Improving COPD Trial Efficiency Using the Win Ratio: Sanjay Ramakrishnan, MD

Unlike the current annualized exacerbation rate, the win ratio prioritizes and combines multiple end points, such as hospitalization risk, exacerbation risk, lung function, and symptoms in chronic obstructive pulmonary disease (COPD), explains Sanjay Ramakrishnan, MD, senior lecturer, University of Western Australia.

This transcript was lightly edited; captions were auto-generated.

Transcript

Why is the win ratio approach particularly valuable in understanding treatment effects in COPD, and how might it shift ways to evaluate therapies in future clinical trials?

A quick introduction of how we currently do things in COPD; we use what we call an annualized exacerbation rate. That's the main end point, the phase 3 end point for clinical trials for new medicines in COPD, which means we count how many exacerbations someone has in a year, we average it, and then we compare it to medicine and not medicine. That's how we report at the moment. This is what we've done for 20-something years. Can we do better?

Win ratio is an end point that's already being used by cardiology trials, intensive care trials, where we prioritize different end points within the same end point. Composite end points are not new, so we've had composite end points forever, which means you're hitting many end points within the same target. Win ratio prioritizes that. You're looking at what is more important within that composite so you're not just getting a positive composite of all 3 or all 5. You can get what is more important to get first and follow by another one, another one.

Why does it work? In COPD, we have lots of events, lots of people ending up in hospital, lots of people having exacerbations, but patients also care about symptoms and lung function. And currently, the way we look at trials only does exacerbations, we can't ask or evaluate within that the benefits the patient gets from symptoms and function improvement. Win ratio allows us to combine that so we don't just stick with what we already have. We can expand on that, and by doing that, we help communicate better where the benefits are both to the funder, to the reader, to the physicians, and to the patients, but we also improve the power of the trial. It means that the amount of patients that need to be randomized is fewer, so less people getting placebo. And the results will come out faster, because you need fewer patients to answer the clinical question.

What do your findings suggest about the potential for dupilumab to change the standard of care for patients with COPD and type 2 inflammation?

Dupilumab works for COPD in people who type 2 inflammation; that's already shown in BOREAS [NCT03930732] and NOTUS [NCT04456673], and it reduces exacerbations by over 30%. Huge! But how do we communicate that? What win ratio allows us to do is to specifically break down these different things. Before this, we couldn't quite legitimately claim these findings, but now we can. To reduce any risk of death or hospitalization, you only need to treat 50 patients. So a number needed to treat of 50 to prevent that, which is huge in a mortality study. That's a very impressive finding. If you combine that with any prevention of any exacerbation, so you've got a group of people who are exacerbating and give them the dupilumab, you'd stop all exacerbations every 16th person you treat. Number needed to treat is 16. That is incredible for any kind of medicine. These are the ways win ratio allows us to communicate better. You couldn't do that with annualized exacerbation rate. You couldn't give that kind of concrete results that win ratio allows us to do.