A British physician is hoping to change the future of medical research by asking pharmaceutical companies to document every clinical trial study they conduct.
Ben Goldacre believes doctors are only “imagining that we’re practicing evidence-based medicine” because less than half of all clinical studies ever get published.
Goldacre says that there are many reasons why a large portion of clinical data goes unreported, but he has three main arguments.
Get Rid of the Negative
One of the biggest reasons why studies go unreported is because they have negative side effects. While no company wants to be known for producing a harmful drug, Goldacre says successful trials are much more likely to be reported.
“The best currently available evidence comes from systematic reviews on the problem of missing trial data, which show that about half of all trials conducted and completed for the medicines we use today haven’t gone on to be published, and that trials with positive results are twice as likely to be published as trials with negative results,” said Goldacre.
On top of negative consequences, Goldacre says trials go underreported because there was a fatal error in the procedure. Companies don’t want to admit that they paid millions of dollars for a new drug only to see it fail because of a controllable error, so they don’t publish the results. Not publishing the results won’t bring their money back, and future studies could learn from the failed trials.
Loose Reporting Restrictions
The second reason why clinical trials go unpublished is because medical regulations are loosely enforced, and there are loopholes that allow the companies to “legally” refrain from publishing the complete data.
Goldacre said that in 2005, the International Committee of Medical Journal Editors enacted a regulation that required every study to be registered in public before it was published in a journal.
“The idea was if that everybody who’s got a positive result wants to publish it in a journal, then that’s a real carrot that journal editors can use to force people to register their trials,” said Goldacre.
The idea was well-intended, but it was loosely enforced.
“A paper published five years after these regulations came into force looked at every trial published in the top 10 journals in the big five fields of medicine,” said Goldacre. “Half of them weren’t registered properly, and a quarter of them weren’t registered at all.”
Goldacre says the Food and Drug Administration is also at fault. In 2007, the FDA enacted a law stating that the results of every clinical trial must be published to ClinicalTrial.gov within one year of completion, yet there was only 22% compliance among drug companies.
“Four out of five trials ignored this law, and yet no fine has ever been levied by the FDA,” said Goldacre. “Even if one had been levied at $10,000 a day, that’s basically a parking ticket to a big drug company making a few billion off one drug.”
The More Eyes, the Better
The final reason clinical trial data goes underreported stems from the idea that regulators want to keep their work to themselves so they can discover the cures on their own. Goldacre says the public suffers behind this close-minded approach.
“There’s an idea among regulators that it’s okay for them to make decisions behind closed doors and just tell doctors what to do,” said Goldacre. “I think that doesn’t work anymore because science isn’t about just telling someone the answer. Science is about being clear, open, and transparent about your methods and your results.”
Simply put, the more people that have access to a problem, the greater the chance that it can be solved quicker and more efficiently.
“Problems with Vioxx weren’t spotted by the FDA; they were spotted by an independent cardiologist, he said. “Problems with Avandia weren’t spotted by regulators; they were spotted by individual academic researchers.”
A Change on the Horizon
Goldacre hopes to change to face of clinical trial reporting by getting pharmaceutical companies to agree to release their data, regardless of the results. He hopes that awareness of the issue will also lead to patients putting pressure on drug companies.
“I believe very strongly that when patients come to realize the extent to which we’ve failed them by not addressing missing data, they will be, well, disappointed is the most relaxed word I can think of,” said Goldacre. “I think they’ll be appalled.”
To assist in trial reporting, Goldacre has created the website AllTrials.net. He has been talking with major pharmaceutical companies and smaller patient groups in hopes of getting their support. So far over 80 patient groups have agreed to register their studies, and Goldacre even received support from GlaxoSmithKline, one of the largest drug companies in the world. Goldacre hopes GSK’s support will lead to more companies registering their studies.
“I don’t think GSK will be the only company to sign up,” he said. “I think we’re going to enter a very interesting era where potentially the market is differentiated by ethical companies who’ve made a commitment to sharing all their trial results, and unethical companies who are still aggressively defending their ability to withhold information from doctors and patients.”
Dr. Silverman comments
The director of my residency program and one of my mentors, Dr. Eric Radin, a pioneer in Orthopaedic surgery and a true clinical scientist, once said that the medical community could learn so much from ‘The Journal of Failed Study’, yet no such publication exists.
Dr. Radin believed so much could be learned from the trials that didn’t work out the way the researchers had intended. If we took away the stigma of a failure we would open the door to such greater and faster learning.
For a minimum, a section entitled ‘poor design’ would be a source of constant education and cost savings. How much money is wasted because true design is faulty from the get go but we can’t see the confounding variable of importance?
But, with respect to my typical conspiracy suspicions combined with the obvious implications of the article, eliminating the bias of making studies that didn’t give results in a company’s favor be published could save lives. Company’s truly should open up and expect the meta-analysis to eventually fall in their favor.
Related source: MedPage Today