So, on biologics, let's talk about what is the cost here. So, in my disclosures, this is actually the support as far as our laboratory work, kind of in this general area of biology. So, we know that orthobiologics are generally not covered by commercial insurance, and certainly, as you've heard, there's mixed data about their effectiveness. So, why is it that some patients really pursue and ask about these various treatments? Certainly, we know there's aggressive marketing. There's the allure of these cutting-edge therapies. You'll see advertisements like this all over. Frankly, our current treatments are not perfect for a lot of these conditions that we see. At the same time, we see the FDA is really scrutinizing indiscriminate use of these therapies. You see these headlines and articles in a lot of the popular press in the last several years. That's interesting. Start over there? Someone's moving on me. Can we reformat the slides? Thank you. Thanks, I guess we're there. So, what about PRP? The global PRP market is estimated at $476 million in 2020 and predicted to grow at an annual rate of about 12%. Again, a lot of that relates to this direct-to-consumer aggressive marketing that we see all over the place. I think there's this perfect storm that leads patients to pursue these treatments, despite what are sometimes very high out-of-pocket costs. We have a patient with a difficult management problem, they may have a cartilage lesion, a big cuff tear. We have, admittedly, imperfect solutions with variable or unpredictable outcomes. You have a patient who wants to return to an active lifestyle they may have disposable income. If you add to the mix this aggressive marketing by industry, you see the result is this stem cell, it's in regenerative medicine, it sounds sexy, it's enticing, there's a real allure for this whole field here. Focusing on PRP, again, not covered by insurance, this is a particular CPT code that should be used for PRP. An ABN, advanced beneficiary notice of non-coverage needs to be signed by your patient. I'll show that more in a moment here. Patient needs to be informed of the cost and the variability and, frankly, unpredictability in outcomes of a lot of these therapies, in PRP in particular. And note the cost may even be higher if it's done in a radiology suite for image guidance where you have facility fees. Moreover, some studies indicate better outcomes with serial injections, three injection series. Well, again, right there you'll have increased costs as well. This is the ABN that we use in our office. I'll highlight here the important points that need to come out here. So we state the most health insurances consider this treatment experimental and the patient needs to sign this form. Number two, this attached ABN must be signed by the patient and we are careful to point out the non-coverage determinations by a lot of the major health insurance. So it's very clear to the patient that there's no coverage for this. Some use PRP intraoperatively, as you just heard Rachel speak about. Some surgeons will go ahead and charge a PRP procedure to the patient prior to the surgery by having them sign an ABN. I've not done that, I've just kind of frankly eat the cost. If you do use PRP to the same surgical site, which is what you would typically do, and the insurer will bundle the codes and only the surgical procedure will be paid. And in fact, at our hospital, this is the supplies for PRP are billed as supplies, just like a suture inc would be, for example. This is a recently published study from our group with some of our physiatrists where we looked at, this is a survey of 100 physicians to survey costs for these different treatments. And here's the cost for peripheral joints and tendon and muscle. If we just focus on the left side of each, the blue there, that's the cost for PRP, about $1,000. It's kind of similar to what you just heard a moment ago for all these different areas. Carlos Lavergne in Miami had surveyed 91 surgeons in his area. The offices were presented with a hypothetical patient end-stage OA who's searching for treatment with the stem cells or PRP. About a third of offices offered PRP and about a quarter offered stem cells, quote-unquote stem cells. The majority of offices were actually transparent on pricing for PRP, whereas less than half would give a price for stem cells. The remaining practices stated that pricing would be determined or discussed during a scheduled visit. But their mean cost to focus on PRP here is about $900 in this particular survey. There's been several cost-effective analyses done. This is from UC San Francisco. This is a review of trials comparing PRP and HA. And they took the MOMAX score and made this and they converted it to a utility score. They got cost data from CMS, so pretty robust methodology here. The total cost included everything, the supplies, the injectable, the clinic appointment. The change in utility scores was then divided by the total cost to determine utility gain per dollar to try to get a sense, you know, is this cost-effective? What they found out, or concluded, is that for PRP to be cost-effective, the total treatment cost would have to be less than about $3,700 for a six-month outcome and $1,200 or so for a 12-month outcome. So their conclusion was that PRP is, in fact, cost-effective from the payer perspective at a total price of less than $1,200 over a 12-month period when you compare that to a time of HANA HA. Another cost-effective study from Cleveland Clinic, this is a Markov model, a patient with knee OA undergoing a series of three PRP injections to look at the value of PRP in delaying the need for total knee. Now, from the healthcare payer perspective, PRP was not cost-effective in the base case of a one-year delay to TKA. So knee arthroplasty, from the outset, produced a higher number of quality-adjusted life years at a lower cost, so that dominated the model. If you assume a $728 price for PRP, which they used from the literature, PRP was only cost-effective if it delayed subsequent TKA by at least 10 years, and the sensitivity analysis gives you a sense, the y-axis looks at time to total knee, and you really have to be nine or 10 years of delay before PRP becomes effective in this model. But if you change your quality-of-life measure, if you put in, if you figure PRP to be more effective, then in fact, PRP therapy was cost-effective with even just a one-year delay to knee arthroplasty. In fact, PRP may have value in particular for that higher-risk patient, you expect complications, things like that, but they concluded that the cost-effectiveness of PRP was not prohibited by cost, but rather by its effectiveness. So keep in mind that there's both of those parts of the equation. One of our former students, now resident, has completed a survey using the Pearl Diver Database, looking at patients with PRP over the decade, 2010 through 2020, over 23,000 patients were in these records here. Most common anatomic location to expect was the knee, followed by the shoulder and elbow. Between 2010 and 2019, knee injections increased, and there was a trend toward an increase in shoulder and elbow, and this graph on the right, knee is in the gray, we see this increase, and that kind of parallels the literature in this area. In this particular study, certainly PRP cost demonstrated significant variability, and here is the average cost from this Pearl Diver Database. Average cost of prices paid, prices paid by patients for PRP hip, $1,700, knee, $1,176, shoulder and elbow, about $1,000, ankle, $711. Real changes in cost over time, depicted in the graph on the right. So from 2011 to 2019, look at what happened to hip PRP prices, went down by well over half. Knee, prices went down. Ankle, in contrast, almost doubled. Shoulder and elbow went up. If you look at the right end of this graph here, around 2019, they all hover about around $1,000, so that's kind of the number you're seeing in the literature here. They think the cost for PRP for knee OA should be considered relative to other commonly used options. Obviously, you can use steroids, they're inexpensive. Short duration of action, certainly potential for adverse effects used in excess. HA, certainly generally longer lasting than steroids, safe and well tolerated. There's some variability in patient's response, and there are some cost issues, potentially, because not all insurers cover this. So if you look at our CPG from our academy just last August, so pretty up-to-date, for HA, they conclude not recommended. Intraarticular corticosteroids provide short-term relief, and for PRP, they conclude may reduce pain and improve function in patient with symptomatic knee OA. So I think a common dilemma is balancing realistic patient expectations versus, frankly, the placebo effect. We need to provide the patient with realistic expectations. This is not magic, I'll tell my patients, and there are certainly variabilities in outcomes. If you take a suboptimal outcome, plus a high-costed patient, that can be an unhappy patient. At the same time, it is well-established that if the physician conveys hope and is optimistic that a treatment will help, patient outcomes better, and I think the placebo effect is real. The quote, the more I pay, the better my knee feels. This is a dilemma I think about every time I'm talking to a patient in the clinic about these treatments. Now, to switch gears a little bit on cell therapy, the standard options available to us, of course, as you've heard, are bone marrow and adipose tissue. The global cell therapy mark was estimated at $9.4 billion in 2020 and estimated to grow at an annual rate of about 9%. Note that perinatal source, and you've just heard some talks on these a moment ago, placental, amniotic fluid, amniotic tissues, all those now can only be used in a clinical trial under a formal IND, so that's different than a year ago. That was as of May 31st, 2021. The majority of cell therapy procedures in our country are generally done in the operating room. These are the codes you should use. This is a particular code, 21999 for marrow, 15771 for a lipo aspiration like you could do in the lipo gyms, and I have no relationship with any of these, by the way. Again, many insurers, most insurers don't pay for these. Now, if you go back to that study from Miami, the 91 surgeons with that hypothetical patient, again, a quarter of the offices were offering quote unquote stem cells, only 42% gave a price for stem cells, but the mean cost across these offices were $3,100, but look at this range, $1,200 to $6,000 for cell therapy injections, and back to our study, our survey of 100 physicians, again, joints, cost for joints and tendon and muscle. Here I've outlined bone marrow concentrate, bone marrow aspirate, and microfragment of fat, and the averages are 3,000 to 5,000 you see here, pretty similar for both, whether you're injecting a joint or a tendon. So in conclusion, what do we as clinicians need to know? Certainly this area has great growth potential. We need further work. We need rigorous studies in this area. We need to combine our laboratory work and translate that to clinical trials. Again, understand most are not covered by insurance. These are the CPT codes, if you're interested to take this down. Patients need to be given realistic expectations before paying these high out-of-pocket costs, and again, the challenge is balancing that, frankly, what is a placebo effect, giving the patient realistic expectations but maintaining some optimism. Certainly the regulatory environment continues to evolve. A good example is now the fact that we can't use these perinatal products. We need to be aware of this ongoing aggressive direct-to-consumer marketing, and it's really on us to advocate for responsible use. We need a rigorous evidence-based approach to this area and really lead the way in avoiding what is sometimes indiscriminate use of these therapies. Thank you.

orthobiologic treatments

platelet-rich plasma therapy

cell therapy

commercial insurance coverage

cost-effectiveness