New Opioid Analgesic Approvals and Outpatient Utilization of Opioid Analgesics in the United States, 1997 Through 2015

Grace Chai, Pharm.D.; Jing Xu, Ph.D., M.A.; James Osterhout, Ph.D.; Mark A. Liberatore, Pharm.D., R.A.C.; Kathleen L. Miller, Ph.D.; Carolyn Wolff, Ph.D.; Marisa Cruz, M.D.; Peter Lurie, M.D., M.P.H. and Gerald Dal Pan, M.D., M.H.S.


Anesthesiology. 2018;128(5):953-966. 

In This Article

Materials and Methods

We obtained data on all new drug applications and abbreviated new drug applications approved for opioid analgesic products between 1997 and 2015.[12] New drug application products include those with new active ingredients, new formulations, and new dosage forms.[13] Abbreviated new drug application products are generic versions of products approved under new drug applications.[14]

National estimates of the number of prescriptions dispensed for opioid analgesics were obtained from a proprietary database available to the U.S. Food and Drug Administration under contract, IQVIA (USA), National Prescription Audit, for January 1997 through December 2015; data before 1997 were not available. The National Prescription Audit captures approximately 3.5 billion prescription claims (88% of U.S. retail prescriptions) annually from a sample of 46,000 out of the approximately 59,400 U.S. outpatient retail pharmacies, which are then projected to provide national-level estimates. Changes to the underlying source data and projection methodologies were conducted by IQVIA over time for greater accuracy. Prescriptions covered by commercial third-party payers, Medicaid, or Medicare, and cash payments are included. Prescription data were analyzed by active moiety (Appendix 1), by formulation (e.g., immediate-release, extended-release), and by "brand" (brand or branded generic) or "generic."

Prescriptions in the National Prescription Audit classified as "brand or branded generic" products include all trade name products. "Generic" products in the National Prescription Audit include products with no trade name. Of note, these classifications of "brand" and "generic" prescriptions do not precisely align with the U.S. Food and Drug Administration's definitions of products based on new drug application or abbreviated new drug application approval. Prescriptions for products approved as new drug applications and abbreviated new drug applications were classified as "brand" prescriptions if they had a trade name,[15,16] while prescriptions for products with no trade name, including some approved as new drug applications (Appendix 2), were captured as "generic" prescriptions. Under the National Prescription Audit classification system, most abbreviated new drug application products are captured as "generic" prescriptions. Because authorized generics are products marketed under existing new drug applications without separate U.S. Food and Drug Administration approvals, they could not be counted as separate approvals,[17] but were captured as "generic" prescriptions.

All formulations of opioid analgesics were included, except for injectable formulations, which are not commonly dispensed in the outpatient setting. Opioid-containing products used as part of medication-assisted treatment for opioid dependence and opioid-containing cough/cold products were not included in our analysis because of their different indications and patterns of use. Thus, methadone dispensed as medication-assisted treatment from methadone clinics was not captured in the database, but all other methadone prescriptions dispensed from retail pharmacies were included in the analysis.

We also quantified the total amount of morphine milligram equivalents dispensed based on standardization of total dispensed opioid prescriptions across the different active moieties, quantity, and strength of doses. To calculate overall morphine milligram equivalents dispensed per year, we calculated the milligrams of opioids dispensed annually by a morphine milligram equivalents conversion factor for each opioid analgesic using conversion factors outlined in a recent publication by the Centers for Disease Control and Prevention (Atlanta, Georgia).[18]

We first reported new opioid analgesic product approvals in the United States from 1997 through 2015 by year of approval for new drug applications and abbreviated new drug applications. Next, we show the total opioid analgesic market for brand and generic products by both the nationally estimated number of total prescriptions and morphine milligram equivalents dispensed and prescriptions dispensed adjusted for the total U.S. population calculated using U.S. Census data.[19] We also calculated the market share of all new opioid analgesic brand products approved between 1997 and 2015. Our analyses also included all prescriptions dispensed for brand OxyContin (Purdue, USA). OxyContin was originally approved in 1995 before our study period; subsequently another new drug application was approved in 2010 as a reformulation of the original OxyContin, at which time the marketing of the original product ceased. We recorded the approval of the reformulated product as a new brand approval, although we did not distinguish between the original formulation and the new formulation in our calculations of total OxyContin prescriptions dispensed.

Additional supplemental analyses were performed to assess generic opioid analgesic approvals and prescription patterns for the years 1997 through 2015. First, we conducted an analysis of new and additional generic products approved after 1997 for the six most frequently dispensed opioid analgesics in 2015. Next, we analyzed opioid analgesics for which the first generic was initially dispensed between 2006 and 2015, as these represent the clearest cases for interpretation in the current opioid market. Descriptive statistics and calculation of morphine milligram equivalents were conducted using Excel (Microsoft, USA); no statistical hypothesis testing was performed.