The pharmaceutical industry's fraudulent research and bought doctors
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The pharmaceutical industry's fraudulent research and bought doctors
24. January 2011 pm. 04:00
Chronicle: The last year has featured a series of scandals in the pharmaceutical industry. Companies 'disclosure of research data and physicians' conflicts of interest is helping to blur the truth of the preparations effects.
By Peter C. Gøtzsche Prof., Dr., dr. with the Nordic Cochrane Centre, Rigshospitalet
There is money in drugs. So many that it is almost impossible to punish pharmaceutical companies illegalities economically. (Photo: Colourbox)
In recent years, many books, articles and reports on the pharmaceutical industry focused on its research and marketing methods (1-26). Methods often have exceeded legal limits, resulting in heavy fines in the U.S..
The world's biggest pharmaceutical company Pfizer, paid for example a record fine of 2.3 billions U.S. dollars in a settlement. Settlement was reached after accusations of fraud and criminal offenses because of the placing of four preparations for different indications, they were not approved (off-label use) (8).
Fines of even that size does not seem to have any deterrent effect.
Doctors submit names to ghost articles
Pfizer promised the U.S. Department of Health not to do it again but it was the fourth time, Pfizer had made this promise. The broken promises is probably linked to the record fine was equal to only 3 weeks of sales for Pfizer (8). The companies earn far more in illegal activities than the cost of fines.
Doctors' financial conflicts of interest relating to the pharmaceutical industry color their perceptions of medicines beneficial and adverse effects and lead to inappropriate use of drugs (1-26).
Many doctors helping the illegal activities by adding its name to articles about off-label use, which companies use in marketing. It is rare for the doctors themselves who articulates the creative approach to drugs, but a ghost writer who wrote the script for the company, after which the physician receives a fee for his outstanding effort, which not infrequently is harmful to patients.
Ghost articles published in high-impact journals
Half of the scientific literature on psychiatric drugs is estimated to be written by anyone other than the doctors themselves. (Photo: Colourbox)
This kind of scientific dishonesty is widespread (26-28), but comes generally not presented because the idea just to keep it hidden.
Proceedings in the U.S. who have opened companies' archives has revealed that many articles are written by the ghosts, whose name is not even clear from a thanksgiving.
David Healy has estimated that about half of the scientific literature on psychiatric drugs is written by ghosts or corporate staff writers or published in supplements to journals without peer review (26).
Ghost Articles published often in high-impact journals, and one should therefore be extra critical when reading articles about drug trials, including in those journals.
New England Journal of Medicine is firms' favorite magazine because it has great advertising value for drug dealers to leave a reprint of this journal.
There is a certain symbiosis, since the magazine sells many reprints and also increases its impact factor by publishing industry attempts (29).
Misleading picture of drug effects
The massive commercial pollution of the literature is a main reason why doctors have a misleading picture of the medicinal benefits and harms. This misconception implies that doctors spend far more drugs than patients need to flourish.
Sales of antidepressants, for example, now so large that 7% of the Danish people can be treated every day, from cradle to grave (30). Nobody is, but it only means that it may be a far greater percentage, which at one time or another come into treatment.
Because the effect of these drugs is modest, with less patients suffering from severe depression (31); as a depression usually lasts only three months (26), and when symptoms are so annoying that only about half the patients continue treatment (26), is this large consumption is inappropriate.
The cheapest is not worse than the most expensive
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One must therefore wonder that the National Board of Health recommends that there should be screened for depression in Denmark (32).
Psychiatrists has itself acknowledged that the main problem is not under treatment, but treatment with psychotropic drugs (33).
And a Cochrane review of 12 trials (5,693 patients) concluded that it is a really bad idea to screen for depression (34).
In the U.S. it is even worse. The best-selling drugs (in dollars) are antipsychotics (35). It's hard to imagine that in such an obese population should be more people who are psychotic than are being treated for hypertension, elevated lipids or diabetes.
Of course, U.S. dollar is not the same as daily doses, but as experiments carried out independently by industry show that the cheapest antipsychotics are not worse than the most expensive (36-41), the consumption of antipsychotics to a worrying extent be driven by industry.
Rule against articles written by stakeholders
Financial conflicts of interest among doctors is so widespread that they can be difficult to avoid for journal editors. Some years ago, the New England Journal of Medicine that listing and editorials could not be written by doctors with a financial interest in a company which manufactured a product that was discussed in the article, or a competing firm.
The rule did not last long. The editors published only one article drug for 2 years and they commented that if they are not published anything, they would not take any risks to convey skewed perceptions (42).
On the other hand, such a silence can not be useful to readers. They therefore changed the rule that the authors might not have any significant financial interest. As an American perceives as a significant financial interest could be a lot of dollars.
Moreover, financial conflicts of interest has nothing to do with the amount. It starts with the first pen, because it's in our genes to requite kindness with kindness. Editors new rule is therefore inconsistent with the evidence (43).
Conflicts of interest are problematic
Would you be comfortable being treated by a doctor who had economic interests in the company behind the drug he prescribed you? (Photo: Colourbox)
Some doctors believe that the declaration of conflicts of interest solves the problem but it does not.
We would not be confident that a judge had shares in a private jail, although the judge had declared his conflict of interest.
There have been a case in the U.S. where a judge with this conflict of interest imposed harsher punishments than his colleagues.
Actually we would not be confident that a judge had any conflicts of interest.
How can it be that doctors are so difficult to realize that their conflicts are problematic and goes beyond the patient's welfare?
Doctors are also judges on behalf of patients, namely over how good or bad drugs are.
The more cooperative and the less critical doctors are facing the industry, the more extensive clinical trials they are put in charge of, and the more research one million prefer the home to the institution they are employed. Medical researchers may be tempted to downplay or do not report adverse effects of the medicines they investigate, as this increases the doctors' popularity in the industry.
Cheating with clinical trials of psychotropic drugs
One such case was exposed, because New York state prosecutor accused GlaxoSmithKline of repeated instances of fraud, which opened the company's archives (25). A study comparing paroxetine with placebo in children and adolescents with depression, had, according to the company's internal documents failed to demonstrate any effect, on the contrary, paroxetine harmful (44).
Since the study was published, it was however quite different: Now paroxetine was effective and well tolerated (45). There was no effect on any of the 8 endpoint, which emerged from the protocol, but it did the company by examining a large number of additional endpoints - at least 19 - and by choosing other endpoint to the article than those who stood in the protocol.
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In the article it said that paroxetine had a significant effect on not less than 4 out of 8 reported endpoints. This maneuver is called "torturing the data to confess' (46).
It is also called 'The Texas sharp shooter ":
If one fires a gun at a scoreboard and misses, and then painting measured breeding over and paint a new one which now has bullet hole at its center, so you are not a sharpshooter, but the scammer.
Suicidality in subjects concealed
First author, psychiatrist Martin Keller, who had been extremely effective at attracting industry sponsorship of her university (25), wrote in the article that power objectives were declared a priori, but the company's own documents showed that it was a lie (25.44).
Nor did the publication that the difference in serious adverse effects - 11 on paroxetine compared with only 2 on placebo - were statistically significant (p = 0.02, my calculation). Five cases of suicidal behavior or thinking was renamed emotional lability, and 3 additional cases of suicidality or self harm disappeared from the publication, where they were called the hospital.
An early draft manuscript prepared for publication in JAMA, which rejected the article (25), discussed no serious adverse effects. A later draft company said worsening of depression, emotional lability, headache, and hostile behavior that resulted or may result reading.
But the publication said only one patient with a headache that investigators believed was related to treatment. The publication did not mention that there was suicidality among 8 patients on paroxetine compared with only 1 on placebo. It was even worse. After the FDA asked GlaxoSmithKline to look at the experiment again, emerged more cases of suicidality up (25), so now there were at least 10 on paroxetine (p = 0.01, my calculation).
'Appropriate to assess the effect'
Pfizer, the world's largest pharmaceutical company, has four times promised to stop fraud with illegal sale of drugs. Here the group's headquarters on 42nd Street in New York. (Photo: Jim.henderson)
This grossly manipulated article is one of the most cited work at all, which was to convince doctors that it was good to children and adolescents treated with antidepressants.
There is quite similar problems in other pharmaceutical companies and with other drugs (1-26).
For example, it follows from a Pfizer document that Pfizer-sponsored studies belong to Pfizer, and no individual, and that the purpose of gathering data to support Pfizer's Marketing (47).
What it means, so we recently.
The German Institute for Medical Technology Assessment had asked Pfizer for data from all trials of the antidepressant reboxetine. But Pfizer would only hand the trials of Pfizer's view was 'fit to assess the effect'! (48)
Lecturers equipped with company slides
After heavy pressure and negative publicity handed Pfizer, most of the missing data, and it appeared that reboxetine, which is approved in several countries including Denmark, have no effect, but it is harmful.
According to an internal document from AstraZeneca was the company's antipsychotic drug Seroquel worse than an old drug, haloperidol (47). But the company buried their negative test, and a meta-analysis of 4 studies presented at a conference and a press release announced that quetiapine was significantly better than haloperidol (47).
Doctors who make presentations to companies, equipped with company slides. In this case showed AstraZeneca slides that quetiapine had no effect on weight. There was even a magazine publication which claimed the same, based on experimental data from schizophrenia patients. But AstraZeneca's internal documents showed that quetiapine cause marked weight gain.
Firms' control over medical experiments
Even when doctors are doing tests on its own initiative, independent of industry, companies still try to influence the processing and interpretation of results.
An internal email from AstraZeneca mentions for example that Eli Lilly provides significant financial support for such experiments, but that they in turn want to control data, the company is able to put spin on the data in many different ways with a powerful author team; and that negative data is usually kept hidden.
Another AstraZeneca-mail says of Janssen, no data from investigator-initiated trial will be permitted to be published without prior checking by Janssen, who has high expectations for investigators to publish favorable results and reward good Janssen (47). If this is true, it is corruption.
I find it hard two Imagine That a system this corrupt kan a good thing, eller at det er på den VAST AMOUNT of Money Spent on IT. (13)
- Marcia Angell, former editor of the New England Journal of Medicine
Fictional patient histories
In an internal email from Eli Lilly (47) the sender is concerned that the company's antipsychotic drug, olanzapine, is associated with weight gain and increase in blood sugar.
He recommends that the following remark deleted from the manuscript: 'Patients who gain weight may develop insulin resistance, which can lead to hyperglycemia and diabetes. "
Eli Lilly told its sales force that we had more data than ever to back up the story that the rates of hyperglycemia and diabetes for the various psychotropic drugs are comparable. Eli Lilly planned to market olanzapine on the indications, the drug was not approved or tested for.
GPs were seen as troublesome because they did not use antipsychotics frequently enough because of concerns over adverse effects. Eli Lilly, however, was determined to "change their paradigm 'and devised fictional patient histories for use by the sales force (47).
European parliamentarians aware of problems
Det er enkelt no longer muligt tror mycket av clinical research som er ut, eller two rely om Judgement of trusted Physicians or Authoritative medical guidelines. I take no pleasure in this conclusion, som I reached slowly and reluctantly over my två Decades som editor of The New England Journal of Medicine. (52)
- Marcia Angell, former editor of the New England Journal of Medicine
It is worth mentioning how Marcia Angell, former editor of the New England Journal of Medicine, looks at all this (see quote box) (49).
Jerome Kassir, also a former editor of this magazine, makes no punches as the title of his book are:
"On the take: how medicine's complicity med big business kan Endangered your health '(14).
Doctors believe that the information they receive from pharmaceutical companies is helpful (1). It must be due to blatant ignorance of the facts.
I've just been in the European parliament and met not a single politician who was in doubt that we have to address the stated problems in pharmaceutical research and information company.
There is for example a report from the Committee on the Environment, Public Health and Food Safety which is a very sharp criticism of the handling of the vaccine issue by the so-called influenza pandemic, which was much milder than normal pandemics (50). The report identified the need for unbiased information and problems with doctors' conflicts of interest.
Danish doctors and the pharmaceutical industry
Medical Association's policy is to downplay the problems and almost pretend that they do not exist. It goes no further. Medical Association and Medical Association should adopt a decision in principle that doctors are not receiving visits from pharmaceutical salespeople because it is harmful for both patients and the economy (1 to 26.49).
More than 2,000 Danish doctors collaborate with the pharmaceutical industry, when one includes both those who are at Medicines Authority's website and those who should be standing there (51). One must wonder what all these doctors be doing.
Many have multiple jobs and Medicines Agency lists a total of 3675 roles, the primary teacher is (1111 Doctors), Advisory Board Member (568) and a consultant or advisor (604). Angell's view is that physicians must become accustomed to receiving money from industry, but unfortunately they most want to remove the smell of corruption, while they keep the money (52).
All the experts bought in advance
It is also a problem of legal certainty that prosecutors who bring actions against firms may encounter all potential expert witnesses are bought in advance (26).
1 Pfizer 586
2 AstraZeneca 334
3 Merck Sharp & Dohme 245
4 Novo Nordisk 204
5 GlaxoSmithKline 197
6 Novartis 190
7 Sanofi 177
8 Bristol-Myers Squibb 166
9 Boehringer Ingeheim 157
10 Roche 118
Total 2374
Top ten companies in Denmark for the number of doctors who have been Medicines Agency's permission to work with a pharmaceutical company (data from Julie Bindslev, November 2010)
The lawyer who investigated Medicines Agency's role in Omniscan affair, could not find a single expert in Scandinavia, which had not cooperated with industry (53).
The pharmaceutical industry buys goodwill and influence among opinion formers.
The 10 companies that have most doctors assigned is shown in the box beside it.
I feel better, leading doctors to put pressure on industry to disclose their many unpublished data.
Doctors are of course unable to select the best products for their patients when they do not know the data.
It is the biggest ethical problem we have, and the companies violate the Declaration of Helsinki, when they keep secret their experimental results.
As we once asked for data from a large unpublished trials UCB announced to us that we could not get; that UCB was an ethical company and that all data is owned by UCB, which has the right to do what the company considers desirable ( 54). Clearer it can hardly be said that both doctors and patients who had taken the body to the company's experiments, was hoodwinked.
What could we do better?
The only thing that companies have respect for are falling earnings. We could therefore consider boycotting the worst firms. You can almost always find an equally good product from a competing firm - and very often even one that is cheaper. The animal preparations are rarely an improvement, it looks just like this, because the pharmaceutical industry have manipulated results.
Each physician could also consider with himself, about the joy of receiving money from industry outweighs the discomfort of some of this money might be raised from criminal activities have gone beyond the patients.
DID YOU KNOW
Declaration of Helsinki was developed by the World Medical Association (WMA) in 1964 as a set of ethical principles for human studies.
It is widely perceived as the most important document in human studies ethics.
It is not legally binding under international law but has exerted great influence on national and regional legislation and regulation in many countries.
And consider why a growing population and the medical journal editors perceive physicians' relationships with the pharmaceutical industry as partially corrupt.
In 1997 meant 79% of those polled Americans that the pharmaceutical industry did a good job, in 2004 it was 44% and in 2005 it was only 21% (16).
Risk losing patients' trust
The important thing is to guarantee in law that not just any results, but also all the raw data from clinical trials will be presented to the public as independent researchers to verify the data analysis.
You could give very large fines if it does not, and it could also impose a quarantine period in which the company is unable to conduct new trials.
In order to have sufficient power, such legislation must be adopted at supranational level, ie in the EU.
You could work with industry without getting paid for it and it would give doctors more freedom. Researchers collaborate with each other without charging fees, and advisory board members in non-profit organizations are usually no fee.
As the BMJ's editor has said, "Just say no '(55). Otherwise, doctors are losing the most important thing they have, besides their income: Patients' trust.
