#186 - Patrick Radden Keefe: The opioid crisis—origin, guilty parties, and the difficult path forward
Peter Attia speaks with Patrick Radden Keefe, author of "Empire of Pain," about the Sackler family and Purdue Pharma's role in the opioid epidemic. They discuss OxyContin's development, its aggressive marketing, regulatory failures, and the devastating impact on public health, including Peter's personal experience with opioid dependence.
Deep Dive Analysis
15 Topic Outline
Patrick Radden Keefe's Motivation for Investigating the Opioid Crisis
Complexity of the Opioid Crisis and Purdue Pharma's Central Role
The Sackler Brothers: Early Life, Careers, and Entry into Pharma
Purdue Frederick's Evolution and Move into Pain Management
Development of OxyContin and its Controversial FDA Approval
Early Awareness of OxyContin Addiction and Purdue's Denial
Marketing Tactics and the Role of the Black Market for OxyContin
Personal Experience with OxyContin Addiction and Recovery
The 'Fifth Vital Sign' and Industry Influence on Pain Management
Facilitators of the Crisis: Regulators, Lobbyists, and Politicians
The 2007 Purdue Pharma Guilty Plea and Lack of Accountability
Sackler Family's Wealth Extraction and Purdue's Bankruptcy
The 'Third-Party Release' and Future of Sackler Family Litigation
Sackler Family's Disconnect from Reality and Lack of Shame
Impact on Legitimate Pain Patients and the Path Forward
4 Key Concepts
Conten System
A coating on a pill designed to regulate the flow of a drug into the bloodstream over several hours, intended to provide continuous pain relief and, in the case of OxyContin, was hypothesized by Purdue Pharma to reduce abuse liability by preventing rapid euphoria and withdrawal.
Fifth Vital Sign
A concept introduced into medical practice, often influenced by pharmaceutical companies, that elevated pain to the status of objective vital signs (like temperature, pulse, respiration, blood pressure). It involved asking patients to rate their pain on a subjective scale of one to ten, which some argue led to over-prescription of opioids.
Soft Corruption
A pervasive form of influence where individuals in regulatory or oversight roles (e.g., FDA, DEA, politicians) are not explicitly bribed, but are influenced by the prospect of future employment or relationships with industry, leading to decisions that favor commercial interests over public safety.
Non-Consensual Third-Party Releases
A controversial legal mechanism in bankruptcy proceedings where a judge can permanently immunize non-bankrupt entities (like the Sackler family) from future litigation related to the bankrupt company's actions, even if plaintiffs do not agree to the settlement.
10 Questions Answered
Keefe was initially interested in the illicit drug trade, specifically the surge in Mexican heroin after 2010, and discovered that the rise was linked to the opioid crisis and the legal drug trade, particularly OxyContin and the Sackler family's involvement.
Purdue Pharma, owned by the Sackler family, is seen as the 'tip of the spear' because OxyContin was a first mover in fundamentally changing prescribing habits in the United States, building a market for opioids that eventually migrated to illicit sources.
The three Sackler brothers, all trained psychiatrists, quickly pivoted into commerce, with Arthur Sackler making his name in pharmaceutical advertising. He later purchased Purdue Frederick in 1952, giving it to his brothers to run, while he focused on marketing blockbuster drugs like Librium and Valium.
MSContin was a morphine-based drug with a 'Conten' (continuous) coating that regulated drug flow over hours, primarily for cancer pain. As its patent neared expiration, Purdue sought to apply the 'Conten' system to oxycodone, a stronger opioid, to create OxyContin and expand into the broader chronic pain market.
Purdue Pharma worked unusually closely with FDA medical examiner Curtis Wright, including helping him write reviews of their studies. A key marketing claim that the 'Conten seal is believed to reduce the abuse liability' was included in the package insert without scientific basis, and Curtis Wright later went to work for Purdue Pharma.
Despite sworn testimony from executives claiming no major problems until 2000, internal documents and sales reports show Purdue was aware of abuse, pharmacy robberies, and overdoses as early as 1997, just a year after the drug's release.
Purdue's strategy was to deny intrinsic danger, blame 'bad people' who abused the product, and focus on ramping up enforcement against abusers, while maintaining that iatrogenic addiction (addiction from legitimate prescription) was 'vanishingly rare'.
The Sacklers hired high-profile lawyers like Rudy Giuliani and Mary Jo White to lobby the Justice Department, which overruled federal prosecutors' attempts to charge executives with felonies. This resulted in a plea deal for misdemeanors for executives and a $600 million fine for the company, without the Sacklers themselves facing charges or significant changes to company operations.
Purdue Pharma is in bankruptcy, having pled guilty to new federal criminal charges in 2020. The Sackler family, who extracted over $10 billion from the company, is seeking a 'non-consensual third-party release' in bankruptcy court to permanently immunize them from all future opioid-related litigation in exchange for a $4.5 billion payment over nine years.
According to Patrick Radden Keefe's research, including private communications, the Sackler family members tend to feel persecuted and exhibit a profound sense of grievance, consistently denying any wrongdoing and showing a significant disconnect from the reality of the crisis's impact.
16 Actionable Insights
1. Guard Against Power Delusion
Individuals in positions of immense power and wealth, surrounded by agreeable advisors, are highly susceptible to delusion and losing touch with reality. Actively seek diverse perspectives and critical feedback to avoid self-deception and acknowledge potential wrongdoing.
2. Recognize Soft Corruption
Be aware of ‘soft corruption’ where government officials may be subtly influenced by the prospect of lucrative private sector jobs, even without explicit quid pro quos. This systemic issue can compromise regulatory integrity and requires vigilance.
3. Scrutinize Industry-Backed Innovations
Exercise critical scrutiny when evaluating medical guidelines or ‘innovations’ that are heavily promoted or underwritten by industry, such as the ‘fifth vital sign’ for pain. Industry backing can influence medical discourse and prescribing habits.
4. Question Revolving Door Lobbyists
Maintain skepticism and apply scrutiny when former government regulators transition to lobbying for the industries they once oversaw. This ‘revolving door’ phenomenon can compromise public interest by leveraging insider knowledge for commercial gain.
5. Seek Expert Opioid Tapering
If physiologically dependent on opioids, never attempt cold turkey cessation due to severe withdrawal risks. Always seek professional medical guidance for a safe and managed tapering protocol, potentially involving other medications.
6. Prioritize Comprehensive Pain Care
For chronic or post-operative pain, advocate for a multi-modal, expert-guided approach that includes non-opioid medications, injections, and physical therapy. This strategy can break the cycle of pain and reduce reliance on addictive substances.
7. Beware Rapid Opioid Escalation
Be extremely cautious of rapid opioid dose escalation, as tolerance and dependence can develop quickly, even with legitimate prescriptions. Understand the potent nature of these drugs and question increasing dosages.
8. Differentiate Pain, Grief
Recognize when medication is being used to blunt psychological pain or grief, rather than solely physical discomfort. Addressing emotional and psychological components of suffering separately from physical pain is crucial for recovery.
9. Build Strong Recovery Support
Cultivate a knowledgeable and supportive network, including medical experts and personal connections, to navigate health crises and addiction recovery. A robust support system is vital for overcoming challenges and preventing relapse.
10. Document Business Risks
In business, thoroughly document all known risks and problems, even if uncomfortable, as attempts to hide information can lead to severe future repercussions. Executives were advised against discussing issues via email, yet sales reports revealed early problems.
11. Incentivize Sales Growth
Design compensation schemes with escalating, uncapped bonuses based on sales volume to drive product adoption and market dominance. This business strategy can lead to massive commercial success.
12. Exploit Market Misconceptions
Identify and strategically leverage customer or professional misconceptions about a product to expand its market without correcting the erroneous beliefs. Purdue executives noted doctors mistakenly thought oxycodone was weaker and chose not to correct it.
13. Embrace Diverse Skills, Hustle
Combine diverse skills and an entrepreneurial spirit early in your career, like Arthur Sackler who managed advertising in high school alongside medical training. This approach can lead to unique opportunities and significant financial success.
14. Pursue Education, Meritocracy
Prioritize education and believe in meritocracy as foundational values for personal and professional growth. The Sackler brothers were raised with these beliefs, which guided their path to building an empire.
15. Analyze Sales for Abuse
Utilize sales data, especially after product changes, to identify and understand the extent of illicit use or abuse of a product. A 25% drop in 80mg OxyContin sales after reformulation indicated significant prior abuse.
16. Influence Discourse via Sponsorship
Influence medical education and prescribing habits by sponsoring academic and medical conferences on relevant topics. This strategy allows for aligning with and promoting specific viewpoints within the professional community.
5 Key Quotes
Today, people are dying in very large numbers from heroin and fentanyl overdoses, not from OxyContin or indeed, you know, from most prescription painkillers. This problem has kind of transitioned into an illicit drug problem.
Patrick Radden Keefe
In our focus groups, doctors erroneously think that oxycodone is weaker than morphine. Let's not do anything to make them realize that they're wrong about the product that we're selling them. Because if we did, it could constrain our market.
Patrick Radden Keefe (quoting Purdue Pharma emails)
The Conten seal is believed to reduce the abuse liability of the drug. And that's a weird thing to have in a package insert in general. It's a great marketing claim, but it's like, is believed doesn't seem very scientific necessarily.
Patrick Radden Keefe
The blood of how many people is on the Sacklers' hands? Conservatively.
Peter Attia
I think the big thing that comes home to me is just that these substances are, they have an awesome power and that's compounded by all of the kind of atmospheric, social, situational things you're talking about.
Patrick Radden Keefe
1 Protocols
Post-Surgical Pain Management (Peter Attia's Experience)
Peter Attia- Inject Marcane (long-acting sodium channel blocker) into the incision site before cutting.
- Wait five minutes for the Marcane to take effect.
- Immediately following surgery, put the patient on an aggressive dose of NSAIDs (Non-Steroidal Anti-Inflammatory Drugs).
- Utilize non-addictive medications like Neurontin (gabapentin) for neuropathic pain.
- Perform injections to cool down flared-up areas.
- Engage in physical therapy (PT) to address the underlying physical issue.