Inaccurate Study: Heroin
OxyContin Reformulation Myth
Debunking the false assertion that the introduction of FDA-approved tamper-resistant OxyContin in 2010 led to an increase in heroin deaths.
2010 Reformulation Theory
There is a false theory that tamper-resistant OxyContin led to increased heroin use and mortality.
Certain academics assert that OxyContin’s tamper resistant reformulation led to increased heroin and fentanyl overdoses from 2010-2017. They imply, but don’t attempt to analyze, that individuals who misused OxyContin before 2010 switched to heroin and fentanyl after reformulation, where they were more likely to overdose and die.
“We find that states with the highest initial rates of OxyContin misuse experienced the largest increases in heroin deaths…”
Alpert, Powell, and Pacula, November 2018[1]
“Reformulation continues to play a meaningful role in explaining the rise in heroin overdoses… we estimate a similar, though delayed pattern for synthetic opioids”
Powell and Pacula, December 2020[2]
These studies do not stand up to scrutiny and have been challenged by peers. There is no direct evidence to support the theory that OxyContin misusers switched to heroin and fentanyl because of the reformulation.
Executive Summary
What do we believe about the theory blaming increased heroin and fentanyl mortality on reformulation?
1. Theory Perpetuates Myth of OxyContin Dominance
- OxyContin represented only 4% of the total oxycodone and hydrocodone market by tablets in 2010.
- When measured in morphine milligram equivalent (MME), OxyContin peaked at 16% of the prescription opioid market in 2001 and 2002.
- Rather than switch to heroin at reformulation, the average OxyContin misuser could substitute five other pain relievers they already had a history of misusing
- At least 87% of OxyContin misusers also misused hydrocodone
- 72% of OxyContin misusers also misused non-OxyContin oxycodone
- Zhang (2021) directly rebuts the theory, showing that generic oxycodone, not OxyContin, explains the statistical observations
2. There Is No Evidence of Actual Substitution
- We don’t see OxyContin misusers initiating heroin use more post reformulation
- We don’t see OxyContin sales declines leading to more heroin deaths
3. Study Authors Ignore Alternative Explanations
- The FDA cannot confirm a causal relationship because of uncontrolled variables and data limitations
- Common sense explanations for geographic variation in heroin mortality are ignored, for example:
- Medicaid expansion
- Naloxone access
- Prevalence of more dangerous heroin
- Diverted prescription opioid street prices
Myth of OxyContin Dominance: Generic oxycodone Was Far More Prevalent & Available
Reality Check: Pain Reliever Sales
Was OxyContin a leader in the oxycodone and hydrocodone market?
Oxycodone & Hydrocodone by Pills – ARCOS Database, Oxycodone and Hydrocodone Products Only
OxyContin Peaked: 16% of the prescription opioid market in 2001 and 2002, when measured by Morphine Milligram Equivalent (MME)
OxyContin has never been more than a fraction of the market.
Poly-Substance Abuse
The NSDUH does specify how OxyContin misusers also misused other pain relievers.
The average OxyContin misuser has misused 5 other pain relievers in their lifetime.
OxyContin Misusers Also Misused:
Rather than switch to heroin at reformulation, the average OxyContin misuser could substitute five other pain relievers they already had a history of misusing.
Reality Check: Illicit Market
Generics played a major role within illicit markets.
“Although not always available, the branded extended-release oxycodone was the next most sought-after prescription opioid …by contrast, the most common and always available opioid was immediate release oxycodone”
James A. Inciardi, Pain Medicine, 2009
Once crushed, immediate release generics and OxyContin produce the same effect…
oxycodone Concentration Post Administration[3]
… at significantly lower street prices[4]
The myth of OxyContin dominance ignores the realities of illicit market dynamics.
Academics & Myth of OxyContin Dominance
Alpert (2018) and Powell (2020) buy into the myth of OxyContin dominance.
Authors frequently overstate the role of OxyContin by ignoring generic oxycodone.
“Only the active ingredients are reported… so we observe the total distribution of oxycodone by state, but not OxyContin specifically. However, OxyContin accounts for a large share of oxycodone distribution…”
ALPERT, 2018
“Many experts have implicated OxyContin as a key driver of the opioid epidemic… the removal of the original formulation was one of the largest reductions in the supply of abusable prescription opioids to date”
POWELL, 2020
“By the time of reformulation in 2010, [OxyContin’s market share] had fallen by more than half… after losing its patent in 2004, other companies took up the torch and surpassed Purdue by selling generic oxycodone”
ZHANG, 2021
Peer Review
Alpert (2018) and Powell (2020) ignore generics.
Alpert and Powell overstate OxyContin’s impact by ignoring generics…
Alpert, 2018
“We estimate that initial OxyContin misuse rates are predictive of large and statistically significant increases in heroin mortality”
Powell, 2020
“The shift to illicit opioids… can be observed by a sudden and persistent rise in heroin overdoses in states [with higher Oxycontin misuse]”
Zhang (2021)
“[Oxycodone] was overlooked by other scholars… leaving out oxycodone misuse …would produce spurious regression results”
“OxyContin exposure is not predictive of heroin deaths once we control for oxycodone”
Difference in findings is not driven by methodology; Zhang reproduces Alpert and Powell’s results when they run their regressions on OxyContin only
“The impact of OxyContin on heroin disappears after controlling for… generic oxycodone”
Zhang, 2021
Broken Logical Links: We Do Not See Evidence of Individual Switching
Broken Linking Steps
Do the linking steps implied by the theory hold up to scrutiny?
The theory’s linking steps do not hold up to scrutiny.
Broken Link: Heroin Initiation
Wolff (2020)[7] directly examined claims that OxyContin reformulation led to heroin initiation.
“While previous studies have suggested that the reformulation led to increases in heroin deaths, our results suggest that any increase that occurred was likely not due to individuals switching from OxyContin to heroin.”
Wolff, 2020
OxyContin Misusers Who Initiated Heroin Use During the Year
“Thus, the reformulation of OxyContin appears to have reduced prescription pain reliever misuse without contributing to relatively greater new heroin use among those who misused OxyContin prior to the reformulation”
WolFf, 2020
There is no direct evidence that OxyContin misusers switched to heroin post-reformulation.
Broken Link: Decreased OxyContin Sales
Are larger decreases in OxyContin sales correlated with larger increases in heroin mortality?
If OxyContin misusers switched to heroin…
… we would expect geographies with the largest OxyContin sales declines…
… to experience the highest increases in heroin overdoses…
“This evidence conclusively rejects the hypothesis that OxyContin is solely responsible”
Zhang, 2021
Alternative Explanations: FDA Does Not Find Proof of Causal Relationship
FDA Perspective on Reformulation Theory
In September 2020, an FDA panel reviewed Alpert (2018) and Powell (2020).
Literature Review: Impact of Reformulated OxyContin on Abuse and Opioid-Related Morbidity and Mortality
September 10-11, 2020
“Despite methods to control for other factors, [it’s] difficult to determine the causal role of OxyContin’s reformulation in these trends
- Data limitations
- Concurrent interventions (e.g., pill mill crackdowns)
- Changes and geographical heterogeneity in heroin availability/use
- Complex drivers of drug abuse behaviors”
FDA review could not find a causal link between reformulation and increased mortality.
Overview of Alternate Explanations
The studies supporting the false reformulation theory are unreliable because the authors fail to account for known causes of variations in heroin mortality.
Authors addressed the following factors…
Alpert (2018)
- Pain Reliever Misuse
- Age
- Gender
- Race
- Population Size
- Heroin Prices
- Impact of Great Recession
- PDMPs
- Florida Pill Mill Crackdown
- Medical Marijuana Access
- Unemployment Rate
Powell (2020)
- Pain Reliever Misuse
- Age
- Gender
- Race
- Population Size
… but ignored state variation in…
- expanded Medicaid eligibility post 2010
- access to naloxone
- heroin supply profile and fentanyl contamination
- street prices for diverted prescription opioids
Powell and Alpert leave alternative explanations unaddressed.
Medicaid Expansion
Medicaid eligibility expansion occurred during the critical post 2010 period.
Authors do not account for the fact that Medicaid expansion occurred at different times in different states.
States by Year of Medicaid Expansion
Widely accepted research suggests that Medicaid expansion is correlated with reductions in overdose deaths.
- Expanded Medicaid provides greater access to healthcare, treatment for opioid use disorder and greater access to naloxone
- Kravitz-Wirtz (2020) concluded that Medicaid expansion was associated with:
- A 6% reduction in total opioid overdose deaths
- A 11% percent decline in heroin overdose deaths
- A 10% percent decline in synthetic opioid overdose deaths
This research was cited by media outlets such as the Washington Post, The Hill, Modern Healthcare, Vox and US News.
Naloxone Access
Naloxone access reduces heroin overdose rates.
Effective naloxone expansion depends on pharmacy distribution…
“Although many states have passed some type of law affecting naloxone availability, only laws allowing direct dispensing by pharmacists appear to be useful”
Abouk, 2019
… but that varies by geography
Naloxone Expansion 2020
Authors do not account for the fact that states have varying levels of access to naloxone.
Variable Risk of Heroin
A significant number of heroin overdoses are accidental.
Cities with Heroin Exhibits that Contained Fentanyl – 2016 Heroin Domestic Monitor Program
“Heroin overdose deaths are increasing in many cities and counties across the United states…possible reasons for the increase in overdose deaths include…high purity batches of heroin in certain markets…and the use of highly toxic heroin adulterants such as fentanyl in certain markets”
2015 National Drug Threat Assessment Summary
Alpert and Powell do not control for state level variation in relative heroin danger.
OxyContin Street Prices
Market prices of diverted opioids varies by state.
Generic Oxycodone Street Prices 2020[9]
“I started taking the pills…after that I progressed into heroin and cocaine because… sometimes the prescription drugs are really expensive… it was just getting too expensive for me”
Female Heroin User in Her Early 30s, 2009[10]
Alpert and Powell do not control for geographic price variability of diverted prescription opioids.