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Empire of Pain

Review: Empire of Pain is a family saga about the Sackler’s, the crime story about Purdue Pharma, and the systemic failures of the FDA & the justice system.

Authur Sackler pioneered medical advertising and marketing. He re-conceived how drugs were sold and brought heaps of creative energy into it. Like he marketed Valium (Diazepam) as a cure-all and could be used by almost every speciality, in turn, it was the first drug in history to generate over $100 million in sales. The advertising models he architected back in the 60s are so effective that pharma companies are still using them today.

In 1996, Purdue Pharma introduced OxyContin. OxyContin is a sustained-release formulation of oxycodone, a chemical cousin of morphine and heroin but roughly twice as potent. The book details how they marketed OxyContin to doctors & patients and their unethical behaviour that fueled the opioid crisis.

OxyContin is the one to start with and to stay with.

"Fewer than 1%" of patients who took OxyContin became addicted.

Those are compelling marketing pitches that they had. And doctors bought into it. This to me was one of the most provoking aspects of this whole thing cause we tend to put a great deal of trust in doctors. But then it’s startling to learn just how easily swayed a doctor can be. A single meal with a value of $20 can be enough to change the way a doctor prescribes, according to a 2016 study. And Purdue would allocate $9 million just to buy food for doctors.

Empire of Pain is a mesmerising read, strongly recommended


Excerpt

There was a sense that doctors were morally upright, and it was a vocation that served the public good and promised prestige and financial stability. […] “First, do no harm,” the very idea of the integrity of doctors was enshrined.

Ch 1: A Good Name
Empire of Pain by Patrick Radden Keefe

This had become a mantra for Isaac. If you lose a fortune, you can always earn another, he pointed out. But if you lose your good name, you can never get it back.

Ch 2:
Empire of Pain by Patrick Radden Keefe

Historically most prescription drugs had been generic, with no brand names and little product differentiation. Besides, drugs weren’t sexy. How do you sell a pill.

Arthur’s answer was to adopt the seductive pizzazz of more traditional advertising—catchy copy, splashy graphics—and to market directly to an influential constituency: the prescribers. […]

So, in selling new drugs, he devised campaigns that would appeal directly to clinicians, placing eye-catching ads in medical journals and distributing literature to doctors’ offices. Seeing that physicians were most heavily influenced by their own peers, he enlisted prominent doctors to endorse his products.

John Kallir, who worked under Arthur for 10 years at McAdams, recalled, “Sackler’s ads had a very serious, clinical look — a physician talking to a physician. But it was advertising.”

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe

One Terramycin ad was designed to look like a vision test at an optometrist’s office.

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe
Arthur Sackler’s Terramycin Ad
credit: buildingpharmabrands

For a drug company, this was a profitable strategy: you don’t want to niche a product; you want to sell it to as great a range of patients as possible. The term “broad spectrum” sounds clinical, but the truth is, it was coined by advertisers: it first entered the medical literature with Arthur’s campaign for Terramycin.

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe

Arthur worked with McKeen to launch an unprecedented marketing blitz. The shock troops in this campaign were the so-called detail men—young, polished sales representatives who could visit doctors in their offices, armed with promotional literature, and talk about the values of a drug. Initially, there were only eight detail men working on Terramycin. […]


By 1957, they would have two thousand. Terramycin wasn’t a particularly groundbreaking product, but it became a huge success because it was marketed in a way that no drug ever had been. It was Arthur Sackler who would be credited not just with this campaign but with revolutionizing the whole field of medical advertising. In the words of one of his longtime employees at McAdams, when it came to the marketing of pharmaceuticals, “Arthur invented the wheel.”

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe

To sell broad-spectrum antibiotics, Arthur would employ a broad-spectrum advertising strategy. In addition to the lavish spreads in medical journals, detail men would drop by doctors’ offices, maybe volunteer to buy them a meal, and leave behind some official-looking medical literature.[…]

Not everyone was thrilled about this new synergy between medicine and commerce. “Is the public likely to benefit if practicing physicians and medical educators must perform their duties amidst the clamor and striving of merchants seeking to increase the sales of drugs?” Charles May, a prominent professor at the Columbia Medical School, wondered. He worried about what he described as “an unwholesome entanglement” between the people who prescribe our medicines and the people who make and market them. […]

But Arthur brushed off such critiques on the grounds that what he was doing wasn’t advertising at all. It was education. There were so many new drugs coming onto the market that doctors needed help knowing what was out there. Arthur was merely a facilitator in a benevolent cycle whereby drug companies developed new lifesaving remedies, admen informed physicians about them, and physicians prescribed the remedies to their patients, saving lives. Nobody was looking to exploit or deceive anybody else, Arthur argued. After all, in his view, doctors were unimpeachable.

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe

“No single individual did more to shape the character of medical advertising than the multi-talented Dr. Arthur Sackler.” It was Arthur, the citation continued, who brought “the full power of advertising and promotion to pharmaceutical marketing.”

Ch 3: Med Man
Empire of Pain by Patrick Radden Keefe

Just a few years earlier, it might have seemed that marketing directly to doctors was enough, but post-Miltown such an approach seemed quaint. Patients had started going to their doctors and requesting each new wonder drug by name.

With each new “indication,” the potential market for the drug expanded. But if Librium was going to be a pharmaceutical for the masses, how could Arthur Sackler and his team at McAdams devise a campaign that would reach them?

Ch 4: Penicillin for the Blues
Empire of Pain by Patrick Radden Keefe
credit: ProCon.org

Before it could launch Valium in 1963, however, Roche faced an unusual challenge: they had just introduced this groundbreaking tranquilizer, Librium, which was still doing gangbusters business. If the company now rolled out a second tranquilizer that performed even better, wouldn’t they just cannibalize their own market? What if Valium rendered Librium obsolete?

The answer to this conundrum lay in advertising—in the province of Arthur Sackler. […]

Librium and Valium were both minor tranquilizers. They both did pretty much the same thing. What Arthur’s team at McAdams had to do was convince the world—both doctors and patients—that actually the drugs were different. The way to do this was to pitch them for different ailments. If Librium was the cure for “anxiety,” Valium should be prescribed for “psychic tension.” If Librium could help alcoholics stay off the bottle, then Valium could prevent muscle spasms. Why not use it in sports medicine? Soon, doctors were prescribing Roche’s tranquilizers for such a comical range of conditions that one physician, writing about Valium in a medical journal, asked, “When do we not use this drug?” To Arthur and his colleagues, this was what made Valium such an easy product to sell. As Win Gerson remarked, “One of the great attributes of Valium is that it could be used by almost every specialty.”

Ch 4: Penicillin for the Blues
Empire of Pain by Patrick Radden Keefe

In 1960, Roche had enlisted a Stanford professor and physician named Leo Hollister to consult on Librium. Hollister worried that if Librium was as great as Roche was saying, it would be abused. So he decided to conduct a test. He administered high doses of Librium to thirty-six patients for several months, then switched eleven of them to a placebo. Ten of the patients who were abruptly taken off the drug suffered unpleasant withdrawal symptoms; two of them had seizures. When Hollister informed Roche, executives at the company were not happy. “I wasn’t trying to kill their drug,” he later recalled. He just thought that patients should know that the image Roche and McAdams were projecting—of a happiness pill completely free from downsides— wasn’t accurate.

Roche was anything but chastened by Hollister’s findings. In fact, when he published his research, the company’s medical director shot back that Hollister was misreading his own study. The withdrawal was not a sign of any dangerous physical dependence on Librium, but an intensification of the underlying condition that the Librium was meant to address in the first place. All the patient needed, in other words, was more Librium. […]

Confronted with this sort of evidence, Roche offered a different interpretation: while it might be true that some patients appeared to be abusing Librium and Valium, these were people who were using the drug in a nontherapeutic manner. Some individuals just have addictive personalities and are prone to abuse any substance you make available to them. This attitude was typical in the pharmaceutical industry: it’s not the drugs that are bad; it’s the people who abuse them.

Ch 4: Penicillin for the Blues
Empire of Pain by Patrick Radden Keefe

Moral panics over drugs in America had tended to focus on street drugs and to play on fears about minority groups, immigrants, and illicit influences; the idea that you could get hooked on a pill that was prescribed to you by a physician in a white coat with a stethoscope around his neck and a diploma on the wall was somewhat new

Ch 4: Penicillin for the Blues
Empire of Pain by Patrick Radden Keefe

If you put your name on something it is not charity, it’s philanthropy. You get something for it. If you want your name on it, it’s a business deal.

Ch 5: China Fever
Empire of Pain by Patrick Radden Keefe

At some point in the early fall of 1956, Nachumi testified, he had been given an assignment, to “revise a speech by Dr. Welch.” The remarks, he was told, would be presented at the Fourth Annual Antibiotics Symposium. Prior to the conference, Nachumi revealed, Henry Welch had delivered to Pfizer a copy of his proposed remarks, “for approval.” The company had then instructed Nachumi to give the speech a quick once-over, to “jazz” it up. […] the one big change he had made was to add to the speech the passage about the “third era of antibiotics.” Someone at Pfizer had dreamed up the line, he explained, as a marketing “theme” for Sigmamycin. It wasn’t that Pfizer admired the FDA man’s sound bite so much that they borrowed it for their ad copy. The company had insinuated its own ad copy directly into the speech. […].

As it turned out, Welch’s final remarks had been published in one of the journals that he edited with Félix Martí-Ibáñez. And, under the terms of his deal with Martí-Ibáñez, Welch was entitled to half of any income generated by the sale of those reprints. And Pfizer, following the symposium, had ordered reprints. Lots of reprints. To be precise, Pfizer had ordered 238,000 copies of the speech. Of course, the ostensible purpose of ordering the reprints was that the company could give them away, as part of its promotional effort. But how many copies of Dr. Henry Welch’s welcome remarks from the Fourth Annual Antibiotics Symposium could you realistically give away? […]

Kefauver moved in for the kill. “What was the reason for buying so many, do you know? If you had no use for them?”

The PR man dissembled. But to anyone who was paying attention, the answer was clear: by buying all those reprints, Pfizer was bribing Henry Welch.

Ch 6: The Octopus
Empire of Pain by Patrick Radden Keefe

The Sackler empire is a completely integrated operation. They could develop a drug, have it clinically tested, secure favorable reports from the doctors and hospitals with which they had connections, devise an advertising campaign in their agency, publish the clinical articles and the advertisements in their own medical journals, and use their public relations muscle to place articles in newspapers and magazines.

Ch 6: The Octopus
Empire of Pain by Patrick Radden Keefe
Sackler Gallery @ The Met (Gallery 206)
credit: sackler.org

When he was approached by Rorimer, Arthur agreed to make a substantial gift, pledging $150,000 for a renovation on the second floor of the museum, on the condition that the space be renamed the Sackler Gallery.

This was a standard ask. When donors gave money, they liked to see their name on the wall. But Arthur also proposed a more exotic arrangement. He suggested that he would purchase from the Met all of the artworks that would fill the new space—a series of Asian masterpieces that the Met had acquired back in the 1920s. He offered to pay the price that the Met had originally paid—the 1920s price—and then donate the works back to the museum, with the understanding that each piece would henceforth be described as a “gift of Arthur Sackler,” even though they had belonged to the museum all along. This would be a convenient way for the museum to generate some additional revenue and for Arthur to attach the Sackler name to more objects. Arthur had also become attuned to the advantages of gaming the tax code, so for tax purposes he declared each donation not at the price he paid for it but at the present market value. It was a classic Arthur Sackler play: innovative, showy, a little bit shady; a charitable gesture in which, considering the tax advantages, he would actually make money. But the museum needed cash, so it agreed.

Ch 7: The Dendur Derby
Empire of Pain by Patrick Radden Keefe

In 1954, their friend Bill Frohlich, the German adman and fourth musketeer, had founded a company in New York called IMS. The idea behind IMS was to aggregate pharmaceutical sales data, gathering information about what drugs doctors were prescribing, and furnishing that data to pharma companies, which would pay a premium for it, in order to hone their marketing.

Ch 8: Estrangement
Empire of Pain by Patrick Radden Keefe

What passes for news in the Medical Tribune is highly filtered editorial comment irrationally favorable to the drug industry.

Ch 9: Ghost Marks
Empire of Pain by Patrick Radden Keefe

It seemed to Kapit that money wasn’t something he [Richard Sackler] worried about, because he didn’t need to worry about it; it had always been there, in abundant supply, to invest or save or waste as he pleased. Like air.

Ch 11: Apollo
Empire of Pain by Patrick Radden Keefe

Inside Purdue Frederick, power was determined entirely by one’s relationship to the family. There were certain old hands in the Norwalk office who were known as “Sackler connections,” meaning that they were personal friends of the family, and thus untouchable. Some of them were, in truth, pretty incompetent, just riding a desk and collecting a check. Nobody could say for certain how they contributed or what they did all day. But they had shown loyalty to the Sacklers, and it was a key feature of the company that such loyalty would be rewarded. In the politics of the organization, if you did not have a direct line to the Sacklers, it was useful to find an ally who did.

Ch 12: Heir Apparent
Empire of Pain by Patrick Radden Keefe
MS Contin pills
Credit: drugs.com

Arthur Sackler liked to opine that the problem with midsized pharma companies was that they often had no research and development capacity with which to discover new drugs. But in England, Mortimer now oversaw Napp Laboratories, a company that had ambitious designs. Napp had been acquired by the Sacklers in 1966 […]

In the late 1970s, Napp produced a new product that was genuinely innovative: a morphine pill. […]

Until that point, morphine had often been administered intravenously, either on a drip or as a regimen of shots. This meant that patients who were suffering from late-stage cancer or other very painful afflictions had little choice but to spend their final days in the hospital so that their pain medication could be administered. But Napp had recently developed a special coating system for pills that allowed the diffusion of a drug into the bloodstream of a patient to be carefully regulated over time. They called the system Continus, and they had already used it for an asthma drug. But what if you applied it to morphine? It would mean that a patient could swallow a pill and the morphine would slowly release into the body, in the same manner that it would on a drip. The new drug, which would become known as MS Contin (p188)

Ch 12: Heir Apparent
Empire of Pain by Patrick Radden Keefe

The sales force went out and started to pitch MS Contin to doctors across the United States as a bold new tool for treating cancer pain, even though the drug did not actually have FDA approval. It was Purdue’s position that the company didn’t need anybody’s approval to market its morphine pills. MS Contin had been on sale for three months when the FDA sent a letter to Norwalk informing Purdue that it had no right to market a new drug for which it had never filed a New Drug Application

Ch 12: Heir Apparent
Empire of Pain by Patrick Radden Keefe

“Pain is the most common symptom that patients have,” Richard would say. The challenge is that it is so subjective. “No doctor can look at you and say, ‘Oh, you’ve got a pain level of three,’ ” Richard explained. “You have to depend on the patient’s report.”

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

Part of the problem, Bonica and Richard agreed, was that physicians had been far too reluctant to administer morphine to people suffering from pain. Morphine could be a very effective drug when it came to relieving pain. The trouble, in Richard’s view, was that it had been stigmatized. It had acquired this stigma, Richard said, “because of a popular understanding shared by both professionals and by laymen that morphine was an end-of-life drug.” Because morphine had long been perceived as a drug with a high risk of addiction, physicians reserved it for particularly severe cases.

MS Contin was meant to address this therapeutic gap, by offering a more approachable delivery mechanism for morphine, in pill form

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

“Addiction does not occur in patients requiring morphine for pain control,” one of the speakers, a doctor from Austria named Eckhard Beubler, asserted in his remarks.

That message was repeated many times throughout the event— that when morphine was used to treat pain, it was not actually addictive.

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

In 1990, Kaiko sent Richard a memo. “MS Contin may eventually face such serious generic competition that other controlled-release opioids must be considered,” he wrote. If Purdue was going to lose the monopoly on its flagship painkiller, perhaps it would be possible to use the Contin time-release system as a delivery mechanism for other opioids, in order to secure new patents. […]

The real innovation in MS Contin was not the morphine but the Contin system, so they had been talking about other drugs that could be used with that system. At meetings, they would constantly discuss the possibilities, and Richard would throw out various ideas. Over dinner that night, Kathe suggested using oxycodone, an opioid that had been synthesized in Germany in 1917.

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

The market for cancer pain was significant, Friedman pointed out: four million prescriptions a year. In fact, there were three-quarters of a million prescriptions just for MS Contin. “We believe that the FDA will restrict our initial launch of OxyContin to the Cancer pain market,” Friedman wrote. But what if, over time, the drug extended beyond that? There was a much greater market for other types of pain: back pain, neck pain, arthritis, fibromyalgia. According to the wrestler turned pain doctor John Bonica, one in three Americans was suffering from untreated chronic pain. If that was even somewhat true, it represented an enormous untapped market. What if you could figure out a way to market this new drug, OxyContin, to all those patients? The plan would have to remain secret for the time being, but in his memo to the Sacklers, Friedman confirmed that the intention was “to expand the use of OxyContin beyond Cancer patients to chronic non-malignant pain.”

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

If you could figure out a way to market OxyContin not just for cancer but for any sort of pain, the profits would be astronomical. It was “imperative,” Friedman told the Sacklers, “that we establish a literature” to support this kind of positioning. They would suggest OxyContin for “the broadest range of use.”[…]

But if Purdue wanted to market a powerful opioid like OxyContin for less acute, more persistent types of pain, one challenge would be the perception, among physicians, that opioids could be very addictive. If OxyContin was going to achieve its full commercial potential, the Sacklers and Purdue would have to undo that perception.

Ch 14: The Ticking Clock
Empire of Pain by Patrick Radden Keefe

Purdue would fight the ticking clock on the MS Contin patent with a radical strategy: the company would unveil this new, more powerful painkiller, OxyContin, and market it against MS Contin— against its own drug—in order to completely upend the current paradigm in pain treatment. This, Richard proclaimed, would be “the first time that we have chosen to obsolete our own product.”

Ch 15: God of Dreams
Empire of Pain by Patrick Radden Keefe

Different drugs have different “personalities,” Michael Friedman liked to say. When he and Richard were trying to decide how to position OxyContin in the marketplace, they made a surprising discovery. The personality of morphine was, clearly, that of a powerful drug of last resort. But oxycodone had a very different personality. In their market research, the team at Purdue had realized that many physicians regarded oxycodone as “weaker than morphine,” Friedman said. Oxycodone was less well known, and less well understood, and it had a personality that seemed less threatening and more approachable

Ch 15: God of Dreams
Empire of Pain by Patrick Radden Keefe

In order to succeed with OxyContin, Purdue officials needed the agency to approve the so-called package insert, the little booklet of fine-print information that would accompany each bottle. The package insert was “the Bible for the product,”[…]

The goal, according to Richard, was not merely to inform the consumer about the risks, benefits, and proper use of the drug but to create “a more potent selling instrument.”

Early on, when Wright saw Purdue’s first draft of the OxyContin package insert, he had remarked that he’d never seen an insert that contained so much promotional and marketing material.

Ch 15: God of Dreams
Empire of Pain by Patrick Radden Keefe

The package insert went through endless drafts and iterations, and at some point a new line of text crept into it: “Delayed absorption, as provided by OxyContin tablets, is believed to reduce the abuse liability of the drug.” This was a peculiar bit of rhetoric. Is believed? Believed by whom? It seemed more aspirational than scientific.

Ch 15: God of Dreams
Empire of Pain by Patrick Radden Keefe

The assurance about how OxyContin’s coating was “believed” to reduce abuse liability ended up staying in the package insert, and on December 28, 1995, the FDA approved OxyContin. […] “Unlike the years that other filings linger at FDA, this product was approved in eleven months, fourteen days.

Ch 15: God of Dreams
Empire of Pain by Patrick Radden Keefe

The pharma rep has no medical training, no pharmacy degree, yet her job is to coax the prescriber into prescribing differently. Reps are door-to-door missionaries. The good ones are naturally persuasive. Their job is to persuade.[…]

Each sales rep was prepared: drilled by instructors, coached on talking points, armed with serious- looking medical literature that spoke to the revolutionary properties of OxyContin. They were on a mission, one Purdue official told them: “Your priority is to sell, sell, sell OxyContin.”

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe
“One to Start and Stay With”
credit: cbc.ca

OxyContin was the painkiller “to start with and to stay with,” the reps said. This was a carefully scripted phrase that they intoned like a mantra. What it meant was that OxyContin should not be regarded as some extreme nuclear solution to which a pain patient might graduate only after lesser remedies had failed. For “moderate to severe pain,” OxyContin should be the first line of defense. And it was good for acute, short-term pain, as well as for chronic, long-term pain; this was a drug you could use for months, years, a lifetime, a drug “to stay with.”

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

In training sessions, they did role-playing exercises in “overcoming objections.” If clinicians expressed concerns about the danger of abuse and addiction, the reps would parrot the language from the package insert, which Curtis Wright, of the FDA, had approved: “The delivery system is believed to reduce the abuse liability of the drug.” They memorized the line and recited it like a catechism.

And the reps went well beyond the dry assurances of the label. They were instructed by Purdue to inform doctors that “fewer than 1 percent” of patients who took OxyContin became addicted.

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

The company established a speakers bureau, through which it paid several thousand doctors to attend medical conferences and deliver presentations about the merits of strong opioids. Doctors were offered all-expenses-paid trips to “pain management seminars” in places like Scottsdale, Arizona, and Boca Raton, Florida. In the initial five years after OxyContin’s release, the company sponsored seven thousand of these seminars.

The marketing of OxyContin relied on an empirical circularity: the company convinced doctors of the drug’s safety with literature that had been produced by doctors who were paid, or funded, by the company.

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

Purdue advertised OxyContin in medical journals, sponsored websites about chronic pain, and distributed a dizzying variety of OxyContin swag: fishing hats, plush toys, luggage tags. The sales reps left a trail of these giveaways wherever they went so that anywhere a doctor turned, she would be greeted by reminders of the product. Often, reps would devise wily strategies for cadging a few minutes of a busy doctor’s time, like showing up at midday with a take-out lunch, compliments of Purdue.

Physicians often scoff at the suggestion that their prescribing habits might be swayed by the blandishments of pharmaceutical companies. This had been a cornerstone of Arthur Sackler’s worldview: the notion that doctors are priest-like figures, immune to flattery or temptation or greed, focused exclusively on the narrow dictates of appropriate medical care. In Arthur’s view, it was laughable—even insulting—to insinuate that a colorful ad or a steak dinner might be enough to sway the clinical judgment of an MD. Doctors, he argued, simply can’t be bought.

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

The way they compensated was unique. Long before OxyContin, they were using the same compensation program. Most pharma companies capped what kind of additional bonus you could make as a rep. Purdue didn’t. It was, in essence, the deal that Arthur Sackler had worked out for himself when he was marketing Valium. If sales grew, you’d get a bigger bonus. There was no cap. “Purdue never capped,” the executive said, “because they wanted their people to be incentivized.”

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

Purdue initiated a costly program to issue free samples of OxyContin to pain patients. This was an old technique in the pharma business. When Bayer marketed heroin at the turn of the twentieth century, it offered free samples of the drug to potential customers. When Roche was seeking a foothold for Valium in Canada during the 1970s, the company gave away eighty-two million Valium pills as free samples in a single year. If you are selling a product that makes people feel good (and may also be highly addictive), that first free hit will generally pay for itself many times over.

For OxyContin, Purdue developed a “card program” in which the company issued coupon cards that patients could use to receive a free thirty-day prescription of the drug. Michael Friedman explained that the free samples were used to “acquaint” patients with OxyContin.

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

OxyContin was priced in such a way that greater dose strength meant greater profits for Purdue. As a consequence, perhaps, another fixation for Richard was the idea of a ceiling effect. Reps were under constant pressure, from headquarters, to urge doctors to “titrate” up, or increase the prescribed dose. Since OxyContin was an opioid, this was particularly relevant, because the body develops a tolerance for opioids

Ch 17: Sell, Sell, Sell
Empire of Pain by Patrick Radden Keefe

Gary Ritchie, who worked at Purdue as a scientist from 1993 to 2003, recalled. “The abuse problem came from users who believed that it was a substitute for other illegal drugs.”[…]

In some ways, Richard’s argument about OxyContin mirrored the libertarian position of a firearms manufacturer who insists that he bears no responsibility for gun deaths. Guns don’t kill people; people kill people. It is a peculiar hallmark of the American economy that you can produce a dangerous product and effectively off-load any legal liability for whatever destruction that product may cause by pointing to the individual responsibility of the consumer.

Ch 18: Ann Hedonia
Empire of Pain by Patrick Radden Keefe

One reason that some patients were becoming hooked on OxyContin might have been Purdue’s own claims about how the drug would provide twelve-hour relief. The truth was that the dangers of OxyContin were intrinsic to the drug—and Purdue knew it. The time- release formula meant that, in principle, patients could safely ingest one giant dose every twelve hours. But internal Purdue documents tell a different story: even before the company received FDA approval, it was aware that not all patients who took OxyContin were achieving twelve-hour relief. In fact, the first patients to use OxyContin, in a study overseen and paid for by Purdue, were ninety women recovering from surgery in Puerto Rico. Roughly half of the women ended up requiring more medication before the twelve-hour mark.

The claim of twelve-hour relief was an invaluable marketing tool.

But prescribing a pill on a twelve-hour schedule when, for many patients, it works for only eight is a recipe for withdrawal and precisely the sorts of “peaks and troughs” that Purdue’s sales reps claimed OxyContin avoided. It is a recipe, in other words, for addiction.

Ch 18: Ann Hedonia
Empire of Pain by Patrick Radden Keefe

Many people who were prescribed OxyContin found themselves experiencing withdrawal symptoms between doses. […] When reps called on physicians, they would hear about patients who were on prescriptions for three pills a day. “As a salesperson, you’re saying, holy shit, it’s supposed to be every twelve hours,” a Louisiana rep named Dodd Davis, “But that’s another dose in the middle of the day, so that’s more pills, more money for me. So you’d say, ‘You know, Doc, I can’t speak to off-label prescribing. But I can tell you, you’re not the first person that’s had to do it.’

Ch 18: Ann Hedonia
Empire of Pain by Patrick Radden Keefe

What kind of business model would drive Purdue reps to pressure a local pharmacist to continue issuing pills to people the pharmacist knew were not legitimate patients?

Ch 20: Take the Fall
Empire of Pain by Patrick Radden Keefe
credit: wsj

At a glance, the pills that started shipping that August looked almost identical to those that had come before. The only visible difference was that the new pills were slightly thicker and each one was stamped not with the “OC” that had traditionally adorned each pill but with “OP” instead. The payload in these new pills was precisely the same: pure oxycodone. It was the coating that had been reinvented.

The new pills were a scientific marvel. If you crushed them, they wouldn’t fragment or break down into a fine powder that could be snorted or dissolved in liquid and injected intravenously. Instead, they squashed, like a piece of candy. You could slam one of the pills with a hammer, and it would crack but not shatter. With some effort, you could pry it into pieces, but if you tried to snort the bits that broke off, they’d get stuck in your nostril.

Ch 22: Tamperproof
Empire of Pain by Patrick Radden Keefe

There was an inexpensive substitute for OxyContin that was cheaper and stronger and widely available: heroin

Ch 22: Tamperproof
Empire of Pain by Patrick Radden Keefe

Just as Purdue had once identified a giant potential market of people suffering from undertreated chronic pain, these young entrepreneurs from Mexico now spotted another huge population that might be induced to try a new drug. […] But in trying to build a robust market for Mexican heroin, these traffickers from Nayarit employed a set of sales tactics that were, in some instances, eerily reminiscent of Purdue’s original marketing playbook for OxyContin. The Sacklers had targeted populations that seemed particularly susceptible to their drug, focusing the initial marketing effort on communities where many people suffered from work-related injuries or disabilities and chronic pain. The heroin crews often scouted new clients in the vicinity of methadone clinics, where people who were already struggling with an opioid use disorder might be found. Purdue had offered patients coupons for a free one- month prescription of OxyContin. The heroin dealers offered free samples to their customers as well.

Ch 22: Tamperproof
Empire of Pain by Patrick Radden Keefe

When somebody who is already addicted to opioids starts to feel the first pangs of withdrawal, a lifetime’s worth of inhibitions can be swiftly cast aside. This is the logic of addiction. Maybe needles make you queasy. But if your body is acting as if you might die if you don’t get a hit, you’ll start doing all sorts of things you might have sworn, in the past, that you would never do.

Ch 22: Tamperproof
Empire of Pain by Patrick Radden Keefe

“Purdue needs a new approach,” some of the new-guard executives proposed. In a meeting, they made a presentation, “A New Narrative: Appropriate Use.” That it would represent a sharp departure from precedent for Purdue Pharma to begin advocating the “appropriate” use of opioids might have been an indication of just how out of touch the Sacklers had become. In any case, they rejected the proposal.

Ch 24: It’s a Hard Truth, Aint It?
Empire of Pain by Patrick Radden Keefe

Purdue and other drug companies that manufacture opioid painkillers spent over $700 million between 2006 and 2015 on lobbying in Washington and in all fifty states. The combined spending of these groups amounted to roughly eight times what the gun lobby spent.

Ch 24: It’s a Hard Truth, Aint It?
Empire of Pain by Patrick Radden Keefe

In August, 2015, the company received F.D.A. approval to market OxyContin to children as young as eleven. […]

Now, if they could secure the pediatric indication, it would potentially entitle them to an additional six months of exclusivity. […] six more months of exclusivity could have “meant more than a billion dollars” in revenue.

Ch 25: Temple of Greed
Empire of Pain by Patrick Radden Keefe

In 2014, Kathe Sackler had been involved in discussions on an initiative called Project Tango. The idea was that one natural area into which Purdue could now branch out was selling drugs that treat opioid addiction.

According to a PowerPoint presentation for Project Tango, the “Abuse and Addiction market” would be a “good fit and next natural step for Purdue.”

Ch 25: Temple of Greed
Empire of Pain by Patrick Radden Keefe

“We are not the only company that marketed opioids,” David Sackler would fume. “Johnson & Johnson was massive,” he exclaimed, whereas OxyContin was just “this tiny, niche little product with tiny market share.”[…]

The only way that the Sacklers could arrive at their 4% market share figure was by including, in the category of opioid prescriptions, even short-term prescriptions for low-dosage medicines like Tylenol-Codeine. OxyContin is an incredibly potent drug. What made it revolutionary was the innovative mechanism that enabled Purdue to pack forty or eighty milligrams of oxycodone into a single pill.[…]

When you take into account the dosage strength of each pill, Purdue actually accounted for a market-leading 27% of all oxycodone sold.

Ch 26: Warpath
Empire of Pain by Patrick Radden Keefe

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