The Opioid Industry Documents Archive: Advancing Public Health Through Industry Document Disclosure.

More than twenty-five years after the first signs of potential harm, the US remains locked in the grip of an opioid epidemic, with more Americans dying from overdoses than ever before.1 Diversion of prescription opioids plays an important role in opioid-related harms. Much of the scientific and public health focus on diversion has been on end-users, given how commonly non-medical prescription opioid use occurs, as well as the proportion of individuals who report that their source of non-medical opioids was friends or family. However, diversion of opioids, as well as their rampant oversupply, can be discerned higher up the supply chain, including among wholesalers, pharmacies and rogue prescribers whose behavior may trigger well-described "flags" warranting further evaluation and action.

Diverting Data and Drugs: A Narrative Review of the Mallinckrodt Documents.

U.S. law imposes strict recording and reporting requirements on all entities that manufacture and distribute controlled substances. As a result, the prescription opioid crisis has unfolded in a data-saturated environment. This article asks why the systematic documentation of opioid transactions failed to prevent or mitigate the crisis. Drawing on a recently disclosed trove of 1.4 million internal records from Mallinckrodt Pharmaceuticals, a leading manufacturer of prescription opioids, we highlight a phenomenon we propose to call data diversion, whereby data ostensibly generated or collected for the purpose of regulating the distribution of controlled substances were repurposed by the industry for the opposite aim of increasing sales at all costs. Systematic data diversion, we argue, contributed substantially to the scale of drug diversion seen with opioids and should become a focus of policy intervention.

Association of State Opioid Duration Limits With Postoperative Opioid Prescribing.

Importance: Since the Centers for Disease Control and Prevention published opioid prescribing guidelines in March 2016, 31 states have implemented legislation to restrict the duration of opioid prescriptions for acute pain. However, the association of these policies with the amount of opioid prescribed following surgery remains unknown. Objective: To examine the association of opioid prescribing duration limits with postoperative opioid prescribing in Massachusetts and Connecticut, the first 2 states to implement limits after March 2016. Design, Setting, and Participants: This interrupted time series analysis and cross-sectional study examined immediate level and slope changes in monthly outcomes after prescribing limit implementation in Massachusetts and Connecticut. These states implemented 7-day limits on initial opioid prescriptions on March 14, 2016, and July 1, 2016, respectively. Using the 2014 to 2017 IBM MarketScan Research Database, 16 281 opioid-naive adults in these states who filled a prescription within 3 days of surgery between July 1, 2014, and November 30, 2017, were identified. Data were analyzed from December 2018 to June 2019. Main Outcomes and Measures: The primary outcome was the prescription size in oral morphine equivalents (OMEs) for the initial postoperative opioid prescription (one 5/325 mg hydrocodone-acetaminophen pill = 5 OMEs). Secondary outcomes included days supplied in the initial prescription and the proportion of initial prescriptions exceeding a 7-day supply. Results: In total, 16 281 opioid-naive patients (9708 [59.6%] female; median [interquartile range] age range, 45-54 [35-44 to 55-64] years) undergoing surgical procedures were included. In Massachusetts, there were 5340 and 5435 patients in the preimplementation and postimplementation periods, respectively. In Connecticut, there were 2869 and 2637 patients in the preimplementation and postimplementation periods, respectively. Limit implementation in Massachusetts was associated with an immediate mean level decrease in prescription size (-38 OMEs [95% CI, -44 to -32 OMEs]) and with a mean decrease in slope (-1.5 OMEs/mo [95% CI, -2.1 to -0.9 OMEs/mo]). Implementation was also associated with an immediate mean level decrease in days supplied (-0.4 days [95% CI, -0.6 to -0.2 days]) and the proportion of prescriptions exceeding a 7-day supply (-5.9 percentage points [95% CI, -7.9 to -3.9 percentage points]). In contrast, limit implementation in Connecticut was not associated with level or slope changes in any outcome. Conclusions and Relevance: Opioid prescribing duration limits had a variable association with postoperative opioid prescribing in Massachusetts and Connecticut. The mean opioid prescription size filled, days supplied, and prescribing exceeding a 7-day supply decreased after limit implementation in Massachusetts only. Given the potential differences in policy dissemination and uptake, efforts to reduce opioid prescribing should also include surgeon education and evidence-based prescribing recommendations.

Scheduling synthetic cathinone substances under the Controlled Substances Act.

BACKGROUND AND RATIONALE: Cathinones are amphetamine analogues that produce stimulant effects with rewarding properties. For many decades, synthetic cathinones have been used in the United States (USA) for abuse purposes, leading to concern about public safety by the federal government. Under the Controlled Substances Act (CSA), the federal government may place drugs with high abuse potential but no currently accepted medical use into Schedule I of the CSA. The process of scheduling an abusable drug involves both the Department of Health and Human Services (HHS), through the Food and Drug Administration (FDA) and the National Institute on Drug Abuse (NIDA), and the Department of Justice, through the Drug Enforcement Administration (DEA). RESULTS: This paper details how numerous synthetic cathinones were placed under CSA control between 1973 and 2018, with an emphasis on 10 cathinones that were placed into Schedule I in 2017 (butylone, naphyrone, pentylone, pentedrone, 3-fluoro-N-methylcathinone (FMC), 4-FMC, 4-methyl-N-ethylcathinone, 4-methyl-pyrrolidinopropiophenone, alpha-pyrrolidinobutiophenone, and α-pyrrolidinopentiophenone). A summary is provided of the scientific and medical analysis performed by HHS, in the form of an Eight-Factor Analysis (8FA), as prescribed by the CSA. This 8FA was then evaluated and signed by the Assistant Secretary for Health at HHS and transmitted to DEA, which permanently placed the 10 cathinones into Schedule I after public notices were published into the Federal Register. DISCUSSION AND CONCLUSIONS: Understanding the scientific data, analysis, and complex process utilized by the US federal government in the CSA scheduling of cathinones with abuse potential and no accepted medical use is important for transparency in governmental decision-making.

The diversion of nonscheduled psychoactive prescription medications in the United States, 2002 to 2017.

PURPOSE: Systematic studies of the diversion of nonscheduled drugs, except for gabapentin, are not apparent. We searched diversion case reports of all other nonscheduled psychoactive prescription drugs in the Researched Abuse, Diversion, and Addiction-Related Surveillance (RADARS) System. METHODS: Case report data are drawn from a quarterly survey of prescription drug diversion completed by a national sample of law enforcement and regulatory agencies. Rates of diversion per 100 000 population were calculated for each year from 2002 to 2017 for prescription medications with greater than 400 reported cases during the period. RESULTS: Cyclobenzaprine, quetiapine, and trazodone met criteria for analysis. We found a significant and steady increase in the diversion of each drug over the period. The 2017 annual rates of diversion per 100 000 population for the three medications range from 0.0428 to 0.0726. Although these rates of diversion are much lower than the rate for total opioid analgesics, they are all more than five times higher in 2017 compared with 2002. While diversion rates for opioids have decreased in recent years, rates for cyclobenzaprine, quetiapine, and trazodone have continued to increase. CONCLUSIONS: A common attribute of the three nonscheduled drugs studied here is that all are used for the treatment and/or self-treatment of opioid withdrawal symptoms, and the increasing diversion of these drugs may be related to the ongoing opioid epidemic and to increasing levels of control over pharmaceutical opioid availability in the United States. Prescribers need to be aware of illicit markets for these medications and prescribe to their patients with appropriate caution.

Physician Training and Qualification to Educate Patients on Attention-Deficit/Hyperactivity Disorder Stimulant Diversion and Misuse.

OBJECTIVES: The increased number of adolescents diagnosed with attention-deficit/hyperactivity disorder (ADHD) in recent years has raised concerns regarding diversion and misuse of prescription stimulant medications. As prescribers of these medications, physicians must be prepared to educate patients on these issues. This is the first study to evaluate physician training and qualification to educate adolescent patients on stimulant diversion and misuse. METHODS: A questionnaire was developed and mailed to a national sample of child and adolescent psychiatrists (CAPs), child neurologists (CNs), and developmental-behavioral pediatricians (DBPs) in the United States. In addition to descriptive statistics, multivariable regressions (log-binomial and ordinal logistic) were performed to identify differences between subspecialists. RESULTS: The final sample consisted of 826 physicians who currently prescribe stimulants. Only 48% of physicians reported receiving formal training on prescription drug diversion (PDD) in medical school, residency, and/or fellowship. Twenty five percent and 48% of physicians felt inadequately qualified to educate patients on the health and legal consequences, respectively, of stimulant misuse and diversion. CAPs were more likely to have received formal training and felt better qualified to educate patients than CNs and DBPs. Physicians who received formal training were 2.4 times more likely to feel adequately qualified to educate patients on these issues. Only 58% of physicians correctly answered a legal question relating to stimulant diversion. CONCLUSIONS: Most physicians have not received formal training on PDD and many feel inadequately qualified to educate patients on the health and legal consequences of stimulant misuse and diversion. Increased training is needed so physicians can effectively educate patients with ADHD.

Association of Hydrocodone Schedule Change With Opioid Prescriptions Following Surgery.

Importance: In 2014, the US Drug Enforcement Administration moved hydrocodone-containing analgesics from schedule III to the more restrictive schedule II to limit prescribing and decrease nonmedical opioid use. The association of this policy change with postoperative prescribing is not well understood. Objective: To examine the hypothesis that the amount of opioids prescribed following surgery is associated with the rescheduling of hydrocodone. Design, Setting, and Participants: An interrupted time series analysis of outpatient opioid prescriptions was conducted to examine the trends in the amount of postoperative opioids filled before and after the schedule change. Opioid prescriptions filled between January 2012 and October 2015 were analyzed using insurance claims data from the Michigan Value Collaborative, which includes data from 75 hospitals across Michigan. A total of 21 955 adult inpatients 18 to 64 years of age who underwent 1 of 19 common elective surgical procedures and filled an opioid prescription within 14 days of discharge to home were eligible for inclusion. Main Outcomes and Measures: The primary outcome was the trends in the mean amount of opioids filled in oral morphine equivalents (OMEs) for the initial postoperative prescriptions before and after the schedule change date of October 6, 2014, compared using interrupted time series and multivariable regression analyses. Secondary outcomes included the total amount of opioids filled and the refill rate for the 30-day postoperative period. Subgroup analyses were performed by hydrocodone prescriptions, nonhydrocodone prescriptions, surgical procedure, and prior opioid use. Results: Data from 21 955 patients undergoing surgical procedures across 75 hospitals and 5120 prescribers were analyzed. Cohorts before and after the schedule change were equivalent with respect to sex (10 197 of 15 791 [64.6%] vs 3966 of 6169 [64.3%] female; P = .69) and mean (SE) age (47.9 [11.2] vs 47.7 [11.3] years; P = .19). After the schedule change, the mean OMEs filled in the initial opioid prescription increased by approximately 35 OMEs (ß = 35.1 [13.2]; P < .01), equivalent to 7 tablets of hydrocodone (5 mg). There were no significant differences in the total OMEs filled during the 30-day postoperative period before and after the schedule change (ß = 18.3 [30.5]; P = .55), but there was a significant decrease in the refill rate (ß = -5.2% [1.3%]; P < .001). Conclusions and Relevance: Changing hydrocodone from schedule III to schedule II was associated with an increase in the amount of opioids filled in the initial prescription following surgery. Opioid-related policies require close follow-up to identify and address early unintended effects given the multitude of competing factors that influence health care professional prescribing behaviors.

The American Academy of Psychiatry and the Law Practice Resource for Prescribing in Corrections.

The practice of prescribing in jails and prisons is often different from that in the community. Serious mental illness is common among inmates, and so are co-morbidities such as substance use, impulse-control, attention-deficit/hyperactivity, and personality disorders. Operational requirements, staffing, and the physical plant of the institution may complicate the provision of treatment according to community standards. Problems related to medication nonadherence, as well as the pursuit of medications for nonmedical reasons, are often seen in these settings and may be managed differently than they are elsewhere. Existing practice resources rarely account for these challenges. Pursuant to a recommendation by the Correctional Committee of the American Academy of Psychiatry and the Law (AAPL), the AAPL Council in May 2015 approved the creation of a task force charged with producing a document on prescribing in correctional facilities.Full Document: Tamburello A, Metzner J, Ferguson E, et al: AAPL practice resource for prescribing in corrections. Journal of the American Academy of Psychiatry and the Law Online Supplement 2018, 46 (2). Available at: http://www.jaapl.org/content/46/2_Supplement.

Controlled Substances Quotas. Final rule.

The Drug Enforcement Administration (DEA) is publishing this final rule to strengthen the process for setting controls over diversion of controlled substances and make other improvements in the quota management regulatory system for the production, manufacturing, and procurement of controlled substances.

Impact of the Hydrocodone Schedule Change on Opioid Prescription Patterns in South Dakota.

INTRODUCTION: Prescription opioid use is becoming increasingly common; consequently, opioid overdose deaths are increasing at an alarming rate. Hydrocodone, one of the most commonly abused opioids, was changed from a schedule III controlled substance to the more stringent schedule II to decrease abuse and diversion, effective Oct. 6, 2014. The objective of this study was to examine the impact of the hydrocodone schedule change on opioid prescribing in South Dakota. METHODS: Opioid prescription patterns were examined in the following six-month phases: the baseline phase before the change, the transition phase when existing hydrocodone prescriptions could still be refilled, and the final phase. The South Dakota Board of Pharmacy Prescription Drug Monitoring Program provided aggregate monthly data for South Dakota opioid prescriptions (i.e., total number of prescriptions and days supplied), including urban and rural stratification. T-tests were performed on the monthly values for each phase to determine the significance of differences in prescription features between phases. RESULTS: The number of hydrocodone prescriptions significantly decreased 14 percent from baseline to final phase, while the days supplied per prescription significantly increased 7.4 percent. These changes were greater in rural areas than in urban areas. Conversely, the number of other opioid prescriptions significantly increased by 6.5 percent over this timeframe. CONCLUSIONS: The number of hydrocodone prescriptions decreased, while the days supplied per prescription increased. These changes were greater in rural areas than in urban areas. In addition, the number of other opioid prescriptions increased. These trends may reflect some unintended effects of the schedule change.

Schedules of Controlled Substances: Extension of Temporary Placement of THJ-2201, AB-PINACA and AB-CHMINACA in Schedule I of the Controlled Substances Act. Temporary order.

The Administrator of the Drug Enforcement Administration is issuing this temporary order to extend the temporary schedule I status of three synthetic cannabinoids pursuant to the temporary scheduling provisions of the Controlled Substances Act. The substances are: [1-(5-Fluoropentyl)-1H-indazol-3-yl](naphthalen-1-yl)methanone (THJ-2201); N-1-Amino-3-methyl-1-oxo-2-butanyl]-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA); N-[1-Amino-3-methyl-1-oxo-2-butanyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA), including their optical, positional and geometric isomers, salts, and salts of isomers. The current final order temporarily placing THJ-2201, AB-PINACA and AB-CHMINACA into schedule I is in effect through January 29, 2017. This order will extend the temporary scheduling of THJ-2201, AB-PINACA and AB-CHMINACA for one year, or until the permanent scheduling action for these three substances is completed, whichever occurs first.

Medication Assisted Treatment for Opioid Use Disorders Reporting Requirements. Final rule.

This final rule outlines annual reporting requirements for practitioners who are authorized to treat up to 275 patients with covered medications in an office-based setting. This final rule will require practitioners to provide information on their annual caseload of patients by month, the number of patients provided behavioral health services and referred to behavioral health services, and the features of the practitioner's diversion control plan. These reporting requirements will help the Department of Health and Human Services (HHS) ensure compliance with the requirements of the final rule, "Medication Assisted Treatment for Opioid Use Disorders," published in the Federal Register on July 8, 2016.

Non-prescription sale and dispensing of antibiotics in community pharmacies in Zambia.

BACKGROUND: In Zambia, antibiotics are categorized as prescription-only medicines. Antibiotics dispensed without a prescription pose a public health threat, which is a concern. Consequently, the aim is to ascertain the extent of non-prescription sales and dispensing of antibiotics in community pharmacies in Zambia. METHODS: The practice of non-prescription sale and dispensing were assessed in 73 randomly selected community retail pharmacies, using a structured interviewer-administered questionnaire with simulated case scenarios. RESULTS: Majority (97%) stated that clients frequently requested non-prescribed antibiotics. Interviewees usually asked clients' indications (94%), counselled on dosing (96%) and suggested changes to antibiotic choices (97%). All (100%) dispensed non-prescribed antibiotics. Commonly dispensed antibiotics included amoxicillin (52%), cotrimoxazole (25%) and metronidazole (23%). Non-prescription sale and dispensing of antibiotics was significantly associated with interviewees' professional qualification in four out of five simulations. CONCLUSION: Non-prescription sale and dispensing of antibiotics is widespread in Zambia. Concerted public and professional interventions are needed coupled with stronger regulatory enforcement to reduce this.

Revision of Import and Export Requirements for Controlled Substances, Listed Chemicals, and Tableting and Encapsulating Machines, Including Changes To Implement the International Trade Data System (ITDS); Revision of Reporting Requirements for Domestic Transactions in Listed Chemicals and Tableting and Encapsulating Machines; and Technical Amendments. Final rule.

The Drug Enforcement Administration is updating its regulations for the import and export of tableting and encapsulating machines, controlled substances, and listed chemicals, and its regulations relating to reports required for domestic transactions in listed chemicals, gamma-hydroxybutyric acid, and tableting and encapsulating machines. In accordance with Executive Order 13563, the Drug Enforcement Administration has reviewed its import and export regulations and reporting requirements for domestic transactions in listed chemicals (and gamma-hydroxybutyric acid) and tableting and encapsulating machines, and evaluated them for clarity, consistency, continued accuracy, and effectiveness. The amendments clarify certain policies and reflect current procedures and technological advancements. The amendments also allow for the implementation, as applicable to tableting and encapsulating machines, controlled substances, and listed chemicals, of the President's Executive Order 13659 on streamlining the export/import process and requiring the government-wide utilization of the International Trade Data System (ITDS). This rule additionally contains amendments that implement recent changes to the Controlled Substances Import and Export Act (CSIEA) for reexportation of controlled substances among members of the European Economic Area made by the Improving Regulatory Transparency for New Medical Therapies Act. The rule also includes additional substantive and technical and stylistic amendments.

Opioid Overdose Deaths and Florida's Crackdown on Pill Mills.

OBJECTIVES: We examined the effect on opioid overdose mortality of Florida state laws and law enforcement operations targeting "pill mills." METHODS: We collected 2003 to 2012 mortality data from the Florida Department of Health and the North Carolina State Center for Health Statistics (the comparison state) to estimate changes in the rates of death from prescription opioid, heroin, or any opioid overdose. RESULTS: Florida's actions were associated with an estimated 1029 lives saved from prescription opioid overdose over a 34-month period. Estimated reductions in deaths grew over the intervention period, with rates per 100,000 population that were 0.6 lower in 2010, 1.8 lower in 2011, and 3.0 lower in 2012 than what would have been expected had the changes in mortality rate trends in Florida been the same as changes in trends in North Carolina. Florida's mortality rates from heroin and total opioid overdose were also lower than anticipated relative to changes in trends in North Carolina. CONCLUSIONS: Findings from this study indicate that laws regulating pain clinics and enforcement of these laws may, in combination, reduce opioid overdose deaths.