When looking at what payers prioritize in Phase III clinical trial results compared to three years out, two opposing rules frame the picture: “change is constant” and “the more things change, the more they stay the same.”

Let’s start with the latter. For formulary decision-making, payers considering Phase III trial results have always prioritized the primary endpoint for efficacy, plus safety data. That was the case three years ago; it is the case now; and, based on conversations with health plan and pharmacy benefit manager pharmacy and medical directors, it will be the case three years from now. Despite the rise in breakthrough treatments, as well as developments in trial design, testing, and the use of artificial intelligence, that focus appears unlikely to change.

What will change is the growing impact of a financial lens governing how payers view trial results and the implications they hold for coverage and access. This trend for Phase III data to be increasingly interpreted through a financial lens can be described from multiple angles. Two discussed here are large and orphan disease populations.

Large disease populations

While timing will differ for different disease states, what payers expect to see over the next three years is an influx of generic and biosimilar options. Consequently, as cost structures change, the value proposition standard for future products will become more severe.

Here, two points stand out for Phase III trial planning. First is the importance of a strong, active comparator.

Second is the importance of the number needed to treat (NNT) compared to the low-cost incumbent. If, in the first case, differences are not expected to produce clinically meaningful differences, and in the second, the NNT is expected to be comparable, manufacturers can anticipate a steep climb for equal access.

For Phase III trial planning, two suggestions may have merit. Include sizeable subpopulations that payers cannot easily dismiss. These might be more acute patients, late-stage patients, patients with comorbidities, and patients with distinct demographic characteristics.

Also, include secondary endpoints payers will recognize as “important” and incumbents are unlikely to match. Varying by disease state, these could include reduction in symptom burden, slower decline in organ function, greater delay in relapse, sustained remission or control, and meaningful functional gains.

The headline for future Phase III planning is that the base case for how payers evaluate trade-offs will favor the financial over the clinical.

Orphan disease populations

Although currently there are often one or two treatments for orphan conditions, payers anticipate greater competition over the next few years. The big access challenge today, then, is securing coverage, with payers relatively hands-off after approval. Call this “access challenge 1.0.” But as additional agents enter the same orphan space, payers will be able to manage access by pitting one against another. Call this “access challenge 2.0.”

For those disease states where a patient’s health status is not irreversibly harmed by an initial agent’s failure, payers can be expected to adopt a preferred agent through prior authorization—with another option “always available.” In effect, the 2.0 orphan landscape will somewhat mirror how payers manage categories such as hypertension, high cholesterol, diabetes, depression, and asthma.

To mitigate these commodification tendencies, three suggestions might be considered for future Phase III planning:

• Adopt trial design features so when payers make cross-trial comparisons, trial differences themselves strengthen how the new brand compares.
• Study efficacy factors likely to all move in the same direction, persuading prescribers to see valuable differentiation.
• Identify one or two clinically meaningful endpoints that are precise, making a risk arrangement for super high cost treatment a viable option.

Gap analysis

With a financial lens gaining greater influence over how payers view future Phase III results, trial planning should address how payers weigh the financial against the clinical.

One suggestion is to understand prescribers’ clinical priorities, payer thinking on standard of care, and the gap between the two. As payers’ ability to act based on financial considerations increases, the need for a gap analysis to inform future Phase III trial planning increases as well.

Ira Studin, PhD, is President, Stellar Managed Care Consulting. He can be reached at istudin@stellarmc.com.