From 1951, a system designed for heroin and cocaine addicts – prescription-only status – was applied to all new drugs. Why? These were after all the first truly effective drugs in medicine. But the ability to do good came with a likelihood of doing harm. There was a trade-off to be made between risks and benefits. The new complex trade-offs could not be put on to the label of a drug or even captured in a forty page package insert. They needed to be individual to each person.
Having seen hundreds of different treatments and people, the patient’s doctor seemed to the US Congress like the person best able to explain the use of a new drug, and knowing their patient, best placed to help them make any trades.
Doctors, almost all men, were seen as skeptical of the latest fashions, if not entirely incorruptible. Patients, mostly women, faced with exaggerated claims for benefits were seen as likely to have their heads turned by the latest claim – and what did they know about medicine anyway.
Hide the Data, Control the Spin
In 1962, there was a sea-change in what there was to know about drugs. There was a switch from the knowledge a doctor might have born from his experience of drugs and diseases in general and of this patient in particular to a knowledge of the average effects of drugs derived from controlled trials. At first blush, this seemed even more scientific and beyond the reach of the average woman in the street.
But data are public – or were in the 1960s – in a way that experience isn’t. And using public data on breast cancer survival rates, women created the need for informed consent. Medicine was temporarily on a road to becoming democratic.
The information in controlled trials has two components. One component is the data that is collected and should always be public or else medicine is a tyranny. The second is the interpretation put on that data – the spin if you will.
Industry resisted the move to prescription only medication. But the pharmaceutical industry has an unrivaled ability to co-opt developments that it initially might not seem to favor them. In this case, controlled trials gave industry a way to displace clinical experience. Hide the Data and Control the Spin.
The result – the heads of incorruptible doctors turned at the first hint of an exaggerated claim for benefits. Adolescents faced with a rack of designer clothes would show more discretion (bottom) than the average doctor.
Hide the Data, Control the Spin, and then check on my precious, my “Learned Intermediary.”
Does My Bottom Look Big in This?
This is how a Texas Court put it in 1974:
Prescription drugs are likely to be complex medicines, esoteric in formula and varied in effect. As a medical expert, the prescribing physician can take into account the propensities of the drug, as well as the susceptibilities of his patient. His has the task of weighing the benefits of any medication against its potential dangers. The choice he makes is an informed one, an individualized medical judgement bottomed on a knowledge of both patient and palliative.
Bottom is a beautiful word that has all but vanished. It referred to professional judgment. Discretion. This is what you paid money for. This is what a leader like Churchill had.
Bottom is what made a Learned Intermediary. This was the person in between you and pharma whom you’d hope in your case had bottom. This is what made a Good Doctor.
Except if this person can be persuaded that any bottom that doesn’t fit into the straitjacket of a controlled trial is just too big to put on public display, then the Learned Intermediary idea makes the perfect cover for a pharmaceutical company.
Despite DTC adverts, drug companies don’t sell to the public – they sell to doctors. If the Doctor is happy with the information they convey – they claim they are relieved of a duty to warn the patient. That’s the doctor’s sacred professional duty, they say.
There is no Law or Statute that says this is the case. It just seems like common sense to many courts like the court in Texas. And if on the basis of this, you have the most clear cut drug induced suicide or whatever, but your doctor says he’s not convinced the drug causes this kind of problem and would have prescribed it to you anyway, to put it politely you don’t have a case against the company.
There is no Law of Statute that says the role of a doctor is to provide cover for a pharmaceutical company, but….
This is where controlled trials and controlling the Spin is important. If a hazard like suicide is more common on treatment than placebo in trial after trial but none of them are significant, and the company can persuade the doctor that if it’s not significant it doesn’t exist, then despite any number of convincing cases she can draw on from her own experience – she’s theirs – unless that is her Bottom is too Big for this. Or some Court decides this is a bad joke.
A Midsummer’s Night’s Study
Between 1994 and 1998, GSK ran a trial of paroxetine v imipramine v placebo in adolescents with “depression” in North America. Study 329. SmithKline, later GlaxoSmithKline, wrote up the results to claim that the study showed Paroxetine is well tolerated and effective – even though there were a host of problems aside from just suicidality.
The investigators on this study became “authors” on the article – some of the biggest names in the field. But their authorship was notional. The article was in fact written by a ghost writer.
Neither the notional authors nor the ghost writer had access to the raw data from the study. All that anyone had access to was data that had been tabulated by the pharmaceutical company and coded in ways that concealed the issues. For instance any of the children who became suicidal were coded as having emotional lability.
The article was published in 2001 in the Journal of the American Association of Adolescent and Child Psychiatry – the journal with the highest impact factor in the field.
Sales boomed even though the drug hadn’t been approved – well what self respecting Learned Intermediary wouldn’t follow what an article by the brightest and the best in the field and published in such a good journal.
But in fact privately years before, the company had already accepted this Study showed the drug didn’t work.
The Play Within a Play
Midsummer’s Night’s Dream famously contains a play within a play.
When New York State became aware that in 1998 SmithKline had decided the data showed paroxetine didn’t work, they instituted a fraud action against GSK which the company resolved by agreeing among other things to post the “data” from Study 329 and other studies on the company website.
They published material that had not previously been in the public domain (Clinical Study Reports) but did not publish the data from the trial. To this day the trial data remains unpublished and unavailable.
Along with colleagues I have had an opportunity to access the Study 329 data. This has led to an article currently under review. Our Spin, if you like, is paroxetine doesn’t work and isn’t safe.
But you don’t have to believe us, the data will be published with the revised article – “when” and wherever it is published. You can make up your own mind – which is how it should be in a democracy.
What this scenario reveals is that once controlled trials were made mandatory for new drugs, the combination of prescription only arrangements and lack of access to the data sets up a situation where it is impossible for a doctor to function as a Learned Intermediary.
They will be faced with the apparent data published in peer-reviewed journals authored by the most distinguished academics. Even when the study is stuffed full of a problem the doctor is seeing daily in his clinic, the article will claim these side effects simply do not happen – and few doctors have either the Balls or the Bottom to argue.
Enter Bottom Stage Left
The Midsummer’s Night’s Dream becomes surreal before Shakespeare wakes everyone up.
In Study 329 a host of children became suicidal on Paxil. Were any of them told the drug was likely to have caused this?
GSK have made it clear that 20 years later they have still not informed any of these that there was even a possibility their treatment caused the problem, when it is probable that it did so in all instances.
Why not? Well they say it’s the role of the patients’ doctor, who in GSK’s opinion knows the patient best, to inform them of this possibility if the doctor thinks it’s in the best interests of the patient to know this. They, GSK, feel they would be intruding on the sanctity of an all but intimate relationship if they were to do so.
This is the first ever recorded appeal to the Learned Intermediary “doctrine” to cover this situation.
What kind of Bottom would these doctor “Authors” have to have if they are to do the right thing by these children – given that in their article they committed themselves to saying the drug was safe, and denying it caused suicide – an article that laid the basis for a successful fraud suit against GSK in 2004, and a $3 Billion fine from the Department of Justice in 2012 – an article that they have been asked to retract but have refused to do so?
What kind of Bottom would it take for them – the supposed Authors – to ask to see the Data?
What kind of Bottom would it take for Doctors generally to say “This is to make an Ass of me.“
Now Wake Up
This is not a fancy story about trials in ancient Athens that makes a slightly scary but ultimately pleasing entertainment before retiring to bed.
This is every drug trial for every drug in every area of medicine, right now.
Meanwhile we have ended up with Doctors without Bottoms. A Doctor without Bottom is like salt without its bite – good for nothing.
Shrugging and saying the course of True Science never did run smooth in the expectation that things will sort themselves out when the curtain falls is not sensible.
There are three things that can be done:
- If my participation in clinical trials, ones in which I have a treatment induced adverse event, can be used to deny that such events happen, then by participating I put my family, friends, and community in a state of legal jeopardy through articles that end up in, say, the New England Journal of Medicine, in which case there is only one sensible course of action….
- Open a petition to have the New England Journal of Medicine forced to change its name to the New England National Enquirer (NE-NE).
- You might think if the law on Learned Intermediaries is as the Texas Court thought it was, then the Law’s an Ass. But in fact there is no law about this. Lawyers need to push this point home.
To be continued…