Jury Kills Vioxx. Penicillin Next?

The other day, I wrote about the left of late lamenting that the machinery of state control that they created, agencies like the FDA and public schools, are being taken over by their political enemies, the "Neanderthal southern religious conservatives".  I observed that they were not apologizing for creating a statist structure to control individual decision-making, but just were upset they lost control of it.

In using the FDA as one example:

Today, via Instapundit, comes this story about the GAO audit of the decision by the FDA to not allow the plan B morning after pill to be sold over the counter.
And, knock me over with a feather, it appears that the decision was
political, based on a conservative administration's opposition to
abortion.  And again the technocrats on the left are freaked.  Well,
what did you expect?  You applauded the Clinton FDA's politically
motivated ban on breast implants as a sop to NOW and the trial
lawyers.  In
establishing the FDA, it was you on the left that established the
principal, contradictory to the left's own stand on abortion, that the
government does indeed trump the individual on decision making for
their own body
  (other thoughts here).
Again we hear the lament that the game was great until these
conservative yahoos took over.  No, it wasn't.  It was unjust to scheme
to control other people's lives, and just plain stupid to expect that
the machinery of control you created would never fall into your
political enemy's hands.

That has spurred a lot of email pointing me to other FDA-related articles.  I posted this one in the updates of that same post, pointing out how the FDA process (and the tort process, by the way) puts a much higher value on a life lost to drug side-effects than to a life saved from drug benefits.

Today I was pointed to this article by Derek Lowe who has been a drug development researcher for a number of years:

As a drug discovery researcher, I can tell you something that might sound
crazy: many of these older drugs would have a hard time getting approved today.
Some of them would never even have made it to the FDA at all.

The best example is aspirin itself. It's one of the foundation stones of the
drug industry, and it's hard to even guess how many billions of doses of it have
been taken over the last hundred years. But if you were somehow able to change
history so that aspirin had never been discovered until this year, I can
guarantee you that it would have died in the lab. No modern drug development
organization would touch it.

Thanks in part to advertisements for competing drugs, people know that there
are some stomach problems associated with aspirin. Actually, its use more or
less doubles the risk of a severe gastrointestinal event, which in most cases
means bleeding seriously enough to require hospitalization. Lower doses such as
those prescribed for cardiovascular patients and various formulation
improvements (coatings and the like) only seem to improve these numbers by a
small amount. Such incidents, along with others brought on by other oral
anti-inflammatory drugs, are the most common severe drug side effects seen in
medical practice....

That brings us up to penicillin, a drug with a clean reputation if ever there
was one. But at the same time, everyone has heard of the occasional bad allergic
reaction to it and related antibiotics. Even with the availability of skin tests
for sensitivity, these antibiotics cause about one fatality per 50 to 100,000
patient courses of treatment. Other severe reactions are twenty times as common.
Those are interesting figures to put into today's legal context: over 9 million
prescriptions were written for Vioxx, for example. Any modern drug that directly
caused that number of patient deaths and injuries would bury its company in a
hailstorm of lawsuits, because (unlike the Vioxx cases) there would be little
room to argue about

5 Comments

  1. honestpartisan:

    What a surprise! Somewhat who works for Big Pharma wants it to be less regulated. Perhaps that accounts for his afactual views on the FDA.

    Here are some facts about the FDA:

    1. Penicillin was not invented until after the 1938 amendment to the Food & Drug Act, which required that drug companies prove that their products were safe before they were marketed.

    2. Penicillin likely would not have been invented if it weren't for this requirement, because the drug industry did not manufacture effective drugs before 1938. Forcing the industry to develop modern testing facilities post-1938 caused more truly new and effective drugs to be invented from 1935 to 1955 than in all previous human history. By the early 1950s, 90% of prescriptions were for drugs that did not exist pre-1938.

    3. Average drug approval times at the FDA have been dropping for years, from sixteen months in 1994 to less than a year by 1999, and from a year in 1994 to six months for priority drugs (to treat HIV, for example).

    4. 100,000 people a year die from drugs that are reviewed and approved by the FDA. Kind of a strange statistic if the FDA is erring too much on the side of keeping unsafe drugs off the market.

    5. The FDA is mainly concerned with whether a drug is more effective in a controlled experiment than a placebo, not so much with side effects. The FDA is not very aggressive in pulling drugs with bad side effects, and usually only does it in high-profile cases like Vioxx.

    6. I find it hard to buy drug company claims that they can't make the drugs they need to when their main preoccupation is with duplicating the function of drugs already in the market, obtaining new patents for them that earn them monopoly profits, even for the large number of drugs developed on the dime of the National Institutes of Health, and advertising the duplicative drugs to doctors.

  2. Otis:

    Item 1. Penicillin was not invented until after the 1938 amendment to the Food & Drug Act, which required that drug companies prove that their products were safe before they were marketed.

    I think the point was that what the legal system has been redefining safe to has changed a great deal since then.

    Item 2. Penicillin likely would not have been invented if it weren't for this requirement, because the drug industry did not manufacture effective drugs before 1938. Forcing the industry to develop modern testing facilities post-1938 caused more truly new and effective drugs to be invented from 1935 to 1955 than in all previous human history. By the early 1950s, 90% of prescriptions were for drugs that did not exist pre-1938.

    So, aspirin, Morphine, Insulin, salvarsan, sulfanilamide were not effective. To Name a few.

    Big surprise here. During a period where our understanding of chemistry and biology advanced enormously, we saw enormous advances in chemicals used to treat biologic systems. We knew virtually nothing about modern medicine before 1900. We only discovered germs at the end of the 19th century.

    There will always be a tendency to prescribe a newer drug since it was developed to meet an unmet need or to improve apon a previous treatment.

    Item 3. Average drug approval times at the FDA have been dropping for years, from sixteen months in 1994 to less than a year by 1999, and from a year in 1994 to six months for priority drugs (to treat HIV, for example).

    And the time seems to have risen again based on 2002 numbers.

    This also ignores that fact that this is the time it takes AFTER all clinical trials have been completed, since the NDA application must include all the data the company has collected. If the FDA decides you failed to do enough upfront testing, you have to go back and do more. Those are the ones that raise the median. Expect a few years worth of tests to precede an NDA.

    Item 4. 100,000 people a year die from drugs that are reviewed and approved by the FDA. Kind of a strange statistic if the FDA is erring too much on the side of keeping unsafe drugs off the market.

    This stat is meaningless without knowledge of how many lives were SAVED by approved drugs. Or at least the number treated. It also neglects to account for the many who die for lack of an approved treatment while waiting for FDA approval.

    Item 5. The FDA is mainly concerned with whether a drug is more effective in a controlled experiment than a placebo, not so much with side effects. The FDA is not very aggressive in pulling drugs with bad side effects, and usually only does it in high-profile cases like Vioxx.

    It was Merck that pulled Vioxx. The FDA pulled silicon breast implants. The minor increased risk Vioxx presents is less than most alternative. And some of those alternatives are not options for some people for other medical reasons.

    Item 6. I find it hard to buy drug company claims that they can't make the drugs they need to when their main preoccupation is with duplicating the function of drugs already in the market, obtaining new patents for them that earn them monopoly profits, even for the large number of drugs developed on the dime of the National Institutes of Health, and advertising the duplicative drugs to doctors.

    Frankly, I don't see what your opinion has to do with anything. Drug patents run 20 yrs from filing with usually means that they have 7-12 yrs available after approval. If they make it to that point. So you have to recover all your R&D from this and many other projects that did not work out in a limited timespan where competitors will often release new and better alternatives.

    And what is wrong with advertising? How will anyone benefit from your work if no one knows about it. For several years the FDA prevented manufacturers from advertising the benefits of aspiring in preventing heart problems since it was not approved for that use. How many thousands died from this lack of knowledge? How many have been saved by those adds?

  3. honestpartisan:

    >>Item 1 - I think the point was that what the legal system has been redefining safe to has changed a great deal since then.

    By "the legal system" do you mean the FDA or tort law? If it's the latter, it doesn't support the argument that the FDA should be abolished, which is the subtext that I read. If it's the FDA that's changed it's standards, what's changed? The main change I'm aware of is that, after the thalidomide fiasco, the burden has shifted from the FDA to the drug companies to prove that a drug is safe and test subjects had to be informed that they using an untested drug - which doesn't implicate the standards that have to be met.

    >>Item 2 - So, aspirin, Morphine, Insulin, salvarsan, sulfanilamide were not effective. To Name a few.

    >>Big surprise here. During a period where our understanding of chemistry and biology advanced enormously, we saw enormous advances in chemicals used to treat biologic systems. We knew virtually nothing about modern medicine before 1900. We only discovered germs at the end of the 19th century.

    >>There will always be a tendency to prescribe a newer drug since it was developed to meet an unmet need or to improve apon a previous treatment.

    During the post-1938 period I'm referring to, companies stopped using 90% of the drugs that were previously on the market because they were junk. It doesn't mean that there wasn't 10% out there that was effective. So either the law forced the companies to develop the modern pharmaceutical industry, with its attendant benefits, or at the very least it didn't hinder it.

    >>Item 3. - And the time seems to have risen again based on 2002 numbers.

    >>This also ignores that fact that this is the time it takes AFTER all clinical trials have been completed, since the NDA application must include all the data the company has collected. If the FDA decides you failed to do enough upfront testing, you have to go back and do more. Those are the ones that raise the median. Expect a few years worth of tests to precede an NDA.

    I'm not aware of this, but to the extent it's true it's an argument for tweaking the procedures. I don't know if the definition of "approval time" I'm using is different than yours or not.

    >>>Item 4 - This stat is meaningless without knowledge of how many lives were SAVED by approved drugs. Or at least the number treated. It also neglects to account for the many who die for lack of an approved treatment while waiting for FDA approval.

    You're missing the point, which may be my fault. I was not saying that the FDA is not being strict enough, which is an argument you seem to be responding to. I'm saying that it's hard to make the argument that the FDA is being excessively fastidious about approving drugs and evaluating side effects when 100,000 people die annually from drugs that the FDA has approved.

    >>Item 5 - It was Merck that pulled Vioxx. The FDA pulled silicon breast implants. The minor increased risk Vioxx presents is less than most alternative. And some of those alternatives are not options for some people for other medical reasons.

    Fine, then that doesn't support the abolish-the-FDA argument.

    >>Item 6 - Frankly, I don't see what your opinion has to do with anything. Drug patents run 20 yrs from filing with usually means that they have 7-12 yrs available after approval. If they make it to that point. So you have to recover all your R&D from this and many other projects that did not work out in a limited timespan where competitors will often release new and better alternatives.

    >>>And what is wrong with advertising? How will anyone benefit from your work if no one knows about it. For several years the FDA prevented manufacturers from advertising the benefits of aspiring in preventing heart problems since it was not approved for that use. How many thousands died from this lack of knowledge? How many have been saved by those adds?

    The drug company line is that they need the profits that they get so that they can plow them back into life-saving R & D. So this gets them quardruply subsidized by the government: (1) they get tax credits for R & D; (2) they get to take out patents that piggybacks on work done by the National Institues of Health; (3) they get a patent, a government-sanctioned monopoly that inflates their profits beyond what they would get on the free market; (4) Medicaid - and now Medicare - pays the inflated prices, and is even forbidden by 2003 law from negotiating with drug companies to buy in bulk and thus reduce costs.

    Now, if all of these subsidies produced the wonder drugs that you talk about, they would be worth it. But I dispute that they do. I've seen figures that show that only about 25% of new drugs actually represent advances over what's already on the market. The other 75% replicate what is already out there, albeit with a different molecular structure to regain the monopoly rents that patents confer.

    How can a company get doctors to prescribe drugs that duplicate what cheaper generics can do? Through advertising. Drug companies spend a percentage of their revenues on advertising that dwarves what they spend on R & D, and also is far greater in proportion to what other businesses spend on advertising.

    Now advertising is all fine and good, but it's not really consistent with a claim to a right to all these subsidies under the banner of saving lives through R & D. Not to mention that it belies the claim (to some extent) that vital drugs out there are not being approved.

  4. Otis:

    Just a couple of final points.

    I don't think tha the FDA needs to be abolished. I do think that the system we have tends to err on the side of caution and that lives are lost because of it. I think that the tort system is much to blame for this as is the political reality that when people die from using a drug, you can count them and name them while those that die from the lack of a treatment are harder to name. I was primarily responding to the fact that you seemed to be demonizing the pharmaceutical indrusty, even if that was not your intent.

    For Item 1.
    I would mention that thalidomide was blocked by the FDA. That is one item they did right.

    For item 2.
    The fact that modern pharmaceutical development blossomed in the mid-19th century provides no evidence of the effectiveness of the FDA. I can see little reason to think that it helped and even to say that it did not hinder seems hard to prove. We have no way of knowing how many more useful drugs might have been made available without the added regulatory burden. I don't doubt that it was probably a worthwhile burden. But it is not a certainty that "at the very least it didn't hinder it."

    Item 4.
    Many of the death you refer to are the result of drug interactions. Many of these could have been prevented with better patient management. It is not that the individual drugs caused the problem. It was the failure to notice that they would interact. Often these are know problems but unless you have complete information about what is being taken, there is little you can do about it.

    Item 6. Our Founding Fathers(doesn't that just stir your patriotic heart?) recognized the value of invention and mandated it be protected in the Constitution. Without that protection there would be little reason for private enterprise to fund that sort of R&D. Or if they did, they would hid the results under the banner of trade secrets and try to maintain the monopoly forever. Would it be better to have no drug for treatment at all rather than whet you think of as an overpriced treatment during the patent period?

    I'm not a tax lawyer. I know that R&D is an expense and therefore goes against profits in computing income but am unaware of any tax credit issues. I generally think tax credits are bad policy in that they distort a free market. I also think that piggy backing on government funded research is wrong but take that up with the clown in DC who make it possible and fund the research.

    As for inflated prices, no one is forced to pay them. If you feel that they are exessive, use something else. As you point out, there are many alternatives, many generic and inexpensive. Yes, may drugs treat the same condition and are similar. They almost all have different side effects, effectiveness, interactions and costs. Any informed consumer would ask about these when getting a prescription. But the system we have here has removed most of the cost burden from many of us so that we don't care. Insurance or Medicare pick up the tab. If everyone had to pay out of pocket for the newest and best drugs, you WOULD see better economic use of money in medicine as more generics, that may be oh so slightly less effective, were used.

    And while the drugs may be for the same condition, not all work well for all patients. My wife and daughter, for example, suffer from some severe seasonal allergies. Of the OTC and prescription drug options they tried only one works well. It happens to be a different one for each of them. So if the drug companies did not produce these different drugs, replicating what was already out there, at least one of these women would have no effective treatment.

  5. Netpowersoft:

    Think About Loan, Think About Us!
    Be relevent Be Quick!

    Look for a relevent loan?
    Look for a relevent loan Provider?
    We have BEST solution regarding this in very efficient way.
    Providing Complete info about Loan and Loan Provider!

    http://www.loanskey.com