Health Warning: Let me put down some markers before riffing on the Grassy Knoll theme. I am a committed believer in what may now be a last millenium concept – the medical model. I think antidepressants – the older tricyclics and ECT, not the more recent SSRI and other antidepressants – can save lives. I figure conflict of interest, crucially important in other areas of life, is of minor importance if not irrelevant in science. Although by science I mean something that can only happen in the presence of publicly available data.
In the case of the antidepressants and other drugs, do people sit down in closed rooms to hatch a plot against “the people” for the sake of profits? Yep, they do. Is this a conspiracy theory? No, its out in the open – nothing personal just business.
Is concern about the operations of the Science Media Center legitimate? Yep. Is it because they’re engaged in a conspiracy? Well – they are in the business of managing perceptions. Is that a conspiracy – even if a well-intentioned one? Difficult call. Anyone who bases their case on Robert Gibbons and related stuff as Pariente and others in SMC have done is either cynical or thick. Sticking a litmus strip into the SMC bilge around Panorama caused the litmus strip to dissolve.
The vast bulk of the academic literature on on-patent drugs, excepting the diminishing number of articles talking about adverse effects, is ghostwritten. Is this a conspiracy? Nope it out in the open but no one spots it on radars in front of them because for most its still as unbelievable as UFOs, or the idea we might incinerate millions of women, children, musicians, artists and scientists.
The entirety of the data from clinical trials of on-patent drugs is unavailable. No-one gets to see it. Is this a conspiracy? Its force majeure – that’s French for fuck off.
The Presidents of American and European Physicians Associations (as well as Royal Colleges) remain quiet about this. Is this a conspiracy? No. Its political maturity, as modeled by Pius XII in the 1940s.
On June 2 New York State’s Attorney General Elliot Spitzer filed a fraud action accusing GlaxoSmithKline of “repeated and persistent fraud” for concealing known problems with efficacy and safety of Paxil (paroxetine) for children and adolescents. He claimed GSK hid the fact that its Paxil trials failed to show efficacy in adolescents and in some cases it was more likely to cause suicidal thinking.
There was a basis for the charge given that Study 329 and other company pediatric trails may represent the greatest divide in all of medicine between what the academic literature says about the drugs and what the data actually show. There was also a smoking gun document unearthed by Panorama which appeared to show GSK intended to deceive doctors and patients with the publication of the Keller paper in 2001.
Spitzer held a press conference arguing his action would change the course of medicine for ever. All companies would be pressured into making their data available to doctors – as it should be. The media attention helped propel him to the Governorship two years later.
On August 26, GSK announced that it had resolved its case with New York. It would pay a small amount of money and publicly disclose all of its clinical drug trials about the safety of paroxetine for children in a “Clinical Trials Registry”.
Showing a mastery of the art of turning problems into opportunities, GSK’s press release stated:
“We are pleased that the Attorney General believes the Clinical Trial Register we have been developing will provide useful information to the medical and scientific community,” said Mark Werner, Senior Vice President for US Legal Operations at GlaxoSmithKline. “We believe that GlaxoSmithKline’s initiative to launch this register is a responsible step in ensuring transparency of our clinical trial data.”
Spitzer was left seething.
He became Governor in 2006, but two years later he was forced to resign after being found in a compromising situation. The first season of The Good Wife and the last episode of Law and Order are thought to have based on these events. There was no end of speculation as to who was behind his downfall.
The Spitzer action didn’t change medicine one iota. It may have helped a few weeks after with pushing through a Black Box Warning that FDA up till the last minute was dead set against. But from GSK’s point of view, Paxil was off-patent, and the warnings may have helped sales of its Lamictal for bipolar disorder – a failure to diagnose which they knew a bunch of doctors were straining at the bit to say was the real reason all these kids were becoming suicidal.
Conspiracy? You have to admire GSK’s nimbleness.
In the late 1980s Stuart Montgomery in London hooked Eli Lilly into a placebo controlled trial of Prozac in patients with recurrent brief depressive disorder, aka intermittent brief depressive disorder, aka borderline personality disorder. The data are unavailable. An article was published years later concealing the suicidality data but tucked away in it was mention of the fact that placebo was roaringly better than Prozac.
A few years later Montgomery persuaded GSK to run the same trial in the same patient group, probably using some of the exact same patients, comparing Paxil (Seroxat) to placebo. The trial ended early. No data were ever published. There was a much higher suicidal event rate on Paxil.
A few years after that again GSK ran a trial in Belgium in the same patient group. Who know what the real figures are – I’ve seen several different sets. In all of them there are very high suicidal act rates on Paxil and placebo – which was the point of the trial.
In 2006, under pressure on the suicidality front, GSK put out a press release, containing these figures.
What this shows is that you can use a problem you know your drug causes to hide a problem your drug causes. This is effortlessly easy to do by mixing superficially similar but in fact different patient groups together. It can be done for Parkinson’s disease, Back Pain, Cancers, and works particularly well when both the disorders and their treatment cause a problem. It’s a harder trick to pull off when you use duloxetine for urinary incontinence and end up with suicidal women.
Anyone like Stuart Montgomery could have sat down and explained to the company what the pay off was going to be from what might have looked like a crazy move.
Company trials are full of moves like this. Is this a conspiracy? No – its a game. On our side, we expect our academics, like Dr Wessely who bills himself as an expert in these kind of things, to spot what’s going on and prevent the buggers from scoring goals.
In 2012, GSK was hit with the then biggest fine in corporate history. As part of its response, as with Elliot Spitzer it took the moral high ground and made a big deal about banning free pens to doctors and eliminating payments to detailers (sales reps) by results. All payments to reps, along with the reps, were being eliminated anyway so this one was easy.
But for Andrew Witty to end up on the front page of the BMJ, just a few weeks after agreeing to the biggest fine in corporate history, billed as the acceptable face of the pharmaceutical industry and the Great White Hope, was a lot more impressive. It must have brought a smile to lots of faces, whatever about the Good Guys in the Department of Justice.
In between paying the fine, and canonization, AllTrials had launched. Most people heard access to trial data but AllTrials proposed nothing like this. They were focused on efficacy as adjudged by experts not data as trawled by people. And in a dangerous world, efficacy sells drugs. Its the nuclear option. Why take risks – nuke it. There is nothing about AllTrials that is not going to increase the sales of drugs. And all sorts of the great and good were swinging their thuribles and chanting “Transparency”, Transparency” around the new sacrament.
Andrew jumped on board. What was not to like about this? Nobody rooting through the data to find evidence of a Third Shooter.
Did Ben Goldacre and Iain Chalmers conspire to offer him a Get out of Jail Free card. Its irrelevant. All it needs is someone in GSK to be able to spot a Get out of Jail Free card in front of their nose and able to persuade the CEO to grab it. And 100,000 people work for GSK so there was every chance this would happen.
The Business Model
The business model of the pharmaceutical industry is:
Pay us what we want because we do research to produce new drugs and if you don’t pay us we will stop doing this and you will die.
Its the next best thing to the barrel of a gun.
They don’t invest the money in making new drugs. The track record in this area is worse and worse. The money goes into maintaining power. With sufficient lawyers, regulators and academics, its a bit like retaining so many monkeys, you can be sure of ending up with a Mozart symphony or Shakespearean play from time to time. The other thing as any great sports coach will tell you is Focus. Industry have a focus – the bottom line.
Medics on the other hand and shrinks in particular are the least focused people in the world – except for those who jump ship into private practice.
Watching Medic behavior however is a good way to check which way the wind is blowing. When there is a dominant power, a bully, medics usually line up to right of the bully. Its called identification with the aggressor. When the Catholic Church held an iron grip on thinking in Ireland, far from offering a voice of liberalism, Irish Medicine took ethical positions on abortion, contraception and everything else to do with sex to the right of the Church. It often left Church leaders looking rather – well Andrew Witty like.
Anyone who expects doctors to save them would probably have thought the Maginot Line looked wonderful, and voted for the canonization of Pius XII.
(Was that a conspiracy? Well he did have a woman who looked after him and she was German, wryly described by some as the most powerful German in the Vatican…..).
(Yanis Varoufakis’ Adults in the Room is a wonderful take on what its like to deal with a dominant power and the ventriloquist’s dummies, the Irish or Lithuanians, who do the speaking for them. Or how people will be clapping your back one minute over a stein of beer and then selling you out the next).