And one of the things that's very important to patients, of course, and the healthcare system, is the cost-effectiveness of the newer treatments that we have. So, Amanda, thank you for taking the time and spending with us today, and talking to us and sharing with us your insights into the recent effort that you put forward that got published in European Urology on cost-effectiveness analyses for BCG-unresponsive CIS options. Take it away.
Amanda Myers: Thank you for the kind introduction. Yes. Today I'll be discussing our cost-effectiveness analysis of treatments for BCG-unresponsive carcinoma in situ of the bladder. So patients with BCG-unresponsive CIS have multiple treatment options. However, we don't have any head-to-head comparisons for the newer FDA-approved drugs. This leaves us trying to decide between efficacy, toxicity, cost, whether to pursue bladder-sparing therapy or move directly to cystectomy. And we don't know how necessarily we want to select or sequence these therapies.
And given the high cost of these drugs and the lack of comparative data, we set out to model the value of these treatments using a cost-effectiveness analysis. So, what we did was we developed a Markov decision analytic model comparing five strategies, radical cystectomy, nadofaragene, nogapendekin with BCG, pembrolizumab, and gemcitabine/docetaxel. We evaluated three index patients. One willing to try a first-line bladder sparing therapy or upfront cystectomy, a second patient willing to try one to two lines of bladder sparing therapy.
And then a third patient willing to try one to two lines of only the FDA-approved bladder-sparing options prior to cystectomy, not considering gemcitabine/docetaxel. We used a three-month cycle over a five-year time horizon to look at cost-effectiveness from a Medicare payer perspective with a willingness-to-pay threshold of $100,000 per quality-adjusted life year, which is standard in these analyses. Now, this is a decision... a simplified decision figure tree that essentially allows you to understand what our model looked at.
We started with our index patient one, and we took them through would they have a cystectomy or a first line bladder sparing therapy. If they had a cystectomy, did they have any complications? What was the pathology? What kind of surveillance did they have after that? And then did they end up developing metastatic disease? If they had bladder-sparing therapy, did they have... did they recur? Did they not recur? Did they have toxicity, including surveillance schedules, maintenance? And if they did progress to muscle-invasive disease treatment for that. And then also the fact that... including the fact that patients could die at any point during the five years.
So, when we look at our results, we can see this table here, and it shows you the cost. And this is the five-year cost, including everything from the drug cost to the surveillance to the maintenance to the recurrences, toxicity, et cetera. So that's an all-inclusive cost on average for five years. The effectiveness is looking at the five-year QALY. The QALY is the quality-adjusted life year. So what that actually is, one QALY is one year in perfect health. So if you live for two years at 50% perfect health, then that would be one QALY—0.5 times two.
So this can show you that essentially, out of five years, these patients were living about 3.8 to 3.9 years of perfect health over that five-year period. And then we also have the incremental cost-effectiveness ratio, which actually allows us to determine the cost-effectiveness. And this is calculated as the incremental cost divided by the incremental effectiveness. And if the ICER is below the willingness-to-pay threshold of $100,000, the treatment is considered cost-effective. We also have the net monetary benefit. That is calculated as the willingness-to-pay times the effectiveness minus the cost.
And this essentially shows us that the treatments that have a higher net monetary benefit are going to have a higher overall value for the patient. So for our index patient one at the top, we can see that if you're willing to try one line of bladder-sparing therapy or upfront cystectomy, we found gemcitabine/docetaxel to be the most cost-effective. For index patient two in the middle, those willing to try one or two lines of bladder-sparing therapy or upfront cystectomy, we found that radical cystectomy was actually most cost-effective in this scenario.
And for our third index patient willing to try one to two FDA-approved options and not considering gemcitabine/docetaxel, pembrolizumab was actually the most cost-effective. What we found in summary is really that the cost-effectiveness varies depending on the treatment strategy and the patient's willingness to undergo a cystectomy. Radical cystectomy was overall the most cost-effective, but not every patient is going to be willing or suitable for this treatment option.
Among bladder-sparing therapies, gemcitabine/docetaxel was the most effective single-line option, and pembrolizumab ranked the highest among the FDA-approved therapies. All this may be due to the lower cumulative costs from early discontinuation of the drug. And really, most importantly, multiple sequential therapies we found offered limited value, mainly due to these very high drug costs and modest QALY gains. Thank you.
Ashish Kamat: Thank you so much, Amanda. Again, it's very important to get these sorts of messages out to folks that are dealing with patients with bladder cancer and also for healthcare systems, right. So, take us through a little bit as to what the thought process was. Obviously, I know what that was, but take our audience through the process. Why did we decide to do this analysis? What was the genesis of this?
Amanda Myers: I think there's really a gap between all these new treatment options. We don't have any head-to-head comparisons. The costs are getting higher for bladder cancer care in general. And we really need to make this about the patients and really have some value-based data to kind of share with our patients so we can set expectations and determine different outcomes for them.
Ashish Kamat: Yeah. And I think it's important because when you consider what a patient is looking at, clearly there are different costs, right. And when we talk about costs, it's not just monetary costs. Patients have costs when it comes to their time, patients have costs when it comes to their social and mental makeup, but then, of course, there's a cost to the system.
And in the US, we might have payers that might be willing to pay for some of these, but in many parts of the world, just because a drug is approved doesn't mean that the insurers will pay for it. And then oftentimes patients have to decide, "Hey, am I going to shell out X amount of dollars out of my pocket? And where is that going to lead me in 1, 2, 3 years?" So with this data that you have available, clearly, we're not saying that pembro is the most effective, right. Nor are we saying that nadofaragene is the least effective. We're not saying any of that.
But using this data, how would you sit down and counsel two things, a patient sitting right in front of you that's looking to pay out of pocket. And then secondly, how would you counsel a healthcare system? Say you're traveling to another country, they're looking to incorporate this into their paradigm, how would you advise the regulators there? So patient first and then a regulator second.
Amanda Myers: So I think a patient, it is very complex having a conversation with a patient sitting down in front of you, even when they're willing to pay out of pocket, because many of the newer agents do offer payment plans or strategies for patients willing to pay out of pocket. So I think that's something to be discussed with the patient and to take into consideration when you're having those conversations.
When you're talking to actually a healthcare system and looking at how we're going to determine what is sustainable, I don't really think at this point any of these prices are... any of these prices are really unsustainable in the long term, and we really need to look at strategies that we can use to decrease costs and find a more sustainable way forward, whether that's through using biomarkers or better patient selection tools to really help us determine who's going to benefit the most from each of these treatments.
Ashish Kamat: And the recent data from John Gore and Angie Smith's CISTO trial, those presented this year, suggest that patients that self-report, at least their experience with radical cystectomy, are actually very happy with that decision that they made.
And then if you couple that with the fact that it is the most cost-effective, and patients are happy, and it's oncologically sound, I think we have to sort of, in many ways, reset our discussion with the patient, right. So it's very important to do that.
Now I'm sure you've got updated analyses planned with the newer agents that are being approved, so I'm looking forward to seeing what that shows, and I'm sure we'll have you back for another discussion. So thanks for taking the time.
Amanda Myers: Thank you so much.