Drug companies occasionally conduct post-marketing studies to collect data on the safety and efficacy of drugs in the real world, after the drugs have been approved by the US Food and Drug Administration (FDA). “However,” writes the anonymous author in the British Medical Journal, “some of the [post-marketing] studies I worked on were not designed to determine the overall risk:benefit balance of the drug in the general population. They were designed to support and disseminate a marketing message.”
Promotion enters into the picture as the company recruits doctors to enrol their patients into the study – a job for which they’re paid. The company tells doctors about the qualities of their drug, and the doctor relays that information to their patients.
According to the whistle-blower, the results of these studies were often dubious. “We occasionally resorted to ‘playing’ with the data that had originally failed to show the expected result,” he says. “This was done by altering the statistical method until any statistical significance was found.” He adds that the company sometimes omitted negative results and played down harmful side effects. After all, post-marketing studies don’t face the scrutiny that pre-approval studies do.
Why would a company resort to devious methods? After spending millions of dollars to develop a drug, companies scramble to recoup their investments in the decade that a patent lasts, writes the author.
Nature was unable to discern who this writer was, but if the two editorials accompanying it provide any indication, the whistle-blower might hail from a diabetes background. The other editorials focus on post-marketing studies of new insulins to treat diabetes. More specifically, they criticize studies conducted by the Denmark-based pharmaceutical company Novo Nordisk.
Some post-marketing studies fall into the category of ‘switch campaigns,’ writes Edwin Gale, emeritus professor of diabetic medicine at the University of Bristol, UK. Although these campaigns, which persuade prescribers to substitute a new drug for an established treatment, were denounced by the US Office of the Inspector General in 2003 and by the European Medicines Agency more recently, they continue today.
“There isn’t a stringent definition of what a post-marketing study is, and so regulators turn a blind eye to what is going on,” Gale says. “But when studies involve half a million people, you have to start asking questions.”
Gale’s case in point is the largest insulin study to date: a 67,000-person trial called A1CHIEVE, sponsored by Novo Nordisk and completed in 2011. With participants enrolled from 28 countries, Novo Nordisk’s explicit goal was to look at the worldwide profile of its drug, a genetically engineered insulin analogue. Gale finds that aim questionable, given that the drug had already been tested in clinical trials, before approval, in 21 of those nations.
In the end, the study found few benefits of the drug over competitors, and risks, such as low blood glucose levels, weren’t measured in a way that was meaningful, writes Gale. “This study is just not science at all,” he says.
What the study might have achieved is a larger market, says Gale, especially if patients remained on the drug after the study ended. “I don’t have proof that this is a marketing study,” he says, “but if it wasn’t a marketing study, what was it?”
The third editorial takes issue with the fact that A1CHIEVE study sites were not in Europe or North America, but in developing nations such as India and China, where the market for insulin is skyrocketing along with rates of type 2 diabetes. The ethics of convincing doctors to switch from human insulin to analogues that cost at least twice as much in countries where people make a dollar per day, are questionable, says John Yudkin, emeritus professor of medicine at University College London.
Although it’s not the case for A1CHIEVE, the FDA sometimes asks drug companies to do post-marketing studies when the agency has lingering questions at the time of drug approval. “That’s a good idea if the drug is important enough to warrant approval before all of the safety studies are done,” says Sidney Wolfe, director of the health research group at Public Citizen, a consumer advocacy group in Washington DC. He says that the new diabetes drugs, including insulin analogues, do not fall into this category because they don’t have significant benefits over their competitors and come with risks. He echoes the sentiment that many post-marketing studies are thinly veiled marketing ploys.
Novo Nordisk disagrees. In an e-mail to Nature, the head of communications at the company writes that the company conducted the investigations to “enable the scientific community to better understand the clinical realities of treating diabetes in today’s world”. He adds that “it is hardly surprising that Novo Nordisk promotes the use of insulin analogues given the body of evidence supporting the clinical benefits of these products over the earlier generation of insulin products.”