All right. Thank you very much. I'm honored to be here, and what a wonderful meeting we've had so far. These are my disclosures. So what is the most cost-effective treatment? And I think we have to think about it in terms of compared to what? No treatment, total knee replacement, you know, drugs. And then the other thing is you need the right tool for the job. So, you know, it may be cost-effective to hire the guy to dig a hole in your backyard for if it's a small hole. But if you need to, you know, make a foundation for a building or you have a really big defect, you may need something else. And, you know, that's when your backhoe or excavator comes in play. So how is cost-effectiveness analyzed? And I think, you know, there's a couple things. Obviously, it depends on cost. And so we're going to be focusing primarily on the U.S. at this point because cost is different in other parts of the world. In Europe, ACI-type procedures are substantially less expensive, maybe only $4,000 to $8,000 per implant. Also depends on effectiveness. And so what is effectiveness? And so your definition of success could be very different things. Sometimes it's an improvement. Sometimes it's a minimally clinically important difference of improvement. It may be returned to sport. It may be returned to activity. And then the other thing is defined over what time period. I always like to think about it in terms of if you have long enough follow-up, we are all dead. So at that point, all the treatments are equal. So anyhow, many of these studies, you know, there's been a lot of good research in it. And, you know, I see a couple of people here who have been involved with that. But there are significant assumptions about what the longer-term outcomes are because some of these things are trying to project 10, 20, 15 years out into the future. The standard unit that we use for cost-effectiveness research is quality-adjusted life years. And the usual U.S. threshold is less than $50,000 per quality-adjusted life year. This is a measure that's been well-established in literature. It's part of the reason why people started thinking they started, this is how they rationed things like dialysis or transplants. So Dave Flanagan, who I see in the audience, Dave, had a great paper in American Journal of Sports Medicine. And specific cost data is sometimes very hard to extract. Your hospitals will usually not tell you all of this. But they were able to get some information from their institution. This is 2017 dollars. And so if you take a look at the base cost, there actually may be higher or some of them lower than you might expect. ACI with periosteum, $65,000. Macy, $65,000. Microfracture, $24,000. OAT, $32,000. Osteochondral allograft, $75,000. And knee arthroplasty, 50, and a scope is around $88,000. Now, $8,800. So this depends in part not only on just the cost of the implant and the surgical procedure, but also downstream costs as well. But still gives you an idea that the costs involved here are actually very substantial. Now, when we look at cartilage procedures, many of the larger studies actually show that most cartilage procedures have fairly similar outcomes. And particularly with regard to comparative effectiveness, with regard to minimally clinically important difference. And this is a term that basically says, yes, there's a difference. And it means something. If the difference between myself and my brother is like half an inch, I'll claim that we're about the same height. But if I'm standing next to my friend who's like six foot four, I think that's a clinically important difference. And so those are differences that actually are meaningful, meaningful to patients. So I think that's a very useful way to think about effectiveness. There have been a few studies actually looking at comparisons between different techniques. So this study came out in American Journal of Sports Medicine in 2013. Rob Brofrey is the senior author looking at microfracture and osteochondral autograft transplantation. Again, this all depends on what studies and what groups you're looking at because it depends on what the outcomes are. They looked at three studies. And they calculated dollars for every point of improvement. For example, it's around $300 per point of improvement in Lyshom scores. And for Lyshom and HSS scores, the microfracture was more cost effective. For the OATS procedure, it was more cost effective for Tegner and ICRS scores. And specifically, with regard to the specific outcome of return to play to sport, osteochondral autograft transplant was better. Their conclusion was net cost and cost effectiveness of microfracture and OATS are comparable. So again, this is an idea, one of the calculations, cost per point improvement, Lyshom scores $339 per point of Lyshom, OATS, 469, et cetera. Another paper that came out a few years ago was by Eric McCarty's group looking at several different modalities, microfracture, osteochondral autograft, and ACI. And they looked at more studies because better, higher quality studies had been done at this point. And they were again looking at dollars per point change. And the results were microfracture and osteochondral autograft transplant were similar. ACI scaffold was slightly better in terms of outcomes, in terms of function. ACI with periosteum actually was the worst. Microfracture was actually found to be the most cost effective. And interestingly enough, if you take a look at the actual data, and you can see these outcomes here, microfracture, OAT, ACI, and second generation ACI, there's a lot of overlap there. I think most of us would agree that a 3.4 centimeter microfracture defect is not something that most of us would treat with a microfracture procedure. So this is actually probably more of an extreme or worst case scenario for microfracture or marrow stimulation. Now Dave Flanagan did a very great paper in AJSM in 2020 looking at 22 studies, not only looking at microfracture, OAT, allograft, osteochondral transplant in a couple of generations of ACI. They looked at quality adjusted life at 10 years and minimal clinically important difference. And what they found is the most cost effective treatment in the base model were microfracture when applied to the smaller lesions, less than 3 centimeters. It did not work very well for lesions larger than that. OATs, and if you had to do three or four plugs, the outcomes were worse than if you did one or two plugs. And the cost was over $50,000 for microfracture greater than 3 centimeters, patello-osteochondral transplants, and bipolar osteochondral transplants. And again, you can see that the IKDC's final scores were actually fairly similar among the groups. Microfracture actually did fairly well, only slightly worse than OAT and actually better than ACI in this study. There is a paper on juvenile articulated articular cartilage by a group out of HSS. I don't think it was with Andreas, though. 67 patients, 2.7 centimeters, follow-up of 30.9 months, and they did a 15-year model. So there was also a lot of confounding variables with this. 81% of these patients had a TTO, which works really well for patients with chondral defects on their patella. And so it's hard to know how much of the improvement is from that or from the transplant. The other thing is, I think it's a little speculative to say, I'm going to build a model projecting out 15 years when I have less than two and a half years of data. What about other technologies? Now, there are a number of different things like microperforations, micro-drilling or nanofracture, needle punch, smaller, deeper holes, biologic enhancement using scaffolds and things like that. And then there's some new implants like agility. We don't really have cost data on that, on the agility yet. But what I will talk about is there is some clinical data on using small holes and scaffolds. And so what the group out of Russia has presented, and I'm looking forward to Brian's talk, micro-drilling is significantly better in terms of treatment of minimally clinically important differences. And so thank you for allowing us to show this slide. The other thing is that scaffolds enhance repair. BSD car gel, biocartilage, and other of these extracellular matrices have been demonstrated to improve clinically important differences. And so, again, if you're looking for something that improves minimally clinically important difference, then these other techniques do seem to help at a relatively low cost. Now there are some more expensive scaffolds like BSD car gel, and it was evaluated at cost of 3,000 euros per scaffold. This is European data. But even in that situation, it was better than microfracture alone. Even when the scaffold cost was an additional $3,000. And then another journal, Journal of Medical Economics, looked at this. Again, this is the only data kind of available on these scaffolds. But looked at an Australian study. It was about $4,200 US. But it was cost-effective compared to microfracture. In conclusion, available cartilage procedures, all of them that we're actually using, are typically cost-effective for society. They meet that $50,000 threshold. Microfracture is the most cost-effective for lesions less than 3 centimeters. Oats and one or two plugs may be better for certain sports activities. Larger defects, the evidence tilts to Macy, especially in the patella. Bipolar patella osteochondral transplants seem to be less cost-effective, but again, it depends on what kind of data you're looking at. Next-generation marrow stimulation using small holes or scaffolds does appear to be more cost-effective than traditional microfracture. And new technologies are still unknown. So, a lot to come in the future. Thanks.

cost-effectiveness

treatment options

knee injuries

ACI

microfracture