Go Figure: A Geek Tragedy
In 1939, in the laboratories of Geigy pharmaceuticals, Paul Mueller discovered that DichloroDiphenylTrichlorethane DDT killed insects more effectively that anything else then available.
Robert Domenjoz, the later creator of imipramine, had the job of evaluating it. He did the testing on lice that was to make DDT one of the best-selling pharmaceuticals in the world. He asked the Salvation Army to bring him two of the paupers who slept there and he bought their shirts – for their lice. He put the lice in small boxes which could be sealed with a sieve so that the lice could breathe. He attached the boxes to his arms so that they could live off his blood. Over weeks, they multiplied. When he had enough, they started testing DDT on them. It worked a treat.
Lice carried typhus, which killed more people in wars since Napoleon than the actual wars had killed. Domenjoz headed straight to the Swiss army who started using it and then presented the results at the American embassy in Bern. When the Americans invaded Italy soon after, the troops were all sprayed with DDT and pretty soon everyone who was liberated from the Germans was liberated from lice also.
After the war was over
After the War it became common to spray the public in cinema queues and at football games across Europe and America for instance as the photo shows. Mueller won the Nobel Prize in 1948. Domenjoz might have thought at the time he should have shared it.
As almost every ghostwritten article about all of the drugs in current use now says, DDT was very clearly safe and effective.
The use of DDT spread. The images most of us have now is of planes dusting crops with plumes trailing behind them.
Then in the early 1960s the wheels came off the bandwagon. By the time Rachel Carson’s Silent Spring was published, DDT was on the road to oblivion, with most of us thankful we had been saved from oblivion. DDT it became clear accumulated in the food chain, with small doses in some insects and crops, ending up as larger doses in the predators living on them,and larger and lethal doses in the birds, fish and other mammals living on them, or in their eggs or milk. And larger doses in us.
We had learnt that the acute effects of a drug given in a particular way might be dramatically different to the effect that came with chronic exposures or from unexpected routes of administration.
Wasn’t this what we learnt?
Geek tragedy
Controlled trials (RCTs) are all about establishing the acute effects of a drug given in a standardized way by drug companies who hope the verdict will be their chemical is safe and effective so that they can head out and put it in the drinking water (metaphorically). People will end up on these chemicals chronically and they will be mixed with lots of other chemicals in ways never imagined when the drug was first tested.
The result is biphosphonate drugs marketed to reduce the risk of fractures which increase the risk of serious fractures. Antidepressants marketed to reduce suicide risk, alcoholism, substance misuse, marriage breakdown etc which increase the risk of all these things, as well as causing Autistic Spectrum Disorder and birth defects. Statins marketed to reduce risks linked to diabetes which increase rates of diabetes, and to reduce the cognitive problems stemming from strokes but causing cognitive problems in their own right. RCTs miss all of these things – and when they don’t miss them as in the case of the antidepressants and suicide the data is fudged, sometimes fraudulently.
Far from recognizing the role of RCTs in producing a new Silent Sprint, RCT enthusiasts are spreading the word that we need more of them. No-one should be on a treatment who isn’t in an RCT. This is the script for a Geek Tragedy.
RCTs do more than miss the long term injuries a drug might do us. They get used to build standards of care to which doctors are obliged to adhere. Anyone who figures it might not be wise to add a sixth drug into the mix a person is on, or that thinks that maybe adolescent crises are not something that need medicating, will find themselves up against these standards of care facing managers who ask Who are you to go against the Standard of Care? Sorry we have to let you go.
Part of the tragedy is that we would in fact save vast amounts of money by giving the pharmaceutical companies 10 times the inflated prices they currently receive for drugs as part of a bargain where their marketing ensures that only 10% of those currently taking lipid-lowering drugs, antidepressants, biphosphonate and other drugs end up on them – and perhaps slightly higher proportions for hypoglycemic drugs, antihypertensives and antibiotics. The savings would come from shutting down osteoporosis screening services. From the savings on not having to treat treatment induced disabilities. From Elective patients (patients on cancer chemotherapy) not having their bed blocked by an antidepressant induced suicide attempt or biphosphonate triggered fracture of the femur, or a hypoglycemic episode (the biggest cause of brain damage) triggered by the use of extra hypogylcemic drugs being used to lower blood sugars elevated by the use of Statins that current standards of care mandate in diabetes.
Most of us thankfully won’t get tangled up in these elements of the tragedy – the final scenes where as in King Lear the corpses are strewn around the stage. For most of us the ending will more like the ending of a play by Samuel Beckett – The Algorithm will See You Now.
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At the risk of being accused of hyperbole, I assert that most living things on our planet are caught up in the human hubris of releasing thousands of chemicals into the environment without knowing the longterm bio-accumulative and synergistic effects. These chemicals include not just pharmaceuticals and pesticides, but also food additives, cosmetics, cleaning products, industrial waste, etc., many of which have been found to be endocrine disrupters or carcinogens. Many of these substances have never been tested for safety (they were grandfathered or generally recognized as safe), but if they were, as you point out, since their short-term acute effects seemed trivial, regulators allowed them into the supply chain, and once they’re in, they’re difficult to remove and in any case will persist in the air, soil, and/or drinking water for many years. Even though DDT was banned in the US in 1972, it’s still found in breast milk and fatty tissue*, and it’s still used in some developing countries.
*Jaga K, Dharmani C. Global surveillance of DDT and DDE levels in human
tissues. Int J Occup Med Environ Health. 2003;16(1):7-20. Review. Corrected and
republished in: Int J Occup Med Environ Health. 2006;19(1):83. PubMed PMID:
12705713.
David, you have the knack of putting into words – actually a whole history lesson – the very ideas that many of us have been putting into (in comparison) very poorly constructed sentences – the knowledge that humans are very poor learners and repeat the same type of mistakes generation after generation!
Surely, we should have been able to deduce by now the truth of the saying ‘if anything sounds too good to be true, it probably is’. Instead, we put all our faith in any new, fashionable idea that comes along – having read only the bits that we want to see before we try them. The saddest fact, to me, is that, these days, despite all that ‘modern science’ can offer, we are only given the ‘truth’ of such a minimal number of trial cases although, in most instances, many different tales are left untold. Maybe that was also true back in the day of DDT trials – but now we KNOW the consequences, shouldn’t it be considered a crime to KNOWINGLY continue in the same vein?
I was amazed by the story of Domenjoz’ “testing” of DDT … on the lice. It killed them reliably, of course. Was there really no testing of the effects on people – or other living things in the areas being sprayed? Yikes.
In medical research, they call this sort of thing a “Surrogate Outcome.” The real outcome, of course, is the long-term health of the people being treated, which might not be captured at all in most RCTs of medicines OR pesticides. In order to do so you’d have to be able to track both the decrease in the number of cases of typhus or malaria, and any increase in illnesses caused by the pesticide. (Not to mention the harms caused to plants and animals, which might take a generation or more to harm the future of humanity.)
A “Surrogate Outcome” is a result that’s faster and easier to track, and that you *assume* will lead to the long-term outcome. Like “number of lice killed.” Or “cholesterol level in blood,” when it comes to statins. Trouble is, the real outcome doesn’t always match the “surrogate outcome”, to put it mildly.
The U.S. Senate is now poised to pass a “21st Century Cures Act” that will, among other things, make it easier to get drugs approved by relying only on surrogate outcomes – or in some cases, without any Randomized Controlled Trials at all, if there are “case studies” showing impressive improvement in a few patients …
What you are saying is so, so frightening Johanna, and yet when I think – and re-think – about it, how different will the situation be really? ‘It’s worked for a few’ without RCTs, as opposed to ‘ we tried it out on many but we’re only telling you about the few positive results’ with RCTs – takes us to almost the same place really, don’t you think? Either way, it takes us nowhere near to the true picture – that’s for sure!
Dr. Healy –
This is an incredibly eloquent, succinct post….
There must be something in the water in North Wales!
Here is another case of ‘money talks’ or ‘never mind the plebs’. This is totally non-medical but relevant inasmuch as there were many protests but no ‘high- ranking listeners’.
A good few years ago, a tranquil, close-knit rural community disappeared under water. Not a natural disaster, oh no, water was needed for an expanding urban area of England – so it was thought a wonderful idea to drown a Welsh community for the benefit of another nation. There were promises galore but the reality is that no amount of money could ever replace that which was lost – and, once lost, if was impossible to reproduce the same atmosphere elsewhere.
A Cautionery Tale..
http://archinte.jamanetwork.com/article.aspx?articleID=1672283
Research
Inconsistent reporting of surrogate outcomes in randomised clinical trials: cohort study
http://www.bmj.com/content/341/bmj.c3653
and..
http://www.fda.gov/aboutfda/innovation/ucm512503.htm
It goes on and on. The lessons of history never seem to over-ride so-called Prgress, things apparently done for the greatest good of the greatest number.
We spent ages campaigning against the genetic modification of foods, and against the cavalier approach of Monsanto. I actually thought we had halted that, but no, it’s creeping back again under the radar.
We’re told we need it to feed the starving peoples of the world. Surely it would be better to find ways of naturally improving (feeding and irrigating poor depleted soil) so they could produce reliable crops of naturally healthy food. Not genetically modify everything so they have to pay Monsanto for the privilege of using their own seed.
A little stream runs through our village. New affordable houses were built, (too many for the little site, we felt, like dark rabbit hutches) with a sewage treatment plant, designed to discharge into it. The village protested ahead of time, when we were cynically told things were open to ‘consultation’. The Water Board said they use ‘models’ to assess likely problems. They wouldn’t listen to us. It went ahead. Our MP played ducks and drakes, pretended to help, but had no intention of so doing. He wasted our time and hope. There have, needless to say, been problems with the smelly treatment plant, which we have alerted the powers-that-be to. The Environment Agency seem powerless to do anything. It is the age old problem of constant frustration – we told them so ahead of time and it was common sense, but money talks. Easy to see how Silent Spring happened.
You can’t take the money when you go, though. I wonder if you can look back (when you get there) with great regret at the destruction you caused in a beautiful world. I do hope so. I especially hope that all the well paid ghost writers and BSers in Big Pharma find themselves experiencing the destruction of their minds and bodies that they’ve inflicted on others, and that the doctors, who didn’t bother to use their intelligence to think carefully about what they were prescribing, experience the hell they’ve facilitated.
brilliantly written, thankyou.
What were we saying about ‘surrogate endpoints’..
https://www.statnews.com/pharmalot/2016/09/19/sarepta-fda-duchenne-behind-the-decision/
Until now, the FDA had not approved a drug to treat Duchenne, prompting parents and some lawmakers to argue for accelerated approval4, a process that relies on surrogate endpoints instead of actual medical benefits to endorse a drug.
https://www.statnews.com/pharmalot/2015/11/19/pharmalot-duchenne-advocacy-fda/
But their victories have also raised uncomfortable questions.
But in late 2013, a bomb dropped: A 186-person trial that was testing drisapersen, the competing drug then being developed by Prosensa Therapeutics and its partner GlaxoSmithKline, failed. The drug did not produce a meaningful difference7 in a six-minute walking test compared with boys who were on a placebo for close to a year.
http://www.gsk.com/en-gb/media/press-releases/2013/gsk-and-prosensa-announce-primary-endpoint-not-met-in-phase-iii-study-of-drisapersen-in-patients-with-duchenne-muscular-dystrophy/
Did the FDA set ‘a dangerous precedent’ with its latest drug approval?
https://www.statnews.com/pharmalot/2016/09/19/fda-sarepta-precedent/
But the approval may have set a precedent that could rocket through the health care system, opening the door for drug makers to get more medicines to market — even with scant evidence that they work.
Annie has touched on an important controversy here – the FDA approval on Monday of a new drug for Duchenne’s muscular dystrophy (DMD). And it don’t look good.
The trial of “eteplirsen” from Sarepta Therapeutics involved only 12 patients. There was no control group – their results were compared to “historical data” on other patients with DMD. And while Sarepta’s drug apparently helped some patients boost their levels of a muscle protein called dystrophin, there was no evidence that this improved their ability to walk. At the very best, the drug produced some improvement on a surrogate endpoint that made no difference in real life. Even FDA head Robert Califf conceded there were “major flaws” in the evidence – but he approved the drug anyway.
Sarepta won, in part, by exploiting desperate parents of young boys with DMD, most of whom progressively lose the ability to walk and die in young adulthood. The boys and their families were trucked to Washington, D.C. to make emotive pleas: “FDA, please don’t let me die early.” Meanwhile, the FDA actually cited the financial state of Sarepta, arguing that the company “needed to be capitalized” in order to guarantee it the money to conduct future research. Sarepta will have until at least 2021 to show the FDA the drug actually works.
On Monday, Sarepta Therapeutics blandly announced that their dubious miracle would cost about $300,000 per year. “We tried to be reasonable,” the CEO said. We don’t even know for sure that this drug is safe to take for a year – much less if it will add either time or quality to anyone’s life. This is not a case of “compassionate access” to an unproven experimental drug for dying patients. This is an uncontrolled but wildly profitable experiment on sick kids, and a highway robbery of their families and communities.
Big thanks to Ed Silverman of Pharmalot for bringing us the whole story …
Ex L’oreal lady takes on Paroxetine as part of her Portfolio Brief:
http://www.gsk.com/en-gb/media/press-releases/2016/emma-walmsley-to-succeed-andrew-witty-as-chief-executive-officer-of-glaxosmithkline/
The CEP Campaign…addressing the .eek tragedy
“Side effects and withdrawal effects can be very severe and last for months and sometimes years, often leading to disability and sometimes suicide”
http://cepuk.org/2016/09/21/support-campaign-recruit-mps-demand-national-helpline-prescribed-drug-dependence/
The All Party Parliamentary Group for Prescribed Drug Dependence (APPG for PDD)
The APPG is addressing the growing problem of prescribed drug dependence (PDD). Increasing numbers of prescriptions for addictive, psychoactive drugs are being given to both adults and children, including benzodiazepines, antidepressants, antipsychotics, stimulants and painkillers. While these drugs may help some people in the short term, there is growing evidence that long-term use leads to worse outcomes, and many patients report devastating persistent withdrawal and other negative effects. The APPG for PDD will engage with this issue by demanding appropriate services for those affected, proper training for medical professionals, reduced prescribing through adherence to new and existing guidelines, better data regarding the prevalence of PDD and more research into long-term harms associated with PDD.
The Chairman of the APPG is Paul Flynn MP. The co-chairs are Lord Patel of Bradford, David Tredinnick MP, Baroness Masham of Ilton and the Earl of Sandwich. The APPG website can be found at prescribeddrug.org.
Wendy Dolin/Paxil/Akathisia/Widowed
https://www.youtube.com/watch?v=cvoIFbR9OPk
A remarkable reminder..from a remarkable woman..her G tragedy
The G interview
http://www.gsk.com/
Journalists behave like psychiatrists.
She mentions China; journalists talk about China fine.
She desists from talking about US.
Journalists desist from talking about $$$3 Billion Fine.
Patient mentions a worry.
Psychiatrist leaps on worry; prescribe an SSRI.
The level of reporting was spontaneous, overnight, knee jerk, and really not revealing; apart from her gender, which seems to have caught their imagination..
Emma is going to develop the Consumer side of things, as with L’Oreal; GSK have lost their wherewithall
http://www.bbc.co.uk/news/business-37416282
http://www.ibtimes.co.uk/glaxosmithklines-new-boss-who-emma-walmsley-1582379
http://www.wsj.com/articles/glaxosmithkline-names-emma-walmsley-as-new-chief-executive-1474353563
A flying start…press on board…the ship keeps sailing…
http://www.madinamerica.com/2016/09/go-figure-a-geek-tragedy/
Serious drug side effects are massively underreported in medical papers
http://www.wired.co.uk/article/drug-side-effects
GlaxoSmithKline has promised..
http://www.gsk.com/media/280827/disclosure-of-clinical-trial-information-policy.pdf
J on September 21, 2016 at 6:32 pm said:
Scary, but informative! People should send this article to their psychiatrists – and anyone else who believes that psychiatrists want to or *can* set limits on their power to “treat” their patients to a date with the grim reaper.
The BMJ @bmj_latest 15h15 hours ago
“Clear eg of the absurdity of industry’s ghostwriting definition is #Study329 ”
#BMJresponse http://www.bmj.com/content/354/bmj.i4578/rr-3 … http://www.bmj.com/content/354/bmj.i4578 …
Re: Ghostwriting: the importance of definition and its place in contemporary drug marketing
21 September 2016
Alastair Matheson
Independent consultant
Toronto, Canada
http://www.bmj.com/content/354/bmj.i4578/rr-3
A hugely fascinating discourse from Aspen Institute on Business in Pharmaceuticals…streamed live at 5.00 pm.yesterday
https://www.youtube.com/watch?v=hHUXGqYjSDU
Competing interests: I am a supporter of innovative pharmaceutical research and have affection for, and friendships within, pharmaceutical corporations and also the marketing and publications trade, whose employees I consider to be ethical and professional. As stated in my article, between 1994 and 2012 most of my income came from consultancy and writing services provided to pharmaceutical corporations, either directly or via marketing agencies. In 2015 I acted as a paid expert witness on behalf of the plaintiffs in a US federal legal action against a drug company.
#study329
https://twitter.com/hashtag/Study329?src=hash
Back to Rachel Carson’s Silent Spring for just a moment. BBC Radio 4 ‘Any Questions’ Friday 22nd Sept at 8pm. The question of Fracking came up. Most of the team and audience are very much against. Unproven safety, why do we need to take such risks etc? My question in my head, want to scream at them, why do we rush headlong into these projects, with the carrot of saving money waving ahead of us. The Tory member of the team defends it. Words to the effect of, yes, I know it’s unpopular to say this but we’ll be running out of power, and anyway, If it doesn’t work, we can stop. He’s got to be kidding, right?
When our water courses are full of muck, and our world even more contaminated, we’ll decide to stop. But cheer up folks, the energy bill will go down a bit, oh, grat.
But of course, when the water courses are full of muck, and the samples show it, it won’t be due to Fracking. It’ll be due to some geological changes that were happening anyway. No muck will stick to that industry. Just like no muck sticks to Big Pharma although it’s been put inside so many thousands.
Come on Jeremy Corbyn – let’s stand up for real Progress, unlimited by corporate bribery. I love the comment I heard made by a journalist yesterday, describing his defence of his leadership campaign against ex-Big Pharma corporate employee Owen Smith; ‘it’s been like a contest between Red Rum and a donkey’. Wonderful. Politics is changing. I bet Jeremy would have no truck with Big Pharma, and he doesn’t have to be PM to do that, he just needs to put a spotlight on them again and again, and get the people’s voice heard and taken seriously once and for all. And whatever we may think of him as a new kind of leader, I cannot imagine him being bought off against principle by anyone. Which, I feel, is why so many are scared of him and want rid of him.
PS – Emily Thornberry, Labour MP and staunch supporter of Jeremy Corbyn is on the APPG team that Annie has alerted us to. Are we all going to submit depositions to them, en masse, putting them in our pictures? There only seems to be a place where we can sign up to be kept informed of how they are doing, shouldn’t we be blitzing them with our APPG experiences? Emily Thornberry would seem a good choice to write to.
Heather, on the APPG site you are able to send comments too. You don’t necessarily get rewarded with a reply, therefore it’s a case of hoping for the best that your concerns have been noted. I’ve a feeling that Jane said that she is linked with the APPG one way or another.
Thanks for this Mary, I guess if lots of us did this, it could all help to raise awareness. One tends to think we are all small and can’t do much to change things, but there is the Butterfly Effect, where a small movement somewhere on earth can have unseen dramatic results elsewhere, so every bit of effort is worth making. You never know what might help to tip the balance!
This BBC Journalist has ideas and wants to share..
http://survivingantidepressants.org/index.php?/topic/13214-bbc-journalist-looking-to-expose-problems-of-withdrawal/
APPG on Opioids:
http://prescribeddrug.org/agm-and-meeting-on-opioid-painkiller-dependence-to-be-held-on-19-october-2016/
Scientic integrity through Data Based Medicine
Inverstigation results
BMJ Publishes Study Revealing How Flawed Drug Research Fails a Trusting Public
Dr. Healy says he believes that the issues uncovered are bigger that what happened with Study 329. “This was not an anomaly, but rather what has become standard industry practice for branded medicines. It raises many questions about drug safety, the limitations of randomized controlled trials, the need for access to individual patient level data, and the question of how to reduce harms from misleading health information.”
Fellow author Dr. Jon Jureidini says, “Our reanalysis of Study 329 reveals that drug regulators, pharmaceutical companies, senior ‘independent’ researchers, and journal editors are all failing patients. The core problem is that the process for safety and effectiveness testing is left to drug manufacturers, who have a vested interest in seeing positive results without the medical and scientific community being able to scrutinize what they are doing.”
http://study329.org/bmj-publishes-study-revealing-how-flawed-drug-research-fails-a-trusting-public-2/
$$$3 Billion seems a very popular figure..
Dear Priscilla and Mark
You are making a wonderful contribution in your pledge of $3 billion to medical research
http://www.alltrials.net/news/open-letter-zuckerberg-pledge-medical-research/
Zuckerberg and Chan aim to tackle all disease by 2100
By Leo Kelion Technology desk editor
21 September 2016
From the section Technology
Facebook’s founder Mark Zuckerberg and his wife Priscilla Chan have pledged $3bn (£2.3bn) to fund medical research over the next decade. …
http://www.bbc.co.uk/news/technology-37435425