Slide 1: Everyone can likely see 2 Faces and a Vase here. The word RANDOM can also be seen two ways. Random behavior was seen as key sign of madness. Now it is seen as the path to Wisdom and Truth.
In the 1960s, phrases like Do not adjust your TV, the World has gone Mad were popular. In the 2020s we need something more like Do not adjust your Reality, the Virtual World has gone Mad.
Slide 2: You might see 3 ordinary guys here or 3 healthcare experts.
The ordinary guys have Post SSRI Sexual Dysfunction – PSSD – a state of sexual wipe-out after you stop an SSRI, which can last forever. In talking about their PSSD on a Podcast, it becomes clear these 3 guys have an extraordinary expertise on what is wrong with healthcare today. Here are some quotes.
Bryn: Getting PSSD undermines your faith in the medical establishment and the whole system of science – the fact that none of these professionals understand this condition or know anything about it when we know we have it – it’s not some vague feeling. Losing you libido is equivalent to going blind or deaf, it’s that level of sensory impairment
Roy: The same can be said for losing your emotions – I felt I lost two senses – my sexuality and my emotions
Simon:
Bryn: If we want to be believed we have to remember just how incredible our story sounds… It’s a hard thing to wrap your head around… My Dad says it’s not possible a drug could cause these effects, it wouldn’t be on the market
Slide 3: Let me translate. Both Bryn and Roy say something like: Doc the hand growing out of my shoulder and my missing arm is because my mother took a pill while she was pregnant with me. the doctors says: don’t be silly your arms look just fine to me. A great pill like thalidomide couldn’t cause a problem like this.
Having a child born with the problems caused by Thalidomide had a huge impact on lots of families as any abuse can. Simon outlines the impact of his PSSD on his family in an extraordinary fashion. What he outlines will be gripping listening for anyone interested in issues like this.
Bryn then introduces his Dad saying that ‘They’ wouldn’t let a drug on the market that caused your hand to grow out of your shoulder or PSSD.
Slide 4: Wonder Drug is about Thalidomide in America. The usual narrative is Americans were saved from the worst but Wonder Drug makes clear this drug was handed out to thousands of American doctors who gave it to tens of thousands of women and there were hundreds of babies born with defects, which FDA went out of their way not to find. What FDA did next caused Roy, Bryn and Simon’s PSSD problem and kills and maims tens of thousands of Americans each year. My talk is about this US contribution to global drug induced deaths and injuries.
Slide 5: Primed by the last slide you may be looking for this child’s birth defects. Its her mother who has the birth defects. Those injured by drugs have thought us a lot about Being Able and shone a light on the way forward in healthcare and life for all us.
Slide 6: Thalidomide had been made in France and tested for tuberculosis, when in 1948 Tony Hill ran the first randomized controlled trial (RCT) – of streptomycin for tuberculosis. Hill used randomization as a method of fair allocation – nothing here about the randomized mysticism you hear about today. This RCT found out less about streptomycin than a prior non-randomized trial in the Mayo Clinic, which showed it can cause deafness and tolerance develops rapidly.
Slide 7: Here is Hill in 1965 taking stock of RCTs. If randomization, double-blinds or placebo got in the way of a doctor evaluating a drug, he said, get rid of them. Hill believed in Evident Based rather than Evidence Based Medicine.
He said RCTs were needed in 1950 to work out if anything worked – a way to eliminate ineffective and unsafe drugs. By 1965 we had lots of drugs that worked – none discovered through RCTs. He never envisaged companies using RCTs to get weaker drugs on the market.
All drugs do a thousand things. An RCT focusses on one which might be useful for treatment. purposes. In focusing on one element, Hill is saying RCTs are not a good way to evaluate a drug. All RCTs generate ignorance. But we can bring good out of ignorance if we remain on top of what we are doing.
RCTs, he said, produce average effects which don’t tell a doctor how to treat the person in front of them. Hill never saw RCTs replacing clinical judgement. If we let that happen we’d have gone mad.
Slide 8: Louis Lasagna was the leading proponent of RCTs in the US. In 1956 he suggested in addition to FDA asking companies to prove their drug is safe, it should also require companies to show their drugs worked. RCTs he figured were a new quick and cheap way to do this. If a drug doesn’t work it can’t be safe.
In 1960, Lasagna ran an RCT which showed thalidomide was an effective sleeping pill. The trial missed the SSRI like agitation, suicidality and sexual dysfunction it causes.
Slide 9: In the Oval Office 61 years ago, John Kennedy signed a new Food and Drugs Act and hands the pen to Frances Kelsey who blocked thalidomide’s approval in the US.
The 1950s was a miraculous decade for new drug discovery – psychotropics, antihypertensives, antibiotics, hypoglycemics, steroids – all without an RCT. Drugs that cured problems getting in the way of us living the lives we wanted to live – unlike today’s drugs.
Kelsey averted a Thalidomide disaster using a 1938 Act, which like regulations for food, cars, stock markets – focused on safety. But something had to be seen to be done about thalidomide.
The new 1962 Act adopted Lasagna’s proposal and required companies to prove their drugs were Effective and Safe. For most people the word effective means ‘works’ which means saves lives or reduces disability. Almost no drugs since 1962 have been shown in company trials to save lives or prevent disability. To show lives being saved would need trials lasting a decade. And, the hurdle to stop thalidomide happening again was one it sailed over in an RCT. The 1962 Act would have licensed it.
Frances Kelsey was the only woman in the room when this Act was signed. The Act replaced her professional judgement, that a sleeping pill, even if effective, should not cause a peripheral neuropathy, with an algorithm that biased development toward efficacy. It wasn’t clear then that company trials would replace clinical judgment – which Hill and Lasagna thought was critical – with algorithms. Designed to contain pharmaceutical companies, the New Act handed control over to companies.
Slide 10: Lasagna made a bad mistake, but with good intentions. RCTs were a poorly understood technique in 1962. Here in the 1990s you have him admitting to a mistake:
In contrast to my role in the 1950s which was trying to convince people to do controlled trials, now I find myself telling people that it’s not the only way to truth.
Evidence Based Medicine has become synonymous with RCTs even though such trials invariably fail to tell the physician what he or she wants to know which is, which drug is best for Mr Jones or Ms Smith – not what happens to a non-existent average person.
Slide 11: Like Vase and Faces you may see both an Older and a Younger Woman here.
Slide 12: The image shows Emer Cooke, CEO of EMA and Albert Bourla CEO of Pfizer.
As with all efforts to regulate pharmaceuticals, the 1962 legislators claimed they did not want to interfere with the practice of medicine. In 1914 they made heroin and cocaine prescription only and extended this to all drugs in 1951 – giving doctors a police function that doesn’t sit well with healing or professionalism.
We think we’re the consumers of drugs. We aren’t. Doctors consume drugs by putting them in our mouth – a situation ripe with a potential for abuse – especially as Pharma figure few doctors have any thoughts in their heads not put there by us or our competitors.
RCTs steered prescription only drug consumption toward diseases. Pharma’s answer was to give us multiple diseases. Are doctors going to stop this? Not when the greatest concentration of marketing power on earth only has to focus on comparatively few consumers
Slide 13: Here is Hill in the same 1965 lecture about Controlled Trials saying:
Clinical Trials have invaded the sales talk: “A double-blind cross-over trial on 22 patients has shown XYZ is the antibiotic of choice.”
What would Drs have made of that 20 years ago? It would not have been a selling point. But clearly it is thought to be so today”.
Like RCTs then – Pharma are the cheerleaders for EBM, which doctors think contains pharma.
Slide 14: At the risk of offence, the Catholic doctrine of Transubstantiation claims the wafer you see here isn’t a wafer – it and the wine are the actual Body and Blood of Christ. It takes the eye of faith for you to see this. I am not saying believers are wrong to see things this way.
The word randomization now has similar religious connotations. Even if done by the company equivalent of a pedophile priest, the evaluation of drugs is mystically transformed – poisons out of which we hope to bring good become sacraments – from which no harm can come. I am saying RCT believers are wrong.
Slide 15: The 1950s gave us the best antihypertensives, antibiotics and psychotropics ever – all without RCT input. Imipramine, the first antidepressant, is stronger than SSRIs. It treats melancholia which SSRIs can’t. Melancholia increases the risk of suicide 80-fold.
Imipramine was launched in 1958. By 1959, while praising it to the skies, doctors practicing Evident Based Medicine could still see it made some people suicidal. Stop the drug the suicidality clears. Re-introduce it, suicidality comes back.
Because it treats this high risk condition, an imipramine v placebo RCT in melancholia should show more red dot suicide attempts on placebo even though imipramine can cause suicide. This would look like evidence imipramine cannot cause suicide.
Slide 16: In the mild depression trials that brought SSRIs to market – there is an increase of suicidal events compared to placebo in people at little or no risk of suicide.
Slide 17: An imipramine comparator in the same trials also caused suicides. Context means the answer RCTs can give on the same drug can be quite opposite. There is no absolute truth.
We get opposite answers because these are Treatment Trials not Drug Trials. Believers claim RCTs control all confounders in all known universes, but if a condition and treatment produce superficially similar effects, RCTs cause confounding that RCTs cannot solve.
If a patient has a problem on a drug in a trial, as Hill said, a doctor needs to work out what is happening but in RCTs now clinicians are not supposed to use their judgment.
Slide 18: Healthy volunteer studies are Drug Trials. In Drug Trials in the 1980s, companies found SSRIs cause volunteers to become suicidal, dependent and sexually dysfunctional. We heard nothing about this when the drugs launched because Drug Trials enabled companies to engineer Treatment Trials to hide these problems. See God Does not Roll Dice for more on this.
Slide 19: In 1998, Don Schell, a tough oilman from Wyoming with a minor sleep problem was put on Paxil. 48 hours later he shot his wife, his daughter, his grand-daughter and himself. His son-in-law took a lawsuit against GlaxoSmithKline (GSK) – Tobin v SmithKline.
In the Tobin case, Ian Hudson, Chief Safety Officer of GSK was asked – Can SSRIs cause suicide. He says GSK practice Evidence Based Medicine (EBM) and base their views on RCTs, which do not show the Paxil sacrament has any side effects – it does not cause suicide or homicide.
Even the Catholic Church recognize the Eucharistic can have side effects and minimize the gluten in it, but these down here on earth considerations don’t bother GSK.
A jury of 12 Wyoming folk with no background in health thought Hudson was Mad. They dismissed EBM in favor of Evident Based Medicine. It was obvious Paxil caused these homicides, they said, and GSK were guilty of negligence.
Hudson, however, later became the CEO of Britain’s drugs regulator, and these Mad views are dug in at the top of FDA, EMA, and WHO.