85% of new drugs ‘offer few benefits’

This from the Independent... it sums up what I’ve learned over the years of writing this blog.

I have to echo Ben Goldacre when he says “I can’t see why any company withholding data should be allowed to conduct further experiments on people. I can’t see why the state doesn’t impose crippling fines”

I can’t see it either.

Drug companies were accused today of conning the public by hyping up patented medicines with little new to offer while downplaying their side-effects.

An estimated 85% of new drugs offer few if any new benefits while having the potential to cause serious harm due to toxicity or misuse, a study has concluded.

The author of the research delivered a damning attack on “Big Pharma” at a meeting of sociology experts in the US.

Professor Donald Light described the pharmaceutical industry as a “market for lemons” – one in which the seller knows much more than the buyer about the product, and takes advantage of this fact.

“Sometimes drug companies hide or downplay information about serious side-effects of new drugs and overstate the drugs’ benefits,” said Prof Light, a professor of comparative health policy at the University of Medicine and Dentistry in New Jersey, US.

“Then, they spend two to three times more on marketing than on research to persuade doctors to prescribe these new drugs. Doctors may get misleading information and then misinform patients about the risks of a new drug. It’s really a two-tier market for lemons.”

He alleged that the pharmaceutical industry owned companies in charge of drug testing and provided “firewalls” of legal protection behind which information about dangers or lack of effectiveness could be be hidden.

Companies were assisted by the “relatively low bar” for effectiveness that had to be crossed to get a new drug approved, he claimed.

Prof Light presented his paper, entitled “Pharmaceuticals: A Two-Tier Market for Producing ‘Lemons’ and Serious Harm” today at the American Sociological Association’s annual meeting in Atlanta, Georgia.

The study includes data gathered from independent reviewers which suggest that 85% of new drugs provide few, if any, new benefits.

Yet toxic side effects and misuse of prescription drugs had made medicines a significant cause of death, said Prof Light.

The professor makes the same claims in a new book, The Risk of Prescription Drugs due to be published this autumn by Columbia University Press.

In both his paper and the book, he describes the “risk proliferation syndrome” involved in drug marketing. This is said to arise from maximising the number of patients exposed to the side effects of new drugs of dubious efficacy.

Hyping a drug began with clinical trials designed to minimise evidence of harm and published literature that emphasised its advantages, said Prof Light.

Building on this foundation, pharmaceutical companies staged massive campaigns to sell the product, when a controlled limited launch would allow evidence of its effects to be gathered, he argued.

Leading clinicians were recruited to try using the drug for conditions other than those for which it was approved, and to promote “off-label” or unapproved uses, Prof Light maintained.

Physicians inadvertently became “double agents” – promoters of the new drug, yet trusted stewards of patients’ health.

When patients complain of adverse reactions, studies show that doctors are likely to discount or dismiss them, according to Prof Light.

He accused companies of conducting a “swamp the regulator” policy – bombarding the bodies that award drug licences with large numbers of “incomplete, partial, sub-standard clinical trials”.

One study of 111 final applications for approval found that 42% were missing data from adequately randomised trials, 40% were supported by flawed testing of dosages, 39% lacked evidence of clinical efficacy, and 49% raised concerns about serious adverse side-effects, he said.

Recently, major reports had focused on “biased, poor trials” involving the diabetes drug Avandia and the antibody cancer drug Avastin.

Avandia has been linked to an increased risk of heart attacks, while controversy surrounds Avastin’s effectiveness as a breast cancer treatment.

A US Food and Drink Administration expert panel has called on the agency to withdraw its licence allowing Avastin to be used for this purpose.

Companies control the generation of scientific knowledge and which findings will go to licensing authorities such as the FDA or be published, Prof Light argued.

“The result is that drugs get approved without anyone being able to know how effective they really are or how much serious harm they will cause,” he said.

“A few basic changes could improve the quality of trials and evidence about the real risks and benefits of new drugs. We could also increase the percentage of new drugs that are really better for patients.”

Prof Light highlighted the marketing of statin cholesterol-lowering drugs as a good example of pharma hype.

Company-supported clinical researchers and medical writers created a global market for controlling cholesterol with statins, he argued.

A complex set of relationships between heart disease and saturated fats and cholesterol had been converted into the simple message that “cholesterol kills”.

Yet two major trials of statins found little evidence that the drugs reduce the risk of heart attacks. In contrast, they showed an increased total risk of harm to health and death from the drugs despite the lowering of cholesterol levels.

One major meta-analysis, which pooled the findings of a number of studies, found that “statins were not associated with reduction in the risk of all-cause mortality”.

Another trial led by a statin manufacturer was stopped early so that adverse side-effects were not recorded.

Mental illness and diabetes were other areas where questionable use of drugs occurred, said Prof Light.

Selective serotonin reuptake inhibitor (SSRI) antidepressants became immensely popular despite evidence that they are little better than “dummy” placebos for most patients.

In his paper, Prof Light concluded: “The evidence here indicates that the two-tier market for prescription drugs is the largest and most dangerous market for lemons in modern society. Neither wars nor used car injuries come close.

“Current incentives for research produce a few that substantially improve patients’ chances of getting better or avoiding death but a large number of barely innovative drugs each year. These new drugs of little benefit consume about four-fifths of all drug costs.

“The incentives and institutional practices around testing and regulatory review predictably result in approvals being based on trials so biased and poorly run that no one knows how much better or worse new drugs are.”

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Drug firms hiding negative research are unfit to experiment on people – writes Dr Ben Goldacre

“Another pharmaceutical giant has settled a big compensation claim. So why are they allowed to go on misleading the public?”

…writes Dr Ben Goldacre in his column Bad Science in today’s Guardian. He continues “I can’t see why any company withholding data should be allowed to conduct further experiments on people. I can’t see why the state doesn’t impose crippling fines. I hope it’s because politicians don’t understand the scale of the harm.”

Without wanting to come over as the arch conspriracy theorist, I think that there is a clear connection between governments, regulators and big business (the drug companies) that allows this to happen all too often.

Remember, Glaxo has a track record of hiding negative clinical trial data that would knock sales of its drugs – the story of Seroxat and Study 329 is truly shocking.

Read more about Seroxat here:
More on Paxil and suicide – “Glaxo was aware of this risk, and hid it”

and here:
Glaxo fails in its responsibility to patients and it hid Seroxat data – it’s official

And what happens in the UK when the MHRA  undertakes a criminal investigation into Glaxo and the withholding of clinical trial data?… and finds Glaxo guilty…?

The answer is nothing happened to Glaxo – nothing at all.

I enjoy reading Ben’s work, but I think he underestimates the scale of the problem – this is simply the way drug companies go about their business. They are happy to manipulate trial data to suit their own ends (and hide negative data) and they set aside billions of dollars in their accounts for the payment of fines and out of court settlements, and I, for one, am convinced they simply see this as just another part of the marketing cost of a new drug.

Here’s the rest of today’s column:

GlaxoSmithKline was sued by the New York attorney general for ‘illegal and deceptive’ reporting of the risks of its anti-depressant Seroxat. This week the drug company AstraZeneca paid out £125m to settle a class action. More than 17,500 patients claim the company withheld information showing that schizophrenia drug quetiapine (tradename Seroquel) can cause diabetes. So why do companies pay out money before cases get to court?

An interesting feature of litigation is that various documents enter the public domain. This is how we know about the tobacco industry’s evil plans to target children, the fake academic journal that Elsevier created for Merck’s marketing department, and so on.

One of the most revealing documents ever to come out of a drug company emerged from an earlier quetiapine case: an email from John Tumas, publications manager at AstraZeneca. In it, he helpfully admits that they do everything I say drug companies do.

“Please allow me to join the fray,” Tumas begins, in response to a colleague. “There has been a precedent set regarding ‘cherry picking’ of data.” Cherry picking is where you report only flattering data, and ignore or bury data you don’t like. The ears of lawyers prick up at any use of the word “bury” in relation to drug company data, as it implies something deliberate, and luckily John uses this word himself. The precedent, he explains, is “the recent … presentations of cognitive function data from trial 15 (one of the buried trials)”.

[And what about this 1997 Glaxo memo Ben?… If neg, results can bury]

In trial 15, commissioned by AstraZeneca, patients with schizophrenia who were in remission were randomly assigned to receive either AstraZeneca’s quetiapine, or a cheap, old-fashioned drug called haloperidol. After a year, the patients on Seroquel were doing worse: they had more relapses and worse ratings on various symptom scales. These negative findings were left unpublished: to use Tumas’s word, they were “buried”.

But in among all these important negative findings, on a few measures of “cognitive functioning” – an attention task, a verbal memory test – Seroquel did better. This finding alone was published in a research paper in 2002. AstraZeneca kept quiet about the fact that patients on Seroquel had worse outcomes for schizophrenia. The research paper went on to become a highly influential piece of work, cited by more than 100 academic research papers. Many researchers can only dream of publishing such a well cited piece of work.

Trial 15 also found that patients on Seroquel gained, on average, 5kg in weight over a year. This put them at increased risk of diabetes, which is what AstraZeneca is now paying to settle on (and in any case, a 5kg weight gain is a serious side-effect in itself).

Psychiatric drugs can do more good than harm overall, but many have serious, common side-effects. It is especially important that doctors and patients know all the risks, so that sensible and informed trade-offs can be made.

Here is the opening of another email in that quetiapine case. Richard Lawrence writes in an internal memo to colleagues: “Lisa has done a great smoke and mirrors job” on trial 15.

The pharmaceutical industry’s behaviour has collapsed into farce. Doctors and academics – who should feel optimism at working with the drug companies to develop new treatments – feel nausea instead, knowing that there are only informal systems to deal with buried data, and these have clearly failed.

In 2005 the International Committee of Medical Journal Editors put its foot down and said its journals would only publish trials that were fully registered before they started, which should make any that went missing much easier to spot. Several years later, as recorded in this column, fewer than half of all the trials that the editors published had been adequately registered, and more than a quarter were not registered at all.

After the New York attorney general sued GlaxoSmithKline over its “illegal and deceptive” reporting of the risks of its anti-depressant paroxetine (tradename Seroxat), GSK agreed to publish all trial data on a website. But, several years later, we saw last month that GSK and the Food and Drug Administration had sat on data showing that rosiglitazone (tradename Avandia) increased the risk of heart problems.

I can’t see why any company withholding data should be allowed to conduct further experiments on people. I can’t see why the state doesn’t impose crippling fines. I hope it’s because politicians don’t understand the scale of the harm.

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