UBC Faculty Research and Publications

The SALOME study: recruitment experiences in a clinical trial offering injectable diacetylmorphine and… Oviedo-Joekes, Eugenia; Marchand, Kirsten; Lock, Kurt; MacDonald, Scott; Guh, Daphne; Schechter, Martin T Jan 26, 2015

Your browser doesn't seem to have a PDF viewer, please download the PDF to view this item.

Item Metadata


52383-13011_2014_Article_324.pdf [ 755.07kB ]
JSON: 52383-1.0074653.json
JSON-LD: 52383-1.0074653-ld.json
RDF/XML (Pretty): 52383-1.0074653-rdf.xml
RDF/JSON: 52383-1.0074653-rdf.json
Turtle: 52383-1.0074653-turtle.txt
N-Triples: 52383-1.0074653-rdf-ntriples.txt
Original Record: 52383-1.0074653-source.json
Full Text

Full Text

METHODOLOGY Open AccessThe SALOME study: recruitment experiences in aclinical trial offering injectnumber of applicants compared with the limited number that could be randomized and treated. Our studyOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3http://www.substanceabusepolicy.com/content/10/1/3East Mall, Vancouver, BC V6T 1Z3, CanadaFull list of author information is available at the end of the articleemphasizes the value of integrating these strategies into clinical addiction research to overcome study-specific barriers.Trial registration: ClinicalTrials.gov: NCT01447212.Keywords: Opioid dependency, Injectable diacetylmorphine, Injectable hydromorphone, Recruitment, Randomizedclinical trial* Correspondence: eugenia@cheos.ubc.ca1Centre for Health Evaluation & Outcome Sciences, Providence Health Care,St. Paul's Hospital, 575- 1081 Burrard St., Vancouver, BC V6Z 1Y6, Canada2School of Population and Public Health, University of British Columbia, 2206for this study took longer than planned. The recruitment chand hydromorphone for opioid dependencyEugenia Oviedo-Joekes1,2*, Kirsten Marchand1,2, Kurt Lock1, Scott MacDonald3, Daphne Guh1and Martin T Schechter1,2AbstractBackground: The Study to Assess Long-term Opioid Medication Effectiveness (SALOME) is a two-stage phase III,single site (Vancouver, Canada), randomized, double blind controlled trial designed to test if hydromorphone is aseffective as diacetylmorphine for the treatment of long-term illicit opioid injection. Recruiting participants for clinicaltrials continues to be a challenge in medical and addiction research, with many studies not being able to reach theplanned sample size in a timely manner. The aim of this study is to describe the recruitment strategies in SALOME,which offered appealing treatments but had limited clinic capacity and no guaranteed post-trial continuation of thetreatments.Methods: SALOME included chronic opioid-dependent, current illicit injection opioid users who had at leastone previous episode of opioid maintenance treatment. Regulatory approvals were received in June 2011 andrecruitment strategies were implemented over the next 5 months. Recruitment strategies included ongoing opencommunication with the community, a consistent and accessible team and participant-centered screening. Allapplicants completed a pre-screening checklist to assess prerequisites. Applicants meeting these prerequisites werelater contacted to commence the screening process.Results: A total of 598 applications were received over the two-year recruitment period; 130 were received on thefirst day of recruitment. Of these applicants, 485 met prerequisites; however, many could not be found or were notreached before recruitment ended. For the 253 candidates who initiated the screening process, the average timelapse between application and screening date was 8.3 months (standard deviation [SD] = 4.44) and for the 202randomized to the study, the average processing time from initial screen to randomization was 25.9 days(SD = 37.48; Median = 15.0).Conclusions: As in prior trials offering injectable diacetylmorphine within a supervised model, recruiting participantsallenges overcome in SALOME were due to the high© 2015 Oviedo-Joekes et al.; licensee BioMedCreative Commons Attribution License (http:/distribution, and reproduction in any mediumDomain Dedication waiver (http://creativecomarticle, unless otherwise stated.able diacetylmorphineCentral. This is an Open Access article distributed under the terms of the/creativecommons.org/licenses/by/4.0), which permits unrestricted use,, provided the original work is properly credited. The Creative Commons Publicmons.org/publicdomain/zero/1.0/) applies to the data made available in thisOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 2 of 9http://www.substanceabusepolicy.com/content/10/1/3BackgroundOpioid dependency remains to be a major public healthconcern in North America and worldwide. Abstinenceoriented treatment has shown to benefit small propor-tions of people struggling with opioid-dependence [1];opioid substitution and maintenance treatment continuesto be the best approach to stop the use of illicit opioids[2]. Oral methadone is the most used and studied of thesetreatments with demonstrated effectiveness at reducingillicit drug use and improving health and psychosocial out-comes [3]. Few other opioids besides oral methadone havebeen studied for the treatment of opioid dependency.Among these other opioids, injectable diacetylmorphine(i.e., pharmaceutical-grade heroin [DAM]), dispensed in acontrolled and medically supervised setting, has shown tobe effective in the treatment of long-term opioid injectorsnot sufficiently benefitting from oral methadone [4].Despite that several randomized clinical trials (RCT)in Europe and Canada have demonstrated the effective-ness of DAM, very few countries have adopted it as partof their addiction treatment system. There is a clear needfor alternative treatments as effective as injectable DAMthat health care systems could adopt to attract and retainlong-term street opioid injectors into treatment. One suchalternative could be HDM [5] and the SALOME (Study toAssess Long-term Opioid Medication Effectiveness) studywas designed to test this. SALOME is a randomized doubleblind controlled trial testing if injectable HDM (a licencedpain medication) is as effective as DAM for the treatmentof long-term opioid-dependent individuals who are notbenefitting sufficiently from conventional treatments, andif a transition to the oral equivalent of HDM and DAMafter six-months is as effective as the injection form.Recruiting participants for clinical trials can be slowand difficult, and much effort is dedicated to reach therequired sample size within a reasonable timescale andbudget [6-8]. For example, a review of RCTs across awide array of medical conditions in the United Kingdomshowed that nearly half of the trials received an extensionof some kind due to the struggle to recruit the plannedsample size [9]. Although it is unclear why some trials re-cruit more effectively than others, it has been suggestedthat studies providing treatments that are desired and/oronly available through the trial, or studies comparing twosimilar treatments, might have fewer challenges with re-cruitment [10-13].Methodological and empirical studies regarding re-cruitment in clinical trials for addiction are sparse. Someevidence suggests that RCTs in this field face similarchallenges to those aforementioned in medical research[14]. However, addiction treatment trialists also encoun-ter barriers specific to this field [15]. For example, mo-tivation to participate may be more challenging whenrecruiting participants who have generally unstable dailyliving conditions and difficulties attending appointments[16]. Studies with similar populations have addressed theimportance of building trust with the target population,support them to keep appointments, and provide ancillaryservices for other needs as part of their recruitment strat-egies [17]. Moreover, traditionally employed strategies formotivating participation, such as telephone reminders [18],may not be feasible with this population. These unique fac-tors necessitate discussion amongst addictions researchersto better inform strategies tailored to benefit recruitmentin forthcoming addiction trials.Context specific challenges related to recruitment forRCTs with DAM treatment have also been documented.Every RCT testing DAM has had longer than expectedrecruitments and in some cases had to enrol fewer par-ticipants than planned [19]. A variety of context-specificreasons explain this. For example, in Spain, by the timethe study was able to start enrolling participants, injec-tion street heroin use had dropped drastically (heroinusers were smoking it instead) and the sample size couldnot be reached [20]. In a Belgian study, one of the mainreasons street heroin users did not apply was the concernover the limited length of access to the study medications[19]. In our prior study, NAOMI (North American OpiateMedication Initiative), the site in Vancouver received morethan 1,000 applications; however, the study criteria did notreflect the realities of the intended sample population andmost applicants did not even meet minimal requirementsat first contact [21].SALOME compared two treatments appealing to thetarget population that were only available through thestudy. Despite the advantages that this scenario presentsfor recruitment, experience in prior RCTs testing DAMsuggested that offering desirable treatments might notbe sufficient to meet the planned sample size within a rea-sonable time. The aim of the present study is to describethe recruitment experiences of the SALOME trial and dis-cuss the strategies that were employed. This paper couldinform the development of recruitment strategies for up-coming clinical trials in addictions research, a field thatfaces unique barriers.MethodsStudy designSALOME is a two-stage phase III, single site (Vancouver),randomized, double blind controlled trial involving a totalof 202 participants. The study population is defined aschronic, opioid-dependent, injection drug users who arecurrently injecting and who have attempted at least oneprevious episode of opioid maintenance treatment. Spe-cific eligibility criteria included: a) minimum age of nine-teen years; b) currently residing in the greater Vancouverarea of British Columbia, Canada; c) current regular use ofinjectable opioids; d) at least two verified prior addictionOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 3 of 9http://www.substanceabusepolicy.com/content/10/1/3treatment attempts, including one episode of opioid sub-stitution treatment; e) at least five years or more of illicitopioid use; f ) poor health or psychosocial functioning; andg) provision of fully informed consent. Participants wereexcluded if they did not meet inclusion criteria, had med-ical conditions contraindicated for treatment with inject-able opioids or criminal justice involvement resulting inprolonged incarceration. The study was reviewed andreceived ethical approval from the University of BritishColumbia/Providence Health Care research ethics board.Sample size requirements for the study were calculatedbased on illicit heroin use as the primary outcome. Usingdata derived from the results of our prior NAOMI trial, anon-inferiority design with an expected decline of 20 days(standard deviation = 11.0) of illicit heroin use from base-line, a margin of 4 days, a power of 0.90, an expected loss-to-follow-up rate of 0.05 and a one-sided alpha level of0.05, requires 202 participants (101 per group) for phase I.With a sample size of n = 202, we can expect that approxi-mately 172 participants will enter into phase II. Under thesame assumptions as above, this will yield a non-inferioritytrial with power = 0.86.In phase I, half of the 202 participants were randomizedto receive injectable DAM, and the other half to receiveinjectable HDM. In phase II, participants still receivingtreatment in phase I were randomized to continue injec-tion treatment exactly as in phase I on a blinded basis orto switch to the oral equivalent of the same medication(DAM or HDM).DAM or HDM, either orally or injected, could only beprescribed and self-administered in the study clinic undersupervision of health care providers, up to three timesdaily. Study treatments were provided for six months ineach phase, followed by a one-month period during whichparticipants still being treated with DAM or HDM were ta-pered and transitioned to other treatments available in thecommunity (e.g., methadone). Upon entry into the trial,each participant had access to a defined range of primarycare services matched to the prevalent conditions seen ininjection drug users. A psychosocial support worker wasalso assigned who provided individual counselling servicesand case management (i.e., coordinated inter-disciplinaryservices such as housing and disability support).Clinic capacity and timelineTo be able to operate, the SALOME trial site requires anExemption under Section 56 of the Canadian federalControlled Drugs and Substances Act. This allows healthcare staff and researchers to use controlled narcotics forscientific purposes. Several security features are needed ina clinic in order to receive such an exemption and onlyone, the Vancouver clinic that was used in our prior NA-OMI study, met these requirements at the time. The studyclinic was planned to accommodate up to 95 participantsreceiving injectable medications. Once study participantscompleted the treatment or were switched to oral medica-tions (phase II) or dropped out from the study, new par-ticipants could be screened and allocated into the study.The limited clinic capacity resulted in a varying enrolmentpace of six to twenty participants per month, instead offour to five per week as planned.It later became clear that in order to meet the serviceneeds of the participants, the clinic could best operate withno more than 85 participants receiving injectable medica-tions per day. In addition to clinic capacity, three externalevents halted enrolment for five months. First, a nationalshortage of hydromorphone occurred four months into thestudy (Figure 1a) and caused a two month halt to recruit-ment while the research and clinical care teams developeda strategy and gained the necessary approvals for the studypharmacy to manufacture hydromorphone for participantsonly. Due to air quality issues requiring construction in thebuilding where the study clinic is placed (an old bank), re-cruitment was halted for one month to reduce the physicaldemands on the clinic. Finally, changes in the ProvincialPharmaNet recording of all drug prescription practices thatwould have led to the potential unblinding of clinic healthcare workers also caused a two month pause to recruit-ment while the clinical team worked with the authoritiesto develop a site specific protection feature. These impedi-ments and the reduced clinic capacity delayed reaching thesample size by seven months approximately.Community engagementRegulatory approvals were received in June 2011 and re-cruitment strategies were implemented over the next fivemonths. A team was assembled and included the principalinvestigator (EOJ), research coordinators (KL; KM), thelead nurse, lead physician (SM), and communications dir-ector. This team engaged in recruitment collaborativelyand remained consistent throughout the study. One of theResearch Coordinators (KL), who had over a decade ofexperience working with the target population in theneighbourhood where the study was conducted, was fullydevoted to overseeing recruitment.Before recruitment opened, the team established a con-veniently located research office, telephone recruitmentnumber, email address, and study website. As part of ef-forts to reach every opioid user in Vancouver, we identifiedagencies, not-for-profit groups and health care providersthat work with the target population and would be able toassist relaying information about the trial. These agencieswere contacted and offered an opportunity to have theteam provide an information session for staff and clients.Over these months, we hosted approximately 20 formalinformation sessions with various agencies, including druguser groups (e.g., Vancouver Area Network of Drug Users,Drug Users Resource Centre), the research ethics board,Oviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 4 of 9http://www.substanceabusepolicy.com/content/10/1/3health care teams (e.g., Vancouver Native Health, Down-town Eastside Women’s Center), social workers, legalagencies, health officers, and politicians. These sessionsincluded a 20 to 30 minute verbal presentation of thestudy and time for questions. Common discussion topicsincluded eligibility criteria, the duration of treatment andtransition planning at the end of the study. InformationFigure 1 Cumulative recruitment, screening and enrolment to the SAof applicants, ineligibles, and participants randomized to the SALOME trialNumber of candidates and randomized participants screened for the SALOpackages were distributed either at the end of the sessionor in lieu of; materials included relevant publications fromthe NAOMI trial, contact information and answers to fre-quently asked questions. The team continued to provideupdates and information sessions during the study as re-quested by these groups or as new information about thestudy became available.LOME trial. a) Cumulative recruitment into the SALOME trial. Numberover time. b) Cumulative screening of candidates in the SALOME trial.ME trial over time.Oviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 5 of 9http://www.substanceabusepolicy.com/content/10/1/3During this time, a Community Advisory Board (CAB)was also established and is comprised of various stake-holders in the community. The purpose of the CAB is toprovide guidance and feedback to the SALOME teamwith respect to accrual, retention, compliance, access, andethical issues surrounding study. The CAB also serves as alink between the community and the SALOME team andhas been a place for discussions of strategies for continu-ation of provision of study treatments.These community engagement activities provided theteam with an opportunity to learn of the perceivedstrengths and weaknesses of the trial and their implica-tions for recruitment and the study itself. Strengthsincluded the benefit of the medication and the need foralternative treatments. The lack of guaranteed continu-ation of study treatments was the main worry expressedby the community and patients. Also, some addictionsphysicians expressed concern over patients leaving suc-cessful treatments and binging in street drug in order toqualify for the study.Recruitment processSince we experienced a combination of positive interestin SALOME as well as opposition, the team preparedthe first day of recruitment (December 19, 2011 between9am and 5pm) taking into account that the number ofapplicants could be high or low. In addition to openingthe recruitment telephone number, recruitment tableswere set up at three key agencies serving the targetpopulation. Information about this first day was dis-played in advance at several local agencies and the CAB.In order to filter minimal requirements without signingconsent and engaging in full screening, applicants wereinterviewed at first contact with a pre-screening checklist,which assessed prerequisites for initiating screening andcollected contact information. The recruitment telephonenumber was the primary method for applying to the studyafter the first day of recruitment. A chronological num-bered list of applicants was created and used to determinetheir processing order. Once an applicant’s number wasreached on this list, the applicant was re-contacted. Uponreaching the applicant, the on-file pre-screening checklistwas reviewed and the applicant was asked if he or she wasstill interested in participating. If so, an appointmentwas made to begin the screening process. If an applicantcould not be found, the chronological order of their ap-plication was not displaced. For example, candidateswho were incarcerated when the team initially contactedthem were able to reconnect and begin the screeningprocess upon release.Screening to the study required a minimum of threeappointments, each lasting an hour or longer in duration.There were no costs to participants and at each stage inthe screening process candidates were provided a modeststipend for their time amounting to $35 CAD over thethree visits (average hourly wage in British Columbia is$10.50 CAD). During the first visit, candidates signed theinformed consent, and the process of verifying eligibilitycriteria was started. At the second screening visit, candi-dates completed the baseline questionnaires. Candidatesmeeting criteria up to the end of the second screeningvisit were scheduled to meet with the study physician for afull medical examination and confirmation of all criteria.This visit was multi-disciplinary and patient centered; can-didates were introduced to the health care providers andservices available at the clinic (reception, nurses, physi-cians, psychosocial team) and a psychosocial assessmentwas completed. This process was effective for screeningand providing an orientation to all aspects of the careavailable at the clinic.Following the medical examination and confirmationof all criteria, the study physician notified the researchteam of participant eligibility. A member of the researchteam then randomized the participant using the trialrandomization database. Randomization notifications werethen distributed to the clinic coordinator and pharmacymanager for preparation of the participant’s treatmentinitiation.AnalysisMean, standard deviation [SD] and proportions were usedto describe time lapse, the flow of applications and meet-ing or not prerequisites or study criteria for applicantsand candidates.ResultsFrom December 2011 to December 2013, a total of 598(196 female, 397 male, 4 transgender-female and 1 withmissing gender) applications were received for the SAL-OME trial. Figure 1a and 1b show the progress of the ap-plications over the two-year period. On the first day 130individuals applied to the study (Figure 1a). These appli-cants were randomly assigned a number that was used todetermine their processing order. Individuals who appliedafter these 130 applicants were added to this list in chrono-logical order. After the first day the number of applicantscontinued to increase steadily over the two-year period at apace faster than the study had capacity to enrol. Therefore,efforts to actively promote recruitment (e.g., recruitmentposters, recruitment tables) were halted.Figure 2 shows the flow of the applications through torandomization. From the total number of applicants, 485(81.1% of total 598 who applied) met the prerequisites onthe pre-screening checklist. Among those eligible forscreening at this stage, 159 were female, 321 were male, 4were transgender-female and one applicant’s gender wasmissing. For various reasons shown in Figure 2, we couldnot re-assess 185 of these 485 applicants (e.g., could notOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 6 of 9http://www.substanceabusepolicy.com/content/10/1/3be found, passed away, etc.) and an additional 29 appli-cants were excluded for no longer meeting study prerequi-sites or no longer being interested in participating. Therate of applicants not meeting the prerequisites on thepre-screening checklist throughout the two-year recruit-ment period remained constant (Figure 1a).A total of 253 (52.2% of those who met prerequisiteson the pre-screening checklist; 76 female, 174 male, 3transgender-female) candidates signed the informed con-sent and initiated screening. Due to the limited cliniccapacity and the external situations that halted recruit-ment, the average time lapse between the point of firstapplication and first screening visit was 8.3 (SD = 4.44;Q1 = 6.33; median = 8.67; Q3 = 11.03) months. Their aver-age age was 44.76 (SD = 9.61; Q1 = 38.0; median = 45.0;Q3 = 52.0). Thirty candidates (11.8% of those who startedscreening; 11 female, 19 male) were excluded due to notmeeting at least one of the inclusion or exclusion criteria.In addition, 14 (5 female, 9 male) candidates started thescreening process but did not continue for unknown rea-sons and 7 (1 female, 6 male) expressed that they were nolonger interested in participating in the study. The pri-mary reasons for exclusion of the 30 candidates was theFigure 2 SALOME screening flow chart. Stages of screening in the SALOregularity of current opioid injection (n = 15) and not suf-ficiently attempted OST or other types of addiction treat-ment (n = 9). For those eligible candidates, the averagenumber of days between the first screening visit andrandomization date was 25.95 (SD = 37.48; Q1 = 9.0; me-dian = 15.0; Q3 = 23.0; Figure 1b). For 28 participants, thetime lapse between first consent and randomization wasmore than 30 days, mainly because of challenges main-taining contact and rescheduling of missed appointments.DiscussionAs in prior trials offering injectable DAM within a su-pervised model, recruiting participants for this studytook seven months longer. However, this additional timecan be attributed to the extraneous events and limitedclinic capacity. Without these events and with a largerclinic, recruitment into the trial would have been evenfaster than expected.The challenges that the research team had to overcomefor recruitment into SALOME were due to the high num-ber of applicants compared with the limited number thatcould be randomized and treated. Our recruitment planwas based on recommendations from recruitment intoME trial and number of applicants at each stage.Oviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 7 of 9http://www.substanceabusepolicy.com/content/10/1/3clinical trials in general, the addictions field and priorexperiences of this research team [21]. The recruitmentstrategies that were instrumental in overcoming thesechallenges included the community engagement process[13,22], the consistent, accessible and experienced team[13] and a participant-centered screening process [12,14].The community engagement process was highly valu-able in forming partnerships with key agencies workingwith the study population and the patients. A very im-portant long-term aim of the community engagementplan was to lay the foundation for future continuation ofsupervised injectable treatment. With these partnershipsand their vested interest in this, we had the opportunity toestablish this groundwork. In addition, the CAB was animportant forum for communicating information aboutarising barriers as well as devising collaborative strategiesfor overcoming them. Throughout the study, there wasopen and ongoing communication between the researchteam and the community. For example, when a physiciancontacted any team member with concerns regarding apatient being included into the study, meetings werepromptly held to discuss these concerns, while upholdingmutual goals to protect participant/patient autonomy andthe scientific integrity of the study.The commitment of the community and stakeholdersstrengthened our ability to recruit the necessary numberof participants despite the many external barriers affect-ing recruitment. In addition, having an experienced teamimproved communication and the consistency of researchprocedures. The team’s cohesion proved beneficial as therecruitment processes remained constant and the team’sskills matured over time as barriers continued to arise.Messages and information relayed about the study werealso homogeneous through media, information materialsand our team. Each message was tailored for the intended(i.e., participant, health care provider) audience, yet wasconsistent to minimize the negative impact arising barriersmight pose to ongoing recruitment. For example, whenwe experienced the hydromorphone shortage, we quicklydeveloped a plan for addressing this issue and a script forcommunication. This reduced uncertainty and maintainedcommunity engagement and support.As in many RCTs, the stages of screening can be aburden on candidates and SALOME was no exceptionto this. In an effort to reduce the loss of candidatesduring the screening stages while maintaining scientificrigor, our procedures aimed to be participant-centered.Overall interactions with candidates were supportive andunderstanding of the daily struggles applicants had. Mostcandidates required additional support from the researchteam or other agencies to, for example, attend the mul-tiple appointments required for screening. Sometimes ateam member met candidates at their residence to accom-pany them to appointments. If the candidate had a socialworker or advocate, the research team worked closelywith that person to support the candidate throughoutthe process. The team understood this process as an op-portunity to engage candidates not just in the study butalso with the health care system, attending to their par-ticular needs and barriers.Precise estimates regarding how many applicants wereneeded to reach the planned sample size was difficult toachieve. For example, in many occasions we would haveto go down the ordered applicant list because manyconsecutive applicants could not be found. Other times,they no longer met the prerequisites, were not interestedor were doing well on other treatments. Due to thisunpredictability, the research team continued to acceptnew applications until the final sample size was reached.This decision was made in collaboration with the clinicalteam and community advisory board. Like other trials[17], it was agreed that the opportunity to make contactwith applicants, provide information about the trial andother treatments was favorable despite the possibility thatrecruitment might be complete before we could enrolthem. In our communication with these applicants, theywere informed of their application number, the numberwe were presently contacting and our best estimate of thetime lapse or the likelihood of being contacted beforereaching the sample size. Applicants’ desire to apply to thestudy despite this and the patience they demonstrated isindicative of their willingness to access alternative treat-ments for their long-term opioid dependency.While our recruitment strategies were effective inreaching the target sample and allowing us to overcomeextraneous challenges, a limitation of the data collectedin this study is the impossibility to ascertain which strat-egy or combination of strategies was most influential orcost-effective. Given that our main strategy for recruit-ment was based on a strong community engagement plan,it is difficult to determine which of these activities contrib-uted to the overall effectiveness of this strategy. For ex-ample, word of mouth was the primary response receivedwhen applicants were asked how they heard about thestudy. With such a response, we are not able to determineif the sample could have been reached, for example, by fo-cusing efforts on information sessions to drug user groupsonly, without contacting health care workers. Also, the ex-tensive time lapse caused by the external events makescomparison with refusal rates from other RCTs problem-atic. Nevertheless, it is important to note that approxi-mately one-third of applicants meeting prerequisites werenot invited to initiate screening because we were unableto find them or because recruitment ended before theirnumber was reached. Since the pre-screening checklistdata was provided prior to consent, the information col-lected was very limited and so we have little data aboutthose we were unable to contact.opioid dependency into treatment. Although we reachedet al. Recruitment to randomised trials: strategies for trial enrollment andOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 8 of 9http://www.substanceabusepolicy.com/content/10/1/3the target sample size, SALOME recruitment faced seriouschallenges specific to the study context. These challengeswere successfully managed through open communicationwith the community, a consistent and accessible team anda participant-centered screening process. Our study em-phasizes the value of integrating these strategies into clin-ical addiction research to overcome study-specific barriers.Competing InterestsThe authors declare they have no financial or non-financial competinginterests.Authors’ contributionsEOJ and MTS designed the SALOME study and wrote the protocol. EOJ, KL,KM and SM made substantial contributions to the recruitment process. DGanalysed the data. KL, KM and EOJ wrote the first draft of the manuscript.All authors contributed to the interpretation of the data and revising forintellectual content. All authors gave approval to the final version of thepaper and are accountable for the integrity of the work.AcknowledgementsThe authors wish to acknowledge and thank the SALOME trial applicants fortheir time and support to the study. At Providence Health Care, Justin Karasikand the communications team, Scott Harrison and the leadership team;Julie Foreman and the clinical team at Providence Crosstown Clinic; AminJanmohamed and the pharmaceutical team at Providence Crosstown Clinic.We wish to extend the acknowledge all SALOME investigators and researchThis study contributes to the building evidence[14,15,17,19,23] regarding the recruitment experiencesand strategies used by addictions trialists who facebarriers unique to this field. The recruitment strategyyielded the necessary sample size but also provided thefoundation for constructive discussion regarding con-tinuation of treatment. The strategies put in place in theSALOME trial and the positive outcomes emphasize theimportance of the time investment in three particularareas. Well before the trial began, a core team was dedi-cated to establishing respectful relationships with thecommunity, which created a supportive system in theface of unpredictable circumstances that affected the re-cruitment timeline. A consistent and committed recruit-ment team was dedicated and maintained through thestudy for this task. Finally, frontline research and clin-ical staff worked toward ensuring applicants had thesupport they needed to complete the screening processand were successfully allocated into the trial. Our expe-riences reflected in this manuscript could help other re-searchers in the planning and implementation of futureRCTs in the addictions field with the potential for im-proving recruitment timelines and retention outcomes.ConclusionsSALOME is searching for evidence-based treatments thatcan attract and retain individuals struggling with long-termteam. Finally, to all the CAB and DSMB members, health care providers andaddiction physicians for their invaluable support and commitment to thepatients and the science.participation study. The STEPS study. Health Technol Assess. 2007;11:ii. ix-105.11. Humphreys K, Maisel NC, Blodgett JC, Finney JW. Representativeness ofpatients enrolled in influential clinical trials: a comparison of substancedependence with other medical disorders. J Stud Alcohol Drugs.2013;74:889–93.12. Mullins CD, Vandigo J, Zheng Z, Wicks P. Patient-Centeredness in the Designof Clinical Trials. 2014;17:471–5.13. Points to Consider about Recruitment and Retention While Preparing aClinical Research Study. [http://www.nimh.nih.gov/funding/grant-writing-and-application-process/recruitment-points-to-consider-6-1-05_34848.pdf]14. Thomson CL, Morley KC, Teesson M, Sannibale C, Haber PS. Issues withrecruitment to randomised controlled trials in the drug and alcohol field: aliterature review and Australian case study. Drug Alcohol Rev. 2008;27:115–22.15. Ashery RS, McAuliffe WE. Implementation issues and techniques inrandomized trials of outpatient psychosocial treatments for drug abusers:recruitment of subjects. Am J Drug Alcohol Abuse. 1992;18:305–29.16. Blanken P, van den Brink W, Hendriks VM, Huijsman IA, Klous MG, Rook EJ,et al. Heroin-assisted treatment in the Netherlands: History, findings, andinternational context. Eur Neuropsychopharmacol. 2010;20 Suppl 2:S105–58.FundingThe SALOME trial is funded through an operating grant from the CanadianInstitutes of Health Research, Providence Health Care, and the InnerChangeFoundation, with additional support from the Canada Research ChairsProgram, the University of British Columbia, Providence Health Care researchInstitute, Vancouver Coastal Health Authority and the Michael SmithFoundation for Health Research.Author details1Centre for Health Evaluation & Outcome Sciences, Providence Health Care,St. Paul's Hospital, 575- 1081 Burrard St., Vancouver, BC V6Z 1Y6, Canada.2School of Population and Public Health, University of British Columbia, 2206East Mall, Vancouver, BC V6T 1Z3, Canada. 3Providence Health Care,Providence Crosstown Clinic, 84 West Hastings Street, Vancouver, BC V6B1G6, Canada.Received: 28 November 2014 Accepted: 17 January 2015Published: 26 January 2015References1. De Jong CA, Roozen HG, van Rossum LG, Krabbe PF, Kerkhof AJ. Highabstinence rates in heroin addicts by a new comprehensive treatmentapproach. Am J Addict. 2007;16:124–30.2. Mattick RP, Breen C, Kimber J, Davoli M. Methadone maintenance therapyversus no opioid replacement therapy for opioid dependence. CochraneDatabase Syst Rev. 2009;3:CD002209.3. Van den Brink W, Haasen C. Evidenced-based treatment of opioid-dependentpatients. Can J Psychiatry. 2006;51:635–46.4. Ferri M, Davoli M, Perucci CA. Heroin maintenance for chronic heroin-dependentindividuals. Cochrane Database Syst Rev. 2011;8:CD003410.5. Oviedo-Joekes E, Guh D, Brissette S, Marsh DC, Nosyk B, Krausz M, et al.Double-blind injectable hydromorphone versus diacetylmorphine for thetreatment of opioid dependence: A pilot study. J Subst Abuse Treat.2010;38:408–11.6. Gates S, Brocklehurst P, Campbell M, Elbourne D. Recruitment tomulticentre trials. BJOG: An International Journal of Obstetrics &Gynaecology. 2004;111:3–5.7. McDonald AM, Knight RC, Campbell MK, Entwistle VA, Grant AM, Cook JA,et al. What influences recruitment to randomised controlled trials? A reviewof trials funded by two UK funding agencies. Trials. 2006;7:9.8. Treweek S, Pitkethly M, Cook J, Kjeldstrom M, Taskila T, Johansen M, et al.Strategies to improve recruitment to randomised controlled trials. CochraneDatabase Syst Rev. 2010;4:Mr000013.9. Sully BG, Julious SA, Nicholl J. A reinvestigation of recruitment torandomised, controlled, multicenter trials: a review of trials funded by twoUK funding agencies. Trials. 2013;14:166.10. Campbell MK, Snowdon C, Francis D, Elbourne D, McDonald AM, Knight R,17. March JC, Oviedo-Joekes E, Romero M, Gomez M, Rodriguez S, Leon MI,et al. [The experimental drug prescription program in Andalusia [PEPSA]:procedure for recruiting participants]. Gac Sanit. 2004;18:245–7.18. Watson JM, Torgerson DJ. Increasing recruitment to randomised trials: areview of randomised controlled trials. BMC Med Res Methodol. 2006;6:34.19. Demaret I, Litran G, Magoga C, Deblire C, Dupont A, De Roubaix J, et al.Why do heroin users refuse to participate in a heroin-assisted treatmenttrial? Heroin Addiction and Related Clinical Problems. 2014;xxx:5–12.20. March JC, Oviedo-Joekes E, Perea-Milla E, Carrasco F. Controlled trial ofprescribed heroin in the treatment of opioid addiction. J Subst Abuse Treat.2006;31:203–11.21. Chettiar J, Lock K, Oviedo-Joekes E, Sievewright K, Schechter MT. Therecruitment of participants to the Canadian heroin trial: Free heroin is notenough. In: 19th International Harm Reduction Conference, Barcelona, Spain.2008. Poster presentation.22. Bond Sutton L, Erlen JA, Glad JM, Siminoff LA. Recruiting vulnerablepopulations for research: revisiting the ethical issues. J Prof Nurs.2003;19:106–12.23. Barratt MJ, Norman JS, Fry CL. Positive and negative aspects of participationin illicit drug research: implications for recruitment and ethical conduct.Int J Drug Policy. 2007;18:235–8.doi:10.1186/1747-597X-10-3Cite this article as: Oviedo-Joekes et al.: The SALOME study: recruitmentexperiences in a clinical trial offering injectable diacetylmorphine andhydromorphone for opioid dependency. Substance Abuse Treatment,Prevention, and Policy 2015 :3.Submit your next manuscript to BioMed Centraland take full advantage of: • Convenient online submission• Thorough peer review• No space constraints or color figure charges• Immediate publication on acceptance• Inclusion in PubMed, CAS, Scopus and Google Scholar• Research which is freely available for redistributionOviedo-Joekes et al. Substance Abuse Treatment, Prevention, and Policy 2015, 10:3 Page 9 of 9http://www.substanceabusepolicy.com/content/10/1/3Submit your manuscript at www.biomedcentral.com/submit


Citation Scheme:


Citations by CSL (citeproc-js)

Usage Statistics



Customize your widget with the following options, then copy and paste the code below into the HTML of your page to embed this item in your website.
                            <div id="ubcOpenCollectionsWidgetDisplay">
                            <script id="ubcOpenCollectionsWidget"
                            async >
IIIF logo Our image viewer uses the IIIF 2.0 standard. To load this item in other compatible viewers, use this url:


Related Items