Deadly Medicines and Organised Crime

by Peter Gotzsche

  Consultancies very often lead to self-censorship. US general practitioner John Abramson describes a flawed trial in the New England Journal of Medicine that recommended a particular statin, but the cost of preventing one stroke was $1.2 million.16 When he asked a specialist to write a criticism of the trial with him, he declined the offer explaining that he did ‘some consulting for the drug companies’.

  When I worked for Astra-Syntex, we had only one important drug, naproxen, an arthritis drug, and we had a consultant who was a specialist in rheumatology. His annual honorarium corresponded to what I earned in 6 months. Year after year, he was paid this huge sum and he didn’t do much more than educate us for about 2 hours in rheumatology and go through brochures produced by our marketing department. He cannot have worked for more than 5 hours to earn what I earned after 900 hours of work. My experience fits well with what others have reported. Our consultant was positive towards our drug, and the marketing people must have felt they got more back than they paid, but how could they know? I had my doubts.

  Our rheumatologist was a very nice man and he sometimes told us we used him too little, considering his honorarium. Whether he made the first contact and suggested himself as consultant, or whether we did, I cannot remember. But I do remember that influential opinion leaders sometimes used their power over the market to extort us, which we felt very badly about. When criticising the drug industry, we should remember that there are villains on both sides of the fence.

  It is attractive for industry to buy specialists and particularly those the industry calls key opinion leaders, as they exert considerable influence on which drugs other specialists and general practitioners use. We combined the list of Danish doctors with permission to work for the drug industry with the Authorisation List from the Danish Medical Association to find out which specialists were most often working for the industry. Table 8.2 lists those specialties where more than one out of five doctors were involved. Unsurprisingly, specialties with highly expensive drugs and a large market potential came high up on the list, e.g. endocrinology, oncology, haematology and cardiology. Why dermatology tops the list I cannot say, but one reason could be that they use steroids a good deal, and many newly patented steroids are very expensive although they are not any better than the ones we have used for decades.

  Table 8.2 Percentage of Danish specialists with permission to work for the drug industry. Data from 2010

  Dermatology and venereal diseases 39%

  Endocrinology 35%

  Oncology 30%

  Haematology 29%

  Cardiology 27%

  Infectious diseases 26%

  Lung diseases 21%

  An Australian survey showed that one-quarter of the specialists had been a member of a company’s advisory board within the last year.17 Most of the specialists said they received less than $4000 a year for their services, but other studies have reported that key opinion leaders may receive £50 000 a year to sit on a company’s advisory board,18 or $400 000 for just 8 days of consulting.19

  John Bell, Regius Professor of Medicine at Oxford University, received €322 450 in 2011 for his role on the board of directors at Roche.20 The editor of the BMJ wrote to Bell in 2012 and reminded him that Roche had not kept its promise of making unpublished Tamiflu studies available to Cochrane researchers (see Chapter 3); that Bell, as company director, was responsible for Roche’s behaviour; and that, by refusing to release these data of enormous public interest, Bell had put Roche outside the circle of responsible pharmaceutical companies.21 Bell didn’t respond other than by saying he had referred the letter to Roche.

  Four of the biggest hip and knee implant companies doled out more than $800 million in 6500 ‘consulting agreements’ with doctors between 2002 and 2006.22 Big money also changes hands in Europe. Some hospital doctors can earn up to €90 000 from the industry for a conference or €600 000 in ‘consultancy’ fees.23

  Internal company documents have shown that the advice the companies want from their thousands of consultants or advisory boards members has little to do with research, but a lot to do with marketing.24 At a meeting with such doctors, a regional business director said: ‘We would like to develop a close business relationship with you.’25 This is illegal in Denmark and should be banned in all countries. According to Danish law,26 an application to get permission to work for a company will generally be rejected if the work contributes to marketing, e.g. writing marketing material, sales training, advice about sales arguments, and writing leaflets for doctors that are sponsored by a drug company and which contains ads for the company’s drug.

  I have no doubt that our rules are being circumvented and that most doctors help the companies with their marketing. I have seen written examples of it and overheard doctors tell other doctors how funny it was when they participated in role plays and played difficult doctors while the salespersons tried to sell the company’s product. It’s surprising doctors can be proud that they have participated in this.

  Next, we’ll have a look at doctors as drug pushers.

  Rent a key opinion leader to ‘educate’

  ‘It is very dismaying to find academic psychiatrists that one has hitherto respected supporting one drug on a Monday and another on Tuesday.’

  ‘I can think of a well-known British psychiatrist I met and I said, “How are you?” He said, “What day is it? I’m just working out what drug I’m supporting today.”’

  Robin Murray, professor at the Institute of Psychiatry, Kings College, London18,27

  The third major category when Danish doctors work for the drug industry is lecturing (see Table 8.1). Close to one thousand doctors had permission to give talks at industry-sponsored meetings or educational arrangements.

  Like the huge number of doctors who are ‘investigators’ and the many who give ‘advice’ to companies, this number doesn’t make sense until we learn what the doctors are used for. A thousand doctors in a country as small as Denmark means one lecturing doctor for every 20 doctors. Since permission is not needed if a doctor only lectures occasionally, most doctors give several lectures every year. Thus, an overwhelming amount of ‘education’ is available for doctors, and in the United States, over 60% of continuing medical education (CME) is being paid for by drug companies.28

  It is of course the generous honoraria that attract such a large army of physician ‘educators’. A 2002 survey found that American psychiatrists were paid about $3000 for a symposium lecture and some earned as much as $10 000.27 The same year, there were 30 ‘free’ symposia sponsored by a drug or device company at the American Heart Association meeting, and a prominent cardiologist bragged he made more than $100 000 at a single meeting for lecturing at symposia.15 Jerome Kassirer, former editor of the New England Journal of Medicine, heard repeatedly from his colleagues that doctors who tour the country for drug companies, changing their talks repeatedly to hawk the products of the company sponsoring their talk, are called marketing whores.15 Similarly, doctors who work for multiple companies are called drug whores by drug reps.29 Such appointments are sometimes used as ‘payback’ for participation in trials, which allows the doctors to say that they had no financial conflicts of interest while doing the trial.15

  The drug industry routinely says it has no influence over the content of its courses, which is decided by the organisers, but such reassurances shouldn’t be believed. The course content is biased and the attendants favour the sponsor’s drugs afterwards.30,31 Leaked documents show that even when the concept of ‘education’ has been aggressively sold to general practitioners in brochures claiming that ‘all content is independent of industry influence’, the professional providers of medical education ask the drug companies to suggest speakers.32 Conversely, companies ask the providers to ensure that the speaker positions the company’s product appropriately. After the educational provider had accepted two doctors to speak at a seminar on women’s health, Organon, now part of Schering-Plough, which sells hormones, wrote back: ‘I would like
to again sincerely thank you for the political help … in respect of orchestrating the favourable consideration of the proposed topic and speaker.’

  The level of generosity also seems to matter: ‘Platinum’ sponsors were routinely offered the chance to ‘work with us to determine a speaker and topic for the programme’.

  Amazingly, the drug industry representative bodies, both in Australia and in the UK, which otherwise routinely deny everything that doesn’t look too good for them, admitted that this is how they do business. Perhaps it’s just too obvious that no matter how it’s arranged, a doctor who doesn’t deliver won’t be asked again.24

  The medical director of the Association of the British Pharmaceutical Industry has admitted that whether it’s called marketing, education, or research, it’s all about marketing, and the companies evaluate the return on investment into their key opinion leaders.

  Companies go to great lengths to avoid wasting their money and they are sometimes whitewashed. Internal company documents have revealed that ‘unrestricted educational grants’ may be redirected to for-profit medical education companies that arrange meetings where the drug company controls the speakers and the content, where unapproved uses of drugs are discussed, and which gain credit from the US Accreditation Education Council of Continuing Medical Education, although this is not permissible for events directly sponsored by drug companies.25 In one such case, the medical education company became anxious after having seen the abstract for a talk to be presented at the American Diabetes Association annual meeting at a satellite symposium. The company requested a copy of the speaker’s slides ‘for our review’ and it developed prewritten questions to be planted in the audience immediately after the talk to counteract negative comments about the drug. This strategy worked, as it led the speaker to address positive aspects of Neurontin.25

  Practical Guide to Medical Education says that potential ‘product champions’ in the medical fraternity are critical to influencing doctors’ thinking and that ‘The key is to evaluate their views and influence potential, to recruit them to specially designed relationship building activities and then provide them with a programme of appropriate communications platforms.’33 A medical education company stated, ‘Medical education is a powerful tool that can deliver your message to key audiences and get those audiences to take action that benefits your product.’15

  Brochures tell the same story. ‘Development & Management of Key Opinion Leaders’ was a course in 2009 about identifying key opinion leaders, interacting with and developing them, and strategic management of them.34 Top doctors as cute little puppies for the industry to raise! The first page of the brochure spoke about ‘Linking business with information’ and also informed that you could save £200 if you registered early. It took five more pages until the denominator was revealed: £1299 for the 2-day course and an additional £573.85 if you couldn’t live without seeing all the lectures again on a CD ROM. This makes sense for a biologist like me. The drug industry parasitises on our societies and other parasites parasitise on the parasites. Just like in nature.

  Drug reps are advised to work with key opinion leaders and turn them into ‘product champions’, and also to find younger people who can be nurtured and have their profile raised so that they also become key opinion leaders.24 A bit like Hitler-Jugend, so that they can go out and terrorise common sense among those who are not yet members of the Party.

  Doctors are more effective salespeople than drug reps. A slide show from Merck, which the Wall Street Journal got hold of, showed that for every dollar Merck invested in a lecture by a doctor, it got 3.66 dollars back, compared to only 1.96 dollars if Merck’s own salespeople held the lecture.35 The honoraria can be very large for doctors who are effective salespeople.15,27,36 Peter Wilmshurst, a British cardiologist and whistle-blower who has exposed many examples of fraud in research involving complicit doctors and editors of specialty journals, wrote in 2000:36

  One pharmaceutical company employs several eminent British cardiologists to lecture to other doctors around the country to promote the company’s drugs. The cardiologists, known to company employees as The Road Show, are each paid 3,000 to 5,000 [UK pounds] … plus travelling expenses for a 1 hour evening talk in the UK … Some members of The Road Show have spoken fortnightly for the company. As a result they receive more money each year from the company than their annual salary from their hospital or university … Some have admitted to me that they have kept silent about adverse effects of drugs to avoid loss of lucrative research contracts with a manufacturing pharmaceutical company. Some opinion leaders involved in pharmaceutical research now command speaker fees that are so high that their engagements are negotiated by an agent.

  A doctor reported how generous Wyeth was when he sold its SSRI venlafaxine (Effexor) to colleagues:37

  We were all handed envelopes as we left the conference room. Inside were checks for $750. It was time to enjoy ourselves in the city … Receiving $750 checks for chatting with some doctors during a lunch break was such easy money that it left me giddy. Like an addiction, it was very hard to give up.

  However, when this doctor said at a lecture that other drugs might be equally effective as Effexor, he was immediately visited by Wyeth’s district manager who asked him whether he had been sick. At that moment, the doctor salesman decided that his lucrative career as an industry-sponsored speaker – on top of his private practice – was over.

  The drug companies received printouts tracking local doctors’ prescriptions every week so that they could see to which extent their doctor salesman paid back. Pharmacies typically will not release doctors’ names to data-mining companies, but they will release their Drug Enforcement Agency numbers, and the American Medical Association makes millions by allowing its licence files of US physicians to be matched up by the data-mining companies with the Agency numbers. In 2005, database product sales, including an unknown amount from licensing Masterfile information, provided more than $44 million to the American Medical Association.38

  That industry money corrupts the integrity patients expect of their doctors and their organisations was also shown in 1964 when the US Surgeon General released a report on smoking and health that condemned smoking. The American Medical Association was the only major health organisation to withhold its endorsement of the report. It had received a total of $18 million over 14 years from the tobacco industry.39

  The bottom of academic prostitution occurs when doctors help companies with illegal off-label promotion activities that harm their patients.25 This should be a criminal offence. Indeed, off-label promotion is generally harmful, as we don’t know whether such use of a drug leads to any benefit, whereas we know that any use of any drug for anything always leads to harm in some patients.

  A notorious example of off-label use of drugs that has harmed hundreds of thousands of healthy people is the so called hormone replacement therapy. The name legitimised the idea that the hormones should be taken not only around menopause but for the rest of the women’s lives. They were touted as being good for virtually anything, including preventing coronary heart disease, but when a randomised trial was ultimately performed it turned out that hormones cause heart disease.40 Wyeth was secretly behind many of the initiatives,41 e.g. funded the book Feminine Forever, which was written by an American physician, and also funded several patient groups that looked as if they were independent.

  After hormones were found to be harmful, Novo Nordisk hired a German PR firm that sent letters to doctors downplaying the harms.42 Schering, Jenapharm and Organon also started massive marketing campaigns denigrating the findings and claiming that somehow they didn’t apply in Germany. A professor sent a ‘critical assessment’ of the trial to all gynaecologists in Germany and the 29% significantly increased risk of heart disease became ‘no decrease in cardiovascular risk’.8 The professor was paid by big pharma and hadn’t written the misinformation himself; it was written by Schering. The misinformation worked. While sales of hormones plumm
eted in the United States, little happened in Germany.

  Once when I lectured specialists in training on these problems, a doctor told me that he belonged to a small specialty with only three professors. There were two main competing drug companies and it was depressing for him to attend lectures by two of the professors, as it was always easy to tell which company was currently their main benefactor. As it happened, these two professors were also accused of scientific misconduct and I was involved with assessing the merits of both cases, which were highly interesting, but under Danish rules, I am not allowed to reveal more.

  I don’t attend international congresses that focus on particular disease areas, but I did go to the annual AIDS congresses when I headed the Nordic coordination office for AIDS trials. I wondered why many of my colleagues presented slides that were so obviously not prepared by themselves but by a drug company. I couldn’t understand why they hadn’t at least made them look as if they were their own. Particularly when they spoke about an industry-sponsored trial they had contributed to, where a more academic look would have instilled more confidence in their work. Slides with company logos, or which smells company influence in other ways, give the listeners a bad taste, as if they were watching a commercial.

  I didn’t know at the time that doctors collaborating with industry work with tied hands. I have no doubt that these doctors generally don’t know – or suppress any emerging feelings about it – that they are being used. When I have discussed with colleagues who lecture for the industry, they have typically argued that they believe the drugs they recommend to other doctors are good ones, and may even be used too little, and that they are therefore providing a good service to their colleagues. Whether this is rationalisation or not I cannot say, but what I miss in this argumentation is how they got the idea in the first place that those drugs are good. Unfortunately, the doctors generally don’t think that far, or it is to their advantage not to think.