key: cord-0876450-mdc8trdh authors: Gomes, Tara; Kim, Katherine Callaway; Suda, Katie J.; Garg, Ria; Tadrous, Mina title: International trends in prescription opioid sales among developed and developing economies, and the impact of the COVID‐19 pandemic: A cross‐sectional analysis of 66 countries date: 2022-04-30 journal: Pharmacoepidemiol Drug Saf DOI: 10.1002/pds.5443 sha: ac31eb3d49467a42809d7310863e962626a97ba8 doc_id: 876450 cord_uid: mdc8trdh PURPOSE: We sought to compare trends in opioid purchasing between developed and developing economies to understand patterns of opioid consumption, and how they were impacted by the COVID‐19 pandemic. METHODS: We conducted a retrospective cross‐sectional study of retail pharmacy opioid sales from 66 jurisdictions between July 2014 and August 2020. We measured monthly population‐adjusted rate of opioid units purchased, stratified by development group and country, and used interventional time series analysis to assess the impact of the COVID‐19 pandemic on rates of opioid purchasing among developed and developing economies separately. RESULTS: Rates of opioid purchasing were generally higher among developed economies, although trends differed considerably by development group. Rates of opioid purchasing declined 23.8% (95% confidence interval [CI] −34.7% to 3.6%) in the 5 years prior to the pandemic in developed economies, but rose 15.2% (95% CI 4.6%–35.6%) among developing economies. In March 2020 there was a short‐term increase in the rate of opioid purchases in both developing (10.9 units/1000 population increase; p < 0.0001) and developed (145.5 units/1000 population; p < 0.0001) economies, which was followed immediately by reduced opioid purchasing of a similar scale in April–May 2020 (−14.8 and −171.8 units/1000 population in developing and developed economies, respectively; p < 0.0001). CONCLUSION: The COVID‐19 pandemic led to disruptions in opioid purchasing around the world; although the specific impacts varied both between and among developed and developing economies. With global variation in opioid use, there is a need to monitor these trajectories to ensure the safety of opioid use, and adequate access to pain management globally. The substantial burden of opioid-related harm in North America, particularly in the decade after the introduction of long-acting oxycodone, has been tied, in part, to aggressive opioid marketing strategies and overprescribing of long-term opioid therapy for chronic noncancer pain (CNCP). 1, 2 Specifically, the United States and Canada are among the highest consumers of opioids worldwide, with 143 million opioid prescriptions dispensed in the US in 2020, and approximately 1 out of 8 Canadians being prescribed an opioid in 2017. 3, 4 While the rate of opioid prescribing in North America remains unparalleled on a global scale, significant increases in prescribing trends have also been observed in other high-income countries. 5 For example, Blanch et al, reported a 15-fold increase in overall opioid prescription numbers within Australia between 1990 and 2015, 6 and England saw a 127% increase in total volume of opioids prescribed between 1998 and 2016. 7 While the use of opioid analgesics for chronic cancer pain is supported with evidence, calls have been made for increased opioid stewardship for acute and CNCP. 8 As a result, many countries have released guidelines providing evidence-informed recommendations to support safe opioid prescribing practices for long-term CNCP management. 9, 10 Since this time, several national studies have reported a decline in prescription for opioids; from 2017 to 2018, the United States reported a 17% decline in the overall volume of opioids prescribed-the largest single-year drop ever recorded. 11 These regulatory changes to opioid availability in North America have led to large reductions in profits for manufacturers, who appear to have shifted their marketing efforts to developing economies. For example, in 2017, the US congress informed the World Health Organization (WHO) of Purdue Pharma's global counterpart Mundipharma International, stating Mundipharma was using many of the same "deceptive" and "reckless" practices to sell oxycodone abroad, that they had once used in North America. 12 Additionally, the International Narcotics Control Board (INCB) has reported a significant increase in the non-medical use of tramadol between 2010 and 2019 among developing economies, particularly in West and North Africa, the Middle East, and South Asia. 13 While increased access to opioids to manage pain may be warranted in regions with historically low access to analgesic medication, unfettered expansion of marketing of opioid prescribing in the absence of appropriate opioid prescribing policies and stewardship activities may put developing economies at risk of increased opioidrelated harm if patterns similar to those observed in North America were replicated. More recently, the arrival of the COVID-19 pandemic has introduced interruptions into the supply of pharmaceuticals worldwide, leading to concerns related to drug shortages, and changes in the ways chronic medications are made available. 14 For example, both the US and Canada have reported substantial reductions in opioid prescribing in the months following March 2020, 15, 16 likely reflecting a combination of COVID-mandated changes in policy, and fewer 2 surgeries and dental procedures during the pandemic. Despite documented trends in North America, there is little information on the impacts of the ongoing pandemic on access to pharmaceutical opioids in other developed economies. Therefore, we conducted a study to compare trends in the rate of opioid purchasing between developed and developing economies around the world, to understand shifting patterns of opioid consumption over time, and to evaluate the impact of the COVID-19 pandemic on these trajectories. We conducted a monthly, cross-sectional study of national retail prescription opioid sales data from 66 countries and jurisdictions between July 2014 and August 2020 using IQVIA's Multinational Integrated Data Analysis (MIDAS) database (Parsippany, NJ, USA), which contains opioid purchasing data from 69 countries/regions. Specifically, data is obtained from annual transactions from pharmaceutical manufacturers to wholesaler distribution centers and represents a national survey of prescription drug sales. We excluded data from hospital and long-term care settings, from countries with no opioid data (N = 2) and from Venezuela where the economic crisis led to a highly irregular pattern of drug purchasing. The 66 countries in our final sample comprised approximately 72.6% of the world's population in 2019 (Table S1 in supplement). Data in the MIDAS database is reported as the number of total standardized drug units purchased, with a unit defined as a single tablet/capsule, patch, vial or 5 ml oral liquid. Data are internally validated each year through a standardized quality assurance program which validates sales data for each product against alternate sources by comparing estimated sales volumes against clients' actual sales volumes. 17, 18 Medication sales data is projected to represent national pharmacy sales across all jurisdictions, regardless of payer. 17 We identified opioid and opioid-combination products within eight classes of opioids that are currently marketed and indicated to manage pain (Table S2 ): (1) codeine, (2) tramadol, (3) oxycodone, (4) hydrocodone, (5) morphine, (6) hydromorphone, (7) fentanyl, and (8) other opioids (butorphanol, dihydrocodeine, levorphanol, opium, oxymorphone, pentazocine, ketobemidone, buprenorphine, and tapentadol). We excluded methadone and buprenorphine/naloxone as they are most commonly used to treat opioid use disorder. Country-level changes in the rate of opioid prescribing varied considerably by development status and by jurisdiction (Figure 2 and Early in the COVID-19 pandemic, there was a temporary disruption in opioid prescribing, which was apparent in both developed and developing economies among all frequently prescribed opioids ( Figure 1 ). In opioids, which could be dispensed to protect unstable drug supplies and prevent gaps in access for patients. 19, 21 Second, as public health restrictions were introduced around the world, many people experienced challenges accessing healthcare providers, and there was a reduction in surgeries and dental services which as often associated with opioid use. Therefore, our findings suggest that gaps in accessing care and pharmacy services may have also led to interruptions in opioid therapy. It is impossible to disentangle these two phenomena with this data, and it is likely that each jurisdiction was impacted differently by drug shortages and pandemic-related public health measures. Although rates of opioid use vary considerably around the world, with differing dynamics within and between developmental groups, the COVID-19 pandemic led to considerable interruptions in opioid purchasing in nearly all jurisdictions studied. As we can anticipate that rates of opioid purchasing will continue to climb in many developing economies as drug supplies are re-established during the COVID-19 pandemic, it is important to work proactively to determine the appropriateness of pharmaceutical marketing practices and changing opioid prescribing to support the safe use of opioids while also addressing needs for pain management. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs, the U.S. government, or of IQVIA or any of its affiliated entities. The statements, findings, conclusions, views, and opinions contained and expressed in this publication are based in part on data obtained under license from IQVIA as part of the IQVIA Institute's Human Data Science Research Collaborative. The authors would like to acknowledge Anita Iacono who supported some elements of the data analysis. The authors declare no conflict of interest. This study was approved by the University of Pittsburgh Institutional Review Board. None. IQVIA supported this work with free access to the data for a limited period of time. Due to its proprietary nature, data from this study cannot be shared by the authors. The data that support the findings of this study are available (at a cost) from IQVIA. 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