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The 21st Century Cures Act: A Giant Piñata

So we have another whopper of a piece of health care legislation before us in the 21st Century Cures Act. I believe that this one runs over 1,000 pages, so anyone who tells you that they’re on top of the whole thing is probably bluffing. Bills like this are giant piñatas, and all kinds of stuff falls out of them when they’re whacked. Here’s an attempt, based on what I know about it, to see what we’re in for, because at the moment the bill looks reasonably likely to pass in its current form. Here’s a rundown from Stat on the bill, one from NPR, a largely negative one from The American Prospect,

First off, there’s plenty of money being spread around. Over ten years, nearly $5 billion is allocated for the Precision Medicine Initiative, the BRAIN Initiative and Biden’s “Cancer Moonshot”. This is basically a large dose of funding for the NIH, which is probably not a bad thing, although NIH funding can be hard to judge. Its budget increased substantially during the G.W. Bush’s first term, although there was a hangover afterwards when it didn’t keep going up in the same manner. As I understand it, these current funding provisions would be subject to a yearly congressional vote (or at least some of them are), which is much different than a solid ten-year chunk of funding. The first four fiscal years, though, would see money going into the “NIH and Cures Innovation Fund”, which (according to IP Watchdog) is to be spent this way:

At least $500 million of these NIH funds would be used for an Accelerating Advancement Program to partner with national research institutes and national centers to accomplish biomedical research objectives. Of the remaining $1.25 billion or less, at least 35 percent will be allocated to early stage investigators which have earned at most one NIH competitive grant; at least 20 percent allocated for “high-risk, high-reward research”; and at most 10 percent reserved for intramural research. The other $110 million left in the yearly budget will be allocated to a cures development program and will fund drug manufacturing studies, health software and obtaining data on disease history.

The NIH is also directed to set up an “Innovation Prizes Program” to try that out as an incentive for research, and I’ll be interested to see how that goes (that is, what they’re going to direct these to and whether the prizes themselves will be sufficient). One provision directs the NIH to specifically set aside funding for “high risk, high reward” research, which is something that I’m in favor of. There’s a lot of other stuff about establishing councils and collaborative bodies that I’m going to skip over, since I’m never sure if these things are useful or not. In other funding, one billion goes to the states directed towards opioid addiction.

The FDA gets increases in the maximum pay for its employees, under the heading of trying to recruit (and keep) better staff, and this surely reflects the problem that their expertise can be more valuable in the private sector than it seems to be at the agency. But the main news on the regulatory side are some potentially big changes in the drug approval process as well, and these are getting a lot of attention. For one thing, the agency is supposed to “establish processes under which patient experience data may be considered in the risk-benefit assessment of a new drug”. And I’m not quite sure what that means, to be honest, since you’d think that the data from clinical trials might well be called “patient experience data”. Unfortunately, my guess is that this is more like directing the agency to take into account the testimony of people who show up before the hearings regardless of what the actual clinical data said. We’ll see. The actual language of the bill says that it’s “data collected by patients, parents, caregivers, patient advocacy organizations, disease research foundations, medical researchers, research sponsors, or other parties determined appropriate by the Secretary that is intended to facilitate or enhance the Secretary’s risk-benefit assessments“. That could go in a lot of different directions, with that “deemed appropriate” clause as the gatekeeper.

Risk-benefit seems to be at the heart of what a lot of people like about the bill and what a lot of people hate about it. In general, it seems to loosen up FDA approval standards in the service of getting things through faster, by several means. This is particularly noticeable in the many provisions in the bill about medical devices, but it shows up some directed towards antibiotics and regenerative therapies as well. That last one is thought by some be a favor from Mitch McConnell to some donors in the business. There’s no way to satisfy everyone here. There are people who seem convinced that the FDA is this huge, agonizingly slow lump sitting in the way of medical progress, and in my own experience, the same people also tend to believe that regulatory agencies in the rest of the world zip right along, approving things that we don’t see in the US for years. The truth, from what I can see, is closer to the opposite. The FDA approval process has been sped up several times over the last couple of decades, and now is generally faster than than Europe or Japan.

And there’s some fundamental confusion here. I really don’t think that there’s this huge backlog of wonderful therapies piling up behind a big FDA roadblock. FDA approval is not what shows that a drug works; clinical data do that. You can instruct everyone to collect less data, but then you will approve – and ask people and their insurance companies to pay for – more things that don’t actually work. How we are supposed to spend less on health care by approving expensive medications that don’t do much good escapes me. I realize that there’s room to argue about this sort of thing, of course – requiring everyone to run nine Phase III trials would ensure that only really, really efficacious therapies make it to market, but there would be damned few of them (and they’d cost the earth). But I think that it’s a basic principle of how things work that just because you can screw up in one direction doesn’t mean that you can’t screw up in the opposite. Too tight is bad, and too loose is bad, too, and the argument here is whether we’ve reached “too loose” or not. (I should note that there are those who say that the FDA has already been directed to do things like this, with inconsistent and contradictory results).

On the drug-company side of things, the bill originally had provisions that would exclude reporting requirements on some continuing medical education efforts, and that really had the potential to not look good. Indeed, this part of the bill was controversial enough that Sens. Warren and Grassley demanded its removal before they could vote for it, and that happened at the last moment. I’m not sure if that removes their last objections, though, and I believe that Sens. Durbin and Sanders have also come out against the bill, last I heard. As far as I know, the only way that the legislation can clear the Senate in time during this session would be by unanimous consent, so issues like this matter a great deal. In general, it would be hard to vote against a bill that increases cancer funding and efforts against opioid addiction, and a lot of other popular things, but if you can characterize it as an unconscionable giveaway to the drug companies you could probably swing it. So we’ll see this week how that shakes out. I would think that attempts at this point to modify the bill would almost certainly shove it into the next congress, and at that point who knows what happens.

17 comments on “The 21st Century Cures Act: A Giant Piñata”

  1. Luckless Pedestrian says:

    I think the “patient experience” piece is directed at the notion of having real-world evidence play a key role in supporting some drug approvals. This could be especially helpful in specific scenarios such as line extensions. For example, this approach could provide solid evidence that a cancer drug approved to treat X different tumor types is also effective in treating other tumor types. The key is that the data would still need to be valid and compelling, but they would derive from sources other than traditional randomized controlled clinical trials (e.g., observational studies, insurance databases). FDA Commissioner Califf seems especially interested in these approaches, but the devil is (as always) in the details.

  2. disappointed says:

    Indeed this is a very mixed bag, and arguably should not all be in one bill. We already know though what happens when the FDA approves a drug based on patient advocacy with the recent approval of Sarepta’s Duchenne’s drug – the insurers might decide they aren’t going to pay for it because it doesn’t work. While I can’t presume to understand the anguish of patients and parents of Duchenne’s, approving drugs based on anecdotes and yearning is not going to end well. There is nothing in this bill about who is going to pay for drugs that don’t meet standards of evidence, the next Congress will undoubtedly make insurance worse not better, so at the least we have more people going bankrupt to pay for drugs that are marginal at best, and at worst some people die as a result of drugs not tested adequately.

  3. dearieme says:

    I would admire Trump if he were to announce that he expected to veto any bill of that size put before him.

  4. David says:

    “post approval studies”? Sounds like counting how many people died at the end of the FY. Not a way of approving drugs or monitoring efficacy I’m a fan of.

    1. Steven K says:

      Phase IV clinical trials have long been a thing. There are sometimes issues arising from long-term use that aren’t seen during the first 3 phases, and only pop up years after being on the market. There are plenty of examples of drugs that have had their approval withdrawn from Phase IV data.

      1. David says:

        Granted. But it sounds somewhat like (at least for new uses?) those earlier trials may not have to be done for approval in the new instance. That and the criteria for what those subsequent trials’ evidence/data may consist of sounds much looser under the 21CCA.

  5. Kelvin Stott says:

    Funding high risk-high reward projects is great, but that strategy only works when you fund lots of small risky projects rather than a few big risky projects. Otherwise you are more likely to end up with a huge loss and waste of money. It’s fine to think big and aim high, but you still have to start small, fail cheap and learn fast.

  6. Barry says:

    It’s reported now (I have not read the bill in its entirety) that it would allow FDA approval of new indications (but not for a first indication?) without submission of full Clinical data
    “The bill opens a path for the FDA to approve new uses, or indications, for existing drugs without demanding thorough clinical tests conducted along customary lines. These include randomized samples, to prove they’re safe and effective for the new indications. Instead, the FDA could rely on “real world evidence,” which includes observations, safety and side-effect claims, and other data not subject to rigorous analysis. “That’s a much lower level of evidence,” Carome says.”

    We recall that it was because a new indication requires submission of full clinical data that we learned of the cardiotox of chronic Vioxx dosing (although that had not shown up in the initial acute clinical for inflammation)

    The whole omnibus that is the 21st Century Care Act should be rejected for this provision alone.

  7. Anonymous Researcher snaw says:
    $REGN’s Len: I’m against making it really easy to get your drug approved. I can’t compete w/ $PFE or $LLY in a pure mrkt place. Innovation is the equalizer, Len says, citing PCSK9 success.
    One of the underbelly secrets in industry is the US is paying a disproportionate price for drugs, I don’t know an easy fix, $REGN CEO says
    $PFE’s Read: We have to get the FDA more efficient. $REGN’s Len shaking his head no.
    $REGN’s CEO: We’re covering up a lack of innovation. People don’t raise prices when you have a strong pipeline.

  8. Anonymous Researcher snaw says:

    Regeneron’s CEO had some interesting things to say about this at a recent forum, as reported by zacharybrennan on twitter (read starting at the bottom):

    Zach Brennan ‏(at) ZacharyBrennan Dec 1

    $REGN CEO: Have to fund the industry w/a lot of $ and give a fair price. If you don’t have enough innovat. prods, you’ll never make it work

    $REGN CEO: Has to be a recognition that capital is agnostic and it will go elsewhere if it can’t get returns #Forbeshealth

    Innovation is the equalizer, Len says, citing PCSK9 success (2/2)

    $REGN’s Len: I’m against making it really easy to get your drug approved. I can’t compete w/ $PFE or $LLY in a pure mrkt place (1/2)

    One of the underbelly secrets in industry is the US is paying a disproportionate price for drugs, I don’t know an easy fix, $REGN CEO says

    Q on exec pay: $PFE’s Read says no, has nothing to do w/anything
    Len won’t even look at him. This literally might turn into a fist fight

    $REGN’s CEO: We’re covering up a lack of innovation. People don’t raise prices when you have a strong pipeline

    $PFE’s Read: We have to get the FDA more efficient. $REGN’s Len shaking his head no.

    $REGN CEO to $PFE’s Ian Read: “You are not entitled to a fraction of the GDP.”

    $REGN CEO: Not a sustainable biz model to have double digit price increases twice a year. $PFE’s Read says he disagrees…

    $REGN CEO: The real reason we’re not liked: We’ve used price increases to cover up the gaps in innovation. That’s just a fact.

    Astellas CEO: We will continue to negotiate w/PBMs on prices. $REGN CEO: This is why we aren’t liked.

  9. Anon2 says:

    I can’t beleive they are considering approvals based on surrogates alone. There is one notorious company that used a survival surrogate as a primary and survival as a secondary endpoint. They barely passed the primary, but failed the secondary. That should mean game over…but under this legislation this company can start hustling uniformed doctors and desperate patients.

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