Alpert Et Al 2021

ORIGINS OF THE OPIOID CRISIS AND ITS
ENDURING IMPACTS∗
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ABBY ALPERT
WILLIAM N. EVANS
ETHAN M.J. LIEBER
DAVID POWELL
Overdose deaths involving opioids have increased dramatically since the

1990s, leading to the worst drug overdose epidemic in U.S. history, but there is
limited empirical evidence about the initial causes. In this article, we examine the
role of the 1996 introduction and marketing of OxyContin as a potential leading
cause of the opioid crisis. We leverage cross-state variation in exposure to Oxy-
Contin’s introduction due to a state policy that substantially limited the drug’s
early entry and marketing in select states. Recently unsealed court documents
involving Purdue Pharma show that state-based triplicate prescription programs
posed a major obstacle to sales of OxyContin and suggest that less marketing was
targeted to states with these programs. We find that OxyContin distribution was
more than 50% lower in “triplicate states” in the years after the drug’s launch.
Although triplicate states had higher rates of overdose deaths prior to 1996, this
relationship flipped shortly after the launch and triplicate states saw substantially
slower growth in overdose deaths, continuing even 20 years after OxyContin’s in-
troduction. Our results show that the introduction and marketing of OxyContin
explain a substantial share of overdose deaths over the past two decades. JEL
Codes: I12, I18.
∗ We thank Molly Candon, Matthew Harris, Mireille Jacobson, Robert Kaest-
ner, Rosalie Liccardo Pacula, Harold Pollack, Paul Steinberg, and seminar and con-
ference participants at the Bates White Life Sciences Symposium, Becker Fried-
man Institute Conference on the Economics of the Opioid Epidemic, Cal Poly State
University, Cornell VERB, Federal Reserve Board, Illinois, Johns Hopkins, Notre
Dame, RAND, Temple, Toronto, Tulane, USC, Health and Labor Market Effects of
Public Policy at UCSB, iHEA, IIMA, Midwest Health Economics Conference, Pop-
ulation Health Science Research Workshop, NBER Health Care Winter Meeting,
and NBER Summer Institute Crime Meeting for helpful feedback. For help obtain-
ing some of the unsealed court documents, we thank Caitlin Esch at Marketplace,
Nicholas Weilhammer in the Office of Public Records for the Office of the Attor-
ney General of Florida, La Dona Jensen in the Office of the Attorney General of
Washington, and Judge Booker T. Stephens of West Virginia. We thank Ray Kuntz
for assistance with the restricted MEPS data. Powell gratefully acknowledges fi-
nancial support from NIDA (P50DA046351) and the CDC (R01CE02999). Evans
gratefully acknowledges financial support from the Institute for Scholarship in
the Liberal Arts at the University of Notre Dame.

C The Author(s) 2021. Published by Oxford University Press on behalf of the President
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The Quarterly Journal of Economics (2022), 1139–1179. https://doi.org/10.1093/qje/qjab043.
Advance Access publication on November 13, 2021.
1139
1140 THE QUARTERLY JOURNAL OF ECONOMICS
I. INTRODUCTION
Since the 1990s, there has been a staggering increase in

mortality from drug overdoses in the United States. Between
1983 and 2017, the drug overdose death rate increased by a
factor of eight, with a dramatic increase beginning in the 1990s
(Figure I). Overdose deaths involving opioids account for 75% of
the growth and, by 2017, two-thirds of all drug overdose deaths
were related to opioids.1 Overdoses involving opioids claimed
the lives of 47,600 people in 2017 (Scholl et al. 2019) and almost
500,000 since 1999 (CDC 2021), about the same number of U.S.
soldiers who died in World War II (DeBruyne 2018). This massive
rise in opioid deaths has contributed to the longest sustained
decline in life expectancy since 1915 (Dyer 2018).
There are many hypotheses about the initial causes of the
opioid crisis. Case and Deaton (2015, 2017) suggest that demand
factors played an important role as worsening cultural and
economic conditions may have sparked a surge in “deaths of
despair”: suicides, alcohol-related mortality, and drug overdoses.
Empirical tests have found mixed evidence on the role of economic
conditions in driving drug misuse and overdoses (e.g., Ruhm
2019a; Pierce and Schott 2020; Venkataramani et al. 2020).
Alternative hypotheses, though not mutually exclusive ones,
consider the role of supply factors. Beginning in the 1990s,
changing attitudes and new treatment guidelines encouraged
doctors to treat pain more aggressively with opioids (Quinones
2015; Jones et al. 2018).2 In addition, in 1996, Purdue Pharma
launched its drug OxyContin, a prescription opioid pain reliever
that quickly became one of the leading drugs of abuse in the
United States (Cicero, Inciardi, and Muñoz 2005).
Despite the discussion of these supply-side hypotheses
throughout the literature, there is surprisingly little empirical
evidence on any individual factor’s importance. Ruhm (2019a)
finds that increased access to opioids overall, rather than economic
conditions, was a major driver of growth in overdose rates since
1999. Powell, Pacula, and Taylor (2020) show that increased opioid
1. Some of these overdoses may involve nonopioid drugs in addition to opioids.

Ruhm (2019b) documents the recent rise in nonopioid overdose death rates.
2. The American Pain Society launched an influential campaign declaring
pain as the “fifth vital sign”; in response, the Joint Commission on Accreditation of
Healthcare Organizations (JCAHO) revised its guidelines in 2001, requiring that
doctors assess pain along with other vitals during medical visits (Phillips 2000).
ORIGINS OF THE OPIOID CRISIS 1141
20

All Drug Overdoses
15
Deaths per 100,000
10
5 Opioid Overdoses
0
83
85
87
89
91
93
95
97
99
01
03
05
07
09
11
13
15
17
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
20
20
20
Year
FIGURE I
National Drug Overdose Death Rates
We use geocoded NVSS data to construct all drug overdose and opioid overdose
deaths per 100,000. See Section III.A for ICD codes used in each period. Opi-
oid overdoses are defined as overdoses that report opioid involvement (including
natural/semisynthetic opioids, methadone, heroin, and synthetic opioids). These
overdoses may or may not also include nonopioid substances.
access through Medicare led to higher rates of opioid diversion

and overdose deaths.3 Existing research is relevant to under-
standing the role of supply versus demand factors in driving the
ongoing crisis; however, none of these studies isolate the causes
of the initial rise in overdose deaths in the 1990s.
In this article, we provide the first quasi-experimental
evidence on the initial causes of the opioid crisis, which is
commonly dated as beginning in the 1990s.4 We examine the role
of the introduction and marketing of OxyContin as a potential
3. In addition, Finkelstein, Gentzkow, and Williams (2018) find that place-

specific factors are important determinants of opioid abuse rather than individual-
level factors; however, their study design does not allow them to separate out the
relative importance of local economic and cultural conditions from opioid access.
4. The CDC marks the first wave of the crisis as beginning in the 1990s
(https://www.cdc.gov/drugoverdose/epidemic/index.html, last accessed December
1, 2020). Maclean et al. (2020) date the first wave beginning in the mid-1990s.
leading cause, exploring its effects on drug overdose deaths over

the two decades since its launch. The aggressive and deceptive

marketing of OxyContin has been the subject of enormous public
and scholarly discussion (e.g., Van Zee 2009; Kolodny et al.
2015; Quinones 2015) and thousands of lawsuits from state and
local governments, which have implicated OxyContin as “the
taproot of the opioid epidemic.”5 Defenders of OxyContin argue
that numerous other suppliers of opioids and the behaviors of
physicians and patients played a larger role (McLean 2019).6
Since OxyContin was launched nationwide, it is difficult to
isolate its effects from other concurrent changes to prescribing
practice patterns, opioid availability, and demand. We address
this issue by exploiting geographic variation in exposure to Oxy-
Contin’s introduction due to a previously unexplored state policy
that substantially limited OxyContin’s entry and marketing in
select states. We obtained information on the importance of this
state policy from recently unsealed court documents we collected
from multiple settled lawsuits involving Purdue Pharma. These
documents provide an unprecedented look at the manufacturer’s
internal marketing strategies for OxyContin. They reveal that
Purdue Pharma viewed state-based “triplicate prescription
programs,” an unusually stringent early prescription drug moni-
toring program, as a significant barrier to prescribing OxyContin.
They suggest that the company did not target marketing to
states with triplicate programs given the lower expected returns.
For example, Purdue Pharma’s focus group research found that
“doctors in the triplicate states were not enthusiastic about the
product [OxyContin] at all, with only a couple indicating they
would ever use it, and then in very infrequent situations” and
recommended that “the product should only be positioned to
physicians in non-triplicate states” (Groups Plus 1995).
Using a difference-in-differences framework, we take advan-
tage of the variation in OxyContin use induced by these triplicate
policies to study drug overdose trends in states with triplicate
5. See the 2019 New York complaint: https://ag.ny.gov/sites/default/files/oag

opioid lawsuit.pdf
6. For example, an attorney for Purdue Pharma argues that the opioid epi-
demic “is not caused by Purdue’s sale of its legal, FDA-regulated medications, but
rather by doctors who wrote improper prescriptions and/or by third parties who
caused persons without valid and medically necessary prescriptions to get opioid
medications or illegal street drugs. Purdue has no control over those persons”
(Satterfield 2018).
programs relative to states without these programs. We consider

the nontriplicate states to be more exposed to OxyContin’s

introduction because the barriers to prescribing were lower and
more initial marketing was targeted to these states. Indeed, we
find that OxyContin distribution was more than twice as high in
nontriplicate states in the years after the launch.
Given this variation in exposure to OxyContin’s introduction,
we estimate the drug’s effect on drug overdose deaths over the
short and long run. Prior to OxyContin’s launch, the two groups
of states had similar trends in drug overdose death rates. These
trends diverged shortly after the launch, with overdose deaths
increasing much more rapidly in nontriplicate states, a trend that
continued even 20 years later. This differential growth is driven
by drug overdoses involving prescription opioids until 2010. After
2010, when the original formulation of OxyContin was replaced
with an abuse-deterrent version, large differences in deaths
involving heroin and fentanyl emerged. This is consistent with
prior evidence that areas with high rates of OxyContin misuse
experienced differential transitions to illicit opioids as people
substituted from OxyContin to heroin (Alpert, Powell, and Pacula
2018; Evans, Lieber, and Power 2019).
Overall, our estimates imply that nontriplicate states would
have had an average of 34% fewer drug overdose deaths and 45%
fewer opioid overdose deaths from 1996 to 2017 if they had been
triplicate states at the time of OxyContin’s launch. Our results
are not explained by other opioid policies, economic shocks, or dif-
ferences in urbanicity and population size. We do not find similar
patterns in the use of prescription opioids not covered by triplicate
programs or other deaths of despair. It is statistically rare to
observe effect sizes of a similar magnitude as our main estimates
when we randomly assign triplicate status to other states.
This research contributes to our understanding of what ini-
tially sparked the opioid crisis. We find that the introduction and
marketing of OxyContin explain a substantial share of overdose
deaths over the past two decades. Although triplicate programs
were discontinued in the years after OxyContin’s launch, their
initial deterrence of OxyContin promotion had long-term effects
on overdose deaths in these states, dramatically decreasing
overdose death rates even today. The triplicate states currently
have some of the lowest overdose death rates in the country.
Our work also speaks to the importance of early regulations in
explaining current geographic variation in overdose deaths.
Although triplicate programs may have discouraged Oxy-

Contin adoption, the enduring mortality differences across states

even after triplicate programs had ended suggest that persistent
marketing practices played a more central role. We evaluate the
role of marketing relative to the independent long-term effects of
triplicate programs by studying former triplicate states that elim-
inated their triplicate programs just before OxyContin’s launch.
Former triplicate states experienced high rates of OxyContin
adoption and overdose mortality growth similar to states that
never had triplicate programs, suggesting minimal legacy effects
of these programs. Instead, the lack of OxyContin marketing in
triplicate states appears to explain the persistent low growth in
overdose deaths.
The remainder of the article proceeds as follows. We provide
additional background in Section II. Section III introduces the
data, and Section IV discusses the empirical strategy. We present
the results and discuss mechanisms in Section V. In Section VI,
we consider alternative explanations for the observed differential
overdose trends. Section VII concludes. All appendix material can
be found in the Online Appendix.
II. BACKGROUND
II.A. OxyContin’s Launch and Promotional Activities
In this section, we provide a brief background on OxyContin
and its promotion (see Online Appendix B for a more detailed
history). OxyContin is a long-acting formulation of oxycodone, a
morphine-like drug, produced by Purdue Pharma. Given its high
potential for abuse, it is classified as a Schedule II controlled sub-
stance. The U.S. Food and Drug Administration (FDA) approved
OxyContin in 1995, and the drug was introduced to the market
in January 1996. OxyContin’s key technological innovation was
its sustained-release formulation that uses a high concentration
of the active ingredient to provide 12 hours of continuous pain
relief. However, crushing or dissolving the pill allowed users to
access the high dosage of oxycodone all at once, producing an
intense high. The high potency of OxyContin made it one of the
leading drugs of abuse in the United States (Cicero, Inciardi, and
Muñoz 2005) and concerns about widespread abuse of this drug
were being reported by 2000 (GAO 2003).
Purdue Pharma launched an aggressive advertising cam-
paign for OxyContin that was unprecedented for an opioid in
terms of the promotional spending (GAO 2003) and the type of

physicians being targeted. They targeted marketing to primary

care physicians to promote the drug for noncancer chronic pain—a
previously untapped market for opioids.7 Such physician detailing
has been shown to be effective at increasing prescribing (Carey,
Lieber, and Miller 2021; Agha and Zeltzer forthcoming).8 Indeed,
OxyContin prescriptions increased at a faster rate for noncancer
pain than for cancer pain from 1997 to 2002 (GAO 2003). The
initial marketing strategy centered on false claims that the drug
had low abuse potential and was safer than other opioid drugs.9
The original FDA product label for OxyContin included the
statement that “delayed absorption as provided by OxyContin
tablets, is believed to reduce the abuse liability of a drug,” which
became a cornerstone of the initial marketing campaign.
Overall, these marketing efforts contributed to OxyContin’s
blockbuster success. Revenue from its sales skyrocketed from $48
million in 1996 to $1.1 billion in 2000 (Van Zee 2009) and $3.1 bil-
lion in 2010 (IMS 2011). The marketing of OxyContin eventually
concerned local and state governments. In 2007, Purdue Pharma
paid fines over $600 million for misleading advertising. In 2020,
another lawsuit resulted in an $8.3 billion settlement.
II.B. Geographic Variation in Exposure to OxyContin’s

Introduction
This study exploits previously unexplored geographic vari-
ation in OxyContin’s introduction and initial marketing. To
understand how OxyContin was marketed, we made Freedom of
7. Purdue Pharma also promoted OxyContin through a variety of other chan-

nels, such as sponsoring pain-related educational programs and conferences, dis-
tributing coupons and gifts, and advertising in medical journals.
8. Purdue Pharma conducted internal research showing that its promotional
activities were effective. From Commonwealth of Massachusetts (2019), the effec-
tiveness of the sales visits was corroborated by an outside consulting firm: “McK-
insey confirmed that Purdue’s sales visits generated opioid prescriptions” (137);
from Commonwealth of Massachusetts (2018): “Purdue knew its sales push drove
patients to higher doses . . . Purdue’s business plans emphasized that ‘OxyContin
is promotional sensitive, specifically with the higher doses, and recent research
findings reinforce the value of sales calls”’ (19); “Director Richard Sackler testified
that the sales representatives were the main way that Purdue promoted its opi-
oids. He testified that the key to getting doctors to prescribe and keep prescribing
Purdue opioids was regular visits from the sales force” (50).
9. For example, marketing materials relied heavily on a 100-word letter to the
editor (Porter and Jick 1980) to support the claim that the risk of addiction among
opioid users was “much less than one percent.”
Information Act (FOIA) requests to obtain recently unsealed doc-

uments in Florida, Washington, and West Virginia from investiga-
tions and settled court cases involving Purdue Pharma.10 Among

these documents, we obtained the launch plan for OxyContin, the
focus group research conducted prior to the launch (see Online
Appendix Figure A1), and annual itemized budgets for OxyCon-
tin from 1996 to 2002. These documents revealed that Purdue
Pharma would have difficulty penetrating markets that had
enacted a state policy known as a triplicate prescription program
and suggested that it would target less marketing to these states.
1. What Are Triplicate Prescription Programs? Triplicate

prescription programs were among the earliest prescription drug
monitoring programs enacted to reduce the diversion and misuse
of controlled substances. Triplicate programs mandated that
doctors use state-issued triplicate prescription forms when pre-
scribing Schedule II controlled substances (which includes many
opioids). The physician was required to maintain one copy of the
triplicate form for their records. The patient was given two copies
to give to the pharmacy; the pharmacy kept one and sent the third
copy to the state drug monitoring agency. States kept a database
of the forms to monitor and investigate prescribing irregularities.
The academic literature on triplicate programs finds that
such programs led to dramatic reductions in the prescribing of
drugs subject to the policy (Sigler et al. 1984; Weintraub et al.
1991; Hartzema et al. 1992; Simoni-Wastila et al., 2004). There
are two main reasons for these reductions. First, physicians in
triplicate states were concerned about government oversight
of their prescribing behavior (Berina et al. 1985). As Purdue
Pharma observed in its focus group research: “The doctors did
not want to provide the Government with any ammunition to
question their medical protocols relative to pain management.
The mere thought of the government questioning their judgement
created a high level of anxiety” (Groups Plus 1995, 24). Although
electronic monitoring programs also involved government
10. The documents come from three main sources. In November 2001, the
Florida attorney general opened an investigation into Purdue Pharma’s marketing
tactics. The investigation was closed about a year later. Purdue Pharma paid the
state of Florida a $2 million settlement. We also received documents from the State
of Washington v. Purdue Pharma L.P. et al. (filed September 2017) and State of
West Virginia v. Purdue Pharma et al. (filed June 11, 2001, settled in 2004).
oversight, relative to electronic systems, “It was felt that paper

forms, tangible reminders of such scrutiny when handled by the

prescribing physician and dispensing pharmacist, would have a
greater effect on reduced prescribing and dispensing than would
an electronic system that remained largely invisible to health
care practitioners” (Simoni-Wastila and Toler n.d., 3).
Second, triplicate programs imposed large hassle costs on
physicians. According to Purdue Pharma’s research: “Writing
triplicate prescriptions was more trouble than others, due to
the details of the forms and the various people that need to be
copied to them. To the extent that they [physicians] can avoid
this extra effort, they will try to follow alternative protocols”
(Groups Plus 1995, 24). Placing this burden specifically on the
prescriber rather than on the pharmacist suggests a key reason
for why triplicate programs are found to have substantial effects
on prescriptions, while some modern electronic prescription drug
monitoring programs (particularly, nonmandate PDMPs) have
more muted effects.11
At the time of OxyContin’s launch in 1996, five states had
active triplicate programs: California, Idaho, Illinois, New York,
and Texas.12 The enactment and end years of the triplicate
programs are listed in Online Appendix Table A1.13 These
11. Must-access PDMPs have been shown to reduce opioid prescribing, while
nonmandate PDMPs have muted effects (Buchmueller and Carey 2018). Notably,
similar to triplicate programs, must-access PDMPs impose a hassle cost on the
prescriber, which can explain a large share of the prescribing reduction from these
programs (Alpert, Jacobson, and Dykstra 2020). The hassle costs were even higher
for the triplicate programs, which may explain their large deterrent effects. Doc-
tors needed to purchase the triplicate forms and store the written prescriptions
for years. In 2001, only 57.6% of physicians in California requested triplicate pre-
scription forms, implying that the other 42.4% were not even capable of prescribing
Schedule II opioids (Fishman et al. 2004).
12. In one case in the internal documents we reviewed, there is an incorrect
reference to “nine triplicate states” when discussing retail pharmacy distribution.
It is possible they were referring to the nine states with paper-based monitoring
systems (including duplicate and single-copy programs), because this statement
appears in the context of pharmacists’ concerns about the “voluminous paperwork”
required in these states, which would be a consideration with any paper-based
system. To the degree that Purdue Pharma was also concerned about other paper-
based programs and marketed less in these states, our results will be attenuated.
13. Idaho adopted its program in 1967, switching to a duplicate pro-
gram in 1997 (Joranson et al. 2002; Fishman et al. 2004, see also
https://legislature.idaho.gov/wp-content/uploads/OPE/Reports/r9901.pdf). Illinois
enacted its triplicate program in 1961, converting to an electronic system in 2000
triplicate programs were adopted decades before OxyContin’s

launch. California adopted the first triplicate program in 1939

(Joranson et al. 2002); other states adopted the program be-
tween 1961 and 1988. Indiana and Michigan also had triplicate
programs, but they ended their programs two years before
OxyContin’s launch.14
The triplicate states all discontinued their programs by
2004. Therefore, our analysis speaks to the long-run effects of the
initial targeting of Purdue Pharma’s marketing due to triplicate
status during the launch. The discontinuation of these programs
provides an opportunity to isolate long-term persistent effects of
marketing from the direct effects of having a triplicate program.
In addition, we separate the legacy effects of triplicate programs
from the marketing effects induced by OxyContin’s launch by
separately analyzing the two former triplicate states (Indiana
and Michigan), which repealed their triplicate programs prior to
1996.15
2. Purdue Pharma’s Marketing in Triplicate and Nontrip-

licate States. Triplicate programs are mentioned repeatedly in
Purdue Pharma’s internal documents given concerns borne out
in their premarket research that physicians in triplicate states
would be less willing to prescribe OxyContin. Purdue Pharma
found that “physicians in the triplicate state did not respond
positively to the drug [OxyContin], since it is a Class II narcotic
which would require triplicate prescriptions. Therefore, only a
(see https://www.isms.org/opioidplan/). New York enacted a triplicate program in

1972 (Joranson et al. 2002), which ended in 2001 (NY Bureau of Narcotic En-
forcement, personal communication, May 3, 2019). Texas adopted a triplicate sys-
tem in 1982 (Sigler et al. 1984), converting to an electronic system in 1999 (see
https://www.pharmacy.texas.gov/DPS.asp).
14. Indiana’s triplicate program began in 1987, but it was replaced with an
electronic and single-copy program in 1994 (Joranson et al. 2002). Michigan en-
acted a triplicate program in 1988 but it ended in 1994 (Joranson et al. 2002).
Washington also adopted a triplicate program, but because of limited funding,
triplicate forms were required only for physicians disciplined for drug-related vi-
olations (Simoni-Wastila and Tompkins 2001; Fishman et al. 2004).
15. We include these two former triplicate states in the set of nontriplicate
states. Purdue Pharma’s internal documents refer to states that have triplicate
programs, which would exclude states that had discontinued their triplicate pro-
grams prior to the launch. There is no mention of former triplicate states in the
Purdue Pharma documents, and we assume they received similar marketing as
other nontriplicate states.
few would ever use the product, and for them it would be on a
very infrequent basis” (Groups Plus 1995, 36).16

Based on this research, the launch plan acknowledges that
“these regulations create a barrier when positioning OxyContin”
(Purdue Pharma 1995, 4). They recommended that “the product
should only be positioned to physicians in non-triplicate states”
(Groups Plus 1995, 55). Furthermore, they noted that “our
research suggests the absolute number of prescriptions they
[physicians in triplicate states] would write each year is very
small, and probably would not be sufficient to justify any separate
marketing effort” (Groups Plus 1995, 49).17
Although we do not have data that breaks down Purdue
Pharma’s initial marketing spending by state to confirm this
strategy directly, we examined their marketing in 2013–2016 us-
ing the CMS Open Payments database as a measure of persistent
differences in marketing. These data report payments made from
pharmaceutical manufacturers to physicians related to the pro-
motion of specific drugs, including payments for meals, travel, and
gifts. Figure II shows that nontriplicate states received 44%–71%
more payments per capita for OxyContin than triplicate states in
each year (Panel A).18 As an alternative metric, we scaled OxyCon-
tin payments by total payments (across all drugs) to account for
state-level differences in marketing (Panel B). The gap between
triplicates and nontriplicates grows wider when using this metric.
16. Other representative examples: “The impact of the triplicate laws was par-
ticularly significant when one realizes that the most common narcotic used by the
surgeons and PCP’s in New Jersey [a nontriplicate state] was Percocet/Percodan,
whereas in Texas [a triplicate state], this was a product/class of drugs prescribed
by most doctors less than five times per year . . . if at all” (Groups Plus 1995, 24).
“Targeting will be a key element to the success of OxyContin . . . Unfortunately,
physicians in triplicate states are going to be harder to convince since they use
less CII medications” (Strategic Business Research 1996, 7). “These triplicate state
physicians are far less likely to use an oxycodone product. . . . Only 14% mentioned
the use of oxycodone products for moderately severe pain, whereas almost three
times this number of the non-triplicate physicians (37%) utilize this class of opioid”
(Strategic Business Research 1996, 13).
17. Purdue Pharma appears to have lobbied for the repeal of triplicate poli-
cies. For example, the 1999 budget plan includes a $750,000 line item to fund a
“Program to impact the regulatory environment for opioid prescribing in triplicate
states” (Purdue Pharma 1999, 68).
18. The evidence of promotional activities for opioids responding to state-level
PDMPs is consistent with findings in Nguyen, Bradford, and Simon (2019) about
more recent adoption of mandatory access PDMPs in the 2010s.
1150 250
THE QUARTERLY JOURNAL OF ECONOMICS
.0003
OxyContin Payments / All Payments
200
Payments ($) per 100,000

.0002
100 150
.0001
50
0
0
13
14
15
16
13
14
15
16
20
20
20
20
20
20
20
20
Year Year
Non−Triplicate States Triplicate States Non−Triplicate States Triplicate States
(A) OxyContin Spending per 100,000 B OxyContin Spending / Total Spending
FIGURE II
OxyContin Promotional Payments to Physicians
We used CMS Open Payments Data to calculate total payments and gifts made
to physicians regarding OxyContin (presented in nominal dollars). In Panel A, we
scaled this measure by population. In Panel B, we scaled this measure by total
promotional spending (across all drugs). The outcomes correspond to August 2013–
December 2016. Because the 2013 data only cover a partial year, we annualize the
rate in that year.
The persistence of the initial targeting based on triplicate sta-

tus is consistent with the marketing strategy discussed in the in-
ternal documents. Early budget plans for Purdue Pharma dictated
that the sales force target calls to the top deciles of physicians
in terms of past prescribing volumes; more recent documents show
that this targeting strategy continued through 2018.19 Thus, if
triplicate states initially received less marketing and this resulted
in lower prescribing, these states would continue to receive less
marketing in future periods as well. This evidence supports our
empirical design of studying the long-term effects of OxyContin’s
launch based on whether a state initially had a triplicate program.
III. DATA
III.A. Mortality Data
We use a restricted-use version of the National Vital Statis-
tics System (NVSS) Multiple Cause of Death mortality files
from 1983 to 2017 that contains state and county of residence
19. For example, “McKinsey recommended doubling down on Purdue Pharma’s

strategy of targeting high prescribers for even more sales calls” (Commonwealth
of Massachusetts 2019, 212).
identifiers.20 These data represent a census of deaths in the

United States. The 1983–1998 data use ICD-9 codes to categorize

causes of deaths, while the 1999–2017 data use ICD-10 codes.
We follow the coding used by the Centers for Disease Control and
Prevention (CDC) to categorize deaths as drug- and opioid-related
across both sets of classification systems.21 The CDC reports that
the transition from ICD-9 to ICD-10 resulted in a small increase
in poisoning-related deaths (not necessarily drug poisonings)
of 2% (Warner et al. 2011).22 Our time fixed effects account for
this transition, given that we would not expect systematically
different effects of the coding change across states.
Given concerns over missing opioid designations on death
certificates for drug-related overdoses (e.g., Ruhm 2018), we favor
using a broader measure of total drug overdose deaths in most
of our analysis, which should be robust to substance-specific
classification errors (Venkataramani and Chatterjee 2019).
However, we also present results for opioid-related overdose
deaths. In addition, we study disaggregated measures of drug
overdose deaths by type of opioid from 1999 to 2017, including
heroin (T40.1), natural and semisynthetic opioids (T40.2) such as
OxyContin, and synthetic opioids (T40.4) such as fentanyl.23
20. We begin in 1983 because the 1981 and 1982 files do not include all deaths.
In select states, only half of deaths were included, and they were included twice.
21. For 1983–1998, we define drug poisonings as deaths involving un-
derlying cause of death ICD-9 codes E850–E858, E950.0–E950.5, E962.0, or
E980.0–E980.5 (see Table 2 of https://www.cdc.gov/drugoverdose/pdf/pdo guide
to icd-9-cm and icd-10 codes-a.pdf, last accessed November 29, 2018). When
we study opioid-related overdoses, we use deaths involving E850.0, E850.1,
E850.2, or N965.0 (Green et al. 2017; Alexander, Kiang, and Barbieri 2018).
For the 1999–2017 data, we code deaths as drug overdoses using the
ICD-10 external cause of injury codes X40–X44, X60–64, X85, or Y10–Y14
(Warner et al. 2011). We use drug identification codes to specify opioid-
related overdoses: T40.0–T40.4 and T40.6. Linking opioid overdoses across ICD-
9 and ICD-10 codes in this manner is recommended in Table 3 of https://
www.cdc.gov/drugoverdose/pdf/pdo guide to icd-9-cm and icd-10 codes-a.pdf. One
exception is our use of T40.6. The inclusion of this code does not change our results,
which we show in the Online Appendix.
22. In Online Appendix Figure A2, we explore this coding change by examining
the national trend in drug overdose deaths around 1999. Although we observe an
increase in 1999, it is comparable to increases in other time periods. The 1999
increase is larger for opioid-related overdose deaths but not uniquely large relative
to other annual changes.
23. The specific type of opioid is not reliably coded before 1999 in a manner
that can be linked to 1999–2017 data.
III.B. Opioid Distribution, Prescriptions, and Misuse

We use state-level data on the legal supply of opioids from

the Drug Enforcement Agency’s Automation of Reports and
Consolidated Orders System (ARCOS). Manufacturers and dis-
tributors are required to report their transactions and deliveries
of all Schedule I and II substances, all narcotic Schedule III
substances, and a number of Schedule IV–V substances to the
Attorney General. This includes all oxycodone and hydrocodone
products.24 We analyze data available online for 2000–2017, and
we collected earlier data for 1997–1999 using the WayBack Ma-
chine.25 In the public data, only active ingredients are reported,
so we observe oxycodone but not OxyContin.26 Because of our
interest in OxyContin, we made a FOIA request for OxyContin
distribution specifically and received these data for 2000–2016.
We report all ARCOS measures in morphine equivalent doses
(MEDs), defined as 60 morphine milligram equivalents.
As complementary measures, we use Medicaid State Drug
Utilization Data for 1996–2005, which reports the number of
Medicaid prescriptions by National Drug Code, quarter, and
state.27 Although the Medicaid population is nonrepresentative,
prescriptions among this group are a potentially useful proxy for
24. Distribution of controlled substances from online or mail-order pharmacies

is included in the ARCOS data but cannot be separately identified. These distri-
butions will be attributed to the location of the supplier, which may add some
measurement error (MEPS/Medicaid reports prescriptions by state of residence).
This could attenuate our ARCOS estimates because the use of online pharmacies
is more likely in the nontriplicate states given higher levels of OxyContin prescrib-
ing. However, this bias is likely to be small, because the use of online pharmacies
for opioids was limited. When online pharmacies were first introduced in 1999,
there was limited internet access (Stergachis 2001) and, over time, state and fed-
eral laws effectively banned opioid sales online (GAO 2000).
25. ARCOS data are available from https://www.deadiversion.usdoj.gov/arcos/
retail drug summary/ (last accessed November 30, 2018). Archived data
are available from https://web.archive.org/web/20030220041015/https://www.
deadiversion.usdoj.gov/arcos/retail drug summary/.
26. The public ARCOS data do not report all scheduled substances for each
state-quarter, especially for the 1997–2001 time period, which raises concerns
about comparability over time. However, oxycodone and hydrocodone—the focus
of our study—are reported in all years and states. Moreover, in the figures we
do not observe any evidence of unusual year-to-year jumps which would suggest
inconsistent reporting for these substances.
27. We end the sample in 2005 because of the introduction of Medicare Part
D. We select on state-years reporting in all four quarters (over 94% of state-years).
Although a recent version suppresses data with fewer than 10 prescriptions, we
rely on an earlier version of the data that is unsuppressed.
state prescribing behavior and represent an important population

disproportionately affected by the opioid crisis (Sharp and Melnik

2015). In addition, we use a restricted version of the Medical Ex-
penditure Panel Survey (MEPS) with state identifiers, accessed
through the AHRQ Data Facility, for 1996–2016. The MEPS
is a nationally representative survey of households, including
pharmaceutical claims.
Finally, we study self-reported rates of opioid misuse in the
past year for OxyContin and all other pain relievers (excluding
OxyContin) using the National Survey of Drug Use and Health
(NSDUH) for 2004–2013.28 OxyContin misuse is first available
in 2004 and is reported in two-year waves. The NSDUH is a
nationally representative survey of individuals ages 12 and older
and is the largest survey collecting information on substance use
in the United States.29
III.C. Summary Statistics

In Online Appendix Table A1, we present summary statistics
for 1991–1995, representing the pre-OxyContin period, sepa-
rately for each triplicate state and aggregated means by triplicate
status. Drug overdose and opioid-related overdose death rates
are higher on average in the triplicate states before OxyContin’s
introduction. Some of these differences can be explained by
disproportionately higher rates of cocaine-related deaths in these
states. When overdoses involving cocaine are eliminated, the
differences between triplicate and nontriplicate states shrink.
With respect to demographic characteristics, triplicate states
have larger populations, and a larger share of the population is
Hispanic.30 Age and education distributions are similar.
IV. EMPIRICAL STRATEGY

To estimate the effect of OxyContin’s introduction, we use a
difference-in-differences framework that compares outcomes in
28. NSDUH defines “misuse” as taking medication that “was not prescribed
for you or that you took only for the experience or feeling they caused.”
29. For more information on these data, see Section II.A of Alpert, Powell, and
Pacula (2018).
30. Demographic information comes from Medicare SEER population data for
1990–2017 and census data for 1983–1989 since SEER only includes population by
ethnicity beginning in 1990. The education variables are calculated using the An-
nual Social and Economic Supplement of the Current Population Study (Ruggles
et al. 2018).
nontriplicate states relative to triplicate states before and after

the launch of OxyContin. We rely on event study models because

of their transparency and because the timing of the effect is of
interest. We report the differential change in overdose death
rates for nontriplicate states relative to triplicate states given
that nontriplicate states were more “exposed” to the introduction
of OxyContin. The event study specification is:
(1)

2017
yst = αs + γt + βk × 1(Nontriplicate)s × 1 (t = k) + εst ,
k=1983
where yst represents annual drug overdose deaths per 100,000

people in state s in year t. This specification includes state (αs )
and year (γt ) fixed effects. 1(Nontriplicate)s is an indicator based
on the initial triplicate status of the state in 1996, and it is
interacted with a full set of year fixed effects. The nontriplicate
indicator is fixed over the entire time period so the estimates refer
to the effects of initial triplicate status. We present the estimates
of βk along with 95% confidence intervals graphically, normalizing
β1995 to equal zero. Our main results are population weighted.
We also summarize the results using a more parsimonious
difference-in-differences specification:
yst = αs + γt + δ1 × 1(Nontriplicate)s × 1(1996 t 2000)s

(2) + δ2 × 1(Nontriplicate)s × 1(2001 t 2010)s
+ δ3 × 1(Nontriplicate)s × 1(2011 t 2017)s + εst ,
The excluded category is 1991–1995 as we limit the sample

to 1991–2017 for the difference-in-differences analyses.31 We
estimate three separate “post” effects to permit some hetero-
geneity while still providing more aggregated effects. The first
post-OxyContin effect (δ1 ) is for the time period 1996–2000,
representing the introduction of OxyContin, the launch of dif-
ferent dosages, and the initial ramp-up of marketing. We also
estimate an effect for 2001–2010 (δ2 ), corresponding to the “first
31. We condensed the preperiod to 5 years (from the full 13 years available)
to provide a more meaningful comparison with the postperiods. As can be seen in
the event study results, the estimates are not sensitive to different choices for the
preperiod.
wave” of the opioid crisis when most deaths are from prescription
opioids. Finally, we estimate a separate effect for 2011–2017

(δ3 ), representing the second and third waves of the crisis when
deaths from heroin and fentanyl became more prominent.
We also present estimates for both equations including
covariates. Our baseline controls include the fraction of the
population that is white non-Hispanic, Black non-Hispanic,
Hispanic, the fraction ages 25–44, 45–64, 65+, the fraction with
a college degree, and log population.
Because we have a small number of untreated states,
traditional cluster covariance estimators produce standard error
estimates that are too small (Brewer, Crossley, and Joyce 2018).
We use a restricted wild cluster bootstrap method at the state
level to account for within-state dependence in all models, relying
on a six-point weight distribution as suggested by Webb (2014)
when there are few clusters. Given p-values for a range of null
hypotheses, we construct and report 95% confidence intervals,
which will not be symmetric using this approach.32 In the Online
Appendix, we show that traditional “clustered” standard errors
produce much smaller confidence intervals. We also conduct
permutation tests, discussed in Section VI.B.
V. RESULTS
Our analysis begins by documenting large differences in
OxyContin use across triplicate and nontriplicate states. We
estimate the effect of these differences on drug overdose deaths
over the short and long run and explore the mechanisms for
persistent mortality effects.
V.A. Effects of Triplicate Status on OxyContin Use

We first show that nontriplicate states were more exposed
to the introduction of OxyContin as measured by OxyContin
distribution per capita in the ARCOS data. Figure III, Panel
A shows the raw trends for OxyContin distribution per capita,
and Panel B shows the differences between nontriplicate and
triplicate states with 95% confidence intervals. In 2000, there
is over 2.5 times more OxyContin distribution per capita in
32. We use the boottest package in Stata (Roodman et al. 2019) to implement
this procedure.
1.5
2
Morphine Equivalent Doses Per Capita
Difference in Per Capita OxyContin

1.5

Morphine Equivalent Doses
1
.5 1
.5
0
00
02
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Year
00
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20
Non−Triplicate States Triplicate States Year
(A) Trends in OxyContin Distribution (B) OxyContin (Differences)

Morphine Equivalent Doses Per Capita
8
6
6
4
Difference in Per Capita
Oxycodone
4
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97
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Year Hydrocodone
Oxycodone in Non−Triplicate States
−2
Oxycodone in Triplicate States

97
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09
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15
17
Hydrocone in Non−Triplicate States
19
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20
Hydrocodone in Triplicate States Year
(C) Trends in Oxycodone and Hydrocodone (D) Oxycodone and Hydrocodone

Distribution (Differences)
FIGURE III
Differences in Opioid Distribution by Triplicate Status
We use ARCOS data, converted to morphine equivalent doses. Panel A shows
raw (per capita) means for OxyContin. Panel C shows raw (per capita) means for
oxycodone and hydrocodone in separate trend lines. Estimates in Panels B and D
represent cross-sectional differences corresponding to Panels A and C, respectively.
95% confidence intervals are generated using a clustered (at state) wild bootstrap.
All figures are population weighted.
nontriplicate states compared with triplicate states. These large

and statistically significant differences persist through 2016.
In Online Appendix Figure A3, we study two complementary
data sources that allow us to observe OxyContin prescriptions
for earlier years. Panel A shows trends for Medicaid OxyContin
prescriptions per 1,000 beneficiaries for 1996–2005. Panel B
shows OxyContin prescriptions per 1,000 people using the MEPS
for 1996–2016. We again observe much higher rates of OxyContin
prescriptions in nontriplicate states. OxyContin prescribing
increases rapidly for several years after its launch; however,
there is a reduction in OxyContin prescriptions in 2005–2006.33

OxyContin prescribing decreases again after Purdue Pharma

replaced the original formulation with an abuse-deterrent version
in 2010. However, nontriplicate states continue to experience
additional OxyContin use throughout these downturns.
We also examine patterns of initial “adoption” of OxyContin.
In Online Appendix Figure A4, we show the distribution of
OxyContin supply per capita across states using the earliest
years of Medicaid and ARCOS data. For both measures, the
triplicate states cluster close to the bottom of the distribution.
Four of the triplicate states (CA, IL, NY, TX) are among the
five states with the lowest number of OxyContin prescriptions
per capita in 1996.34 The pattern is similar in the ARCOS
data. Triplicate states initially had some of the lowest rates of
OxyContin adoption.
V.B. Effects of Triplicate Status on Use of Other Opioids

We examine differences in the use of other prescription
opioids across triplicate and nontriplicate states that could poten-
tially contribute to differences in overdose death trends. Using
ARCOS data, Figure III, Panel C shows raw trends in oxycodone
and hydrocodone distribution in MEDs, which adjusts for their
potency. Hydrocodone (e.g., Vicodin) is a substitute for oxycodone,
but it was primarily classified as a Schedule III drug and would
not be subject to triplicate programs, which cover Schedule II
drugs.35 Panel D plots differences between the two sets of states
for each of these opioid drugs along with 95% confidence inter-
vals. Remarkably, per capita hydrocodone distribution is nearly
33. This decline is due to a patent dispute between Purdue Pharma and two
generic manufacturers (Endo and Teva) that temporarily introduced generic ver-
sions of OxyContin in 2004 and 2005 (Bailey et al. 2006). These generic ver-
sions were pulled from the market by March 2007 because they infringed on
Purdue’s patents. During this short window of time when generics were available,
some branded OxyContin prescriptions would have been filled with equivalent
generics—a direct spillover effect of Purdue’s marketing. While Figure III, Panel
A shows only branded OxyContin, Panel C shows all oxycodone prescriptions,
which include both generic and branded versions and suggests that reductions in
branded OxyContin were offset by increases in generic versions.
34. Idaho is an exception. This may reflect that Idaho was in the process of
replacing its triplicate program. We do not know whether Purdue Pharma antici-
pated this legislative change and adjusted its promotional activities.
35. On October 6, 2014, hydrocodone combinations were switched from Sched-
ule III to Schedule II.
identical in triplicate and nontriplicate states over the whole

time period. However, there are large and statistically significant

differences in oxycodone distribution between triplicate and
nontriplicate states. Finding differences in oxycodone, but not
hydrocodone, suggests that these differences are caused by
triplicate status.
As shown in Figure III, the differences in oxycodone distri-
bution (Panel D) exceed the differences observed for OxyContin
alone (Panel B) and grow over time; this growth suggests
spillovers of OxyContin’s promotion on the use of other oxycodone
products (e.g., combination products, such as Percocet). We ob-
serve evidence of spillovers to other types of oxycodone studying
prescriptions in Medicaid (our only data set with pre-1996 pre-
scriptions). We provide event study estimates in Online Appendix
Figure A5. The outcome is Medicaid oxycodone prescriptions,
excluding OxyContin, per 1,000 beneficiaries. We observe no dif-
ference across states before 1996. After 1996, nontriplicate states
increased their oxycodone prescriptions, and this effect persists
through the end of the sample period. Such spillovers are likely
generated by Purdue Pharma’s marketing strategies that aimed
to expand the opioid market by normalizing the use of strong
opioids for noncancer chronic pain and creating the message that
opioids carry a low risk of addiction (Van Zee 2009).36 Moreover,
individuals introduced to OxyContin will often transition to using
other opioids, especially similar products containing oxycodone.37
Finally, in Online Appendix Figure A6, we show trends in
the rates of misuse of OxyContin versus all other pain relievers
using the NSDUH for 2004–2013. There are large differences in
OxyContin misuse (Panel A) across triplicate and nontriplicate
36. Purdue Pharma’s objective in the early years was: “To convince health
care professional (physicians, nurses, pharmacists, and managed health care pro-
fessionals) to aggressively treat both noncancer pain and cancer pain. The positive
use of opioids, and OxyContin Tablets in particular, will be emphasized” (Purdue
Pharma 1999, 44).
37. First, patients using OxyContin for chronic pain often also receive short-
acting oxycodone for short episodes of “breakthrough” pain (Fishbain 2008). Sec-
ond, short-acting oxycodone can be used to taper opioid use when discontinuing
OxyContin (Berna, Kulich, and Rathmell 2015). Third, individuals abusing Oxy-
Contin may turn to close substitutes whenever they are unable to access OxyCon-
tin. For example, Cicero and Ellis (2015) showed that abusers of OxyContin were
most likely to switch to other oxycodone products when the supply of abusable
OxyContin was restricted. Thus, it is not surprising to observe large spillovers to
other oxycodone products.
25
All Drug Overdose Deaths
15

20
Coefficient Estimate
10
Deaths per 100,000
15
5
10
0
5
−5
0
83
85
87
89
91
93
95
97
99
01
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15
17
83
85
87
89
91
93
95
97
99
01
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19
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20
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
20
20
20
Non−Triplicate States Triplicate States Estimate 95% Confidence Interval
(A) Time Series (B) Event Study

Opioid Overdose Deaths
15
20
10
15
Coefficient Estimate
Deaths per 100,000
10
50
5
−5
0
83
85
87
89
91
93
95
97
99
01
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83
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Non−Triplicate States Triplicate States Estimate 95% Confidence Interval
(C) Time Series (D) Event Study
FIGURE IV
Drug Overdose Death Rates by Triplicate Status
We use geocoded NVSS data to construct all drug overdose and opioid overdose
deaths per 100,000. See Section III.A for exact ICD codes used in each period.
Event study models include state and year fixed effects. 95% confidence intervals
are generated using a clustered (at state) wild bootstrap. Estimates are normalized
to zero in 1995. Weighted by population.
states, but no meaningful differences in the misuse of other pain

relievers excluding OxyContin (Panel B). Taken together, the
above results are consistent with any differences in overdose
rates being primarily attributable to OxyContin.
V.C. Effects of OxyContin Use on Drug Overdose Deaths

1. Overall Results. We examine whether this differential
OxyContin use led to differences in drug overdose deaths over
time. In Figure IV, we show raw trends in drug overdose death
rates for triplicate and nontriplicate states. We also show coef-
ficients and 95% confidence intervals from estimating the event
study specification in equation (1). As is evident in Panel A, the
trends in overdose death rates were similar across the two sets of
states prior to the introduction of OxyContin. Triplicate states had

higher overdose rates initially, but this flips within a few years
of the launch. Nontriplicate states see rapid growth in overdose
deaths, whereas the trend for triplicate states is much flatter. The
corresponding event study estimates, shown in Panel B, are close
to zero and largely statistically insignificant prior to 1996, but
then the estimates diverge and become statistically significant.38
The event study estimate for 1997 indicates that overdose deaths
in nontriplicate states increased by 0.28 deaths per 100,000
compared with triplicate states. These effects increase to a
statistically significant 2.20 deaths per 100,000 in 2002 and 11.32
deaths per 100,000 by 2017.39 It is not surprising that these
mortality effects are delayed, given the expansions in OxyContin
promotion and sales over time and the FDA’s relabeling in 2001
that expanded its market for chronic use.40 In addition, it would
take time for a person to transition from an initial prescription
for OxyContin to dependence and an overdose.41
We find similar patterns for opioid-related deaths in
Figure IV, Panels C and D, demonstrating that the overall drug
overdose effects are largely driven by opioids. The event study
estimates are similar without population weights or when we
condition on covariates (see Online Appendix Figure A7). The
results are also robust to adding census region-year interactions
to account for geographic differences in overdose rate growth (see
Online Appendix Figure A8).
To quantify the magnitude of these effects, in Table I,
we present difference-in-differences estimates for the three
38. Although the individual event study estimates do not become statistically
significant until after 2001, a joint test (Table I) shows that the pooled 1996–2000
estimate is statistically significant relative to the 1991–1995 preperiod.
39. Notably, we do not observe a large differential jump in the event study
coefficients in 1999 when the switch to ICD-10 codes occurred, suggesting that the
rise is not a data artifact.
40. Purdue Pharma doubled its sales reps from 1996 to 2001 (Table 1, GAO
2003) and tripled marketing spending (Figure 1, GAO 2003). Prescriptions in-
creased from 316,786 in 1996 to 7.2 million in 2001 (Table 2, GAO 2003).
41. For example, a study of injection drug users shows a median of 7.7 years
between initiation of injecting and death (Evans et al. 2012). Another study finds
an average of four years between initiation and death (Guarino et al. 2018).
TABLE I
DIFFERENCE-IN-DIFFERENCES ESTIMATES: DRUG OVERDOSE DEATH RATE

Nontriplicate × (1) (2) (3) (4)
Panel A: All drug overdose deaths per 100,000

1996–2000 1.173** 1.290*** 1.267** 1.229**
[0.390, 2.374] [0.421, 2.449] [0.062, 2.274] [0.017, 2.483]
2001–2010 3.667** 4.488*** 3.561*** 3.232**
[1.521, 6.210] [2.201, 6.395] [1.321, 5.687] [1.011, 5.318]
2011–2017 6.061** 7.806*** 5.240*** 4.714***
[2.812, 9.371] [4.023, 10.439] [3.213, 7.274] [1.811, 7.253]
Joint p-value .016 .000 .001 .015
Weighted No Yes Yes Yes
Covariates No No Yes Yes
Region-time dummies No No No Yes
Mean 1991–1995 3.890 4.436 4.436 4.436
N 1,377 1,377 1,377 1,377
Panel B: Opioid overdose deaths per 100,000

1996–2000 0.634** 0.620** 0.725 0.821*
[0.083, 1.573] [0.112, 1.614] [−0.244, 1.621] [−0.189, 1.761]
2001–2010 2.614** 2.940*** 2.081** 2.271**
[1.115, 4.382] [1.232, 4.249] [0.151, 4.192] [0.297, 4.402]
2011–2017 5.002** 5.899*** 3.334*** 3.284**
[1.480, 8.292] [1.764, 8.895] [1.415, 5.613] [0.703, 6.012]
Joint p-value .039 .010 .034 .118
Weighted No Yes Yes Yes
Covariates No No Yes Yes
Region-time dummies No No No Yes
Mean 1991–1995 1.189 1.476 1.476 1.476
N 1,377 1,377 1,377 1,377
Notes: *** Significance 1%, ** significance 5%, * significance 10%. Outcome is all drug overdose deaths or
opioid overdose deaths per 100,000. The reported coefficients refer to the interaction of the given time period
and an indicator for whether the state did not have a triplicate program in 1996. Estimates are relative to
preperiod 1991–1995. 95% confidence intervals reported in brackets are estimated by clustered (by state) wild
bootstrap. All models include state and year fixed effects. Covariates include the fraction non-Hispanic white,
fraction non-Hispanic Black, fraction Hispanic, log of population, fraction with college degree, fraction ages
25–44, fraction ages 45–64, and fraction ages 65+. “Joint p-value” refers to the p-value from a joint hypothesis
test that all three nontriplicate post effects are equal to zero and is also estimated using a restricted wild
bootstrap.
postperiods from equation (2).42 In column (1), we present

unweighted estimates. In column (2), we present population-
weighted estimates, which are slightly larger. Relative to the
baseline period, we estimate that nontriplicate states experi-
enced an additional 1.3 overdose deaths per 100,000 people in the
earliest years after the launch (1996–2000), which is statistically
42. Alternatively, in Online Appendix Table A2, we present averages of the

event study year-specific estimates for the three aggregated time periods. These
results are similar to those estimated from equation (2).
1162 8
THE QUARTERLY JOURNAL OF ECONOMICS
6
8
Change in Deaths per 100,000


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FIGURE V
Drug Overdose Death Rate Changes: Triplicate States versus Bordering States
We construct the change in all drug overdose deaths per 100,000 for 1996–2005
relative to 1986–1995. We plot this change for each triplicate state relative to its
bordering states.
significant at the 1% level. The “counterfactual” fatal overdose

rate for nontriplicates during this time period was 4.2 per 100,000,
implying a 31% increase.43 The estimated effect grows to 4.5 in
2001–2010, representing a 68% increase, and 7.8 in 2011–2017,
a 76% increase over the counterfactual. Column (3) shows that
the estimates are robust to including time-varying covariates.
Column (4) shows robustness to census region-year interactions.
The bottom panel of Table I shows the results for opioid-
related overdose deaths. The patterns are similar. The 1996–2000
estimate in column (2) implies a 40% increase for nontriplicate
states and the 2011–2017 estimate indicates an increase over
100%.
2. State-Specific Results. We examine the mortality effects

for each state separately. In Figure V, we compare the growth in
overdose death rates for each triplicate state with its bordering
neighbor states for the 10 years before and after OxyContin’s
43. The counterfactual is the overdose rate of the nontriplicate states minus
the estimated coefficient on the nontriplicate indicator in that time period. The
“counterfactual” fatal overdose rate in nontriplicate states (had they been triplicate
states) is 4.166 (= 5.456 – 1.290), with an implied percentage increase of 1.290
4.166 =
0.31.
introduction. Online Appendix Figure A9 repeats this exercise

but uses the most recent 10 years. In almost every case, the

triplicate state had the lowest growth in drug overdose rates
compared with its neighbors.44 Thus, the overall results are not
driven by a single outlier triplicate state experiencing uniquely
low growth in overdose deaths. Instead, we observe this pattern
for all triplicate states. This suggests that it was the triplicate
program, not other characteristics of the states or regions, that
drove the uniquely low mortality growth rates.
3. Heroin and Fentanyl Overdose Deaths. We examine

trends in overdose deaths by the type of opioid. Online Appendix
Figure A10 shows cross-sectional annual differences in opioid-
related overdose deaths for natural and semisynthetic opioids,
heroin, and synthetic opioids for 1999–2017. Prior to 2010, the
only meaningful difference in overdose mortality between tripli-
cate and nontriplicate states was for natural and semisynthetic
opioids, the category that includes OxyContin. After 2010, we ob-
serve a large relative increase in heroin-related fatal overdoses in
nontriplicate states, although the differences are not statistically
significant. We also find that sharp differences in synthetic opioid
overdose death rates emerged in 2014. These patterns are consis-
tent with the main hypothesis of this article, combined with the
earlier findings in Alpert, Powell, and Pacula (2018) and Evans,
Lieber, and Power (2019). In 2010, Purdue Pharma introduced an
abuse-deterrent version of OxyContin, and the original formula-
tion was discontinued. This earlier work showed that states more
exposed to OxyContin (measured by having high prereformula-
tion rates of OxyContin misuse) experienced much faster growth
in heroin deaths after 2010 as people substituted from OxyContin
to heroin. These states later saw faster growth in synthetic opioid
deaths (Powell and Pacula 2021) when fentanyl became mixed
with the United States heroin supply (Ciccarone 2017; Pardo
et al. 2019). The timing of these drug-specific trends shows that
the introduction of OxyContin affected drug overdose deaths
through each wave of the opioid crisis. States less exposed to
44. While Idaho had a higher OxyContin adoption rate than other triplicate
states, many of its neighbors did too, suggesting meaningful regional differences.
For Idaho, this higher rate of adoption did not translate into a high growth rate in
overdoses, which might suggest a high demand for legitimate uses of the product
in this state.
OxyContin’s introduction were also (as predicted by the prior

studies) less affected by transitions to illicit drugs after OxyCon-

tin’s reformulation in later years of the opioid crisis.
V.D. Mechanisms
1. Effects of Triplicate Programs or Marketing? We consider
two possible mechanisms for the lower OxyContin use and over-
dose death rates in triplicate states. First, triplicate programs
themselves and the prescribing culture that developed from them
may have independently protected states against OxyContin
adoption and overdose growth, even after these programs were
discontinued. Second, these effects could be due to the lack of
initial OxyContin marketing targeted to triplicate states.
We conducted two tests to disentangle these mechanisms.
In the first test, we compare triplicate states to two former
triplicate states—Michigan and Indiana—that had discontinued
their triplicate programs in 1994, prior to OxyContin’s launch.
These former triplicate states serve as a useful counterfactual
because they show the long-term effects of having a triplicate
program, independent of marketing effects.45 In Figure VI, we
reestimate our main results while permitting different effects
for two groups of nontriplicate states: (i) former triplicate
states and (ii) never-triplicate states. Using the five triplicate
states as the comparison group, Panel A shows estimates of
cross-sectional differences in OxyContin distribution for former
triplicate states and never-triplicate states relative to tripli-
cate states. Panel B estimates our main event study for drug
overdose death rates, allowing separate coefficients for former
triplicate and never-triplicate states. These figures show that
triplicate states had much lower rates of OxyContin use compared
to former triplicate states that eliminated their programs just
two years before OxyContin’s launch.46 Triplicate programs also
experienced persistently lower overdose rate growth relative
45. Using CMS Open Payments Data for 2013–2016, Online Appendix Figure
A11 (comparable to Figure II) shows that former triplicate states have rates of
OxyContin promotion that are close to never-triplicate states. This suggests that
Purdue Pharma did not avoid marketing to former triplicate states and viewed
them in a similar way as other nontriplicate states.
46. Compared with states that never had triplicate programs, former trip-
licate states had lower mean OxyContin distribution rates but similar median
distribution rates (see Online Appendix Figure A12).
15
Difference in Per Capita OxyContin
.8

Estimated Coefficient
10
.4 .6
5
.2
0
0
00
02
04
06
08
10
12
14
16
83
85
87
89
91
93
95
97
99
01
03
05
07
09
11
13
15
17
20
20
20
20
20
20
20
20
20
19
19
19
19
19
19
19
19
19
20
20
20
20
20
20
20
20
20
Year Year
Former Triplicates Never Triplicates Former Triplicates Never Triplicates
(A) OxyContin Distribution (Differences) (B) Drug Overdose Deaths (Event Study)
FIGURE VI
Former Triplicate States: OxyContin Distribution and Drug Overdose Deaths
Panel A estimates the annual differences in OxyContin morphine equivalent
doses per capita between never-triplicate and triplicate states and the annual
differences between former-triplicate and triplicate states. Panel B estimates our
main event study for all drug overdoses per 100,000 (as in Figure IV) using the
triplicate states as the comparison group, allowing separate coefficients for never-
triplicate states and former-triplicate states. The event study model estimated in
Panel B includes state and year fixed effects. Regressions are population weighted.
to the former triplicate states. In fact, former triplicate states

had nearly identical overdose trends as states that never had
triplicate programs. Thus, the triplicate programs themselves do
not appear to explain the enduringly low overdose rates because
these programs are only predictive of low overdose rate growth
if they were in effect in 1996, when Purdue Pharma targeted
its marketing based on triplicate status. This evidence points to
marketing practices as the main driver of the overdose trends.47
In the second test in Online Appendix Figure A13, we com-
pare triplicate states to five nontriplicate states that had similar
initial prescribing cultures. Specifically, we select states with
the lowest oxycodone prescribing rates in 1991–1995 (see Online
Appendix Table A4 for list of states). For OxyContin distribution
47. One alternative explanation for this pattern is that former triplicate states
had triplicate programs for shorter time periods than triplicate states. Reduced
exposure to the program may have lessened the persistence of any developed pre-
scribing culture. However, Indiana and Michigan had similar oxycodone prescrib-
ing rates as the five triplicate states even in 1995 after eliminating their programs
(Online Appendix Table A3); this suggests that the triplicate programs induced low
oxycodone prescribing habits even in that shorter time period. Moreover, Texas,
which adopted its program in the same decade as Indiana and Michigan, experi-
enced much lower overdose death growth than these states.
(Panel A) and overdose death rates (Panel B), the estimates are
similar to the main results. Triplicate states used OxyContin at

much lower rates and had lower overdose growth compared to
nontriplicate states that initially had similar prescribing habits.
These results are difficult to explain by entrenched prescribing
culture, further supporting the marketing channel.
2. Persistence in Marketing Effects. The persistent dif-

ferences in OxyContin use and overdose deaths following the
elimination of all triplicate programs by 2004 are consistent with
serial correlation in Purdue Pharma’s marketing practices. As
discussed in Section II, the company’s strategy was to target sales
force visits to the top deciles of physicians based on past prescrib-
ing volume.48 Thus, given initial differences in marketing and the
resulting higher prescribing in nontriplicate states, nontriplicate
states would in turn continue to receive more marketing in future
years (as shown previously in Figure II) and higher prescribing
would persist. Without these marketing differences, it is difficult
to explain why the triplicate states as of 1996 experienced such
enduringly low overdose growth after eliminating their triplicate
programs, but states that had discontinued their programs just
two years before the launch experienced overdose trends almost
identical to states that never had these programs.
It also does not appear that Purdue Pharma significantly
increased marketing to triplicate states after their programs were
eliminated. In Online Appendix Figure A14, we plot estimates
from an event study examining Medicaid prescriptions around
triplicate repeal dates.49 We observe a downward trend over time,
consistent with the general separation between nontriplicate
and triplicate states due to marketing, but no independent effect
48. Purdue Pharma’s early budget plans regularly highlight the plan to target
the top one to three deciles of doctors based on past prescribing behavior. This
is echoed in their more recent internal communications: “Purdue ranked the pre-
scribers based on their aggregate opioid prescriptions in deciles from numbers 1
through 10, with 10 being the highest. From 2010 to 2013, Purdue instructed its
sales force to primarily focus on the top three deciles of prescribers. The purpose
of focusing the sales force on these highest deciles of prescribers was to cause an
even higher volume of prescriptions to be written by them” (DOJ 2020, Addendum
A, 8).
49. We use Medicaid prescriptions so we can include all triplicate states in the
analysis. The ARCOS OxyContin data are available beginning in 2000, so we do
not have a sufficient preperiod for all states.
of triplicate repeal. Although this does not rule out subsequent

targeting of marketing to the triplicate states, it suggests that

there was not a dramatic increase in marketing intensity. The
CMS Open Payments data shows that there is still a large gap
in marketing across triplicate and nontriplicate states that has
continued to the present day. The likely reason for this is that
Purdue Pharma’s marketing strategy was to target the highest
prescribers, which, given earlier targeting, were predominantly in
nontriplicate states.50 In addition, even if marketing did increase
after repeal, it would likely be less effective than during the initial
campaign, which could also explain the low demand response.51
VI. ROBUSTNESS TESTS

In this section, we explore alternative explanations for our
findings and test the robustness of our results. The main set of ro-
bustness tests for drug overdose deaths are presented in Table II
(see Online Appendix Table A5 for opioid-related overdose deaths).
VI.A. Alternative Explanations

1. Population Size. It is notable that four of the triplicate
states are among the largest states in the country. One concern is
that states with large populations may have experienced different
trends in overdose deaths independent of their triplicate status.
In Table II, column (2), we select the four largest nontriplicate
states (FL, PA, OH, and MI) as comparison states for the four
largest triplicate states.52 The estimates are larger than the main
estimates, indicating that triplicate states have uniquely low over-
dose growth, even compared with the largest nontriplicate states.
A related concern is that the triplicate states are more urban
than nontriplicate states. In Online Appendix Figure A15, Panel
50. When the program was repealed, doctors in triplicate states would have
much lower OxyContin prescribing and would likely generate a lower return from
marketing than targeting existing high prescribers in nontriplicate states.
51. By the early 2000s when triplicate programs were being repealed, there
was greater knowledge of OxyContin abuse and scrutiny of the misleading adver-
tising practices had increased. Also, the misleading claim on the FDA label had
been removed. As a result, Purdue Pharma may have scaled back its claims that
OxyContin had lower abuse potential than other opioids, making it more difficult
to convince doctors to switch to their product.
52. We use 1990 population size. We exclude Idaho from this analysis, although
results are similar if we include it.
TABLE II
ROBUSTNESS TESTS: DRUG OVERDOSE DEATH RATE

Baseline Select on Select on PDMP Control for
Nontriplicate × results population size states in 1996 policy variables
(1) (2) (3) (4)
1996–2000 1.267** 2.919** 2.163 1.348**

[0.062, 2.274] [0.452, 5.067] [−0.978, 4.828] [0.176, 2.453]
2001–2010 3.561*** 5.543*** 5.869* 3.628***
[1.321, 5.687] [2.671, 8.591] [−0.711, 11.369] [1.671, 5.322]
2011–2017 5.240*** 6.045** 9.299*** 5.808***
[3.213, 7.274] [0.535, 12.242] [3.528, 14.946] [3.528, 8.030]
Joint p-value .001 .073 .005 .000
Mean 1991–1995 4.436 5.090 5.294 4.436
N 1,377 216 405 1,377
Notes: *** Significance 1%, ** significance 5%, * significance 10%. Outcome is all drug overdose deaths
per 100,000. The reported coefficients refer to the interaction of the given time period and an indicator for
whether the state did not have a triplicate program in 1996. Estimates are relative to preperiod 1991–1995.
95% confidence intervals reported in brackets are estimated by clustered (by state) wild bootstrap. All models
include state and year fixed effects and time-varying covariates (see Table I for details). Column (1) repeats
the column (3) results from Table I. Column (2) selects on the four nontriplicate states with the largest
populations in 1990 along with the four largest triplicate states. Column (3) selects on states with some form
of PDMP (triplicate, duplicate, electronic) in 1996. Column (4) includes policy controls for PDMPs (any PDMP,
electronic PDMP, “must access” PDMPs), pain clinic regulation, medical marijuana laws, and operational/legal
medical marijuana dispensaries. “Joint p-value” refers to the p-value from a joint hypothesis test that all three
nontriplicate post effects are equal to zero and is also estimated using a restricted wild bootstrap.
A, we replicate our event study at the county level with county

fixed effects, selecting only on urban counties (826 counties).53
In Panel B, we select counties with the largest population size:
“central counties of metro areas of 1 million population or more”
(175 counties).54 The patterns are remarkably similar to our main
results, showing that triplicate status predicts large differences
in overdose deaths among the largest metropolitan areas in the
country.
2. Adoption of Other Policies. Triplicate states were some

of the earliest adopters of drug monitoring programs and were
potentially at the frontier of reducing prescription drug abuse in
the years following OxyContin’s introduction. If triplicate states
followed different policy paths that addressed opioid misuse more
effectively than the policies in nontriplicate states, this could be
confounding our results. In Table II, column (3) we examine drug
53. We use the 1993 categorization by the Office of Management and Budget
which divides counties into metropolitan (“urban”) and nonmetropolitan (“rural”).
54. We use the 1993 categorization defined by the Department of Agriculture’s
Economic Research Service.
overdose death rates in triplicate states compared to states with

other types of PDMPs in 1996—electronic PDMPs and duplicate

programs (Horwitz et al. 2018). States with other types of
monitoring programs might also be “ahead of the curve” in
moderating opioid misuse, and we would expect them to ex-
perience slower growth in overdose death rates. However, the
estimates increase when we select on this sample of states.
As a complementary approach, in column (4), we replicate the
difference-in-differences analysis for the full sample of states
while controlling for a set of opioid-related policy variables.55
Again, the results are similar implying that triplicate states did
not adopt systematically different opioid policies after 1996.56
3. Deaths of Despair. The deaths of despair hypothesis

discussed in Case and Deaton (2015, 2017) suggests that we
would have observed an increase in mortality even in the absence
of a rise in opioid supply because of worsening cultural and
economic factors. In this section, we study other types of deaths of
despair: suicides (excluding overdoses) and alcohol-related liver
deaths. Online Appendix Figure A17 presents the event study
estimates for these outcomes by triplicate status. Suicides trend
upward in the nontriplicate states relative to the triplicate states
beginning in the preperiod and continuing through the end of
the sample period (Panel A). Alcohol-related liver deaths also
exhibit preexisting trends that continue throughout the period
(Panel B). We present detrended event studies in Panels C and D.
55. We include three indicators for PDMPs from the RAND/USC Schaeffer
OPTIC PDMP (2021) data base: enactment of a PDMP; enactment of a mod-
ern, electronic system; and adoption of a “must access” provision. In addition,
we include indicators for pain clinic regulations, medical marijuana laws, and
legal/operational medical marijuana dispensaries. We code dates for pain clinic
regulations using the Prescription Drug Abuse Policy System. Data on marijuana
laws and dispensaries are from the RAND Marijuana Policy database (see Powell,
Pacula, and Jacobson 2018; Williams, Pacula, and Smart 2019).
56. We also test for differences in PDMP strength over time across triplicate
and nontriplicate states using an index introduced in Pardo (2017) that aggre-
gates together several different PDMP dimensions (e.g., mandatory use, timely
reporting). Online Appendix Figure A16 shows differences in PDMP strength for
nontriplicate states relative to triplicate states, selecting on states that had any
type of PDMP as of 1996. There is little difference in how PDMP strength evolved
between triplicate and nontriplicate states, yet we found much larger growth
in fatal overdoses in nontriplicate states relative to these other PDMP states
(Table II, column (3)).
Overall, we find little evidence that other deaths of despair follow

the same patterns as drug overdose deaths across triplicate and

nontriplicate states, suggesting that there is not a confounding
underlying factor that is common across these causes of death.
This shows that OxyContin played a crucial independent role
in the opioid crisis. Moreover, the lack of a decline in suicides
and alcohol-related liver mortality suggests that fatal opioid
overdoses were not substitutes for these types of deaths.
4. Additional Alternative Explanations. We conducted

numerous additional robustness tests that are discussed in
detail in Online Appendix C. Our results are unchanged if we
account for changes in economic conditions by controlling for the
unemployment rate or for economic shocks using Bartik-type
instruments. The results are also unaffected if we exclude fatal
overdoses involving unspecified narcotics. Finally, we implement
a leave-one-out analysis where we exclude each state in turn. The
findings are not driven by a single triplicate or nontriplicate state.
VI.B. Parallel Trends Assumption

In this section, we further evaluate the parallel trends
assumption in our main analysis and consider the robustness of
the results to possible violations of this assumption.
1. Synthetic Controls. First, we use a synthetic control ap-

proach (Abadie, Diamond, and Hainmueller 2010, 2015) to account
for systematic differences in pretreatment outcomes. We discuss
details of the implementation in Online Appendix D. Online
Appendix Table D1 presents estimates for our three postperiods.
The estimates are close to our main difference-in-differences es-
timates and statistically significant at the 1% level. For example,
when we population weight the state-specific estimates (column
(2)), we estimate that nontriplicate states experienced a differ-
ential increase in overdoses per 100,000 of 2.1 in 1996–2000, 5.1
in 2001–2010, and 6.9 in 2011–2017. The similarity between the
main estimates and the synthetic control estimates suggests that
the main results are not driven by any preexisting differences
in levels or trends between triplicate and nontriplicate states.
Online Appendix Figure D1 presents the results graphically. We
observe little evidence of pretreatment differences between the
triplicate states and their synthetic counterfactuals.
We compare 10-year overdose death rate growth in each

triplicate state to its synthetic control state in a manner similar to

Figure V (see Online Appendix Figure D2). Each triplicate state
had much lower growth than its corresponding synthetic control.
2. Permutation Test. Second, we consider the uniqueness of

the post-OxyContin overdose rate trends for triplicate states. We
conduct a permutation-like test where we randomly assign tripli-
cate status to five nontriplicate states and then estimate placebo
effects for three postperiods. We discuss this procedure further
in Online Appendix E. We present a histogram representing the
distribution of placebo estimates in Online Appendix Figure E1
and the distribution of t-statistics (recommended in MacKinnon
and Webb 2020) in Online Appendix Figure E2.
In comparing our main estimates to the placebo estimates,
we never observe differences in overdose rates between triplicate
and nontriplicate states as large as our actual estimated effects.
Our main estimates are outliers, ranking first in the placebo
distribution for each time period. In fact, it is impossible to find
any combination of five nontriplicate states that experienced the
same low rate of overdose rate growth as the triplicate states in
each of our three postperiods.
We also study whether the triplicate states had uniquely low
overdose rate growth before 1996. We randomly assign triplicate
status to five nontriplicate states and estimate the differential
growth in overdoses between 1991 and 1995. As shown in Online
Appendix Figure E3, the estimates for the actual triplicate states
are in the middle of this placebo distribution. Combined with the
results of the previous permutation tests, this implies that even if
we selected nontriplicate states in which the pretrend was simi-
lar to the pretrend for triplicate states, triplicate states still have
uniquely low growth in overdose deaths over the entire postperiod.
3. Effect of Cocaine Deaths on Trends. Third, in Online

Appendix Figure A18, we exclude overdoses involving cocaine
to evaluate the effect of the crack epidemic on pre-1996 trends.
The differences between triplicate and nontriplicate states in the
preperiod become even smaller, but the post-1996 effects remain.
Conversely, as a placebo test, we show event study results for
cocaine overdose rates alone in Online Appendix Figure A19. We
do not observe a comparable posttreatment upward trend, sug-
gesting that this rise was unique to overdoses involving opioids.
4. Deviations from Parallel Trends. Finally, we test the

sensitivity of our estimates to deviations from the parallel trend
assumption using the method of Rambachan and Roth (2020).57

This approach relaxes the parallel trends assumption by imposing
inequality constraints that permit deviations from preexisting
(treatment-specific) linear trends in the postperiod. Specifically, if
nontriplicates states experience differential annual linear growth
prior to treatment equal to θ , then the inequality constraints
permit posttreatment differential annual secular growth between
θ − M and θ + M. In Online Appendix Figure A21, we plot
confidence intervals for the three aggregated postperiods for
different values of M.58 The estimates in all time periods are
statistically different from zero when including a treatment
group-specific linear trend (M = 0) and even when permitting
annual deviations from a linear trend by as much as 0.015.
To interpret these magnitudes, Rambachan and Roth (2020)
recommend benchmarking the results to outcome patterns in
nontreated units. This practice relates to our permutation test.
We replicate Online Appendix Figure A21 but assign placebo
triplicate status to the five nontriplicate states with the lowest
overdose rate growth. This exercise is designed to find the highest
placebo values of M for the three postperiods in which it is
still possible to statistically reject zero overdose rate growth for
nontriplicate states. In Online Appendix Figure A22, we show
that the maximum values of M for which it is possible to reject
zero are smaller than those observed in Online Appendix Figure
A21 for the true triplicate states. This evidence suggests that it
would be extremely rare for the relative trend shift observed for
triplicate states to occur randomly.
VII. CONCLUSION
Despite the importance of the opioid crisis, there is little
empirical work exploring its initial causes. This article demon-
strates the importance of the introduction and marketing of
57. In Online Appendix Figure A20, we show event studies adjusting for state-
specific trends. We estimate a linear trend for each state prior to 1996 and project
it into the postperiod. The estimates are similar with or without state-specific
trends.
58. Estimates are averages of the event study coefficients for the three time
periods, as in Rambachan and Roth (2020).
OxyContin in 1996 as a key driver of the opioid crisis. We show

this by exploiting early variation in OxyContin’s promotion and

market entry due to state triplicate prescription programs. Our
results imply striking differences throughout the opioid crisis
stemming from variation in these initial conditions. States with
more exposure to OxyContin’s introduction experienced higher
growth in overdose deaths in every year since its launch in 1996.
Our estimates (from Figure IV) show that nontriplicate states
would have experienced 4.21 fewer drug overdose deaths per
100,000 on average from 1996 to 2017 if they had been triplicate
states and 3.16 fewer opioid overdose deaths per 100,000. Over
this time period, nontriplicate states had an average of 12.32
fatal overdoses per 100,000 annually, and 6.98 of those involved
opioids. This implies that if nontriplicate states had the same
initial exposure to OxyContin’s introduction as triplicate states,
they would have had 34% fewer drug overdose deaths and 45%
fewer opioid overdose deaths on average from 1996 to 2017.
We use our results to provide a back-of-the-envelope calcu-
lation of how much of the growth in drug overdose deaths can be
accounted for by the introduction and marketing of OxyContin.
This exercise is explained in detail in Online Appendix F. Online
Appendix Figure F1 shows the estimated counterfactual national
overdose death rate trend in the absence of OxyContin. This ex-
trapolation exercise suggests that the introduction of OxyContin
explains 79% of the rise in the overdose death rate since 1996.
In the absence of OxyContin, overdose death rate levels would be
substantially lower and unlikely to rise to the level of an opioid
crisis. In fact, the estimated counterfactual overdose rate does not
rise above the 1995 overdose death rate until 2006. We conduct
a similar extrapolation exercise for all-cause mortality focusing
on non-Hispanic whites ages 45–54, a population highlighted in
Case and Deaton (2015) as experiencing the largest reversal in
mortality trends after 1998. For this population, we estimate that
OxyContin’s introduction can explain about one-third of the rise
in all-cause mortality since 1998.
Our estimates capture both the direct and indirect conse-
quences of initial exposure to OxyContin’s introduction, including
spillovers of OxyContin promotion to other opioid drugs and
transitions to heroin and fentanyl in the later waves of the
epidemic. They also internalize downstream indirect effects of
OxyContin’s introduction on the behaviors of other entities in the
supply chain—distributors, pharmacies, and doctors—which may
have further amplified OxyContin’s effects. Our findings do not

rule out the possibility that economic and cultural factors also

contributed to a meaningful share of the rise in drug-related mor-
tality. Also, although these results quantify the harms associated
with OxyContin use, our analysis does not speak to the potential
benefits of improved opioid access through the introduction of
OxyContin. Opioids may be effective pain management tools in
some cases, and we do not attempt to estimate the gains from
pain reduction stemming from OxyContin’s launch.
Finally, the evidence in this article suggests that Purdue
Pharma’s marketing practices, in particular, played an impor-
tant role in explaining growth in drug overdose rates. When
triplicate states are compared to states that had recently elim-
inated their triplicate programs or other states with similar prior
oxycodone prescribing rates, they still have uniquely low over-
dose death rate growth. This suggests that it was not the trip-
licate programs themselves that independently influenced Oxy-
Contin adoption. Instead, the evidence is more consistent with
the idea that differences in marketing led to persistent differ-
ences in overdose death rate growth. Overall, we find strong
evidence that the marketing practices for OxyContin interacted
with state-level policy conditions led to dramatically reduced over-
dose death rates in triplicate states. Even though triplicate pro-
grams are now obsolete, by deterring OxyContin’s widespread
introduction in 1996, these programs protected some states
against the long-term fatal overdose trends experienced by most
other states.
UNIVERSITY OF PENNSYLVANIA AND NATIONAL BUREAU OF ECONOMIC

RESEARCH, UNITED STATES
UNIVERSITY OF NOTRE DAME, NATIONAL BUREAU OF ECONOMIC RE-
SEARCH, AND ABDUL LATIF JAMEEL POVERTY ACTION LAB, UNITED
STATES
UNIVERSITY OF NOTRE DAME AND NATIONAL BUREAU OF ECONOMIC
RESEARCH, UNITED STATES
RAND CORPORATION, UNITED STATES
SUPPLEMENTARY MATERIAL
Supplementary material is available at The Quarterly Jour-
nal of Economics online.
DATA AVAILABILITY
Data and code replicating the figures and tables in this article

can be found in Alpert et al. (2021), in the Harvard Dataverse,
https://doi.org/10.7910/DVN/P866NB.
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ORIGINS OF THE OPIOID CRISIS AND ITS

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Overdose deaths involving opioids have increased dramatically since the

∗ We thank Molly Candon, Matthew Harris, Mireille Jacobson, Robert Kaest-

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1. Some of these overdoses may involve nonopioid drugs in addition to opioids.

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access through Medicare led to higher rates of opioid diversion

3. In addition, Finkelstein, Gentzkow, and Williams (2018) find that place-

leading cause, exploring its effects on drug overdose deaths over

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5. See the 2019 New York complaint: https://ag.ny.gov/sites/default/files/oag

programs relative to states without these programs. We consider

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Although triplicate programs may have discouraged Oxy-

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terms of the promotional spending (GAO 2003) and the type of

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II.B. Geographic Variation in Exposure to OxyContin’s

7. Purdue Pharma also promoted OxyContin through a variety of other chan-

Information Act (FOIA) requests to obtain recently unsealed doc-

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1. What Are Triplicate Prescription Programs? Triplicate

oversight, relative to electronic systems, “It was felt that paper

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triplicate programs were adopted decades before OxyContin’s

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2. Purdue Pharma’s Marketing in Triplicate and Nontrip-

(see https://www.isms.org/opioidplan/). New York enacted a triplicate program in

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Non−Triplicate States Triplicate States Non−Triplicate States Triplicate States

(A) OxyContin Spending per 100,000 B OxyContin Spending / Total Spending

The persistence of the initial targeting based on triplicate sta-

19. For example, “McKinsey recommended doubling down on Purdue Pharma’s

identifiers.20 These data represent a census of deaths in the

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III.B. Opioid Distribution, Prescriptions, and Misuse

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24. Distribution of controlled substances from online or mail-order pharmacies

state prescribing behavior and represent an important population

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III.C. Summary Statistics

IV. EMPIRICAL STRATEGY

nontriplicate states relative to triplicate states before and after

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where yst represents annual drug overdose deaths per 100,000

yst = αs + γt + δ1 × 1(Nontriplicate)s × 1(1996 t 2000)s

The excluded category is 1991–1995 as we limit the sample

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V.A. Effects of Triplicate Status on OxyContin Use

Difference in Per Capita OxyContin

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(A) Trends in OxyContin Distribution (B) OxyContin (Diﬀerences)

Difference in Per Capita

Oxycodone in Triplicate States

(C) Trends in Oxycodone and Hydrocodone (D) Oxycodone and Hydrocodone

nontriplicate states compared with triplicate states. These large

there is a reduction in OxyContin prescriptions in 2005–2006.33

1996–2000 1.267 2.919 2.163 1.348**