Transcription Laura Housman, MPH, MBA, DrPH: Hi, I'm Laura Housman. I'm a Practice Director here at Avalere Health. I'm joined today once again by my colleague and friend, registered pharmacist and our Clinical Team Lead here at Avalere Health, Amy Schroeder. We're here today for the third in our series discussing compendia. In our first conversation, we discussed the background of compendia and provided an overview of their utility in the life sciences market. In our second discussion, we took a deeper dive into the ways that compendia can be beneficial for supporting clinical decision-making and driving access for patients and providers. Today, we are excited to talk about US label use and how and in what way compendia can be valuable for incorporating more evidence for off-label application of much-needed therapies. Amy, it’s so good to see you again today. Amy Schroeder, BS Pharm, RPh: Yes, nice to see you too, Laura. Laura: Sometimes, from my time in pharma, and likely yours as well, "off-label" always felt like a term that gave everyone a little bit of pause. The MSLs would be trained; the market leads would be trained. It really felt like a very charged word. But for compendia, it actually can be a very beneficial utility. Can you share a little bit more about how those dynamics work? Amy: Sure. So, if we think about clinical drug compendia, in the 1950s, that's when they first started really evaluating uses of drugs. At that time, they were more focused on  the labeling, but eventually started looking at experimental uses of drugs. And then when this really came to light was in the early 1990s when CMS actually began recognizing certain clinical drug compendia for their evaluations of off-label uses in terms of efficacy and safety of those drugs, to inform healthcare provider prescribing and health plans whether or not those uses actually met what is considered to be medical appropriateness. They have also expanded to include biologics and cell and gene therapies. What's been so interesting is that in 1993 — when we first saw CMS recognize compendia; back then it wasn't even specific to a certain therapeutic area; it was just overall drug use if it met certain criteria. Those criteria at the time were: it must first be FDA approved for some use. And then following that: Was there evidence that it could be effectively and safely used in a different disease? A different population? A different line of therapy? A different combination or route of administration? Anything that was not explicitly stated in FDA labeling could then be reviewed by compendia. And then from that point, providers were very much informed with further evidence for their decisions because they had more confidence prescribing drugs off label, but also health plans started using compendia criteria to determine if they were going to pay for them. Laura: This criteria is something that's been very interesting to me over the years. It's analogous almost to USPSTF grading—this grading of evidence—is there an appreciation that this rubric is well-considered and independent from influence or bias? What goes into that? Do you have some thoughts? Amy: Yes, there are a lot of different compendia that are out there but not all of them are recognized by health plans. So, that's where we actually see some of that extra rigor, in that health plans tend to recognize more than one, understanding that each compendium has its own criteria for evaluation, how they rate a use, etc. So, it's very interesting because you can actually see one drug for a particular off-label use, and five different compendia have given it five completely different ratings, so it’s really important that there’s a lot of variability out there right now. Together they bring more perspective. Laura: That’s interesting—and one area that I think could be confusing for providers and patients: do they compendia shop? What is the best way to get a clear assessment on what can be prescribed? Amy: Yes, the compendia content for FDA-approved uses are pretty consistent. They tend to stick with the FDA labeling, but some of them will actually rate the FDA-approved use, which is quite interesting, because they don’t always rate the entire population in that FDA-approved use  with an equivalent status rating. And so, for instance, they can say certain subgroups within the FDA-labeled use are very well supported with high level evidence, for where for others it's lower. I've actually seen some providers and health plans react: Well, I'm a little bit hesitant if they're going to rate it lower in that group, should I really use the drug in that population? And the health plan on the other side is: Should I really pay for it in that population? But across the board, the compendia are very different in what their evidence views are and also what they will consider. And that's something that we try to help clients with—whether they're submitting for an FDA-approved indication of use in the beginning or whether they’re trying to determine the benefits versus risks of submitting for an off-label use—we try to help them decide if that's something that they should pursue. We assess level of evidence against rating criteria and if that strengthens support for that use. Laura: And I think that would be a tremendously valuable area of collaboration for us with clients to both assess the level of evidence, put it against some grading criteria, and also help them strengthen for their off-label indication as needed. Amy: Yeah. In situations where it's an off-label use that has really good evidence support, it can be very clear that it makes sense to submit to compendia because you're getting that out there. The compendia are going to rate that. It's going to be publicly available information, which really provides more confidence in the use of that drug, where it was a little bit sketchy before that. And where we try to help clients is in situations where perhaps a drug is already used off label, but it might be under the radar right now; no one's really paying attention to it. But if you submit to compendia and your evidence does not meet their support standard and they rate it lower, from that point forward when that rating becomes publicly available, we've actually seen situations where drugs that were previously covered by health plans off labe, from a point forward, they were no longer covered. This actually has potential to affect the patient in the middle of treatment. And so this is something that we really help clients understand, benefits and risks, so that they can make educated decisions about what they want to do, understanding that it is going to affect patients at the end. Laura: Which, you know, our whole ethos here is an EVERY PATIENT POSSIBLE, and we want to make sure that they have the greatest opportunities and our clients have the greatest understanding of the risks as you put them forth. So, I think that's tremendously valuable insight and always wonderful to see you, Amy. Thanks so much for the time today. Amy: Thank you so much, Laura.