Chapter 2
Dallas, Texas, 2007
Inside a Dallas conference hall, the lights dimmed and Dr. Evil from the movie Austin Powers: International Man of Mystery appeared on a large screen.
It was about 9 a.m. and the hall at the Gaylord Texan Resort & Convention Center was packed with sales representatives for Cephalon, a pharmaceutical manufacturer headquartered in Frazer, Pennsylvania, just northwest of Philadelphia. The salesmen were in town for a rah-rah retreat. Their work, encouraging doctors to prescribe opioids, had catapulted Cephalon, founded just twenty years earlier, onto the Fortune 1000 list of U.S. companies. In 2006, it posted $1.7 billion in revenue, a 46 percent increase over the previous year. The sales reps were not in Texas just for a collective pat on the back. Cephalon wanted more revenue, much more—and it wanted it from a new opioid tablet the company had brought to market.
The voice of comedian Mike Myers, who played Dr. Evil in the Austin Powers movies, was dubbed over by a Cephalon executive. The parody opened with ominous music and the subtitle “Somewhere outside Frazer, Pa.” Dr. Evil—bald, scarred, and wearing a gray Nehru suit—was seated at the head of a conference table, addressing his nervous acolytes while stroking his white cat. “I want to go over some problems we are having with Fentora,” the dubbed voice said, referring to the new fentanyl tablet Cephalon had created. The company had introduced Fentora the previous year with a corporate stage show that included fireworks and the U2 song “Beautiful Day” blasting in the background. Cephalon wanted Fentora to be a bestseller.
Dr. Evil said he was unhappy with the child-resistant packaging the Cephalon team had designed for its version of fentanyl—a synthetic opioid that is fifty times more powerful than heroin and typically used for anesthesia and cancer pain. “It’s a pain in the butt to open,” Dr. Evil said. He then pushed a button, causing one of those sitting around the table, the executive responsible for the packaging, to plunge into a pit of fire. “Let this be a reminder to you all that this organization will not tolerate failure,” Dr. Evil said, before urging his executives to push Fentora as a treatment for lower back pain—a radical reorientation of the drug’s use. Fentora had been approved by the Food and Drug Administration to treat what is called “breakthrough pain” from cancer, but the company now was pitching it to doctors to treat everyday ailments.
“Tell the Street,” Dr. Evil said, “a billion in sales this year!”
The use of opium to relieve pain dates back thousands of years. Opium poppies were cultivated in 3400 BC in lower Mesopotamia, where the Sumerians called them “joy plants”; Greek and Roman physicians used opium to induce sleep and soothe pain. In the United States, from the Civil War through the early 1900s, doctors treated pain with opium gum and morphine, without fully understanding their potential for addiction. By then, there were about three hundred thousand morphine addicts, many of them war veterans originally treated with the drug for their injuries. They were said to have the “soldier’s disease.”
In 1914, the federal government passed the nation’s first drug enforcement law, the Harrison Narcotics Tax Act, regulating the production and distribution of opioids. During congressional hearings before its passage, Donald McKesson, an executive of the company, founded in 1832, testified in favor of the legislation. He told the House Ways and Means Committee, “We have been ever since against the sale of habit-forming drugs and all that kind of thing. Orders which have come to us from suspicious people, we have put in the hands of the proper authorities for tracing and prosecution if necessary.”
Ten years later, the use of heroin was outlawed. The opioid was first introduced in 1898 by the German pharmaceutical company Bayer as a cough suppressant and headache treatment. For much of the twentieth century, opioids were reserved for late-stage cancer patients and short-term, in-hospital treatment after major surgery. American doctors would not prescribe powerful opioids for chronic ailments; the fear of addiction outweighed pain management gains. Doctors instead sought to provide relief for their patients with other therapies. It wasn’t until 1970 that Congress passed the Controlled Substances Act to regulate dangerous and addictive drugs, including opioids. Three years later, it created the Drug Enforcement Administration.
Even though opioids were heavily regulated and had earned a reputation as dangerously addictive, a movement started to gather strength in the early 1990s to use them for pain management. It was led by doctors such as Russell Portenoy at New York City’s highly prestigious Memorial Sloan Kettering hospital, who pushed for the wider use of opioids. Portenoy argued that many patients were suffering needlessly and the risk of opioid addiction was low, bolstering his claims with reports and data that were discredited years later.
But it was the pharmaceutical company Purdue Pharma, based in Stamford, Connecticut, that changed the culture of prescribing opioids in the United States and rewrote the narrative around pain management. Purdue, owned by the Sackler family, introduced OxyContin in 1996. Its main ingredient was oxycodone, an opioid first synthesized by German researchers in 1916. Purdue added a time-release feature and promoted OxyContin as a wonder drug for continuous pain relief with the slogan “The One to Start With and the One to Stay With.” So many people started and stayed with OxyContin that it became one of the most sought-after opioids on the street.
In a promotional video Purdue sent to fifteen thousand doctors in 1998, a doctor trumpeted that “the rate of addiction amongst pain patients who are treated by doctors is much less than 1 percent.”
The new uses of fentanyl, like Cephalon’s Fentora tablets, and other painkillers grew out of that industry-wide pitch: Less than 1 percent of people prescribed opioids become addicted. It was a falsehood, but a beguiling one. The lie permitted both the drug makers and the doctors to jettison a century of medical caution in the United States about addiction to painkillers.
The false statistic that would launch a thousand marketing campaigns—and seed the epidemic that has killed half a million Americans—emerged from a one-paragraph letter to the editor of the New England Journal of Medicine in 1980. The 104-word note was written by Hershel Jick, a doctor and drug specialist at Boston University School of Medicine, and Jane Porter, his assistant. They reported their observations on hospital patients who were provided opioids. Their finding was summed up in the headline that accompanied their letter: “ADDICTION RARE IN PATIENTS TREATED WITH NARCOTICS.” Jick and Porter reported that they had observed only four cases of addiction out of 11,882 patients.
In interviews more than thirty years later, Jick said that he put his findings in the letter because they couldn’t be considered a study. The claim that pain pills carried a small risk of addiction for all patients was “not in any shape or form what we suggested in our letter,” he said. He said he was “amazed” that the drug companies had used his letter for “pushing out new pain drugs.” No one from Purdue or the other companies that later used the less-than-1-percent statistic had ever asked him about his letter or its use in their advertising.
“I’m essentially mortified that that letter to the editor was used as an excuse to do what these drug companies did,” Jick said.
The 1 percent statistic spread and mutated in pain literature and the general media. At one point, Time magazine called the Jick letter “a landmark study.” But the real rate of addiction was far higher—at least 8 to 12 percent of patients prescribed opioids for chronic pain became addicted.
By 2007, other drug manufacturers had taken a page from the highly successful Purdue playbook. The companies paid doctors, who often cited the 1 percent claim, to speak at medical conferences and continuing medical education seminars as well as on national television and professional society dinners. Portenoy, the New York pain doctor, served as a spokesman for Purdue. And the companies quietly funded advocacy groups that encouraged wider use of opioids for pain patients.
The Joint Commission on Accreditation of Healthcare Organizations—a nonprofit that evaluates hospitals and medical programs—urged the medical community in 2001 to consider pain as the “Fifth Vital Sign” along with body temperature, blood pressure, and respiration and pulse rates. Doctors, nurses, and other health care providers were encouraged to ask their patients to rank their pain from 1 to 10—and not to be concerned about treating these self-diagnosed pain levels with opioids.
Aggressive sales reps who visited doctors’ offices to pitch their wares were the linchpin of the marketing strategy. Like most drug reps, they wined and dined doctors. They also showered them with little gifts of coffee mugs, golf balls, and fishing hats. But the reps pushing pain pills were particularly aggressive and cavalier. Some handed out stuffed toy gorillas wearing blue OxyContin T-shirts, as if the drug they were hawking was a plaything instead of a potential killer. The companies dangled big bonuses for sales reps who sold the most pain pills at the highest doses and rewarded the best performers with Caribbean cruises and expensive watches.
Between 1996 and 2001, the annual number of prescriptions for OxyContin soared from three hundred thousand to six million; the number of oxycodone-related deaths increased 400 percent during the same period. There was some pushback from concerned doctors, and even warnings from a handful of Purdue sales representatives, but their voices were drowned out by the marketing deluge and the intoxicating profits Purdue and other drug companies were posting.
Drug manufacturers also paid movie stars to promote more aggressive pain treatment. One was Jennifer Grey, famous for her role in the 1987 romantic drama Dirty Dancing. After she suffered a severe neck injury in a car crash, Purdue hired Grey as a spokeswoman for its “Partners Against Pain” campaign. She appeared on television programs to urge people in pain to become advocates for themselves. She later said she didn’t know she was being used to “potentially advance a darker agenda.”
Joe Rannazzisi was incensed by what he was witnessing, but powerless to address misleading marketing; that was the purview of the Food and Drug Administration. What he could speak out about—and what he knew from his training as a pharmacologist—was the addictive power of opioids. Joe and his team of investigators put together a slide show on the history of opioid addiction and the advent of the internet pharmacies. He began to present the slide show to medical boards, law enforcement officers, community organizations, pharmacy associations, congressional committees—anyone who would listen—to counter the messaging of the drug companies.
“All of a sudden the whole medical community says, ‘Oh, you know what, they’re not as addictive as we thought they were,’” Joe said during his presentations. “That’s crazy because we have had a hundred years-plus of addiction here based on these drugs.”
Someone always stood up and asked, “What about the study that shows that less than 1 percent of people get addicted to opioids?”
“That’s ridiculous,” Joe told his audiences. “I just want to see some evidence other than somebody saying that they’re not as addictive as we once thought they were. I want somebody to show me some peer-reviewed articles with a large population of patients. Not a letter to the editor in the New England Journal of Medicine.”
He left these meetings wondering if anyone was listening.