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Drug Alcohol Depend. Author manuscript; available in PMC 2021 September 01.
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Drug Alcohol Depend. 2020 September 01; 214: 108137. doi:10.1016/j.drugalcdep.2020.108137.
The State of the Science in Opioid Policy Research

Megan S. Schuler1, Sara E. Heins2, Rosanna Smart3, Beth Ann Griffin4, David Powell2,
Elizabeth A. Stuart5, Bryce Pardo4, Sierra Smucker3, Stephen W. Patrick6, Rosalie Liccardo
Pacula7, Bradley D. Stein2,8
1.RAND Corporation, 20 Park Plaza #920, Boston MA USA 02216
2.RAND Corporation, 4570 Fifth Ave #600, Pittsburgh PA 15213
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3.RAND Corporation, 1776 Main Street, Santa Monica CA 90401

4.RAND Corporation, 1200 S Hayes Street, Arlington VA 22202
5.Departmentof Mental Health, Johns Hopkins Bloomberg School of Public Health, 624 N.
Broadway, Baltimore MD 21205
6.Vanderbilt
Center for Child Health Policy, Vanderbilt University Medical Center, 2200 Children's
Way, 11111 Doctors' Office Tower, Nashville TN 37232
7.Schaeffer
Center for Health Policy and Economics, University of Southern California, 635
Downey Way, Verna and Peter Dauterive Hall, Los Angeles CA 90089
8.Department of Psychiatry, University of Pittsburgh School of Medicine, 3811 O'Hara Street,
Pittsburgh PA 15213
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Abstract
Objective: Characterize the state of the science in opioid policy research based on a literature
review of opioid policy studies.
Methods: We conducted a scoping review of studies evaluating the impact of U.S. state-level and
federal-level policies on opioid-related outcomes published in 2005–2018. We characterized: 1)
state and federal policies evaluated, 2) opioid-related outcomes examined, and 3) study design and
analytic methods (summarized overall and by policy category).
Results: In total, 145 studies were reviewed (79% state-level policies, 21% federal-level policies)
and classified with respect to 8 distinct policy categories and 7 outcome categories. The majority
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Corresponding Author: Megan Schuler, 20 Park Plaza #920, Boston MA 02216, mschuler@rand.org, (p) 617-338-2059 x8602.
Contributors: MSS led analyses and manuscript writing. SEH conducted analyses and significantly contributed to manuscript writing
and review. BDS and RLP conceptualized the literature review; MSS, SEH, RS, BAG, DP, BP, SS, and RLP conducted literature
review. All authors contributed substantively to the content of the manuscript, as well as contributing to the manuscript writing and
review. All authors have approved the final version of the manuscript.
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Conflict of Interest: No conflict declared
Financial disclosure: No financial disclosures were reported by the authors of this paper.
Schuler et al. Page 2
of studies evaluated policies related to prescription opioids (prescription drug monitoring

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programs (PDMPs), opioid prescribing policies, federal regulation of prescription opioids, pain
clinic laws) and considered policy impacts with respect to proximal outcomes (e.g., opioid
prescribing behaviors). In total, only 29 (20% of studies) met each of three key criteria for
rigorous design: analysis of longitudinal data with a comparison group design, adjustment for
difference between policy-enacting and comparison states, and adjustment for potentially
confounding co-occurring policies. These more rigorous studies were predominately published in
2017–2018 and primarily evaluated PDMPs, marijuana laws, treatment-related policies, and
overdose prevention policies.
Conclusions: Our results indicated that study design rigor varied notably across policy
categories, highlighting the need for broader adoption of rigorous methods in the opioid policy
field. More evaluation studies are needed regarding overdose prevention policies and policies
related to treatment access. Greater examination of distal outcomes and potential unintended
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consequences are also warranted.
Keywords
opioid policy; state policy; federal policy; statistical methodology; review
1. INTRODUCTION
The country is in the midst of an opioid-related public health crisis, characterized by
increased opioid misuse and dependence and accompanying sequalae, including fatal opioid
overdose. National survey estimates indicate that in 2018 nearly 10 million people misused
prescription opioids, approximately 800,000 used heroin, and 2 million people had an opioid
use disorder (OUD) (SAMHSA, 2019), although household surveys likely significantly
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undercount heroin use (Midgette et al., 2019). Mortality rates from opioid overdoses
increased by nearly 400% between 2000 and 2018 with important spatiotemporal
heterogeneity in opioids involved in fatal overdoses (Hedegaard et al., 2020). As highlighted
by Heins (2019), prescription opioids have persistently been a major contributor to overdose
deaths, while heroin overdose deaths began notably increasing in 2010 (Ciccarone, 2017).
More recently, the rise of synthetic opioids, including illicitly manufactured fentanyl, has
particularly affected Appalachia, New England, and the Midwest (Pardo et al., 2019).
Fundamentally, there is important heterogeneity regarding the nature and impact of the
opioid crisis, with respect to geographic region, rurality, race/ethnicity, gender, and age
(Marsh et al., 2018; SAMHSA, 2020; Schuler et al., 2020; Singh et al., 2019).
In response, states and the federal governments have enacted a broad array of policies,
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producing a complex and dynamic policy landscape. Given the multi-faceted nature of the
opioid crisis, these policies target multiple stakeholders (including healthcare providers,
patients, substance use treatment providers, individuals using heroin or street-sourced
opioids, and communities affected by opioid misuse) and are intended to impact a wide
range of outcomes. Broadly, opioid-related laws and regulations have focused on deterring
high-risk opioid prescribing behaviors; improving access to treatment, including medications
for OUD treatment (e.g., buprenorphine, methadone); and expanding overdose prevention
efforts (e.g., increasing access to naloxone, an overdose reversal medication). Furthermore,
numerous evaluation studies have also examined impact of broader policies (e.g., Medicaid
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expansion, state marijuana laws) on opioid-related outcomes. The growing opioid policy
literature can provide policymakers and other stakeholders with key insights regarding how
various policies may impact different aspects of the opioid crisis, yet published studies vary
regarding methodological rigor.
To characterize the state of the science in opioid policy research, we conducted a scoping
review of studies evaluating the impact of U.S. state-level and federal-level policies on
opioid-related outcomes published in 2005–2018. Our primary focus was to characterize: (1)
which state and federal policies have been evaluated, (2) which opioid-related outcomes
have been examined, and (3) study designs and analytic methods employed. We empirically
define categories of policies and outcomes examined across studies, highlighting those that
have received more extensive, as well as more limited, evaluation to date. For each policy
category, we summarize study design and analytic methods across studies. Overall, our
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review characterizes the current opioid policy evidence base and highlights important
methodological challenges and analytic considerations facing the field.
2. METHODS
2.1 Data Sources and Search Strategy
We conducted a scoping literature review of U.S. state- and federal-level opioid policy
evaluation studies published between 2005 and 2018. The search included English language
articles within 13 medicine, social science, economic, and legal databases using a defined set
of search terms (full search strategy including list of databases and search terms detailed in
Appendix 11). Search criteria required studies to contain at least one search term from each
of three categories: (1) policy terms (e.g., prescription drug monitoring program, pain clinic,
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Good Samaritan), (2) opioid terms (e.g., oxycodone heroin), and (3) opioid-related outcome
terms (e.g., opioid overdose, measures of opioid prescribing). The search term list was
compiled iteratively by study team members, with input from Advisory Board members of
the RAND-USC Schaeffer Opioid Policy Tools and Information Center (OPTIC).
2.2 Screening Strategy and Inclusion Criteria

Studies identified in the search were screened and selected for full review if they met both of
the following criteria: (1) quantitatively evaluated at least one policy (i.e., legislation or
regulation) implemented in the U.S. at the state or federal level, and (2) included as a
dependent variable at least one opioid-related outcome. Eligible studies included articles
published in peer-reviewed journal articles or Morbidity and Mortality Weekly Report as
well as economic working papers (e.g., NBER). We excluded purely descriptive studies,
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qualitative studies, editorials, dissertations, and review articles. Prior to the start of the
screening process, the screening protocol was refined by research team members applying it
to a small random sample of studies; study team members discussed protocol inconsistencies
or ambiguity until consensus was reached and the screening protocol was refined
accordingly.
1Supplementary material can be found by accessing the online version of this paper at http://dx.doi.org and by entering doi…
Studies flagged as eligible for full text review during screening were cross-checked by a
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second reviewer; a small random sample of studies flagged as ineligible for full text review
were cross-checked by a second reviewer. Studies flagged as ineligible for inclusion during
full text review were cross-checked by a second reviewer. Study team members discussed
studies for which reviewers disagreed until consensus was reached.
2.3 Data Extraction and Synthesis

For studies eligible for full text review, research team members extracted details regarding
study design and analytic approach from each article using a standardized extraction form
and accompanying codebook. Key study features assessed included: (1) primary opioid-
related policies evaluated, (2) all opioid-related outcomes assessed, and (3) details on study
design and analytic methods. Policies were classified as primary if stated as the exposure of
interest in the study objectives. Policies that were controlled for in the main analyses or only
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evaluated in sensitivity analyses or supplemental materials were not classified as primary

policies. Study characteristics of interest included: policy level (federal or state); study
design (longitudinal data with a comparison group; longitudinal data with no comparison
group; cross-sectional data with a comparison group; cross-sectional data without a
comparison group); length of study period; adjustment for covariate differences across
policy and comparison groups (if applicable); specification of primary policy (single binary
variable or more complex specification); and adjustment for co-occurring opioid-related
policies.
We identified categories for the opioid policies evaluated in the studies reviewed. A priori
policy categories enumerated by the study team were refined based on literature review
results; categories were iterated among the study team until consensus was reached.
Similarly, we identified broad categories of opioid-related outcomes examined, using
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empirical results to refine a priori categories (see Appendix 22). We note that neither policy
nor outcome categories are intended to represent an exhaustive description of all opioid
policies and outcomes; instead they provide a classification schema for policies and
outcomes examined in the literature published to date. We present analytic results from our
extraction database including descriptive statistics regarding frequency of policies and
outcomes, as well as study design characteristics (overall and by policy category).
3. RESULTS
The database search yielded 5,113 studies for screening (Figure 1). Preliminary screening of
titles and abstracts eliminated 4,829 studies, most commonly because they did not conduct
an evaluation of a U.S. state- or federal-level policy. The remaining 284 studies underwent
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full-text assessment; 139 did not meet inclusion criteria, whereas 145 met criteria and were
included in our review (see listing in Appendix 33). All 145 studies were observational (i.e.,
nonexperimental) in nature. The number of opioid evaluation studies published annually has
increased significantly in recent years (Figure 2), with approximately 60% of evaluated
studies published in 2017 and 2018. Overall, 21% of studies evaluated federal policies while
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the remaining 79% evaluated state-level policies.
3.1 State and Federal Policies Evaluated

Based on the primary policies evaluated across studies, we defined 8 distinct policy
categories (Figure 3), described below and further detailed in Appendix 24. We report the
percentage of studies that evaluated policies in each category; the sum across categories
exceeds 100% as some studies evaluated more than one primary policy.
Prescription Drug Monitoring Programs—The most commonly evaluated category

was state prescription drug monitoring programs (PDMPs), electronic databases that track
prescribed and dispensed controlled substances, evaluated in 52 (35%) studies. While some
states have had a PDMP for decades, the opioid crisis has fueled the adoption of PDMPs
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across the country – currently, the District of Columbia and all states with the exception of
Missouri operate a state-wide PDMP (PDAPS, 2019).
Opioid Prescribing Policies—The next most common category comprised policies

targeting opioid prescribing, evaluated in 31 (22%) studies. State-level policies included
Medicaid formulary restrictions (e.g., (Cochran et al., 2017; Keast et al., 2018)), Medicaid
controlled substance lock-in programs (Roberts et al., 2016; Skinner et al., 2016), and state-
level prescribing guidelines (e.g., (Johnson et al., 2011; Penm et al., 2018; Weiner et al.,
2017)). While most prescribing policies were enacted at the state level, federal-level
initiatives included Medicare formulary restrictions (Chen et al., 2017), the Veterans Health
Administration’s Opioid Safety Initiative (Lin et al., 2017), and the 2016 Centers for Disease
Control and Prevention’s (CDC) Guideline for Prescribing Opioids for Chronic Pain
(Bohnert et al., 2018).
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Federal Regulation of Prescription Opioids—Federal regulations relating to the

approval, formulation, or scheduling of prescription opioids were evaluated in 20 (14%)
studies. Specific policies examined included: up-scheduling hydrocodone combination
products to Schedule II (e.g., (Kuo et al., 2018; Murimi et al., 2019; Raji et al., 2018),
introduction of the abuse-deterrent reformulation of OxyContin (e.g., (Alpert et al., 2018;
Cicero and Ellis, 2015; Larochelle et al., 2015), FDA approval of generic OxyContin (Bailey
et al., 2006), and FDA-requested withdrawal of propoxyphene from the U.S. market
(Delcher et al., 2017; Larochelle et al., 2015).
Treatment Access Policies—Policies relating to substance/OUD treatment access were

evaluated in 17 (12%) studies. State-level policies included state Medicaid expansion,
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including through the Patient Protection and Affordable Care Act (e.g., (Meinhofer and
Witman, 2018; Sharp et al., 2018; Wen et al., 2017a)); changes to state Medicaid coverage
for methadone or buprenorphine (e.g., (Bachhuber et al., 2017; Saloner et al., 2016)); and
targeted funding for substance use treatment programs (Abraham et al., 2018). Federal-level
policies included the Patient Protection and Affordable Care Act and federal waiver
requirements for buprenorphine prescribing (e.g., (Dick et al., 2015; Feder et al., 2017; Stein
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et al., 2015)).
State Marijuana Laws—State marijuana laws (i.e., laws that decriminalize possession of
marijuana, legalize medical marijuana, or legalize recreational marijuana) were evaluated in
14 (10%) studies (e.g., (Shi, 2017; Shi et al., 2019; Wen and Hockenberry, 2018; Wong and
Lin, 2019)). A hypothesized mechanism is that marijuana, particularly medical marijuana,
may have a substitution effect with opioid analgesics.
Pain Management Clinic Laws—Pain management clinic laws (also referred to as “pill
mill laws”) were evaluated in 13 (9%) studies. These laws impose regulations regarding the
licensing, personnel, operation and inspection of medical facilities that primarily diagnosis
and manage chronic pain. The majority of these studies focused exclusively on Florida’s
pain clinic laws (e.g., (Chang et al., 2016; Chang et al., 2018; Kennedy-Hendricks et al.,
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2016; Rutkow et al., 2015)), with only a single study conducting a multi-state evaluation
(Dowell et al., 2016).
Overdose Prevention Policies—Policies aimed primarily at reducing opioid overdoses

(e.g., naloxone access laws, overdose education/naloxone distribution (OEND) initiatives,
and Good Samaritan laws) were evaluated in 13 (9%) studies. Naloxone, an opioid
antagonist that can be administered by a layperson via nasal spray or intramuscular injection
(using an automatic injection device), can rapidly reverse an opioid overdose (Robinson and
Wermeling, 2014; Sumner et al., 2016). Naloxone access laws evaluated included a broad
range of provisions including: third-party provisions that allow naloxone to be dispensed/
used by someone other than to whom it was prescribed; provisions that permit naloxone
possession without prescription; layperson dispensing provisions that allow naloxone
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dispensing by individuals who are not otherwise authorized to dispense prescription

medication; immunity provisions that protect clinicians from liability associated with
naloxone administration; and standing order provisions that allow naloxone dispensing
without a prescription to any person in need (e.g., (Gertner et al., 2018; Lambdin et al.,
2018; Rees et al., 2017; Xu et al., 2018)). OEND programs provide overdose prevention
training and naloxone education and distribution (Bounthavong et al., 2017; Walley et al.,
2013). Good Samaritan laws are intended to increase bystander assistance to individuals
experiencing a drug overdose by providing some legal immunity regarding drug
possession/use by the bystander respondent’s and limiting liability in the case of an
unsuccessful intervention (Nguyen and Parker, 2018; Rees et al., 2017).
Punitive Drug Use Policies—Criminal justice laws targeting drug use, including
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mandatory sentencing minimums for drug distribution/possession (e.g., (Davies, 2010)) and
expansion of child neglect/abuse laws to include use of opioids while pregnant (e.g.,
(Angelotta et al., 2016)) were examined in 6 (4%) studies.
3.2. Opioid-Related Outcomes Evaluated

Based on the opioid-related outcomes evaluated across studies, we defined 7 distinct
outcome categories. We report the percentage of studies that evaluated outcomes in each
category; the sum across categories exceeds 100% as some studies evaluated outcomes in
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more than one category. Figure 4 shows the distribution of policy and outcome combinations
evaluated. As this figure highlights, the majority of studies examined proximal outcomes
(e.g., effect of PDMPs on opioid prescribing, effect of treatment access policies on treatment
utilization), yet some studies considered more distal outcomes (e.g., effect of marijuana laws
on opioid-related mortality) or unintended consequences (e.g., effect of PDMPs on heroin
use). We note that not all outcome categories would necessarily be expected to be impacted
by a given policy; thus, an absence of studies examining a specific policy-outcome pairing
does not necessarily imply an evidence “gap” in the literature.
Opioid Prescribing Behavior—Measures of opioid prescribing behavior were examined

in 81 (55%) studies. Specific measures included: type of opioids prescribed, days of opioids
prescribed, total number of opioid prescriptions, morphine milligram equivalents of
prescribed dose, high-dose prescribing, number of unique opioid patients per physician,
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opioid prescription refill rate, and prescriber use of PDMPs. Measures of prescribing
behavior were generally obtained from state PDMP administrative records, the Drug
Enforcement Administration’s Automation of Reports and Consolidated Orders System
(ARCOS), IQVIA retail pharmacy data, or insurance claims data (e.g., Medicaid, Truven
Marketscan Research Database).
Opioid-Related Morbidity and Mortality—Opioid-related morbidity or mortality were

examined in 55 (38%) studies. Specific outcomes included: fatal opioid-related overdoses,
opioid-related hospitalizations and emergency room visits, opioid-related emergency
medical service responses, and opioid-related poison center calls. Data on fatal overdose
rates were obtained from the CDC’s National Vital Statistics System. Measures of healthcare
utilization for acute opioid-related outcomes were primarily derived from insurance claims
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or administrative data.
Prescription Opioid Misuse and Opioid Use Disorder—OUD and prescription

opioid misuse (including nonmedical use of prescription opioids and potentially high-risk
prescription opioid behaviors) were examined in 32 (22%) studies. In studies using national
survey data (in particular, the National Survey on Drug Use and Health), prescription opioid
misuse measures included self-reported nonmedical use of prescription opioids, source of
prescription opioids used for nonmedical purposes, and motivation for nonmedical use.
Measures of high-risk prescription opioid use or drug-seeking behavior included: the
number of different pharmacies where an individual filled opioid prescriptions, number of
physicians from whom an individual received an opioid prescription, purchase of opioid
prescriptions with cash, early refills or overlapping prescriptions for opioids, and patient
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disenrollment following formulary restrictions. These measures were generally

operationalized using self-reported survey data, PDMP data, or insurance claims data. OUD
was operationalized in national survey data as a self-reported diagnosis from a healthcare
provider or based on survey items corresponding to DSM criteria for abuse or dependence
(for either prescription opioids or heroin) and operationalized in administrative/claims data
based on International Classification of Diseases (ICD) codes for opioid abuse or
dependence.
Heroin and Other Illicit Opioid Use—Measures of heroin and other illicit opioid use
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were examined in 25 (17%) studies. Note that this category of outcomes does not include
measures that encompass both prescription opioids as well as heroin/illicit opioids (e.g., any
opioid misuse, OUD). Specific outcomes included: heroin or illicit opioid use, heroin use
abuse/dependence, overdose deaths involving heroin or synthetic opioids, heroin-related
poison control calls, sales volume of heroin and illicit opioids through U.S. cryptomarkets,
and street prices of heroin/illicit opioids. These measures were operationalized in survey
data as self-reported heroin use or based on survey items corresponding to DSM criteria for
heroin abuse or dependence and operationalized in claims data based on ICD codes for
heroin abuse or dependence. Overdose data were obtained from the Centers for Disease
Control and Prevention’s National Vital Statistics System and street price data were obtained
from RADARS’ StreetRx Program.
Treatment Access and Utilization—Measures of treatment access and utilization were

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examined in 25 (17%) studies. Measures included: any OUD treatment, any OUD
medication treatment, type of OUD medication treatment, treatment setting, treatment
referral source, treatment adherence, number of buprenorphine waivered physicians per
capita, and treatment admission rate per capita. Data sources included self-reported
utilization measures from national surveys, insurance claims and administrative data, as well
as data from RADARS’ Opioid Treatment Program and the Survey of Key Informants’
Patients Program.
Opioid-related Crime—Measures of opioid-related crime, primarily diversion of

prescription opioids, were examined in 10 (7%) studies. Specific measures included opioid-
related arrests, rate of prescription opioid diversion cases, listings for prescription opioids on
online cryptomarkets, and street prices of prescription opioids. Data sources include the
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Federal Bureau of Investigation’s Uniform Crime Reports, the National Incident-Based

Reporting System, the Drug Enforcement Administration’s System to Retrieve Information
From Drug Evidence (STRIDE) data, and the RADARS System.
Naloxone Use—Measures of naloxone use were examined in 7 (5%) studies, primarily in

the context of evaluating naloxone access laws and OEND initiatives. Measures included the
number of naloxone prescriptions, volume of naloxone stocked at pharmacies, volume of
naloxone dispensed, and pharmacist intention to stock and dispense naloxone. Data sources
included administrative and claims data from commercial insurers, Medicaid, and the
Veterans Health Administration as well as survey data from pharmacists.
3.4 Study Design and Analytic Methods used in Evaluation Studies

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Prescription Drug Monitoring Programs studies—Of the 52 PDMP studies, 31

(60%) analyzed longitudinal data with a comparison group design (i.e., the gold standard for
observational research), 16 (31%) analyzed longitudinal data with no comparison group, and
5 (9%) analyzed cross-sectional data with a comparison group design. Of the 36 studies with
a comparison group design, the majority accounted for differences between policy and
comparison states using regression adjustment (n=27) or propensity scores (n=2), yet 7
studies (19%) did not, which may result in biased effect estimates. Additionally, 32 studies
(62%) did not control for the potential impact of co-occurring policies, which may also bias
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effect estimates. Comparing across policy categories, a strength of PDMP studies is their
relatively longer study period lengths: 18 (35%) had a study period of 8 years or longer.
Another strength of PDMP studies was their examination of policy heterogeneity, with 34
(65%) operationalizing the policy with more complexity than a binary variable in order to
assess distinct policy components. Specifically, multiple studies compared mandatory access
PDMP, non-mandatory access PDMP, and no PDMP (e.g., (Ayres and Jalal, 2018; Dhaval et
al., 2018)). Alternatively, several studies differentiated between PDMPs with mandatory
enrollment, with mandatory access, both mandatory access and enrollment, and neither
mandatory access nor enrollment (e.g., (Ali et al., 2017; Wen et al., 2017b)). Other studies
considered even more PDMP characteristics – Pauly et al. (2018) contrasted the
effectiveness the following 5 characteristics: (1) PDMP operational status, (2) controlled
substance schedules monitored by the PDMP, (3) frequency of data reporting to the PDMP
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central server, (4) provisions for unsolicited reporting of patients’ controlled substance
prescription history, and (5) provisions regarding mandated prescriber access. Finally, some
studies evaluated differences among mandatory access laws – Buchmueller and Carey
(2018) defined three subtypes of these laws: (1) limited laws that apply only to certain drugs
or settings of care, (2) discretionary laws that mandate PDMP access upon provider
suspicion and (3) broad laws that apply to all drugs and settings and do not rely on provider
suspicion.
Opioid Prescribing Policies studies—Opioid prescribing policies have increasingly

been evaluated in recent years, with 25 (81%) of the 31 total studies published during 2016–
2018. Overall, 24 (77%) examined state-level policies and 7 (23%) evaluated federal-level
policies. A relative weakness of these studies is that 22 (71%) did not employ a comparison
group design (in part due to the prevalence of federal policy studies). Overall, only 8 (26%)
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employed the strongest design (longitudinal data with a comparison group), whereas 21
analyzed longitudinal data with no comparison group, 1 analyzed cross-sectional data with a
comparison group, and 1 analyzed cross-sectional data without a comparison group.
However, all 9 studies with a comparison group design accounted for differences between
policy-enacting and comparison states, using either regression adjustment or propensity
scores. Additional weaknesses include that 27 (87%) did not adjust for co-occurring policies
and only 12 (39%) examined policy components via more complex specifications of the
policy variable. Additionally, these studies had shorter study periods on average: 23 (75%)
had study periods less than 6 years.
Federal Regulation of Prescription Opioids studies—Of the 20 studies, 12 (60%)

were published in 2016–2018 and 7 (35%) were published in 2011–2015. Identifying an
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appropriate comparison group for federal policies is challenging – as such, 19 studies (95%)
did not use a comparison group design. Instead, many performed an interrupted time series
analysis, in which the pre-policy trend is used to extrapolate the counterfactual trend of how
the outcome would have evolved in the absence of policy implementation. While this is one
of the most rigorous quasi-experimental study designs, studies without a comparison group
are subject to potential bias arising from exogenous factors that also impact the outcome. As
such, it is particularly notable that 17 studies (85%) did not control for any co-occurring
policies. Additionally, these studies had shorter study periods: 17 (85%) had study periods
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less than 6 years. Given that the federal policies evaluated did not differ across states, none
of these studies utilized more complex specifications of the policy variable to examine
policy heterogeneity.
Treatment Access Policies studies—Of the 17 studies, 15 (88%) examined state-level

policies and 2 (12%) evaluated federal-level policies. Overall, 9 (53%) analyzed longitudinal
data with a comparison group design, 4 (24%) used longitudinal data with no comparison
group, and 4 (24%) used cross-sectional data with a comparison group. Of the 13
comparison group design studies, 12 accounted for differences between policy and
comparison states using covariate regression. A relative strength of these studies is that the
majority (9; 53%) accounted for co-occurring policies, with 8 studies adjusting for 2 or more
co-occurring policies. Additionally, 9 studies (53%) used more complex specifications of the
policy variable. These studies also had relatively longer study periods -- 6 (36%) had a study
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period of 8 years or longer.
State Marijuana Laws studies—Studies examining the impacts of state marijuana laws
on opioid-related outcomes were more likely to be published in recent years, with 12 (86%)
of the 14 studies published during 2016–2018. Compared to other policy categories, this
category had the highest percentage of studies employing a comparison group design with
longitudinal data (n=12; 86%), all of which accounted for differences between policy and
comparison states. Half of all studies (n=7) used more complex specifications of the policy
variable (e.g., to differentiate states that permitted marijuana dispensaries versus only home
cultivation). Another relative strength was that these studies were the most likely to account
for co-occurring policies (n=11; 79%), with 8 studies controlling for 2 or more co-occurring
policies. It is possible that addressing potential confounding of co-occurring policies (e.g.,
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PDMPs) may be perceived as more salient for this policy category, given that marijuana laws
do not directly target opioid-related outcomes. A relative weakness of these studies is their
shorter study period length (9 studies (64%) were less than 4 years), due to the recency of
state marijuana laws.
Pain Management Clinic Laws studies—Of the 13 pain clinic studies, 8 (62%)
analyzed longitudinal data with a comparison group design, and the remaining 5 (38%) used
longitudinal data with no comparison group. Of the 8 studies with a comparison group
design, 3 (38%) did not account for differences between policy and comparison states,
which may bias policy effect estimates. Furthermore, 9 studies (69%) did not adjust for co-
occurring policies. The majority (n= 7; 54%) did not examine policy heterogeneity through
more complex specifications of the policy variable, largely due to a preponderance of studies
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that only considered a single policy state (e.g., Florida, Texas). Notably, due to the near
simultaneous enactment of Florida’s PDMP and pain clinic laws, two studies strictly
estimated the joint effect of both policies (Chang et al., 2016; Chang et al., 2018). A relative
strength of pain clinic studies is their relatively longer study periods -- 39% (n=5) had a
study period of 8 years or longer.
Overdose Prevention Policies studies—Given the recency of policies targeting opioid

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overdose prevention, 12 (92%) of the 13 studies were published in 2016–2018. Compared to

other policy categories, this category had the second highest percentage of studies
employing a comparison group design with longitudinal data (n=11; 85% of studies). Of the
11 studies with a comparison group, 2 (18%) did not account for differences between policy
and comparison states, which may bias policy effect estimates. Furthermore, 8 (62%) of the
13 studies did not adjust for the potential effect of co-occurring policies. Overall, 7 (54%)
considered policy heterogeneity through more complex specifications of the policy variable.
Naloxone law studies varied in their classification scheme, with studies considering four
categories (i.e., third party, standing order, prescriber immunity, and layperson dispensing)
(Gertner et al., 2018), five categories (i.e., third party, standing order, possession, prescriber
immunity, and dispenser immunity) (McClellan et al., 2018), and six categories (i.e., third
party, standing order, possession, prescriber immunity, dispenser immunity, and layperson
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dispensing) (Lambdin et al., 2018). A relative weakness of these studies is their relatively
shorter study periods: 31% of studies (n=4) had a study period less than 2 years.
Punitive Drug Use Policies studies—Overall, only 6 studies examined the impact of
punitive drug use policies on opioid-related outcomes; as such, a primary weakness is the
limited number of published evaluation studies. Overall, 3 (50%) analyzed longitudinal data
with a comparison group design, 2 (33%) used longitudinal data with no comparison group,
and 1 (17%) used cross-sectional data with a comparison group. Relative strengths included
that all 4 studies with a comparison group design adjusted for differences between policy
and comparison states and 4 of the 6 studies accounted for co-occurring policies in the
primary analyses. Only 1 study considered policy heterogeneity through more complex
specifications of the policy variable. A relative weakness of these studies is their relatively
shorter study periods, as 33% (n=2) of studies had a study period less than 2 years.
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4. DISCUSSION
This study provides a novel overview of the state of the opioid policy literature between
2005 to 2018, focusing on evaluation studies of U.S. state and federal policies on opioid-
related outcomes. In contrast to prior systematic reviews regarding specific opioid policies
(e.g., (Fink et al., 2018; Finley et al., 2017)), we provide a more expansive perspective on
the state of the field by considering the breadth of policies and outcomes evaluated to date.
Furthermore, our study is distinct from recent opioid policy scoping reviews (Beaudoin et
al., 2016; Haegerich et al., 2019; Mauri et al., 2020) in that: (1) we provide a detailed
characterization of study design and methods by policy category and (2) we include policy
categories that are not specifically targeting opioids but have been evaluated in terms of their
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impacts on opioid-related outcomes, including state marijuana laws and Medicaid expansion
through the Affordable Care Act.
We identified 8 categories of policies evaluated across studies, listed from most to less
frequent: (1) prescription drug monitoring programs, (2) opioid prescribing policies, (3)
federal regulation of prescription opioids, (4) treatment access policies, (5) pain
management clinic laws, (6) overdose prevention policies, (7) state marijuana laws, and (8)
punitive drug use policies. Similarly, we identified 7 categories of opioid-related outcomes
examined, listed from most to least frequent: (1) opioid prescribing behavior, (2) opioid-
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related mortality and morbidity, (3) prescription opioid misuse/OUD, (4) heroin and other
illicit opioid use, (5) treatment utilization, (6) naloxone use, and (7) opioid-related crime.
Currently, the majority of existing studies examined policies aimed strictly at prescription
opioids (PDMPs, opioid prescribing policies, federal regulation of prescription opioids, pain
clinic laws). Furthermore, the majority of studies evaluated policy effectiveness with respect
to proximal outcomes (e.g., effect of PDMPs on opioid prescribing, effect of treatment
access policies on treatment utilization). We note that the research objectives and study
design of published studies, in part, have been driven by data availability. The preponderance
of studies of prescription opioid-related policies likely reflects the fact that many of the
earliest policies enacted targeted opioid prescribing, resulting in richer data availability (e.g.,
greater number of implementation states, longer window of post-policy data). Furthermore,
data on prescription opioids is accessible via administrative data, whereas reliable data
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regarding use of heroin and other illicit opioids is relatively scarce.
Our results indicated that study design rigor varied notably across policy categories,
highlighting the need for broader adoption of rigorous methods in the opioid policy field. Of
the 145 studies, only 29 (20%) met each of three key criteria for rigorous design: analysis of
longitudinal data with a comparison group design, adjustment for difference between policy
and comparison states, and adjustment for potentially confounding co-occurring policies.
These 29 studies were predominately published in 2017–2018 and primarily evaluated
PDMPs (n=11), marijuana laws (n=9), treatment-related policies (n=6), and overdose
prevention policies (n=5). In addition to the greatest number of rigorous studies, key
strengths of PDMP studies were that (1) the studies included more years of data and (2) the
majority (65%) examined policy heterogeneity (i.e., compared distinct PDMP components).
While opioid prescribing policies was the second-most common category evaluated, a
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notable weakness of these studies was that the majority (71%) did not employ a comparison
group design. While a limited number of studies evaluated marijuana laws and overdose
prevention policies, these studies were more likely to have rigorous designs (with respect to
the three aforementioned criteria) relative to studies in other policy categories.
While challenging in the context of a federal-level policy, the use of comparison group
design significantly strengthens inference when evaluating state-level policies. Confounding
due to systematic differences between policy and comparison groups may bias effect
estimates if not rigorously controlled for. While the commonly-used DID design can account
for unobserved confounders if assumptions are upheld (Wing et al., 2018), these may not
always be plausible. In particular, policy and comparison groups may have differential
outcome trends over time or state population composition may change significantly across
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time (Stuart et al., 2014). While the majority of comparison group design studies reviewed
adjusted for some set of observed covariates, the most common method was regression
adjustment. Policy researchers should consider more robust approaches such as propensity
score methods (Austin and Stuart, 2015; Linden and Adams, 2011; Stuart et al., 2014) and
synthetic control designs (Abadie et al., 2010; Kreif et al., 2016; Xu, 2017), or, in the
context of time-varying confounding, marginal structural models or a principal stratification
framework (Cole and Hernan, 2008; Robins et al., 2000; Santacatterina et al., 2019;
Shinohara et al., 2013).
Another key methodological consideration our review identified was the importance of
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controlling for co-occurring policies. While addressing potential confounding of co-

occurring opioid policies may be viewed as more necessary for face validity when
examining the impact of policies that don’t directly target opioid-related outcomes (e.g.,
marijuana laws), we underscore that all evaluation studies are subject to potential bias when
co-occurring policies are not accounted for. Furthermore, co-occurring policies may yield
synergistic policy effects, although such additive or interactive effects have rarely been
examined to date. Going forward, it is imperative that evaluation studies more rigorously
account for concurrent policies when estimating the effects of a given policy as well as
estimate more expansive policy effects, such as potential additive effects of concurrent
policies. Recent methodological work has focused on causal inference methods in the
context of concurrent treatments (Ellis and Brookhart, 2013; Jackson, 2016; Lusivika-
Nzinga et al., 2017).
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As the state-level policy landscape has become more complex, increasing attention has been
paid to heterogeneity in state policies and resultant variation in policy effectiveness. Indeed,
nearly half of all studies and 65% of PDMP studies used more complex specifications (e.g.,
categorical or composite variables) to examine effectiveness across distinct policy
components or characteristics. We note that early studies of a given policy are often unable
to examine policy heterogeneity due to the limited number of enactment states; as more
states implement a given policy, it is increasingly possible to rigorously examine differences
across policy components or characteristics. Yet, as highlighted in our findings, there is
currently tremendous variation in how studies classify and operationalize heterogeneity
across policies, suggesting the need for a more structured and systematic approach (Grant et
al., 2020). Going forward, an essential challenge for the field is defining and
operationalizing meaningful policy categories in evaluation studies.
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Finally, our findings highlight several policies and outcomes for which more evidence is
needed. More studies are needed regarding overdose prevention policies (e.g., naloxone
access laws, overdose education/naloxone distribution initiatives, Good Samaritan laws),
particularly as the prevalence of overdose deaths due to synthetic opioids is rising in some
regions (Hedegaard et al., 2020). Additional research regarding treatment-related policies is
needed, as the policy landscape continues to evolve regarding state Medicaid coverage of (or
alternatively, restrictions relating to) medication treatment (Kaiser Family Foundation, 2019;
Leslie et al., 2019) as well as federal policies regarding buprenorphine waiver requirements
(McBain et al., 2020). Also, few studies to date have examined punitive drug use policies,
such as laws that stipulate that substance use during pregnancy may be grounds for
terminating parental rights – despite enactment in 23 states, it is unclear whether these laws
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promote maternal and child well-being. Furthermore, examination of more distal outcomes
of policies is needed, including the impact of PDMPs and opioid prescribing policies on the
use of non-opioid pain management techniques and patient functional ability. Similarly,
existing studies of overdose prevention policies have primarily assessed the impacts on
overdoses and naloxone use, yet the potential effects on opioid misuse or treatment
engagement post-overdose has not been well-characterized. Unintended consequences of
policies also deserve more attention; for example, a recent study found that punitive state
policies related to substance use during pregnancy were linked with increased neonatal
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abstinence syndrome rates (Faherty et al., 2019).
4.1 Limitations of the current study

Several limitations of the current study deserve mention. The scope of our literature review
was U.S. state and federal level policies – many opioid-related policies and initiatives have
also been adopted at the community or health system level. We did not include gray
literature publications, unpublished evaluation studies, dissertations, or abstracts from
conference proceedings. Given that our study objective was a scoping review of the state of
the field, we did not systematically review evidence regarding effectiveness of specific
policies nor did we conduct a meta-analysis to obtain pooled estimates of policy
effectiveness.
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5. CONCLUSION
The current opioid policy literature is rapidly evolving, but still has limitations. More
evaluation studies are needed regarding overdose prevention policies and policies related to
treatment access. Greater examination of distal outcomes and potential unintended
consequences are also warranted. There are still important methodological challenges and
considerations facing the field, including standardized classification of opioid policies and
heterogeneous policy components, identifying an optimal comparison group and rigorously
controlling for differences across policy and comparison groups, and disentangling effects of
co-occurring policies. Increasing the methodological rigor of opioid evaluation studies is
imperative to identifying and implementing opioid policies that are most effective at
reducing opioid-related harms.
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Supplementary Material
Refer to Web version on PubMed Central for supplementary material.
Acknowledgments
Role of funding source: This work was funded by awards P50DA046351. The content is solely the responsibility
of the authors and does not necessarily represent the official views of NIDA, the NIH or the US Government.
Funding: P50DA046351
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[PubMed: 28296674]
Wen H, Schackman BR, Aden B, Bao Y, 2017b States with prescription drug monitoring mandates saw
a reduction in opioids prescribed to Medicaid enrollees. Health Aff. (Millwood) 36, 733–741.
[PubMed: 28373340]
Wing C, Simon K, Bello-Gomez RA, 2018 Designing difference in difference studies: Best practices
for public health policy research. Annu. Rev. Public Health 39, 453–469. [PubMed: 29328877]
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prescription medication misuse among adolescents in the U.S. Addict. Behav 90, 48–54. [PubMed:
30359847]
Xu J, Davis CS, Cruz M, Lurie P, 2018 State naloxone access laws are associated with an increase in
the number of naloxone prescriptions dispensed in retail pharmacies. Drug Alcohol Depend 189,
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models. Polit. Anal 25, 57–76.
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Highlights
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• Conducted a scoping review of U.S. opioid policy evaluation studies from

2005–2018
• 145 studies were reviewed: 21% examined federal policies, 79% state policies
• Majority of studies evaluated policies related to prescription opioids
• Our results indicated that study design rigor varied notably across policy
categories
• Greater adoption of more rigorous study designs and statistical methods is

warranted
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Figure 1.
Flow chart of literature search and study sample selection
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Figure 2.
Publication dates of opioid policy evaluation studies reviewed (n=145)
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Figure 3.
Categories of opioid-related policies evaluated across the 145 studies reviewed
Note: The sum across categories exceeds 145, as some studies examined multiple policies.
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Figure 4.
Categorization of studies by both policies evaluated and outcomes examined.
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Table 1.
Study characteristics for 145 studies reviewed
Opioid Fed. Reg. of Overdose

Treatment State Marijuana Pain Clinic Punitive Drug
Overall PDMP Prescribing Prescription Prevention
Access Policies Laws Laws Use Policies
Schuler et al.
Policies Opioids Policies

N=145 N=52 N=31 N=20 N=17 N=14 N=13 N=13 N=6
Publication Year
2005–2010 7 (5%) 4 (8%) 0 (0%) 1 (5%) 1 (6%) 0 (0%) 0 (0%) 0 (0%) 1 (17%)
2011–2015 33 (23%) 13 (25%) 6 (19%) 7 (35%) 3 (18%) 2 (14%) 3 (23%) 1 (8%) 0 (0%)
2016–2018 105 (72%) 35 (67%) 25 (81%) 12 (60%) 13 (76%) 12 (86%) 10 (77%) 12 (92%) 5 (83%)
Policy level
State-level policy 115 (79%) 52 (100%) 24 (77%) 0 (0%) 15 (88%) 14 (100%) 13 (100%) 12 (92%) 5 (83%)
Federal policy 30 (21%) 0 (0%) 7 (23%) 20 (100%) 2 (12%) 0 (0%) 0 (0%) 1 (8%) 1 (17%)
Study design
Longitudinal data, 68 (47%) 31 (60%) 8 (26%) 1 (5%) 9 (53%) 12 (86%) 8 (62%) 11 (85%) 3 (50%)
comparison group
Longitudinal data, no 64 (44%) 16 (31%) 21 (68%) 19 (95%) 4 (24%) 2 (14%) 5 (38%) 2 (15%) 2 (33%)
comparison group
Cross-sectional data, 11 (8%) 5 (10%) 1 (3%) 0 (0%) 4 (24%) 0 (0%) 0 (0%) 0 (0%) 1 (17%)
comparison group
Cross-sectional data, 2 (1%) 0 (0%) 1 (3%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
no comparison group
Adjusted for differences between policy and comparison groups
Covariate regression 62 (43%) 27 (52%) 6 (19%) 0 (0%) 12 (71%) 11 (79%) 5 (38%) 9 (69%) 4 (67%)
adjustment
Propensity score 6 (4%) 2 (4%) 3 (10%) 0 (0%) 0 (0%) 1 (7%) 0 (0%) 0 (0%) 0 (0%)
method
No adjustment 11 (8%) 7 (13%) 0 (0%) 1 (5%) 1 (6%) 0 (0%) 3 (23%) 2 (15%) 0 (0%)
Not applicable - no 66 (46%) 16 (31%) 22 (71%) 19 (95%) 4 (24%) 2 (14%) 5 (38%) 2 (15%) 2 (33%)
comparison group
Policy coding other than single binary indicator
Yes 69 (48%) 34 (65%) 12 (39%) 0 (0%) 9 (53%) 7 (50%) 6 (46%) 7 (54%) 1 (17%)
No 76 (52%) 18 (35%) 19 (61%) 20 (100%) 8 (47%) 7 (50%) 7 (54%) 6 (46%) 5 (83%)
Accounted for any co-occurring policies
Primary analyses: 14 (10%) 7 (13%) 1 (3%) 2 (10%) 1 (6%) 2 (14%) 2 (15%) 2 (15%) 2 (33%)
Single co-occurring
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Opioid Fed. Reg. of Overdose

Treatment State Marijuana Pain Clinic Punitive Drug
Overall PDMP Prescribing Prescription Prevention
Access Policies Laws Laws Use Policies
Policies Opioids Policies
N=145 N=52 N=31 N=20 N=17 N=14 N=13 N=13 N=6
Primary analyses: 2+ 29 (20%) 8 (15%) 2 (6%) 1 (5%) 8 (47%) 8 (57%) 1 (8%) 3 (23%) 2 (33%)
Schuler et al.
co-occurring
Secondary / 8 (6%) 5 (10%) 1 (3%) 0 (0%) 0 (0%) 1 (7%) 1 (8%) 0 (0%) 0 (0%)
sensitivity analyses only
No 94 (65%) 32 (62%) 27 (87%) 17 (85%) 8 (47%) 3 (21%) 9 (69%) 8 (62%) 2 (33%)
Length of study period
< 2 yrs 33 (23%) 10 (19%) 8 (26%) 5 (25%) 5 (29%) 2 (14%) 3 (23%) 4 (31%) 2 (33%)
2 yrs - < 4 yrs 32 (22%) 11 (21%) 7 (23%) 9 (45%) 2 (12%) 7 (50%) 3 (23%) 2 (15%) 1 (17%)
4 yrs < 6 yrs 20 (14%) 5 (10%) 8 (26%) 3 (15%) 1 (6%) 1 (7%) 2 (15%) 2 (15%) 2 (33%)
6 yrs < 8 yrs 12 (8%) 8 (15%) 3 (10%) 0 (0%) 3 (18%) 1 (7%) 0 (0%) 0 (0%) 0 (0%)
8 yrs < 10 yrs 14 (10%) 6 (12%) 2 (6%) 1 (5%) 3 (18%) 1 (7%) 1 (8%) 1 (8%) 0 (0%)
10 yrs 34 (23%) 12 (23%) 3 (10%) 2 (10%) 3 (18%) 2 (14%) 4 (31%) 4 (31%) 1 (17%)
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The State of the Science in Opioid Policy Research

3.RAND Corporation, 1776 Main Street, Santa Monica CA 90401

of studies evaluated policies related to prescription opioids (prescription drug monitoring

consequences are also warranted.

2.2 Screening Strategy and Inclusion Criteria

2.3 Data Extraction and Synthesis

evaluated in sensitivity analyses or supplemental materials were not classified as primary

the remaining 79% evaluated state-level policies.

3.1 State and Federal Policies Evaluated

Prescription Drug Monitoring Programs—The most commonly evaluated category

Opioid Prescribing Policies—The next most common category comprised policies

Federal Regulation of Prescription Opioids—Federal regulations relating to the

Treatment Access Policies—Policies relating to substance/OUD treatment access were

Overdose Prevention Policies—Policies aimed primarily at reducing opioid overdoses

dispensing by individuals who are not otherwise authorized to dispense prescription

3.2. Opioid-Related Outcomes Evaluated

Opioid Prescribing Behavior—Measures of opioid prescribing behavior were examined

Opioid-Related Morbidity and Mortality—Opioid-related morbidity or mortality were

Prescription Opioid Misuse and Opioid Use Disorder—OUD and prescription

disenrollment following formulary restrictions. These measures were generally

Treatment Access and Utilization—Measures of treatment access and utilization were

Opioid-related Crime—Measures of opioid-related crime, primarily diversion of

Federal Bureau of Investigation’s Uniform Crime Reports, the National Incident-Based

Naloxone Use—Measures of naloxone use were examined in 7 (5%) studies, primarily in

3.4 Study Design and Analytic Methods used in Evaluation Studies

Prescription Drug Monitoring Programs studies—Of the 52 PDMP studies, 31

Opioid Prescribing Policies studies—Opioid prescribing policies have increasingly

Federal Regulation of Prescription Opioids studies—Of the 20 studies, 12 (60%)

Treatment Access Policies studies—Of the 17 studies, 15 (88%) examined state-level

period of 8 years or longer.

Overdose Prevention Policies studies—Given the recency of policies targeting opioid

overdose prevention, 12 (92%) of the 13 studies were published in 2016–2018. Compared to

regarding use of heroin and other illicit opioids is relatively scarce.

controlling for co-occurring policies. While addressing potential confounding of co-

abstinence syndrome rates (Faherty et al., 2019).

4.1 Limitations of the current study

women. Womens Health Issues 26, 595–601. [PubMed: 27773527]

109–118. [PubMed: 27194195]

11. Health Aff. (Millwood) 34, 1028–1034. [PubMed: 26056209]

propoxyphene. JAMA Intern. Med 175, 978–987. [PubMed: 25895077]

Economic Research, Cambridge, MA.

Intern. Med 175, 1642–1649. [PubMed: 26280092]

792–799. [PubMed: 31792871]

patterns. Int. J. MCH AIDS 8, 89–100. [PubMed: 31723479]

• Conducted a scoping review of U.S. opioid policy evaluation studies from

• Majority of studies evaluated policies related to prescription opioids

• Greater adoption of more rigorous study designs and statistical methods is

Study characteristics for 145 studies reviewed

Opioid Fed. Reg. of Overdose

Policies Opioids Policies

Opioid Fed. Reg. of Overdose

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