Deadly Medicines and Organised Crime

by Peter Gotzsche

  22

  Having the last laugh at big pharma

  What I have described in this book is so tragic that I felt it needed a good-humoured ending. I shall start with a tragicomic industry-sponsored meeting. In 2011, the vice-chairman of the Danish Medical Association, Yves Sales, and I were invited to give talks at a meeting arranged by the Danish Society for Rheumatology. The theme was: Collaboration with the drug industry. Is it THAT harmful?

  A chief physician at my hospital had suggested the theme but was met with protests when he suggested the title, Collaboration with the drug industry. Is it harmful? Some of the members of the society’s board were in the pocket of the industry, whereas the standard at his department was to have no contact with sales departments in companies. Opinions were divided about whether the society should continue to have industry-sponsored meetings, and they felt a need for information and provocation. The Danish Association of the Pharmaceutical Industry first declined to participate but sent its vice director, Henrik Vestergaard.

  I was told that there would be industry people in the audience although they didn’t appear in the list of 115 participants. Ah, well, of course. A society called Young Rheumatologists had just held a meeting with about 30 rheumatologists and about 60 people from the drug industry. Like the parents, so the children.

  During a pre-meeting dinner, the chairman of the meeting asked me not to be too tough with the industry; I smiled and said it was too late to change my talk. I don’t go to sponsored meetings, unless I have a chance of influencing the prevailing culture among doctors, which was the case here. In my talk, I took the five sponsors, Merck, Pfizer, UCB, Abbott and Roche, one by one, from the bottom up:

  Roche was a drug pusher that had built its fortune on selling heroin illegally in the United States; made millions of people hooked on Librium and Valium while the company denied they caused dependence; and had lured European governments into buying Tamiflu for billions of Euros, which I considered the biggest theft in European history.

  Abbott and its hired gun, a Danish cardiologist (see Chapter 11), blocked the access the Danish drug agency had granted us to unpublished trials of the slimming pill, sibutramine, which was later withdrawn from the market because of cardiovascular toxicity.

  UCB in Belgium sent us a letter stating that UCB is an ethical company and that all data are proprietary solely to the UCB who has the exclusive right to make whatever it deems desirable.1 I remarked that talking about being an ethical company and at the same time concealing trial data was bullshit.2 We performed a meta-analysis of a natural hormone, somatostatin, used for stopping bleeding although the effect is doubtful,1 and we discovered that the biggest trial ever done had not been published.

  Pfizer lied at an FDA hearing about the cardiovascular harms of celecoxib; it agreed to pay a record fine of $2.3 billion for promotion of off-label use of four drugs; it entered a Corporate Integrity Agreement with the US Department of Health and Human Services, which probably wouldn’t work, as Pfizer had entered three such agreements previously. I explained that the reason Pfizer was the world’s biggest company might be that it was more criminal than other companies.

  Merck had caused the unnecessary deaths of tens of thousands of patients with rheumatological problems through its ruthless behaviour; it selectively targeted doctors that raised critical questions about the drug; it concealed the cardiovascular risk both in publications and marketing; and the only thing that happened to its CEO, Raymond Gilmartin, was that he became immensely rich.

  After this introduction, I fired some more torpedoes about habitual fraud and crimes in the drug industry with devastating consequences for the patients and ended my talk by quoting the BMJ’s editor, Fiona Godlee: ‘Just say no.’3 I also told the society that if they still couldn’t see there was a problem in receiving money from activities that were partly criminal, then why not get a sponsorship from Hells Angels?

  Yves Sales supported me in the discussion although he told me later that he felt my direct approach might have pushed some people away who were undetermined. The chairman of the society argued that their meetings would be very expensive without industry support, to which Sales bluntly replied that there was no reason to shed tears if industry sponsorship was banned, and that it wasn’t correct that the society couldn’t arrange meetings without such support. I drew attention to the fact that other academics educate themselves without industry support and noted that the general practitioners had observed that there was little difference in their costs after they had banned industry support of their annual gathering.

  Henrik Vestergaard was very angry. He talked about my outrageous and insulting allegations, which is typical industry speak. How can facts be ‘allegations’? The industry has committed the crimes themselves, and if it’s insulting to tell the truth, then perhaps the industry should consider improving on its practices. Vestergaard was highly offended and refused to reply when I asked him if it wouldn’t be in his organisation’s interest if fines for illegal activities became so high that they were perceptible. This would force the companies to compete at a higher ethical level, which would also benefit those working in the industry, as it would become more attractive to work there. Vestergaard used the standard tactic, hinted at the lone bad apple, and said that when the public purse wouldn’t pay for postgraduate education, the industry had to do it. This hypocrisy was too much for a rheumatologist who remarked that the industry did it because it paid off, not because of some humanistic motive.

  The passions ran really high. Merete Hetland, a rheumatologist with many links to industry, claimed I was employed to quarrel, that I threw suspicion on the industry, and that we were able to collaborate with the Germans although they were Nazis during the Second World War. Industry speak again. To tell the facts about companies is not to throw suspicion, and industry routinely rejects uncomfortable facts by saying they are things of the past and that it has become much better, which it never has, as I had just demonstrated.

  A year later, I looked at the society’s homepage. It still had industry-sponsored meetings, and it was still possible for drug firms to become members. Provided they paid 10 times as much as a doctor. This was a bit depressing and another doctor who is against industry sponsorship accomplished greater change than I did:4

  The audience … seemed immensely interested – and acutely aware of the rarity of an occasion in which the relationship between medicine and the drug industry was questioned … Immediately after my talk, one pharmaceutical company representative announced to the organiser that her company would no longer support the annual conference. Another packed up his exhibit and walked out. Other drug representatives were observed muttering angrily into their cell phones, which may, or may not, have been related to the near total exhibitor boycott the next day. Only one exhibitor showed up, prompting a physician friend of mine to remark, ‘Maybe he missed your talk.’

  In 2010, the chairman for the Danish Society for Pulmonary Medicine invited speakers to introduce a round-table discussion about drug trials in Denmark, with an estimated 80 attendants. The meeting would last 75 minutes and was sponsored by GlaxoSmithKline. There was an honorarium of $1000 for a 5–10 minute introduction. The invitation noted that ‘It is necessary to sign a contract before the meeting.’ I asked Glaxo why they required a contract and asked to see it. They didn’t send it but explained it was required according to the industry’s guidelines when they hired a doctor as a consultant. But why sign a contract when hiring a person for 10 minutes and why were 80 people expected for a 1-hour meeting about drug trials? I suspect the real aim of the meeting was to help Glaxo market its asthma products. In fact, the inviting company person was a ‘marketing coordinator’ and the headline for the meeting was: ‘Exclusive course, Respiratory Scientific Forum’. The invitation said that the meeting venue was about a 60 minutes’ drive from Copenhagen, but nonetheless people could stay for the night at the hotel while Glaxo paid the expenses. For 80 people. What an expense f
or so little, unless the company was buying doctors. Doctors who participate in such arrangements bring shame on themselves.

  In 2001, German doctors were invited to Bayern with a scientific programme that lasted 10 minutes, just after they had arrived.5 The rest of the time was their own. Another option for German doctors was to start 20 patients on a certain company’s drug, which would earn them what seemed to be an all-expenses paid 3-day trip to Paris that included the finals in the football world championship. This time the doctors didn’t have to waste 10 minutes of their precious time listening to a lecture.

  Money doesn’t smell

  I am not much exposed to advertisements for drugs, but twice a year a company sends me an envelope by mistake. And I mean by mistake, as I must be blacklisted in all drug companies. For example, I received an advertising circular from Meda that said that ‘About 300 000 people in Denmark suffer from overactive bladder.’ On the rear side, there was a reference to this statement, Continence News no. 4 – 2010. So much for the science behind a claim that 6% of the whole population, including children, suffer from peeing too often or too suddenly. The solution was trospium chloride (Sanctura, perhaps a sanctuary for hyper-urinators?), an anticholinergic drug, which would cost you the price of two beers a day, which, however, would only worsen your peeing problem.

  Before smart marketing people dubbed it overactive bladder, we used to call it urge incontinence. It feels very intrusive that the industry doesn’t even leave our disease names alone. It’s none of their business to name diseases but, unfortunately, doctors now also call it overactive bladder.

  Pfizer mingled with what we have called impotence for centuries. When it discovered that a drug developed to treat hypertension caused erection as a side effect, impotence was renamed erectile dysfunction, which sounds more socially acceptable than being impotent:

  ‘I have a physiological dysfunction.’

  ‘Oh, poor you, what’s the problem?’

  ‘I am not sure I want to tell you, but luckily, there is a drug that works.’

  The poor guy’s friend might think he suffers from thyroid disease, type 1 diabetes, chronic foul-smelling diarrhoea, or worse.

  I don’t deny that some people are troubled by peeing too often or too suddenly. But I have always known that the effect of anticholinergic drugs is highly doubtful. The Cochrane review confirms this. The effects are statistically significant, but as everything gets statistically significant, no matter how small the effect is, if only there are enough patients, we should always look at the data. The number of leakage episodes per 24 hours in the largest study was 3.2 on drug and 3.3 on placebo, and the number of pees (called micturitions in doctor’s language) was 10 on drug and 11 on placebo in the two studies that reported on this.6 That doesn’t seem a worthwhile effect, does it? Particularly not when you consider that all drug have harms. Frequent and disturbing side effects are: dry mouth, blurred vision, constipation and confusion. These are just the common ones; there are many others, e.g. dry eyes, dry nose, headache and gas. Some harms can be serious and require you call your doctor immediately: difficulty urinating, rash, hives, itching and difficulty breathing or swallowing. Such information on drugs can be found on the homepage of the US National Library of Medicine:

  www.nlm.nih.gov/medlineplus/druginfo

  By the way, how does a patient decide whether a few drops of urine are a leakage or not? Given the conspicuous side effects of the drugs, it’s likely that many patients on active drug have guessed they are on it, and such unblinding will be expected to lead to biased assessments in favour of the drug over placebo (see Chapter 4). Furthermore, a patient who knows she is on active drug might suppress the urge to go to the toilet, and if this happens one time more per day than for a patient treated with placebo, it corresponds to the difference seen in the trials. So maybe there is no effect at all of these drugs? I consider that quite likely.

  When the Roman emperor Vespasian was criticised for the tax he imposed on public urinals, he replied that money doesn’t smell. In our time, the way money is made on urine can smell so strongly that it comes close to scientific misconduct. Yamanouchi, which later became Astellas, submitted a comparative trial for publication in 2005 with a Danish professor’s name, Gunnar Lose, on the paper, although he had never seen the manuscript, the raw data or the more extensive clinical study report, which wasn’t written until months later.7 The paper showed that Yamanouchi’s drug was better than Pfizer’s drug, but Lose didn’t feel that the statistical analysis or the paper was fair and balanced, and he required it be retracted.

  The company refused to retract the paper, refused to show Lose the data, and later also refused to show him the clinical study report, although the contract with the company specified that he would get access to the report. Lose found the data analysis so doubtful that he withdrew his contribution as author. The clinical study report was submitted to the Danish drug agency, as required by law, but the agency refused to check whether the published data were reliable and even refused to share the report with Lose.8

  Lose was right. The published trial report is not only miserable, it is extremely miserable,9 a school example of how one should not report a trial. It was appropriately criticised by other researchers,10 and, to take just one example, percentages were given to two decimal places, e.g. 3.58%, whereas there were no standard deviations or other measures of uncertainty in the data. I have no doubt it was a seeding trial. Enrolling 1177 patients in a micturition trial is far over the top, and the trial involved 17 countries and 117 study sites, i.e. only 10 patients per site. If one wants reliable data, it is preferable to use a few large sites with skilled investigators.

  These events also show that drug agencies don’t prioritise. While the trial was running, Lose had been visited by a monitor from the agency who checked whether signatures corresponded to the correct dates. But whether the public was misinformed about the merits of a new drug didn’t have the agency’s interest. According to the European ombudsman, clinical study reports are not the property of the sponsoring firm, they belong to society, which means that the agency shouldn’t have refused to give Lose the report. Further, it is absurd to deny Lose the report of a trial to which he had himself contributed.

  Creating diseases

  What diseases could you have without knowing? A Danish newspaper did an amusing investigation. It collected news stories throughout 3 months about what Danes suffer from and came to the conclusion that, on average, each one of us suffers from two diseases.11 In fact, it’s much worse because the journalists searched on Danes suffer from, which means that a lot of diseases were overlooked. Maybe the reason that we Danes come out as the happiest people on earth in poll after poll is that we don’t know we are terribly ill.

  The 300 000 who were said to suffer from overactive bladder weren’t on the list of 12 million diseases in Danes, so we should add these 300 000. It is good to know that we can reduce human suffering by not asking people whether they have peeing problems and by not treating them with sanctuary drugs.

  In 2007, The Danish Association of the Pharmaceutical Industry had lobbied our politicians in Parliament and convinced some of them that regular health checks would be a good idea in order to prevent diseases. When asked by a journalist whether it wasn’t more a matter of selling more drugs, e.g. against elevated blood pressure or cholesterol, the industry spokesman admitted that this was the case.12

  In 2011, our new government had regular health checks on the menu, but I asked for a meeting with the minister of health where I told her that the Cochrane review we had just completed, and which includes 16 trials, almost 250 000 participants and almost 12 000 deaths, found no effect of health checks on total mortality, cancer deaths or cardiovascular deaths.13,14 One of my colleagues told her about a large Danish trial he had just finished that also failed to find an effect.15 Health checks lead to more diagnoses of diseases or risk factors, which lead to more drug use and more harms. Our conclusion was therefore ver
y firm: health checks should not be used. The minister agreed and said it was the first time the new government had broken a pre-election promise in an evidence-based manner. Our review will save billions for taxpayers and a lot of suffering, too.

  Here is an example of the misery that a seemingly innocuous health check could cause. A highly prolific writer had suddenly lost his appetite for his hectic life.16 The days were endless and terrible to such an extent that he contemplated suicide as the only way out. He was convinced that he had become old and didn’t have strength any more. After a month, it suddenly dawned on him that it could be the pills. These pills were a beta-blocker, and his doctors had forgotten to tell him that they could cause depression. He stopped taking them and became himself again.

  This story didn’t start with a health check, but it could have. Very often, it doesn’t occur to the patients that their worsened condition might be caused by the pills they take. Unfortunately, their doctors may not recognise either that the new symptoms are side effects of the first pill and may therefore prescribe a second pill against the symptoms, and so on.

  The drug industry and its paid doctors don’t even leave young, strong people alone. Applying European guidelines for cardiovascular disease on a Norwegian population, researchers found that 86% of males were at high risk of cardiovascular disease at age 40.17 The irony is that Norwegians are some of the most long-lived people in the world. In another study, the researchers found that 50% of Norwegians had a cholesterol or blood pressure level above the recommended cut-off for treatment at age 24!18

  Osteoporosis is similar. In 1994, a small study group associated with the WHO defined normal bone mineral density as that of young adult women.19 Pretty foolish, as virtually everything in us deteriorates as we get older. We’ll be off limits in all sorts of ways if we compare ourselves with young women. The group – completely arbitrarily – defined osteoporosis as present if the bone mineral density was 2.5 standard deviations below that in a young woman, and didn’t even stop there, but defined osteopenia as present if the measurement lay between 1.0 and 2.5 standard deviations below. These criteria were intended for epidemiological research but were a bonanza for the drug industry, as they rendered half of all older women ‘abnormal’. The drug industry sponsored the meeting where these definitions were created, so there might have been some influence.