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Epidemiology
Original research
State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA
  1. Jay P Solgama1,
  2. Edward Liu1,
  3. Mellar Davis1,2,
  4. Jove Graham3,4,
  5. Kenneth L McCall5,6,
  6. Brian J Piper1,3
  1. 1Geisinger Commonwealth School of Medicine, Scranton, Pennsylvania, USA
  2. 2Palliative Care, Geisinger Health System, Danville, Pennsylvania, USA
  3. 3Center for Pharmacy Innovation and Outcomes, Geisinger, Danville, Pennsylvania, USA
  4. 4Center for Health Research, Danville, Pennsylvania, USA
  5. 5Binghamton University, Binghamton, New York, USA
  6. 6University of New England, Portland, Maine, USA
  1. Correspondence to Jay P Solgama; JSolgama{at}som.geisinger.edu

Abstract

Objectives This study aims to characterise oxycodone’s distribution and opioid-related overdoses in the USA by state from 2000 to 2021.

Design This is an observational study.

Setting More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them.

Methods The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics.

Results There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007–2011), Delaware (2003–2020) and Tennessee (2012–2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000–2001, 2008, 2010–2021), Colorado (2008–2021) and DC (2000–2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics.

Conclusions Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

  • EPIDEMIOLOGY
  • PALLIATIVE CARE
  • EPIDEMIOLOGIC STUDIES
  • Chronic Pain
  • PUBLIC HEALTH

Data availability statement

Data are available in a public, open access repository. ARCOS data are publicly accessible at https://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/arcos-drug-summary-reports.html. CDC WONDER data are publicly accessible at https://wonder.cdc.gov/. A python script to extract data from ARCOS Report 5 PDFs (provided at: https://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/arcos-drug-summary-reports.html) and process the data can be found at https://github.com/solgamaj/VARCOS.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/bmjopen-2023-073765

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STRENGTHS AND LIMITATIONS OF THIS STUDY

  • Automation of Reports and Consolidated Orders System (ARCOS) is publicly accessible, comprehensive and includes institutions that are unavailable in other commonly used databases (ie, data available from the contract research organization IQVIA).

  • Diversion of oxycodone or whether the prescribed amounts were used cannot be determined from ARCOS data.

  • Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research is a publicly accessible database that provides important mortality data, but it is difficult to relate these data directly to oxycodone distribution.

  • These complementary results from two databases may not generalise to other countries with more restrictive oxycodone policies.

Introduction

The USA is amid an opioid crisis that has been worsening since the start of the century. The most recent data show that 80 725 individuals died from an opioid overdose in 2021.1 Prescription opioids put pain management patients at risk for developing an addiction and provide a potential source for opioid misusers. Since the 1990s, many people were introduced to opioids through prescription drugs, and some moved on to cheaper alternatives such as heroin.2 Regulations and guidelines often apply at the state level, and heterogeneity in culture, politics and socioeconomics plays a role in the disproportionate impact of the crisis in different regions. In this study, we aimed to characterise the US distribution of oxycodone, a prevalent opioid that has contributed to the crisis, across states.

The opioid epidemic can be described in three discrete waves, with different drugs implicated in the emergence of each wave. The first wave began in the 90s with misuse of prescription opioids, followed by a second wave of heroin-related deaths and a third wave related to illicitly manufactured synthetic opioids like fentanyl.3–5 A fourth wave, associated with a combination of synthetic opioids and stimulant drugs, has been developing in the USA.6 7 As we examine oxycodone over the past two decades, it is important to keep in mind the concurrent changes in distribution and mortality related to opioids broadly as variations in supply and demand of each drug are interrelated.

Oxycodone was the most commonly consumed opioid globally from 2009 to 2019, with the USA being the largest consumer.8 The generic product and other formulations (eg, OxyContin, Percocet, Percodan and Roxicodone) were misused by 1.1% of the US population in 2020, behind only hydrocodone.9 Oxycodone is of particular concern due to its high abuse liability.10 Its danger is demonstrated by high rates of overdose death, as it was involved in 33 154 deaths between 2011 and 2016 and is the third behind heroin and fentanyl.11

Few studies have investigated trends in oxycodone distribution throughout the USA. One investigation used the Drug Enforcement Administration’s Automation of Reports and Consolidated Orders System (ARCOS) database, finding a concerning 69.7% increase in amount of oxycodone distributed from 2000 to 2010.12 In a more recent report, a detailed analysis for both oxycodone and hydrocodone in the US commuting zones using Washington Post ARCOS data was performed, and it was found that population size influenced scaling behaviour of pills, and there were regions of high distribution in the Appalachians, Ozarks and the west coast.13

Here, we explore oxycodone distribution by state using the US Drug Enforcement Agency (DEA) ARCOS over a larger time frame than any previous studies, which included reports on prescription opioids in the US territories, Texas and throughout Delaware, Maryland and Virginia.14–16 Past works frequently rely on the IQVIA database, which is limited by gaps in oxycodone, including data from Veteran’s Affairs, Indian Health Services facilities, hospitals and independent pharmacies.17 Using states as the geographical unit allows results to be interpreted in the context of laws and regulations which apply at that level. We include analysis of distribution by three business types: pharmacies, hospitals18 and practitioners, to provide more detailed information.

We also use the Centers for Disease Control and Prevention (CDC) Wide-ranging ONline Data for Epidemiologic Research (WONDER) database which provides public health information, including mortality data by ICD-10 codes.19 We report on the number of deaths related to heroin, other opioids, methadone, other synthetic narcotics and other and unspecified narcotics, as is available in the database. Mortality data provide some context to the variations of oxycodone distribution over time and possible effects of those variations.

Methods

Procedures

Data were collected from the ARCOS Report 5. The database is provided by the DEA and reports on distribution of Schedule I–IV controlled substances.20 Oxycodone distribution was reported in grams grouped by business type (hospitals, pharmacies, practitioners, mid-level practitioners, narcotic treatment programmes, teaching institutions) per state for 2000–2021 alongside the number of buyers. Oxycodone from teaching institutions was addressed elsewhere.21 Pharmacies, hospitals and practitioners were chosen for individual analysis in addition to the total of all business types. The CDC WONDER data were filtered to include drug poisonings that were unintentional (X40–X44), suicide (X40–X64), homicide (X85) or undetermined (Y10–Y14). Diagnosis codes T40.1 (heroin), T40.2 (other opioids), T40.3 (methadone), T40.4 (other synthetic narcotics) and T40.6 (other and unspecified narcotics) were used to extract number of opioid-related deaths.

Data analysis

Microsoft Excel, GraphPad Prism and RStudio were used to analyse and visualise the data. Grams of oxycodone were converted to morphine milligram equivalents (MME) using a standard oral conversion factor of 1.5.22 MME per buyer was calculated by dividing MME and the provided number of businesses that made purchases. The total MME per state was divided by the corresponding year’s population, as reported by the U.S. Census Bureau’s American Community Survey, to calculate MME per person. The same populations were used to divide opioid-related deaths to calculate deaths per 100 000 individuals in total and for each diagnosis code.

MME per person was plotted across time for each state to identify the peak year of oxycodone distribution. The five states with the highest average distribution and the five states with the lowest average distribution were plotted for pharmacies, hospitals and the total of all business types. Data for practitioners were much more varied, and 10 states with the highest distribution and notable patterns were plotted. Opioid-related deaths were plotted across time to identify patterns of change over the study period.

States whose values that fell outside the range of ±1.96 SD from the mean were identified, and a Pearson correlation coefficient, r, was calculated for MME per person and MME per buyer for each business type (online supplemental file 1—online supplemental figure 1).

Choropleth maps of the US states were created for each year from 2000 to 2021 for MME per person, total opioid deaths and each of the five subcategories contributing to total opioid deaths (online supplemental file 2 - maps 1–7).

Patient and public involvement

Patients and the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.

Results

Total oxycodone distribution

The USA distributed 1404.01 metric tons in MME of oxycodone from 2000 to 2021. Total MME per person increased rapidly and by +280% from 2000 to the peak in 2010. There was a more protracted decrease of −54% from 2010 to 2021. Notable differences arose when distribution was grouped by business type. Pharmacies constituted the largest proportion of oxycodone distribution (>94%) and drove the pattern of total distribution. Pharmacies showed a +293% increase from 2000 to 10 and a −54% decrease from the peak to 2021. Hospitals were far less variable in their distribution between years, with an increase of +80% to a later peak in 2012 and a subsequent slow decline of −51% by 2021. Practitioners showed a pronounced increase in their oxycodone distribution by +15 567% leading up to 2010 but declined by −87% the following year. There was a −99% reduction from the peak by 2021. MME per person was positively and strongly correlated with MME per buyer for each grouping, with an r value of +0.95 for all businesses, +0.94 for pharmacies, +0.70 for hospitals and +0.85 for practitioners (figure 1).

Figure 1
Figure 1

Total oxycodone distribution in total and by business activity in the USA from 2000 to 2021 as reported by the Drug Enforcement Administration’s Automated Reports and Consolidated Orders System. MME, morphine milligram equivalents.

Oxycodone distribution by state

MME per person distributed by states showed large variations between each other, in total, and for each business type. The difference between population corrected distribution was 8-fold in 2000 (Alaska=177.7, Illinois=23.4), peaked at 15-fold in 2010 (Florida=993.5, Texas=66.7) and decreased to 6-fold in 2021 (Tennessee=250.8, Illinois=45.2). Florida (2007–2011), Delaware (2003–2020) and Tennessee (2012–2021) showed consistent and substantial elevations in combined MME/person compared with other states (ie, greater than 1.96 SD higher than the mean). Texas (2012–2021) and Illinois (2006, 2013–2021) were on the other end of the spectrum, with considerably lower oxycodone distribution. The national peak in 2010 was highly influenced by the few states distributing large amounts of oxycodone (online supplemental file 1—online supplemental figure 2) (figures 2 and 3).

Figure 2
Figure 2

Morphine mg equivalent (MME) per person of oxycodone by business type 2000–2021 as reported by the US Drug Enforcement Administration’s Automated Reports and Consolidated Orders System for (A) all business types, (B) pharmacies, (C) hospitals and (D) practitioners. Areas outside ±1.96 SD of the average state are in grey.

Figure 3
Figure 3

Choropleth map of the morphine mg equivalent (MME) per person in the peak year (2010) as reported by the Drug Enforcement Administration’s Automated Reports and Consolidated Orders System (A). Bar graphs showing the per cent increase from 2000 to 2010 (B) and per cent decrease from 2010 to 2021 (C). States outside *±1.96 or #±1.0 SD of the mean.

MME per person from only pharmacies constituted the preponderance (>94%) of the total and displayed a similar pattern as the combined distribution. Florida (2007–2011), Delaware (2003–2020) and Tennessee (2012–2021) had substantially higher values, while Texas (2012–2021) and Illinois (2006, 2013–2021) had substantially lower values, over many years. Most states showed some growth leading up to the years around the national peak in 2010 followed by a decline until 2021.

States tended to peak in the few years following 2010 when examining oxycodone distributed by hospitals. There were still large differences in magnitude between states. Hospitals in Alaska (2000–2001, 2008, 2010–2021), Colorado (2008–2021) and DC (2000–11) purchased the largest quantities of oxycodone. Only Illinois distributed amounts of oxycodone that were lower than 1.96 SD from the mean, from 2000 to 2002.

The data for practitioners showed notable variations between states in the magnitude of oxycodone distribution as well as patterns of change. Florida stood out with nearly 15-fold the MME/person for the average state from 2006 to 2010. Florida was also 26 152-fold elevated relative to West Virginia in 2010. Delaware showed a sharp spike in 2011 that dropped back within ±1.96 SD of the mean by 2013. Hawaii had notably high values in more recent years from 2014 to 2015 and 2017–2021. No states distributed amounts of oxycodone that were 1.96 SD lower than the mean.

Opioid-related deaths

Total opioid-related deaths have continued to increase over time, with a +806% increase since 2000 and a peak of 29.7 deaths per 100 000 people in 2021. Heroin-related deaths were relatively stable until a surge starting in 2010, resulting in a nearly 4-fold increase to a peak of 4.8 deaths per 100 000 people in 2016. Since 2016, there has been a steep decline to 2.76 deaths per 100 000 people. Deaths related to other opioids steadily rose to a peak in 2016 at 4.5 deaths per 100 000 people, followed by a decrease before rising again in 2020 and 2021. Mortality related to other synthetic narcotics increased slowly until 2013, after which there was a large, 75-fold increase by 2021. Methadone-related deaths increased to a peak in 2006 at 1.83 deaths per 100 000 people. This was followed by a decline until 2019, with a recent increase in 2020 and 2021. Deaths related to other and unspecified narcotics decreased slowly by −58.9% from 2000 to 2021 (figure 4).

Figure 4
Figure 4

Opioid-related deaths from 2000 to 2021 by diagnosis codes T40.1 (heroin), T40.2 (other opioids), T40.3 (methadone), T40.4 (other synthetic narcotics) and T40.5 (other and unspecified narcotics) as reported by the Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research database.

Discussion

This study used the comprehensive ARCOS database to characterise the US distribution of oxycodone by pharmacies, hospitals, practitioners and in total for two decades. We saw a large increase in total oxycodone distribution from 2000 until 2010, during which time MME per person grew by fourfold. This was followed by a decrease by more than half over the next 11 years. There were stark differences in the patterns of change between states. Some, like Florida16 or Delaware,15 increased substantially leading up to 2010 and dropped off just as quickly. Others like Texas14 or Illinois maintained consistently low distribution, and many states fell somewhere in between. Differences between states peaked at nearly 15-fold in the peak year (2010), and never dropped below 5-fold. It is important to put the peak oxycodone MME in Delaware (918 MME/person) in context. The MME for 10 opioids including oxycodone in 2016 in North Dakota was almost half (485) of this.22 These pronounced and persistent state-level disparities may offer opportunities for continued vigilance in opioid stewardship.

Pharmacies distributed nearly 95% of the oxycodone over the timeframe of the data, following a pattern close to the total distribution. Again, many states displayed large increases leading up to the peak year, preceding a slow decline. Comparison of the magnitude of distribution revealed about 7-fold, 15-fold and 6-fold differences in 2000, 2010 and 2021, respectively. Practitioner distribution also showed pronounced variation between states. Differences started at 928-fold in 2000, peaked at an astounding 26 152-fold in 2010 and settled at 3,192-fold in 2021. Overall, there was a rapid increase and decrease around the peak, but many states showed multiple peaks while others (eg, West Virginia, Rhode Island, Montana) distributed relatively low amounts of oxycodone for all years. Oxycodone distributed by hospitals18 showed a far less drastic peak in 2012, later than the other groups, and slowly declined until 2021. Interestingly, differences between states peaked at 20-fold much earlier in 2005, eventually decreasing to 10-fold in 2021.

Practitioners account for a small portion of the total MME of oxycodone distributed. Distribution by practitioners shows both a steep increase and decrease around the peak in 2010. This pattern is likely driven by physicians who were dispensing oxycodone for personal financial gain but were impacted greatly by targeted legal action against these practices.23 24 Pharmacies and hospitals account for greater than 90% of the total MME of oxycodone distributed, and their trends have more in common than differences. Both pharmacy and hospital distribution in MME/person increased yearly until their respective peaks, followed by a decline until 2021. Both inpatient and outpatient opioid prescribing have declined since their peak most likely due to opioid stewardship programmes, prescription drug monitoring programmes, state regulations regarding acute pain quantity limits and heightened awareness by prescribers of the risk of opioid addiction.25 26 Hospitals more aggressively decreased their opioid distribution following the peak; oxycodone MME/person distributed by hospitals in 2021 actually falls below that of 2000, while the amount for pharmacies in 2021 remains above the level in 2000.

Opioid-related deaths as reported by the CDC WONDER database may provide some insight into the effects of variations in oxycodone distribution. There has been over an eightfold increase in deaths from 2000 to 2021. The rise in heroin-related deaths after 2010 is of particular interest, as it closely follows the decrease in oxycodone distribution seen in ARCOS. The decrease in availability of oxycodone may be linked to the increase in use of heroin as a cheaper, more available option.2 As oxycodone distribution continued to drop since 2010, there has been a surge of deaths related to other synthetic narcotics. However, there are several factors to consider, including the availability of opioids other than oxycodone, when interpreting these trends.

While the current, fourth, wave of the opioid epidemic is largely driven by clandestinely produced synthetic narcotics such as fentanyl analogues, prescription opioids including oxycodone continue to play a substantial role. According to the 2022 National Survey on Drug Use and Health, 1.3 million people aged 12 and older initiated prescription pain reliever misuse in 2022. A total of 8.5 million people aged 12 and older misused prescription pain relievers that year, 2.5 million (30.7%) of whom misused oxycodone products.27 Of the people who misused prescription pain relievers, 41.3% received a prescription or stole them from a healthcare provider while 44.6% of them received, bought, or took them from a friend or relative.27 Although opioid deaths due to illicit narcotics are rising at an alarming rate, prescription opioid misuse is still affecting millions of people. Furthermore, restrictions on lawful access to prescription opioids may be leading some proportion of people to seek alternatives from illicit sources.

The distribution of oxycodone peaking in 2010 is possibly due to a reformulation of OxyContin to a more abuse-deterrent form which was harder to crush, for nasal insufflation, and dissolve, for intravenous injection.28 There is support for this change decreasing the misuse potential of the drug,29 30 likely leading to decreased demand for misusers. Also in 2010, there was legal action taken against ‘pill mill’ physicians, who inappropriately prescribed controlled medications, particularly in Florida.31 In the following years, attempts to decrease these harmful practices extended to many other states. However, it is also important to recognise that prior ACROS analyses noted that the peak was only slightly later (2011) for 10 Schedule II opioids22 indicating that provider, payer and patient attitudes towards prescription opioids have undergone substantial changes over the past decade.32

The US stands out considerably from other countries in the world regarding oxycodone consumption. In 2020, the USA accounted for 68.2% of global oxycodone consumption, dwarfing the other major consumers, Germany (5.2%), Canada (3.2%), France (3.1%), China (2.8%), Australia (2.4%) and the UK (2%).33 Regulations in the USA also differ greatly from other countries, where national regulations are more common and guidelines have a larger impact on clinical practice.34 Although the USA develops guidelines at a national level, individual states are responsible for their implementation. A 2019 report from the Organization for Economic Cooperation and Development took an in-depth look at the opioid crisis and policies to address it in its 38 member countries.35 They found that several evidence-based policies were effective in improving outcomes in some countries or US states, such as patient education programmes, training/education initiatives for providers, interventions against stigma, naloxone programmes and syringe programmes. Opioid prescribing guidelines in the USA have been shown to be effective in mitigating opioid prescriptions.36 Although there is much research to be done to validate and develop methods to reduce harm from opioid misuse, there are already actions that can be taken to save lives.37

There are some strengths and limitations to this novel report due to the nature of the data. The ARCOS data are accessible by the public and provide pharmacoepidemiological information that includes Veteran’s Affairs, Indian Health Services facilities, hospitals and independent pharmacies that are unavailable in the IQVIA database.17 However, the database includes all transactions and may be a slight overestimate due to shipments between the same distributors.38 A modest amount of oxycodone reported by ARCOS in the pharmacy, practitioners and teaching institutions21 business activity is used by veterinarians. The database provides licit distribution of oxycodone, and any diversion of the drug to unintended recipients is not publicly available. Similarly, it cannot be determined if patients used the quantity of drug that they were subsequently prescribed. The American Community Survey data are a likely underestimate of actual population due to limitations in counting undocumented individuals.39 Although oxycodone was among the most prescribed and misused opioids from 2000 to 2021 (12 289 518 prescriptions in 2020),40 further research with greater spatial resolution within a single state (eg, Florida) or on other opioids may provide valuable information.

Opioid-related deaths are of particular interest, but linking currently available data to oxycodone in particular may be challenging. While the CDC WONDER data are valuable, it has a few limitations that make it difficult to adequately contextualise the influence of oxycodone in particular. It is not possible to isolate oxycodone from other substances, as the data only go as far as the diagnosis codes for heroin (T40.1), other opioids (T40.2), methadone (T40.3),41 other synthetic narcotics (T40.4) and other and unspecified narcotics (T40.6). This complicates separating the effect of changes in oxycodone distribution from other drugs in the same category. Similarly, it is not possible to parse the relative contribution of oxycodone in cases where multiple substances were involved.

Future work can build on these novel findings by interpreting them through the lens of guidelines and regulations that control the prescribing and distribution of oxycodone as well as justifiable hesitation among some patients to be prescribed opioids for chronic pain. The results of this report can provide beneficial information for development and revision of public health policies. Guidance from governmental agencies is necessary to address problems that are as pervasive and widespread as the opioid epidemic. This oversight is constantly evolving including with the implementation of the CDC’s 2022 update of its Clinical Practice Guideline for Prescribing Opioids.42 It is also important to view these data in relation to the escalating problem that needs to be more fully addressed, opioid overdose deaths.1 The process of decreasing availability of prescription opioids holds the risk of increasing demand from illicit sources, potentially increasing deaths. Investigating the socioeconomic and geopolitical context of states during changes in oxycodone distribution and overdoses may shed some light on how to approach the opioid epidemic in the coming years as the USA continues to correct for prior excesses.43 44 We are cautiously optimistic that other countries will continue to be more judicious with oxycodone than the USA.

Data availability statement

Data are available in a public, open access repository. ARCOS data are publicly accessible at https://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/arcos-drug-summary-reports.html. CDC WONDER data are publicly accessible at https://wonder.cdc.gov/. A python script to extract data from ARCOS Report 5 PDFs (provided at: https://www.deadiversion.usdoj.gov/arcos/retail_drug_summary/arcos-drug-summary-reports.html) and process the data can be found at https://github.com/solgamaj/VARCOS.

Ethics statements

Patient consent for publication

Ethics approval

Not applicable.

Acknowledgments

Audrey L Valentine is appreciated for her contribution to data collection.

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Supplementary materials

Footnotes

  • Contributors JPS: guarantor of the overall content, conception and design of the study, acquisition and analysis of ARCOS/WONDER data, drafting of the manuscript, manuscript revisions and approval. EL: manuscript revisions and approval. MD, JG and KLM: revision and approval of the manuscript. BJP: conception and design of the study, revision and approval of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests BJP was (2019–2021) part of an osteoarthritis research team supported by Pfizer and Eli Lilly and is currently supported by HRSA (D34HP31025) and the Pennsylvania Academic Clinical Research Center. JG was (2019–2021) supported by Pfizer and Eli Lilly.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.