers have more of a dichotomy of positions, however. Some are very support­ive while others are worried that there isn't enough evidence of effectiveness.

However, there are really two components to the adaptive pathways concept. One is early market access for patients with severe diseases and unmet medical needs. The second is the iterative development plan, which looks at evidence from each trial or each marketed indica­tion coming in, and plans for the next stage using that information. I think this is a concept that should be expanded; in the future, we should be doing it for all medicines.

To be honest, I don't know whether adaptive pathways will succeed because of the reluctance of some of the HTA bodies and the payers. My guess is that some European countries will go for this and some won’t. Although there is an early initial authorization, only some HTA bodies and payers will allow market access. I do think, howev­er, that the concept of the iterative development plan will stay with us no matter what happens with the rest of the adaptive pathways.

This article was reprinted from Volume 20, Issue 47, of CWWeekly, a leading clinical research industry newsletter providing expanded analysis on breaking news, study leads, trial results and more. Subscribe »