“New Hope for Millions of Americans Suffering from Persistent Pain” was the headline on the May 31, 1996, press release from Purdue that announced the on-sale date of OxyContin.1 “The first and only 12-hour oxycodone” was heralded as “a significant advance in the treatment of persistent pain.” OxyContin was, according to the release, the end of patients enduring “anxious ‘clock-watching’ when pain must be controlled over long periods.” (No regulations required that Purdue disclose that a third of patients in clinical trials did not get twelve hours of pain relief.)2 Pushing the limits of the conditions for which the FDA had approved the drug, Purdue claimed Oxy was for “moderate to severe pain lasting more than a few days… such as the pain associated with arthritis, cancer, injuries, lower back problems, and other musculoskeletal problems.”3 According to the press release, “drug dependence is treatable… and ‘addiction’ to opioids legitimately used in the management of pain is very rare.”
The detail team fanned out across the country for its sales blitzkrieg. The Sacklers knew that money was the best motivator for sales representatives. Purdue made it simple. Most drug companies paid their reps based on how many prescriptions the physicians they had visited later wrote. For OxyContin the sales force’s compensation was based on the dollar amount of the prescriptions dispensed by the doctors each had visited. The IMS Cornerstone 3.0 software Purdue bought eliminated the difficulty of figuring out if a sales rep had influenced a doctor to write more scrips. Through the 1980s, a physician’s dispensing data were a quarterly snapshot. By the time of OxyContin’s release, drug companies tracked the exact number of scrips written daily.
In high-volume states, salesmen visited each “core dispenser” a minimum of two hundred times annually.4 Some called daily. Each one-on-one visit cost Purdue about $200.5 That translated into $40,000 for each top-tier doctor, an amount that added into the millions. The Massachusetts attorney general in a complaint filed in 2019 against Purdue and the Sackler-family directors noted that “Purdue did not spend $40,000 per doctor so sales reps could watch doctors write prescriptions that they were already going to write anyway. Instead, Purdue paid to lobby these doctors because Purdue knew its reps would convince them to put more patients on opioids, at higher doses, for longer periods. Those extra prescriptions paid back Purdue’s investment many times over.”6
Carl Elliott, a doctor and professor of bioethics, has reviewed decades of the changing relationships between drug reps and physicians. He noted that over a five-year period starting in 1996, the year OxyContin went on sale, the number of industry detail reps doubled to ninety thousand. This era introduced what old-timers disparaged as Pharma Ken and Pharma Barbie, attractive young reps whose pharmaceutical know-how was not as important as their ability to sell. For drugs exceeding $200 million annually in sales, which OxyContin achieved, the average return was tenfold for every dollar spent on the detail team.7
Purdue’s revised compensation meant that the sales team, especially top performers, were among the highest paid in the pharmaceutical industry. Large bonuses sometimes doubled a sales rep’s annual salary and became a much sought-after incentive for generating the largest OxyContin sales.8 Purdue had fulfilled a promise set out in an internal memo to the “Entire Field Force” just after the drug went on sale. Employing an analogy from The Wizard of Oz, it assured the detail team that for those reps who sold the most, “A pot of gold awaits you ‘Over the Rainbow.’ ”9 Two months later, a memo that reminded sales reps to encourage the more profitable, higher-dose pills was titled: “$$$$$$$$$$$$$ It’s Bonus Time in the Neighborhood!”10
Purdue was not alone in empowering its sales force. Many of the biggest companies had long capped how much reps could earn. When Anthony Wild, a former Sandoz chemist, became Parke-Davis president in 1995, one of his first directives was to remove the limits on detail team bonuses. “Why not let them get rich?” he answered to some long-serving executives who questioned the decision. Wild’s view was that the more the sales team made, the more Parke-Davis earned. When he announced the decision at a San Francisco company conference, “the sales force went nuts!” he later recounted.11
It took little time before the sales team realized there was more profit for Purdue and more money for them by pushing higher doses of OxyContin. When it first went on sale, there were three strengths: 10, 20, and 40 milligrams. An 80 mg tablet was released a month later (15, 30, 60, and 160 mg would arrive in a few years).12 Purdue’s production costs across the board were virtually the same since oxycodone, the active ingredient, was cheap to manufacture. However, it charged more for each higher strength.13 On average, a bottle of 20 mg pills cost twice as much as the 10 mg variety. Eighty milligrams were about seven times more expensive than the low-dose. If a patient took 20 mg pills twice a week, internal documents put Purdue’s profit at less than $40. The same patient prescribed 80 mg pills twice a week returned over $200 to the company, a 450 percent increase (that profit exceeded $600 a bottle in another five years).14 Prescribing physicians typically had no idea what Oxy cost, nor did most care. Since they did not pay for the drugs, they passed the worry to patients and their medical insurance companies.15 I 16
Purdue created a campaign it called “Individualize the Dose” to help the detail team push the strongest doses. Sales reps told doctors that the company’s own studies showed that instead of starting patients on low strengths to see if that worked, it was best to start on a medium to higher dose. That way the drug would relieve pain faster and allow the patient to stop using it quicker. Moreover, in any instances in which doctors reported that they were dispensing OxyContin three or even four times daily because their patients were not getting the promised twelve hours of pain relief, sales representatives assured doctors that higher doses would make the drug last longer.17 The detail team had been instructed not to ever suggest more than twice-a-day dosing. Purdue feared that would be the fastest way for the company to run afoul of the FDA. And insurance companies and hospitals that had agreed to cover OxyContin had done so on the basis it was a twelve-hour drug. If it proved otherwise, insurance companies might stop paying for it.18 II 19 The higher doses, Purdue representatives assured physicians, could be dispensed even to people who had never used opioids, all without adverse effects. The field reps contended that the higher-dose pills were no more likely to cause addiction.20
That was not true. Internal documents later revealed that Purdue’s detail team knew that stronger doses carried a much higher likelihood of dependence, addiction, even respiratory suppression that could be lethal. While the company’s press releases claimed that “dose was not a risk factor for opioid overdose,” internal communications are replete with references to the dangers of “dose-related overdose.”21
Besides encouraging physicians to dispense higher doses, Purdue ran a parallel campaign to extend OxyContin’s treatment period for as long as possible. Sales reps told doctors that a common error was putting patients on the drug for too short a period since that resulted in a rebound in pain.22 Longer treatment was a gold mine for Purdue and the sales reps. A patient given 80 mg pills twice a day brought Purdue $200 profit. The company earned $11,000 if that patient stayed on the drug for a year. Internal correspondence reveals that patients were 30 times more likely to die of an overdose if they took OxyContin for three months, 46 times more likely after six to eleven months, and 51 times more likely to die if they remained on OxyContin more than a year.23
All the aggressive promotion took place without any public objection from the FDA. Although the FDA does not have to preapprove ads, pharmaceutical companies are required to submit all promotional material to the agency before using it. At the time, the office assigned that responsibility was understaffed and overwhelmed. Thirty-nine employees oversaw some 35,000 promotional items annually.24 In the case of OxyContin, the FDA would not complain to Purdue for two years, and when it finally did so, it was about a video distributed to doctors that had not been sent first to the agency. Purdue claimed it was an oversight and submitted it. The FDA did not review that video for another four years, at which time it ordered it withdrawn for minimizing the risks of OxyContin and overstating its benefits. There was no penalty for Purdue having made the false claims, just a promise not to do it again.
As the sales team encouraged doctors to extend their prescriptions of OxyContin, the company introduced a savings card that encouraged chronic pain patients to at least try the drug. It offered a substantial discount on their first prescription (later it offered one free refill).25 A long-term Purdue planning document concluded that “more patients remain on OxyContin after 90 days.” The card got them started. It worked better than even the company’s most optimistic forecast for its return on investment. For each million dollars Purdue spent on the freebies, the patients who tried the drug and stayed with it brought in $4.28 million in additional sales.26
The same year OxyContin went on sale, Purdue hired Dr. J. David Haddox. As the company’s medical director, Haddox became the public face for Oxy at physicians’ conferences and training courses. He reassured his colleagues that the risk of addiction was only “one-half of one percent,” something that was “exquisitely rare.”27 Many who heard Haddox make the case for OxyContin were not pain specialists but general practitioners who had not paid close attention to the opioid reevaluation movement. For them, his presentation was new and persuasive.
Haddox also developed a separate strategy that would have made Arthur Sackler proud. Some in the detail team were not sure how to handle instances in which physicians raised the possibility that one or more of their patients on OxyContin might be addicted. Most doctors, Haddox told them, misinterpreted pseudoaddiction as true addiction.28 Those doctors were likely just observing their patients’ reaction to severe pain and the stress of failed treatments. The only way to eliminate pseudoaddiction was to eliminate the underlying pain. That meant whenever physicians thought patients showed signs of addiction, the sales representatives recommended they stay with the drug and increase the dose.29 That persuaded a surprising number of doctors. For physicians who were reluctant to sometimes double the dose, some dispensed the same strength but increased the frequency.
One topic forbidden in Purdue was what might happen if someone scraped off Oxy’s patented coating or crushed the pill. Purdue had conducted its own tests before OxyContin’s release and knew what would happen. When someone bypassed the extended release shell, about 70 percent of the oxycodone, as opposed to the time released 10 percent, went straight to the brain. That produced a euphoric high that rivaled heroin.30 The FDA thought it had addressed the matter by requiring that Purdue put an all-caps warning on the prescription insert: “TABLETS ARE TO BE SWALLOWED WHOLE, AND ARE NOT TO BE BROKEN, CHEWED OR CRUSHED. TAKING BROKEN, CHEWED OR CRUSHED TABLETS COULD LEAD TO THE RAPID RELEASE AND ABSORPTION OF A POTENTIALLY TOXIC DOSE OF OXYCODONE.”31 It took the Centers for Disease Control twenty years to determine that was a deadly flaw in the pill’s design.32
Although there were no supporting studies or empirical evidence, the FDA also had allowed Purdue to claim on the drug’s insert that OxyContin’s delayed absorption was “believed to reduce the abuse liability.”33 It was the first time the FDA had approved such an assertion. It accepted Purdue’s theory that since drug addicts needed a narcotics rush, they would always want fast-acting painkillers such as Vicodin and Percocet. “That contention proved disastrously wrong,” later wrote Barry Meier, the New York Times reporter who covered Purdue and OxyContin.34
Purdue realized that the FDA language was invaluable and a pre-sales marketing memo said it might serve as the drug’s “principal selling tool.”35 No wonder Richard Sackler was so confident that he promised his family directors and Purdue executives that “the launch of OxyContin Tablets will be followed by a blizzard of prescriptions that will bury the competition. The prescription blizzard will be so deep, dense, and white.”36 An initial marketing plan set forth a goal that seemed like hyperbole but demonstrated how ambitious the plans were for Oxy: “Purdue Pharma’s corporate goal is to be one of the Top 10 pharmaceutical companies by 2010.”
Richard Sackler was right. OxyContin was a big hit.37 Doctors wrote more than half a million prescriptions for non-cancer-related pain in its first year. Dr. Curtis Wright, the FDA official who had approved OxyContin for sale, left his government post and joined Purdue the year after it was on sale. His hire likely added to the perception that OxyContin was on its way to changing how physicians treated pain. Two years after it went on sale Oxy returned a remarkable 80 percent of Purdue’s profits and was double MS Contin’s top revenue year.38 Sales soared from $48 million in 1996 to $1.1 billion in 2000, the first drug in Purdue’s history to join the pharmaceutical industry’s small billion-dollar-in-sales club.39 By then, Purdue’s detail team was earning over $40 million in year-end bonuses.40
I. Twenty years later, when the CDC pressed for explicit warnings and voluntary prescription limits on the highest doses, Purdue calculated how much money it would lose if physicians followed the recommendations.
II. In 2004, Purdue paid $10 million to settle a lawsuit filed by the West Virginia attorney general. The suit demanded reimbursement for the extra costs incurred by the state on its prescription benefit programs for the elderly and poor. Purdue’s twelve-hour dosing claim, contended the attorney general, was deceptive marketing. In the settlement, Purdue admitted no wrongdoing.