Big pharma hides negative results of trials to wring in more money

Grievances against the pharmaceutical industry are common in new media spaces. Influencers on Instagram tell us to shun drugs and embrace the “natural.” Diatribes are shared on Facebook against the profit-seeking motives of Big Pharma. Podcasts, websites, and videos try to convince us that the prescription drug business simply cannot be trusted. Joe Mercola, an osteopath who has set himself up as the one-stop shop alternative to medicine, recently declared on his site that “the drug industry has become the #1 cause of death and disability worldwide, hands down.”

This bag of grievances carries a heavy and myriad load of claims, some more believable than others. And it is precisely those more believable claims that help the conspiratorial pill go down.

“Something is wrong in medicine”

In his unsparing criticism of the drug industry, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, Dr. Ben Goldacre writes about a drug called reboxetine as an example of one of the many problems with how drugs are developed. Reboxetine (known commercially as Edronax) is an antidepressant. Dr. Goldacre, a psychiatrist by training, remarks in his book that he had prescribed reboxetine in the past. Why? Because the published scientific evidence showed that it was quite effective.

The problem is that Dr. Goldacre, like every other doctor, had been misled. A total of seven trials pitting reboxetine against placebo had been run. All except for one had shown no difference between the two. But the only trial whose results were actually published was the one showing reboxetine was better than placebo.

Six negative trials. One positive trial. The six negative trials were buried and didn’t see the light of day until a research team unearthed them. This is one of the major problems with the pharmaceutical industry: there are tremendous incentives to only publish the results of clinical trials that favour them and to never share the results of negative trials. This skewing of the medical literature will necessarily impact the decisions doctors make. How can a physician judge the true worth of a drug when the portrait that emerges from the literature has been doctored?

The system in which drugs are developed and marketed is further warped in a multitude of ways. Drugs can be approved based not on the hard endpoints that we care about, like death and disease, but on surrogate markers, like an abnormal heart rhythm. It’s easier and faster to show that a drug reduces the risk of an abnormal heart rhythm, but this is not the same as showing that it will reduce the risk of dying from this abnormal heart rhythm. Clinical trials can also be stopped early. Sometimes, there is an arguably good reason for doing so: the difference between the drug and what it is compared to is so vast that it would be unethical to withhold the drug from the other participants. But sometimes, a trial is prematurely terminated simply because the data collected at this point favours the drug. It’s not unlike playing rock-paper-scissors and, when you lose, suddenly deciding to do best-of-3… or best-of-4.

The pharmaceutical industry has also found ways to reduce the risks of studying new drugs and to wring out more money from pharmaceuticals whose patents are close to expiring. When a new type of drug has been shown to work and is approved for sale, other pharmaceutical companies can invest money into developing a slightly different version of this drug, what is referred to as a “me too” drug. Some of these molecules can be useful, by being safer or more effective in certain people, but they take time and money away from the trailblazing work of discovering brand-new classes of drugs. And when a profitable drug’s patent comes to an end, opening the door for other companies to manufacture it and sell it at a much lower price, the patent holder can use a trick of chemistry to hold onto their profits. Molecules can be left-handed or right-handed, mirror images of the same formula. As Dr. Goldacre reports in Bad Pharma, AstraZeneca was selling a heartburn medication known as omeprazole (Prilosec, Losec), which was a mixture of the left-handed and the right-handed forms of the drug. As the patent was running out, it launched esomeprazole (Nexium), which was a purified version of only the left-handed molecule. No difference in benefit, but AstraZeneca invested a lot of money in a direct-to-consumer campaign to convince patients this was the patented drug they needed.