This post gives the content of a public lecture organized by Dan Johnson and Jennifer Williams – see In Memory of Dexter Johnson. The slides and text are below.
There are two video recordings – the official version is by Thomas Paul which is White Coat Storm. A just to be safe second version – Beware Doctors Bearing Gifts – was done given the problems Tom had to juggle with for the original recording. There are slight differences between them but Tom’s is the better version.
Beware Doctors Bearing Gifts
Usually at this point a speaker says it’s good to be here. It is good but in this case it’s also emotional.
Slide 2: I will mention the Blackfoot and other First Peoples at the end of the talk but first I want to acknowledge a brave man – Dan Johnson sitting here – and his son, Dexter, who, when he was 15, was put on Prozac, without Dan knowing it, became worse, the dose was put up, Dexter got worse , the dose was put up and he became suicidal – and the dose was put up. Dexter died just over a year ago. From the records I’ve seen it seems evident that Prozac killed Dexter. I’m here as part of Dan’s search to find out how this could happen.
Slide 3: You will likely guess the Title of this Talk is linked to the Trojan Horse. The key word is Gift as will become clear later in the talk.
Seeing a title like this and hearing me say that the Art of Medicine involves bringing good out of the use of a poison, you would be forgiven for thinking I am anti-drugs or the medical model. Just the opposite, I believe in using medicines but the skillful use of drugs involves knowing when not to use them.
Slide 4: At the end of last August, the New York Times had a feature about American teens ending up on 10 or more psychotropic drugs. Hundreds of people commented on the accuracy of the article – even the New York Post, who never agree with the Times.
But while everyone agreed on the state of affairs, no one pinpointed why this is happening. This lecture will try to shed light on the Why.
Slide 5: The chain of events that led to our children being put on these drugs and that killed Dexter began 30 years ago with this paper, in which 3 clinicians claimed fluoxetine caused 6 people to become suicidal. Their claim was based on analyzing the cases closely and followed traditional clinical approaches for determining cause and effect. The cases were people who survived and could talk to them – they did not include a 14 year old boy who killed himself on Prozac.
Slide 6: Ten or more other groups reported similar findings, including this group from Yale who reported on 6 children becoming suicidal – 6 from 42 which is one in every seven children.
Slide 7: I contributed to this debate, outlining the cases of 2 men, challenged with an SSRI, with the problem clearing on dechallenge and coming back on rechallenge. There was no other way to explain what happened except that fluoxetine had caused it. This was Evident Based Medicine.
Slide 8: Almost the week my article came out, an article by Eli Lilly, the makers of Prozac, claimed that an analysis of their clinical trial database showed no evidence fluoxetine made people suicidal. The cases reported were sad but anecdotal and the plural of anecdotes is not data. Depression was the problem not fluoxetine. Clinical trials are the science of cause and effect. The question to doctors, the public, the media, politicians was – are you going to believe the science or the anecdotes?
Lilly’s article created what we now call Evidence Based Medicine.
In fact, the original phrase is the plural of anecdotes is data – otherwise Google wouldn’t work.
The idea the disease was responsible for suicide attempts and suicides in healthy volunteers is hard to believe but companies can get experts to claim just that.
My aim is to show you the Evident Based earlier papers are the science – the Lilly paper is the Artefact.
I will not dwell on the fact that Lilly cooked the books – even their trials showed Prozac caused suicide. It’s important you know Lilly’s Data lined up with your and my Evident Based judgement calls.
But even if done by Angels, my position is that RCTs can be useful but are a blunt instrument compared to the sensitive judgement calls you and I have to make.
My problem is that unlike you and I who figure RCTs can be useful, Lilly are saying here that we have no right to make judgement calls. Lilly are proposing a new religion where you and I have to believe in them. To add to our problem drug regulators, guideline makers, Justin Trudeau, Joe Biden and the Pope go along with them not us.
At present health is being standardized and this festoons antidepressants with numbers. Data. This looks like science but isn’t. You as patients and I as a doctor make judgments and choices about medicines – these cannot be standardized. They don’t come with numbers and do not look like science but are.
Slide 9: We often contrast the Art and Science of Medicine. Those in the soft human sciences contrast their rich qualitative context with the experimental context, where hard scientists eliminate confounders. This Janssen Advert assumes doctors will figure that paying heed to the soft side of things is a touch twentieth century.
My argument is the Science of Medicine lies in making hard judgement calls not in a made by algorithm Artefact – RCTs. Adhering to the artefact dooms Us. By Us I mean the chance of a community. Following the Artefact isolates and alienates doctors and patients from Us.
Making judgments about a medicine is not just science – it’s a moral enterprise.
Slide 10: So what is science? The usual story about the origin of science points to the foundation of The Royal Society in 1660. This established the ground rules of Science.
The ground rule was the Society did not deal with theology or philosophy – it dealt with things that could be settled with data. Whether you were Xtian, Hindu, Jew, Muslim, or Atheist, you left these badges at the door and had to explain what you saw happening in the apparatus in front of you without appealing to a Book or Authority. You could run the experiment again, adapt the apparatus, check it out for tricks – but you couldn’t refuse to come to a Verdict about the data.
The way this history is told focusses on the Data part of Settled by Data. I will focus on Settled.
Slide 11: This account of our history overlooks an equally important event 44 years earlier, when Walter Raleigh had his head chopped off – supposedly for being too close to those pesky Europeans. Raleigh was convicted on the basis of things said about him by people who did not come into court to be cross-examined.
Legal systems worldwide recognized the injustice of this and introduced Rules of Evidence. Hearsay could not be used as evidence. The only evidence that can be used in court is material that can be put in front of jurors who can see the people or material being examined and cross-examined. The process of forcing 12 people with very different biases to come to a Verdict about what is in front of them is the essence of science.
Verdicts and diagnoses are provisional – the view that best fits the current facts. If the facts change, we reserve the right to change our mind. This might appear to contrast with the objectivity of science, but scientific views are similarly provisional. Scientists attempt to overturn verdicts with new data.
If years ago, I gave an SSRI to Jennifer and she became suicidal. I can examine and cross-examine her, run lab tests and scans, raise the dose, stop the drug, add an antidote, check with colleagues has anyone else seen anything like this or can they explain it other than blaming the drug.
If Jennifer and I conclude the drug has caused the problem and report this to FDA or Health Canada, the first thing the regulator does is to remove her name. No-one can now examine or cross-examine her and come to a scientific view about whether there is a link or not. Her injury has been transformed into Hearsay.
If Dan is trying to take a case about Dexter and says look there are 10s of 1000s reports of the suicides on SSRIs on FDA’s adverse event reporting system, he cannot bring this evidence into court because no-one can be brought into court. It’s Hearsay, not evidence.
Company assays are all Hearsay. In company trials no-one can be brought into Court to give evidence – the patients don’t always exist and not even the apparent authors as you will see wrote the papers. Names count. Jennifer in this case is the data and accessing the data means accessing her.
If Jennifer and I report her case in a medical journal, with our names on it, either of us can be brought into Court. This is the best evidence we currently have in clinical psychiatry.
Slide 12: Matt Miller, a 13 year old boy committed suicide a week after being put on Zoloft. He became agitated on the drug and hung himself in the bathroom between his parent’s bedroom and his bedroom. It was Evident the Zoloft killed him.
Pfizer sent investigators to comb the carpet of the room for semen – they wanted to argue this was auto-erotic asphyxiation gone wrong – in a 13 year old boy. The judge said this was crazy but she had been told that Clinical Trials had to show the drug could cause the problem before you could blame it.
Slide 13: A set of independent experts said that Pfizer’s Zoloft trials show no evidence of this problem. This was baloney – the publications didn’t show a problem, but the Pfizer data like the Lilly data did. The court however wouldn’t let the data in. Three years later the data forced FDA to put a black box warning on Zoloft for suicide.
Why am I showing you a slide of a Plaster Cast. Well, if you break a limb and go to an ER and they say they are running an RCT- randomly assigning a plaster case to one of your 4 limbs – not necessarily the broken one – the plaster cast will beat placebo. Practicing medicine on the basis of this Evidence rather than on the basis of the Evident correct thing to do would be – crazy.
Slide 14: The events leading to Dexter’s death came more clearly into view in 2001 with this article which has an authorship line to die for, including a Canadian Liberal Party Senator, Stan Kutcher. It’s in the Journal with the highest impact factor in child psychiatry. This is Study 329 a trial of paroxetine in pediatric depression. The paper claims it works wonderfully well and is safe.
This was a good study, run to high standards. What I am about to tell you essentially applies to all industry trials across medicine.
Slide 15: Three years earlier, in 1998, GlaxoSmithKline were mulling over this internal document which says Study 329 was negative for efficacy and safety. What were they going to do? They were going to pick out the good bits of the data and publish them. The good bits formed the Keller et al 2001 paper.
This 1998 document led New York’s Attorney General to file a fraud action against GSK. As part of the resolution of this, GSK agreed to make their paroxetine trial data public. A decade later, GSK resolved a Dept of Justice action, which also involved Study 329, for $3 Billion dollars.
Slide 16: After the $3 Billion settlement, a team of us got together to Restore Study 329. We had more of the raw data on this study than FDA or Health Canada had seen for any study.
Slide 17: The 8-week acute phase of the study showed no difference between paroxetine, imipramine, and placebo. Ditto for the never published 6 month continuation phase.
Slide 18: Paroxetine had over 500 side effects in 93 teens. The Keller paper admitted to half of these. Keller noted 6 emotionally labile events in the trial, some of which might have been suicidality, 4 on paroxetine. But in our hands roughly a fifth of the children on Paxil had a significant behavioural event mostly suicidality.
Slide 19: Suicide is not what I want to focus on. It’s the ability of company studies to hide adverse events. Before going there, just note the 3 sentences here on the right – these are the last 3 sentences of the paper and quite unlike anything you will find anywhere else.
Slide 20: Our paper lists 10 ways to hide things – I will focus on 3. Coding is top of this list – this is the first act of authorship but no one pays any heed to it. You’ve seen GSK use emotional lability to hide suicidal events.
In a Pfizer trial around this time a man on their drug got agitated, poured petrol on himself and set fire to it intending to kill himself but he only died from his burns 5 days later. You can code him as death by burns or suicide. If the coder opts for death by burns, the data will look very different. This is a real example – just as emotional lability was.