Most scientific papers are probably wrong

[Darth Wong]

The company does not have to fake data; they only have to use insufficiently rigorous test methods. And this happens all the time, whether you admit it or not.

Right a jury is never going to hammer your ass for gross negligence and depraved indifference, both of which are viable charges. Every drug company we've worked for has been quite adamant that their overriding concern is not to be sued; several went so far as to inform us that if they were sued due to deficienies on our part they'd be sueing us.

If it happens "all the time", would you care to provide say three examples in the last five years where companies used tests below the level of rigor required by the FDA (or other applicable regulatory body)?

Rezulin was brought to market in the US after being banned in Britain for safety reasons, you lying little shit.

[tharkûn]

Oh look an example from more than five years ago that prompted industry wide reforms and changes in FDA requirements, color me surprised.

[wolveraptor]

You're kidding me right? You here about drugs having previously undiscovered side-effects all the time. You're seriously telling me that you've never heard one of those reports? They've been posted on here, for fuck's sake. Viagra-blindness, Vioxx-some heart problem, numerous psychoactive drugs-...etc.

[tharkûn]

Viagra blindness was not the result of bad science. That condition effects literally one in a hundred thousand or less. No scientific study could ever discover that with a practical clinical trial.

Vioxx is the same thing. Merck found that people were twice as likely to die from heart attacks while taking Vioxx as taking naproxen. Merck, correctly, pointed out that naproxen is known to prevent heart attacks and reported this to the FDA.

Give me names for the others if you want a serious reply.

Most of the adverse drug reactions are only discovered when you go from having maybe 10,000 patients monitored for a short period of time to having millions of patients monitored (abeit less rigoriously) till they die. Numerous side effects that effect only a very small percentage of patients will be absent in the clinical trials, but show up when you have a million patients. No amount of science can overcome the basic stastistics.

Why not have larger clinical trials? How many people do you want to suffer while you recruit, test, and evaluate a million volunteers? How much more do you want your drugs to cost to reflect two orders of magnitude higher vetting costs?

The cost/benifit analysis for drug science has moved heavily away from "get it to market" and towards "don't get your assed sued".

[Darth Wong]

Oh look an example from more than five years ago that prompted industry wide reforms and changes in FDA requirements, color me surprised.

Way to evade the point, asshole. You claimed that no corporation would ever put short-term profit ahead of public safety because of the risks. I produced an example that proved you wrong. So you move the goalposts. How predictable.

If these companies are so conscientious, why did the FDA have to put in special regulations to avoid a repeat of that fiasco? Why would the company put the drug on the market in the first place? Face it: you are wrong about the drug companies' concern for public safety. Dead wrong. They will push the regulatory agency to the limits of what it will allow, and they will throw common sense to the winds, and they will shit on public safety if it will let them bulk up on stock options, cash out, and retire before the shit hits the fan.

The reality of the pharmaceutical industry is that every day is a constant struggle between the regulatory agencies, who are trying to protect the public, and the corporations, whose only agenda is profit and who will risk public safety for a stock price boost, despite your apologist bullfuckery.

Don't tell me that the company couldn't have possibly foreseen a problem without special regulations covering just this contingency. It was a loophole in the regulations and the company exploited it. Because they are every bit the rapacious assholes I describe them to be, and not the cautious overprotective stewards of public safety that you laughably paint them to be.

[tharkûn]

Way to evade the point, asshole. You claimed that no corporation would ever put short-term profit ahead of public safety because of the risks. I produced an example that proved you wrong. So you move the goalposts. How predictable.

BS. My point is that in the present environment the "amoral, greedy corporate suits" aren't willing to risk being SUED. That aren't doing this because they are are altruistic, but because bad science hammers their PROFIT MARGIN.

If these companies are so conscientious, why did the FDA have to put in special regulations to avoid a repeat of that fiasco?

They aren't. The change has been in the cost of getting sued. The payouts have been ever increasing and the profit to made by getting a marginal product on the market is not going to cover your ass when the inevitable lawsuits come. They aren't doing this because they are altruistic, but because they have run the damn numbers and found that they MAKE MORE MONEY if they are honest. It is FEAR and GREED that motivates the drug companies to wish to avoid bad science and getting their asses sued off.

Why would the company put the drug on the market in the first place?

Because they had reason to beleive they would make money and most of the side effects you sight are things BELOW THE THRESHOLD of detection in most clinical trials. Take Vioxx, the number of deaths that were witnessed failed to show up in the 5,000 patient trial in '99. In another trial (after having met the FDA requirements for approval) Vioxx showed increased heart trouble, this would be because the trial was longer, while also showing fewer GI complications. These results were released to the FDA who agreed that the drug should have more stringent labeling, but should still be sold. After that trial Merck went forward with a long term study of chronic use, after this study showed dangerous correlations the drug was voluntarily withdrawn, something the FDA did not require. The initial study was NOT BAD SCIENCE. It was a matter of finding side effects in a small population on the drug for a limited amount of time. Why was it approved under those conditions? Because Vioxx prevented GI toxicity which kills some people.

Face it: you are wrong about the drug companies' concern for public safety

Face it: you are wrong, I never mentioned the words "public safety" and I never implied they were. I have consistently put forward that it is not in their amoral greedy self-interest and hence they don't do it. This is about greed, not public altruism.

The reality of the pharmaceutical industry is that every day is a constant struggle between the regulatory agencies, who are trying to protect the public, and the corporations, whose only agenda is profit and who will risk public safety for a stock price boost

Risking public safety will drop stock price. Oh wait you mean you missed it when Merck's stock nosedived when the lawsuits were announced?

Killing your customers tends to be bad for business, even more so when their relatives get to pleade before a jury for punative damages. Since Rezulin and a few spectacular cock-ups before it the industry has been reforming because the old rules LOSE MONEY.

Don't tell me that the company couldn't have possibly foreseen a problem without special regulations covering just this contingency. It was a loophole in the regulations and the company exploited it. Because they are every bit the rapacious assholes I describe them to be, and not the cautious overprotective stewards of public safety that you laughably paint them to be.

Oh quit with the strawmanning. Let's again return to my initial characterization of them: Amoral, greedy corporate suits. I'm not sure how much more explicit I can be. Without morals but with greed, do you have a reading comprehension problem?

I grant that in the past the profit to be made by fudging the data outweighed the costs of litigation. That is no longer true. Merck pre-empted regulatory action when withdrawing Vioxx, not because it is a studious custodian of public health but in an attempt to sheild its ass from punative damages.

This is why I asked for examples of less than rigorous data from within the last five years. The rules have changed in a very short amount of time. What was profitable behaviour then, isn't profitable now. This isn't about safegaurding the public, indeed in some cases the more conservative behaviour of the drug companies is hurting the public interest, however it is about the BOTTOM LINE. Pushing a drug and getting your ass sued off is less profitable than just dumping the drug.

[Gil Hamilton]

I forget what was the exact figures for this, Tharkun, so maybe you can help me. How many babies were born with flippers because the company that made Thalidomide marketed a drug that horribly failed the placental barrier tests for pregnant women?

[Crown]

Way to evade the point, asshole. You claimed that no corporation would ever put short-term profit ahead of public safety because of the risks. I produced an example that proved you wrong. So you move the goalposts. How predictable.

BS. My point is that in the present environment the "amoral, greedy corporate suits" aren't willing to risk being SUED. That aren't doing this because they are are altruistic, but because bad science hammers their PROFIT MARGIN.

Mike is establishing a modus operandi for big cooperations based on previous historical fact. You are stating an opinion based on wishful thinking. It's like saying; no one would ever risk killing someone because of the law which includes a death sentence.

On the face of it, the statement is reasonable, but hardly grounded in fact since people do engage in murder. In essence you assume that big cooperations operate at a sane and logical level.

Don't get me wrong, I don't believe cooperations, today, are going to release a drug that kills people, but I'm sure they would be blase about the side effects if it can give a white man an erection, or say cure boldness.

[Admiral Valdemar]

Have you been reading New Scientist again? You might want to look to that.

I believe it was in two magazines, I tend to read Scientific American as well sometimes. Either way, a whole new branch of statistics was created to deal with biology and I have heard it could help other scientists if they applied it to their own fields rather than stick with older methods.

In either case, I have defended NS in the past as being merely a reporting paper on current science affairs. It is NOT a journal and should never be accepted as such. Any editorial should be taken with a grain of salt and I do likewise with similar magazines. Only when I read Nature do I genuinely see what is written as de facto unless otherwise stated. It's like comparing a tabloid to a broadsheet really, one is for non-specialists and the other is much more accurate and specialised.

[Spoonist]

->Tharkûn

Unless you are really high up in the medical community I would say that your personal experience is good and reassuring but not relevant to the point.
There are lots of examples of american/canadian/EU drugs that was approved in their own market but when they applied for another market the tests showed that they had high secondary effects and where not approved for sales. This however hasn't stopped the commercial sales in their home market. So how come that it is easier to get sales permits in their own market? Easy, it's influence/contacts/pressure.

You see the problem with your reasoning regarding the fear of being sued only apllies to the company and not the executives making the decisions.
As the executives only is interested in short term progress and can then move on it leaves a whole lot of moral dilemmas. Especially since it's not their personal wealth that is being sued but their company's wealth.

It's not that companies are Evil by themselves but large investments have a way of gaining influence, and influence puts pressure on people, such pressure could make you hesitate if you think that something is bad but you can't prove it. In corporate hierarchies it usually doesn't pay to be the Nay sayer.

[tharkûn]

I forget what was the exact figures for this, Tharkun, so maybe you can help me. How many babies were born with flippers because the company that made Thalidomide marketed a drug that horribly failed the placental barrier tests for pregnant women?

Roughly 12,000 using a broad definition of "flippers". Again I'm not argueing about past sins of the drug companies even more recently than the good ole days when smoking was healthy; it was for more profitable to get the drug to market than prevent the company from being sued. That is no longer true.

I'm not saying the drug companies are or were saints, I'm saying that shoddy science loses money these days. It hurts your PR, it hammers your stock price (which can raise your interest rate), and gets your ass sued. There is a reason why Merck was more agressive at pulling Vioxx than the FDA: CYA.

Frankly it's Mike's burden of proof to show that this happens "all the time". Past behaviour doesn't cut it.

Mike is establishing a modus operandi for big cooperations based on previous historical fact. You are stating an opinion based on wishful thinking. It's like saying; no one would ever risk killing someone because of the law which includes a death sentence.

Mike is establishing a MO from when the markets responded differently, the rules were different, and the cost/benifit analysis was not comparable. He's perfectly right for back then, I challenge him to provide evidence that his thesis holds in the last five years.

Don't get me wrong, I don't believe cooperations, today, are going to release a drug that kills people, but I'm sure they would be blase about the side effects if it can give a white man an erection, or say cure boldness.

It isn't being blase, finding these side effects is not trivial. In May, 2005 there were a whopping 15 known cases of nonarteritic ischemic optic neuropathy. Do you ANY idea what type of clinical trial you'd have to go through to detect that? You could run 100,000 people through the clinical trial and STILL legitimately miss it.

The ascertion was that not that you find side effects after vetting the drug, you ALWAYS will given a large enough population taking the drug long enough. The ascertion was that shoddy science was why these weren't seen before. Fine, all I'm asking for is 3 examples within the last five years for proof that it happens all the time.

Unless you are really high up in the medical community I would say that your personal experience is good and reassuring but not relevant to the point.

We've done independent validation. In order to do that we had to be bonded for a staggering amount of money. The people who signed the contracts forked out lots of cold hard cash for good science and wrote in clauses about bad science.

There are lots of examples of american/canadian/EU drugs that was approved in their own market but when they applied for another market the tests showed that they had high secondary effects and where not approved for sales. This however hasn't stopped the commercial sales in their home market. So how come that it is easier to get sales permits in their own market? Easy, it's influence/contacts/pressure.

Different countries have different standards. Some Europe operates off a precautionary principle while the US operates off a prove-failure standard. If you can cite specific examples from within the last 5 years we can discuss them; otherwise you are making an unnamed appeal to authority.

You see the problem with your reasoning regarding the fear of being sued only apllies to the company and not the executives making the decisions.
As the executives only is interested in short term progress and can then move on it leaves a whole lot of moral dilemmas. Especially since it's not their personal wealth that is being sued but their company's wealth.

Under the current laws they can be brought up on criminal charges if the science is sufficiently shoddy. Further it is their money, as an executive who destroys a company is likely not to be hired back into a comfortable executive job elsewhere. If you have specific evidence, let's hear it.

It's not that companies are Evil by themselves but large investments have a way of gaining influence, and influence puts pressure on people, such pressure could make you hesitate if you think that something is bad but you can't prove it. In corporate hierarchies it usually doesn't pay to be the Nay sayer.

Which is why drug companies are having outside scientists do some tests on a contract basis. You have no positition within the hierarchy and you get paid the same no matter your conclusion.

Again I ask for recent evidence. Three cases of insufficient rigor in the last five years, surely with so many people holding your position one of you can find three examples in the last five years - "it happens all the time".

[SirNitram]

If one is making a claim.. Like, oh, everything's changed! Past events don't matter!... One is expected to provide evidence to that effect.

[ClaysGhost]

I believe it was in two magazines, I tend to read Scientific American as well sometimes. Either way, a whole new branch of statistics was created to deal with biology and I have heard it could help other scientists if they applied it to their own fields rather than stick with older methods.

Was it the article I linked to? It was wrong. I don't remember seeing anything on the same subject in Scientific American. Your original post sounded pretty confident; can you provide any more details/references on this new branch of statistics, or on how previous systems are "simply flawed"?

In either case, I have defended NS in the past as being merely a reporting paper on current science affairs. It is NOT a journal and should never be accepted as such. Any editorial should be taken with a grain of salt and I do likewise with similar magazines.

The problem is not with the editorials, at least, not for me it isn't; I expect editorials to be opinionated and outspoken. The problem is with the abysmal standards that are currently applied to the headline articles. I don't know about other fields, but what I have seen in astronomy has varied from dubious to just plain wrong. This was quite different about 5 or 6 years ago, I feel.

[tharkûn]

If one is making a claim.. Like, oh, everything's changed! Past events don't matter!... One is expected to provide evidence to that effect.

When the rules have changed, the political situation has changed, and the dynamics of the market have changed; it is of course the bedrock assumption of economics and game theory that the actions of players remain constant

Again Mike stated "it happens all the time". Fine he made a universal claim, ergo he needs to provide universal evidence. If said it happened all the time, then he would not need to provide evidence that it still occurs, he choose to make a universal claim, it isn't my problem if none of you can maintain it.

[Darth Wong]

If one is making a claim.. Like, oh, everything's changed! Past events don't matter!... One is expected to provide evidence to that effect.

When the rules have changed, the political situation has changed, and the dynamics of the market have changed; it is of course the bedrock assumption of economics and game theory that the actions of players remain constant

It is for the purpose of your argument, asshole. You claimed that fear of lawsuits would keep corporations from ever risking public safety in the name of short-term profit. That mechanism has not strengthened an iota in the last five years, you lying shitcake. Ergo, your argument fails and you are desperately trying to use your usual "change the subject" and "move the goalpost" rhetorical bullshit techniques. In fact, the corrective mechanism of liability lawsuits has been weakened by right-wing caps on liability damages and other political efforts to reduce or eliminate liability lawsuits. Caps that people like you have been urging for some time now, I might add. Case in point: the current lawsuits underway against Vioxx, one of which includes evidence that the manufacturer was pressuring doctors to downplay evidence of harm. Very high damages awarded to initial plaintiffs have already been drastically reduced due to these caps.

Again Mike stated "it happens all the time". Fine he made a universal claim, ergo he needs to provide universal evidence.

I already provided some. That's when you moved the goalposts, with this absurd "if there aren't three separate cases meeting very specific criteria and all within the last five years, it doesn't count" bullshit. Since when does corporate history start in the year 2000, asshole?

[tharkûn]

It is for the purpose of your argument, asshole. You claimed that fear of lawsuits would keep corporations from ever risking public safety in the name of short-term profit. That mechanism has not strengthened an iota in the last five years

Really? Then why did Merck pull Vioxx before required to do so by law? TO THIS DAY the FDA has still approved Vioxx and if Merck wants to sell it THEY CAN.

Something has changed, if for no other reason than their insurance premiums have gone up multiplicatively. Me, I'd law money on the direct to patient advertising by the law firms in the class action suits, a practice not as common five years ago. In the case of Vioxx literally the SAME day the drug company voluntarily withdrew it from the market the lawfirms began their marketing blitz. You also have more active governments, like the New York comptroller who is sueing Merck over it - that is new. Another fun bit is that more lawyers are opting their clients out of class action lawsuits, resulting in higher payouts.

The climate HAS changed. Lawyers are using new tactics and the government is less friendly than back when Newt Gingrinch and friends wanted to break the FDA's regulatory power.

Ergo, your argument fails and you are desperately trying to use your usual "change the subject" and "move the goalpost"

BS. I have been speaking in the present tense the entire frigging time. When you were challenged on your claim that it happens "it happens all the time" you cited several instances of GOOD science and old cases.

I'm not argueing about past behaviour, and I never have been. I'm pointing out that regardless of what Mike Wong, M.E. thinks the higher ups at Merck have a different view of situation. They were doing studies above and beyond those required by the FDA, they reported their initial data as soon as it was in, and when they had more conclusive data they halted large clinical trials (millions of dollars down the tubes) and pulled the drug (billions of dollars down the tube). The actions of Merck speak quite loudly of a change in the status quo, none of your opinion can refute that.

In fact, the corrective mechanism of liability lawsuits has been weakened by right-wing caps on liability damages and other political efforts to reduce or eliminate liability lawsuits.

So why can't you name 3 instances in the last five years?

Caps that people like you have been urging for some time now, I might add. Case in point: the current lawsuits underway against Vioxx, one of which includes evidence that the manufacturer was pressuring doctors to downplay evidence of harm. Very high damages awarded to initial plaintiffs have already been drastically reduced due to these caps.

Unlike you I can see both sides. If you hold every drug until you've found every side effect, you will never release any new drugs. If you take every potentially lethal drug off the market there will be NO drugs on the market. I favor pain and suffering caps, not punative ones. I'm also for greater criminel liability for executives who are negligent or fraudulent. But hey why let that interrupt your strawmanning.

There is a tradeoff between being safe and being too conservative so that people die while drugs get to market and the cost rises enough to curtail R&D and impact healthcare costs. No matter what you do TANSTAAFL bites your ass; the best trade-off well I leave that to experts in the field not the two of us.

By the way, the big suit you are bitching about, the man died of cardiac arrhythmia. Vioxx kills via heart attacks not arrhythmia. But why let a little BS science and ignorant jury in a legal trial ruin the story.

I already provided some.

Yes you provided some that are old, some that were GOOD science, and have been doing nothing but strawmanning.

For the record:

Crestor didn't show negative side effects in clinicals. Those came out when Tufts examined a national patient database and had a sufficiently large database of chronic users to find them.

Zyprexa is yet another drug where chronic use is different than what you can measure in clinical trials, at the time they filed the lawsuits a whopping 384 cases of diabetes found by the FDA, those type of odds are not visible in a short term 10,000 patient clinical trial. Also the warning about hyperglycemia was on the bottle at the time, the suit alleges that the warning was "buried" in the information given to prescribing physicians.

Prempro was found to be carcinogenic - after they had long term chronic use data.

Baycol was another Cox-II inhibitor, except that it had less clinical data than Vioxx - without a large body of chronic users monitored longterm you won't have clinical evidence.

Accutane has been known to dick over your mental health since forever, it has had suicide warnings for forever and day, the FDA beleives it serves the public good to keep it on the market even though it kills people.

Oxycontin is a form of heroin, so what? Do you know what dimorphine is? Heroin. The only difference between morphine, still in ubiquitious use, and heorin is how fast and hard it jumps the blood/brain barrier. All these drugs hit the opiate receptors and HAVE to be chemically similar.

Finding side effects isn't trivial, for most drugs you have a year or so of clinical data over 10,000 patients in a good solid trial. Hence any condition that either: effects less than .01% of the patient population or requires chronic use of over two years WILL NOT BE OBSERVED. It is not necessarily bad science when a new side effect is discovered. If it takes years to build up damage, as was the case with Vioxx, the six month clinical required by the FDA won't catch it. If it takes a million patients to find the side effect, like with Viagra, then no clinical trial will catch it.

So again, do you have three examples of shoddy science - not just new side effects discovered - in the last five years. Don't BS about finding new side effects, that has been happening since aspirin and penicillin - tell me about BAD SCIENCE.

[Darth Wong]

It is for the purpose of your argument, asshole. You claimed that fear of lawsuits would keep corporations from ever risking public safety in the name of short-term profit. That mechanism has not strengthened an iota in the last five years

Really? Then why did Merck pull Vioxx before required to do so by law?

Because they were already being sued, perhaps?

How does this support your "fear of lawsuits in the future will stop them from doing shit now" argument, particularly when Merck is getting its ass kicked in court for, among other things, downplaying risks even after they became known?

I'm sick of arguing with someone as manifestly and unapologetically dishonest as you; it is virtually impossible to deal with even the simplest point without you distorting it into a strawman and then vomiting forth an enormous cloud of bullshit and handwaving to focus everyones' attention on just how much you know about this strawman.

Once again, you claimed that no company would ever take irresponsible actions because of the threat of lawsuits, and that claim is patently false. The fact that companies fear lawsuits does not mean that the fear of lawsuits alone is sufficient to keep companies from taking irresponsible actions, and all of your long-winded bullfuckery will not change that fact.

TO THIS DAY the FDA has still approved Vioxx and if Merck wants to sell it THEY CAN.

TO THIS DAY they are STILL being SUED, moron. It is not fear of hypothetical lawsuits which stopped them; it was actual lawsuits already being filed. Short-term thinking, exactly as I said.

BS. I have been speaking in the present tense the entire frigging time. When you were challenged on your claim that it happens "it happens all the time" you cited several instances of GOOD science and old cases.

More bullshit; your argument was based on the fear of lawsuits, which is no greater today than it was five years ago. You keep trying to distract from this fact, but I have no plans to let you do so.

Case in point: the current lawsuits underway against Vioxx, one of which includes evidence that the manufacturer was pressuring doctors to downplay evidence of harm. Very high damages awarded to initial plaintiffs have already been drastically reduced due to these caps.

Unlike you I can see both sides. If you hold every drug until you've found every side effect, you will never release any new drugs. If you take every potentially lethal drug off the market there will be NO drugs on the market. I favor pain and suffering caps, not punative ones. I'm also for greater criminel liability for executives who are negligent or fraudulent. But hey why let that interrupt your strawmanning.

Interesting how that really doesn't address the point about evidence of downplaying harm at all.

There is a tradeoff between being safe and being too conservative so that people die while drugs get to market and the cost rises enough to curtail R&D and impact healthcare costs. No matter what you do TANSTAAFL bites your ass; the best trade-off well I leave that to experts in the field not the two of us.

By the way, the big suit you are bitching about, the man died of cardiac arrhythmia. Vioxx kills via heart attacks not arrhythmia. But why let a little BS science and ignorant jury in a legal trial ruin the story.

See above.

So again, do you have three examples of shoddy science - not just new side effects discovered - in the last five years. Don't BS about finding new side effects, that has been happening since aspirin and penicillin - tell me about BAD SCIENCE.

Yet again, you insist that nothing outside of the past 5 years counts, and that evidence of companies suppressing evidence of harm doesn't count, and that we should just ignore the fact that your argument about fear of lawsuits keeping corporations from doing harm has been proven wrong.

[Darth Wong]

Oops:

Drug trials risk to patients

Audit shows flawed tests are a danger to health, scientists argue

Sarah Boseley

Health Correspondent

Trials of new medicines to establish that they are safe and effective are so badly flawed that they endanger the health of the patients who take part and those who will take the drug once it has been licensed, according to scientists who have been auditing them in confidence for 10 years.

Wendy Bohaychuk and Graham Ball are appalled at the poor standards they have consistently found. "Frankly, after 10 years of detailed auditing, I would never go into a clinical study myself and I would certainly try to discourage anyone in my family from doing so," Dr Bohaychuk writes in an editorial for the industry journal Clinical Research Focus.

Problems she and Dr Ball have found include medicines being stored at the wrong temperatures, patients not being properly informed of what will happen in the trial, and the side-effects of new drugs not being reported.

In a sample of 226 trials, they found that 43% of patients were not given clear instructions for using the medicine. In 55%, there was inadequate proof that the drugs had been properly stored: one patient complained that a gel ran down his leg after it had been kept through a hot summer in the doctor's attic. In a prostate cancer drug study, the GP was not given proper instructions from the drug company on its use on the grounds that it was already on the market. It was - for treating high blood pressure. In a third of the trials, they found "significant under-reporting" of side-effects.

On the basis of these trials medicines are given a licence, the seal of approval for general use. But if they have been wrongly conducted, says Dr Ball, we cannot be sure the drug is safe. "If the data are not adequate, there is a risk to the patient who will be exposed to the drug in the future."

The scientists' company, Good Clinical Research Practices, is called in by pharmaceutical companies to establish whether trials meet international standards. Drug companies are obliged to have an audit, but not obliged to disclose the result to anyone. The audit certificate that goes to the licensing authority - the medicines control agency (MCA) in this country - states only that the audit has been carried out.

Because of the secrecy surrounding clinical trials information, the MCA and the government are in no position to know about the failings, argue the auditors. "The government has no idea what is going on," said Dr Ball.

The doctors are concerned that patient safety is not at the heart of these trials. "I think patients probably don't know what is happening to them in the vast majority of cases. They are not adequately informed. If they are informed, it is a biased information process," he said. "They are not aware that a clinical study is putting them at risk."

The MCA admits that there is a problem. "The whole business of clinical trials and good practice is down to a voluntary code," said a spokeswoman. It has been invited by drug companies to do only about 30 voluntary inspections since 1997. But the EU is considering a draft directive, which the industry is fighting, that would make inspections mandatory. If that comes into force the situation could change radically.

The Association of the British Pharmaceutical Industry said it would expect members to adhere to guidelines on trials. It denied that there were widespread failings.

Admittedly, it's from Britain rather than the US. But it does highlight the sort of problems which really can't be identified by examining a researcher's own published conclusions. Unless GCP audits are aggressive and frequent, there is no reason to believe that North America is exempt from these problems.

[Darth Wong]

Here's one from the US:

http://pn.psychiatryonline.org/cgi/content/full/39/14/1

I don't want to quote the whole article, but it details considerable evidence of bad science and poor clinical studies regarding anti-depressant drugs.

[Admiral Valdemar]

Was it the article I linked to? It was wrong. I don't remember seeing anything on the same subject in Scientific American. Your original post sounded pretty confident; can you provide any more details/references on this new branch of statistics, or on how previous systems are "simply flawed"?

As far as the article went by memory, I guess it was that one linked. I do know that biology has created a lot of statistical methods used today in science simply because the nature of, well, nature meant something that would be okay for physics or chemistry wouldn't suit ecology for instance. But I can't say I ever looked into the other fields being backwards, just different in attacking problems.

The problem is not with the editorials, at least, not for me it isn't; I expect editorials to be opinionated and outspoken. The problem is with the abysmal standards that are currently applied to the headline articles. I don't know about other fields, but what I have seen in astronomy has varied from dubious to just plain wrong. This was quite different about 5 or 6 years ago, I feel.

The headline articles are always going to be rather shaky, that's why I regard them much the same way I would an article in a newspaper. The reason I still buy NS is because it's a cheap, general overview of what is going on in science and technology. I, naturally, wouldn't believe everything I read in it anyway because I have all too often come across articles that try to defy convention and really end on a note saying "Well, if these tests play out this way, it may be so" which isn't definitive. Anything I find really interesting I will try and find in a proper journal.

In anycase, I find myself overlooking biology articles in there more than anything now simply to see what could influence my career path, though I tended to ignore those kinds of pieces a few short years ago.

As for the anti-depressant fiasco, I recall a good Horizon programme on the way the gov't regulates such pharmaceuticals. If I can find an article on it, I'll post it. Basically, the nature of the product what with all the tests needed and studies and three general phases before full production, it's hard to really control such drugs effectively at the best of times. If you get no nasty side-effects from a 1,000 person study and decide to go full-scale deployment, you may suddenly find that one in every 10,000 people drop dead from an unseen reaction. The gov't bodies that overlook these things could shape up themselves I hear, along with having more moral drugs companies.

[tharkûn]

Mike:

So let me get this straight you hold that the suits that run pharma will willingly commit gross negligence for a buck, but won't - in a industry that lives 10 years in the future - think out liability issues long term? They are so greedy they will risk lives, but not greedy enough to examine long term outlays in lawsuits? Do you think they cry out Ultimate Power as well?

Lawsuits go into the bean counting, more importantly the 7% drop in share price that immediately followed the voluntary recall gets figured in even more. You can piss and moan about how you think the suits are greedy, yet stupid enough not to see the dangers of bad science ... but the market still punishes it and they have to deal with it.

Frankly your point about the lawsuits is nonsensical. The only reason the public, and the lawyers, knew about the dangers at the time was because Merck was doing testing above and beyond that required by law. They released the data to the public, which again is above and beyond the minimal requirements of the law.

Once again, you claimed that no company would ever take irresponsible actions because of the threat of lawsuits, and that claim is patently false.

No, unlike you, I don't state things in absolutist terms unless I have a ludicriously strong case for them. My initial statement which you seem unable to address without strawmanning:

The company stands to lose billions of dollars if they fake the data and the inevitable class action lawsuit comes along. Amoral, greedy corporate suits want good science, backing something unsafe will eventually burn you far worse than dumping the product now.

Nowhere do I say it will NEVER happen. There will be idiots who don't see the direct correlation between being sued and watching your stock lose 10% of its value immediately thereafter, but the industry as a whole has a disincentive to commit fraud or negligence that wasn't there before. The lawyers are more aggressive in sueing your ass and the government is more aggressive in catching you with your pants down.

the fact that companies fear lawsuits does not mean that the fear of lawsuits alone is sufficient to keep companies from taking irresponsible actions

impossible, no. Less likely absolutely. The fact that they fear the wrath of shareholders who lose 10% of their equity makes that fear just a bit stronger.

TO THIS DAY they are STILL being SUED, moron. It is not fear of hypothetical lawsuits which stopped them; it was actual lawsuits already being filed. Short-term thinking, exactly as I said.

You do realize that the drug industry works on a fifteen year timeframe or more? That today's lawsuits, are often based off research done 10 or fifteen years ago, particularly when the problem requires chronic dosage.

your argument was based on the fear of lawsuits, which is no greater today than it was five years ago. You keep trying to distract from this fact, but I have no plans to let you do so.

The market disagrees. Drug companies lose more equity with lawsuits today than they did five years ago.

Interesting how that really doesn't address the point about evidence of downplaying harm at all.

Maybe because you provided no evidence of such a claim

Yet again, you insist that nothing outside of the past 5 years counts,

The numbers changed. Hell today there is a good chance that a major unweaselable cock-up would result in direct congressional action and no drug company wants that.

hat evidence of companies suppressing evidence of harm doesn't count

WHAT EVIDENCE to date you've quoted a rehash from the popular press that says side effects are underreported. Of course they don't specify wether it is the patients, the GPs (which in Britain work for the government), or the drug companies who did the underreporting.

Do you have a link to the actual data Drs. Bohaychuk and Ball published?

[Gil Hamilton]

Frankly your point about the lawsuits is nonsensical. The only reason the public, and the lawyers, knew about the dangers at the time was because Merck was doing testing above and beyond that required by law. They released the data to the public, which again is above and beyond the minimal requirements of the law.

I remember seeing that pamphlet that they released the info about the dangers in. It was filled with text so small you practically needed a magnifying glass to read it and filled with dense jargon that requires someone in the pharmaceutical industry to translated it. Their release of information existed to cover their ass, not inform the public, because there was no way that anyone in the public would have been able to distill any useable information from it.

[Darth Wong]

If it goes above and beyond the requirements of the law to do this testing, and it goes above and beyond the requirements of the law to report findings in your possession, then either you are lying or the law is incredibly fucked up despite your bullshit claims of massive widespread industry-wide reforms and regulatory improvements. Which is it, tharkie?

In my profession, you are required to proactively inform the public about any risks of harm that you are aware of. Are you saying that the pharmaceutical industry sets a lesser standard for itself than the automotive industry or the paint thinner industry? Is this supposed to make me feel better about the pharmaceutical industry?

As for bad science, did it ever fucking occur to you that independent verification is part and parcel of good science, and this is not required at all in pharmaceutical drug testing? The company performs its own test, no independent third-party verification is required, and the drug is approved for sale. The entire system is bad science, and all of your worthless hand-waving and long-winded distraction tactics won't change that. All you're saying is that irresponsibility, lack of transparency, and bad science are actually built into the system rather than being done as an act of defiance on the part of the corporate suits. Well gee, that makes me feel a whole lot better.

And don't give me this bullshit about how it's impossible to perform more safety trials because they're so expensive; generic drug manufacturers have to do their own independent clinical safety trials in order to do an ANDS in Canada (they only get to skip the efficacy trials for the active ingredient), so the cost of safety trials can't be that high or their drugs wouldn't be so damned cheap.

[tharkûn]

I remember seeing that pamphlet that they released the info about the dangers in. It was filled with text so small you practically needed a magnifying glass to read it and filled with dense jargon that requires someone in the pharmaceutical industry to translated it.

The release I am familiar with was for prescribing doctors and seemed to be no more difficult or easy to comprehend than other releases.

Their release of information existed to cover their ass, not inform the public, because there was no way that anyone in the public would have been able to distill any useable information from it.

Really, what did I just say, oh that's right:
.
There is a reason why Merck was more agressive at pulling Vioxx than the FDA: CYA.

I'm not saying Merck was being a paragon of virtue, I'm saying they had the opt of going public and covering their asses or hunkering down and waiting for the problem to eventually bite them in the ass. They chose the former, not because they were altruistic, but because the suits thought it would have a smaller negative impact on stock price.

DW:
The law required Merck to do a six month sub-10,000 patient clinical trial. They did that. The side effects did not show up in that one. They did a longer study (around a year as I recall), inconclusive results showed up. They reported those to the FDA who put some warning language about possible problems which was forwarded to prescribing physicians. Merck then did a three year study and about eighteen months in the problems started to show up (the problem involves chronic exposure and cumulative risk) at that point Merck terminated the study, withdrew the drug, and reported it all to the FDA.

Merck's legal obligations ended once it finished the six month study. At the point it was officially declared safe and the rules say that you now have to prove it unsafe. There are reasons why this was the case, the short version is that Vioxx would save lives by avoiding GI toxicity, but that is the LEGAL situation.

In my profession, you are required to proactively inform the public about any risks of harm that you are aware of.

Have you ever seen the full side effect list for any given drug? Only the obscure drugs don't run into pages just listing the possible risks (more or less every side effect reported is recorded and availible to any physician who wants to read it). The truth is ALL medicines are inherently poisons, we are just dosing you below the threshold where most people would die. Given the fact that there are 5 billion unique sets of body chemistry there will always be failures.

Should pharma be reporting everything to qualified outside experts? Sure. Are they required to? No. Is it evident to everyone when the risks are significant enough to report? No.

re you saying that the pharmaceutical industry sets a lesser standard for itself than the automotive industry or the paint thinner industry? Is this supposed to make me feel better about the pharmaceutical industry?

Neither the automotive nor paint thinner industries work in an area where you can legitimately say "We don't know why it works, but it works." When those industries have a problem it is far easier to find, fix, and repair. Likewise nobody dies if they don't buy a car or stop using paint thinner. With drugs creating public health scares over inconclusive data KILLS people when they decide to stop drugs on dubious grounds.

The company performs its own test, no independent third-party verification is required, and the drug is approved for sale.

And yet I have been hired to do independent third party verification of certain things. Oh wait that's something that doesn't exist in your world.

The entire system is bad science, and all of your worthless hand-waving and long-winded distraction tactics won't change that. All you're saying is that irresponsibility, lack of transparency, and bad science are actually built into the system rather than being done as an act of defiance on the part of the corporate suits. Well gee, that makes me feel a whole lot better.

You originally claimed the companies stood to lose millions if their science didn't get the drug to market, I replied that they stood to lose billions when bad science bit them in the ass. Since then you've decided that the amoral greedy bastards running big pharma must be idiots and ignore the long term finicial impacts of bad science. As far as profit motive, rational business players have an incentive to get good science.

As far as lack of transperency, hey I'd like more, but that comes with its own price. Data is opaque because of the data rights issues, you are either going to have expand IP rights (such as lengthening the patents in return for greater transparency) or fight through a strong bi-partisan lobby to do it via legislative fiat. In the latter case you will still run the risk that data rights will be infringed and still have negative effects. Personally I think we need a sliding patent length system. If you have a new life saving drug - you get a longer patent. If you have completely open trial data - you get a longer and a bit broader patent.

generic drug manufacturers have to do their own independent clinical safety trials in order to do an ANDS in Canada (they only get to skip the efficacy trials for the active ingredient), so the cost of safety trials can't be that high or their drugs wouldn't be so damned cheap.

They're not. The average Canadian generic drug is 70% more expensive than the average American generic drug. Currently only two of the major generic firms in the world service the Canadian market; those declining cite policy, increased regulation, and profit restraints. Now the entire price disparity doesn't come from this particular regulation, but it helps. Such a policy easily increases your drug expenditures by millions of dollars, but it likely does save a few lives.

Of course any increase in per unit cost from generics has to multiplied by at least three for brand names as each successful drug has to pay off three released drugs that don't recover R&D expenditures (including clinical trials). Depending on what stage you require these increased safety measure the multiplier could be as high as twenty.

[CmdrWilkens]

By the way, to address tharkun's argument that no pharmaceutical corporation would be stupid enough to risk major lawsuits for negligence, I would like to point out that prior to Enron, he would have undoubtedly argued that no corporation would be stupid enough to risk prosecution for incredibly blatant fraud either. Corporate suits have a history of short-term thinking and arrogant, foolish decisions, and then trying to use their influence to cover up for those decisions. Why do you think there's such a powerful political panic to shut down liability lawsuits even though the health care industry's liability payouts are not rising?

For the record the greatest arguments have NOT been about drug company lawsuits but rather about small and medium-practice doctors being sued in malpractice lawsuits. The argument (and I have no statistics to know if it is true or not) is that the rapidly rising cost of malpractice insurance is driving these doctors (who remain the first line of defense in preventing illness for most folks) out of buisness because they simply cannot afford the cost of malpractice insurance without charging exorbidant rates from their patients. Again that's the reasoning for the rush to limit medical liability lawsuits not liability from the drug companies (though they are certainly trying to get onboard).