Prepared for: North Carolina Division of Public Health, Injury and Violence Prevention Branch

Reducing Unintentional Prescription Drug Overdose Deaths in North Carolina: Policy Implications based on Current Public Health Surveillance Systems and Law Enforcement Records Prepared for: North Carolina Division of Public Health, Injury and Violence Prevention Branch Prepared by: Emily Tiry Master of Public Policy Candidate Sanford School of Public Policy Duke University Faculty Advisor: Philip J. Cook April 19, 2013

Executive Summary Background In North Carolina, the number of deaths from unintentional drug overdoses has increased more than 300 percent in just over a decade, from 279 in 1999 to 1,140 in 2011. An increasing proportion of these deaths come from prescription drugs as opposed to illicit drugs. In particular, prescription opioids are involved in a majority of unintentional drug overdose deaths. Prescription drug overdose deaths are preventable, yet the death toll continues to increase. This dramatic increase is a relatively new phenomenon and the regulatory structure around prescription drugs differs in important ways from the one around illicit drugs. With that in mind, the goal of this paper is to examine and evaluate the current public health surveillance systems and law enforcement records with regard to unintentional prescription drug overdoses in North Carolina. In particular, it looks at the extent to which these systems record information about the source of the drugs involved in the overdose. Before we can design effective interventions to reduce unintentional overdoses, we need to know how victims obtain the drugs that contribute to their deaths, as well as whether and where that information exists. Policy Options There are many paths through which those at risk of a fatal prescription drug overdose may obtain the drugs that contribute to their deaths, including through legitimate prescriptions; doctor shopping; non-legitimate prescriptions ( pill mills ); receiving, purchasing, or stealing from family or friends; and purchasing on the street. Each path requires a different type of intervention; therefore, determining the relative importance of each path will guide recommendations for improving existing policies or implementing new ones. Several programs have already been implemented in North Carolina, each primarily addressing one source. These include Project Lazarus (legitimate prescriptions), the North Carolina Controlled Substances Reporting System (CSRS) (doctor shopping), the State Bureau of Investigation s Diversion and Environmental Crimes Unit (nonlegitimate prescriptions and purchasing on the street), and Operation Medicine Cabinet (receiving or stealing from family or friends). i

Data and Methods Using a data set compiled by the North Carolina Division of Public Health s Injury and Violence Prevention Branch, I analyzed the characteristics of the unintentional pharmaceutical-related overdose deaths in North Carolina from 2010. This data set included information from death certificates, medical examiner files, and controlled substance prescription records. The analysis included categorizing cases according to the number and currency of controlled substance prescriptions as well as according to the types of drugs contributing to death. I also looked for evidence of diversion among the cases. This included identifying doctor shopping using three different criteria as well as identifying other types of diversion from information available in the medical examiner narratives. Finally, I evaluated how providers, pharmacists, and the State Bureau of Investigation are using the North Carolina Controlled Substance Reporting System. Results Of the 707 cases that were analyzed, unintentional prescription overdose victims were more likely to be male, white, and/or between the ages of 35 and 54. Over half of the cases (57 percent) had at least one current prescription for a controlled substance at the time of death. Additionally, of those who did have at least one current prescription, 72 percent had a current prescription for a drug that also contributed to their deaths. Opioids were by far the most common type of drug to contribute to death. Overall, opioids contributed to 94 percent of deaths, followed by benzodiazepines at 28 percent. In fact, all of the top ten specific drugs (e.g., oxycodone, alprazolam) to contribute to death were either an opioid or a benzodiazepine. Opioids and benzodiazepines were also more likely to contribute to death for those cases who had at least one current prescription for a contributory drug than for those who did not. The three doctor shopping criteria produced widely varying estimates, from a low of 16 cases using medical examiner narratives to a high of 252 cases using a criterion of filling prescriptions from at least five different prescribers in one year. The medical examiner narratives contained information about diversion sources for 78 cases, the most common source mentioned being receiving or stealing from family or friends. Fewer than half of the cases were looked up in the CSRS by anyone in the year before their deaths, which may have contributed to excessive prescriptions. ii

Conclusions and Policy Implications Although North Carolina currently has a system in place that is intended to ensure that controlled substances are prescribed and used safely, unintentional overdoses from these drugs continue to increase. Though they are not definitive, these results provide at least preliminary evidence about where the system is failing, which can in turn guide potential policy changes. The following recommendations are based on my evaluation of the current public health surveillance system and law enforcement records: Promote and evaluate increased use of the CSRS among prescribers and pharmacists when prescribing or dispensing an opioid or benzodiazepine. Develop criteria to identify unusual or suspicious patterns of prescribing by providers. Develop police investigation guidelines for collecting consistent information related to intent and to the source of the contributing drug(s). Create a comprehensive surveillance system to monitor and analyze prescription drug overdose trends over time. However, any policy to reduce overdose deaths should minimize a chilling effect, which would unnecessarily restrict access to these drugs for those who have a legitimate need for them. Additionally, a comprehensive strategy to reduce overdose deaths should also attempt to reduce spillover from prescription drug overdoses to heroin overdoses, as well as address the demand side of prescription drug abuse. iii

Introduction In North Carolina, the number of deaths from unintentional drug overdoses has increased more than 300 percent in just over a decade, from 279 in 1999 to 1,140 in 2011. An increasing proportion of these deaths come from prescription drugs as opposed to illicit drugs. In particular, prescription opioids are involved in a majority of unintentional drug overdose deaths. Prescription drug overdose deaths are preventable, yet the death toll continues to increase. This dramatic increase is a relatively new phenomenon and the regulatory structure around prescription drugs differs in important ways from the one around illicit drugs. With that in mind, the goal of this paper is to examine and evaluate the current public health surveillance systems and law enforcement records with regard to unintentional prescription drug overdoses in North Carolina. In particular, it looks at the extent to which these systems record information about the source of the drugs involved in the overdose. Before we can design effective interventions to reduce unintentional overdoses, we need to know how victims obtain the drugs that contribute to their deaths, as well as whether and where that information exists. Using a data set compiled by the North Carolina Division of Public Health s Injury and Violence Prevention Branch, I analyzed the characteristics of the unintentional pharmaceutical-related overdose deaths in North Carolina from 2010. This data set included information from death certificates, medical examiner files, and controlled substance prescription records. The analysis included categorizing cases according to the number and currency of controlled substance prescriptions as well as according to the types of drugs contributing to death. I also looked for evidence of diversion among the cases. This included identifying doctor shopping using three different criteria as well as identifying other types of diversion from information available in the medical examiner narratives. Finally, I evaluated how providers, pharmacists, and the State Bureau of Investigation are using the North Carolina Controlled Substance Reporting System. Of the 707 cases that were analyzed, 41 percent had a current prescription for a drug that also contributed to their deaths. Opioids were by far the most common type of drug to contribute to death. In fact, all of the top ten specific drugs (e.g., oxycodone, alprazolam) to contribute to death were either an opioid or a benzodiazepine. The medical examiner narratives contained information about diversion sources for only 78 cases. Fewer than half of the cases were looked up in the CSRS by anyone in the year before their deaths, which may have contributed to excessive prescriptions. 1

In light of these findings, I recommend four policies: (1) promote and evaluate increased use of the CSRS among prescribers and pharmacists when prescribing or dispensing an opioid or benzodiazepine; (2) develop criteria to identify unusual or suspicious patterns of prescribing by providers; (3) develop police investigation guidelines for collecting consistent information related to intent and to the source of the contributing drug(s); and (4) create a comprehensive surveillance system to monitor and analyze prescription drug overdose trends over time. In the remainder of the paper, I will briefly describe the history of unintentional prescription drug overdoses, the regulatory scheme for prescribing controlled substances, the mechanisms through which victims may obtain prescription drugs, and what we know so far about which populations are at greatest risk. Then, using the possible mechanisms for obtaining drugs as a framework, I discuss the policy options for reducing unintentional overdoses. Then, I explain the data sources I used and how they are created. In the next section I give the results of my analysis, and finally, I end with a discussion of the findings and what they mean for possible policy options. Background In North Carolina, the number of deaths from unintentional drug overdoses has increased more than 300 percent in just over a decade, from 279 in 1999 to 1,140 in 2011. From 1999 to 2010, the rate increased from 3.2 to 9.4 overdose deaths per 100,000 population (Hirsch 2012). The proportion of unintentional overdose deaths from prescription opioids has also increased; opioids now account for more deaths than cocaine and heroin combined both nationwide and in North Carolina (CDC 2011; Harmon 2010). 2

Total Overdose (Poisoning) Deaths by Intent in North Carolina, 1999-2011* 1200 1000 1140 800 600 400 Unintentional Suicide Undetermined 200 0 195 32 * Data from CDC WONDER Online Database In the decade from 1997 to 2007, the volume of prescribed opioids increased from 100 to 700 morphine milligram equivalents (MME) per person, paralleling the increase in unintentional opioid overdose deaths (Paulozzi 2011). This increase in prescribing came as a result of several factors, including a Joint Commission recommendation that pain should be assessed as the fifth vital sign, the use of pain scores to measure patient satisfaction, and the release of clinical guidelines in 1997 that expanded the use of longterm opioid treatment for chronic non-cancer pain (Perrone 2012; Hall et al. 2008). Regulation of prescription opioids and other Schedule II-IV controlled substances necessarily differs from regulation of Schedule I illicit substances. By definition, non- Schedule I substances have a recognized medical benefit (NC Controlled Substances Act 1971). Prescription drugs themselves are not illicit; however, the manner in which they are used may be. In light of this, the supply of prescription drugs is likely to be much different from that of illicit drugs (Fischer et al. 2010). For example, nearly all prescription drugs involved in overdoses are originally prescribed by a doctor (as opposed to being stolen from a pharmacy, say), whereas illicit drugs cannot be prescribed. However, many overdose victims do not get their drugs directly from a doctor s prescription. There are several sources through which people at high risk for a fatal drug overdose may obtain prescription drugs (and thus several possible points for intervention). One category is obtaining prescription drugs from a legitimate medical 3

source, which mainly occurs through prescriptions from a non-complicit doctor. 1 The other main category is diversion, which includes several mechanisms for obtaining prescription drugs, such as sharing among family and friends, doctor shopping, receiving prescriptions from a complicit doctor ( pill mills ), buying on the street, and obtaining through forgery or theft (Fischer et al. 2010). Results from the 2010 National Survey on Drug Use and Health showed that 71 percent of nonmedical users of prescription pain relievers obtained the drug they most recently used from family or a friend (SAMHSA 2010). However, few studies have been done to determine the drug sources for fatal overdose victims, who may differ from nonmedical users who are still alive and may include both medical and nonmedical users. A recent study from Utah conducted interviews with the next of kin or best contact of opioidrelated overdose victims about the victims most common source of prescription pain medication. The categories are not mutually exclusive because some victims obtained drugs from multiple sources, but the most common source was obtaining them directly from a health care provider (92 percent), followed by obtaining them for free from family or friends (24 percent), obtaining them from someone without their knowledge (18 percent), and by purchasing from family or friends (16 percent) (Johnson et al. 2012). Additionally, a study in West Virginia suggested that methods of diversion differed among subpopulations of fatal overdose victims. Those who obtained prescription drugs through doctor shopping were less likely to fit the traditional conception of drug abusers and were more likely to be older, female, and live in higher income counties. Those who obtained prescription drugs through other methods of diversion than doctor shopping were more likely to be associated with the traditional characteristics of street drug users (Hall et al. 2008). Another West Virginia study looked at the doctor and pharmacy shopping behavior of controlled substance overdose victims. The authors used a doctor shopping criteria of receiving a prescription from at least four providers within six months and a pharmacy shopping criteria of filling a prescription at at least four pharmacies within six months. They found that about 25 percent of cases fit the criteria for doctor shopping and 17 percent fit the criteria for pharmacy shopping (Peirce 2012). High-risk groups for fatal prescription drug overdose include chronic pain patients, people with a history of substance abuse, and people with mental health problems. Several studies have documented an association between non-medical prescription opioid use and both mental health issues and chronic pain (Amari et al. 2011). This association also holds for unintentional prescription drug overdose deaths: nearly half of 1 Complicit is defined as prescribing a controlled substance other than for a legitimate medical purpose 4

decedents in West Virginia in 2006 had a history of mental illness, and over half had a history of chronic pain (Toblin 2010). Policy Options There are many paths through which those at risk of a fatal prescription drug overdose may obtain the drugs that contribute to their deaths, including through legitimate prescriptions; doctor shopping; non-legitimate prescriptions ( pill mills ); receiving, purchasing, or stealing from family or friends; and purchasing on the street. Each path requires a different type of intervention; therefore, determining the relative importance of each path will guide recommendations for improving existing policies or implementing new ones. Legitimate Prescribing Because nearly all prescription drugs involved in overdoses are originally prescribed by a doctor, much of the focus has been on interventions that address prescribing, both for legitimate patients and doctor shoppers. A possible intervention to reduce overdoses from legitimately prescribed drugs is provider education and health system policy changes. Project Lazarus, a multifaceted community-based overdose prevention program that began in Wilkes County in 2005, includes a provider education component for managing chronic pain and safe opioid prescribing (Albert et al. 2011). In addition to educating providers about safe prescribing, it may also be necessary to educate patients about misuse of controlled substances, especially about taking only the amount prescribed and about possible interactions that could occur when taken with other medications or alcohol. Doctor Shopping One current strategy that states have been developing to deal with the prescription drug overdose problem is the use of prescription drug monitoring programs (PDMPs). These programs are designed to track prescribing of controlled substances, including opioids. Every state except Missouri has either an operational PDMP or has enacted legislation authorizing one (NAMSDL 2012). North Carolina passed legislation authorizing the Controlled Substances Reporting System (CSRS) in 2005; it became operational in July 2007. The legislation requires 5

pharmacies to submit records of every dispensed prescription for a controlled substance in North Carolina within seven days of dispensation. Certain situations do not require reporting into the CSRS, such as when controlled substances are administered on site in opioid treatment programs and hospitals. The law also specifies what information pharmacies must report, as well as who can access the data. 2 Groups that are allowed access to the CSRS include anyone licensed to prescribe controlled substances, pharmacists, medical examiners, and agents of the State Bureau of Investigation (NC Controlled Substances Reporting System Act 2005). The CSRS is housed in the Division of Mental Health, Developmental Disabilities, and Substance Abuse Services (DMHDDSAS). CSRS staff are responsible for monitoring unusual patterns of prescribing for patients, which is currently defined as receiving a prescription from at least ten prescribers or filling a prescription at at least five pharmacies within 90 days. A staff member generates a report of people meeting these criteria and a report of the top ten recipients of prescriptions for controlled substances. Providers also call to notify CSRS staff of patients of concern. Anyone under suspicion is investigated further to determine whether to report them to the Attorney General. For example, they look for evidence that the person has recently gone into treatment for opioid addiction, in which case they would not turn the case over to the Attorney General (William Bronson, personal communication). The cases that they do report to the Attorney General s office are looked into further to determine if they should be reported to the State Bureau of Investigation. To be able to prescribe controlled substances, practitioners must apply for a federal license from the Drug Enforcement Administration (DEA). However, the DEA may only license practitioners who are authorized to prescribe controlled substances by the state in which they practice. In all states, individual practitioners who are physicians, dentists, veterinarians, or podiatrists may apply for a DEA controlled substance license. However, states differ in which midlevel practitioners they will allow to prescribe controlled substances. North Carolina authorizes nurse practitioners, physician assistants, pharmacists, ambulance services, animal shelters, optometrists, and nursing homes (US DEA 2012, Mid-level Practitioners ). Anyone who is federally licensed to prescribe controlled substances can access the CSRS but is not required to do so. To be able to access the CSRS, the practitioner must send in a notarized paper application and a photocopy of his or her identification (William Bronson, personal communication). When practitioners receive their DEA license, they are assigned a DEA identification number, which also acts as their CSRS user name and identification. 2 See Appendix A. 6

Beyond the CSRS, northwest North Carolina s Medicaid authority has set up a pilot project for a subset of Medicaid patients that requires patient-provider agreements (or pain contracts ) and locks the patients into using one pharmacy and one provider for all opioid therapy (Albert et al. 2011). Non-Legitimate Prescribing ( Pill Mills ) In some cases, providers may be complicit in overprescribing; that is, prescribing controlled substances without a legitimate medical purpose and outside the usual course of professional practice. Between 2003 and April 2012, the DEA participated in the investigation, arrest, and prosecution of four prescribers in North Carolina for prescribing without a legitimate medical purpose (US DEA 2012, Cases Against Doctors ). The North Carolina State Bureau of Investigation (SBI) has original jurisdiction in drug investigations. Its Diversion and Environmental Crimes Unit conducts specialized investigations concerning diversion of controlled substances both by individuals (including prescribers) and organized drug rings (SBI Special Operations). The CSRS could help in identifying and reporting to SBI prescribers who are operating outside of usual professional practice. However, CSRS staff do not currently monitor unusual patterns of prescribing for prescribers. They are currently working on developing criteria for this with the Injury Prevention Research Center at the University of North Carolina (William Bronson, personal communication). Receiving, Purchasing, or Stealing from Friends or Family Once controlled substances have been prescribed and dispensed, different strategies must be employed to reduce prescription drug overdoses. Examples include providing education about the dangers of sharing controlled substances and offering opportunities for safe storage and disposal of unwanted medications. North Carolina s Operation Medicine Cabinet disseminates information about safe storage of prescription drugs so that it is less likely that someone could steal them. The organization also coordinates drug take back events where people can anonymously dispose of leftover and unwanted pills and helps communities across the state set up permanent drop boxes for disposing of these medications (Operation Medicine Cabinet 2012). 7

Purchasing on the Street The most obvious strategy to reduce overdoses from prescription drugs obtained through the street market is increased law enforcement. The CSRS plays a critical role in identifying possible forgeries and other diversion and reporting these cases to the Attorney General and SBI for investigation. Additionally, Project Lazarus has helped local law enforcement agencies hire and train two officers dedicated to investigating the diversion of prescription drugs (Albert et al. 2011). Data and Methods Data Sources Medical Examiner Files In North Carolina, any suspected poisoning death is required by general statute to be reported to a medical examiner (ME) (Public Health Law of North Carolina, 1983). The death can be reported by anyone who has knowledge of the death or who finds the body, but usually this will be an attending physician or emergency room, a law enforcement officer, or an emergency medical technician (NC OCME Guidelines, Rules, and Statutes). The Chief Medical Examiner appoints a medical examiner to each county from a list of physicians licensed to practice in the state. Jurisdiction for a case is determined by the county where the body is found. The medical examiner personally examines every body under her jurisdiction, obtains a medical history to help explain the cause and manner of death, and consults with law enforcement when relevant (NC OCME Guidelines, Rules, and Statutes). Additionally, the ME should order an autopsy in all suspected drug-related deaths. In the process of the investigation, the ME completes a Report of Investigation, which documents her findings and the circumstances of death. The Report of Investigation includes a narrative summarizing the case. The ME must also complete a Medical Examiner Certificate of Death. Once complete, the Report of Investigation and Certificate of Death are then sent to the Office of the Chief Medical Examiner and become public record. Medical examiner information is missing for some cases in which the files could not be abstracted because they were missing from the shelf. Additionally, in some cases a toxicology screen was not performed, usually because of a family request or because the death occurred on a military base. 8

When the medical examiner files were being abstracted, the source of the drugs contributing to death was not the primary question to be answered, and thus, that information may not have been abstracted even though it exists in the medical examiner files. To explore this possibility, I selected a sample consisting of 10 percent of the cases and looked at the original medical examiner s report at the Office of the Chief Medical Examiner in Chapel Hill to get an estimate of how often drug source information was included in the narrative but not abstracted into the data set. In total, I found two cases out of 66 with additional source information, which I decided was not a substantial enough number to justify the time required to review the medical examiner narratives for the entire population. Police Incident Reports Because the primary purpose of the medical examiner s investigation is to determine only the intent and cause of death, police reports may contain more information relevant to the drug source. To get a sense of what kind of information the police reports contain, I examined the available Durham County police incident reports for 2010 overdose deaths. Of the 20 cases, seven did not have an incident report filed, which can happen if the police are not called or if the victim is transported to the hospital before the police arrive at the scene. Of the remaining 13 cases, five involved illicit or over-the-counter drugs only or had no source information. Four reports recorded the probable source as a prescription and two others implied that a prescription was the source. The remaining two cases included diversion source information: one had the same information that had been recorded in the medical examiner narrative, but the other case did contain new information. I decided not to examine police reports from other counties because I thought the amount of new information I could collect would not outweigh the time spent collecting it. It is possible, however, that the Durham County police reports are not representative of those in the rest of the state. For example, deaths in rural counties would be less likely to contain as many cases involving illicit drugs as urban counties such as Durham County. Law enforcement officers must file an incident report for every call to which they respond. The incident report describes the scene and any investigation or interviews that occur during the first response. However, the incident report will not contain any information collected from further investigation. Because it is rare that the first response to an overdose death will immediately lead to the source, police incident reports do not 9

provide complete information. Additionally, police are not always called to an overdose situation, so there may not be an incident report corresponding to every death. According to Judy Billings, ASAC at the North Carolina SBI, any follow-up information collected while investigating the death (including the source of contributory drugs) is kept separately and is not public record. Most of the time investigators need to wait for the autopsy and toxicology results so that they know what specific drugs are involved before they can continue an investigation. Through my interviews I also discovered that there is some inconsistency across the state when it comes to when overdose deaths are routed through the medical examiner s office and when overdose death investigations are conducted as criminal cases. Especially in small communities, law enforcement officers sometimes call the decedent s attending physician to sign the death certificate rather than sending the case to the medical examiner (Billings, interview). This process goes against the general statute noted above that requires all suspected poisoning deaths be reported to a medical examiner. If the death certificate lists the proper ICD-10 code, the number of overdose deaths and the intent of the deaths would still be accurate. However, if no toxicology screen is done because the case does not go through the medical examiner, the ability of public health surveillance to have access to accurate or sufficient data is limited. Interviews 3 Judy Billings is an Assistant Special Agent in Charge (ASAC) for the Diversion and Environmental Crimes Unit of the North Carolina State Bureau of Investigation. This unit investigates drug diversion (both controlled or uncontrolled substances), health care facility drug theft, prescription forgery and doctor shopping, elder abuse in adult care, as well as prescription drug overdose deaths as requested. Deborah Radisch is the North Carolina Chief Medical Examiner. The North Carolina Medical Examiner System is a network of medical doctors and allied health professionals throughout North Carolina who investigate deaths of a suspicious, unusual or unnatural nature. Ruth Winecker is the Chief Toxicologist at the Office of the Chief Medical Examiner. The Toxicology Laboratory serves the entire state and provides forensic testing of specimens and evidence for approximately 10,000 medical examiner cases each year. 3 See Appendices C and D. 10

Construction of Data Set The original data set was compiled in early 2012 by Annie Hirsch, CDC/CSTE Epidemiology Fellow at the Injury and Violence Prevention Branch of the North Carolina Division of Public Health. The creation of this data set came out of an effort by the Injury and Violence Prevention Branch to better understand the characteristics of fatal unintentional overdose victims by linking several data sources: death certificates, medical examiner files, and CSRS prescription records (Hirsch 2012). The resulting combined data can provide insights that the individual sources cannot, such as determining the exact drugs that contributed to death and whether the decedent had a recent prescription for any of those drugs. The goal of gaining these insights would be to use them to guide prevention efforts. The data set contains information from the death certificates, medical examiner files, and CSRS records of the 891 North Carolina residents who died of an unintentional drug overdose in 2010. Cases were identified from death certificates using ICD-10 codes X40-X44 and Y10-Y14 (meaning the underlying cause of death was a drug or medication overdose). The cases were also limited to those of unintentional or undetermined intent because of the fundamental difference in prevention strategies between suicides and unintentional overdoses (Hirsch 2012). Thus, some prescription drug overdose deaths may be relevant but are excluded here, either because the intent was misclassified as intentional or because the cause was misclassified as something other than a drug overdose death. Determining intent in drug overdose deaths is heavily context-dependent and there is no national standard for doing so. Medical examiners use toxicology results in combination with information about the circumstances gathered by law enforcement to determine intent. Typically, suicides are fairly easy to identify. Toxicology results for suicides will show both a high concentration of the drug(s) as well as a high parent-to-metabolite ratio, meaning that the decedent ingested a large quantity of the drug(s) at once, dying before most of it could be metabolized (Winecker, interview). The medical examiner will also look at CSRS records and police investigation files, ask the police to gather particular information, or interview the decedent s family herself to verify that the circumstances surrounding the death are consistent with a suicide. Deborah Radisch, North Carolina s Chief Medical Examiner, tends to require strong evidence of a suicide before she is willing to declare it as such. Unintentional deaths comprise the majority of drug overdose deaths. Cases classified as unintentional often have high concentrations of contributory drugs but lower parent- 11

to-metabolite ratios and no other evidence of a suicide. If a case shows evidence of recreational drug use, it is most likely classified as an accident (Radisch, interview). Evidence of recreational drug use includes illicit drug use, a lack of prescriptions for the drug(s) contributing to death, or possibly mentions of recreational drug use from investigation files. The most difficult cases to determine are ones in which the decedent has a history of taking prescription drugs for chronic pain, a history of suicide attempts, and high concentrations of the contributory drug(s). These are most often the cases that are left as undetermined (Radisch, interview). As noted above, there is no national standard for determining the intent of drug overdose deaths, so statistics may not be comparable among jurisdictions. For example, the default in North Carolina tends to be unintentional unless there is strong evidence of a suicide or the cases have a particularly unclear combination of attributes. In contrast, Baltimore s default tends to be undetermined unless there is strong evidence of a suicide. Although different jurisdictions throughout the country have different protocols for determining intent, the breakdown of pharmaceutical-related overdose deaths by intent is fairly similar when comparing North Carolina s statistics to national statistics. North Carolina s proportion of intentional deaths was similar to the national numbers. However, North Carolina classified a slightly higher proportion of its pharmaceuticalrelated overdose deaths as unintentional than the country overall. The state also had a slightly lower proportion of deaths classified as undetermined compared to the national statistics. These differences could reflect the differences in protocols for determining intent, particularly differences like those between North Carolina and Baltimore. Table 1: Comparing Pharmaceutical-Related Overdoses by Intent Intent North Carolina (%) National (%) (Jones et al.) Unintentional 78.5 74.3 Intentional 17.7 17.1 Undetermined 3.8 8.4 Given that intent can never be determined with certainty, some deaths may be misclassified. In truth, all undetermined deaths are technically misclassified, but in North 12

Carolina it is unclear if the real intent is biased toward suicides or accidents. Because only strong evidence is used to declare a suicide, it is possible that unintentional deaths are overstated and intentional deaths are understated. The setup of the current system of determining intent has several implications for surveillance and research. Because each jurisdiction has its own procedure, estimates that are based on intent cannot necessarily be compared across jurisdictions. Additionally, a large number of misclassified cases could result in skewed results. For example, if many unintentional cases are actually suicides, the characteristics of unintentional overdose victims may not reflect the population who is actually at risk of an unintentional overdose. In creating the data set, cases were matched to medical examiner files using a unique identifier and the results of the toxicology screen and select elements of the medical examiner narrative were abstracted. Drugs contributing to death were categorized by the toxicologist as playing either a primary, additive, or contributing role. Based on the dosage found in the body, drugs categorized as playing a primary role were capable of causing death independently. Additive drugs were capable of causing death only in combination with other drugs, and contributing drugs contributed to the death indirectly (i.e., by influencing behavior). CSRS data were collected by manually searching each case using the first five letters of the last name and date of birth. Matches were considered exact when the first name or nickname, last name, and date of birth matched exactly and no prescriptions were dispensed after the decedent s date of death. Controlled substance prescription records from the year before death were abstracted for all exact matches (Hirsch 2012). However, only prescriptions dispensed in North Carolina are available from the CSRS; prescriptions filled in other states are not in the data set. CSRS query data were collected in June 2012. This data contains two types of information: prescribers registration status and queries performed on the decedents. We obtained access to the CSRS registration database containing the name, DEA or other identification number, and registration date of everyone who is registered to access the CSRS in North Carolina. We noted the registration status of each prescriber in the previous data set as of June 12, 2012 (the day we received the registration file from CSRS staff). We also recorded the registration date in order to compare that date with each decedent s date of death. The data set also contains records from the CSRS of all queries performed on the decedents. The population for this portion of the data collection was restricted to any 13

decedent who had at least one prescription record for a controlled substance in the year before death. These cases were manually searched using the first name or nickname and last name and matched on first name or nickname, last name, and date of birth. Records of queries by prescribers, pharmacists, and SBI agents in the period between one year before death and one month after death were abstracted. To add any drug source information from the medical examiner narrative, I reviewed the medical examiner files for all cases for which it was available and coded any mention of where the decedent may have obtained their drugs through diversion. I did not code mentions of prescriptions because that information is available from the CSRS prescription records. The categories include doctor shopping, being obtained from family or friends, purchased on the street, purchased online, obtained through pharmacy theft, and obtained through unspecified methods of diversion. The categories for online purchasing, pharmacy theft, and unspecified diversion were combined because there were so few cases in each. Although technically not diversion, I also coded any mention of the decedent participating in an opioid treatment program because, under current requirements, those drugs would not appear in the decedents prescription records. Analysis All deaths from illicit drugs only and from over-the-counter drugs only were excluded because these cases are not pertinent to the research question. I also excluded cases for which there was no toxicology information available in the medical examiner file because it would not be possible to link the drugs that contributed to death with any prescription records. The number of total controlled substance prescriptions was calculated for each of the remaining cases. The cases were then further narrowed according to whether the prescription was current and whether it was contributory. A prescription was defined as current if the number of days supply listed was greater than the number of days elapsed between the date the drug was dispensed and the date of death. Due to reporting error, some prescription records list the number of days supply as zero; I defined these prescriptions as current if the number of days elapsed between dispensation and death was less than 30 and the quantity supplied was greater than the number of days elapsed. A contributory drug was defined as any drug determined by the medical examiner to have contributed to death (i.e., any primary, additive, or contributing drug). 14

Additionally, I ranked both the prescription drug types and specific drugs by how many deaths they contributed to. The number of different prescribers and pharmacies used in the year before death were also calculated for each case. Because there is no universally accepted definition of doctor shopping, the cases were assessed for doctor/pharmacy shopping using three different criteria. The first and second involve counting the number of different providers or pharmacies the decedent used within a certain time period. The first criterion is the one used by Hall et al.: at least five prescribers in one year. For the second method I used the criteria defined by the CSRS staff as an unusual pattern of prescriptions: receiving prescriptions from at least ten providers or filling prescriptions at at least five pharmacies within 90 days. The 90-day reference period was the 90 days before death. Finally, the third method is by mention of doctor shopping in the medical examiner narrative. In addition to using medical examiner narrative information to identify doctor shopping, I also used it to categorize cases based on other specific types of diversion. Additionally, I noted any mention of the decedent attending an opioid treatment program (OTP) or methadone clinic. Because OTPs are not required to submit records into the CSRS, there may be some cases where the decedent did not have a prescription for a drug contributing to their death (usually methadone) but was receiving it legitimately from an OTP. Those cases may be incorrectly classified as using diverted drugs. There may also be additional cases that are still incorrectly classified because there was no mention of an OTP in the medical examiner narrative. Use of the CSRS was measured by categorizing the cases based on whether they were ever queried before death. Queries were further categorized based who accessed the database: providers, pharmacists, or SBI agents. Providers who accessed the database were divided by whether or not they had prescribed to the patient(s) they queried. Results Of the 891 unintentional or undetermined drug- or medication-related overdoses, 180 cases were dropped because only illicit drugs contributed to death. An additional four cases were dropped because no toxicology information was available. 15

Table 2: Cases by Demographic Characteristics, (n = 707) Number Percent of cases Sex Male 430 60.8 Female 277 39.2 Age Group 4 15 24 71 10.1 25 34 150 21.3 35 44 176 24.9 45 54 221 31.3 55 64 82 11.6 65+ 6 0.9 Race White 664 93.9 Black 27 3.8 American Indian 14 2.0 Asian 2 0.3 The 707 remaining cases involved only prescription drugs or a combination of prescription and illicit drugs. Table 2 shows the remaining cases by several demographic characteristics. A majority of the decedents were male and an overwhelming proportion of them were white. Over half were between the ages of 35 and 54. These 707 cases filled a total of 14,806 controlled substance prescriptions within a year of their deaths. The average number of prescriptions per person was 21, with a maximum of 105. (A full list of the cases by number of prescriptions is available in Appendix B.) 4 For age group, n = 706. The age groups used here exclude one infant death. 16

Of the 707 cases, 132 had no prescription records in the year before their deaths. An additional 171 had at least one prescription, but none that were defined as current. The remaining 404 cases (57.1 percent) each had at least one current prescription for any controlled substance and among them had a total of 1,177 current prescriptions. Table 3: Cases by Current Prescription Status Number Prescription status Percent of cases No prescriptions 132 18.7 Non-current prescriptions 171 24.2 Current prescriptions 404 57.1 Total 707 100.0 Among those 404 cases with current prescriptions, 290 of them had current prescriptions that were also for drugs that appeared on the toxicology screen. There were a total of 542 of these current prescriptions for contributory drugs, an average of 1.9 per person. Additionally, 167 cases (41.3 percent of those with any current prescriptions) had a current prescription for every drug that contributed to their deaths. 17

Table 4 sorts the cases by the type of prescription drug contributing to death and by whether the decedent had any current prescriptions for a contributory drug. Nonprescription drugs are not included here. Opioids contributed to almost all (94 percent) of the 707 deaths, while benzodiazepines contributed to over a quarter of the deaths. Opioids and benzodiazepines contributed to a higher proportion of deaths for the group that had at least one current prescription for a contributory drug than for the group that had no current prescriptions for contributory drugs. The other prescription drugs mainly consist of antidepressants, antihistamines, muscle relaxants, anticonvulsants, and blood pressure medications. Table 4: Cases by Type of Prescription Drug Contributing to Death and Current Prescription Status 5 Prescription drug type No current prescriptions for contributory drugs (n = 417) At least one current prescription for contributory drugs (n = 290) All cases (n = 707) Cases Percent Cases Percent Cases Percent Opioid 379 90.9 283 97.6 662 94.0 Benzodiazepine 91 21.8 109 37.6 200 28.0 Other 75 18.0 51 17.6 126 18.0 In many cases, a combination of prescription drugs with illicit drugs, alcohol, or over the counter medications contributed to death. A higher proportion of deaths resulting from a combination of prescription drugs and illicit drugs actually occurred among the group with at least one current prescription, whereas deaths resulting from a combination of prescription drugs and alcohol were more common among the group with no current prescriptions. 5 Cases do not add up to 707 and percentages do not add up to 100 because in many cases, multiple drugs contributed to death. 18

Table 5: Cases by Type of Drug Contributing to Death and Current Prescription Status 4 Drug type No current prescriptions for contributory drugs (n = 417) At least one current prescription for contributory drugs (n = 290) All cases (n = 707) Cases Percent Cases Percent Cases Percent Prescription 417 100.0 290 100.0 707 100.0 Illicit 60 14.4 29 29.0 89 12.6 Alcohol 83 19.9 21 7.2 104 14.7 Over the counter 1 0.2 3 1.0 4 0.6 A total of 68 different prescription drugs were determined by a medical examiner to have contributed to death in at least one of the cases. Table 6 lists specific drugs according to how many deaths they contributed to. (Only those drugs that contributed to at least 10 deaths are shown here; the full list is available in Appendix B.) Consistent with the prescription drug type results above, all of the top ten drugs listed here are either an opioid or a benzodiazepine. Oxycodone contributed to almost one-third of deaths, the most of any specific drug. Table 6: Cases by Specific Drugs Contributing to Death 6 Drug Number of cases Percent Oxycodone 223 31.5 Methadone 191 27.0 Alprazolam 147 20.8 Hydrocodone 105 14.9 Fentanyl 101 14.3 Morphine 83 11.7 Oxymorphone 61 8.6 Diazepam 57 8.1 Clonazepam 41 5.8 6 Cases do not add up to 707 and percentages do not add up to 100 because in many cases, multiple drugs contributed to death. 19

Tramadol 22 3.1 Propoxyphene 7 18 2.5 Amitriptyline 17 2.4 Citalopram 17 2.4 Carisoprodol 12 1.7 Hydromorphone 11 1.6 Buprenorphine 10 1.4 Diphenhydramine 10 1.4 A total of 2,336 different prescribers wrote prescriptions for these cases within a year of their deaths. There was an average of 4.3 prescribers per person and the greatest number of prescribers in one year was 47. (The full list of cases by number of prescribers is available in Appendix B.) A total of 992 different pharmacies were used to fill the controlled substance prescriptions. Those who used only one pharmacy to fill controlled substance prescriptions in the year before their deaths made up the largest group, but the maximum number of pharmacies in one year was 25. 7 Propoxyphene was taken off the market in November 2010 because it was associated with an increased risk of cardiac abnormalities. 20

Using these calculations, the cases were assessed for doctor shopping behavior in three ways. The first method (at least 5 different prescribers in one year) resulted in over one-third of total cases meeting the criterion for doctor shopping. The second method was much more restrictive, reducing the number of cases to less than five percent of total cases. Finally, mentions of doctor or pharmacy shopping behavior in the medical examiner narratives resulted in the fewest number of cases. Table 7: Comparison of Doctor/Pharmacy Shopping Estimates Criterion Number of cases Percent (of 707 total cases) 5 prescribers/year 252 35.6 10 prescribers OR 5 pharmacies/year 31 4.4 ME narratives 16 2.3 Upon reviewing the abstracted data from the medical examiner narratives, I found a total of 78 cases with diversion source information, including the doctor shopping behavior discussed above. Of those cases with information, receiving or taking drugs from friends or family was the most common source, followed by doctor shopping. The narrative mentioned that the decedent was a patient at an opioid treatment program in 21