Between 2002 and 2004, giving antidepressants to teenagers and the risks of triggering suicidality became one of the most high profile issues in medicine. Raising a profile should be the way to put things right but things are getting much worse. The lack of access to services is leading to adolescents self-harming to such an extent this is now accepted by the British government as the area of greatest failure in Britain’s Healthcare System.
What’s gone wrong?
Blowing up the Fishpond
It was BBC’s Panorama and a Los Angeles law firm, Baum-Hedlund who initially raised concerns. Panorama threw a hand grenade into the mostly East Coast fish pond that was American medicine. This led to a series of FDA hearings in 2004, and a derailing of company plans to get their antidepressants licensed for children.
The central event was a document obtained by Panorama which revealed that Study 329, a trial comparing paroxetine, imipramine and placebo, had been negative but was going to be portrayed as positive. New York State took a fraud action against GlaxoSmithKline.
The document crystallized recognition that close to every article on every on patent drug in any area of medicine was ghostwritten and there was zero access to clinical trial data.
Faced with this crisis, there were two obvious courses of action.
One was go after the docs who were willing to let their names be put on ghostwritten articles whose data they had never seen and who presented these data at meetings – for a fee.
The other was go after the data. In 2004, the British Guideline maker, NICE, considered the second option but funked it.
New York State thought they had secured a commitment from GSK to make the data available which would set a precedent for other companies. But GSK ran rings around them, making some company authored study reports available that concealed everything about everybody that had anything to do with any of their trials.
The first was the sexy option. It offered stories the media could understand – docs on company payrolls prepared to say anything. Everyone could understand Conflict of Interest and agree it was a bad thing. Chasing this fitted a zeitgeist which said all problems could be solved with Transparency.
The second was more difficult. Unless you are involved in clinical care it sounds esoteric and geeky. It also risked blowing up a lot the guys we think of as the good guys like BMJ, Lancet, NEJM and JAMA. And it quickly became clear there would be resistance. Let’s call this Cisparency.
When BBC threw their hand-grenade into the healthcare pond stunned fish floated to the surface. Baum-Hedlund picked the fish up and started dumping them on Congressional and Senatorial desks. Most of the fish were ugly and had thwarted data access stamped all over them. A few others were colorful eye-catching dudes.
The key desk turned out to be Senator Grassley’s, where a formidable woman, Emilia di Santo, ran the operation and an energetic staffer, Paul Thacker, got engaged.
Some colorful flashy fish called Alan, Marty and Charlie, the type to feature in Disney movies – a great title would be Three Amigos – caught senatorial or other eyes, rather than the uglier critters. There was nothing notable about the three flashy guys in terms of contributions to medical or mental health science, but at the time details about the conflicting interests of all three were tumbling into the public domain. Charlie had become the poster boy for conflict of interest across medicine.
If you’re a Senator what’s not to like about a guy who was willing to let himself be featured on the front of a glossy publication as The Boss of Bosses with a question Is Charlie Nemo the most powerful man in psychiatry. Marty was the first author on Study 329, the trial that had kicked everything off, then on its way to becoming the most famous trial in medicine.
Nemo was a Harvey Weinstein like character, capable it seems of charm with those who played ball with him and of being a thug to others. Close to the entire field of US psychiatrists enabled him.
He was probably a greater embarrassment to GSK and other companies than he was to academic psychiatry. GSK could not have wanted him to behave like a loose cannon in the way he did. He was probably central to losing them the Tobin case, which led to Panorama interest, and a bunch of dead fish, which they are still grappling with.
Enter Stage Left
Because of the Toronto episode Paul Thacker called wanting to know anything if I could tell him about Nemo. I told him – nothing much apart from what is in the public domain. I tried to persuade him Nemo was not the problem. He was irrelevant. He could even do some good if he could be turned. He and some others like Stuart Montgomery could show us where some of the bodies were buried. Chop their heads off and others would replace them.
PT wasn’t listening. Nemo had become too juicy a morsel to give up. But very little came out of his investigations beyond what was already in the public domain.
Let the Sun Shine In
The collapse in August 2007 on the grounds of pre-emption of a Baum Hedlund lawsuit, centered on the suicide of a 13-yr-old boy while taking Paxil, coincided with the introduction in September of a Physicians Payments Sunshine Act by Senators Charles Grassley (R-IA) and Herb Kohl (D-WI). This act aimed to “shine a much needed ray of sunlight on a situation that contributes to the exorbitant cost of health care”, according to co-sponsor Senator Charles Schumer (D-NY). It would require manufacturers of pharmaceuticals and medical devices with annual revenues of more than $100 million to disclose gifts or payments to physicians in any form, whether cash, trips, or other.
The most bizarre aspect of this was the idea that letting the Sunshine in would bring down drug costs – See Raiders.
But the Bill fit the perceptions of many ethicists, journalists and others that the root of the healthcare problem lay in payments to opinion leaders. Transparency was crowned king despite a complete lack of evidence of opinions being changed by payments.
This model locates opinion leaders as experts – the cream of the profession. They are only the cream in the sense of being rich and thick. No pharmaceutical company wants someone who can think. The first qualification for being picked by pharma is to be mediocre, and the second is to remain on message.
The model views other doctors and patients as airheads who will rely on a few puppets made over as smart dudes to tell them what to think. No one would pay any heed to what some cartoon puppets were saying were it not for the iron fist inside the puppets that has all too obviously silenced BMJ, JAMA, Lancet and NEJM – see Vampire Medicines.
The Benefits of Transparency
Baum Hedlund contacted Emilia di Santo again in 2007. It put the Ugly Fish back on her desk. While Grassley wrote to the Department of Health and FDA raising cisparency issues, the die was already cast. The transparency fish were already sitting in their bowl, scales glinting in the bright sun light. Rather than chase cisparency, Grassley continued with the low hanging fruit of transparency, scooping up a number of other prominent psychiatric academics on the way none of whom seem to have been harmed by the attention.
Just this year Karen Wagner, one of those named and supposedly shamed became the current President of the American Association of Child and Adolescent Psychiatry, despite multiple depositions conceding her articles are all ghost-written and she wouldn’t know what to do with data even if she saw it.
On July 12, 2008, the New York Times reported:
“But now the profession itself is under attack in Congress, accused of allowing this relationship to become too cozy. After a series of stinging investigations of individual doctors’ arrangements with drug makers, Senator Charles E. Grassley, Republican of Iowa, is demanding that the American Psychiatric Association, the field’s premier professional organization, give an accounting of its financing.”
The following year APA voted Alan Schatzberg in as its President.
After a brief period under a cloud, Nemo moved from Emory to Miami and was welcomed into the bosom of places like London’s Institute of Psychiatry who know a thing or two about supporting people who have been vilified by the enemies of psychiatry. A President of the World Psychiatric Association in waiting?
On March 23 2010 Grassley and Kohl’s Physician Payment Sunshine Act was enacted as part of the Patient Protection and Affordable Care Act.
The resolution of New York States’ fraud action against them in 2004 involved an agreement by GSK to post details of their clinical trials on their website. This led to a set of Clinical Study Reports (CSRs) for paroxetine trials in children being posted.
GSK also posted 3-7 page summary reports of trials in other therapeutic areas, including trials of their blood sugar lowering blockbuster, rosiglitazone (Avandia). Reviewing these summaries Steven Nissen, from the Cleveland Clinic, found an increased rate of mortality on Avandia compared to placebo. Avandia was withdrawn from the European market and restricted in the US. These data laid the basis for the Department of Justice to pursue GSK for both Paxil and Avandia.
In 2009. Peter Doshi from Johns Hopkins and Tom Jefferson from Rome, working with colleagues on a review of Tamiflu, Roche’s antiviral drug for influenza, became headline news, when the data they assembled suggested Tamiflu didn’t work.
Governments around the world had stockpiled billions of dollars’ worth of Tamiflu having been told it saved lives by reducing transmission of the virus, kept people out of hospital and got them back to work faster. Fiona Godlee and BMJ helped make Tamiflu a campaign for transparency.
Then in October 2012, facing criminal charges for promoting its antidepressants for unapproved uses and failing to report safety data about Avandia, GSK accepted a $3 Billion fine, then the largest settlement in a Department of Justice lawsuit.
Far from being on the back foot, just as they had out-maneuvered New York State in 2004, GSK took the initiative. They announced plans to make their clinical trial data available to researchers on a secure website, if an independent panel of experts agreed the research proposal met a scientific need – mature transparency.
A few weeks later, AllTrials was born. The idea might have begun with Fiona Godlee. The family present at the birth included Sense about Science, the Cochrane Collaboration, the Centre for Evidence Based Medicine, Iain Chalmers, along with BMJ and PLoS, with the lot now fronted by Ben Goldacre.
The AllTrials ask was for access to the protocols for all clinical trials. The impression given was that AllTrials was seeking access to clinical trial data. It wasn’t. It was named AllTrials rather than AllData. It supported proposals that might enable some investigators, approved by companies, to access certain efficacy data. Exactly what GSK were proposing.
GSK promptly signed up to AllTrials. Within a few months of a record fine in the US, Andrew Witty, GSK’s CEO, featured on the March 9 2013 cover of the BMJ hailed as the acceptable face of the pharmaceutical industry.
A few years later the time came to dump fish in a Chicago jury box in the Dolin case. Trying to spear Nemo wasn’t going to get anyone anywhere with a Windy City jury – he mightn’t have been visible in a Green River anyway.
It was the ugly brutes the jury got told about. GSK’s lawyers spent their time desperately trying to block any mention of Study 329 and trying to stop jurors seeing the harms data from paroxetine trials, or hearing about the ways the company had tried to thwart access to data.
GSK’ s lawyers went apoplectic at a mention of the idea that if you owe a bank a million dollars, you have a problem but if you owe a billion, the bank has a problem. This could be reprized as – if Senator Grassley catches GSK out in a little lie – hidden payments to Nemo – GSK has a problem but if the entire thing is a lie Senator Grassley is fucked.
Transparency, efficacy and Nemo were irrelevant in Chicago. Its the Great White Lies about Harms that count, not a few little tiddlers.
To be continued..