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Foregone Conclusions
The Public is being Regularly Deceived by the Drug Trials funded by Pharmaceutical Companies, Loaded to Generate the Results they Need
by Richard Smith
 

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 unfavorable 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 unfavorable 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 favorable 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 favorable 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 unfavorable 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

© Guardian Newspapers Limited 2004

 

 

Unborn babies soaked in chemicals, survey finds

Last Updated: 2005-07-14 11:03:36 -0400 (Reuters Health)

WASHINGTON (Reuters) - Unborn U.S. babies are soaking in a stew of chemicals, including mercury, gasoline byproducts and pesticides, according to a report to be released on Thursday.

Although the effects on the babies are not clear, the survey prompted several members of Congress to press for legislation that would strengthen controls on chemicals in the environment.

The report by the Environmental Working Group is based on tests of 10 samples of umbilical cord blood taken by the American Red Cross. They found an average of 287 contaminants in the blood, including mercury, fire retardants, pesticides and the Teflon chemical PFOA.

"These 10 newborn babies ... were born polluted," said New York Rep. Louise Slaughter, who planned to publicize the findings at a news conference on Thursday.

"If ever we had proof that our nation's pollution laws aren't working, it's reading the list of industrial chemicals in the bodies of babies who have not yet lived outside the womb," Slaughter, a Democrat, said.

Cord blood reflects what the mother passes to the baby through the placenta.

"Of the 287 chemicals we detected in umbilical cord blood, we know that 180 cause cancer in humans or animals, 217 are toxic to the brain and nervous system, and 208 cause birth defects or abnormal development in animal tests," the report said.

Blood tests did not show how the chemicals got into the mothers' bodies.

MERCURY AND PESTICIDES

Among the chemicals found in the cord blood were methylmercury, produced by coal-fired power plants and certain industrial processes. People can breathe it in or eat it in seafood and it causes brain and nerve damage.

Also found were polyaromatic hydrocarbons, or PAHs, which are produced by burning gasoline and garbage and which may cause cancer; flame-retardant chemicals called polybrominated dibenzodioxins and furans; and pesticides including DDT and chlordane.

The same group analyzed the breast milk of mothers across the United States in 2003 and found varying levels of chemicals, including flame retardants known as PBDEs. This latest analysis also found PBDEs in cord blood.

The Environmental Working Group report coincided with a Government Accountability Office report issued on Wednesday that said the Environmental Protection Agency does not have the powers it needs to fully regulate toxic chemicals.

The GAO, the investigative arm of Congress, found that the EPA's Toxic Substances Control Act gives only "limited assurance" that new chemicals entering the market are safe and that the EPA only rarely assesses chemicals already on the market.

"Today, chemicals are being used to make baby bottles, food packaging and other products that have never been fully evaluated for their health effects on children - and some of these chemicals are turning up in our blood," said New Jersey Democrat Sen. Frank Lautenberg, who plans to co-sponsor a bill to require more testing of toxic chemicals.

Pollutants and other chemicals are believed to cause a range of illnesses. But scientists agree the only way to really sort out the effects is to measure how much gets into people and then see what happens to their health.



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