History of Treatment Access and Drug Use among Participants in a Trial Testing Injectable Opioids under Supervision for Long-Term Heroin Injectors

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Journal of Addiction Medicine and Therapy
Cite this article: Oviedo-Joekes E, Marchand K, Guh D, MacDonald S, Lock K, et al. (2015) History of Treatment Access and Drug Use among Participants in
a Trial Testing Injectable Opioids under Supervision for Long-Term Heroin Injectors. J Addict Med Ther 3(1): 1015.
*Corresponding author
Eugenia Oviedo-Joekes, St Paul’s Hospital, 575-1081
Burrard St Vancouver, BC. V6Z 1Y6, Tel: 604-682-2344;
Fax: 604-806-8210; E-mail:
Submitted: 08 April 2015
Accepted: 30 April 2015
Published: 04 May 2015
ISSN: 2333-665X
Copyright
© 2015 Oviedo-Joekes et al.
OPEN ACCESS
Research Article
History of Treatment
Access and Drug Use among
Participants in a Trial Testing
Injectable Opioids under
Supervision for Long-Term
Heroin Injectors
Eugenia Oviedo-Joekes1,2*, Kirsten Marchand1,2, Daphne Guh1,
Scott MacDonald3, Kurt Lock1, Suzanne Brissette4, Aslam H.
Anis1,2, Michael Krausz1,5 and Martin T. Schechter1,2
1Centre for Health Evaluation & Outcome Sciences, Providence Health Care, St Paul’s
Hospital, Canada
2School of Population and Public Health, University of British Columbia, Canada
3Providence Health Care, Providence Crosstown Clinic, Canada
4Centre Hospitalier de l’Université de Montréal, Hôpital Saint-Luc, Canada
5Department of Psychiatry, Detwiller Pavilion 2255 Wesbrook Mall, Canada
INTRODUCTION
Agonist maintenance treatment has shown to be an effective
approach to treat opioid dependency, which is a chronic relapsing
disease [1-3]. Only a relatively small proportion of patients
are able to stop using illicit opioids after abstinence oriented
treatment [4,5]. Methadone maintenance treatment (MMT) is the
most widely studied and available treatment for this condition.
      
buprenorphine, diacetylmorphine, morphine, and possibly
hydromorphone, offered in different program modalities is
required to reach and meet the individual needs of all those
affected by opioid dependency [6,7].
Randomized controlled trials (RCT) in Europe and Canada
have shown supervised injectable diacetylmorphine (the active
ingredient in heroin; [DAM]) to be effective for the treatment
of long-term opioid dependency [3,8-12]. These RCTs testing
injectable DAM recruited long-term opioid (mostly heroin)

      
currently available treatments (primarily methadone) [12,13].
Baseline characteristics across these studies, despite differences
between the settings, were quite similar. Overall, participants
Keywords
•Opioid-dependence
•Injection drug use
•Randomized controlled trial
•Injectable diacetylmorphine
•Injectable hydromorphone
Abstract
Background: For opioid-dependent patients not benetting from conventional treatments (i.e., oral methadone), evidence suggests that supervised
injectable medications are effective. The present study aims to describe participants’ baseline characteristics in a study comparing injectable diacetylmorphine
and hydromorphone and factors independently associated with prior access to methadone at high doses.
Methods: SALOME (Study to Assess Longer-term Opioid Medication Effectiveness) is a phase III, randomized, double blind controlled trial comparing
injectable diacetylmorphine and hydromorphone in 202 chronic, opioid-dependent, current injection opioid users in Vancouver who had at least one prior
episode of opioid maintenance treatment (OMT). Measures included questionnaires and drug dispensation records. In addition to descriptive statistics,
multivariable logistic regression was used to determine characteristics associated with reaching a stable weekly average methadone dose of 100 mgs daily
or more during a methadone treatment episode.
Results: Participants had a mean of fteen years of illicit opioid use, several OMT attempts, medical problems, criminal justice histories, unstable housing,
daily use of illicit opioids and regular use of cocaine. Multivariable analysis showed that individual characteristics, such as separation from biological parents,
prior prescription of opioids for pain and other medical conditions, and preferred methadone dose were independently associated with prior methadone
episodes that reached 100 mgs.
Conclusions: These data emphasize that study participants were in need of alternative treatments at the time of enrolment and t the prole of patients to
whom supervised injectable treatment should be offered. Adding specic dose and duration requirements with respect to prior OMT might exclude individuals
who would benet signicantly from injectable treatment.

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Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 2/11
in these trials were in their late thirties, had used heroin for
   
presented with poor physical and psychological health and many
psychosocial problems such as unstable housing, illegal activities,
repeated incarceration and unemployment [9,14,15].
Although these studies reached very similar target
populations, eligibility criteria regarding prior and current
      
example, currently being on MMT was an inclusion criterion in
the trials conducted in the Netherlands and the United Kingdom
[8,16], while for the Canadian trial it was an exclusion criterion

MMT attempt was an inclusion criterion for the trials in the
Netherlands [8], Spain [11], Canada [12] and Belgium [15], and


It has been proposed that treatment with injectable DAM
should be offered as a second line option, after the patient has
attempted maintenance treatment with oral methadone (or

other treatment [13]. Current guidelines state that most MMT
patients will achieve stability on daily maintenance doses of
     
when patients cannot reach abstinence or minimal use of illicit

of the DAM trials (i.e., continuing regular use of illicit opioids), the
average MMT dose of the methadone arm in most of these trials
         
medications such as DAM, should be restricted only to those who
have previously experienced extended exposure to methadone

Even though there is some evidence suggesting that higher
        
using illicit opioids, a high dose is not necessarily the appropriate

for MMT [18]. Roux et al. [23] recently showed that perceived
methadone dose inadequacy (too low or too high), and not MMT
dose itself, was independently associated with long-term non-
adherence. Together with the fact that the DAM trials reached
similar populations despite differences in MMT entry criterion
suggests that prior detailed MMT requisites might not be enough
or adequate as a clinical indicator of treatment with injectables.
Moreover, recent evidence showed that DAM was more effective
than MMT for those without a prior history of MMT [24]. This
opens the possibility that offering injectable maintenance
treatment only to individuals who have a history of MMT might
further neglect many heroin-dependent individuals who have
always remained outside of treatment. Injectable medications are
an effective approach to attracting such people into treatment,
who may later transition into MMT [25].
SALOME (Study to Assess Longer-term Opioid Medication
Effectiveness) is an ongoing randomized double-blind controlled
trial testing whether injectable hydromorphone is as effective
as diacetlymorphine for the treatment of long-term opioid-
      
        
describe participants’ characteristics at study entry; and second,
to determine factors independently associated with prior
methadone episodes in which participants received high doses.
These results could provide clinicians and policy makers with
evidence to decide whether high doses of prior MMT should be
required to be eligible for treatment with injectable medications.
METHODS
Design, Setting, Participants
SALOME is a two-stage phase III, single site (Vancouver),
randomized, double blind non- inferiority controlled trial
            
participants were randomized to receive injectable DAM, and
the other half to receive injectable hydromorphone on a double-
blind basis. In stage II, participants still retained in stage I
treatment were randomized to continue injection treatment
exactly as in stage I or to switch to the oral equivalent of the same
medication (DAM or hydromorphone). Double-blinding was
maintained in stage II. Study treatments were provided for six
months in each stage and were delivered following a similar
supervised protocol as in our previous clinical trial [12]. The
study received ethical approval from the Providence Health
Care/University of British Columbia Research Ethics boards.
Prior to administration of research procedures and collection
of participant data, participants reviewed the study procedures
with research staff and provided informed consent.
       
dependent, injection drug users who were currently injecting
and who had attempted at least one previous episode of opioid
maintenance treatment. Eligible participants were aged 19 and
older, residing in the greater Vancouver area, had a minimum
          
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
[26], regular injection of illicit opioids in the prior year and at
least two prior addiction treatment episodes, one of which must
have been in opioid maintenance treatment. Volunteers were
excluded if they had severe medical conditions contraindicated
for treatment with DAM or hydromorphone (e.g., respiratory
problems, stage II or greater hepatic encephalopathy), were
pregnant or planning on becoming pregnant, or had an imminent
period of extended incarceration. Self-report data, administrative
records (e.g., Provincial pharmacy records), urine drug screens
 
criteria. A total of 253 volunteers were screened for the study,
which required a minimum of three appointments with the
research and clinical care teams and an average of 25.9 (median =
15) days to complete. A full explanation of screening procedures
is available elsewhere [27].
Measures
Baseline data were collected during the second screening
visit, which occurred prior to randomization and treatment
        
characteristics at study entry, standardized questionnaires
included the following: 1) European Addiction Severity Index
     
for Nicotine dependence (nicotine dependence) [29]; 3) Opioid


Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 3/11
       
quality of life) [32] and 6) Client satisfaction questionnaire
(satisfaction with addiction treatment) [33]). Complementary
questionnaires regarding participant’s socio-demographic (e.g.,
ethnicity, housing), health services utilization (e.g., emergency
departments, primary care visits) and histories of addiction
treatment (e.g., residential treatment, outpatient counseling)

present study design and context. This questionnaire package
was administered by experienced and trained members of the
research team [27], who operate independently of the clinical
team and in a separate site.
In addition to questionnaire data, laboratory records were
collected to determine participant’s current medical status,
including HIV and hepatitis C virus. Historical administrative
records for methadone and Suboxone treatment (licensed
         
British Columbia (BC) provincial drug dispensation database
(PharmaNet). Daily dispensation records were examined from
the earliest date available (September 1, 1995) to the date of
study treatment allocation. It should be noted this database does
not track methadone or Suboxone dispensed in the correctional
or acute care systems, or in settings outside of BC.

and then transferred to the data center for entry and storage.
Data were accessible only by authorized persons of the research
team (Principal Investigator, research coordinators, statisticians,
programmers, research assistants) and the clinical team did not
have access to any research data.
Statistical analysis
Descriptive statistics (means and frequencies) were used
to analyze the baseline characteristics of study participants.
        
           
MMT treatment where there was no interruption in doses of
   
  
      
selected as it represented the high end of the stated range for
stabilization [18] as well as the average methadone dose in the
MMT arm of prior studies testing heroin assisted treatment [9-
12].Chi-square and t-tests were performed for categorical and
continuous variables respectively for bivariable analyses of

A multivariable logistic regression model was built to test the
independent association between participant characteristics and
        
the bivariable analyses were selected to enter the model using

terms for age and gender, age and education and Aboriginal
ancestry and separation from biological parents using the
same model selection criteria. At each stage, covariates for age,
gender and Aboriginal ancestry were forced into the model. The
    
selected based on the smaller Akaike information criterion. Data
presented from the model are the adjusted odds ratios (OR) and
 
age and gender, OR and 95% CI were estimated holding the

level. All analyses were performed in SAS version 9.4 [35] and R
[36].
RESULTS
        
informed consent and were randomized to SALOME. The mean
age of participants was 44.3 years (standard deviation [SD]
  
         
of 74 participants were originally from BC. Among those not
   
in the two years prior to study start (data not shown). Aboriginal
        

    
by those with Aboriginal ancestry (57.1% versus 71.7%; Chi-


average of 14.1 (SD=13.7) days in the month prior the baseline
evaluation. Regarding health status, 55.4% of participants had
a chronic medical problem that interfered with their life, and
lab results showed that 86.1% and 14.9% were positive with
hepatitis C and HIV antibodies, respectively (Table 1).
Table 2 outlines participants’ lifetime and prior month
illicit drug use at study enrolment. Participants reported an
average of 15.4 (SD= 9.4) years of heroin injection. Ninety-two
participants also reported regularly injecting illicit morphine or
hydromorphone for an average of 8.7 (SD=9.3) and 8.1 (SD=8.8)
years, respectively. In the prior month, participants used illicit
opioids an average of 28 (SD=4.2) days, of which heroin injection
had the highest average days of use (Mean = 25.4; SD=8.1). In
addition to injecting illicit heroin, participants reported smoking

Treatment and health services use are described in Table 3.
Based on BC PharmaNet records, participants had an average
of 5.1 (SD=3.4; range 1 to 21) methadone episodes since 1995
            
had an average of 2.8 (SD=2.1) methadone episodes. A total of
92 (45.5%) participants stated they did not want methadone
when asked about their preferred MMT dose. Among those
who indicated a dose preference, their average preferred dose
was 93.7 (SD= 65.4) mgs. In the month prior study enrolment,
participants received an average of 16.1 (SD= 13.6) days of
methadone treatment. In addition to opioid agonist treatment,
participants also reported attempting outpatient withdrawal an
average of 5.6 (SD=7.7) times in their life and 63% of participants
had accessed outpatient counseling. Other health services used
in the month before enrolment were emergency department
visits and health care providers (e.g., addiction physician, nurse),
which were accessed by 9.4% and 79.7% of the participants,
respectively.
      
          


Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 4/11
Socio-demographic Characteristics Total  At least one MMT-
 (n=93) 

Mean [sd] / N (%) Mean [sd] / N (%) Mean [sd] / N (%)
Age 44.3 [9.6] 45.7 [9.7] 43.2 [9.4]
 62  25 (26.9) 37 (33.9)
Currently has an intimate partner 74 (36.7) 33 (35.5) 41 (37.6)
Aboriginal ancestry 62  22 (23.7) *
  (53.5) 56  52 (47.7)
Ever separated from biological parents d 123  48 (51.6) 75 (68.8)*
Placed into foster care e 48 (23.8) 19  29 (26.6)
Years spent in foster care f 3.2 [3.3] 2.7 [3] 3.5 [3.4]
Any non-stable housing in prior 3 years g 141 (69.8) 62 (66.7) 79 (72.5)
Any street housing in prior 3 years 45 (22.3) 16 (17.2) 29 (26.6)
 119 (58.9) 54 (58.1) 65 (59.6)
Income from current non-illicit work h   
Ever paid in exchange for sex 82  33 (35.5) 49 (45)
Paid in exchange for sex in the prior month i 19 (9.4) 8 (8.6) 11 
Months ever incarcerated  37.9 [71.2] 36.96 [59.8]
 14.1 [13.7] 13.3 [13.5] 14.9 [13.9]
Money spent on drugs in prior month j   
Health
Ever attempted suicide 52 (25.7) 22 (23.7)  (27.5)
Ever had unintentional overdoses 136 (67.3)  (64.5) 76 (69.7)
Has chronic medical problem(s) k 112 (55.4)  (45.9) 62 (56.9)
Hepatitis C Positive 174 (86.1) 77 (82.8) 97 (89)
HIV Positive  (14.9)   *
OTI - Physical health l 22.5 [11.9] 21.2 [11.1] 23.7 [12.5]
   
   
Table 1: 
Statistics are p-values for t-test or chi-square test: *
Table Notes:





both biological parents simultaneously.
f. Among those who were ever in foster care (n=46; n missing = 2).
   
public places.
h. Median [interquartile range] Canadian dollar value of money/goods/services earned from legal employment activities, including employment and
alternative employment, such as returns on recycling.


j. Median [interquartile range] Canadian dollars.
k. European Addiction Severity Index- self-reported chronic medical problems that interfered with life.




Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 5/11
Total  At least one MMT-
 (n=93) 

Mean [sd] / N (%) Mean [sd] / N (%) Mean [sd] / N (%)
 22.1 [7.4] 23.1 [7.8] 21.3 [7]
 146 (72.3) 74 (79.6) 72 (66.1)*
Lifetime regular use
Injected heroin, years 15.4 [9.4] 15 [9.7] 15.9 [9.1]
Ever used heroin non-injection 76 (37.6) 33 (35.5) 43 (39.5)
Injected hydromorphone or morphine 92 (45.5) 34 (36.6) 58 (53.2)*
Years of hydromorphone injection 8.1 [8.8] 7.7 [8.7] 8.3 [8.9]
Years of morphine use injection 8.7 [9.3] 12 [8.6] 7.1 [9.3]*
Used cocaine powder or crack cocaine  (84.2) 72 (77.4) 98 (89.9)*
Years of cocaine powder injection 11.8 [9.3] 11.8 [9.5] 11.8 [9.2]
Years of crack cocaine non-injection 11.2 [7.9] 12.1 [8.3]  [7.7]
Prior month use in days
Any illicit opioids 28 [4.2] 28.8 [3.3] 27.3 [4.7]*
Heroin, injection 25.4 [8.1] 25.7 [8.5] 25.1 [7.7]
Times of heroin use on a typical day 3.4 [2.5] 3.3 [2.2] 3.5 [2.9]
Hydromorphone, injection 2.5 [6.4] 3.2 [7.6] 1.8 [5.1]
Morphine, injection 3 [7.1] 3.4 [8] 2.6 [6.3]
Speedball, injection 3.4 [7.5] 2.5 [6.6] 4.2 [8.1]
Cocaine powder, injection 4.8 [9.1] 3.9 [8.5] 5.6 [9.6]
Amphetamine, injection 3.2 [7.1] 2.1 [5.7] 4.1 [8.1]*
Crack cocaine, smoked  [12.7] 8.5 [12.1] 11.9 [13.1]
Times of crack cocaine use on a typical day 4.4 [8.7] 3.6 [7.8] 5 [9.4]
Sedatives, oral  [3.7] 1 [3.9]  [3.5]
Cannabis, oral or smoked 6.3  5.2 [9.6] 7.3 [11.5]
Alcohol over threshold c  [2.5]  [3.3]  [1.4]
 4.4 [2.4] 4.3 [2.6] 4.4 [2.4]
Table 2: Substance use history of SALOME participants at baseline.
Statistics are p-values for t-test or chi-square test: *
Table Notes:

          

episode.
           
alcohol taken to the point of intoxication.

with Aboriginal ancestry, history of separation from biological
parents, lifetime regular hydromorphone and morphine use,
         
addition, there were opioid treatment related characteristics that
        
maintenance prescription, years of regular opioid maintenance
treatment, ideal and preferred doses, ever prescribed opioids for
pain or other medical conditions and days of MMT in the prior
month.
Table 4 shows the results of the multivariable model for
characteristics independently associated with at least one MMT
         
demographic characteristics independently associated with the
   
between age and gender, and being separated from biological


Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 6/11
Total No MMT-100a At least one MMT-
 (n=93) 

Mean [sd] / N (%) Mean [sd] / N (%) Mean [sd] / N (%)
Opioid Maintenance Treatment History
Age of regular prescribed opioids for addiction 33.6 [9.3] 35.1 [9.1] 32.4 [9.2]*
Years of regular prescribed opioids for addiction 5.5 [5.3] 4.4 [4.5] 6.5 [5.8]**
Times ever attempted MMT since 1995 c 5.1 [3.4] 4.7 [3.1] 5.4 [3.7]
Times attempted MMT in prior 5 years c 2.8 [2.1] 2.8 [2.1] 2.8 [2.1]
Highest daily dose of methadone in milligrams c d   ***
Ideal dose in milligrams e 93.7 [65.4] 58.5 [39.2] 121.4 [68.7]***
Methadone dose preferences: f
 38 (18.8) 29 (31.1) 9 (8.3) ***
 55 (27.2) 12 (12.9) 43 (39.5)
Does not want methadone 92 (45.5) 39 (41.9) 53 (48.6)
Unsure 15 (7.4) 12 (12.9) 3 (2.8)
Ever attempted suboxone c  (14.9) 18 (19.4) 12 (11)
Days suboxone ever dispensed c 122.2 [251.9] 65.5 [79.1] 
Maximum suboxone dose in milligrams c 15.2 [17.6] 15.4  14.8 [11.7]
More than 6 months ago since last OMT access c 41  23 (56.1) 18 (43.9)
Days of MMT in prior month c 16.1 [13.6] 13.2 [13.4] 18.6 [13.3]**
   
Other Health Services Use
Times attempted outpatient withdrawal 5.6 [7.7] 5.7 [7.5] 5.5 [7.8]
Ever accessed outpatient counselling 127 (62.9) 57 (61.3)  (64.2)
Regular lifetime use of safe injection site 87 (43.1) 44 (47.3) 43 (39.5)
Regular prescribed opioids for pain or medical
conditions 93 (46) 33 (35.5) **
Ever prescribed sedatives  48 (51.6) 55 
Ever prescribed stimulants 41  17 (18.3) 24 (22)
Days received outpatient counseling in prior month   
Days accessed the safe injection site in prior month 9.9 [11.3] 11 [11.7] 8.8 
Visited the emergency department in prior month 19 (9.4)   9 (8.3)
Accessed health care provider in prior month 161 (79.7) 71 (76.3)  (82.6)
Table 3: 
Statistics are p-values for t-test or chi-square test: * *****
MMT = methadone maintenance treatment; OMT = Opioid Maintenance Treatment
Table Notes:



c. Based on current Pharma Net records since 1995, all participants had at least one methadone attempt since 1995.
d. Median [interquartile range]


  
             
treatment or selected unsure (n missing = 2).
  
this questionnaire in reference to methadone treatment, 14 in reference to suboxone and one in reference to a prior abstinence oriented treatment.

Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 7/11
Variable  OR 95% CI
Constant 1.743 (1.63) - -
Age *** - -
Gender Ref
Man
 -3.92 (1.87) *- -
Age * Gender a
Man Ref
 *- -
Separated from biological parents
No Ref Ref
Yes *2.18  - 4.54
Regular injection of illicit HDM or morphine
No Ref Ref
Yes *  - 4.25
Regularly prescribed opioids for pain or other
medical conditions Ref Ref
No
Yes ** 2.51 1.18 - 5.31
Preferred methadone dose b Ref Ref

Does not want methadone c ** 4.69 1.71 - 12.87
 *** 12.67 3.93 
Table 4: 
* *****

Notes: Model was built with 194 observations (8 observations were removed: 4 participants responded about preferred dose in reference to suboxone;
2 participants stated ‘prefer not to answer’ to the question about being separated from biological parents; 2 participants had a missing response to the
   


 






age and gender suggests that the odds of having an MMT-
         
            
    

ages.
          
mg MMT episode was higher for participants with a history
of regular prescription of opioids for pain or other medical
conditions (OR = 2.51; 95% CI = 1.18-5.31) and regular injection
 
4.25). In addition, compared to participants who indicated an

    
          

     

DISCUSSION
       
similar to prior clinical trials with injectable diacetylmorphine,
including the preceding Canadian trial [8-11,15,37]. Participants
         

Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 8/11
several attempts at MMT, and had medical problems, histories
with the correctional system and current involvement in illicit
activities, unstable housing, daily use of illicit opioids, mostly
heroin, and regular use of cocaine and crack cocaine. As in the
prior Canadian study, Aboriginal people were overrepresented in
       
approximately 5%).
Treatment with supervised injectable DAM is aimed at
reaching long-term illicit opioid users with major physical and
social complications and for whom oral, long-acting opioid
         
SALOME participants shows profound disadvantages in social

prevalence of separation from biological parents with a slightly
higher prevalence among those with Aboriginal ancestry. More
than half of the participants expressed they had a chronic medical
condition that interfered with their lives and approximately nine
out of ten participants were hepatitis C and/or HIV positive.
This is also an older cohort (average age was 44) despite the
inclusion criterion was a minimum age of nineteen). As in other
studies with similar populations, women were younger [38,39]
         
showing that women progressed to opioid dependence more

addition, participants had attempted oral methadone treatment
          
         
months prior to enrolling in SALOME. Therefore, it is clear that
the SALOME participants belong to the drug using population

those offered in the trial.
        
DAM should be offered after attempting maintenance treatment
with oral methadone (or buprenorphine) [13], it remains unclear
if high doses and longer time engaged in prior MMT should be
required to offer this treatment. This study tested variables


years. Age, gender, separation from biological parents, history of
regular illicit morphine or hydromorphone injection, having been
regularly prescribed opioids for pain or other medical conditions
and preferred MMT dose were independently associated with
     
the factors related to treatment conditions such as treatment
retention (e.g., years on MMT), access to treatment (e.g., number
of times attempted MMT), satisfaction with treatment or access
to counseling was independently associated with higher doses.
         
MMT in the past might be an inadequate indicator of the type of
treatment participants need at present.
       
regularly for pain management or other medical conditions
was independently associated with reaching higher doses of

receiving MMT have reported chronic pain [43-45]; however,
       
       
while receiving MMT might be avoided for safety reasons (e.g.,
drug interactions) or concern about diversion [44,46]. Results
regarding the relationship between the use of MMT to manage
both pain and opioid dependence are mixed. Some studies have
found that among MMT patients, those in need of pain treatment
had higher methadone doses compared to those who did not
[44,45], while others have shown that there were no differences
in methadone doses between opioid dependent patients with
   
lack of adequate doses due to concerns over safety or diversion,
may be one explanation for participants’ continued illicit opioid
use and combinations of illicit opioids used [22]. In the present
study, history of regular hydromorphone or morphine injection
        
relationship of pain and regular use of non-prescribed opioids

       
treatment for pain and addiction.
This study also provides additional support for the importance
of integrating patient preferences in the provision of treatment.
Participants’ dose preferences were strongly and independently
        

use of illicit opioids [49], perceived dose inadequacy has been
associated with poor outcomes [23], and dose-adjustment should
       
Incorporating patient perspectives [51] and improving patient-
provider relationships [52] are necessary for optimal patient
outcomes with maintenance treatment.
Maintenance treatment with injectable medications is an
        

body of evidence in the chronic disease literature shows that
patients’ illness state and treatment regimen are closely related
[53]; for example, as patients experience acute symptom episodes,
more comprehensive treatments are necessarily prescribed.
     
with its attendant social and medical problems, who continue to
use illicit opioids despite the availability of effective treatments,
it is conceivable that one treatment regimen may not be effective

maintenance treatments, offered in different program modalities,
are likely required to meet every individual’s needs over time
[6,7,25].
The centralized drug dispensation database in British
Columbia allowed us to determine characteristics of prior
methadone (or Suboxone) treatment attempts by participants
enrolled in the study. However, administrative databases have
limited capacity to explore the potential relationship between
episode characteristics with the care delivered, due to the nature
          
information about the prescribing physician’s approach, whether
the clinic was low-threshold or if other ancillary services were
offered. Although our baseline questionnaires included extensive
questions on addiction treatment and health services received,
we cannot match them to the drug dispensation dataset. The
aim of this study was not to determine the effectiveness of prior
MMT episodes at an individual basis, but such evidence would

Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 9/11

program offering more intensive injectable treatments.
Most of the participants in this study had accessed and
received stable and high doses of MMT and were currently
injecting street opioids regularly. Thus, we must consider
alternative treatments to reduce the harms associated with illicit
opioid use for this particular group. Our data demonstrate that
these participants were in need of alternative treatments at the
 
      
support the importance of individualized treatment planning

authorities with enough and adequate information regarding
which patients should have access to injectable treatment in the

ROLE OF FUNDING SOURCES
The SALOME trial is funded through an operating grant from
the Canadian Institutes of Health Research (CIHR), Providence
       
support from the Canada Research Chairs Program, CIHR
New Investigator program, the University of British Columbia,
Providence Health Care research Institute, Vancouver Coastal
        
Research.
Contributors
EOJ, MTS, MK, SB and AHA are investigators in the SALOME
study. EOJ, KM, KL and SM made substantial contributions to the
          
           
          
     
accountable for the integrity of the work.
CONFLICT OF INTEREST

Informed Consent
All procedures followed were in accordance with the
ethical standards of the responsible committee on human
experimentation (institutional and national) and with the
         
consent was obtained from all patients for being included in the
study.’
ACKNOWLEDGEMENTS
The authors wish to acknowledge and thank the SALOME
trial applicants for their time and support to the study. Also, at
Providence Health Care, Justin Karasik and the communications
        
and the clinical team at Providence Crosstown Clinic; Amin
Janmohamed and the pharmaceutical team at Providence
    
DSMB members, Dr. David C. Marsh, CHEOS and the SALOME
investigators and research team.
Clinical trial registration: 
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
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Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 10/11
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
25.       
assisted treatment effective for patients with no previous maintenance
        

26.       
et al. Differential long-term outcomes for voluntary and involuntary
transition from injection to oral opioid maintenance treatment. Subst
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27.          
pitch perception for spoken words in an able adult with autism.

28. 
MT. The SALOME study: recruitment experiences in a clinical trial
offering injectable diacetylmorphine and hydromorphone for opioid
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29. 

1992; 9: 199-213.
        


31.            
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32.          
          
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33. 
     
instrument in a heroin-dependent population. Drug Alcohol Depend.
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34.         
       
use of psychological testing for treatment planning and outcome
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36. 
et al. External chest compressions using a mechanical feedback device

37.     

38.      
         
Conference of the Canadian Society of Addiction Medicine Vancouver,

39.           
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
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         
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et al. Substance abuse treatment entry, retention, and outcome in
          
1-21.
43.            
comorbidity among individuals with opioid use disorders in the

44.   
management of pain among people who inject drugs in Vancouver.

45. Dunn KE, Brooner RK, Clark MR. Severity and interference of chronic
       

46. Dhingra L, Masson C, Perlman DC, Seewald RM, Katz J, McKnight C, et al.
Epidemiology of pain among outpatients in methadone maintenance

47.  
innocent: a qualitative study of the management of chronic non-
cancer pain among patients with a history of substance abuse. Addict

48.            
Prevalence and characteristics of chronic pain among chemically
dependent patients in methadone maintenance and residential

49. Ilgen MA, Trafton JA, Humphreys K. Response to methadone
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    
Predictors of non-use of illicit heroin in opioid injection maintenance
    

Central
Oviedo-Joekes et al. (2015)
Email:
J Addict Med Ther 3(1): 1015 (2015) 11/11
81-86.
51. 


52.            
satisfaction surveys in addiction services: Opioid maintenance
treatment as a representative case study. Patient Preference and

53.              
Predictors of non- prescribed opioid use after one year of methadone
treatment: an attributable-riskapproach (ANRS-Methaville trial).

54.           
complexity: a functional, patient-centered model of patient complexity
 

55.       
   

Oviedo-Joekes E, Marchand K, Guh D, MacDonald S, Lock K, et al. (2015) History of Treatment Access and Drug Use among Participants in a Trial Testing Inject-
able Opioids under Supervision for Long-Term Heroin Injectors. J Addict Med Ther 3(1): 1015.
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