Risk of Opioid Overdose Death in North Carolina by Type of Opioid and

Other Controlled Substances Prescribed

Nabarun Dasgupta, PhD

Epidemico, Inc.University of North

Carolina at Chapel Hill

CPDD – Phoenix

June 15, 2015

Slides Twitter @epidemico

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Disclosures

Nabarun is a full-time employee of Epidemico, Inc., a public health informatics company, which is a subsidiary of Booz Allen Hamilton.

No opioid manufacturers were involved in this study.

This research was conducted in fulfillment of a doctoral dissertation requirement and funded in part by CDC.

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Research Questions

1. Does 100 daily MME represent a threshold for increase in overdose mortality risk?

2. What proportion of clinicians prescribe (ER) opioids?

3. Are there dose-dependent differences in overdose mortality between ER vs IR opioid analgesics, or benzodiazepine exposure?

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Literature Review

Dasgupta 2013

n=2,182,374

Single year; +/-codeine [NC]

Paulozzi 2012 n=730,381 Includes illicit drug OD [NM]

Gomes 2011a n=607,156Gov’t drug benefit programme; 10 years [ON]

Gomes 2011b n=154,411Non-cancer pain; -hydrocodone [ON]

Bohnert 2011 n=143,684Military veterans; -fentanyl [US]

Dunn 2010 n=9,940Non-cancer pain; private insurance; +propoxyphene, +tramadol [WA]

Coplan 2013 n=74,991General practice EHR; non-fatal OD [UK]

Bohnert 2015 n=420,386Military veterans; intentional and unintentional OD; -methadone [US]

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Range of Highest and Reference GroupsPaulozzi 2012

OR 11.3 (8.1, 15.8) for >120 mg/dayRef: 0-40 mg/day

Gomes 2011a

aOR 2.9 (1.8, 4.6) for 200+ mg/dayRef: 1-19 mg/day

Gomes 2011b

IRR 2.2 for 201-399 mg/dayIRR 2.3 for 400+ mg/dayRef: >0-200 mg/day

Bohnert 2011

Cancer HR 12.0 (4.4, 32.5) for100+ mg/dayNon-Ca HR 7.2 (4.8, 10.6) for 100+ mg/dayRef: 1-20 mg/day

Dunn 2010 HR 8.9 (4.0, 19.7) for 100+ mg/dayRef: 1-<20 mg/day

Coplan 2013aRR 1.15 (0.87, 1.53) for 121+ mg/dayRD 0.30 (0.09, 0.52)Ref: 1-30 mg/day

Bohnert 2015

No benzodiazepine aHR 3.3 (2.6, 4.2) for 100+ mg/dayFormer benzodiazepine aHR 3.0 (2.2, 4.1) for 100+ mg/dayCurrent benzodiazepine aHR 3.9 (3.2, 4.8) for 100+ mg/dayRef: >0 to < 20 mg/day

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Study Design

Prospective cohort All NC residents, 2010

Outcome

Overdose death involving opioid analgesics- primary or contributing role- solid oral and transdermal: codeine, fentanyl, hydrocodone, hydromorphone, morphine, methadone, oxycodone, oxymorphone

Exposure Average Daily MMEApproximately 20 mg increments

Models Poisson, GEE (independent)

Offset Person-days - Following intent-to-treat principle

Assumptions

- Uniform risk over interval- Prescription status in one period does not influence prescription status in subsequent period- Risk not influenced by: prior exposure, other substances, number of prescriptions or pharmacies, opioid formulation

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Morphine Equivalents & Overlapping Scripts

Used by epidemiologists to standardize potency across opioids(Do or do not use as clinical guide during opioid rotation?)

Pharmacological potency relative to morphine (1.0)

Conversion factors suggested by CDC

MME = milligrams per unit x quantity of units x conversion factor

Days supply = Days the prescription is intended to be used

Average daily MME =

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MMEdays supply

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Study FlowNumbers of participants

Data Processing9

Numbers of dispensed prescription records

Opioid Analgesic Patients (n=2,182,374)

22.8% of NC residents received opioid analgesics

IR: 22.5% versus ER: 1.4%

89.6% of all licensed clinicians prescribed opioid analgesics

IR: 88.5% versus ER: 40.0%

80% of opioid analgesic patients prescribed benzo in previous year

Overdose Decedents (n=629)

76% received opioid analgesic Rx in 365 days prior to death 43% of these opioid analgesic decedents had received ER51% has active opioid analgesic prescription at time of death61% of opioid analgesic overdose deaths also implicated benzos

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Opioid Utilization in Context & Access to Care

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Opioid analgesic + benzo: 7.0 per 10,000 person-years (95% CI: 6.3, 7.8)Only opioid analgesics: 0.7 per 10,000 person years (95% CI: 0.6, 0.9)

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IR only: 1.3 per 10,000 person-years (95% CI: 1.2, 1.5)ER + IR: 14.9 per 10,000 person years (95% CI: 12.9, 17.1)

Of “higher dose” (150 daily MME) IR-only patients, 14.1% were on opioidanalgesic therapy for more than 6 months.

Limitations

Exchangeability - why do patients receive higher doses?

Assumption of continuous risk during time exposed

Previous therapy and opioid tolerance not assessed

External factors that influence opioid mortality (e.g., ADFs)

Identification of overdose deaths and causality assessment

Adherence to therapy and exposure to diverted opioids

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Source: Dasgupta 2014, Drug & Alcohol Dependence

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Linkage of Prescription and Mortality Data

Conducted by A. Hirsch at NC Division of Public Health

Identify deaths by vital statistics [X40-44, Y10-14] (n=896)

Toxicology results available (n=824)

Deaths involving opioid analgesics in primary/additive roles (n=629)

Identify CSRS records using first 5 letters of last name and DOB

Extract prescription dispensing history for 365 days prior to death

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