Rising painkiller addiction shows damage from drugmakers’ role in shaping medical opinion

“There were very few studies then that suggested that any more than 8 percent of people on prescription opioids exhibited addiction-type behaviors,” Ballantyne said. Now, she said, the understanding is that the number may be as high as 50 percent.

How did all these studies — co-authored by doctors with university affiliations and published in academic journals — lead to conclusions that now are in dispute?

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Prescriptions for opioid painkillers are rising.

One reason, according to critics, is that most of the studies were conducted by drug companies.

“A pharmaceutical company that has a vested interest in promoting their product should not be seen as a reliable source of safety information,” said Orman Hall, director of the Ohio Department of Alcohol and Drug Addiction Services. “Some of those estimates are ludicrous.”

Consider the 16 clinical trial reports that Ballantyne highlighted and used in her article, which reflect the medical literature at the time. Her summary did not discuss sponsors of the studies. But of those 16, six were sponsored by Purdue Pharma or co-authored by its employees, one was sponsored by Mundipharma, which distributed OxyContin and other opioids, and two were sponsored by another drug company or co-authored by drug company employees.

In the trials, patients were given an opioid for pain, but in most, there were no systematic checks for withdrawal symptoms or addiction. Instead, in most of the trials, regardless of whether they were sponsored by drug companies, the investigators generally found that the benefits of pain relief outweighed the risks of side effects such as constipation and dry mouth.

If investigators were looking for signs of addiction, they weren’t looking hard.

“In the absence of rigorous evaluation and surveillance, it’s hard to know whether the low levels of addictive behavior reported in those studies are accurate,” said David A. Fiellin, a professor of medicine at Yale with an expertise in addiction.

Fiellin noted that the design of a study can dramatically change the results and that entrusting the design to scientists with conflicts of interest could introduce bias. What patients are admitted to the trial? How are side effects measured? How large are the doses?

“All of those are scientific decisions that should be made by people without any regard for how the findings will affect the company’s bottom line,” Fiellin said, adding that the government could play a larger role in funding.

Data discrepancy

In one of the studies sponsored by Purdue that Ballantyne covered, and that played a large role in the marketing of OxyContin, there appear to have been significant discrepancies between the data that were gathered and those that were published.

A March 2000 issue of the Archives of Internal Medicine published a study that followed 106 arthritis patients treated with OxyContin for several months.

Six times during the trial, researchers intentionally stopped the doses.

Remarkably, according to doctors who study addiction and dependence, there were no reports of withdrawal during those respites.

Two patients had withdrawal problems, but one was at the end of the study, and the other had simply run out of the medication.

“Withdrawal syndrome was not reported as an adverse event for any patient during the scheduled respites,” the authors reported.

The trial also showed that the drug was effective and was embraced by the Purdue marketing team, which ordered 10,000 reprints to distribute to its sales staff, with instructions to highlight the finding on withdrawal.

But according to company documents disclosed in a court case, the paper left out several cases of withdrawal.

Inside Purdue, supervisors and employees reviewed a more complex set of data, according to a document signed by company attorneys and prosecutors, which accompanied a 2007 settlement in which federal prosecutors charged Purdue with misbranding the drug.

The document has not previously been linked to the Archives article.

“Multiple” patients, a company review said, “directly stated or implied that an adverse experience was due to possible withdrawal symptoms.”

Eleven study patients “reported adverse experience due to possible withdrawal symptoms during these periods,” according to the court document.

How did this discrepancy arise?

One of the authors of the Archives article, Roy Fleischmann, a clinical professor of medicine at the University of Texas Southwestern Medical Center at Dallas, said the authors were given the data by Purdue.

“We reported on the data which was provided to us,” he wrote.

He said the discrepancy may have arisen because some of the side effects — such as insomnia, nausea and anxiety — were not characterized by Purdue “as withdrawal symptoms, although, in retrospect, they probably were,” he said in an e-mail.

Doctors who have treated OxyContin addicts, and some former addicts, moreover, say that considering the doses given to the patients in the trial and its duration, even the internal document undercounted patients reporting withdrawal symptoms. They say the majority of patients were likely to have suffered withdrawal symptoms when the drug was cut off.

At the doses given in the trial, most patients are “pretty consistently” going to have withdrawal symptoms, said Phillip Prior, a board-certified addictionologist in the Portsmouth area who has treated thousands of patients addicted to opioids.

He said the lower estimates are “flawed conclusions from a very flawed study.”

“I’ve never seen anyone come off of them and not get withdrawal,” said Billie Taylor, 42, a former addict who works at a treatment center in Portsmouth. “I would have quit a lot earlier if it had not been for the withdrawal. You feel like you want to die. Even if you take them at prescribed levels, you get withdrawal.”

“You could say these marketing tactics are merely concerning,” Prior said. “But I think of them as satanic. What the data are telling us is that these drugs are ruining people’s lives.”