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. Author manuscript; available in PMC: 2021 Jun 26.
Published in final edited form as: Subst Use Misuse. 2020 Jun 26;55(12):1912–1918. doi: 10.1080/10826084.2020.1781176

OVERDOSE RISK AND ACQUIRING OPIOIDS FOR NONMEDICAL USE EXCLUSIVELY FROM PHYSICIANS IN VANCOUVER, CANADA

Tessa Cheng a,b, Will Small a,b,c, Ekaterina Nosova b,d, Robert Hogg a,e, Kanna Hayashi a,b, Thomas Kerr b,d, Kora DeBeck b,f
PMCID: PMC7480281  NIHMSID: NIHMS1618353  PMID: 32589497

Abstract

Background:

A primary response to the alarming rise in overdose and mortality due to nonmedical prescription opioid (PO) use has been to restrict opioid prescribing; however, little is known about the relationship between obtaining opioids from a physician and overdose risk among people who use POs nonmedically and illicit street drugs.

Objectives:

Investigate the relationship between non-fatal overdose and acquiring POs exclusively from physicians for the purposes of engaging in nonmedical PO use.

Methods:

Data were collected between 2013 and 2016 among participants in two harmonized prospective cohort studies of people who use drugs in Vancouver: the At-Risk Youth Study (ARYS) and the Vancouver Injection Drug Users Study (VIDUS). Analyses were restricted to participants who engaged in nonmedical PO use and used generalized estimating equations.

Results:

Among 599 participants who used POs nonmedically, 82 (14%) individuals reported acquiring POs exclusively from a physician and 197 (33%) experienced a non-fatal overdose at some point over the study period. Acquiring POs exclusively from physicians was significantly and negatively associated with non-fatal overdose in the bivariate analysis (Odds Ratio=0.60, 95% Confidence Interval (CI): 0.39–0.94) but not the final multivariate analysis (Adjusted Odds Ratio =0.87, 95% CI: 0.53–1.44).

Conclusions:

Compared to individuals who acquired POs from friends or the streets, participants who acquired POs exclusively from a physician were not at an increased risk of non-fatal overdose. Although responsible opioid prescribing is an important priority, additional strategies to address nonmedical PO use are urgently needed to reduce overdose and related morbidity and mortality.

Keywords: nonmedical prescription opioid use, street youth, substance dependence, risk behavior, overdose

INTRODUCTION

Drastic increases in rates of overdose morbidity and mortality have been documented in numerous settings across Canada and the United States (Fischer, Gooch, Goldman, Kurdyak, & Rehm, 2014; Rudd, Aleshire, Zibbell, & Gladden, 2016). These alarming increases have been attributed in part to medical and nonmedical prescription opioid use (NMPOU), and prompted swift responses from policy-makers and health professionals. A key focus of the response has been to reduce opioid prescribing by physicians (Alexander GC, 2015; National Advisory Committee on Prescription Drug Misuse, 2013), as new national prescribing guidelines championed in Canada and the United States involve an emphasis on increased prescription monitoring programs to promote safe prescribing, restrictions on opioid dosages, and broadly increased caution regarding prescribing opioids (Busse et al., 2017; Dowell, Haegerich, & Chou, 2016). Although these efforts have been widely adopted, the impact of restrictive opioid prescribing policies and guidelines across different populations of people who use drugs (PWUD) is not well-understood.

While aimed at preventing individuals from developing opioid dependence, emerging reports link restrictive opioid prescribing policies and guidelines to increased illicit substance use such as heroin (Pitt, Humphreys, & Brandeau, 2018; Rothstein, 2017) often as a result of patients having difficulty obtaining effective pain treatment (Rothstein, 2017). The sequelae of engaging in illicit substance use to manage pain has been associated with an increased risk of overdose (Dassieu, Kaboré, Choinière, Arruda, & Roy, 2019; Yarborough et al., 2016), notwithstanding the established relationship between illicit substance use generally and overdose (Degenhardt & Hall, 2012). In addition, research to date has found that a low proportion of those who engaged in NMPOU and died by overdose received a prescription for opioids (Gagajewski & Apple, 2003; Hall et al., 2008; Roxburgh et al., 2013). However, another study found that a prescription for certain pharmaceutical opioids (POs), specifically, buprenorphine, fentanyl, hydromorphone, methadone, or oxycodone, was associated with an increased risk for overdose (Paulozzi et al., 2012).

In the context of swift and rapid action to address the acute public health overdose crisis, there is an urgent need to identify factors associated with NMPOU-related overdose and investigate whether acquiring POs from physicians is associated with an increased or decreased risk of experiencing an overdose. While acquiring POs from a physician for nonmedical use may signal intensive substance use that increases overdose risk, physician-acquired POs may also reduce overdose risk by supporting linkages to healthcare and providing PWUD with a substance of known dosage and purity along with a treatment regimen. Given this knowledge gap and the urgent need to inform policy responses, this exploratory study sought to examine the relationship between physician-acquired POs and risk of non-fatal overdose among people who engage in NMPOU and use illicit drugs.

MATERIALS AND METHODS

The data for this study draw on two harmonized open prospective cohort studies: The At-Risk Youth Study (ARYS) and the Vancouver Injection Drug Users Study (VIDUS). Both cohorts use extensive snowball sampling, self-referral, and street outreach to recruit participants. Participants in the ARYS study must be between the ages of 14 and 26, have recently used a street drug other than or in addition to cannabis in the last month, and be “street-involved”, defined as being recently homeless or having used services designated for street-youth (DeMatteo et al., 1999; Marshall, 2008; Roy et al., 2004; Wood, Stoltz, Montaner, & Kerr, 2006). Participants in the VIDUS cohort must have injected drugs at least once in the previous month, speak and understand English, and be ≥18 years of age at enrolment. All enrolees provided informed consent to participate and were given a stipend ($30 CDN) for their time. Participants in both cohorts completed a harmonized interviewer-administered questionnaire at their baseline study visit and every six months thereafter. The ARYS and VIDUS studies received ethical approval from the University of British Columbia/Providence Health Care Research Ethics Board.

Participants who reported ever engaging in injection or non-injection NMPOU (yes vs. no) in 2013 and 2016 were eligible for these analyses. Participants were specifically prompted about non-medical use of OxyNEO, Oxycontin, Percocet, Tylenol 3, Morphine, Dilaudid, Demerol, Methadone/Methadose, Fentanyl, Hydrocodone, Talwin, and Suboxone; the non-medical use of other POs was also accepted. The primary outcome of these analyses was experiencing a non-fatal drug overdose in the last six months (yes vs. no) based on responses to the question “In the last 6 months, have you overdosed by accident (i.e., where you had a negative reaction from using too much drugs)?” The key independent variable of interest was reporting acquiring POs exclusively from a physician for the purposes of NMPOU in the last six months (yes vs. no) based on responses to the question “What sources have you used in the last 6 months?” Response options included: Doctor: legitimate prescription; Doctor: illegitimate prescription; given by or taken from family member; given by or taken from partner; given by or taken from friend; bought from a friend; bought on the street / from a drug dealer; other. Data on opioid prescriptions obtained from other healthcare professionals (e.g., nurses with advanced training) were not collected. Reports of acquiring POs from a single or multiple physician(s) (either through a legitimate or illegitimate prescription) were coded as “yes”, while reports of acquiring POs from a physician and/or diverted sources (e.g., friends, family, street) were coded as “no”. To test the relationship between non-fatal overdose and acquiring POs exclusively from a physician, we considered secondary explanatory variables that we hypothesized as potentially confounding this relationship of interest (all dichotomized as “yes vs. no” unless otherwise specified). The following socio-demographic variables were included: younger age (per year younger); female gender; white ethnicity; and homelessness, defined as having no fixed address, sleeping on the street, couch surfing, or staying in a shelter or hostel. Substance use variables included: any injection or non-injection heroin use; any injection or non-injection crack cocaine use; any injection or non-injection cocaine use; any injection or non-injection crystal methamphetamine use; using drugs more often than usual, subjectively defined as a period of using injection or non-injection drugs more often than usual; and immediate access to POs, defined as being able to acquire POs from any source within 10 minutes in the area where the participant typically obtains drugs. The analyses also included the following risk factors: moderate to extreme pain, defined as reporting “I have moderate pain or discomfort” or “I have extreme pain or discomfort ” based on the participant’s health state “today” (Euroqol-5D); unemployment, defined as not having a regular job, temporary work, or being self-employed; drug dealing, defined as selling drugs as a source of income; ever engaging in sex work, defined as exchanging sex for money, drugs, gifts, food, clothes, shelter or favors; incarceration, defined as being in detention, jail, or prison; difficulty accessing services, defined as reporting difficulty accessing health and social services, based on responses to the question “‘In the last six months, was there a time you were in need of a service (e.g., housing, counseling) but could not obtain it?”; and addiction treatment, defined as accessing any kind of addiction treatment. All variables were time updated and refer to activities, behaviors, and experiences in the previous six months unless otherwise indicated.

To investigate whether acquiring POs exclusively from physicians was independently associated with non-fatal overdose, we conducted a series of analyses. First, a preliminary analysis was conducted to investigate correlates associated with acquiring POs exclusively from a physician using the above-mentioned independent variables. Baseline frequencies and bivariable analyses stratified by acquiring POs exclusively from a physician (yes vs. no) were conducted using Pearson’s chi-square test for categorical variables and the Mann-Whitney test for continuous variables. Characteristics for participants who reported acquiring POs exclusively from physicians were measured at their first visit (during the study period: 2013–2016), which involved a report of acquiring POs exclusively from physicians. Characteristics for all other participants were measured from the first study visit during the study period.

Second, baseline frequencies and bivariable analyses stratified by non-fatal overdose were conducted using Pearson’s chi-square test for categorical variables and the Mann-Whitney test for continuous variables. Baseline characteristics for participants who reported non-fatal overdose were measured at their first visit during the study period, which involved a report of non-fatal overdose. Characteristics for all other participants were measured from the first study visit during the study period.

Third, we conducted bivariate generalized estimating equations (GEE) analyses testing the relationship between each independent variable and the outcome, non-fatal overdose. Given that the key independent variable of interest (acquiring POs exclusively from physicians) was associated with non-fatal overdose in the bivariate analysis (p<0.05), we fit a series of confounding models. This step was based on an automated a priori approach (Maldonado & Greenland, 1993; Rothman & Greenland, 1998) where all potential confounders are included in a multivariate model and then removed one at a time in a stepwise manner. This process constructs a series of reduced models, and the relative coefficient of change for our primary explanatory variable of interest (acquiring POs exclusively from physicians) was calculated for these reduced models. Secondary explanatory independent variables that resulted in the smallest relative change in the coefficient for acquiring POs exclusively from physicians were removed iteratively. This process was continued until the smallest minimum relative change in the coefficient for the effect of acquiring POs exclusively from physicians and non-fatal overdose exceeded 5% of the value of the coefficient. Remaining variables were considered confounders and included in the final multivariate analysis. All statistical analyses were performed using R software version [5.3.0] (R Foundation for Statistical Computing, Vienna, Austria). All p-values are two sided.

RESULTS

A total of 599 participants reported engaging in NMPOU between 2013 and 2016, and were eligible for this study. Among this sample, 211 (35%) were female, 364 (61%) were of white ethnicity, and the median age was 31 (Inter-Quartile Range [IQR]: 24–48) years. At baseline, a total of 197 (33%) participants reported experiencing a recent non-fatal overdose, and 82 (14%) participants reported acquiring POs exclusively from physicians. A total of 268 (45%) of participants attended at least one study follow-up visit, with a median of 1 study visit (IQR: 1–2). The sample contributed a total of 1,069 observations, with 265 observations of non-fatal overdose and 147 observations of acquiring POs exclusively from a physician.

A number of independent variables were significantly associated with acquiring POs exclusively from a physician as shown in Table 1. Moderate to extreme pain (Odds Ratio [OR]=1.65, 95% Confidence Interval [CI]: 1.08–2.53) and unemployment (OR=1.59, 95% CI: 1.01–2.50) were positively and significantly associated with acquiring POs exclusively from a physician. Factors negatively associated with this outcome included younger age (OR=0.95, 95% CI: 0.93–0.97), homelessness (OR=0.44, 95% CI: 0.28–0.68), any crack cocaine use (OR=0.65, 95% CI: 0.43–0.99), any crystal methamphetamine use (OR=0.35, 95% CI: 0.23–0.53), and difficulty accessing services (OR=0.53, 95% CI: 0.34–0.83).

TABLE 1.

Characteristics of participants stratified by acquiring POs exclusively from physicians among participants who engage in nonmedical prescription opioid (PO) use at baseline, 2013–2016 (n=599).

Characteristica,b Total (%)
(n=599)		 Physician Prescription
 Odds Ratio
(95% CI)		 p - value
Yes (%) (n=114) No (%) (n=485)
Non-fatal overdosec 149 (24.9) 21 (18.4) 128 (26.4) 0.63 (0.38 – 1.05) 0.076
Younger age [Med (IQR)] 31 (24–48) 45 (29–54) 29 (23–44) 0.95 (0.93 – 0.97) <0.001
Female gender 211 (35.2) 44 (38.6) 167 (34.4) 1.20 (0.79 – 1.82) 0.402
White ethnicity 364 (60.8) 68 (59.6) 296 (61.0) 0.94 (0.62 – 1.42) 0.767
Homelessc 260 (43.4) 32 (28.1) 228 (47.0) 0.44 (0.28 – 0.68) <0.001
Any heroin usec,d 440 (73.5) 77 (67.5) 363 (74.8) 0.70 (0.45 – 1.09) 0.112
Any crack cocaine usec,d 271 (45.2) 42 (36.8) 229 (47.2) 0.65 (0.43 – 0.99) 0.045
Any cocaine usec,d 244 (40.7) 42 (36.8) 202 (41.6) 0.82 (0.54 – 1.25) 0.347
Any crystal meth usec,d 365 (60.9) 46 (40.4) 319 (65.8) 0.35 (0.23 – 0.53) <0.001
Using drugs more often than usualc,d 342 (57.1) 58 (50.9) 284 (58.6) 0.73 (0.48 – 1.09) 0.124
Immediate PO availability 378 (63.1) 71 (62.3) 307 (63.3) 0.91 (0.59 – 1.39) 0.659
Moderate to extreme pain 330 (55.1) 74 (64.9) 256 (52.8) 1.65 (1.08 – 2.53) 0.019
Unemploymentc 200 (33.4) 29 (25.4) 171 (35.3) 1.59 (1.01 – 2.50) 0.045
Drug dealingc 225 (37.6) 35 (30.7) 190 (39.2) 0.69 (0.44 – 1.07) 0.093
Sex workc 98 (16.4) 17 (14.9) 81 (16.7) 0.87 (0.50 – 1.54) 0.642
Incarcerationc 81 (13.5) 13 (11.4) 68 (14.0) 0.79 (0.42 – 1.48) 0.458
Difficulty accessing servicesc 238 (39.7) 32 (28.1) 206 (42.5) 0.53 (0.34 – 0.83) 0.005
Addiction treatmentc 379 (63.3) 75 (65.8) 304 (62.7) 1.14 (0.75 – 1.76) 0.535
Open in a new tab
a.

Characteristics for participants who reported acquiring POs exclusively from physicians were measured at their first visit (during the study period: 2013–2016), which involved a report of acquiring POs exclusively from physicians. Characteristics for all other participants were measured from the first study visit during the study period.

b.

Comparison is yes versus no unless otherwise specified.

c.

Refers to activities, behaviors, and experiences in the last six months.

d.

Includes injection and non-injection drug use.

Baseline descriptive frequencies and bivariable analyses stratified by non-fatal overdose are displayed in Table 2 and the GEE bivariate analyses are displayed in Table 3. In bivariate analyses, acquiring POs exclusively from a physician was negatively and significantly associated with non-fatal overdose (OR=0.60, 95% CI: 0.39–0.94). After extensive adjustment for confounding, acquiring POs exclusively from a physician was not independently associated with non-fatal overdose (Adjusted Odds Ratio [AOR]=0.87, 95% CI: 0.53–1.44) in the final multivariate model (Table 3). Factors that remained positively and independently associated with non-fatal overdose included younger age (AOR=1.02, 95% CI: 1.00–1.04), homelessness (AOR=1.58, 95% CI: 1.08–2.29), any crystal methamphetamine use (AOR=2.28, 95% CI: 1.51–3.45), drug dealing (AOR=1.53, 95% CI: 1.12–2.10), and incarceration (AOR=1.93, 95% CI: 1.25–2.97).

TABLE 2.

Characteristics of participants stratified by recent non-fatal overdose among participants who engage in nonmedical prescription opioid (PO) use at baseline, 2013–2016 (n=599).

Characteristica,b Total (%) (n=599) Overdose
 Odds Ratio (95% CI) p - value
Yes (%) (n=197) No (%) (n=402)
Acquire POs exclusively from physiciansc 82 (13.7) 19 (9.6) 63 (15.7) 0.57 (0.33 – 0.99) 0.044
Younger age [Med (IQR)] 31 (24–48) 28 (23–37) 34 (25–49) 1.04 (1.02 – 1.05) <0.001
Female gender 211 (35.2) 69 (35.0) 142 (35.3) 0.99 (0.69 – 1.41) 0.943
White ethnicity 364 (60.8) 129 (65.5) 235 (58.5) 1.34 (0.94 – 1.91) 0.105
Homelessc 257 (42.9) 116 (58.9) 141 (35.1) 2.68 (1.89 – 3.81) <0.001
Any heroin usec,d 443 (74.0) 171 (86.8) 272 (67.7) 3.14 (1.98 – 4.99) <0.001
Any crack cocaine usec,d 266 (44.4) 91 (46.2) 175 (43.5) 1.11 (0.79 – 1.57) 0.538
Any cocaine usec,d 248 (41.4) 98 (49.7) 150 (37.3) 1.66 (1.18 – 2.35) 0.004
Any crystal meth usec,d 369 (61.6) 156 (79.2) 213 (53.0) 3.38 (2.27 – 5.02) <0.001
Using drugs more often than usualc,d 351 (58.6) 153 (77.7) 198 (49.3) 3.65 (2.47 – 5.39) <0.001
Immediate PO availability 379 (63.3) 121 (61.4) 258 (64.2) 0.89 (0.62 – 1.27) 0.506
Moderate to extreme pain 328 (54.8) 107 (54.3) 221 (55.0) 0.97 (0.69 – 1.37) 0.879
Unemploymentc 405 (67.6) 135 (68.5) 270 (67.2) 1.06 (0.74 – 1.54) 0.738
Drug dealingc 226 (37.7) 93 (47.2) 133 (33.1) 1.81 (1.28 – 2.56) 0.001
Sex workc 102 (17.0) 43 (21.8) 59 (14.7) 1.62 (1.05 – 2.51) 0.029
Incarcerationc 80 (13.4) 47 (23.9) 33 (8.2) 3.49 (2.15 – 5.67) <0.001
Difficulty accessing servicesc 235 (39.2) 94 (47.7) 141 (35.1) 1.69 (1.19 – 2.39) 0.003
Addiction treatmentc 379 (63.3) 136 (69.0) 243 (60.4) 1.46 (1.02 – 2.10) 0.041
Open in a new tab
a.

Characteristics for participants who reported non-fatal overdose were measured at their first visit (during the study period: 2013–2016), which involved a report of nonmedical prescription opioid use. Characteristics for all other participants were measured from the first study visit during the study period.

b.

Comparison is yes versus no unless otherwise specified.

c.

Refers to activities, behaviors, and experiences in the last six months.

d.

Includes injection and non-injection drug use.

TABLE 3.

Bivariate and multivariate analyses of factors associated with recent non-fatal overdose among participants who engage in nonmedical prescription opioid (PO) use, 2013–2016 (n=599).

Characteristica Unadjusted Odds Ratio (95% CI) p - value Adjusted Odds Ratio (95% CI) p - value
Acquire POs exclusively from physiciansb 0.60 (0.39–0.94) 0.025 0.87 (0.53–1.44) 0.591
Younger age (per year younger) 1.04 (1.03–1.05) <0.001 1.02 (1.00–1.04) 0.018
Female gender 1.07 (0.76–1.50) 0.693
White ethnicity 1.27 (0.91–1.77) 0.159
Homelessb 2.60 (1.91–3.55) <0.001 1.58 (1.08–2.29) 0.017
Any heroin useb,c 2.61 (1.76–3.86) <0.001
Any crack cocaine useb,c 1.21 (0.90–1.63) 0.211
Any cocaine useb,c 1.45 (1.08–1.94) 0.012
Any crystal meth useb,c 3.60 (2.52–5.14) <0.001 2.28 (1.51–3.45) <0.001
Using drugs more often than usualb,c 3.12 (2.28–4.25) <0.001
Immediate PO availability 0.91 (0.66 −1.24) 0.551 0.94 (0.66–1.35) 0.750
Moderate to extreme pain 0.82 (0.62–1.08) 0.156 0.80 (0.59–1.10) 0.173
Unemploymentb 1.28 (0.94–1.75) 0.112 1.23 (0.87–1.75) 0.231
Drug dealingb 1.90 (1.42–2.53) <0.001 1.53 (1.12–2.10) 0.008
Sex workb 1.73 (1.17–2.55) 0.006
Incarcerationb 2.78 (1.86–4.15) <0.001 1.93 (1.25–2.97) 0.003
Difficulty accessing servicesb 1.52 (1.12–2.06) 0.007 1.15 (0.80–1.64) 0.457
Addiction treatmentb 1.47 (1.07–2.02) 0.016
Open in a new tab
a.

Comparison is yes versus no unless otherwise specified.

b.

Refers to activities, behaviors, and experiences in the last six months.

c.

Includes injection and non-injection drug use.

DISCUSSION

This study found that one-third of participants who engaged in NMPOU had experienced a recent non-fatal overdose. Participants who acquired POs exclusively from physicians were significantly less likely to be homeless, use crack cocaine, use crystal methamphetamine, receive income from regular employment, and report difficulty accessing services; these participants were also more likely to report moderate to extreme pain. In the primary analyses, acquiring POs exclusively from physicians was negatively associated with non-fatal overdose in bivariate analyses but not in the multivariate analysis. The results indicate that the relationship between acquiring POs exclusively from physicians and non-fatal overdose was not statistically significant, and numerous other risk factors confounded this relationship in the final multivariate model: younger age, homelessness, crystal methamphetamine use, drug dealing, and incarceration.

At baseline, a relatively small proportion of participants reported acquiring POs exclusively from physicians (14%), which is lower than a nationally-representative survey of Americans who engaged in NMPOU that found 20% of participants acquired their POs exclusively from physicians (Becker, Tobin, & Fiellin, 2011). Obtaining POs exclusively from a physician was not independently associated with reporting a recent non-fatal overdose in the final multivariate model, suggesting that the burden of NMPOU-related overdose may not be linked exclusively to opioid prescribing by physicians in this population. In addition, the negative association observed between acquiring POs exclusively from a physician and non-fatal overdose in bivariate analyses may have been driven by this population’s higher likelihood of being housed and lower likelihood of crystal methamphetamine use.

These results align with recent research from the British Columbia (BC) Centre for Disease Control which found that POs were not driving the overdose crisis in BC (Woo, 2018). Previous research also found that obtaining POs from physicians was not associated with markers of higher intensity NMPOU that may be linked with risk for overdose (Ford & Lacerenza, 2011). It should also be noted that counterfeit Oxycontin pills containing fentanyl were circulating in the street drug supply in 2014 (Jafari, Buxton, & Joe, 2015), which may partly explain why participants who did not obtain POs exclusively from a physician were found to have a higher risk of non-fatal overdose. In addition, it is important to note that the study period for these analyses ended in 2016, which is when the proportion of fatal overdoses involving fentanyl in the province of British Columbia more than doubled (from 29% to 67%) (British Columbia Coroners Service, 2017).

Within the context of restrictive opioid prescribing guidelines that encourage low doses of opioids, titration down to low opioid doses, and avoiding the prescription of opioids altogether (Busse et al., 2017; Dowell et al., 2016), further research investigating the relationship between acquiring POs from physicians and overdose is warranted. A stronger evidence base to inform opioid prescribing policies and services for PWUD who engage in NMPOU is particularly important since 63% of participants in this study noted that POs were immediately available from any source within the area where they typically obtain drugs, and this was also not associated with overdose in the bivariate analyses or final multivariate model. Ongoing research to monitor the intersection of NMPOU, the contamination of the street drug supply, opioid prescribing practices, and overdose are needed to develop effective policies that reduce risk for overdose among those who engage in NMPOU and those who use street drugs.

Limitations

This study has limitations. ARYS and VIDUS participants are recruited using nonprobability sampling techniques, therefore the generalizability of these findings may be limited. Data was collected using self-report that may be biased by recall and social desirability response biases. This may be particularly concerning for accurately measuring reports of NMPOU; however, study staff described POs using both the generic and brand names, and showed photographs of POs to clarify the question or assist participants. In addition, self-report of substance use has previously been found to be both reliable and valid (Shane Darke, 1998), and is often the only option for measuring non-fatal overdose as emergency services are not always present at overdoses (S. Darke, Ross, & Hall, 1996).

Our operationalization of two independent variables also have limitations. First, the variable ‘using drugs more often than usual’ is subjectively defined and may capture substance use practices that are less intense than usage that is typically associated with binging on drugs and related harms. Recall and social desirability bias remain a concern with all self-reported measures of socially sensitive behavior; however, there is no standard definition of binging that is relevant for both stimulant and depressant substance use. In addition, the ‘using drugs more often than usual’ variable (as defined in this study) has been independently associated with a range of negative outcomes among youth and adults in this setting (Miller et al., 2006; Nolan, DeBeck, Nguyen, Kerr, & Wood, 2014; Wood et al., 2002), which indicates that this pattern of drug use is an important marker of risk. Second, the definition of overdose was not restricted to overdoses caused by POs. Participants who engaged in poly substance use may have overdosed on other substances which would be expected to bias our results towards the null. Our statistical modeling did consider other substance use patterns in an attempt to isolate the relationship between physician-acquired POs and overdose risk, but there remains a risk of unmeasured confounding.

This study did not control for doctor shopping among study participants. Doctor shopping is a key factor linked to the NMPOU crisis and research from the United States of America found that those who engage in doctor shopping are at risk for overdose as they obtain (on average) higher cumulative morphine-equivalent amounts of POs (Han, Kass, Wilsey, & Li, 2014). It is worth noting, however, previous research in this setting found that 66.5% of PWUD reported being denied POs by physicians; the most commonly reported actions that were taken after being denied POs were buying the medication off the street or using heroin to treat pain (Voon et al., 2015). This study setting may represent a unique environment of PO acquisition for nonmedical use, and future research is needed to further investigate doctor shopping and determine if there are different risk profiles for individuals who source POs for non-medical use from a single physician versus multiple physicians.

Lastly, the outcome for the main analysis was non-fatal overdose, which has previously been established as a key risk factor that predicts fatal overdose (Caudarella et al., 2016; S. Darke, Mills, Ross, & Teesson, 2011; Ontario Agency for Health Protection and Promotion (Public Health Ontario) & P., 2017). Given the increasing contamination of the street drug supply with fentanyl and corresponding rise in overdoses, the risks for fatal overdose in this new era may be different than previously established. Therefore, the relationship between source of POs and fatal overdose may be markedly different than that between source of POs and non-fatal overdose.

Conclusion

Compared to individuals who acquired POs from friends or the streets, participants who acquired POs exclusively from a physician were not at an increased risk of non-fatal overdose. Although further research is needed to investigate NMPOU and overdose at a time when synthetic opioids such as fentanyl are contaminating the street drug supply, the results from this study indicate that strategies to address NMPOU should extend beyond regulating opioid prescriptions.

ACKNOWLEDGEMENTS

In accordance with the submission portal’s instructions, all identifying information has been removed from the manuscript.

The authors thank the ARYS and VIDUS study participants for their contribution to the research, as well as current and past researchers and staff. The study was supported by the US National Institutes of Health (U01DA038886) and the Canadian Institutes of Health Research (MOP–286532). Dr. Kora DeBeck is supported by a MSFHR / St. Paul’s Hospital Foundation–Providence Health Care Career Scholar Award and a Canadian Institutes of Health Research New Investigator Award. Dr. Will Small is supported by a Michael Smith Foundation for Health Research Career Investigator Scholar Award. Dr. Kanna Hayashi is supported by a CIHR New Investigator Award (MSH-141971), a Michael Smith Foundation for Health Research (MSFHR) Scholar Award, and the St. Paul’s Foundation.

Footnotes

DECLARATION OF INTEREST STATEMENT

No potential conflict of interest was reported by the authors.

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