(upbeat music) Welcome to Plenary Session. I'm Vinay Prasad, I'm an associate professor at the University of California, San Francisco. I'm a practicing he-mongued doctor and my interests are medicine, oncology, and health policy. And that's what you're gonna get on plenary session. This is season four, #ZeroCovid. It's zero COVID 'cause we're not gonna talk about COVID. We're back oncology, medicine, health, policy. We've got a lot in store for you. But first, a plug. If you like this podcast, leave us a rating or write us a review. It helps new listeners find the show. You can follow us on Twitter at plenary_session. You can email us at
[email protected]. Give us your suggestions on what we should be covering. And we got a new YouTube channel, Vinay Prasad, MD, MPH, follow us on YouTube. I'm putting up a 10-part series on reading and interpreting cancer clinical trials. You'll wanna watch it there. And if you really love this show, you can back us on patreon.com. Patron backers get access to slides for lectures I give on plenary session. And with that, let's start the show. I think we're rolling. I'm back plenary session, video edition, joined by Meet Sarpattwari. Professor Sarpattwari is an assistant professor at the Harvard Medical School. He's in the portal group, the program on regulation, therapeutic sim law, and he is an expert in epidemiology and legal affairs and regulatory science. And he is a friend of the show. I mean, it's great to have you back here again. - It's great to be here. Good to see you somewhat face to face. - Face to face. As face to face as it's gotten in a long time. - Exactly. - Well, there's so much to talk about. The FDA just keeps hitting the ball out of the park, making sure innovation happens in this country. But before we get to all the fun of adjacanemab or adjacanemab, or whatever the hell you wanna call it, let's talk a little bit about the Exodus. And I'm talking about the Exodus from the Academy. Dr. Sarpattwari, the Academy. So in the last few weeks, we've seen some people who I think are quite good. And I'll be honest to say, I think they are sharp. People will know, I've of course, I've had my disagreements with Peter Bach over the years. But I've had a lot of agreements with Peter Bach over the years, but one thing I will concede is that Peter Bach is a clever person. And sometimes I read his papers often, and I say, you know, I hadn't thought of that. And there's just not a lot of people in this business that you read their papers and you say, I hadn't thought of that. And when you find people like that, you put them up in a certain rung. I mean, that's rare. I mean, let's be honest, this is the Academy, but a lot of people you read what they say, and you know what's coming. Neil Shaw, Neil Shaw, cost of care, Neil Shaw from the Harvard Medical School and Goanday's laboratory. He's going to a company. And there was another person in your department who went to consulting about a year ago, Joshua. - Mm-hmm. Josh Kackney, yep. - Josh Kackney, you've done a lot of good work. - But now it's over at Johnson & Johnson, and adding their epidemiology group. - He's already to J&J, huh? - Yep. - The Siren Call of J&J. Okay, so, and Peter's going to some small startup company that's working on blood-based cancer screening, which is gonna be interesting, because I think Peter has been a thoughtful person and cancer screening. And I think he knows you need randomized control trials, measuring clinical endpoints before you adopt new screening tests. And Neil is going to do something with safer delivery. And Joshua is working for J&J. Okay, here's my question to you. What's going on here? You know, a lot of thoughtful people, a lot of people who, you know, people may not like everything they've ever written, but no one can take away the fact that these are thoughtful people. They're going to the industry. They're going to companies. They're not staying in the academy. What is going on in meat? Why is this happening? - I'm not sure that there's necessarily anything a miss or a foul here. I think people are having families. I think in the case of Peter, you probably have someone who is looking at the last stage of his career and where he thinks he can be most impactful. I think that, you know, there's no doubt the appeal of financially is there. So there have, are we better than many other sectors of academia in terms of what we're able to offer academics? Yes. Does that compare at all with what you can get in the private sector? No. And so that is definitely a motivating factor as people start having families, as deep we will start considering school and college and things like that. But I think in general, there's also a sense and that people think that they can have more of an impact. And it is perhaps true in some respects that we know and we can talk about this a little bit more about how difficult it is to actually shape policy. And that's oftentimes what you're trying to do in academia, at least in the positions we're in. But I think you definitely know that, you know, whether it is developing a safety profile of a new drug, helping to get a company off the ground that you think is doing something good for society. There's a more sense, I think, a gratification or a sense that there would be a gratification of getting those things done and feeling like you've actually accomplished something with all of your heart work. So I definitely think that's true. What I think is difficult is the realization once you're probably in some of those types of positions that just like in academia, there's going to be a massive bureaucracy. And so a little bit different for a small startup that can pair it to a behemoth like a J&J. They've got their own culture and they've got their own sort of cogs in the wheel that might slow things down. And so I think it's a case of a combination of finance and a desire to get something done. - I think you're onto something. And I guess I would say that one component is clearly the financial reimbursement, which is gonna be much better at any of those places, at any rank. And as you get further in your career, I think the gap is even gets bigger and bigger and bigger. And so the further you along you are, the difference the amount of money you might otherwise make is I think a far higher. The next thing I think you talk about is I think, you know, make an interesting point. I think somebody like Peter would have been ideal to bring on to Medicare, Medicaid, FDA. He's at that stage of his career where, you know, Democratic president is probably his best chance of doing it. This president probably a good chance as any. And if you feel like you get passed over for those opportunities that, you know, when you're in your late 50s, you know, I think people may feel slighted and they feel like that they're missing like the last chance to make a big impact in the field in one's career. I think the other problem is that, you know, it's push and pull. So you were talking about the pull a little bit. What's the push? I think the academy is doing a lousy job. It's very lousy. Why do they do a lousy job? You know, every year goes by. I find people emailing me to do things that not really in my wheelhouse, lots of paperwork. Everything is difficult. It's making much more difficult now. You know, somebody comes and rotates with you. They want an evaluation. And the old days you just fill out that piece of paper and you turn it right in. Now, how many logins, how many passwords, how many fucking passwords are you going to put in to get this evaluation in? How much time do I have to spend resetting passwords to put an e-valent? I mean, why is my, I don't make my life better? Exactly. We're submitting to different journals and oh god, kill me. Well, you know, I don't even, you know, I don't even personally, I've, I don't do it. That's one of my. That's where it's at you. Thank you. I'm sorry. I've found some people to help me with that because, yes, submitting the papers, are they kidding you? That's part of it. And I think that, yeah. I guess I could say I haven't been around long enough in academia to sort of know what, whether or not their work, or reduce or not. I'm always a bit skeptical that the grass is always greener. I'm sure there was always problems to begin with. But I do get a sense that there is a significant burnout and I'm not a clinician. So I think one of the sense, someone clinicians too, is, you know, the amount of time you're staring at a screen versus actually interacting with patients and is a huge factor in this burnout. And so that's clear. But even within your more research positions, yes, we haven't adapted to the times in the sense of what does, what does transformative scholarship mean? We talk about transformative innovation. And so we're still under the rigid sort of get your grants. Yes. Get your publications and make sure that those are empirical publications, not necessarily viewpoints or policy pieces that may bring new insights into play. And so you're still operating in that traditional hierarchy and it's not well suited towards the times in terms of what most people, even in the community actually want or need. And I think that disconnect is a factor in all of this. But yeah, there's definitely something that needs to be done to retain your impactful people
like Peter and get them, those ideas don't come for many people. And so that's right. That's what I'm saying. Yeah. Peter, Peter's essay that, you know, you could buy Gilead, rather than pay for their hep C drug, that at market, at market cap. That's a very clever idea. You know, not a lot of people have that idea. And he has one of many ideas he has. Not a lot of people have clever ideas. I'll be honest with you. I really think that it's very few. And losing clever idea people to these other sectors is a failure of the academy. In fact, it's probably the greatest failure because of all the bureaucracy and bullshit in the academy. The fact that some handful of people actually doing clever innovative work is the thing that keeps it going. The things I'll say about the clinical side, I think, you know, you talk about the glory, you know, was there a glory day? I will say that paper to electronic has made many things worse. When you deal with paper, it's as fast as your brain and hand can work from notes to evaluations. Computer is as slow as your password logins and two factor authentication and all this stuff. I don't want to waste my time with, frankly. And every time I do a note on the epic, there's 120 millisecond lag every click, every single click. My brain is not wired for 120 millisecond lags. And if Twitter or Facebook had 120 millisecond lags, they'd fire the whole engineering staff. They'd fire them all and say people will not use our product. They'll get bored and look elsewhere. I think that's a huge failure. And you talk about the grants and policy work. I think that's a great point, which is that you all in portal have written some of the most impactful essays about policy. And those aren't quote, unquote, original articles. And so there's sort of a, you know, people may look down upon that. Related to that, I think is at some point in one's career, writing grants is frankly, I think a waste of time. You know, I published enough papers, you published enough papers, you know, written books, people know what you're going to get. And you know, you know, you're going to get a certain output. You know, you're going to get certain sort of examination of certain issues. What do you need? What do you need all this grant repaper for grants for? And the people who are scoring the grants, frankly, they're ill-suited to even evaluate the grant. They're not in the field. They don't know shit about it. And maybe they're not even good in their own field. I mean, frankly, that's how I feel sometimes. And so I think these, these factors are bad. It's a bad recipe. If you lose a Peter, if you lose a Neil Shaw, I mean, these are clever people. I think it's, it's really troubles me. Agreed. And we haven't even gotten to the elephant in the room, which is what the pandemic has done in terms of particularly female academics and the ability to, you know, have the flexibility that's needed to juggle all of the balls that are oftentimes needed to be juggled. And so, yeah, there's definitely one silver lining of all of this, I think, is at least my institution. And I think many others have, but I think this equally applies to the private sector. So maybe there's not a relative advantage. But the understanding that we can do a lot of these things, not as rigidly as we did before. So a little bit more flexibility from working from home, a little bit more flexibility in terms of how you hold your meetings. All of that sort of stuff, I think, can help. But again, is that if the private sector is already caught on to that as well, that's not necessarily going to be a relative. Exactly. So I am hopeful that, you know, it is a sense that at least one of the things, again, with the pandemic is the notion that we buch so many things in terms of our rollout in terms of our preparation. And hopefully that motivates a new generation of scholars to get into the mix. And that's my hope. But I think you are noticing what a lot of people are noticing in that you see you are seeing an exodus. And yeah. Okay. And let's go to add you can't imagine people going to want to talk about this. Okay. This is an Alzheimer's drug. It's a monoclonal antibody. It is directed. And its goal is to reduce amyloid plaque formation. And it's not the only kid on the block. I mean, there have been a lot of other drug products from a number of different companies. They've all failed spectacularly. Spectacular failure. And in addition to that, Alzheimer's is a key disease that robs six million Americans of their future. And it robs them of their sense of identity. It's one of the, I think, most pernicious and horrible illnesses takes away who we are. It also is a huge economic burden. I mean, not only is the person suffering, but they require care. It often that care is not well compensated in the system. And so loved ones have to give up work and give up their own ambitions to take care of a loved one with Alzheimer's disease. So catastrophic disease. And people have tried for years all sorts of different things. And we have a few things that are approved prior to this biogen pharmaceutical drug approval. They don't work that well. I mean, they're not really fundamentally disease modifying agents. They have very small impacts on different measures of cognitive function. No one would call them a cure. No one would call them even sort of fundamentally changing the disease trajectory. They're really sort of maybe just treat some symptoms of the disease at best or very very slight drugs. And many, many drugs have failed. Why do I say all this? This should give you the idea that the pre-test probability that anything new is going to work is rock bottom says low as it goes. It's the lowest pre-test probability that you got a drug that works. Enter biogen, biogen, you know, I think they had a phase one, two study, they saw some promising reductions in amyloid plank. They launched two concurrent phase three randomized control trials in mild to moderate Alzheimer's dementia. They halted both those trials about a year ago and announced that they had been halted for futility. They failed. In those trials in one of the two, there was a change in the dose to sort of a higher dose. And the other one they used a set of doses that are considered low doses. The low dose trials just like totally fail your fail. You didn't improve any sort of measure of cognitive function. In a post-talk analysis of the other study that was halted early for futility. In the group of people that got the higher dose, they claimed that there is a quote trend towards benefit. So here you are. Two keys. Two keys. They're post-talk and trend. Yes. Post-talk trend and subgroup. Yeah. And you've already halted for futility. And we know from work by Montaurian colleagues that when you are halted for futility, whatever you're going to see is likely to be exaggerated. And it's probably going to go regress to the true effect with further conduction or with conducting trial further. So what do we do with these data? It reduces amyloid plaque in the brain, sure. But whether amyloid plaque is a bystander or has anything to do with the causal pathway, no one knows. No one knows it. And again, our past record of trend drugs that have an effect on plaque reduction suggests, no, and pretty conclusively suggests, no. And so unless you have something magic, something, a smoking gun, let's suggest that this, this is somehow different, but you don't here. And so yes, we have to have to carry on this conversation. But yeah, I think you set the stage well in terms of what FDA had received. And I think there's a decision point here. There's tremendous pressure. I mean, you've noted the billions that have been spent on drug development. You've noted the, you know, billions if we want to put a dollar sign on it, but the significant human toll of Alzheimer's disease. And there's a huge amount of pressure to let's find something that works. But what does that mean? It doesn't serve anyone, except for the manufacturer. It doesn't serve the public. It doesn't serve their families. It doesn't serve society and the healthcare system to lower the bar for drug approval to provide some sense of hope to patients that yes, we have something new. We don't need something new. We need something that works. And I think I can understand the pressure that the agency is on. I can understand the anger and the desire and the fervent hope to get new treatments from the patient community. That is clear. But I think we have the FDA there for a reason. It's a agency that is formed. The modern FDA is a creation of historical lessons and tragedy in the pharmaceutical market. And we completely sort of wipe the slate clean in terms of learning the lessons of history here. And the implications are potentially massive. And so, you know, I don't think I think if you talk to most, it would have been really remarkable about the adicent of ab decision is the near unanimity among pharmaceutical policy experts of various stripes. And you've got people like Peter Buck and Craig Garthway co-authoring op-eds usually on opposite sides of the divide. Really going to task on what a failure.
failure this was and my colleague, obviously, and I am Tesla, I'm called this, sorry, you'll believe the worst decision in FDA history in recent years. And I think there is a lot to try to understand here in terms of what decision the FDA made and how it was influenced. But I think before we even get into further into that decision, I think we need to take stuff and say, this is not coming out of the blue. - Yes. - This is an ongoing trend. And if there's anyone who's noted this ongoing trend, it's you, then I mean, we can start in the cancer drug space, but the history of increasingly approving drugs on the basis of more limited evidence is something that's been going on for the past decade. - Yes. - And that is the number of pivotal trials that's required to support drug approval, whether or not the duration of those trials, whether or not they were surrogate endpoints or hard endpoints. I mean, in every case what we're doing is, in a sense, allowing drugs on the market with more limited evidence. And here is a remarkable case. I mean, what is different about this is that the evidence was virtually not. - Let me stop. Let me dive on that a little bit more because I want to come to these broader issues, but I just want to finish smashing this to little bits. (laughing) Okay, so we talked about pre-test probability. We talked about the two studies. We talked about inconclusive results, early stopping, subgroup analysis, post-talk analysis. You put all that together and somebody might say, well, what's the chance this drug actually helps people? 50/50. - Hey, 50/50. It's like 2%, it works 98% it doesn't. It's not 100%, it don't work. It's not 100% it doesn't work, but it's not 50/50. It's closer to the bottom. In fact, much closer to the bottom. That's based on the pre-test probability. That's based on the fact that these type of evidence is not very persuasive. It's a lot of smoking mirrors, but it's not a lot of actual evidence that it has a therapeutic effect on outcomes people care. And this is putting aside the fact that the magnitude of the effect might not be clinically meaningful, but that aside, we're just talking about any statistical effect. Then enter the fact that in a normal world, the FDA would just tell them to go away. You're done, you're rejected. Bye-bye. Do the three studies. - One other study. - Do the J3 study. - Exactly. - You know, is it okay to think 2% is promising to do another phase three study properly? - Sure, that's a company's prerogative. The FDA should say, do your study. If you have a good result, if you do two studies, if you really confirm this effect, one more slide point. This is kind of a space where two studies make sense because so many candidate compounds have failed. Nothing is really transformative. You really want to make sure you're not chasing a flash in the pan. You really have something substantive. So that's why I think two studies has a much stronger post test probability that something's a real effect rather than a spurious effect. So anyway, the FDA should have rejected it. They had advisory committees. They had a couple. Aaron Kesselheim was one of the members on the committee, Caleb Alexander, a lot of thoughtful people in policy. Different than the oncology drug advisory committees, by the way, which pick people who are oncologists who know very little of policy. Here you pick people who know a lot of a drug policy. And I think that's partly why this committee was sensible and said, no, no go. This is not sufficient for regular marketing authorization, which is what the sponsor sought. They sought that. - 10 votes, 10 votes, no. And one of the abstentions. One abstemption, yeah. It's a slam dunk. Don't do this. And yet, when the pedophadate came, the FDA pulled out of nowhere and accelerated approval and gave it to biogen. That approval was on the basis of amyloid plaque reduction, which they themselves in a 2018 guidance document said is not an end point suitable for accelerated approval because it is not reasonably likely to pretty clinical benefit. So the statutory language, of course, for an accelerated approval endpoint is that it is a surrogate reasonably likely to pretty clinical benefit. Here, the FDA says just three years ago, this ain't that. Amyloid reduction is not that because we just don't know if an amyloid reduction constitutes any chance that you have a meaningful benefit. - And to date, well, I mean, what we've discussed is purely the science. And I think you've made a very convincing case that the likelihood of this drug having a statistically significant effect on some sort of meaningful clinical end point, regardless of the magnitude of that effect is low. What is perhaps even more troubling here is a little bit of what I would say at worst misleading at best, perhaps non-forthcoming, but the fact that the advisory committee was never given a chance or never provided an opportunity to discuss accelerated approval. Now, we had after the fact and after some. - The camera has just paused. - Just we're considering. - Fit it apart again. You cut out for a second. You said after the fact. After the fact. - Yeah, after the fact. - So we had here after the FDA had said, well, this is something that we considered after the fact. And I think there was a recent stat news expose which suggested that FDA was knee deep in consideration of the accelerated approval pathway as a viable option for getting this drug to market well before this advisory committee was set to meet. And so there you've got a sort of a backtracking and a non-very conflicted statements from the FDA as to what point was it seriously weighing this because I think the concerns you raised about the accuracy or the, I guess, whether or not this drug met the criterion for accelerated approval. I think the advisory committee would have had some very knowledgeable things to say about that. And I think they were, yeah, they were not given the chance to do so. So now we've got it, we've got a question of very low evidence. We've got a cool question of transparency and regulatory capture in terms of the degree to which biogen and FDA were working in a way that, you know, I think there have been prior higher ups in FDA who said, "Cooperation between industry and FDA is important, it is vital." But this degree of non-transparent cooperation where the FDA is almost acting as an advocate on behalf of the company and ignoring its consumer protection, although is very troublesome. - Cooperation is okay, collusion is not, and this is very. - Where is that line drawn? Yeah, exactly. - That's what he just said. Yeah, but I mean, I guess I hate to say it, but, you know, I guess just one more thing about the story. And then afterwards, of course, three panelists resign, including Aaron because this decision is spectacularly bad. Some of the unique things here is, I think, like, why does this decision get more attention than other decisions? I just wanna mention, like, you know, cancer drugs, I joked, but there's a lot of truth to it that we have six aducanemabes a year in cancer medicine. But the reason it doesn't get the same attention is a couple things. One, each of our bad drug approvals does not have a market share of six million Americans. It doesn't have that size and budgetary impact and cost are two different things. Cost is the price per unit. Here, we're talking about 56 grand per person per year. Budgetary impact is the price per unit per time, multiple of the number of people who are gonna get it. And budgetary impact of cancer drugs, even if it's 200 grand, 400 grand, if the number of people getting it is 1,000, 10,000, it's one thing. If the number of people getting it is a million, now the budgetary impact is like hep C drugs. It's crushing. It's soul crushing. So that's one of the distincting things here. The other thing is, every time you approve a drug that doesn't actually do it, doesn't work and people take it, it actually makes it harder to do clinical trials in that space. You either have to do it after or in concert with this drug that doesn't work, it muddies the water, makes it difficult. So I think these are some of the reasons why these policy people, you wanna say something. - Yeah, I think you nailed it on the head in terms of implications. You talked about the budgetary impact, huge budgetary impact. I think that there's also, you talked about the future, the futility now of evidence generation, that's gonna get us the actual answer that we want. And this notion that there's gonna be a nine year window in which this confirmatory to trial will be done under the accelerated approval pathway. - So they have a long time before their check is due. They have a long time to bleed the public of cash and offer this questionable product, probably worthless. I think the probability that it helps is very low. Before they're asked to pay the check and it'll be difficult to accrue and people will cross over potentially, which they will say is the reason why they didn't find a statistical significant effect. [BLANK_AUDIO]
problem I think is the trials were from mild and moderate Alzheimer's and they gave a blanket approval. So of course, naturally, people will be giving this problem. That's a huge important point too. That was another thing that confused many experts was, why was the indication made so broad? And we simply don't know. So the implications go beyond that. Now you've given people false hope that this is a drug that is going to do something meaningful. We don't have the evidence to suggest that it will. And I think as part of this, we've, people have talked about the floodgates being open, but particularly in the Alzheimer's phase, the notion that now this is an acceptable surrogate endpoint that many companies can now use to get onto the market, where we know that this surrogate has issues in terms of its association with the actual clinically meaningful hard endpoint that we care about. That's hugely problematic as well. And so, and we've seen that. Lily said they're going to file by the end of the year. Yep, exactly. And so this is, when we're talking about, well, we want to, this speaks to, again, we've talked about this before, but I guess this notion of the false sense of how you promote innovation. This is not what does innovation mean? And sure, we have a ton of new drug approvals of which, at a kind of others now, one, but are those the drugs you want? And what is the implication of FDA allowing these drug to market? Yes, you get patients to access them. But if they don't work, then patients are actually getting harm or wasting money. And we're bringing and incentivizing companies to bring drugs to market that have this effect, rather than drugs that show a real clinically meaningful improvement. And so that's not the innovation we want. And I guess the real, I mean, I mean, I don't think anyone thinks the FDA is the agency that should make sure we have drugs that have a 2% chance of working, but no lower. I mean, if you get to such low percentages, and I keep throwing that number out there, I don't have. I can't prove you that it is that number. In fact, no one can prove the number because doing this sorts of Bayesian calculations impossible when there've been such a, there's no real success in which one can extrapolate numbers from. But yet, I suspect it is quite, quite low if you look across drug development broadly. Anyway, I'm happy to talk about that. That could be another, like, we could write a whole paper on that topic. But I think that, I mean, you're the deeper question here is, I mean, I think I think we've hit most of the I can key points that the clinical trial evidence is limited. They've expanded the indication, accelerated approval. They didn't discuss that. They didn't listen to the advisory committee. This is the only time in my knowledge they've ever went against a 10-0, sorry, a 10-0-1 vote. Sometimes they go against a split vote and approve it anyway. But never, you unanimous vote that says don't do it without talking to the committee. People have resigned. It's gotten everyone in a furor. It's going to potentially bankrupt Medicare, which I don't think they'll have a legal avenue to escape paying for this. Even if one in three people with all the timers takes this drug, it's a $112 billion outlay according to SACs and Bagley in Health Affairs. It's going to bang this all. And really, when you talk about a drug that doesn't work, that everyone pays for, it's not a drug or medicine. It's a financial product that helps and rich shareholders at the expense of the general public. But I think the expense of every family is the general family. They're the victim of it because they're given false hope. We could have a system with false hope. We just abolish the FDA and then it'll be false hope city. But we don't do that. We have a restrictive system which uses the FDA. And here they don't enforce any real efficacy requirement, which is even actually I think worse than not having it at all. But we could debate that. But here's my question for you. The capture. I mean, I personally, I do not believe the FDA is actually an agency that is invested in the public interest at all. I think they're an agency that there are a lot of people there who want to keep their jobs or get promoted. And there are a lot of people there who want to leave their jobs and get a much better job in the industry. And they're an industry that works to serve the corporate interest and provide window dressing that we're doing safety and efficacy testing and really not enforce either and keep corporate profits high. And that's the real goal. Their goal is not to protect the American public. Am I? Have I become too cynical? I don't think you're cynical in terms of what the outcomes are. I would say, you know, I work closely with the FDA. I think very highly of many people in the agency. And I think that in many ways, this is the same sort of thing we talk about with financial conflicts of interest among clinicians. We've got to get away from thinking at the individual level. Is this individual agent at the FDA somehow captured? No, it operates at a systemic level. And basically what the systemic effects are, we have increasingly put FDA's operating budget into the hands of manufacturers through a user fees. Now, there's a natural implication here. Who is your master? Is it the public at this point? Or is it the industry? And increasingly, I think the notion is that FDA sees its mission as facilitating what the industry wants. It doesn't help that every five years, you have to renegotiate the doofah agreement to figure out to keep the agency running. And so what's being lost in all of this is the fact that I mean, if you go to FDA, so protecting the public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices, one of its stated missions. That is a mission that seems to be failing. And I think it is, you know, harder in a sense of regulatory capture is one thing. But capture of patient support groups is another thing as well. And so there's a lot of capturing the industry going on. And it is to be, it is easy for those groups that have been captured to say, well, we are doing what patients want. Well, we are doing what some captured groups might want. But I don't think we're necessarily doing what your average American wants in terms of ensuring that we get drugs to the market that actually work. And we know what happens. We've talked about this, you know, in the last cycle where they were thinking about putting an FDA commissioner in who didn't believe in having the FDA. Yes. Yelp for drugs was volatile. Yeah, exactly. Precheck for efficacy. We know where that leads. That's the reason we put that in place. And in the 60s was because that didn't work. And so we are, we are destined to, you know, tragically, we learn the history. The other implication of this is that FDA is essentially making its role in the pharmaceutical market less relevant by doing what it's doing. Essentially, what is going to happen? And this is by necessity. Right. We're going to have payers take a more active role in who gets access to what medications. Well, actually, I'd rather have scientists at the FDA dictating a little bit about what drugs get to market rather than having my insurer tell me that I can only get this, this, or this drug because the cost are too high. But let me put on something there. The insurer, their incentive will be to buffer a year to year. They don't want big year to your variability. But in the long haul, their incentive is to grow this pie as big as it can get. They want to, they get, they're limited by medical loss ratio at a certain fraction of revenue that flows through the system. So a society that spends 50% of GDP on health care is great for insurers. So they will grow it. They just grow it slowly. And in a way that balances some of their money. That's a good point. That's a, that, that is a good point. But the way in which they grow it is, is also a question I have in terms of. Which, exactly. Is it going to be based on actual clinical evidence or not? Is, is an interesting question. But I mean, ultimately, you know, what is the potential silver lining here? The silver lining is, I mean, if FDA continues down this path, the pressure for pricing and drug pricing reform is going to grow and grow. And, you know, we've already have some strange bedfellows who are thinking about passing legislation that may help along this path. I think that pressure will grow. Now, I am a bit of a skeptic like you and a cynic to some degree. I think that pressure needs to be overwhelming. And that is the degree that it needs to reach before Congress will actually pass something like HR 3 will, will need to be overwhelming before we can get there. But I think we do are going to see more states take action in terms of pricing reform. And I think at some point you will get the federal government seriously.
getting close if not actually passing drug pressure reform. - Let me say this, let me say this on this topic. I think that as you can, a MAB is a very visible symbol as you point out of a trend that's been going on long before it and it'll continue even after it, I fear. And I think there's a deeper symbol, there's of course a symbol of this particular regulation question, but I think it's how the left has lost and let me tell you why I think that we've lost on the political left, political left, those of us who believe that government can have powers to make lives better for average people, for poor people, for middle class people and create opportunities of upward mobility. We have lost in a number of fronts. Once we lost the Supreme Court, I mean that's gone. We lost that, we gotta admit that, that's an easy vote. We've also lost the universities. While we were snoozing, we have created a university system where most academics I know are addicted to pharmaceutical money. And there is not really like the state university professor who actually has any support to do any thinking. Everyone is just got their hat in hand, going out to Genentech trying to get a few more trials. It's the easiest way to a career. So we've turned a whole university. You know, I read a book, Genentech, the origin story and it talked about how boy or when he was at UCSF and he created Genentech, people like look down their nose at him to like look at this guy trying to profit from science, you know. And now of course everybody's like the whole goal in life is to have some bullshit spin off company. They don't care if it works or not, you know, and maybe blood based cancer screening will be the next one, you know. I mean, they don't even, they don't even want to randomize trial to be the barrier. That's gonna make it harder for them to make their loot. So we lost, you know, I think we've lost the universities. I think Beidot has some good things, but it also was a tremendous loss for what it means to be an academic. We've lost the FDA. And I guess what irritates me the most and this is a big conceptual thing is that there are many people who claim to be progressive left people. They obsess about visual displays of purity, purity testing and virtue signaling and that's what all Twitter and social media is just so enriched with that. They don't, they're losing half of America by just coming across as such condescending little bastards. We're losing all these issues. This constant virtue signal, not a single one of them wants to invest the mental energy to actually chase the money because the real problems with society are, they are these very esoteric decisions like Adjicanimab. Adjicanimab is not, you know, when Trump runs for office and he says that, you know, the system is rigged and it resonates with people who have seen stagnation in wages, who've seen lower opportunity than their parents, but he's wrong about why it's rigged. It's rigged by people like him, you know, it's rigged by that kind of politicking. And this is why it's rigged. Adjicanimab is the rigged system. It means less wages, less upward mobility. We didn't talk about the fact that we'll pay for an Adjicanimab. We won't pay for a caretaker. We can talk about that. You know, that was a really insightful point. It steals money from average Americans, makes it harder to rise through the ranks. It robs us to the American dream. It is giving you a product that probably doesn't work. And it's all done in the name of science and medicine, which makes it all the more sinister in my mind. And it is how the left is really losing. And our eye is off the prize. We're so distracted and nobody wants to talk about this issue. And that's what really angers me. So I think, I think you've made a really compelling critique. I think that, you know, the increasing inequality of the house and have not have nots in society. And the fact that systems are operating right now to increase that, rather than decrease that. You can talk about, you know, I have my disagreements with certain elements of the critiques of a pandemic response. But I think the point is well taken that the disproportionate burden of a lot of these policies are felt by those with less means. And I think that's undeniable. You can't get around that. And I think you're right. I want to focus just a bit on the sinister aspect. People are being told that this is what is necessary to have medical innovation. And I think that's the real tragedy is that this is not good innovation. And this is not what we want. And what we want we can have with a lot better redesign of the system. And we are, you know, screaming at test cases like this, we parade at Alimimab's manufacturer as the CEO before Congress. We do dog and pony shows about what is wrong with drug pricing. Drug pricing has been an issue foremost in people's concerns about health care for the past 10 years or so. But are we actually making a dent right now in addressing the problem? No, there seems to be a lot of virtue signaling about it. And so what is unfortunate about all of this is we are given sort of tokens and being told that we are making progress. The fact is that major reform of the system is fundamentally needed. Now in our, you know, structure of politics, those reforms usually don't happen without some sort of exogenous shock. And the real question is how much further widening of inequality are we going to get? And further rating of the taxpayer funds are we going to get by manufacturers producing drugs that aren't very effective before we say enough enough, we need to do something. And it's, it is an interesting position to be in as a academic because you can only draw attention to the issue. You don't necessarily get a chance to try to shift it, but figuring out how to actually drive social movements. It's not in the academics wheelhouse. And so, you know, we need to do a better job of, our job is to provide the evidence. Our job is to make sure that that evidence is relatable, that it is easily digestible. But there needs to be more coordination if we're talking about a progressive movement that is wants to get things done in terms of turning that into, into action. And so-- - I can't beat him, join him, which is what I see all around. But I will say, I mean, this is a question for you, which is, our Democrats even better than Republicans. I mean, we've lived through, let's talk about Clinton, Obama, Bush, Trump, you know, just the last four. And here's what my honest observations. I mean, of course, Clinton's fiscal policy was actually very right, it was very centrist or right. It wasn't truly a liberal progressive economic policy. The FDA under, you know, Biden or Trump or Obama or Bush, in my mind, is an agency that has the same. It's just been drifting the same way towards pro-industry girls. We had Exandis, wasn't that, that was Trump. Exandis was under Trump, and Adjicanimab is under Biden. Ironically, Exandis is a lot cheaper budgetary impact 'cause there's not a lot of kids, but it depends on the muscular dystrophy. There's a lot bigger impact. We see, let's talk about liberal progressives. I'm gonna have an article about, but Howard Boschner's gone. Poof, he's gone, he's resigned, and I'm gonna have an article, hopefully, where I'll articulate what I think are the things in that issue, but Janet Woodcock's there. And there is no outpouring of criticism for Janet Woodcock to go. Even though-- - Or from politicians about Adjicanimab. - Yeah, from that. - It's beyond us. - Yeah. - So I guess my question is, I guess for you and I, we're very much aligned on these issues. You, I, Walid, Joe Ross, Aaron, et cetera, et cetera. There are many sort of people who are, I think, pro-regulation as a force of good. For us, I guess the question I have is, who should we vote for? Who is, what's the path for us? - Yeah, and I think one of the interesting things about pharmaceutical regulation and pharmaceutical policy is the pharmaceutical lobby is so powerful and its ties are just as deep in the Republican community as they are in the Democratic community. So in terms of, is it necessarily a party issue? No, I don't think so. And I think what you've said in terms of how the administrations have all consistently helped in the swing of this pendulum to less consumer protection, to more promotion of industry growth is a legacy that's been inherited from administration to administration. And so honestly, when it comes time to it, I appreciate the sort of work that something like patients for affordable drugs does. In attempting to identify politicians regardless of party who are advocating for sensible pharmaceutical policy reform. So I'll say, at least within the pharmaceutical policy space, the differentiation between the parties is not as great as I think it is in other areas. That being said, the Democrats are the ones who have pushed forward at least HR three. And so maybe I am under
you're selling the differences. But I think there are key Democrats who are obstacles in the way of pharmaceutical reform. - I agree. Yeah. Okay, that's well put. I know our time is up. I'll give you the last word. People should follow your writings, I think. These issues are nuanced, they're complex. The system is rigged, but you need to know exactly where is it rigged? How is it rigged? And how might you combat that? And what are the ways to fix it? And there's no better right around that than you amete and your colleagues there in the portal group. I'll give you the final word, Adjicanimab. Good drug, great drug. No, I just kidding. (laughing) Adjicanimab canary and a coal mine. And so this is one of the last wake up calls we're gonna get about a system that has increasingly put the real needs of patients to the side and increasingly put the interests of manufacturers on a pedestal. And I think that in terms of the last word, what does this all mean? It means we really need a change of leadership at the FDA. We need a change in culture at the FDA. But we're not gonna get that without the administration knowing that this series of decisions that have happened are catastrophic in the sense of what it means for the health system and that these are not going to give patients relief that they're actually gonna get more hardship from this. This is gonna create more inequality, more have-nots. And we need to keep that drumbeat going because unless we get changed at the agency, we are going to have a better or worse rationing that's going to come from other parties within the pharmaceutical system. And that rationing I can sense will be far worse than what we have now in terms of actually getting the drugs we need to the people who need them. - I meet separate right, thank you so much. - Thanks, Ana. - Thanks for listening to Plenary Session. Plenary Session was produced by Keana Klossner, Music by Ian Strailey and Audrey Tran. Plenary Session is not medical advice. The views and opinions expressed on Plenary Session are those of whoever said it. (upbeat music) Until next time.
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