Editorial Note: This is the sixth in the Lasagna series of posts that began with Not So Bad Pharma, April Fool in Harlow, Tragedy of Lou Lasagna, Empire of Humbug: Bad Pharma and will continue through to Witty A: Report to the President.
Faced with questions about the $3 Billion fine imposed on GSK – Is it just the cost of doing business? Andrew Witty, GSK’s CEO, snapped back:
Although corporate malfeasance cases end up looking very big, they often have their origin in just… one or two people who didn’t quite do the right thing. It’s not about the big piece. The 100,000 people who work for GSK are just like you, right? I’m sure everybody who reads the BMJ has friends who work for drug companies. They’re normal people… Many of them are doctors”.
This interview came about after an earthquake. For 50 years since 1962, the tectonic plates of regulation and science had been grinding up against each other. This led to an eruption in 1987, a quarter of a century after 1962, when pressure to get drugs on the market for AIDs led to a regulatory crisis. Lou Lasagna was called in to chair a committee to find a way forward. This ultimately led to speedier drug approvals and the Prescription Drug User Fee Act (PDUFA), whereby to the dismay of many industry ended up paying the FDA piper. This crisis played a significant part in the development of GSK, whose rise to global dominance was linked to AIDs treatment.
A quarter of a century later again there was a further eruption. For years there had been evidence of growing pressure on the fault-line between regulation and science with a range of campaigners pressing for access to clinical trial data. Then Peter Gøtzsche from Copenhagen hit pay dirt when he secured a ruling from the European ombudsman that the European Medicines’ Agency had no option but to make trial data available to anyone who applied for it. For a brief period, researchers could access the data from any trials held by EMA. It was other companies who in fact applied most often for the data.
The BMJ launched a campaign to ensure that rights of access to trial data would be maintained. The centrepiece of their campaign was Peter Doshi and Tom Jefferson’s efforts to get access from Roche to the data on Tamiflu.
Witty appeared to give a boost to the campaign by promising access to GSK’s trial data. The BMJ featured him on their front cover in Barack Obama political poster Shepard Fairey mode with the word HOPE underneath and a strapline – GSK’s Andrew Witty…The acceptable face of big pharma? They noted inside that, in response to his commitment to make data available:
[Witty] was singled out for praise by one of the industry’s harshest critics with Ben Goldacre calling it a “cartwheel moment”.
Many thought Pharma appeared split. Witty, the acceptable face of big pharma, appeared to be in favour of transparency but other companies filed an action against EMA in the European Court for infringing among other things their right to privacy, right to confidentiality, copyright and violation of legitimate expectations. The first time Pharma has taken the regulator to a Supreme Court since the Panalba case (see Tragedy and Witty A).
So if the problem is not bad people what is it that needs treating? Andrew made the point that there are few differences between him and us. But he wasn’t asked to take off a GSK hat, and answer as someone with a healthcare problem whether any of the points below that concern some of us would concern him. He wasn’t asked to distinguish between the efficacy of the current system in getting GSK’s drugs to market rather than its effectiveness in maintaining your and his health.
“This is your last chance. After this, there is no turning back. You take the blue pill – the story ends, you wake up in your bed and you believe whatever you want to believe”. Morpheus to Neo in The Matrix.
Having taken the Red pill, Neo wakes up to find the following:
Trials in branded pharmaceuticals from 1960 to 2000 were done in Western clinical centers where the patients did not always exist. Publications based on these non-existent patients litter the academic literature without retraction or even a cautionary note in the case of trials where it is known the patients didn’t exist or the investigators have been jailed.
Since the mid-1990s trials have increasingly been done in South Africa, Russia, India and other countries were patients have little idea what is going on and where if the patients exist and are injured they are routinely lost to follow-up.
In this case the Disappeared are those suffering from treatment induced deaths and disabilities. The means of disappearance range from elaborate methods to avoid collecting the data, to concealment of evidence and of company determinations that our drug caused that, to statistical and controlled trial techniques to make deaths and injuries vanish.
Treatment induced death has become at least the 4th leading cause of death, perhaps even the normative mode of death, but there are no concerted efforts to tackle this.
The lengths to which companies go to get an efficacy message out – ghostwriting trials, hiding data, and legal threats – pale in comparison to what they are prepared to do to hide or deny responsibility for the bodies of the Disappeared (See American Woman, American Woman 2).
This now extends to a growing number of children with birth defects miscarried or born to suffer and be stigmatized. We seem very unlikely to get a religious leader, Papal or other, willing to speak out about this.
Effective treatments should lead to a reduction in healthcare costs and in levels of disability but healthcare costs and levels of disability are rising. We have some very sophisticated drugs but behind the high tech façade healthcare is crumbling with patients in some cases more scared to go into hospital or even see a doctor than they have been for close on a century or would be in a Developing Country
(Helmut Schmidt in the 1980s described the Soviet Union as Upper Volta with Missiles).
Most Western countries have signed up to TRIPs which maximises pharmaceutical company profits to an extraordinary extent. It also puts in place a range of punitive sanctions should a country deem the needs of their citizens outweigh the right to profit of a pharmaceutical company.
Aside from the punitive sanctions, if a country does not support their marketing, companies threaten to relocate their operations elsewhere. Countries (viz. the UK) will do almost anything to keep a company operating within their borders – even offering up their citizens as all but involuntary participants in company trials that are run by doctors whom the taxpayer has educated and salaried. And these clinicians who used to be the critics and conscience of society have been told they must partner industry.
Consent forms were put in place in industry studies by Louis Lasagna in 1962 as a means of safeguarding patients. These have been transformed into an instrument of legal jeopardy, with patients unwittingly consenting that their data will be hidden from everyone for ever. This means that even when people have been injured in trials companies will say in public and in court we have no evidence for any injury on our drug.
Studies are undertaken on drugs that almost certainly have been undertaken in the knowledge that the drug causes death or injury and detailed knowledge of this hazard has been used to construct RCTs that will help hide the hazard. Neither the patients nor other doctors involved in such trials have any idea what is going on.
Close to all of the published literature about on-patent drugs is ghostwritten. Prestigious medical journals have encouraged this for the last 30 years. In terms of ensuring the integrity of the primary sources of a story and ensuring the authors are who they appear to be we would all be safer if clinical trials were published in the New York Times than in the New England Journal of Medicine.
Even the most prestigious medical journals are scared to publish articles raising hazards about drugs, or even articles by anyone identified as someone who raises issues about treatment, for fear of legal action from companies. The situation is every bit as bad as the level of censorship in the former Soviet Union. Anyone who has tackled pharmaceutical companies on the one hand or Dan Brown’s Angel and Demon Vatican, knows that the Vatican is kids play compared to Eli Lilly or Pfizer.
Academic journals and societies show an auto-immune response to what should be the life-blood of therapeutics.
Not only has most of the academic literature become one big advert for branded pharmaceuticals but when hazards are raised, companies have learnt how to use any concerns about a drug as a means to increase sales of the drug, and as a means to bind even more doctors ever more closely to the company bosom.
After lecturing about the suicide risk on Prozac a decade ago, I was greeted warmly by a woman who said she was responsible for PR for Prozac in the UK and she was really pleased to meet me as I was doing more for the sales of Prozac than anyone else.
Regulators never take it upon themselves to establish if a drug has a hazard. Their role is to manage risks. This does not mean that they warn about a hazard a drug might pose. It means they manage public perceptions or beliefs about a risk. Doubt is their product.
In the case of thalidomide the possibility that it caused birth defects met a regulatory response as to whether we have ruled out the possibility that it prevents the miscarriages of babies with birth defects. In the case of Matt Miller, a 13 year old boy who hung himself a week after going on Zoloft, it met a response that we cannot rule out that this was auto-erotic asphyxiation gone wrong and until we can it would be a mistake to blame the problem on Zoloft.
Guidelines depend completely on the published ghostwritten literature on which all data has been withheld. Once guideline makers treat company articles as though they are science they allow their guidelines to be captured by Pharma. By skilful publication strategies Pharma can always ensure that their latest on-patent drug features on top of the most independent guidelines. Economic pressures have forced a standardisation of healthcare in an effort to contain costs and this has transformed what was guidance into tramlines. These tramlines increasingly dictate what doctors have to prescribe.
Anyone raising the profile of a drug’s hazards is likely to get harassed, marginalized or terminated. The harassment will include having people in the audience to challenge everything said, reviewing everything written to see does it provide the basis of a legal suit, actively targeting and spreading malicious gossip and disinformation through PR networks, calling colleagues or friends to “get the dirt”, “reading everything you have ever written Dr”, triggering tax inspections etc. We just need a viral video clip to compete with Gangham-Style.
Anyone talking about the hazards of a treatment is marginalized by their clinical colleagues and any group seeking a balanced approach to treatment is likely to be stigmatised as Scientologists or as Ideological. This creates a Spiral of Silence where others observing what happens learn to remain silent.
The norm in science is that there is free access to the data underpinning experiments. If free access is denied, it’s not science. In the case of branded pharmaceuticals, we do not even know what trials have been done. There is a denial of access to any raw data from any clinical trials. We have even less knowledge of what drug trials (healthy volunteer trials) are done and again no access to data even though there are no issues of clinical confidentiality. What is put in the public domain is not data. What will be put in the public domain under Andrew Witty’s proposal is managed access which is likely to be worse for everyone than no access.
The selected highlights of a football game and the comments of the pundits afterwards don’t change the score. The selected highlights of Pharma studies and the comments of pundits routinely change the score.
Any attempt to seek substance behind the rhetoric is likely to lead to vilification, intimidation and harassment.
Clinicians and the public are routinely sold a biobabble about drugs and diseases that is as ideological as anything found in Soviet Lysenkoism. The problem in this case doesn’t lie in the biological sciences it lies in the social sciences and anthropology as well as the humanities which have been used to produce an informational reductionism and standardization on the one side and to develop marketing on the other. (For a first use of Biobabble – see 1999).
Instead of the old-Soviet style Five Year plan we have the rolling marketing campaign linked to patent expiration. In sequence people have to be persuaded they are anxious, then converted to depression, and after that converted to bipolar disorder, or moved from pain plain and simple to fibromyalgia, or from ulcers to GERD.
Linked into the same processes, doctors are rewarded with financial incentives for adhering to guidelines for illness that may have only been invented a few yeas before – seen as The Method to good health by governments. Many of these incentives relate to targets like ‘the proportion of patients taking Brand X or Y.’ Doctors are coerced with targets to persuade patients into taking drugs, incentivized by payments with the quality care measured in volumes of pills or vaccines and adherence to policy.
Few are aware that almost all drugs are made available under police state provisions and supervision. The availability of medicines on a prescription-only basis was introduced as a means to control heroin and cocaine addicts in 1914. The War on Drugs initiated then has become a permanent War in which all citizens are treated as addicts and all doctors as police.
Extending prescription-only privileges to all drugs was sold to the wider population as a means through which medical scepticism would temper patient zeal for treatment. But doctors now funnel drugs to people in the Matrix in amounts that have many of pleading for respite or else surreptitiously dumping our medicines.
Rachel Liebert outlines how recent school shootings have led to the creation of a Homeland Security apparatus in our schools and colleges aimed at detecting any signs of abnormality in any students and getting them on medication.
There are lots of Good Germans in the system. All tyrannies have passed – up till this anyway. You have to survive till then, and life is more comfortable in the Matrix than outside. Unless they have come to take you or someone you know away, its better keep your head down and eyes averted. Keep taking the blue pills.
“The 100,000 people who work for GSK are just like you, right? I’m sure everybody who reads the BMJ has friends who work for drug companies. They’re normal people… Many of them are doctors.”
Any German in the 1930s or 40s could have said the same of his fellow-countrymen. And the subjects in the famous Milgram experiments were no doubt just like you and me also.
In the 1960s, there was great concern at the development of medical techniques that looked likely to lead to a control of behaviour. These concerns played a large part in the rise of post-modernism which was a protest before the event against the ideas that took shape in the 1990s that Prozac, Genetics and the New Biology would usher in a New Man.
Astonishingly, these concerns reached the level of a Congressional Hearing as far back as 1967. Seymour Kety, then the head of the NIH, attempted to put the developments in context for Congress:
“The manipulation of the brain by any of the biological techniques which can be developed in the foreseeable future would involve such drastic invasions of privacy, integrity and the unalienable rights of the individual that in their application behavioral control would already have been achieved even if the electrodes carried no current and the pill were placebo”.
Our pharmacological and biological techniques have not moved on much since then. The therapeutic armamentarium is in many respects weaker now rather than stronger but in its weakness it reveals that what has changed is that control has been achieved even when the electrodes carry no current and the pills are placebo or more harmful than placebo.
This was an outcome predicted by some in the 1960s, such as Jacques Ellul in The Technological Society, in which he argued that the techniques to really worry about were our public relations and marketing techniques rather than our engineering or biological techniques. The social scientists and students of rhetoric (media studies) of the 1960s, coached in post-modernism, migrated from universities to populate the marketing departments of pharmaceutical companies (see Factories of Post-modernism). They brought with them a means of control through a set of techniques first pioneered by Edward Bernays but greatly developed since then.
We operate now in a post-fascist state. Back in the 1960s the totalitarianism of the Soviet Union was a horror but Soviet citizens could very clearly see the enemy. The problem in the West now is that control can be far more complete because the mechanisms and levers are invisible. We volunteer into rather than are coerced into running the apparatus of repression. We live in a Benevolent Fascism.
From this point of view there are lots of reasons to think we might be better off if Pharma’s current legal action against EMA succeeds leaving us clearly able to see Bad Pharma withholding data than if data access is maintained but we get our access through a proposal put forward by someone just like you or me.
Illustration: HOPE: Pills You Can Believe In, 2013 created by Billiam James
Copyright © Data Based Medicine Americas Ltd.
Hi David. Terrific, thought-provoking article. I’m interested in the points you make in (8) Propaganda 101: How do the Pharma spinners turn criticism to their advantage? Any recommended reading where I can learn more about this?
Also, I thought the Milgram reference was most appropriate. This is precisely the response exhibited by most patients when receiving ‘advice’ from their medical practitioner. If a drug is offered, it is accepted.
I laughed at the Vatican/Eli Lily comparison. The difference would seem to be that the Cardinals believe they have some higher authority looking over their shoulder, and Big Pharma knows that they don’t. Yet.
All the best
“We live in a Benevolent Fascism”. You are so right Dr Healy- we in the west cannot see the enemy. Your perceptive comment reminded me immediately of the letter Aldous Huxley wrote to George Orwell in 1949, soon after 1984 was published, in which Huxley argued that his imagined totalitarian future of Soma and consumerism would win out over the “boot in face” totalitarianism of Orwell. And it surely has done just that.
“Anyone who has tackled pharmaceutical companies on the one hand or Dan Brown’s Angel and Demon Vatican, knows that the Vatican is kids play compared to Eli Lilly or Pfizer.” A June 14-15 conference, hosted by the Vatican,will examine the evidence for (and against) the rise of psychiatric medication and fall of psychosocial treatment for children. Does this strike anyone as a bizarre location for the discussion of what can only be described as a form of abuse of children? If we do live under Benevolent Fascism (an oxymoron if ever there was) it is perhaps fitting that the conference is being held in the land of Mussolini. Not politically correct, I know, but then I consider “political correctness” as an oxymoron too.
A few hours after the last sentence in this blog was posted, Guido Rasi of EMA sent this email notifying people of a suspension of EMA’s access to clinical trial data provisions.
———- Forwarded message ———-
, Jablonski Tomasz , Rampal Olmedo Nathalie , Spina Alessandro , Harvey Allchurch Martin
From: Rasi Guido
Date: 30 April 2013 12:55
Subject: Update on EU Court interim measures decision in AbbVie and InterMune court cases
Cc: Eichler Hans-Georg
Dear friends and colleagues
I write to update you on developments in the Court cases concerning the Agency’s access to documents cases.
The President of the General Court signed interim relief orders on Friday 25 April 2013 that prevent the Agency from providing access to documents requested in the AbbVie (T-44/13) and InterMune (T-73/13) cases.
In making the ruling, the Court has taken into account that it is the first time that the Agency’s policy is being legally challenged and that it raises difficult issues that could not be ruled on in the context of an interim ruling. As such it decided to maintain the ‘status quo’ that existed prior to our implementation of the 2010 policy.
I am naturally disappointed by the ruling and I have asked my Legal Service to consider the possibility to appeal the interim ruling.
I will issue a public statement on the Court rulings at 13:30 London time today, but wanted to inform you of this in advance.
As part of the process of drafting our planned policy on proactive publication of clinical trial data, we will also publish later this afternoon (14:30 London time) the final advice from the five advisory groups which were formed to inform the Agency on specific aspects to the policy, together with a short news story.
Finally, while we have no immediate plans to release the information, I would also like to ask whether your organisation would give permission for us to name you as having given support to us in this endeavour.
If you are happy for us to do so, could you please contact Martin Harvey (firstname.lastname@example.org) to let us know.
Thank you again for your support.
European Medicines Agency
7 Westferry Circus, Canary Wharf
London E14 4HB
Tel. +44 (0)20 7418 8406
Fax +44 (0)20 7418 8409
Toby Tyler Watson commenting on Facebook wrote:
“I had Mental Health America threaten to sue me for indicating they would not attend a seminar to discuss the problems of medicating young children with SSRIs. They said by saying they would not come, it lent credibility to my claim that SSRIs posed an increasing danger to them. oh how the times have begun to change….Dr. Oz.”
See Jim Murray on
Pharma vs The European Medicines Agency – the case of InterMune
Like AbbVie, described in my last post, a second American company, InterMune, has taken legal action to prevent or restrict the European Medicines Agency from disclosing certain clinical trial data after a medicine is approved for marketing.
On 4th March a federal appeals court upheld the conviction of the former chief executive of InterMune, W. Scott Harkonen, relating to the dissemination of false and misleading statements about the results of a clinical trial of the medicine Actimmune. (Mr Harkonen may launch further appeals.)
According to an earlier statement from the FBI:
“Evidence at trial further showed that Harkonen caused InterMune to issue a false and misleading press release publicly announcing the results of a clinical trial of Actimmune for the treatment of IPF on Aug. 28, 2002. Although the clinical trial had failed, InterMune’s press release falsely stated that the results of the clinical trial established that Actimmune helped IPF patients live longer. The headline of the press release read, “InterMune Announces Phase III Data Demonstrating Survival Benefit of Actimmune in IPF,” with the subheading “Reduces Mortality by 70% in Patients with Mild to Moderate Disease.”
In 2006, the company itself had reached a Deferred Prosecution Agreement with the Department of Justice and agreed to paid fines and penalties of $36 million. One clause in the agreement states that it “does not provide any protection to any former employee of InterMune”. Mr Harkonen had left the company in 2003.
Actimmune was promoted as treatment for idiopathic pulmonary fibrosis (IPF), a rare but fatal disease. Treatment cost around $50,000 per annum, generating revenue of over $100 million, mostly for treatment of IPF. (Doctors may prescribe but companies may not promote medicines for uses for which they have not received an authorisation. )
In so far as the offending press release had a basis it seems to have come from the selective use of the data from a clinical trial labelled GIPF-001 – a practice sometimes known as data mining or data dredging. From the beginning, there were some sceptical voices about the company’s claims and in January 2004 an article in the New England Journal of Medicine concluded that Actimmune “did not affect progression-free survival, pulmonary function, or the quality of life”.
Another case for timely and full disclosure.
On the indictment of Mr Harkonen, Intermune issued a press release, of which this is an extract:
“Since 2004, InterMune has been a transformed company with a new management team, a rigorous compliance program and a promising pipeline focused on serious pulmonary and hepatic diseases.”
Still, it’s a pity that the earlier experiences of InterMune and AbbVie/Abbott have not convinced them of the merits of more transparency on the part of the European Medicines Agency… END
Pharma vs the European Medicines Agency- the case of AbbVie(Abbott)
Posted by jim on 01/05/13
Two American pharmaceutical companies, AbbVie and Intermune, have taken legal action to prevent or restrict the European Medicines Agency from disclosing certain clinical trial data after a medicine is approved for marketing.
In my opinion, both companies have been involved in activities that seem to prove the need for more transparency and not less.
AbbVie is a new company founded to carry on the work of most of the former medicines division of Abbott Laboratories. This was not a third party takeover, but a split of one company into two separate entities. AbbVie is basically the old medicines division of Abbott and therefore inherited the Corporate Integrity Agreement signed between Abbott and the US Government last October.
In October 2012, Abbott was required to pay $1.5 billion in criminal fines and civil settlements for promoting a medicine, Depakote, to treat dementia and schizophrenia. The medicine was not authorised for these indications.
According to the US Dept of Justice:
“Abbott has pleaded guilty to misbranding Depakote by promoting the drug to control agitation and aggression in elderly dementia patients and to treat schizophrenia when neither of these uses was FDA approved. In an agreed statement of facts filed in the criminal action, Abbott admits that from 1998 through 2006, the company maintained a specialized sales force trained to market Depakote in nursing homes for the control of agitation and aggression in elderly dementia patients, despite the absence of credible scientific evidence that Depakote was safe and effective for that use. In addition, from 2001 through 2006, the company marketed Depakote in combination with atypical antipsychotic drugs to treat schizophrenia, even after its clinical trials failed to demonstrate that adding Depakote was any more effective than an atypical antipsychotic alone for that use”.
According to the Agreed Statementof Facts, Abbott delayed for years in disclosing the full results of clinical trials showing that Depakote was no more effective than a placebo, and aggressively promoted Depakote through its sales force, special “educational” material, speakers fees, and selective use of study results.
For schizophrenia, Abbott submitted to the FDA in January 2002 the results of a trial described as “negative” by the company itself. (This was a trial of Depakote combined with another medicine.) Patients showed some improvement up to 21 days, but not up to 28 days – the primary “endpoint” of the study. However, Abbott used the 21 day results, the “secondary endpoints to promote Depakote to health care providers as a treatment for schizophrenia” at least up to 2006. The promotion was expensive and intensive and is described in the Agreed Statement.
Abbott carried out a second study on Depakote and had concluded by January 2005 that the results were negative. However, they continued for a very long time to use the first study in their promotion and did not disclose, even to their own reps, the results of the second study. In August 2006 they published a synopsis of the second study, which spoke of the Depakote combination as being “well tolerated”. It did not mention that patients treated with Depakote were more than twice as likely to suffer from “somnolence” than those treated with the alternative.
If the company had made a full and timely disclosure of their clinical trial results in this case they could not have continued to misbrand this medicine for as long as they did.
I will say something, also interesting, about the other company, InterMune, in a later post. END