Practical Applications of Ototoxicity Monitoring: Patient Case Studies

Welcome to this Week in Hearing. Hello, I’m Bob Traynor, your host for this session. And this episode is going to be the second episode in our discussion of ototoxicity monitoring. And today my guest is, again, Rene Lefrancois, the director of audiology at Shoebox. Renee is a 25 year audiology veteran in our profession, and one of the individuals that is behind the ototoxicity monitoring at Shoebox in its research, development, and actual administration. Today, we are in a second session and we want to first define a little bit about the various forms of ototoxicity and some of the clinical measurement of these forms of ototoxicity. And hopefully, Renee, you can kind of help us with that as we move through our definition of this topic. Thanks very much for that warm introduction, Bob. And yes, I’d be happy to move forward in terms of some of those clarifying definitions, because we live in very exciting times, and there have been some monumental discoveries in terms of drug interactions with the hearing and balance systems. Ototoxicity today in 2024, we really want to separate three different areas that can be negatively impacted by certain medications ionizing radiation, solvents, etcetera. Firstly, is the most commonly known, and that’s the cochleo-toxicity. Cochleotoxicity can take two forms in terms of hearing loss or tinnitus. Often, tinnitus can be the first sign prior to signs showing up on the audiogram of threshold deviation. However, there are also alternate forms. One is known as a vestibulotoxicity, which affects the vestibular system. And also it encompasses on neurotoxicity as well in terms of the auditory nervous system. Today, in terms of what Bob and I are going to be discussing, we’d like to focus on the cochleotoxicity, mainly measurement of hearing levels, but also audiometers can be used to as clinically, validly as possible measure tinnitus levels by doing some tinnitus matching, which you can do on a fairly, you know, normal audiometer. So if an audiometer can present a tone at different frequencies and different intensities, then typically you can do at least a rudimentary form of tinnitus masking. Thanks, Bob. Oh, that’s great. Well, and I’d like to remind our group that although many of us have done monitoring for ototoxic medications for cancer patients in many parts of the world, you mentioned in our previous episode that one of the main things that is done in other parts of the world is for screening for malaria as well as tuberculosis and pretty much everywhere. Now, with all the new medications for cystic fibrosis that prolong the lifetime for these individuals, monitoring is absolutely essential there also. You’re absolutely correct, Bob. And I’d like to add a few more conditions to that. One would be lassa fever, which is a west african disease that is contracted from eating animal meat. And it can in itself as a disease, cause hearing loss, but also the treatment and physical condition of having you know, being in a febrile state can also contribute. So those patients have kind of a double whammy of risk factor for hearing loss. So our system has been used remotely in countries in West Africa to monitor that. And we also mentioned, you know, as well, the cystic fibrosis movement is really changing on a worldwide landscape. And so the monitoring that just wasn’t high enough on the priority list for many individuals with CF now that’s changing. So we’re seeing groups cystic fibrosis experts really focusing on taking a look at aspects that weren’t in the past of front of mind for these patients. You know, I think that all of us here in North America, we kind of focus here. A lot of times we focus on the cancer patients and things that we see routinely. But we’ll often not think as much about the world implications of some of the products and the procedures that are being developed here in North America. Maybe you can give us some insight into some of the cases that you guys have seen throughout the world relative to some of the specific disorders that you guys have been monitoring over the last few years. I’ve been eager to share this use case. We at Shoebox are very proud to have been an instrument in the monumental change in drug delivery for MDR-TB, which is multidrug resistant tuberculosis, as the name implies. And this is typically treated with aminoglycoside antibiotics. And as the name implies, as time has gone on, we’re coming up to about 80 years in which tuberculosis was officially identified as the disease. And in years prior to 1953 it was a disease, and it did exist. It just wasn’t known as tuberculosis at that time. There are 12 common aminoglycoside antibiotics that are used, or have been used historically. Ten of those have been deemed ineffective or not as effective as needed. And of the two that were left kanamycin is a very low cost drug. However is quite ototoxic. We’ve seen percentages of up to 70% of adults who complete a full treatment will have significant hearing loss following this treatment. I really need to give credit to the organizations such as US AID, the Union Against Tuberculosis and lung disease, and all of the researchers and infectious disease specialists that are out there. But there was a five year clinical trial in which it was comparing kanamycin injectables, with a new drug called bedaquiline. Bedaquiline, like all new drugs, was very expensive. And because tuberculosis is often in low resource settings even just providing hearing tests in those settings, in countries that often didn’t even have hearing, healthcare professionals was a stretch to come in and say, well, we want to preserve hearing, but here’s a drug that, for example, is 10% the cost, or ten times the cost of the current antibiotic. Well, thanks to that clinical trial and the subsequent publications that were made, the World Health Organization, in their annual report in hearing from 2021 that was published in 2022, basically stated that all countries now should use bedaquiline as it is non ototoxic. So to make such a staunch directive worldwide, knowing full well that the costs of that drug are significantly higher than the other drug that had been used systematically, is just such an amazing development knowing that people’s hearing is now going to be preserved despite the cost. As I said, there were many hundreds of individuals, researchers, clinicians, patients. We thank patients for agreeing to participate in these trials the drug manufacturers. And so Shoebox was the tool that was used in many locations to measure whether or not a hearing loss was being identified with kanamycin. And that information in itself was the real premise for making this change. Wow. So it’s possible then, that people can. Have these kinds of treatments without actually incurring hearing impairment and to see people have this kind of benefit without getting the impairment that’s been going along with these treatments forever is quite a breakthrough. What about some other case stories, some particular patients that maybe have done well or success stories that the individuals using the Shoebox system have had in their assessments of ototoxicity and monitoring that throughout a treatment regimen? So here we are in 2024, and on a case by case basis, patients can actually be given a Shoebox system to take home with them to do regular hearing tests at their leisure. And those results are encrypted and uploaded to a protected portal that can be viewed essentially simultaneously by clinicians and specialists. And so the barriers we’re really beginning to knock them down. We’re knocking down the barriers for those individuals who are traveling hours and hours to come in for medical treatment. Also able to lower the struggle that individuals that are quite ill have in terms of maintaining all of those appointments and going in and exposing themselves to the various viruses and bacteria in medical establishments. We’re able to take it one step further, protect them from that, and still allow them to do clinically valid hearing testing where noise monitoring is being applied, because noise monitoring needs to happen for it to be clinically valid. You can’t just test hearing in any environment. But thanks to the iPad technology, we’re able to use integrated microphones to do continuous noise monitoring throughout the test to ensure the validity of those results. Wow. So being able to look at all these things and uploading. Now, my understanding is, because we talked about telehealth a little bit last time and although it’s a pretty good procedure here in North America, when you get out in the outlying areas of the world, it’s probably not as. Not as easy to. To take home and audiometer and upload the results and those kinds of things. But how often do people usually monitor their hearing when they have their own equipment at home? So it does depend it depends on the schedule of, for oncology patients, their chemotherapy and radiation schedule. But I’d like to give in another case study that also contributed to some clinical trials, and that was with Meniere’s disease. So Meniere’s disease is not ototoxic per se, but you do have fluctuating hearing. And measurement of that hearing can be somewhat challenging in terms of people might not be close to an area where they can just call in the morning of and say, I feel like my hearing’s dropped. Can you measure me? So what some researchers have done I believe with over 90 cases of Meniere’s patients, is they sent them home with a device, and they basically said, when you feel that you’re experiencing an episode or a drop in hearing, please measure your hearing. Now typically with Menieres, you do have an asymmetry in terms of hearing levels, so masking is imperative. But we were able to apply that to, once again, together with the noise monitoring and the masking, provide us clinically valid results as we would expect to see in the clinic for Meniere’s patients. That is huge. How many times have all of us said oh, call us up when you’re having an episode. We’ll clear the schedule. By the time they get there, the episode’s kind of subsided or whatever. So having this kind of technology available, it will be a substantial move forward for the diagnostic implications and the treatment of. Of Meniere’s. So now, are there some kinds of barriers within healthcare facilities toward the use of these systems? There can be one. You need to have someone who’s a champion for the system, who takes care of charging the device who we’re pretty good about notifying our customers, about when calibration is due on an annual basis. So you don’t necessarily need to have someone on top of that. But you do need to have someone who’s receiving those emails to know when a newly calibrated set of headphones needs to be coupled with the system. Also, security. Because we’re on a tablet, it is preferable for it to be locked up. But if it has a home in the clinic and everyone knows where it is, then that’s helpful, as opposed to it being passed from room to room, and no one’s necessarily taking ownership. But I have to say, we’ve really seen some people step up to the plate, and we haven’t had as many issues as that as we did, for example, ten years ago, when this was a brand new concept. Other barriers can sometimes be the ventilation systems. Typically, if you have a room with a door that doesn’t have any machinery in it, such as a clinical exam room, that’s typically quiet enough to perform hearing testing. However, if you are underneath a very large square fan or it happens to maybe you’re in the south. And it’s a very hot day in Texas and the air conditioning is running full speed. That is going to impact your lower frequencies. Now, we have worked with certain individuals who weren’t able to get around that due to patient isolation cases. Thankfully. Thankfully ototoxicity typically happens in the high frequencies, and high frequencies are less impacted by ambient noise. That’s where working together with an audiologist can be really helpful. Typically, that’s what happens with these clinical trials that we’ve been involved in. A little plug for Shoebox again, we’ve been involved in over 100 clinical trials of various medications, treatments, medical conditions, and we find that depending on the cadence of testing, et cetera oftentimes a team lead can take charge of most of the data and know when to call in the expert hearing healthcare specialist, whether that be an audiologist or an ENT. And so the audiologist doesn’t need to be on site, and they also don’t necessarily need to be logging in every day. We can actually create definitions for the study teams to say when the audiologist should be called in, or what we call automatic triage in our portal, which can be set up to only alert the audiologist when there’s actually been a change in hearing. So, benefiting from a lot of the technological advancements that we see in other aspects of technology other apps and programs. Well, and of course, you mentioned last time in our episode that there was a huge meeting at AAA a couple of years ago where, because there was, audiologists ought to be in charge. Well, then the oncologist thought they should be in charge, and as it turns out, kind of both of them are now working more together in how to pursue the monitoring and so on. It sounds to me like when you’re ahead giving the patients something to take home with them and say, you do this and this and this and this, and they’ve been instructed as to how to do that. That’s a giant step forward in itself. In addition to the overall monitoring of the procedures, I just wanted to. Add a little clarification, was that the oncologists actually felt that the audiologists should take control, and the audiologists felt that the oncologists should take control. And the issue is, one of availability is that the audiologists would be happy to see these patients. However, they’re often not at the same site, so it requires somebody to connect the patients with audiology that often is just not part of their realm or training. And so it was interesting that both the group of oncologists and group of audiologists, they all agreed, over 90% agreed, that ototoxic monitoring was important and needed. The question is how to do it. And you’re right, we have made significant, significant, you know, steps forward in that front. Technology has helped with that. There’s still a long way to go, but if we can continue on this trajectory, it’s just going to be best for patients and all involved. Well, in that light, then. And Renee what do you see as some of the future for this kind of procedure in the context of ototoxicity monitoring? What kinds of advancements do you hope to see in the future as far as Shoebox is concerned, but even as the overall area progresses within this particular area of. Ototoxicity monitoring, so interestingly enough, one of the case studies that I didn’t get to is one that’s quite Oh, no. One that’s very much emerging, and it’s for actually thyroid eye disease. And there are some eye drops that have been rushed through FDA approval processes because they are so impactful to thyroid eye disease. Now, it might be something that people might think, oh, this is quite rare. I don’t hear about this very much. It’s actually not that rare. Now, the FDA has accelerated their approval with a caveat, because in the trials and in the animal trials, it was shown to be ototoxic. Yes, believe it or not, eardrops can also be ototoxic. So now the FDA has said, you can have this drug, you can prescribe this drug, but it must be accompanied with regular auditory monitoring. Wow. So when you ask about the future, I think so. Now we have clinics that are specializing in the delivery of this drug, and they’re calling up and saying, we need audiometry. We’ve never been trained. I’ve had some really entertaining conversations with ophthalmologists. Yeah. Who are obviously brilliant in their field but have just had no exposure to hearing. It’s just not their specialization. But they’re willing to bring this in because the drug is so impactful to their patients. They’re like, teach us how to do this and we’ll make it happen. More mandating coming into play and less people falling through the cracks and you know. Yes. Is this going to cost some money? It is going to cost money, but thanks to technology, we are able to cut those costs significantly. So, for example, 15-20 years ago, you might have had to send someone across town and pay a premium rate because of an audiogram that’s needed sooner rather than later and not able to wait for the waitlist in order to be seen. Whereas now you don’t have to make all those phone calls. And those professionals trying to get that appointment is that you can take control of it in your own clinic and separate and deliver the system as is needed per your patient base. So a lot more control for you, a lot more control on the data as well. You can imagine that if these individuals are seeing potential cases of hearing loss, that they will be more motivated. To ensure that everybody has hearing monitoring. Wow. And of course, when you talk about costs yes, it’s going to cost some to do this, but think about the cost that goes into the hearing impairment itself and all the issues that happen and the psychosocial employment kinds of things that go into the hearing loss itself. And those are costs also. So do you see more improvement in the products that are used to evaluate the patients as well? I do. And there have been several companies that have really come to the forefront here. There are some that are on phones, smartphones, there’s some that are computer based, some that are tablet based. And so, as we continue to innovate on some of those technological aspects, such as headphones and attenuation and making it easy and comfortable for patients to have regular hearing tests the more testing we’re going to be able to do successfully. Wow. So now I think I have a better idea of number one. What is ototoxicity and where it resides, as well as all the new kinds of disorders that at least new to me. The kinds of disorders that we can evaluate and monitor and reduce the incidence of hearing impairment among individuals that possess these problems. As well as looking at the benefits. And we talked about some of the limitations, but there’s many less limitations than there are benefits to the procedure itself. And are there some things that we’re missing here in our secondary discussion of ototoxicity, Renee, that we may need to hit here in our discussion? Thanks for opening that up. Yes certainly. Collaboration as you touched on earlier with other healthcare professionals, we need to be mindful that as hearing healthcare specialists, we have an obligation as well, to education and training and collaboration. And that is something that it has been just such a pleasure to work with all of these healthcare professionals in terms of knowing that hearing is only a small percentage of their overall responsibilities. And so we need to make it easy to understand and give them confidence in terms of the testing that they’re doing. The tool is doing the test, but there’s always patient interaction. And as we know, hearing testing is never fully objective, because you do have the responses from the patient, whether it be a hand raise or working on a tablet, and that patient ease that we use, we know that. For example, when we have someone that gives us too many false positives, well, we’ll counsel them in accordance with that. But on the flip side, our next patient could give too many false negatives, and so we need to counsel in a different way. So that’s something that the tools themselves are trying hard to replicate or facilitate in the background, in the algorithms of the testing equipment. But they’ll always be that human component. And especially as we get into different groups, whether it be pediatrics or geriatrics, sometimes a little help is very beneficial for patients. There is a subset of people who actually do get quite anxious, and they feel that a hearing test is something that they pass or fail. And that’s not the case at all. It’s more a question of, we want to know what your hearing is today so that we can make the best decisions for your hearing going forward. And so, really empowering those individuals, whether they be medical assistants, nurses, other healthcare specialists, to be able to deliver some of those instructions, et cetera, in an effective way, is, I believe our duty as hearing healthcare specialists to share that knowledge. Well, you know, there’s a group here in the US we call the National Academy of Practice, national academies of practice, which you may or may not have heard of, and our audience may or may not have heard of them either, but they’re the. Their particular instruction is, you don’t practice in a silo, you practice with a group, and people put their heads together with certain cases and so on. It sounds like this system is developing into that kind of a system where we’re using all the specialties necessary to facilitate a forward movement of a patient toward monitoring of their disorder. So well, today we have kind of gone through a few of the benefits and the actual progression of ototoxicity monitoring not only here in North America, but also around the world. And my guest has been Rene Lefrancois, the director of audiology at Shoebox. And I want to thank Renee for being with us and informing us not only in one session, but in a second session, as well as to all the benefits and places where we can use ototoxicity monitoring. I also want to thank our group for being with us for the second time again. And so thank you very much for being with us at This Week in Hearing.