Miracle Cures

SayUncle wonders why with all the press about miracle cures, life is still pretty much putting up with horrible diseases until finally one kills you. I actually most like this explanation for how these stories end up in the media, from the comment section over at Uncle’s. I don’t blog much about work topics, mostly because they pay me to make computers solve drug discovery problems, and I don’t like mixing work and hobby. But I can speak on this topic a bit.

The short answer is that taking breakthrough scientific discoveries and turning them into a pill your doctor can prescribe you is a very difficult, long path that spans more than a decade typically, and that assumes you’re successful in the end, which you probably won’t be. As much as libertarians will want to blame the FDA for this, the FDA isn’t really entirely responsible for this state of affairs. That’s not to say the FDA is blameless, but, for the most part, the problem is rooted in the fact that most of the easy drugable targets have been hit already, and what the industry is left with are harder problems.

Moreover the current industry paradigm for discovering drugs is poorly suited to more difficult targets. The best way I can put it is that if our industry built airplanes, we’d throw thousands of workers at the problem, without too much of a plan, assembling parts and hurtling them up in the air to see if they flew. Do that enough, eventually you’ll probably get some hastily assembled hunk of metal to fly for a bit. But it’s not very efficient at getting a final product. When the industry was hugely profitable, and easy targets were plentiful, this was a successful model. When the problem got harder — we not only need planes that can glide for a bit, we need jetliners — that method no longer works. The problem is, the industry is just starting to figure this out, but they don’t have a paradigm to replace it yet. We still don’t really know how to build airplanes in a systematic way, going back to the analogy.

There have been companies that have developed a more systematic way to discover new compounds that can hit more difficult targets. I currently work for a company that is trying to do drug discovery using supercomputers (which is where I come in). But even doing things this way just offers you a better chance at success. It doesn’t automatically make getting a pill your doctor can prescribe you an easy problem. In the mean time, the industry is in the process of imploding, as patents run out and pipelines dry up. There aren’t enough new drugs to replace what’s going off patent, and that is going to have an effect on research into new drugs.

So where does the FDA come in? The FDA approval process is a significant reason why investigational new drugs fail. Most of the times drugs fail this process, it’s for good reasons, like a really poor side effect profile, which is a nice way of saying the drug slowly cooks your liver, or damages your heart (think Vioxx). Other reasons are that they aren’t efficacious. And having watched this process happen, I can tell you if the FDA approval process, or something like it, weren’t in place, the industry would put drugs on the market that kill people. Not because we’re evil, but because it’s relatively easy to convince yourself of things that aren’t necessarily true, fail to do the right tests, and overlook things. The problem with the FDA is they’ve take their primary role and taken it way beyond basic safety and efficacy. The joke is you couldn’t get Tylenol approved today (toxic to the liver in doses not much higher than the therapeutic dose) nor could you get Aspirin (promotes gastrointestinal hemorrhaging) approved, even though both are generally regarded as safe by the FDA. To me the FDA’s role is essentially to prevent fraud — if you’re marketing a drug to do X, and saying it’s safe and effective, you need to prove that first. Obviously a drug that fries your liver shouldn’t be acceptable. But there are many cases where the FDA is taking their mission way beyond what’s good for society as a whole, and are erring way too much on the side of caution. That’s good for covering the asses of bureaucrats, but not too good for getting life altering and life saving treatments into people’s hands.

28 thoughts on “Miracle Cures”

  1. Without the FDA, I suspect that reputable drug companies would put more internal checks on new drugs to make sure that what you are describing (overlooking problems) wouldn’t happen. Reputable drug companies would have huge power in a free market, because people know that taking the wrong thing can kill them. Loss of reputation would be financially devastating.

    Of course, it’s debatable whether free market solutions would result in more deaths due to bad drugs. But I don’t think it’s debatable that the FDA assumes everyone has the same risk profile, when that’s clearly not the case. If I’m dying of some disease and have a prognosis of a month or two, shouldn’t I be given the opportunity to take a potentially unsafe drug? I mean, who cares if it will cook my liver in ten years? Under the FDA no one is allowed to take risks above what the government thinks is proper, while under a free market, individuals who are willing to take larger risks would be able to.

  2. Another problem is the way biotech companies are funded and the huge amounts of money they eat through every year. Typically they start with something promising that may or may not work out. To keep the money rolling in, they promote every tiny bit of news as a “breakthrough” of some sort. This keeps a lot of investors happy.

    Many drugs get into Clinical Trials but never make it beyond the first round.

    I used to invest in biotechs because, like you, I worked in the industry.

  3. Heh. Try some Tylenol and an aspirin at the same time and watch while you pee out your kidneys.

    I think one of the reasons why the FDA is slow in approving things is that they really don’t want a repeat of Vioxx or hormone replacement therapy. Two miracle cures that later turned out to kill people (don’t forget the thalidomide flipper babies). Unfortunately this means they err on the side of not approving things. I think that if we wanted to impove the agency, we would have more scientists and doctors making decisions and less politicos and bureaucrats deciding things.

    That, and the general public is dumb when it comes to science

  4. “Without the FDA, I suspect that reputable drug companies would put more internal checks on new drugs to make sure that what you are describing (overlooking problems) wouldn’t happen. ”

    What you’re saying is that the drug companies are going to forego profit and spend raise costs in case they miss a potential ruinous cost that might develop later. What in our current economy has shown you that major corporations are operating with that sort of foresight? In actuality, the execs would bring out the new drug with insufficient testing, cash out when the stock price soars, then be on to the next job by the time the corporation has to pay the piper. Perhaps you could charge them with a crime, but probably not.

    The real problem with the FDA is that they’re exercising oversight on things that aren’t pharmaceuticals. I remember seeing a piece about a guy trying to get a breast exam product on the market. It was a sandwich of two layers of plastic around some silicone. It essentially acted like a lump amplifier and would have retailed for a few bucks. He had an awful time trying to get it through the FDA, finally ran out of money, and had to give up. Why did he have to get it through the FDA at all? It’s not a food or a drug. It isn’t ingested. Even if it was, it’s made of completely non-toxic materials. Why does the FDA have oversight over this product?

  5. The FDA just needs to be out of the business of deciding what is and is not “too dangerous to put on the market.”

    They need to ensure that drugs/treatments are effective, risks are assessed and are transparently available to the Dr. and patient. Nothing more.

    The final determination of whether the risks of a drug/treatment outweight the potential benefit needs to be made by the Dr. and patient only.

    Take the Vioxx example. Yeah it may cause damage to your heart. But assume for a minute that you’re 85 or 90 years old with with severe arthritis pain. You’re pretty close to deaths door any way you cut it. Its entirely feasible that people in that situation would trade the chance of heart damage and a somewhat shorter life for increased quality of life through pain reduction in the remaining years.

    As of now, nobody gets to make that choice though. We can’t be treated like adults after all.

  6. “What in our current economy has shown you that major corporations are operating with that sort of foresight?”

    I’m unaware of an across-the-board decline in the quality of consumer merchandise over the last few years. Companies known for producing high quality goods are in general still producing such goods.

    Furthermore, if this became an issue, consumers and stockholders would demand external auditing by insurance companies or independent auditing firms. Otherwise they wouldn’t buy the drugs or the stock.

  7. There’s always going to be issues with a drugs side effect profile for some people. In the case of Vioxx, I think it should not have been pulled from the market. For some the benefits outweighed the risks. But for most drugs that have a safety profile, there’s going to be people the drug greatly benefits, and some that it will kill. The question is where’s the balance? I don’t think the FDA gets that right. But I’m not sure the market is going to get that right either, in the absence of any government regulation. Why? Because there’s not enough information available to people to make informed decisions absent government regulation.

    Just one example of why… I can give you a sugar pill, and tell you it will treat your arthritis, and make you feel less pain. Most people will report less pain. Some people will say it was a miracle cure. But it’s just a sugar pill. The purposes of the FDA, at its root, is to prevent fraud, and that, even is a relatively libertarianish person, I think the government does have a role in.

  8. Since everyone is talking about the FDA, don’t forget they also regulate how foods and drugs are manufactured (no contamination). Without them, I doubt you would ever see a recall of dangerous food items.

  9. I don’t have an issue with government punishing fraud, but attempting to prevent fraud is another issue. Kind of like punishing murderers but not preventing us all from owning guns ;-) (don’t worry; I’m only slightly serious)

    “In a free market, would patent protections still apply?”

    More and more hardcore libertarians are moving away from intellectual property rights. They would say that because intellectual “property” is not scarce (i.e., making a copy of a book does not harm the owner of the book), that it should not be treated as “property” and thus not protected by law.

    That’s a pretty extreme position right now, even among libertarians, but it’s growing. See Kinsella’s “Against Intellectual Property” (available for free online, obviously!) for more.

  10. “Without them, I doubt you would ever see a recall of dangerous food items.”

    Kind of like how we never see recalls of cars, right?

  11. I’m going to argue you can’t prevent fraud in drugs after the fact, like you can with most products. Understand that most of what goes into a drug is information, not the physical process of manufacturing it. There is almost no way, after the fact, that you can discover all the information that’s in the drug, or find out whether there’s really any information in there at all.

    The FDA is process is really about making sure you do everything you’re supposed to in order to make sure that what you’re giving people is safe and effective. I will agree we take this kind of regulation way too far in this country, in too many areas it doesn’t need to go. For instance, I think the market can decide what ketchup is, and what constitutes good ketchup. We don’t need regulators for that. But if you want to find out what went into the pill you’re taking, I don’t see a way to do that without some kind of government process.

    Now granted, you could make an argument that the industry could be kept honest through tort law rather than regulatory law. I think there could be an argument made there. But you’d still have to have some kind of process associated with discovery, and what constitutes best practices, to show that for a specific drug they were not followed. And someone has to decide what those practices are. Again, that will likely fall back to regulators, unless you want judges deciding those sort of things, which I wouldn’t.

  12. Good points.

    Some food for thought: there are examples of “best practices” being established by industries without government intervention. One example (not research-related but still a matter of life-and-death) is the NFPA, which establishes standards for firefighting equipment (among other things). It’s not a government agency; instead, it has insurance companies, fire departments, and manufacturing associates as members. And yet pretty much every bit of gear you find in any fire station throughout the country has an NFPA tag on it.

  13. It’s probably possible to think of a non-governmental body like that which could work for pharmaceuticals, but I’ve given up on doing these kinds of mental gymnastics to try to arrive at a more libertarian solution. You still have to look at what the incentives are going to be, and how easy it’s going to be to game the requirements.

    The only problem we have with using torts is you can’t use a tort until there’s a harm. Generally speaking, with mass marketed drugs, there could be a lot of harm before the tort comes into play.

  14. Huh, I’m the only reader who read ‘blah blah blah supercomputing’. Large virtual parallel computing, I take it?

  15. Not virtual as in VMWare virtual, more like PVM. Or it could be a more distributed or grid style or other. An actual Cray style monolithic supercomputer is relatively rare these days.

  16. Our molecular simulations are actually pretty embarassingly parallel. It’s only in the protein modeling stuff do you start to get cross node chatter, and that works fine over Gigabit Ethernet. For some reason the developers didn’t use MPI or some other type of parallel library. They grew their own, but it works roughly the same way.

  17. Jujube: “In a free market, would patent protections still apply?”

    Sebastian: “Probably not. In which case there would be no incentive to discover new drugs.”

    “Against Intellectual Monopoly” does a good job of describing how companies can prosper without patents; indeed, it makes the case that patents actually distort the market, by influencing companies to produce “me-too” drugs that are as expensive to discover as the original, but do pretty much the same things.

    I, for one, would like to see theh FDA disbanded, and replaced with either: a private organization (or several!) that provides drug testing, independent of manufacturers, or several (say fifty or so) individual regulatory agencies, each beginning with letters like UFDA, TFDA, MFDA, PFDA, etc, where the first letter is the first letter of the name of a state (say, Utah, Texas, Tennessee, Massachusetts, Minnesota, Pennsylvania, etc).

  18. It’s not the patent system alone that encourages “me too” drugs, it’s also the fact that “me too” drugs are easier to discover, easier to get into pre-clinical trials, and more likely in the end to make it through clinical trials. In other words, it’s relatively easy for the industry to do, so they do it. I also don’t think there’s anything wrong with me too drugs. They have significant social benefit because people react to drugs differently. What might be a miracle cure for one person is either ineffective or dangerous in another. A different “me too” drug with a different side effect profile might be just what that patient needs.

    Also, why is having 50 different regulatory agencies better than one? Are we speaking of a system where you only need approval from one regulator? In the case, Pharmas are going to forum shop, and you’re going to end up with bad incentives on both sides.

    I’ve read the arguments you mention against patents in Pharmaceuticals. I agree with arguments that patents in other areas, particularly software, and business process patents, stifle innovation, but the arguments for pharmaceuticals is weak. Barriers to entry for marketing new drugs is very high, and practically speaking, no one is going to bother with it if they can’t charge monopoly prices for a while.

  19. In having fifty regulatory agencies, there would undoubtedly be shopping around–both on the part of the drug companies, but also on the part of those who are going to take the drugs. I would expect that there would also be “gold-standard” states, where states would recognize the approval by other state regulatory agencies that they have determined they could trust.

    Of course, for such a system to work, customers would have to be free to use any given drug, regardless of approval by regulatory agencies (it drives me nuts when the FDA discovers a problem with a drug like Vioxx, but won’t let customers weigh the risks versus benefits on their own); having many regulatory agencies, rather than just one, however, would allow the agencies to compete to balance cost of testing, risk, caution, and any other factors that may come into play.

    Having one agency–the FDA–forces us to accept their decrees. Sometimes the FDA throws caution to the wind, and approves a harmful drug. Sometimes the FDA is too cautious, and asks for “just one more test”, while terminally ill patients die waiting for the drug, and testing costs are driven up. The situation is even worse because the FDA has the power to ban any drug from use, regardless of what risks an individual may be willing to take.

  20. Yeah the real issue with the FDA’s one size fits all approach is the folks at the margin. If I have three months left, I’m willing to try radical experimental treatments. Legally though, you can’t, because the FDA works from a baseline assumption of normal health. Which is crazy, because people taking medication don’t have normal health. The risk calculations, the cost versus benefit, change drastically depending on how sick you are.

    If a patient is at the point where the only thing doctors can do is turn the morphine drip up, why shouldn’t he be able to try drugs that haven’t made it through the final stamp of approval? What has he got to lose?

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