Do laws impact opioids consumption? A breakpoint analysis based on Italian sales data

Purpose: In Italy, where the adoption of opioid analgesics in pain management has been historically poor, an increase in opioids consumption occurred between 2000 and 2015. The aim of this study is to assess, through specific time series analyses for trend changes, the impact of different intervening factors \u2013 such as the availability of new drugs, the observance of clinical guidelines, changes in prescription regulations, and in reimbursement policies \u2013 on opioids sales to community pharmacies in Italy, focusing on the time period 2000\u20132010. Materials and methods: Five opioids were considered: codeine, tramadol, buprenorphine, morphine, and fentanyl. The analysis is based on sales data collected at wholesale distributors. For each one of the five drugs, time series of the number of Defined Daily Doses per thousand inhabitants per day in the period 2000\u20132010 were analyzed, and an estimation of breakpoints was performed using segmented linear regression. Results: Drug sales underwent a sharp increase in 2000\u20132010, although on different scales. Segmented regression analysis highlighted different potential breakpoints, corresponding to either a significant change in value and/or in slope. Sales of the five opioids were affected by at least one relevant event, often due to a synergy of regulatory, marketing, and technological factors. The effect of reimbursement changes has proved important. Conclusion: Between 2000 and 2010, regulatory, technological, and reimbursement changes significantly influenced opioid sales to community pharmacies in Italy. The sales of relatively new drug products seem to be less influenced by changes in reimbursement and regulatory policies than that of more established products, suggesting that physicians are more comfortable with \u201cold\u201d drugs, since their clinical use is supported by established clinical guidelines and protocols