Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the BCG Drug Shortage - Brian Chun
June 7, 2023
Ruchika Talwar hosts a conversation with Brian Chun to discuss Chun's study on the impacts of the BCG drug shortage, a problem that has plagued urologists nationwide for nearly a decade, on the treatment of non-muscle invasive bladder cancer. Chun's research, conducted through a review of Medicare claims data from 2010 to 2017, reveals a decrease in BCG use across the country and a considerable state-by-state variation. In response to the shortage, many practitioners turned to alternative therapies like mitomycin C. Despite limitations of the study, which include its retrospective nature and the focus on single agent therapies, the findings prompt important considerations for future practices. Chun highlights the urgency to develop and approve alternative therapies, reducing dependence on single-source drugs. While a challenging situation, it has accelerated the search for other options, offering an optimistic perspective on patient treatment possibilities.
Biographies:
Brian Chun, MD, Urologist, Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA
Ruchika Talwar, MD, Urologic Oncology Fellow, Department of Urology, Vanderbilt University Medical Center, Nashville, TN
Biographies:
Brian Chun, MD, Urologist, Department of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA
Ruchika Talwar, MD, Urologic Oncology Fellow, Department of Urology, Vanderbilt University Medical Center, Nashville, TN
Read the Full Video Transcript
Ruchika Talwar: Hi everyone. Welcome back to UroToday's Center of Excellence in Health Policy. In today's video, we'll be covering a recent article published in the Gold Journal entitled Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the BCG Drug Shortage. I'm really excited to be joined today by Dr. Chun, who is at the University of Pittsburgh. Thanks so much for being with us today.
Brian Chun: Thank you for having me.
Ruchika Talwar: We'll be covering an interesting topic that has been a pain point for urologists all over the country for several years now, and that is the BCG shortage. High risk non-muscle invasive bladder cancers already a really challenging disease state and this issue has been very much exacerbated by drug shortages that sort of ebb and flow without much predictability over time. Why don't you give us a little bit of insight into your study?
Brian Chun: Absolutely. I think it's no surprise to anyone in the urology community that there's been a shortage of BCG for quite some time now, probably the better part of a decade when the Sanofi plant in Toronto was shut down in 2012 due to a fungal infection. And since then, it's been an ongoing battle with urologists across the country, making sure patients are able to get the available BCG treatments. And there's been clinical data coming out looking at the implication of what that means for patients. But deep down, there's been an understanding that BCG availability has driven treatment protocols at a number of institutions, but no one has really looked at how those have been affected and quantifying those changes. So that was sort of the basis of our study.
Ruchika Talwar: Great. Tell me a little bit about the patient population that you used in your methods.
Brian Chun: We leveraged the Medicare database looking at claims data from 2010 to 2017. We looked at patients who were newly diagnosed with bladder cancer and received intravesical therapy within one year of diagnosis. We also looked at clinical billing codes to confirm receipt of intravesical therapies and also the number of therapies that they received.
Ruchika Talwar: Okay. And what intravesical therapies specifically were you looking at?
Brian Chun: We looked at BCG, mitomycin, gemcitabine and also grouped a number of other anti-tumor intravesical therapies that are not specifically coded.
Ruchika Talwar: Okay. And what did you find?
Brian Chun: So it was fairly interesting. Overall, it was not surprising, but we did find that BCG utilization decrease across the board across the country about 5.9%, but what was most striking was that the variability in the amount of decreased BCG use by state was highly variable ranging between 5% and up to 36% when you compared to the pre drug shortage eras. And there did not appear to be any kind of regional distribution on which states were heavily affected, but it was very striking just to see the variation across the board.
Ruchika Talwar: When BCG utilization rates decreased, did you see an increase in the other intravesical therapies?
Brian Chun: Absolutely. So one agent in particular, supplanted BCG in those prime years of shortage, which was around 2015, and that was mitomycin C. In fact, if you trend the use of BCG over those years, there's almost like a switching of BCG use and mitomycin use in those periods. A couple years after the plant was shut down, the prime years of the BCG shortage, we suspect that a lot of practitioners facing these BCG shortages utilized alternate therapies such as mitomycin as an alternative treatment modality for these patients.
Ruchika Talwar: And what about gemcitabine?
Brian Chun: Yeah. Over the course of our study period, we found that gemcitabine actually remained pretty stable. Our data only goes up to 2017, which predates a lot of when the newer efficacy data on gemcitabine and certainly combination of gemcitabine and docetaxel was coming into light. So it would be interesting to sort of look at where those trends would be today.
Ruchika Talwar: Yeah, I did notice that. I think you're right. I think that perhaps if we were to repeat the study with a more contemporary period on the tail end, you would see a change in gemcitabine perhaps mirroring the change you saw in mitomycin. But I do think that there's been widespread adoption with the newer trial data. What's really interesting is the variation in state utilization that you've noticed. Just anecdotally, I have heard lots of stories about even within the same city or within the same state, there being major variations in areas that are even just 30 minutes apart as to who has access to BCG and who doesn't.
A lot of that has remained frustrating for providers and patients. There's not a lot of insight from Merck as to why that's happening and what's driving those distribution of variations. But I think it's become a major pain point over the years as we continue to have this cycle repeat. The nice thing is there's been a lot of advancements in intravesical therapy, both with the widespread use of things like gemcitabine, docetaxel, but also other clinical trials that are using novel agents. So it'll be interesting to take a look at a similar analysis in a few years.
Brian Chun: Absolutely. I can especially say, at least in Pittsburgh, we face those same limitations within our city, just a couple hospitals in our area. There's a wide variability in the allocation of BCG. When Sanofi left the market in 2017, that effectively made Merck the sole supplier of BCG for the entire country. There are consequences to having supplies pretty much from one supplier. It's been an ongoing battle allocating BCG effectively across the country. And Merck has reported that they base allocation on historical demand, but the granularity of how that's calculated is not entirely clear.
Ruchika Talwar: Historical demand is so challenging to calculate when you're doing so in an era of ongoing shortage. How are you going to know that there's demand for the drug when providers have to adopt their treatment strategies to deal with the fact that there is no drug? A lot of this rationing will also complicate that, giving things like one-third dosing, splitting doses, scheduling patients appropriately. Really interesting stuff. I think from a health policy perspective, it really is critical to do the source of studies that you've done and show these variations in care so that we can establish that the quality of bladder cancer care provided actually decreases when we have these external influences from drug shortages. I definitely applaud you and the co-authors on this study. What are some limitations of your analysis?
Brian Chun: With any type of retrospective review, there's always going to be some limitations. We're kind of limited by the billing and claims data that is used in Medicare, and we specifically limited our study to single agent therapies. Any kind of combination therapies were not included to simplify our analysis, but that's certainly a limitation.
Ruchika Talwar: How should we as urologists use this data to inform our future practice?
Brian Chun: Yeah, that's a great question. I think that we're still trying to find the answers to that. I think a silver lining with this whole BCG shortage is that it's really expedited alternative therapies and trying to decrease our dependence on a sole drug and also coming from a sole supplier. There have been ongoing studies looking at getting different strains of BCG from different suppliers approved in the US and also a new BRIDGE trial, new phase three clinical trial comparing gemcitabine docetaxel head-to-head with BCG for high risk BCG naive patients. So I think a lot of this has been expedited with the climate of the drug shortage, and that is a silver lining of the situation or environment that we face right now.
Ruchika Talwar: I totally agree with you. I think in a tough situation, the one advantage has been that it's accelerated us looking at alternative therapies and providing more options for our patients. So that's definitely an optimistic view. Thank you so much, Dr. Chun, for joining us today, and congratulations on a great study asking some tough questions.
Brian Chun: Thank you for having me.
Ruchika Talwar: Thanks to our UroToday audience for joining us in this installment of the Health Policy Center of Excellence for UroToday. We hope to see you again soon.
Ruchika Talwar: Hi everyone. Welcome back to UroToday's Center of Excellence in Health Policy. In today's video, we'll be covering a recent article published in the Gold Journal entitled Variation in Statewide Intravesical Treatment Rates for Non-Muscle Invasive Bladder Cancer During the BCG Drug Shortage. I'm really excited to be joined today by Dr. Chun, who is at the University of Pittsburgh. Thanks so much for being with us today.
Brian Chun: Thank you for having me.
Ruchika Talwar: We'll be covering an interesting topic that has been a pain point for urologists all over the country for several years now, and that is the BCG shortage. High risk non-muscle invasive bladder cancers already a really challenging disease state and this issue has been very much exacerbated by drug shortages that sort of ebb and flow without much predictability over time. Why don't you give us a little bit of insight into your study?
Brian Chun: Absolutely. I think it's no surprise to anyone in the urology community that there's been a shortage of BCG for quite some time now, probably the better part of a decade when the Sanofi plant in Toronto was shut down in 2012 due to a fungal infection. And since then, it's been an ongoing battle with urologists across the country, making sure patients are able to get the available BCG treatments. And there's been clinical data coming out looking at the implication of what that means for patients. But deep down, there's been an understanding that BCG availability has driven treatment protocols at a number of institutions, but no one has really looked at how those have been affected and quantifying those changes. So that was sort of the basis of our study.
Ruchika Talwar: Great. Tell me a little bit about the patient population that you used in your methods.
Brian Chun: We leveraged the Medicare database looking at claims data from 2010 to 2017. We looked at patients who were newly diagnosed with bladder cancer and received intravesical therapy within one year of diagnosis. We also looked at clinical billing codes to confirm receipt of intravesical therapies and also the number of therapies that they received.
Ruchika Talwar: Okay. And what intravesical therapies specifically were you looking at?
Brian Chun: We looked at BCG, mitomycin, gemcitabine and also grouped a number of other anti-tumor intravesical therapies that are not specifically coded.
Ruchika Talwar: Okay. And what did you find?
Brian Chun: So it was fairly interesting. Overall, it was not surprising, but we did find that BCG utilization decrease across the board across the country about 5.9%, but what was most striking was that the variability in the amount of decreased BCG use by state was highly variable ranging between 5% and up to 36% when you compared to the pre drug shortage eras. And there did not appear to be any kind of regional distribution on which states were heavily affected, but it was very striking just to see the variation across the board.
Ruchika Talwar: When BCG utilization rates decreased, did you see an increase in the other intravesical therapies?
Brian Chun: Absolutely. So one agent in particular, supplanted BCG in those prime years of shortage, which was around 2015, and that was mitomycin C. In fact, if you trend the use of BCG over those years, there's almost like a switching of BCG use and mitomycin use in those periods. A couple years after the plant was shut down, the prime years of the BCG shortage, we suspect that a lot of practitioners facing these BCG shortages utilized alternate therapies such as mitomycin as an alternative treatment modality for these patients.
Ruchika Talwar: And what about gemcitabine?
Brian Chun: Yeah. Over the course of our study period, we found that gemcitabine actually remained pretty stable. Our data only goes up to 2017, which predates a lot of when the newer efficacy data on gemcitabine and certainly combination of gemcitabine and docetaxel was coming into light. So it would be interesting to sort of look at where those trends would be today.
Ruchika Talwar: Yeah, I did notice that. I think you're right. I think that perhaps if we were to repeat the study with a more contemporary period on the tail end, you would see a change in gemcitabine perhaps mirroring the change you saw in mitomycin. But I do think that there's been widespread adoption with the newer trial data. What's really interesting is the variation in state utilization that you've noticed. Just anecdotally, I have heard lots of stories about even within the same city or within the same state, there being major variations in areas that are even just 30 minutes apart as to who has access to BCG and who doesn't.
A lot of that has remained frustrating for providers and patients. There's not a lot of insight from Merck as to why that's happening and what's driving those distribution of variations. But I think it's become a major pain point over the years as we continue to have this cycle repeat. The nice thing is there's been a lot of advancements in intravesical therapy, both with the widespread use of things like gemcitabine, docetaxel, but also other clinical trials that are using novel agents. So it'll be interesting to take a look at a similar analysis in a few years.
Brian Chun: Absolutely. I can especially say, at least in Pittsburgh, we face those same limitations within our city, just a couple hospitals in our area. There's a wide variability in the allocation of BCG. When Sanofi left the market in 2017, that effectively made Merck the sole supplier of BCG for the entire country. There are consequences to having supplies pretty much from one supplier. It's been an ongoing battle allocating BCG effectively across the country. And Merck has reported that they base allocation on historical demand, but the granularity of how that's calculated is not entirely clear.
Ruchika Talwar: Historical demand is so challenging to calculate when you're doing so in an era of ongoing shortage. How are you going to know that there's demand for the drug when providers have to adopt their treatment strategies to deal with the fact that there is no drug? A lot of this rationing will also complicate that, giving things like one-third dosing, splitting doses, scheduling patients appropriately. Really interesting stuff. I think from a health policy perspective, it really is critical to do the source of studies that you've done and show these variations in care so that we can establish that the quality of bladder cancer care provided actually decreases when we have these external influences from drug shortages. I definitely applaud you and the co-authors on this study. What are some limitations of your analysis?
Brian Chun: With any type of retrospective review, there's always going to be some limitations. We're kind of limited by the billing and claims data that is used in Medicare, and we specifically limited our study to single agent therapies. Any kind of combination therapies were not included to simplify our analysis, but that's certainly a limitation.
Ruchika Talwar: How should we as urologists use this data to inform our future practice?
Brian Chun: Yeah, that's a great question. I think that we're still trying to find the answers to that. I think a silver lining with this whole BCG shortage is that it's really expedited alternative therapies and trying to decrease our dependence on a sole drug and also coming from a sole supplier. There have been ongoing studies looking at getting different strains of BCG from different suppliers approved in the US and also a new BRIDGE trial, new phase three clinical trial comparing gemcitabine docetaxel head-to-head with BCG for high risk BCG naive patients. So I think a lot of this has been expedited with the climate of the drug shortage, and that is a silver lining of the situation or environment that we face right now.
Ruchika Talwar: I totally agree with you. I think in a tough situation, the one advantage has been that it's accelerated us looking at alternative therapies and providing more options for our patients. So that's definitely an optimistic view. Thank you so much, Dr. Chun, for joining us today, and congratulations on a great study asking some tough questions.
Brian Chun: Thank you for having me.
Ruchika Talwar: Thanks to our UroToday audience for joining us in this installment of the Health Policy Center of Excellence for UroToday. We hope to see you again soon.