Foregone conclusions

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http://www.guardian.co.uk/medicine/story/0,11381,1122721,00.html

 

Foregone conclusions

 

The public is being regularly deceived by the drug trials funded by

pharmaceutical companies, loaded to generate the results they need

 

Richard Smith

Wednesday January 14, 2004

The Guardian

 

Drug companies spend hundreds of millions of pounds to bring a new drug to

market, and tens of millions of pounds to do the clinical trials that are

necessary for both registration and marketing. Understandably, they would prefer

not to get results from these trials that are unfavourable to their drug. And,

despite the ubiquitous uncertainties of science and medicine, they rarely do.

How do they manage it?

In 1994, Canadian researchers looked at 69 trials of anti-arthritis drugs funded

by drug companies and published in prominent medical journals. In every case the

drug made by the company was as good as the comparative treatment, and in a

quarter of the trials it was better. Not once did a company fund a trial that

proved unfavourable to it.

Yet the whole scientific point of doing such trials is to answer so far

unanswered questions. Supposedly, researchers conduct trials when they are in a

charmed state called " equipoise " , which means they are genuinely uncertain which

is the best treatment. If they think one treatment is better than another, then

they shouldn't be conducting the trial.

A review published in 2003 found 30 studies that had compared the results of

trials funded by drug companies with those funded from other sources. Trials

funded by companies were four times more likely to have results favourable to

them than those funded by others.

Yet the technical quality of the trials funded by drug companies was always as

good and often better than the quality of those funded by other sources. This is

not surprising, as drug company trials are tightly regulated. There are explicit

high standards, and companies can afford to hire the best to conduct the trials.

How then do companies usually manage to fund research that is favourable to

them? An answer is supplied in a recent issue of the BMJ by Dave Sackett and

Andy Oxman, two tireless campaigners for the better use of scientific evidence

in medicine. They have founded a spoof company called Harlot - which stands for

How to Achieve positive Results without actually Lying to Overcome the Truth.

They created the company after it finally dawned on them that " being good and

being poor are causally related: being good doesn't pay " .

Harlot plc promises to give drug companies and others the results they want.

Your drug may be wholly ineffective, Sackett and Oxman promise, but as long as

it isn't a lot worse than a sip of triple distilled water, then Harlot can

produce positive results from a trial. Importantly, these results are not

usually achieved by doing poor quality trials. The trick is in the question

asked and the design of the trial. Sackett and Oxman, both experts on the design

and analysis of trials, describe 13 methods for getting the results you want.

One of the commonest methods is to test a new drug not against an effective

treatment but against a placebo. Ironically, regulators often require companies

to do this. But what matters to patients is not whether a company's drug is

better than nothing, but whether it is better than established treatments.

Companies are nervous about these " head-to-head " trials, particularly if many

drugs are being tested - because there may be only one winner and many losers. A

huge publicly funded head-to-head trial of treatments for high blood pressure

was published recently and threw companies into a tizz because it showed that

long-established drugs that are off patent were better than newer, much more

expensive drugs.

A company gets huge benefit from showing that its drug is better than a

competitor's. But the company needs to control the trial, and Harlot suggests

that a company compares its product with an inadequate dose of a competitor's

product. This may have been the reason why previous trials on drugs for high

blood pressure suggested that newer drugs were better.

A variant on this technique is to compare the drug with an excessive dose of the

competitor's product: it is then possible to show that the company's drug has

far fewer side-effects (because side-effects are more common with higher doses

of a drug). This may have been the method for showing that new and expensive

drugs for schizophrenia have fewer side-effects than older drugs.

Perhaps the most common method to avoid unfavourable results is to make sure

that a trial is not big enough to show that a competitor product is either

better or worse. Such trials are very common, and Silvio Garattini, a leading

Italian researcher and critic of the drug industry, has proposed a consent form

for them: " I understand that this trial is worthless for science and medicine,

but will be of great use to the marketing department of Shangri-la

Pharmaceuticals. "

All this matters greatly because 70% of trials in major medical journals are

funded by the drug industry. Often companies will buy reprints of these articles

to use in promoting their drug. Sometimes they may spend up to £750,000.

Virtually all research on drugs is funded by the industry, because governments

have taken the view that public money can be better spent elsewhere. The end

result is that information on drugs (on which Britain spends £7bn a year) is

distorted.

The Harlot article was written to amuse, but is as deadly serious as anything

else published in the BMJ in the past 10 years. The public is being regularly

deceived and exploited.

· Richard Smith is the editor of the British Medical Journal

rsmith

 

 

 

 

 

 

 

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