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Cathy O’Neil: How Big Pharma Cooks Data –The Case of Vioxx and Heart Disease

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By Cathy O’Neil, a data scientist who lives in New York City and writes at mathbabe.org

Yesterday I caught a lecture at Columbia given by statistics professor David Madigan, who explained to us the story of Vioxx and Merck. It’s fascinating and I was lucky to get permission to retell it here.

Disclosure

Madigan has been a paid consultant to work on litigation against Merck. He doesn’t consider Merck to be an evil company by any means, and says it does lots of good by producing medicines for people. According to him, the following Vioxx story is “a line of work where they went astray”.

Yet Madigan’s own data strongly suggests that Merck was well aware of the fatalities resulting from Vioxx, a blockbuster drug that earned them $2.4b in 2003, the year before it “voluntarily” pulled it from the market in September 2004. What you will read below shows that the company set up standard data protection and analysis plans which they later either revoked or didn’t follow through with, they gave the FDA misleading statistics to trick them into thinking the drug was safe, and set up a biased filter on an Alzheimer’s patient study to make the results look better. They hoodwinked the FDA and the New England Journal of Medicine and took advantage of the public trust which ultimately caused the deaths of thousands of people.

The data for this talk came from published papers, internal Merck documents that he saw through the litigation process, FDA documents, and SAS files with primary data coming from Merck’s clinical trials. So not all of the numbers I will state below can be corroborated, unfortunately, due to the fact that this data is not all publicly available. This is particularly outrageous considering the repercussions that this data represents to the public.

Background

The process for getting a drug approved is lengthy, requires three phases of clinical trials before getting FDA approval, and often takes well over a decade. Before the FDA approved Vioxx, less than 20,000 people tried the drug, versus 20,000,000 people after it was approved. Therefore it’s natural that rare side effects are harder to see beforehand. Also, it should be kept in mind that for the sake of clinical trials, they choose only people who are healthy outside of the one disease which is under treatment by the drug, and moreover they only take that one drug, in carefully monitored doses. Compare this to after the drug is on the market, where people could be unhealthy in various ways and could be taking other drugs or too much of this drug.

Vioxx was supposed to be a new “NSAID” drug without the bad side effects. NSAID drugs are pain killers like Aleve and ibuprofen and aspirin, but those had the unfortunate side effects of gastro-intestinal problems (but those are only among a subset of long term users, such as people who take painkillers daily to treat chronic pain, such as people with advanced arthritis). The goal was to find a pain-killer without the GI side effects. The underlying scientific goal was to find a COX-2 inhibitor without the COX-1 inhibition, since scientists had realized in 1991 that COX-2 suppression corresponded to pain relief whereas COX-1 suppression corresponded to GI problems.

Vioxx Introduced and Withdrawn From the Market

The timeline for Vioxx’s introduction to the market was accelerated: they started work in 1991 and got approval in 1999. They pulled Vioxx from the market in 2004 in the “best interest of the patient”. It turned out that it caused heart attacks and strokes. The stock price of Merck plummeted and $30 billion of its market cap was lost. There was also an avalanche of lawsuits, one of the largest resulting in a $5 billion settlement which was essentially a victory for Merck, considering they made a profit of $10 billion on the drug while it was being sold.

The story Merck will tell you is that they “voluntarily withdrew” the drug on September 30, 2004. In a placebo-controlled study of colon polyps in 2004, it was revealed that over a time period of 1200 days, 4% of the Vioxx users suffered a “cardiac, vascular, or thoracic event” (CVT event), which basically means something like a heart attack or stroke, whereas only 2% of the placebo group suffered such an event. In a group of about 2400 people, this was statistically significant, and Merck had no choice but to pull their drug from the market.

It should be noted that, on the one hand Merck should be applauded for checking for CVT events on a colon polyps study, but on the other hand that in 1997, at the International Consensus Meeting on COX-2 Inhibition, a group of leading scientists issued a warning in their Executive Summary that it was “… important to monitor cardiac side effects with selective COX-2 inhibitors”. Moreover, in an internal Merck email as early as 1996, it was stated there was a “… substantial chance that CVT will be observed.” In other words, Merck knew to look out for such things. Importantly, however, there was no subsequent insert in the medicine’s packaging that warned of possible CVT side-effects.

What the CEO of Merck Said

What did Merck say to the world at that point in 2004? You can look for yourself at the four and half hour Congressional hearing (seen on C-SPAN) which took place on November 18, 2004. Starting at 3:27:10, the then-CEO of Merck, Raymond Gilmartin, testifies that Merck “puts patients first” and “acted quickly” when there was reason to believe that Vioxx was causing CVT events. Gilmartin also went on the Charlie Rose show and repeated these claims, even go so far as stating that the 2004 study was the first time they had a study which showed evidence of such side effects.

How quickly did they really act though? Were there warning signs before September 30, 2004?

Arthritis Studies

Let’s go back to the time in 1999 when Vioxx was FDA approved. In spite of the fact that it was approved for a rather narrow use, mainly for arthritis sufferers who needed chronic pain management and were having GI problems on other meds (keeping in mind that Vioxx was way more expensive than ibuprofen or aspirin, so why would you use it unless you needed to), Merck nevertheless launched an ad campaign with Dorothy Hamill and spent $160m (compare that with Budweiser which spent $146m or Pepsi which spent $125m in the same time period).

As I mentioned, Vioxx was approved faster than usual. At the time of its approval, the completed clinical studies had only been 6- or 12-week studies; no longer term studies had been completed. However, there was one underway at the time of approval, namely a study which compared Aleve with Vioxx for people suffering from osteoarthritis and rheumatoid arthritis.

What did the arthritis studies show? These results, which were available in late 2003, showed that the CVT events were more than twice as likely with Vioxx as with Aleve (CVT event rates of 32/1304 = 0.0245 with Vioxx, 6/692 = 0.0086 with Aleve, with a p-value of 0.01). As we see this is a direct refutation of the fact that CEO Gilmartin stated that they didn’t have evidence until 2004 and acted quickly when they did.

In fact they had evidence even before this, if they bothered to put it together (in fact they stated a plan to do such statistical analyses but it’s not clear if they did them- or in any case there’s so far no evidence that they actually did these promised analyses).

In a previous study (“Table 13″), available in February of 2002, the could have seen that, comparing Vioxx to placebo, we saw a CVT event rate of 27/1087 = 0.0248 with Vioxx versus 5/633 = 0.0079 with placebo, with a p-value of 0.01. So, three times as likely.

In fact, there was an even earlier study (“1999 plan”), results of which were available in July of 2000, where the Vioxx CVT event rate was 10/427 = 0.0234 versus a placebo event rate of 1/252 = 0.0040, with a p-value of 0.05 (so more than 5 times as likely). This p-value can be taken to be the definition of statistically significant. So actually they knew to be very worried as early as 2000, but maybe they… forgot to do the analysis?

The FDA and Pooled Data

Where was the FDA in all of this?

They showed the FDA some of these numbers. But they did something really tricky. Namely, they kept the “osteoarthritis study” results separate from the “rheumatoid arthritis study” results. Each alone were not quite statistically significant, but together were amply statistically significant. Moreover, they introduced a third category of study, namely the “Alzheimer’s study” results, which looked pretty insignificant (more on that below though). When you pooled all three of these study types together, the overall significance was just barely not there.

It should be mentioned that there was no apparent reason to separate the different arthritic studies, and there is evidence that they did pool such study data in other places as a standard method. That they didn’t pool those studies for the sake of their FDA report is incredibly suspicious. That the FDA didn’t pick up on this is probably due to the fact that they are overworked lawyers, and too trusting on top of that. That’s unfortunately not the only mistake the FDA made (more below).

Alzheimer’s Study

So the Alzheimer’s study kind of “saved the day” here. But let’s look into this more. First, note that the average age of the 3,000 patients in the Alzheimer’s study was 75, it was a 48-month study, and that the total number of deaths for those on Vioxx was 41 versus 24 on placebo. So actually on the face of it it sounds pretty bad for Vioxx.

There were a few contributing reasons why the numbers got so mild by the time the study’s result was pooled with the two arthritis studies. First, when really old people die, there isn’t always an autopsy. Second, although there was supposed to be a DSMB as part of the study, and one was part of the original proposal submitted to the FDA, this was dropped surreptitiously in a later FDA update. This meant there was no third party keeping an eye on the data, which is not standard operating procedure for a massive drug study and was a major mistake, possibly the biggest one, by the FDA.

Third, and perhaps most importantly, Merck researchers created an added “filter” to the reported CVT events, which meant they needed the doctors who reported the CVT event to send their info to the Merck-paid people (“investigators”), who looked over the documents to decide whether it was a bonafide CVT event or not. The default was to assume it wasn’t, even though standard operating procedure would have the default assuming that there was such an event. In all, this filter removed about half the initially reported CVT events, and about twice as often the Vioxx patients had their CVT event status revoked as for the placebo patients. Note that the “investigator” in charge of checking the documents from the reporting doctors is paid $10,000 per patient. So presumably they wanted to continue to work for Merck in the future.

The effect of this “filter” was that, instead of it seeming 1.5 times as likely to have a CVT event if you were taking Voixx, it seemed like it was only 1.03 as likely, with a high p-score.

If you remove the ridiculous filter from the Alzheimer’s study, then you see that as of November 2000 there was statistically significant evidence that Vioxx caused CVT events in Alzheimer patients.

By the way, one extra note. Many of the 41 deaths in the Vioxx group were dismissed as “bizarre” and therefore unrelated to Vioxx. Namely, car accidents, falling of ladders, accidentally eating bromide pills. But at this point there’s evidence that Vioxx actually accelerates Alzheimer’s disease itself, which could explain those so-called bizarre deaths. This is not to say that Merck knew that, but rather that one should not immediately dismiss the concept of statistically significant just because it doesn’t make intuitive sense.

VIGOR and the New England Journal of Medicine

One last chapter in this sad story. There was a large-scale study, called the VIGOR study, with 8,000 patients. It was published in the New England Journal of Medicine on November 23, 2000. See also this NPR timeline for details. They didn’t show the graphs which would have emphasized this point, but they admitted, in a deceptively round-about way, that Vioxx has 4 times the number of CVT events than Aleve. They hinted that this is either because Aleve is protective against CVT events or that Vioxx is bad for it, but left it open.

But Bayer, which owns Aleve, issued a press release saying something like, “if Aleve is protective for CVT events then it’s news to us.” Bayer, it should be noted, has every reason to want people to think that Aleve is protective against CVT events. This problem, and the dubious reasoning explaining it away, was completely missed by the peer review system; if it had been spotted, Vioxx would have been forced off the market then and there. Instead, Merck purchased 900,000 preprints of this article from the NE Journal of Medicine, which is more than the number of practicing doctors in the U.S.. In other words, the Journal was used as a PR vehicle for Merck.

The paper emphasized that Aleve has twice the rate of ulcers and bleeding, at 4%, whereas Vioxx had a rate of only 2% among chronic users. When you compare that to the elevated rate of heart attack and death (0.4% to 1.2%) of Vioxx over Aleve, though, the reduced ulcer rate doesn’t seem all that impressive.

A bit more color on this paper. It was written internally by Merck, after which non-Merck authors were found. One of them is Loren Laine. Loren helped Merck develop a sound-byte interview which was 30 seconds long and was sent to the news media and run like a press interview, even though it actually happened in Merck’s New Jersey office (with a backdrop to look like a library) with a Merck employee posing as a neutral interviewer. Some smart lawyer got the outtakes of this video made available as part of the litigation against Merck. Check out this youtube video, where Laine and the fake interviewer scheme about spin and Laine admits they were being “cagey” about the renal failure issues that were poorly addressed in the article.

The Damage Done

Also on the Congress testimony I mentioned above is Dr. David Graham, who speaks passionately from minute 41:11 to minute 53:37 about Vioxx and how it is a symptom of a broken regulatory system. Please take 10 minutes to listen if you can.

He claims a conservative estimate is that 100,000 people have had heart attacks as a result of using Vioxx, leading to between 30,000 and 40,000 deaths (again conservatively estimated). He points out that this 100,000 is 5% of Iowa, and in terms people may understand better, this is like 4 aircraft falling out of the sky every week for 5 years.

According to this blog, the noticeable downwards blip in overall death count nationwide in 2004 is probably due to the fact that Vioxx was taken off the market that year.

Conclusion

Let’s face it, nobody comes out looking good in this story. The peer review system failed, the FDA failed, Merck scientists failed, and the CEO of Merck misled Congress and the people who had lost their husbands and wives to this damaging drug. The truth is, we’ve come to expect this kind of behavior from traders and bankers, but here we’re talking about issues of death and quality of life on a massive scale, and we have people playing games with statistics, with academic journals, and with the regulators.

Just as the financial system has to be changed to serve the needs of the people before the needs of the bankers, the drug trial system has to be changed to lower the incentives for cheating (and massive death tolls) just for a quick buck. As I mentioned before, it’s still not clear that they would have made less money, even including the penalties, if they had come clean in 2000. They made a bet that the fines they’d need to eventually pay would be smaller than the profits they’d make in the meantime. That sounds familiar to anyone who has been following the fallout from the credit crisis.

One thing that should be changed immediately: the clinical trials for drugs should not be run or reported on by the drug companies themselves. There has to be a third party which is in charge of testing the drugs and has the power to take the drugs off the market immediately if adverse effects (like CVT events) are found. Hopefully they will be given more power than risk firms are currently given in finance (which is none)- in other words, it needs to be more than reporting, it needs to be an active regulatory power, with smart people who understand statistics and do their own state-of-the-art analyses – although as we’ve seen above even just Stats 101 would sometimes do the trick.

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118 comments

  1. Jim3981

    Thanks for the article. However, it is the tip of the iceburg.

    “We are a group of citizens who are disturbed by the increasingly failing health of those in our society. Among us are those who have been injured by the medical industry, those with children or loved ones who have been harmed and killed by the medical industry, medical professionals who are upset with what is happening in their field and those who endeavor to preserve human health in spite of increasingly corrupt and failing medical establishment.

    In 2010, a group of parents of children who were suffering from neurological and autoimmune disorders, and who had been active for years in their efforts to get mainstream medicine to address the causes of, and find treatments for, their children’s poor health, faced the realization that while they had been earnest in their engagement of both the private medical industry and government public health officials, the medical establishment was not working in good faith with them. They decided that if anything was to be done about the epidemic levels of childhood chronic illness in the US, it would have to be a result of real political pressure to clean up the corruption in the medical establishment that was allowing bad pharmaceuticals, bad medical practices and bad public health policy to assault human health on such a wide scale.”

    http://www.canaryparty.org/

    1. John L

      Tip of the iceberg it is. But Andrew Wakefield’s work linking vaccines to autism is part of the iceberg – a fraud.

      The problem with big pharma’s war on truth is that it lowers the bar for everybody.

      1. dearieme

        You’re letting Wakefield off far too lightly by blaming his misbehaviour on Merck. You might as well say that Merck behaved badly because so many Presidents of the USA behaved badly. Let’s all blame JFK. That way madness lies.

          1. Sharon

            LOL! John L is trying to bring Dr. Wakefield into a discussion because he has been pharma’s scapegoat for a decade now. Dr. Wakefield has filed a defamation lawsuit against Brian Deer, the British Medical Journal and Fiona Godlee in Texas for a January 2011 article they published. I hope he wins so that it will shut them up for good.

            Watch Hot Coffee…this is what is going on with Wakefield. Pharma is using him relentlessly so they can continue to poison with impunity. No one in their right mind believes vaccines are benign anymore and pharma is trying too hard to cover it up so they use Wakefield to divert attention away from vaccine safety because they know they can’t win that discussion.

    2. Joel3000

      We don’t know what the story is on vaccine safety because anyone in a position to do meaningful research on the subject will be severely bullied and harrassed if they should dare to say anything beyond “they’re perfectly safe, move along folks. ”

      Researchers are smart enough to know which questions will get them into hot water with their funders. There has been no open scientific debate on vaccine safety.

      1. hyperpolarizer

        I am an active biomedical researcher by profession, although not an immunologist — but with decades of post-doctoral experience. On the one hand I believe that immunology is the poetry of Western medicine; on the other hand it is highly non-obvious to me that an infant’s immune system can reliably withstand the challenge of multiple vaccinations, such as now are given as a matter of course. There is also the question of the safety of the fluid media used.

        What I can most reliably state is that it is heresy and apostasy to raise such questions within my professional cohort.

        1. JamesW

          Both you and Joel3000 make some outstanding points, and believe there are now at least several studies extant which correlate to the amount of immunizations given to babies under 1-year of age, and the relation to autism.

          Another contributing factor is the cutting of costs in vaccine manufacture by offshoring the work, then subcontracting and subcontracting to where there is little or no actual oversight.

          Then there are those peculiar accidents of Baxter Pharmaceuticals and Baxter International, seemingly occurring like clockwork, whereby they ship out contaminated vaccine samples to labs around the world, in spite of those Bio Safety Level III protocols, etc.

          A number of variables and factors.

          And that recent article in Sweden concerning the swine flue vaccine and narcolepsy cases???

        2. LeonovaBalletRusse

          Why not go the *Republican* Authoritarian route, as in my day (I nearly died of rubella): Don’t vaccinate, let the virus swarms come in turn, and *let God sort it out*.

          My generation had to *tough it out* in childhood. We may live to 100 or more. Itsn’t it *God’s will*? Let them have their way, but while IN QUARANTINE.

        3. just me

          Can anyone tell me if this anecdote is true or not? The Amish don’t vaccinate and their children don’t get autism.

      2. joel3000

        I am a researcher myself, although not in any sort of biological science.

        I am free to research whatever I want in my field, provided I can get someone to fund it. That severely limits the boundaries of what can be researched.

      3. Francois T

        “We don’t know”?
        150 million dollars and 5 large scale international studies aren’t enough? How much more will we have to spend to make people look at the goddamn data, not what they think the data should be?

        Wakefield was a fraudster who did what he did in cahoots with lawyers for 2 alleged “victims of vaccines”.

        1. joel3000

          Vaccines are $20+ billion dollar annual business.

          $150 million in studies over 5 years = $30/million year. It is a tiny fraction of the business.

          Studies can be easily manipulated by the choice of researchers and funding rules. Once again, a researcher who dares question the safety and efficacy of vaccines will be viciously attacked from multiple fronts.

          The studies that need to be done to truly validate the safety of vaccinations have not been done.

          1. Sharon

            And I might add that the insurers know what is going on and they have the data. It’s only a matter of time now that the truth will come out. Before I was poisoned by pharma I use to look at massive amounts of data and I could make it speak to an audience and tell stories. Claims data is rich in answers as to what is making our children sick and now 20 of the largest employers will be looking at combined claims information as well as claims information from Medicare. The data doesn’t lie and because health insurers and employers profits are directly impacted by the mass poisoning that is going on they will get to the bottom of what is causing disease where conventional medicine has failed. When a hypothesis presents itself you can bet there will be follow up studies. Remember pharma’s profits inversely affect the profits of self-insured employers and health insurance companies so I’m confident we now (those of us that are pro-vaccine safety and choice) will get the answers we so richly deserve.

  2. Jim3981

    “As with anything that changes current-day paradigms, Burzynski’s ability to successfully treat incurable cancer with such consistency has baffled the industry. Ironically, this fact had prompted numerous investigations by the Texas Medical Board, who relentlessly took Dr. Burzynski as high as the state supreme court in their failed attempt to halt his practices.

    Likewise, the Food and Drug Administration engaged in four Federal Grand Juries spanning over a decade attempting to indict Dr. Burzynski, all of which ended in no finding of fault on his behalf. Finally, Dr. Burzynski was indicted in their 5th Grand Jury in 1995, resulting in two federal trials and two sets of jurors finding him not guilty of any wrongdoing. If convicted, Dr. Burzynski would have faced a maximum of 290 years in a federal prison and $18.5 million in fines.”

    http://www.burzynskimovie.com/

    1. John L

      Other researchers have failed to reproduce his results. Just because big pharma’s corrupt doesn’t mean Burzynski’s not a fraud.

    2. Nancy

      Burzynski and the movement getting behind his cancer treatment claim to be against the burn, cut, radiate methods of Western cancer treatment in favor of something he calls antineoplastons.

      But if you look at the testimonies of his own patients on his web site, they talk about going through a “mild chemotherapy” in conjunction with his own treatment.

      1. Francois T

        Is that the way you dismiss views that are contrary to yours? Just label them “special interests for big pharma” and we’re done.

        Classy!

        1. Jim3981

          I see these characters every day on the web. They masters of deception.

          Anybody else who uses social media, and reads commentary from ordinary people understand what I am talking about. This has been proven time and time again.

      2. John L

        Jim, I just call out frauds and liars. I don’t care if they’re called Merck, Wakefield, or Burzynski.

        1. JamesW

          Awhile back I read (sorry, forget where now) that something like two-thirds or three-quarters of studies are funded by lobbyist groups??? Regarding some type of drug category?

        2. Sharon

          John L I don’t believe you like I don’t believe GE telling us that injecting a toxic heavy metal(Omniscan and other GBCAs)so that their multi-million dollar equipment can get pretty pictures while poisoning the patient population was true. The frauds by pharma are legendary and not even comparable. It’s a nice try on the spin but I for one am not buying it.

          1. LucyLulu

            Sharon,
            I won’t deny that Pharma does not attempt to cover-up their mistakes in attempts to avoid liability, or sometimes, even to maximize profits. Irregardless, I don’t think that anybody should assume that putting ANY foreign substance into their body is risk-free. As always, it should be a decision based on perceived risk-benefits. Tylenol, used on a regular basis, is hepatotoxic and can prove fatal. This includes the alleged “all-natural” remedies (which have even less oversight and ingredients can vary substantially from what the label claims). Recall that cocaine, heroin, strychnine, and hemlock are examples of “all-natural” products that are far from safe.

            Omniscan has caused serious issues for some with severe renal disease. It’s used as contrast media in MRI’s. IMO, we do too many MRI’s in this country, unnecessary MRI’s. If we had a 60 day waiting list for MRI’s, many would be cancelled due to spontaneous recovery. But patients are impatient and want immediate answers and the latest technology. Physicians are all too willing to appease them. (I’m not implying those who had issues with Omniscan fall into this group. I assume, or I hope, that their compromised renal function would have been considered and resulted in a higher perceived risk/benefit ratio.)

          2. Sharon

            LucyLuLu

            “Omniscan has caused serious issues for some with severe renal disease.”

            I’m afraid you are not correct, you do not need severe renal disease or for that matter renal disease to get gadolinium induced systemic fibrosis sometimes called nephrogenic systemic fibrosis. One can be dehydrated, have acute kidney injury (which can occur after the exam and cannot be pre-tested) or zinc or iron overload which causes the disease when the chelate used breaks away from the gadolinium because it has a preference for the zinc and iron and leaves the gadolinium in its free toxic state. At least 1% of every dose is retained and some doctors believe an epidemic is emerging and millions will need to be followed. In addition the amount of the dose and the time between doses all impact the severity of the disease but one thing is certain retaining 1% of each dose is toxic to the body and even if the injury rate is only 10% the additional cost in healthcare is in the trillions.
            By the way they are finding gadolinium in brain tumors and the reproductive organs of men and women of childbearing yeats.

          3. John L

            Please don’t believe me. Don’t believe anyone. Educate yourself and evaluate the facts as best you can. Evaluating the facts as best I can tells me that all three of the parties I mentioned are frauds and liars either in covering up side effects, claiming “cures” work, or claiming links that don’t exist. If you reduce this to who you believe rather than what you understand then you’re entering yourself in a gullibility contest.

  3. Klassy!

    The thing about the ad campaign is that it really did seem to present the message that these drugs were more effective at treating pain. More than a few people told me that they had to have celebrex because it “worked better”. I tried to explain that the chief benefit of the COX2 inhibiting NSAIDS was that they protected the gut. As it turns out they really didn’t do that much of a better job– perhaps the risk reduction was presented in relative rather than absolute terms in the ad campaign?
    At any rate, there was no real reason that they should be more effective with pain than ibuprofen. Still, pain is subjective so I guess if someone is under the impression that an analgesic is more effective, it may well become more effective.
    But yes, this is a most excellent example of why we need a publicly funded drug trial system.

  4. Fraud and Death Admin Inc

    “A serious side effect of this drug was shown to be liver failure. Signs of impending liver failure include a loss of appetite, an upset stomach, or a jaundicing (yellowing) of the skin and eyes. Two women who had taken Serzone for just 14 to 28 weeks had such severe liver damage that they suffered liver failure and needed immediate transplants. Serzone Lawsuits have been filed charging that Bristol-Myers Squibb Company (Serzone’s manufacturer) knew and ignored the life-threatening aspect of their drug. “

  5. Joseph j7uy5

    It is important to note, also, that the mortality related to Vioxx would have been much smaller if physicians had not engaged in off-label prescribing. Off-label prescribing is appropriate in many circumstances, but it should be done cautiously, if at all, with new products.

    1. John L

      A former family doctor told me that he, like most others he knew, got most of his continuing education from pharmaceutical companies. Off label use is a known side effect.

    2. MB

      A good “fictionalized” account of off label prescribing is seen in the movie “Love and Other Drugs”. The other drug referred to is Viagra. The movie is a story of a woman with a progressively disabling condition and her pharma drug salesman boyfriend and his sales process and relationship with a doctor friend. I can only say that the feeling I got from the pharma scenes felt accurately portrayed. It should give anyone pause when you look up the info on any new drug your MD suggests you take.

      1. jake chase

        The sad truth about Pharma is quite simple: drug studies are manipulated to gain FDA approval; the FDA is another alphabet agency staffed by bureaucrats asleep at the switch; drugs are approved as safe without anything resembling common sense caution; Americans are brainwashed to seek medical attention for every ache, pain, reduction in function, mood change, you name it. All these drugs are a ticking bomb on the one hand and a monopolist wet dream on the other. The moral is simple. Exercise sensibly, watch what you eat, avoid drugs. When you reach middle age, take a daily aspirin. A daily ounce of whiskey is also good. Something will kill you, but at least it won’t be organized medicine.

        1. LeonovaBalletRusse

          jake, none of this will stop, until the Health Care System is NOT for profit. The *for profit* System is the result of the “SHOCK DOCTRINE” imposed on the sly.

  6. voislav

    This is typical of the pharmaceutical industry today. Developing new drugs is increasingly risky, because not only do they need to work, they need to work better than what’s already on the market. With all the low hanging fruit gone, the failure rate for new drugs is steadily increasing and the patent clock on the old ones keeps ticking. It’s a deeply flawed business model, wholly reliant on blind luck.

    1. Klassy!

      That is an exellent point. Many of these new drugs do not work any better than older drugs. Older drugs also have the advantage that they have a longer track record and side effects are more well known. And, they are available as generics– something pharmaceutical companies do not see as an advantage, of course.

      1. JamesW

        Yes and aren’t there a number of cases now where only a slight, molecular change was made to an old drug so it could pass FDA and be marketed as a new drug???

        1. Sam

          Yep, Prilosec and Nexium. First one was already on the market. Second one is exactly the same except for an atom or molecule or two. Ginned up completely for profit to the drug company.

  7. Mark

    “But yes, this is a most excellent example of why we need a publicly funded drug trial system.”

    A worthy goal but it won’t change the following set of facts:

    “The process for getting a drug approved is lengthy, requires three phases of clinical trials before getting FDA approval, and often takes well over a decade. Before the FDA approved Vioxx, less than 20,000 people tried the drug, versus 20,000,000 people after it was approved. Therefore it’s natural that rare side effects are harder to see beforehand.”

    The above is true for all drugs and would continue to be true even with publicly funded trials. Bottom line: Unless a new drug has the potential to save your life, don’t take it until it’s been on the market for at least a year, maybe more.

    The problems with drugs like Vioxx and Fen-Phen is in the cheating that goes on in the post-marketing surveillance programs that look for those rare side effects. I would advocate that the taxpayer take over that part of the process (as well as stronger penalties for marketing for unapproved indications).

  8. Lambert Strether

    Madigan thinks Merck isn’t evil? One can only wonder what he thinks is evil. And how much of it there is.

    * * *

    If the peer review system is, well, let me just say broken, then where do we go? Very few of us have time to assess the claims made in (say) vaccination studies, and the world is full of delusional constructs into which people have put immense labor (including defending them). Not all such constructs are paid for by corporate money, either.

    So how do we get beyond “he said”/”she said” on this? It seems like the best answer is to wean ourselves from Big Pharma entirely (in fact, Big anything) but that doesn’t work for somebody seeking help now….

    1. Jessica

      This looks like a good candidate for another area where we could start building the next society now. There is clearly a need for honest examination of everyone’s data, Big Pharma’s and alternative medicine’s too. The current society can not meet this need.
      Although honest and transparent data will probably need to be kept offshore to protect it from the copyright Stasi.
      (Oh and I did mean to keep this short, but when you see laws being passed in the name of anti-piracy, please understand that they will be used to suppress honest information about medical issues in order to protect dishonest/negligent information.)

    2. JamesW

      And wasn’t it Kaiser Permanente who was aware of Vioxx, yet didn’t sound off about it because they felt they weren’t “incentivized to”????

      Evil, indeed!

  9. Sharon

    I too was poisoned by Pharma. I had many MRIs with gadolinium based contrasting agents (GBCAs) and there are literally hundreds of studies showing that these products are neurotoxic, nephrotoxic and a known carcinogen and they are still injecting them into people. They are finding gadolinium in the reproductive organs and in the brain tumors of those that have had studies with contrast. The two worst products are Omniscan (GE) and Magnevist (Bayer) in the US. Over 300M bolus doses have been administered since 1988 and of each dose at least 1% is retained. Recently a group of doctors including Shawn Cowper, the gatekeeper of the NSF registry at Yale came out with guidelines on diagnosing NSF “Nephrogenic systemic fibrosis: Clinicopathological definition and workup recommendations”. They reported no conflicts of interest and yet the very companies that are being sued sponsored the paper like Bayer Healthcare and GE Healthcare. They made the guidelines so restrictive that most that are ill will go without a diagnosis pushing the cost of this disease on the government and health and disability insurance companies. The scam doesn’t stop there once disabled, patients can’t get treated and are left to die. No diagnosis no disability and no healthcare.
    Another said that this was the tip of the iceberg and he was right. Conventional medicine has become predatory and we are just profit centers. They want us consuming their products from cradle to grave. But who pays for the mass poisoning of the population? It is you and I and all other insurance premium payers and again as tax payers. Predatory healthcare must be stopped.

  10. 700 Lobbyists Plus

    Big Drug far exceeds the crooked Military Industrial Goon Complex as the biggest defrauder of the Gubb’mint based on payments obtained under the False Claims Act.

  11. softowl

    POSTULATED: Vioxx was only used by the elderly, who are the ones with arthritis.

    THEREFORE: Withdrawing it from the market can only have a negative impact on society, since those old people will live longer; voting for republican presidents, and sucking money out of social security.

  12. Patrick

    When you take into account Big Pharma’s lobbying to make sure Americans continue to pay the highest prices for drugs in the industrial world (Billy Tauzin and Obama’s back room deals), their marketing on television of drugs that have limited or no improvement over older (cheaper) generic versions, and the patent games they play in order to dodge generic competition I would say evil is close to appropriate.

  13. Jessica

    We as a society need a completely different way to deal with information. We need to appropriately reward those who find and spread useful information, but we also need to let the information flow as free as possible. Free flow of information includes transparency.

    Pharmaceuticals are perhaps the most extreme example of how inherently dysfunctional it is to deal with information using the rules and social patterns developed for dealing with things. Pharmaceutical companies are paid nothing for the real work they do (= part of the research for finding new drugs), but in return they are allowed to charge monopoly rents for the part that is usually comparatively easy (the manufacturing). On top of that they use advertising (ie deliberately deformed information) to warp decision making by both medical personnel and patients. But under our current system, for them to do anything less would be neglect of their fiduciary responsibility to maximize profits.
    Clearly, we are not facing the invisible (infallible) hand of Mr. Market but rather a pair of rotting zombie hands groping for our necks.

      1. PunchNRun

        Also nicely put. We have created this legal fiction — the corporation — and charged it with maximizing financial gains. The result is that they run amok, destroying everything in their path like runaway bulldozers, in a blind rage to make profit. It does not have to be like this. Where does it say that corporations must have no social responsibility? Might there not be some way to dilute this single motivation by adding qualities into the mix?

        It seems that external entities and influences such as the legal framework are having little impact. They have become impediments to be avoided or destroyed rather than the charts needed to navigate the waterways.

        Perhaps corporations should have finite lifespans. Else the cancerous growths eat the entire organism, and the resulting monster destroy what it was created to support.

        1. Jessica

          I think that corporations of anything like the power of the ones we have now will always try to alter the rules to their own benefit. They are like black holes altering the very fabric of space-time.
          It may be that the only lasting solution will be a much more even distribution of money and power than would be possible with anything like our current corporations, even if we tried to give them missions other than profit.

          1. PunchNRun

            But even now there is such a thing as a non-profit corporation. Certainly there are issues with runaway salaries for C-level staff, but that may be largely spillover from the standard versions.

          2. JamesW

            Back in the early 1900s, Louis Brandeis successfully identified the “black hole” that small group who owned everything!

            Today, they have successfully confused and befuddled people into not realizing just how important this is.

            Who actually owns JPMorgan Chase, BP, GE, Goldman Sachs, the rest of the banks, oil companies and pharmaceuticals?

            Quite probably the very same — with just a few changes — of people!

  14. Hondo

    Regulators have let the citizens down in every industry…why in fact do we need them and the cost associated with them. Buyer beware is all you need.

    1. Jessica

      I would vastly prefer to live in a society where I can get reliable data. I can’t do that on my own. I need some kind of social structure to help me.
      We live in an information-driven society in which our deepest social structures all but require that many different actors block or pollute the information flow. Regulators are hardly the only malefactors in this regard.

    2. nonclassical

      regulators don’t have to “let us down”-when they are reduced by 90% by bushitters…one remaining field biologist in Western Washington beyond bush..

  15. F. Beard

    Meanwhile, opiates are far safer but we mustn’t allow people access to drugs that might make them feel good? Cause God would not approve?

    Give strong drink to him who is perishing,
    And wine to him whose life is bitter.
    Let him drink and forget his poverty
    And remember his trouble no more.
    Open your mouth for the mute,
    For the rights of all the unfortunate.
    Open your mouth, judge righteously,
    And defend the rights of the afflicted and needy.
    Proverbs 31:6-9 New American Standard Bible (NASB)

    1. Susan the other

      Hello again Beard. I was just thinking the same thing. Opiates. Well, legalizing opiates might interfere with my favorite industry – the alcohol industry. But when I reach the point where I can no longer trick myself out of pain, I will want some refined, standardized, effective opiate. And I do not understand why people who suffer nerve pain, and other intractable forms of pain should not have opiates. It is unconscionable. Especially in view of the fact that we probably just cornered the opium trade in Afghanistan.

      1. F. Beard

        Ironically, I don’t enjoy alcohol much and am allergic to morphine. However, with a few amphetamines I can usually ignore pain and amuse myself by counting the ridges on a box of checkers, for example. :)

        No, I don’t recommend drugs for amusement but there is a lot to be said for letting adults get their fill of them, learn their limitations and move on.

  16. EmilianoZ

    This is one of the greatest posts I’ve read on NC.

    This is general problem. Everybody in every walk of life has realized that it pays to game the system. Is it how societies collapse?

      1. JamesW

        That was truly a brilliant, and short, book by Ms. Jacobs (sadly she passed) and she brilliantly dealt with, and dispatched, Jared Diamond is just several sentences.

        Only one error in the entire book: when she made that unfortunate assumption that American foreign policy (economically speaking) was accidental, and not a purposeful design — which those of us activists who have diligently studied USAID, OPIC, etc., know to be true — as those Wall Streeters who bounce back and forth between The Street and those aid agencies, just like they bounce back and forth between Treasury and The Street, are there for the very same reasons.

    1. Nyeve

      EmilianoZ asks “Is it how societies collapse?”

      I’m not sure this really answers that question, but I’ve recently discovered Secular Cycles by Turchin and Nefedov, and they have a model where the common population and elite population go thru a boom and bust cycle, but the elite population’s peak happens later. While the common people see that a peak has occurred, the elites are experiencing a ‘golden age’. Right at that point there is a fundamental disconnect between what the elites experience versus what the common people experience. Now, their model applies to agrarian societies, and but still seems relevant.

  17. Ashley

    I researched this “cooking” of data for a paper in university. It really is startling what drug companies are allowed to get away with. So much seems to be unregulated or at least overlooked or skewed. Many people seem to think that research is objective. They hear about a study and think that the “evidence” is absolute. Infallible. Your post is so clearly written and is such a thorough analysis of the issues, that those people (consumers, journalists, etc.) will rethink “evidence” and will analyze research methodologies before sharing or believing information is fact.

    I fully support your call for third-party testing and market removal.

    1. Klassy!

      This also speaks to the limits of the use of evidence based medicine. If you are relying on a meta analysys of garbage studies, you’re going to get garbage.

    2. Susan the other

      Third party testing would definitely be good. And it would/will create lots of new jobs. And also lots of innovation for the field of “testing.” For instance, with third party testing we might actually get the questions we need to fix the failure and create the answer.

  18. Robert Callaghan

    So Crazy It Might Work Dept.

    Breaking Bad –
    How to Topple Banks and Oil Giants

    by Robert Callaghan

    Green energy proponents fail to understand why the poor and soon-to-be-poor middle class don’t want a bird in the bush for the two in their hand. Money is dirty energy producing C02, C04 and N20. That’s how we live. The Greens want a massive wealth transfer from rich to poor – not bloody likely. Let’s end the standoff, there is another way.

    Banks use the American dollar as the world reserve currency for protecting Gulf oil fields. Their greatest fear is loss of the U.S. dollar as a hegemonic power. If we #occupy a new electronic world currency, we can beat the banks and oil giants at their own game. Bitcoin has already become a new world black market sensation. After all, what is money except little blips on computers. Money is electronic. It has a value because the world agrees it does. The new currency would be democratic and open based on the production of green energy. If green energy is bought and sold in a new world electronic currency, we could start a new gold rush. We could also use this currency in trading organic food. But, we have to get started.

    We are standing the middle of the collapse of a failed economy based on the private creation of currency and credit. It’s time to grow up and leave the old world behind. The alternative is an endless war of attrition in retreat to the poles.

    1. Susan the other

      But don’t you have to sign up in dollars and other currencies to establish an account in Bitcoin? And then when you cash out, you take some currency in exchange? Still don’t get how it works.

      1. ArmchairRevolutionary

        Bitcoin does not make sense to me either other than that it is a different form of fiat currency except that it cannot be legally used for anything. I would be interested in Bitcoin if monies given to Bitcoin were transferred into rolling diverse commodities futures; thus, instead of a fiat currency it would really be a store of value.

        1. F. Beard

          Bitcoin is a fixed money supply based on the Austrian theory that prices should adjust downward to meet a fixed supply of money. It is a hoarder’s dream and thus an economic nightmare.

          1. Lidia

            There’s a fixed supply of resources at any one time, why not a fixed supply of money?

            The money supply should decrease according to resource diminishment to be coherent.

          2. F. Beard

            There’s a fixed supply of resources at any one time, why not a fixed supply of money? Lidia

            One reason is a fixed money supply rewards risk-free hoarding. But progress requires risk-taking so a fixed supply of money would tend toward economic stagnation or worse.

          3. F. Beard

            The money supply should decrease according to resource diminishment to be coherent. Lidia

            You conflate economic growth with resources.

          4. ArmchairRevolutionary

            It is like a reverse Ponzi. Instead of an ever increasing number of items, there are the same number of items ever divided. So, if I join the reverse Ponzi today and more join tomorrow, they will pay more; not because the fiat they pay with has devalued, but simply because there are more participants dividing the stack. Hence, it is a Ponzi of sorts. Same logic applies to gold.

            Apologies to all of you on topic posters, but I find this subject most interesting.

          5. F. Beard

            but I find this subject most interesting. ArmchairRevolutionary

            Ethical money creation is a fascinating topic but the solution was implied nearly 2000 years ago in Matthew 22:16-22 – government money for government debts (plus voluntary usage for private debt) and private money good only for private debts.

            Excellent observation that Bitcoin and gold are a sort of a Ponzi scheme.

  19. KingSalomon

    The conclusion suggest a third party and should mention a public, not for profit third party. We have experienced first hand the failure of financial rating companies to do their jobs while preserving their market share and their profits.

  20. Wade Riddick

    I was once on Vioxx. I experienced horrendous pain during that period. While the cardiovascular deaths that resulted from the Vioxx fraud were certainly bad, they pale in comparison to the ongoing damage caused to autoimmune patients by the entire class of COX-2 inhibitors still on the market.

    COX-2 inhibitors block the synthesis of prostaglandins in the body like PGE2 and PGD2. These short-lived chemical messengers can trigger pain and inflammation but they are also responsible for fighting infection, rebuilding damaged tissue via stem cell mobilization and training the immune system to tolerate innocuous antigens. This later function has been known since the 1990s, but research published in 2005 by Baratelli et al. and Sharma et al. explicitly proved for the first time that prostaglandins control regulatory T-cell (Tregs) behavior and COX-2 inhibition impairs these cells.

    While COX-2 inhibition is good for fighting tumors that use Tregs to escape immune system surveillance, it’s counterproductive and even harmful in patients who are already autoimmune – like those with rheumatoid arthritis, to whom drugs like Celebrex are still advertised. Patients can become allergic, autoimmune and asthmatic in the first place when these Tregs don’t function properly (i.e., the hygiene hypothesis). This is, in fact, one of the common side effects of successful chemotherapy – the body continues attacking itself long after the cancer is go anyway.

    Let me restate this in simpler terms. Drugs like Celebrex and Advil are advertised to autoimmune patients because they’re supposedly great for rheumatoid arthritis but then these same companies turn around and push these drugs on cancer patients exactly because they make them autoimmune.

    Which is it?

    These drugs are good for autoimmune patients because they cure autoimmunity or they’re good for cancer patients because they cause autoimmunity?

    We’ve known with certainty for eight years now that the later answer is the correct one – yet physicians continue to prescribe these drugs to autoimmune patients and drug makers continue to advertise them.

    How many people need to die before this stops?

    In case you thought this was an obscure fact, a search on Pubmed this morning turned up 68 hits going back well beyond 2005.

    For those with allergies, asthma, autoimmunity or other conditions caused by depressed Tregs, using omega-3 fish oils shunts the production of prostaglandins produced by the COX-2 pathway to a more beneficial form. It turns out we’ve given ourselves these health problems by pushing omega-6-rich food oils which displace the omega-3s, causing chronic inflammation. These kinds of oils derived from corn, safflower and soybeans are supported by our tax dollars via farm price supports, which in turn bring in campaign contributions. I believe a similar cycle has kept the FDA from acting to ban the use of COX-2 inhibitors to treat chronic pain and inflammation in autoimmunity.

    A company pled guilty to this Vioxx fraud. If companies are people too, why aren’t they in prison for these deaths? A drunken trucker who mowed down hundreds of people would certainly get jail time.

    All my family is left with are horrendous medical bills.

    1. tert

      “one of the common side effects of successful chemotherapy – the body continues attacking itself long after the cancer is go anyway”

      You are describing immunotherapy, not chemotherapy. Most tumors are treated with chemotherapy (which typically suppresses immune response) although immunotherapy is becoming more common. But what you say is factually incorrect — chemotherapy does not induce any autoimmune response. And I’m not so sure that this is such a “common side effect” of immunotherapy either.

  21. Hondo

    It shows you could really die by someone cheating the system for money and lacks regulatory over-site that gives people a false sense of security. One should always take the buyer beware attitude…do research yourself to the extent you can and always remember the distribution curve is not Gaussian and can be shifted on purpose for profit…..

  22. LAS

    “Second, although there was supposed to be a DSMB as part of the study, and one was part of the original proposal submitted to the FDA, this was dropped surreptitiously in a later FDA update. This meant there was no third party keeping an eye on the data, which is not standard operating procedure for a massive drug study and was a major mistake, possibly the biggest one, by the FDA.”

    I would agree with this and take it further. The Data Safety and Monitoring Board is for the safety of human subjects in human subjects research. Without this, the clinical trial should not have been permited to continue. We need to know more about what happened here. The DSMB is the cornerstone of a clinical trial among humans.

  23. LD

    Okay, my last post was censored. How about Dr. Paul Craig Roberts words, the former US Assistant Secretary of the Treasury for Economic Policy:

    “Washington would “continue to emphasize what we believe is the importance of realizing the aspirations and rights of all people.”

    Think about that for a minute. Washington is now in the second decade of murdering Muslim men, women, and children in six countries. Washington is so concerned with human rights that it drops bombs on schools, hospitals, weddings and funerals, all in order to uphold the human rights of Muslim people. You see, bombing liberates Muslim women from having to wear the burka and from male domination. 

    One hundred thousand, or one million, dead Iraqis, four million displaced Iraqis, a country with destroyed infrastructure, and entire cities, such as Fallujah, bombed and burnt with white phosphorus into cinders is the proper way to show concern for human rights. 

    Ditto for Afghanistan.  And Libya. 

    In Pakistan, Yemen, and Somalia Washington’s drones bring human rights to the people.

    Abu Ghraib, Guantanamo, and secret CIA prison sites are other places to which Washington brings human rights. Obama, who has the power to murder American citizens without due process of law, is too powerless to close Guantanamo Prison.” http://www.paulcraigroberts.org/

    Noticing a US malfeasance pattern yet?

  24. Dave of Maryland

    I thought about the Mess in Medicine, what to do with it, and I came to the following conclusions:

    There is too much money in medicine. In particular, too much money in the med schools. Good ‘ole American hucksterism hard at work. There are many effective household remedies (back in earlier centuries they were collected into popular “cookbooks”), virtually none of which are known today.

    Why? Because patent medicine salesmen (today known as Big Pharma) saw an opportunity to make a profit. You don’t want that cheap home-made remedy, they said. You want our pure, distilled, concentrated version instead. Yes it costs more (and makes us lots of money) but you’ll be better off.

    Push that five patent generations down the road and the results are drugs of marginal effectiveness that will kill you. It’s also a medical community so dumbed-down they think medicine can only come from a big factory. NOT TRUE.

    One of the very best books on medicine, in general, is the Smith’s Family Physician, published in Canada c.1872. (There is a modern reprint from an obscure house.) It was the Physician’s Desk Reference (PDR) of its day and, for my money, is still superior. Why isn’t Smith’s better known? Well, you know, it’s OLD and has funny names in it (“quartan ague,” can you believe that?!!) and well, we do better now. We’re more modern, but before you swallow that, get a copy, read it and then tell us what you think. You can find it on-line via Google Books, if anyone is interested. People are still people, and disease is still disease. Remember the patent medicine boys have an interest in promoting imaginary new-fangled ailments, and have done so with abandon.

    In 1901, Brother Aloysius, Dutch monk who had ministered for some decades, published Comfort to the Sick, which was translated and published by Samuel Weiser in 1998 as A Healer’s Herbal. He was a student of Monseigneur Kneipp. His book is full of healing recipes, many using common household ingredients.

    For epilepsy, Aloysius gives eight recipes, ending with two spoonfuls of olive oil mixed with sugar, taken daily. Which to his amazement, worked better than any of his fancy formulas. (And which, by the by, has been intensely studied in recent years.) Elsewhere he has formulas for breast cancer, with a patient who made a recovery even though the breast had been eaten to the bone (no. 12 on pg. 30).

    The solution is obvious: We need a crusader, a Ralph Nader, a member of the medical profession, preferably a resident at a major teaching hospital, who will make a comprehensive survey of what DOES and DOES NOT work, and will survey not only the current literature, but will go back to AT LEAST 1500 AD. At the same time he should make full use of Astrology, because without Astrology medicine is entirely in the dark and has no hopes whatever. I have personally spent the past year running rings around Johns Hopkins Wilmer Eye Clinic. A greater bunch of fools (albeit sincere fools) I have rarely seen.

    Indeed, the current medical malaise can be traced directly to the removal of Astrology from society some 300 years ago. Even then there was a clear split, between regular doctors who stumbled from one disaster to another, and their despised brethren, the astrologers, who, even then, were excluded from the exclusive club. One notable late 17th century astrological doctor from Reading, England, Joseph Blagrave, achieved notable results merely by harvesting his herbs at sunrise on the appropriate days of the week. He would have practiced in London to much greater acclaim and success, but that a doctor’s license was denied to him because he was an astrologer. A lot of 17th century astrologers, in fact, made their fortune with horary (“lost and found astrology”) in the big cities before retiring to the countryside as itinerant doctors.

    The primary differences between the late medieval and the modern world is that we’re a lot richer and they were a lot smarter.

    We don’t need more crappy drugs. We don’t need more expensive trials. (Well, we badly need court-type trials.) We need a comprehensive survey of WHAT WORKS.

    Will this ever happen? I want to say not a chance in the world, but then I think of Ralph. Even in America, where a civil war to end slavery largely failed, miracles are possible.

    1. Mel

      For one example, Smith’s not very good on cholera. He’s still blaming it on the quality of the air, advising measures that will dry the air, improve drainage, avoid (for instance) throwing garbage just outside the door where it will putrefy and corrupt the air. You can see a groping toward the modern idea — ingesting sewage causes cholera.

      Typhus.. he quotes a Dr.Murchison “Fever my be generated spontaneously, independent of contagion. The poison [...] is generated by the concentration of exhalations from living beings, whose bodies and clothing are in a state of great filth.” We now say, much more precisely, that Rickettsiae carried by fleas, lice, mites, or ticks are the cause.

      So much has changed since 1873.

      Many common diseases are more or less tolerable, and you can fight them off yourself with very little help. Smith’s folk knowledge might provide that help in those cases. OTOH our “epidemics” of long-distance travel and crowded urban living are promoting once esoteric diseases to common status. I think it takes all our medical smarts to cope.

    2. JTFaraday

      “At the same time he should make full use of Astrology, because without Astrology medicine is entirely in the dark and has no hopes whatever.”

      I couldn’t agree more. I am making good use of the Year of the Dragon. Because the Dragon likes me, one of the few who does! :)

  25. Maximilien

    “He doesn’t consider Merck to be an evil company by any means, and says it does lots of good by producing medicines…”

    Okay, Merck’s not evil. It’s just sleazy.

    My proof? Remember the Repub debate in September of last year? The one where Rick Perry took heat for mandating the HPV vaccine for Texas schoolgirls? The HPV vaccine (Gardisil) made by Merck? Okay. Now here’s the other part of the story, the part that proves Merck’s sleaziness.

    Having suffered this hit to a drug that it had been relentlessly promoting to governments everywhere, Merck sprang into action. And behold! A mere three nights later on the NBC Nightly News, the LEAD story highlighted a study implicating HPV in the incidence of head and neck cancers and extolling the efficacy of Gardisil in preventing the virus (and thus the cancers).

    Now. How does Merck get what was nothing more than a free 5-minute commercial (disguised as news) on a major newscast, when it most needs it? One can only assume that Merck did something sleazy to get it. And therefore that Merck is a sleazy company. If not evil.

  26. S Silverstein MD

    That library scene looks like the science library at Rahway of which I was Director 2000-2003, until being laid off with 4,400 others in Nov. 2003 “Equinox” layoffs.

    If I’d known about this, I’d have thrown them out.

  27. travizm

    I think EVIL should be applied to regulators…….there job is due diligence and they have failed.

    You cant expect capitalism to deliver ethical outcomes…..thats stupid…

    Companies wouldn’t behave this way if the cost of doing business in this manner was PENAL.

  28. JTFaraday

    And to top it off, Obamaromneycare mandates people pay into the ponzi financing scheme that funds big pharma, whether they want to or not.

    1. Sharon

      JTFaraday, I have a theory about forced placed insurance and it might be just what the doctor didn’t order. I say this because insurance companies profits will be inversely affected by the poisoning of the population and this is huge the expensive drugs. This in turn will get passed on in the form of higher premiums to consumers or the insolvance of insurance companies and ultimately the government taking it over. At least for a while I think it’s a good idea to let insurance companies reduce their costs by reeling in pharma. I believe the Supreme Court will rule against the forced placed insurance mandate for this very reason. Pharma their paymasters will be hurt by this and no one gets in the way of pharma poisoning with impunity, not even the Supreme Court. My opinion of course.

  29. Marilyn Mann

    Cathy,

    Thanks for this post. A couple of small points.

    “Importantly, however, there was no subsequent insert in the medicine’s packaging that warned of possible CVT side-effects.”

    I’m not exactly sure what you mean by a packaging insert, but after VIGOR, Merck and the FDA engaged in protracted negotiations over how the cardiovascular signal in VIGOR would be reflected on the Vioxx label. Eventually, in April 2002, information on the VIGOR results was added to the “precautions” section of the label. There was nothing in the “warnings” section of the label on cardiovascular risk. The precautions section, under the heading “Cardiovascular Effects,” stated that “caution should be exercised when Vioxx is used in patients with a medical history of ischemic heart disease.” That section also stated that “The significance of the cardiovascular findings from these 3 studies (VIGOR and 2 placebo-controlled studies) is unknown. Prospective studies specifically designed to compare the incidence of serious CV events in patients taking Vioxx versus NSAID comparators or placebo have not been performed.” My point is that there was (eventually) a change to the label that discussed the safety signal in VIGOR, but it was not strong enough and it was buried in the “precautions” section where not many doctors saw it.

    “[Vioxx] was approved for a rather narrow use, mainly for arthritis sufferers who needed chronic pain management and were having GI problems on other meds”

    This is incorrect. Vioxx was originally approved for the following indications (from the original label dated 5/99):

    “Vioxx is indicated:
    The relief of the signs and symptoms of osteoarthritis.
    For the management of acute pain in adults (see CLINICAL STUDIES).
    For the treatment of primary dysmenorrhea.”

    The labels are available at this link:

    http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Label_ApprovalHistory#apphist

    I have blogged on post-approval drug safety here:

    http://marilynmann.wordpress.com/2011/06/12/assessing-drug-safety-post-approval-lessons-from-vioxx-avandia-and-meridia-part-1/

  30. Marilyn Mann

    Also, I suggest the following for further reading:

    Joseph S. Ross, MD, MHS; Kevin P. Hill, MD, MHS; David S. Egilman, MD, MPH; Harlan M. Krumholz, MD, SM. Guest Authorship and Ghostwriting in Publications Related to Rofecoxib: A Case Study of Industry Documents From Rofecoxib Litigation. JAMA. 2008;299(15):1800-1812.

    Keven P. Hill, MD, MHS; Joseph S. Ross, MD, MHS; David S. Egilman, MD, MPH; Harlan M. Krumholz, MD, SM. The ADVANTAGE Seeding Trial: A Review of Internal Documents. Annals of Internal Medicine. 2008;149(4):251-258.

    Joseph S. Ross, MD, MHS; David Madigan, PhD; Kevin P. Hill, MD, MHS; David S. Egilman, MD, MPH; Yongfei Wang, MS; Harlan M. Krumholz, MD, SM. Pooled Analysis of Rofecoxib Placebo-Controlled Clinical Trial Data: Lessons for Postmarket Pharmaceutical Safety Surveillance. Archives of Internal Medicine. 2009;169(21): 1976-1985.

    Joseph S. Ross, MD, MHS; David Madigan, PhD; Marvin A. Konstam, MD; David S. Egilman, MD, MPH; Harlan M. Krumholz, MD, SM. Persistence of Cardiovascular Risk After Rofecoxib Discontinuation. Archives of Internal Medicine. 2010;170(22):2035-2036.

    Snigdha Prakash, All the Justice Money Can Buy: Corporate Greed on Trial (2011) (book by former NPR reporter Snigdha Prakash on the Vioxx saga — focuses on a particular Vioxx trial).

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