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NAOMI: The trials and tribulations of implementing a heroin assisted treatment study in North America Gartry, Candice C; Oviedo-Joekes, Eugenia; Laliberté, Nancy; Schechter, Martin T Jan 21, 2009

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ralssBioMed CentHarm Reduction JournalOpen AcceCase studyNAOMI: The trials and tribulations of implementing a heroin assisted treatment study in North AmericaCandice C Gartry*1, Eugenia Oviedo-Joekes2, Nancy Laliberté2 and Martin T Schechter3Address: 1CIHR Canadian HIV Trials Network and the Centre for Health Evaluation & Outcome Sciences (CHEOS), 620B – 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada, 2Centre for Health Evaluation & Outcome Sciences (CHEOS), 620B – 1081 Burrard Street, Vancouver, BC, V6Z 1Y6, Canada and 3UBC School of Population and Public Health, 5804 Fairview Ave, Vancouver, BC, V6T 1Z3, CanadaEmail: Candice C Gartry* - cgartry@shaw.ca; Eugenia Oviedo-Joekes - eugenia@mail.cheos.ubc.ca; Nancy Laliberté - nlaliberte@shaw.ca; Martin T Schechter - martin.schechter@ubc.ca* Corresponding author    AbstractBackground: Opioid addiction is a chronic, relapsing disease and remains a major public health challenge.Despite important expansions of access to conventional treatments, there are still significant proportionsof affected individuals who remain outside the reach of the current treatment system and who contributedisproportionately to health care and criminal justice costs as well as to public disorder associated withdrug addiction.The NAOMI study is a Phase III randomized clinical trial comparing injectable heroin maintenance to oralmethadone. The study has ethics board approval at its Montréal and Vancouver sites, as well as from theUniversity of Toronto, the New York Academy of Medicine and Johns Hopkins University.The main objective of the NAOMI Study is to determine whether the closely supervised provision ofinjectable, pharmaceutical-grade opioid agonist is more effective than methadone alone in recruiting,retaining, and benefiting chronic, opioid-dependent, injection drug users who are resistant to currentstandard treatment options.Methods: The case study submitted chronicles the challenges of getting a heroin assisted treatment trialup and running in North America. It describes: a brief background on opioid addiction; current standardtherapies for opioid addiction; why there is/was a need for a heroin assisted treatment trial; a descriptionof heroin assisted treatment; the beginnings of creating the NAOMI study in North America; what is theNAOMI study; the science and politics of the NAOMI study; getting NAOMI started in Canada; variousrequirements and restrictions in getting the study up and running; recruitment into the study; working withthe media; a status report on the study; and a brief conclusion from the authors' perspectives.Results and conclusion: As this is a case study, there are no specific results or main findings listed. Thecase study focuses on: the background of the study; what it took to get the study started in Canada; theunique requirements and conditions of getting a site, and the study, approved; working with the media;recruitment into the study; a brief status report on the study; and a brief conclusion from the authors'perspectives.Published: 21 January 2009Harm Reduction Journal 2009, 6:2 doi:10.1186/1477-7517-6-2Received: 5 July 2008Accepted: 21 January 2009This article is available from: http://www.harmreductionjournal.com/content/6/1/2© 2009 Gartry et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 14(page number not for citation purposes)Trail Registration: ClinicalTrials.gov registration number: NCT00175357Harm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2BackgroundOpioid addiction is a chronic, relapsing disease andremains a major public health challenge in North Americawith an estimated 80,000 opioid users in Canada alone[1]. It is estimated that there are 20,000 opioid dependentpersons in Vancouver and at least 6,000 in Montréal, theserepresenting only two of Canada's larger cities [1]. Despiteimportant expansions of access to conventional treat-ments, there are still significant proportions of affectedindividuals, many with multiple co-morbidities, whoremain outside the reach of the current treatment systemand who contribute disproportionately to health care andcriminal justice costs as well as to public disorder associ-ated with drug addiction [2].Untreated opioid addiction can lead to overdose, infec-tious diseases, loss of regular social and economic func-tioning, and extensive engagement in both drug-relatedand drug acquisition crime [3-6]. Opioid addiction is alsohighly correlated with mental illness and the combinationof these two is a predictor of poorer treatment outcomes[7-9]. At a societal level, there are associated costs to pub-lic health and health care as well as to the welfare andcriminal justice systems in dealing with these risk andharm phenomena. In Canada, illicit drug use costs in2002 were estimated at $40 billion or $1,267 per capitawith the three highest contributors being loss of produc-tivity, direct health care and law enforcement [10]. In1996, Vancouver's Medical Health Officer reported thatthe increase in injection drug use seen in Vancouver wasresulting in an increased incidence of HIV/AIDS and Hep-atitis, increased hospital and emergency service utilizationfor treatment of HIV-related diseases, septicaemia andendocarditis, as well as increased ambulance responsesand emergency room visits related to drug overdoses. Inaddition, the report noted a related increase in fetal expo-sure to addictive substances, increased pressure on com-munity-level outreach nursing and medical services, andan increased need for community-level hospice palliativecare [11].Methadone maintenance therapy (MMT) has been the pri-mary substitution treatment for opioid addiction in NorthAmerica since the 1960's [12,13]. MMT efficacy has beenlargely proved with respect to various outcomes [14-17] –it decreases the cravings, decreases the number of injec-tions, and can sometimes lead to abstinence. However,like other treatments for diseases such as cancer or HIV,MMT is not effective for everyone. Some patients on MMTare not retained long enough to benefit from the programor show limited response, continuing to use illicit drugsoutside of the treatment setting [18]. Several factors havebeen highlighted as predictors of lack of efficacy of MMTfees; punitive urine testing (e.g. complete abstinence fromany drug use required for continued MMT); and lack of a'high' associated with MMT. While many of these factorscan be improved upon, even when MMT is optimallydelivered (i.e. high dosage, psychosocial support, treat-ment of co-morbidities), there remains a sub-sample ofbetween 15% and 25% of patients who do not benefitfrom this treatment [26,27]. For example, the MMT groupin the German Heroin Assisted Therapy (HAT) trialreceived an optimized version of MMT (compared to whatis available in their communities) and still 30% and 50%were considered 'non-responders' with respect to theirhealth and illicit drug use scores respectively [28]. As such,MMT is effective but can be sub-optimal and it is notalways successful.Buprenorphine, particularly suboxone (a combination ofbuprenorphine and naloxone) – a partial agonist, hasbeen approved in the United States, and recently in Can-ada, for substitution therapy. While there is limited dataon the effectiveness of this treatment in addiction therapy,use of suboxone has shown that it may only be truly effec-tive for those who use low doses of opioids or who are onlow doses of methadone. In fact, a recent review of 13clinical trials, 12 of which were double blind, comparingbuprenorphine maintenance with either placebo or MMTfor opioid dependence concluded that buprenorphineappeared to be significantly less effective than methadonein retaining patients in treatment [29].Why the need for a HAT trial?The first question that can be asked is 'Is there really aneed for a trial of heroin assisted therapy?' The need forsuch a trial was noted in the Le Dain Commission's Reportin 1972 [30]. This report was produced by the CanadianGovernment Commission on Inquiry into the Non-Med-ical Use of Drugs. Included in this report is a recommen-dation for the "implementation of a heroin prescriptiontrial for addicts who could not be attracted into conven-tional forms of opioid addiction treatment".In the United Kingdom (UK) heroin prescription has beenpart of the addiction treatment system since 1926 [30-32].In the nineties, Switzerland opened heroin assisted treat-ment (HAT) clinics in response to the public health prob-lem caused by the use of illicit heroin [33,34]. The Swissexperience showed that heroin prescription deliveredunder supervision in clinics was both safe and feasible[33,34]. Moreover, these patients improved their health,reduced their use of illicit drugs and illegal income, andalso committed fewer drug and property related offences[35,36]. These improvements were sustained over time,even after leaving the treatment [37]. In 1999 a WorldPage 2 of 14(page number not for citation purposes)or barriers to access (and retention) in the program [19-25]. These include: inadequate methadone doses; userHealth Organization's expert panel issued a report inwhich they recognized this success; however, the panelHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2also felt that it was not possible to determine whetherthese improvements were due to HAT or the ancillary psy-chosocial services that the participants received [38].After the success of the Swiss model, several Europeancountries followed their initiative. The Netherlands, Ger-many and Spain, followed later by Canada and the UK,implemented randomized controlled HAT trials in orderto better answer the question of the effectiveness of super-vised HAT in their contexts [26-28,39-41]. In addition, in2008 Denmark announced the approval of HAT as part oftheir addiction treatment program and Belgium started aRandomized Controlled Trial (RCT) comparing injectedand inhaled heroin (Dutch model [26]) versus oral meth-adone. The Dutch, German and Spanish trials resultsshowed that HAT was more effective than oral MMT in theareas of improved health, psychosocial adjustment andillicit drug use among long-term, socially excluded her-oin-dependent people who were not benefiting from theavailable treatments [26-28,40].In Switzerland and the Netherlands, HAT is now part ofthe addiction treatment system, and Germany is in theprocess of requesting registration for diamorphine(DAM). However, in Spain the government denied therequest of HAT for opioid-dependence treatment and cur-rently only allows it under compassionate use.Although evidence is building that HAT is an effectivetreatment alternative for opioid dependence, more workis still to be done. Even with the study results on HAT cur-rently published, many countries still do not support theuse of heroin as a treatment option for opioid dependencelargely due to the stigma associated with this drug, as wellas the politics associated with treating those dependent onheroin with heroin. Some feel that while HAT worked insome countries, it may not work in their own because ofdifferent cultural and societal issues.While Denmark approved HAT without a clinical trial,Belgium researchers have been trying for some time to getHAT approved and, at this point, only have approval for aRCT using MMT as an active comparator. In Switzerland,the provision of HAT was approved after a referendumwas passed and the German trial went ahead only after achange in their government. In Spain, the debate went onfor years before a RCT of HAT was approved. Thus, despitethe recommendations made by the Le Dain Commissionso many years ago, the successful experiences in othercountries, and that addiction treatment policies, like anymedical or public health practice, should be evidencebased – and evidence does exists [42], the only hope ofpossibly having DAM registered as a treatment for opioidUnderstanding HATHeroin (injected) assisted treatment is aimed at a veryselect group of opioid users. The target population forHAT have been using heroin (or other illicit opiates) forseveral years, have severe health and psychosocial prob-lems associated with their drug use, and have not bene-fited currently or in the past from available therapies suchas MMT. HAT should not be considered as a replacementfor MMT or buprenorphine, but rather as an additionaltreatment option for a specific sub-population and forwhom MMT and/or buprenorphine have not been effec-tive. Supervised HAT clinics require daily visits (up to 3per day) and participants are subject to close monitoringand evaluation while in the clinic. Medically prescribedheroin, while provided at no cost to participants, is not'free heroin' as it is a tightly controlled and very demand-ing treatment [43,44].If one considers the Swiss HAT treatment model as a ref-erence, with 23 clinics working at 91% capacity, HATaccounts for 8% of the substitution treatment [45] beingprovided in that country. Thus, HAT is clearly an alterna-tive for the most vulnerable and severely affected popula-tion of opioid dependent people, who, without HATtreatment, would likely remain outside of the treatmentsystem. The amount of attention and controversy aroundthis treatment, given this important but circumscribedrole within the realm of addiction treatment, is to say theleast, disproportionate [46].NAOMI – the early daysIn September 1998 the first North American Opiate Med-ication Initiative (NAOMI) Working Group was formedwith treatment experts, research scientists and bio-ethi-cists from both the US and Canada. The mandate of thegroup was to examine HAT as a treatment modality forchronic opiate-dependence and, if thought feasible,develop a scientifically rigorous and ethically defensiblestudy proposal.The NAOMI Working Group held a series of protocoldesign meetings from 1998 to 2000 during which time asix-centre RCT proposal was developed. Three sites wereto be established in Canada (Vancouver, Toronto andMontréal) with the other three to be established in the US.In 1999 an external international review panel was com-missioned by the investigators to review the proposalwhile at the same time discussions were being held toidentify possible sites and funding in the US. As time wenton, it became increasingly clear that no US sites would beable to participate nor could any US funding be identified.As a result, the Canadian investigators decided to apply asa Canadian three-site study to the Canadian Institutes ofPage 3 of 14(page number not for citation purposes)addiction in Canada meant that a RCT of HAT was neededto examine whether HAT would be effective in the Cana-dian context.Health Research (CIHR), and the NAOMI study was offi-cially born.Harm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2NAOMI – what is it?The NAOMI study is a Phase III RCT comparing injectableopioid agonist maintenance (primarily with heroin butalso with hydromorphone) to oral methadone. The studyis funded by CIHR, Canada's premier scientific researchfunding body, and has ethics board approval at its Mon-tréal (Université de Montréal) and Vancouver (Universityof British Columbia and Providence Health Care) sites.The study also received ethical approval from the Univer-sity of Toronto, the New York Academy of Medicine andJohns Hopkins University.The main objective of the NAOMI Study is to determinewhether the closely supervised provision of injectable,pharmaceutical-grade heroin is more effective than MMTalone in recruiting, retaining, and benefiting chronic, opi-oid-dependent, injection drug users (IDUs) who areresistant to current standard treatment options.The final version of the NAOMI study was a two-site study(Montréal and Vancouver) with 251 participants rand-omized to receive either injectable opioid or methadonefor 12 months of treatment (plus 3 months of transitionoff of injectable medication), plus 12 months of researchfollow up. Participants randomized to the injection armself-injected medications under the supervision of clinicstaff and could add oral methadone at any time duringtheir treatment in consultation with their physician. Thetarget population for NAOMI included men and womenover the age of 25 who were chronic, opioid dependent,daily IDUs and who had previously failed MMT. Furtherinformation on the trial design and methodology aredescribed elsewhere [47].NAOMI – science vs. politicsThe line between science and politics can be blurred attimes. Generally, researchers are most concerned with thebest science; however, in addiction research, getting a RCTapproved and funded sometimes means that certain com-promises must be made. This can prove to be challenging,as was the case with NAOMI, as researchers worked todesign a study that would be politically acceptable whileat the same time maintaining scientific integrity andensuring that the protocol would be scientifically rigor-ous. This issue brought the distinction between pharma-cology and phenomenology to the forefront of explainingand educating people on opioid addiction.The harms of heroin use can be categorized into twoclasses, pharmacological and phenomenological. Phar-macology refers to the science of drugs, including theircomposition, uses and effects, while phenomenologyincorporates the fact that events and peoples' lives occurcological harms associated with heroin use include:euphoria and/or sedation; withdrawal; constipation; andflushing, many of which are also associated with othercommonly prescribed opioids. However; the phenome-nological harms associated with heroin use, the ones mostoften discussed, include: overdose; viral infections; bacte-rial infections, violence, illegal activity; and social disinte-gration. The latter are not attributable to thepharmacology of the drug but rather to drug prohibitionwhich leads to the use of dirty needles, unsanitary/non-sterile water, crime, prison, disease and overdose. Thequestion that comes to mind is 'What if all these 'addi-tives' were removed from street heroin? What would beleft?' The answer is diacetylmorphine or DAM, the activeopioid contained in heroin.Heroin has a documented history of being prescribed andused as an analgesic dating back to at least 1901 whenBayer® Pharmaceutical Products were marketing it.Between 1919 and 1923 there were several morphine andHAT clinics operating in the USA until their terminationby the US government. By 1926 UK physicians were offi-cially allowed to prescribe heroin; however, limitationsand controls were placed on heroin prescription in 1965resulting in only limited numbers of patients being cur-rently prescribed heroin in the UK [32].Due to the controversial nature of the drug being tested inNAOMI, the study design of the protocol was driven insome places, specifically in the design of the eligibility cri-teria for the study. For example, the study could notrecruit participants currently in MMT or who had been inMMT in the prior 6 months because of the 'fear' that someindividuals would drop-out of treatment in order to applyfor the NAOMI trial. This criterion was an amendment tothe original protocol in response to health authorities andMMT providers. In contrast, two of the other trials pub-lished on HAT required that participants 'must' be onMMT in order to participate because HAT was projected tobecome part of the addiction treatment system. As aresult, many advocates and drug users felt that the NAOMIstudy entry criteria were far too restrictive and that, if theintent was to truly help this largely underserved popula-tion, the criteria should be more flexible and inclusive.Another somewhat political NAOMI issue was the with-drawal of the Toronto site from the study. Constructionhad begun at the Toronto site; however, they experiencedvarious delays in the renovation process. This togetherwith the previous commitment of the Toronto site to runanother study in the renovated clinic before they couldstart NAOMI, meant that there would be a significant timedelay between when Toronto could start the trial andPage 4 of 14(page number not for citation purposes)in a complex and multi-faceted environment where thesocio-political systems affect people's lives. The pharma-when the other two sites would be starting. In addition,there was a lack of consensus amongst the physicians andHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2researchers at the Toronto site as to whether heroin ordiverted prescription opioids were really the primary issuein that city. This lack of consensus then extended to thefeasibility of the Toronto site being able to fully recruitinto NAOMI and what the potential value of HAT wouldbe in the Toronto context. Interestingly, a 2003 paperwritten by researchers from the Centre for Addiction andMental Health in Toronto (CAMH) analyzing a popula-tion survey conducted amongst adults residing in Ontarioregarding public opinion of safe injection facilities andHAT showed that 62.3% of participants questioned feltthat medically prescribed heroin should be available forlong-term heroin addicts who have tried and failed allother treatment options [48].NAOMI in CanadaThe NAOMI protocol was submitted to CIHR in March2001; however, at the time CIHR was not able to providefull funding for the trial. Consequently, CIHR spent sev-eral months trying to identify additional sponsors. (TheUS National Institutes of Health (NIH) were approachedbut declined to co-sponsor the study.) In January 2002full funding approval was granted for NAOMI after CIHRreceived an overall funding increase.An important point to note about the NAOMI study isthat, unlike its counterparts in Europe, NAOMI was cre-ated and conducted by private citizens. In contrast, theEuropean HAT studies were government initiated andthus already had the support of government and fundingbodies. This distinction is important in understandingmany of the hurdles in starting recruitment and treatmentinto this type of study in North America.With CIHR approval and funding in hand, a Clinical TrialApplication (CTA) needed to be written for submission tothe Regulatory Branch of Health Canada. Since there wasno pharmaceutical company 'sponsor' for the NAOMIstudy, the Principal Investigator became the sponsor andthus the study team prepared and submitted the CTA.During this somewhat lengthy process, the first hurdle(aside from funding) appeared. The study team wasinformed that the bulk powder form of heroin that hadbeen planned to be used for the study was not acceptableto Health Canada due to contamination/sterility con-cerns. Instead, Health Canada required that the narcoticbe imported in lyophilized/freeze-dried form resulting ina cost that was approximately eight times more expensivethan originally planned.Final CTA approval for the study was granted in January2003, which enabled the team to focus on the next stepsof getting the trial up and running, specifically identifyingreceive, and administer the heroin/DAM without the staffor participants being arrested. This is the same exemptionthat Vancouver's Supervised Injection Site required/s;however, the requirements to obtain this exemption var-ied greatly between the NAOMI study and the SupervisedInjection Site (also know as Insite).Identifying study sitesIt was thought that identifying study sites would be a rel-atively straightforward and uncomplicated task, as was thecase with the Montréal study site. However, identifying aVancouver study site was anything but uncomplicated.One of the first sites discussed for Vancouver was St. Paul'sHospital, the city's inner-city hospital, which predomi-nantly deals with Vancouver's IDU population. However,at the outset multiple concerns were raised. First, St. Paul'sHospital is a Catholic Hospital and, as such, was fearful(at the time) about being perceived as condoning or sup-porting injection drug use; Second, there was concern bythe hospital that having the study site located within itswalls would result in those addicted to heroin movinginto the neighbourhood in order to have easier access tothe site, known as the 'honey pot effect'; and finally, afterfurther consideration, it was the study team's feeling thathaving the site at St. Paul's Hospital would be an impedi-ment to participation as the target population would haveto travel three times per day to get to the site. Although thehospital is only located 1.25 miles away from the currentsite in Vancouver's Downtown East Side (DTES),NAOMI's target population is deeply rooted in this com-munity due largely to poverty, housing, welfare, andstigma issues.Vancouver's DTES is often described as the "poorest urbanpostal code in Canada" and is home to approximately5,000 IDUs. The median household income in the DTESin 1996 was $12,900 compared to the City average ofapproximately $48,000 [49]. According to a March 31,2008 Expert Advisory Committee report to Canada's Fed-eral Minister of Health, results based on 1,000 users sur-veyed in the DTES showed that 20% are homeless andmany more live in unstable and/or single resident rooms.80% have been incarcerated at some point, 38% areinvolved in the sex trade, 59% reported a non-fatal over-dose in their lifetime and 51% used heroin as their pri-mary drug of choice. A report prepared by Coroner J.V.Cain (Report on the Task Force into Illicit Narcotic Overdosesin British Columbia) [50] reported that overdose deaths inVancouver had risen from sixteen in 1987 to two-hundredin 1993. In 1997 researchers at the British Columbia Cen-tre for Excellence in HIV/AIDS reported that the preva-lence rate of HIV/AIDS in the DTES had reached epidemicPage 5 of 14(page number not for citation purposes)study sites, seeking import/export permits for the heroin/DAM, and obtaining a special section 56 exemption toCanada's Narcotics Control Act to allow the team to import,proportions and was 27% among injection drug users atthe time. In a September 1997 report by the Chief MedicalHealth Officer of the Vancouver Richmond Health BoardHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2it was reported that many individuals in the DTES werecoping simultaneously with poverty, lack of affordablehousing, lack of transportation, inter-generational abuseand violence, and poor access to services. The majority ofusers in the DTES are either on welfare, are unemployed,or do not qualify for welfare. These factors make travel toSt. Paul's Hospital up to three times per day, seven daysper week, 365 days per year, a significant challenge. Basedon this and other circumstances, it was decided that thestudy site should be established in the DTES.Identifying a final study site in Vancouver took almost twoyears. During this time many sites were considered. Somewere proposed by the local health authority, some pro-posed by local service organizations, and others found bymembers of our team walking the streets of the DTESlooking for vacant buildings. Unfortunately, the sites ini-tially identified in the DTES all had one major issue incommon, they all required large amounts of renovations,often estimated at close to $1 million Cdn worth, just tobe able to obtain an occupancy permit. Moreover, this $1million price tag often did not include the cost of the sig-nificant safety and security additions that the governmentwould require in order to obtain the necessary Section 56exemption to legally store and administer the drug.The first viable potential site identified was located in aneighbourhood just on the outer edge of the DTES. Thissite was centrally enough located so that the participantscould easily access it, and was also manageable in terms ofrenovation costs. However, some members of the localcommunity had concerns about having the site for thistype of clinical trial in their backyard (the 'Not in MyBackyard' or NIMBY issue) and thus petitioned the Cityagainst our use of it. In its reasons for not wanting theNAOMI site in their neighbourhood, the community citedthat they felt that the overall area already housed manyservice organizations and, thus, did not need another one.Because of these issues, this site had to be abandoned.It took nine months from that point to identify, secure,and sign a lease for what is now the site of the VancouverNAOMI clinic. This site is in the heart of the DTES in aformer bank, complete with a vault, thus reducing someof the renovation expenses in terms of the requirementsfor the Section 56 exemption. In order to proceed withrenovations, the Vancouver study team needed to apply tothe City of Vancouver for a development permit. At thetime, the study team thought that this process would berelatively painless as the site was not in a predominantlyresidential neighbourhood; however, once again the sitebecame a political issue as some residents had concernsabout the site, specifically the NIMBY issue and thea full City Development Board review. The review processresulted in the need for a public City Development Boardmeeting to be called where both the study team and con-cerned residents could voice their feelings. Within a fewmonths the meeting was convened and concerns in thecommunity had died down resulting in only two peopleattending the meeting to speak out against the site loca-tion. With the backing of some local service organiza-tions, including the invaluable support of Vancouver'sPolice Department, approval of our application wasgranted and renovations could start; however, not withoutsome unique conditions.City conditions for the Vancouver siteIn response to the community's initial concerns, andgiven the challenges that the City of Vancouver (and othercities) face in managing the broader environment of facil-itating increased services in a neighbourhood that alreadyis perceived by many to have too many services, some spe-cific conditions were attached to the development permitapproval of the Vancouver site by the City of Vancouver,including: 1) A twenty-four hour emergency contact tele-phone number be established and posted on the doors ofthe site as well as distributed to the community so that, inthe event that members of the local community had anyconcerns, they could contact the study team at any time. Itis noteworthy that this line did not receive a single callwith a complaint about the study site. 2) The study teamhad to guarantee that there would not be line-ups outfront of the clinic at any time and, should such occur, theteam would disperse the line up. This is a demonstrationof some of the stigma that affects this already marginal-ized group, especially given that businesses, such as ticketstores, box offices and electronics store, as well as busi-nesses that serve alcohol such as bars, lounges and nightclubs, are generally allowed to have line ups in front oftheir establishments. 3) The study team had to develop a'Good Neighbour Agreement' which each participant wasrequired to sign upon receiving their designation (injecta-ble opioid or methadone). This agreement required theparticipants to agree that they would not loiter near theclinic, not line up outside of the clinic, not arrange to meetpeople directly outside of the clinic, and not deal anydrugs in the area directly surrounding the clinic. 4) Thestudy team had to strike a Neighbourhood Advisory Com-mittee (NAC), to which any interested groups in the areasurrounding the clinic (businesses and housing strata-committees) were to be invited to participate. This com-mittee was to meet on a regular basis, with Vancouverstudy team members in attendance, so that they couldvoice any concerns about the study and its effect, if any,on the neighbourhood. The NAC started meeting in early2005 and continued to meet until the clinical portion ofPage 6 of 14(page number not for citation purposes)number of service organizations already in operation inthe DTES. This resulted in our application having to go tothe trial completed. During this time the NAC did notraise any concerns regarding the study. As a matter of fact,Harm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2the NAC describes the study as a 'non-event' in terms of itseffects on the community. This is to be expected consider-ing the study is only able to treat 192 of the estimated5,000 IDUs in the DTES. 5) Due to concerns raised overthe 'honey pot effect', specifically those addicted to heroinmoving into the already crowded DTES from other areasin order to access the study, the study was restricted torecruiting only those participants who lived within a one-mile radius of the study site. While this restriction cer-tainly limited recruitment to participants that were trulythe most visible chronic opioid addicts, it also excludedmany people with a heroin addiction who truly did needhelp, were ready for treatment, and met all of the inclu-sion criteria except the latter residency restriction. To ourknowledge no other clinical trial has had restrictions onrecruitment by geographic area placed upon it by the Cityof Vancouver. All of these conditions speak to the chronicinstitutionalized discrimination affecting drug users.It is important to note that the residency criteria for enter-ing the study was relaxed somewhat in the late summer of2005. The research team and the City of Vancouver agreedto expand the definition of 'residency' to include peoplewho could prove that they were clearly accessing serviceson a regular basis within the one-mile catchment area. TheCity required that the NAC approve of this change, whichhappened in September 2005, before the change couldtake affect.Lastly, as part of our development permit, we wererequired to provide 'elevation drawings' to the storefrontand façade of the study site with the stated intent being to'improve the appearance of the storefronts to ensurepedestrian interest'. This condition is ironic because theCity and the Federal Government did not want to drawattention to the site or what was happening within itswalls.Health Canada requirementsAside from the aforementioned City requirements, inorder to gain the approval of the Office of Controlled Sub-stances of Health Canada and obtain a Section 56 exemp-tion, additional security requirements had to be met at thestudy sites. As previously mentioned, the Section 56exemption is the same exemption that Vancouver's Super-vised Injection Site is required to have. However, due tothe NAOMI study storing, preparing, and administeringnarcotics many additional security features were requiredfor the study sites.The first restriction placed upon the study team was oneof confidentiality. Health Canada's Office of ControlledSubstances was very concerned that news of the NAOMItion in the press while it was still under consideration forapproval. Due to this restriction, when news of the firstsite broke and media were informed about the site andour intentions, the study team was not able to commentto the media about the specifics of the trial, nor that it wasa scientifically approved RCT with ethical approval at allof the study sites. This inability to consult with the localcommunity played a large part in the loss of the first studysite. This issue continued to be problematic until, finally,there was agreement that the need to inform and educatethe public about the trial outweighed any possible bene-fits that could be gained by remaining silent on the issue.In addition to the confidentiality issue, Health Canadaput forward a host of additional security restrictionswhich needed to be satisfied in order to gain a Section 56exemption. The level of security required is determined bythe maximum street value of heroin to be stored at thefacility at any one time based on Health Canada estimatesof street value. However, contrary to common knowledgeabout the street value of heroin (approximately $30 CDNper 0.25 gram on June 13, 2008), Health Canada policyvalued heroin at $3 million per kg or approximately $750per 0.25 gram, roughly twenty-five times more than theactual street value.This Health Canada policy resulted in the securityrequired for the study sites to soar to a whole new level.The long list of Health Canada requirements included:specially reinforced glass; a sealed medication room witha specially designed one-way tray through which nursespassed medications to participants; a chute in the reversedirection through which participants returned usedsyringes under observation; multiple security camerascovering every angle, including overlap, to ensure that noheroin was diverted, either by participants or staff; vesti-bules to be built so that there was a 'secured' area and peo-ple could not directly enter the clinic through one door –this would provide the clinic staff with the opportunity tovet, via security camera, those who entered the vestibulebefore they were actually permitted access to the clinicproper; although the site was only able to keep a three daysupply of heroin on the premises due to other HealthCanada restrictions, the heroin had to be stored in alocked fridge within a safe to which only the clinic man-agers had keys and passwords; specific safety training wasrequired for all staff including how to deal with a hostagesituation (Health Canada was concerned about membersof organized crime wanting to obtain the heroin stored atthe clinic); and the development of a specific and detailedsystem to log and monitor every milligram of heroin fromthe time of delivery to administration. In addition, everytime point had to be recorded for each participant visitPage 7 of 14(page number not for citation purposes)study would get out to the Canadian public in advance oftheir final approval and granting of the Section 56 exemp-tion. They did not want news of the NAOMI trial applica-including when they enter the premises, when they passtheir pre-assessment, when they began and completeadministering their dose, whether the patient left any drugHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2visible in the syringe, when they pass their post-assess-ment, when they are discharged, and any other interactionwith study nurses, physicians, social workers, addictioncounsellors, medical office assistants, or clinic managers.As the Vancouver site was not attached to an institutionsuch as a hospital, it had additional requirements placedupon it, including: only a very select few could have keysand passwords to enter the clinic when it was not in oper-ation – clinic staff would have to be granted entry accessfrom a clinic manager already inside the clinic; and vibra-tion sensors had to be installed on all of the outside doorsand windows. Given the nature of all of these require-ments, there were significant corresponding costs associ-ated with establishing these clinics that could not becovered by the original scientific grant. These additionalsecurity requirements, as well as the change in the heroincompound that Health Canada would allow the studyteam to utilize, resulted in roughly an additional $2 mil-lion Cdn needing to be raised in order to establish, recruitinto, run, and complete the study. The final funding forthe study is derived from several different funding part-ners, each with their own restrictions on expenses andindividual reporting requirements, thus necessitatinginternal accounting staff dedicated to the management ofthe NAOMI study budget, including transaction process-ing and financial reporting. The final budget for the study,including one-time costs such as renovations and security,is approximately $10.5 million Cdn.The last issue to be resolved with Health Canada was howthe heroin would be delivered to the clinics. While it wasacceptable to have the heroin delivered to the hosting,institutional pharmacies by regular couriers who rou-tinely deliver medicines, Health Canada was very specificthat the study medication be delivered to the study sitesby armoured car. In fact, there was a point when the studywas not going to proceed despite the work to-date becauseHealth Canada was insisting on daily deliveries of thestudy drug (meaning that only a one day supply of drugcould be stored on-site as opposed to a three day supply).This resulted in lengthy discussions during which thestudy team outlined to Health Canada that should a strikeoccur (at the armoured car company), or should weatherimpede the daily delivery of study medication (which wasvery likely at some point in Montréal), then the studyteam would not be able to provide the medication as out-lined in the protocol. Further, this would be considered abreach of ethics as well as a breach of Good Clinical Prac-tice (especially since such a delay could be foreseen andprecautions taken against it).Finally, a compromise was reached. Health Canada andat any one time, thus no longer necessitating dailyarmoured car deliveries.Other challenges – our neighbours to the southOne of the other challenges is the proximity and closerelationship of Canada and the US. While there are manysupporters of harm reduction policies and practices in theUS, the Bush administration is not among them and iswell known for its lack of support for important harmreduction programs such as needle exchange programs, aswell other addiction treatment initiatives. When it comesto clinical trials providing heroin for treatment of heroinaddiction or Supervised Injection Sites, there is no ques-tion about how the Bush administration feels about suchinterventions. In 2003 US Drug Czar John Walters referredto Vancouver's Supervised Injection Site as "state spon-sored personal suicide" [51], and in interviews on Cana-dian television made what some would call veiled threatssaying that it would be "regrettable" if Canada started hav-ing trouble getting their goods across the (US/Canada)border [52].While the general expectation is that politics should notinfluence science and research, the fact is that politics canplay a significant part. Aside from the political issues ear-lier identified with respect to the eligibility criteria for thestudy, there were, and continue to be, politics aroundareas of harm reduction. In the Canadian context, the cur-rent Conservative Federal Government has been workingto strengthen ties with the US Government and is oftenunwilling to confront the US government, especially for acause as controversial as HAT.In 2004 the NAOMI team in Vancouver received a requestfrom the US Consulate in Vancouver for a meeting. USEmbassy officials visited the Principal Investigator and amember of the NAOMI study team and, while the firstpart of the conversation was centred around the studyitself, the officials also requested (and were denied) a listof our US collaborators, specifically the US members ofthe NAOMI Working Groups established in 1998.Recruitment into NAOMIIn March 2005 recruitment into NAOMI commenced inboth cities. A lot of time and energy was spent on devel-oping recruitment strategies. Due to the nature of thestudy, and also because the study had been receivingmedia attention prior to the start of recruitment, the studyteam expected a deluge of calls once the recruitment lineswere open. With only a relatively small amount ofresearch assistants available due to budget constraints, thephone lines were initially open two days per weeks for twohours at a time. Posters describing the basic entry criteriaPage 8 of 14(page number not for citation purposes)the researchers were able to come to an agreement on theamount of heroin that could be stored at the clinical sitesinto NAOMI, the call in telephone numbers, and thehours when the phones would be manned, were put upHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2around the DTES and in the City of Montréal, at needleexchanges, community services and at VANDU (the Van-couver Network of Drug Users). However, the expecteddeluge of calls did not materialize. Some of the factorsleading to this were that: 1) many of the people NAOMIwas trying to reach were homeless; 2) limited access to tel-ephones during the few hours the lines were open; 3) thegag order imposed by Health Canada before the studybegan had limited general education about the NAOMIstudy; and 3) some doctors and community services/organizations were incorrectly informing potential partic-ipants that the study was already full. In response to this,a new recruitment strategy needed to be developedquickly.The first change was to open up the recruitment lines dur-ing normal business hours. The study teams also designednew posters, created a schedule to regularly go out into thecommunity and replace torn posters, and hired outreachworkers. These outreach workers were charged with goinginto the community and talking with users. They visitedneedle exchanges, community centres, local organiza-tions, and the Supervised Injection Site (in Vancouver).Outreach workers would conduct a 'pre-screening' ques-tionnaire to determine if a person might potentially qual-ify for the study, and would then book an appointment oreven accompany the participant to the research officewhere full eligibility could be firmly determined.In addition to the outreach workers, team members con-ducted information sessions for community groups andservices, as well as for groups of doctors, nurses and otherworkers in the communities and in other addiction are-nas. In order to reach the population that the NAOMIstudy was seeking, advertisements were placed in the local'free' papers, team members wore NAOMI t-shirts whenthey were out in the community, recruitment and infor-mation sessions were held where users were known tocongregate, and matchbooks were created and distributedwhich listed the basic entry criteria into the study and thetelephone call-in numbers.Not surprisingly, recruitment into the study took longerthan expected, finishing in April 2007. However, the mainimpediment to recruitment was not the factors listedabove, but rather the highly restrictive nature of the inclu-sion/exclusion criteria. It is noteworthy that delays inrecruitment have been a barrier in most of the trials aimedat hard-to-reach drug using populations [53,54]. Forexample, the German HAT RCT had to be extended anadditional year due to unexpected delays in recruitmentinto the study [55]. In the case of NAOMI, the primarybarriers to study entry were in relation to previous addic-many potential candidates had not reached a dose of 60mg of methadone and/or had not remained on metha-done for at least one month in their previous attempt(s).Many individuals currently or recently on MMT but notdoing well came forward but were generally ineligiblebecause only those without any addiction treatment in thelast 6 months were able to participate. Other issues withless impact were: not having resided for at least one yearin the city/site location, and for Vancouver participants,not living within 1 mile of the clinic, not meeting the(later) relaxed criteria of being a resident of the DTES, orself-report of living within the one mile radius but notable to obtain any documentation to verify the claim.In Montréal, some of the issues surrounding recruitmentdiffered from the Vancouver site. Unlike Vancouver, Mon-tréal's heroin users are spread over the island and there isno large concentration of heroin addicts in one area com-parable to the DTES. Also, without a central provincialprescription database like Pharmanet in British Colum-bia, obtaining the required verification of previous MMTtreatments for potential Montréal participants was diffi-cult. Further, because Montréal's IDU population is fairlyspread out, many would have to travel up to an hour tothe clinic up to 3 times per day, which was not seen as veryattractive even with the provision of 'free' heroin.At the end of the recruitment phase, the profile of the par-ticipants who entered the NAOMI trial represented someof the most chronic and marginalized opiate users in Van-couver and Montréal [56].Working with the mediaAnother challenge relating to NAOMI has been mediaattention. Since publicly announcing the start of the trial,the study has received considerable attention in local,national and international media. While media interestcan be beneficial in raising the profile of harm reduction,the media's need for headlines can throw off the balancebetween scientific integrity and public education.Treating heroin addiction with heroin tends to evoke aknee-jerk reaction. Lack of understanding, restrictions ontime and resources, and the need for a catchy headlineoften lead to sensationalism by the media. As previouslymentioned, opposition both within Canada and the USalso contributed to misleading reports from local,national, and international media. The resulting focus hasbeen on a seeming shift in Canadian drug policy in directcontradiction to the US war on drugs, rather than on thescientific or medical merits of the NAOMI study.With the NAOMI study being the only study of its kind inPage 9 of 14(page number not for citation purposes)tion treatment attempts and of not being on MMT at thetime of recruitment. The research assistants found thatNorth America, and with its two study sites located withinclose proximity to the Canada/US border, increasedHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2media attention was unavoidable. Despite the fact that theNAOMI study targets a very specific and marginalizedgroup within restricted geographic locations, regularbursts in media attention have required the team toextend strategic communications and outreach to a muchbroader audience.Some of issues raised in opposition to NAOMI are similarto those raised for HAT in general. Many of them arebased on fear and misinformation, while others are basedon different moral values. Like many new treatmentmodalities, critics exist who are opposed to NAOMI aswell as HAT. These criticisms are seen as improvementopportunities for those who support HAT. A lot has beensaid about this issue, and the authors refer the readers tothe early papers that discuss this topic in depth [57-59].One myth about HAT is that it is a better treatment thenMMT and thus would replace MMT. In fact, HAT is notmeant to replace MMT, but to be another available treat-ment option. One that would have a small but veryimportant role in the addiction treatment system [46].Even in two of the three countries where HAT exists as aregular program, participants in the program account forless than 10% of those in substitution treatment in thosecountries [31,45]. Another common myth is that HATpatients will start using more cocaine (and/or otherdrugs) because they no longer have to purchase heroin.The results of all the RCTs showed that the use of cocaineremains stable among HAT patients or even declines[37,40,55,60].Also an issue for some of the critics of HAT is that heroinis a respiratory depressant and daily injection is less safethan non-administration [40,41]. While injecting threetimes per day, or even daily, is clearly more harmful thannot injecting, the analysis of patient safety should takeinto account that if the patient is not receiving HAT he/shewould likely be injecting street heroin (cut with otheradditives) in an unsafe environment, not to mention theillegal activity that many enter into in order to purchasetheir drug(s). This rationale is supported by the Swissstudy where in a seven-year period the mortality rate ofthe Swiss participants was 1% per year, which is very lowcompared to the general mortality ratio of Swiss opioidusers (2.5–3%) [61].Further complicating the issue, North America's onlySupervised Injection Site (Insite) operates only blocksaway from NAOMI's Vancouver site. This had lead to con-fusion amongst media and in turn the public who maynot fully understand the difference between NAOMI (arandomized controlled clinical trial) and the SupervisedScience and media work in different ways and have differ-ent priorities. Bridging this communications gap canprove to be challenging and frustrating. The NAOMI teamaddressed this issue through a concerted effort to educatelocal communities, to maintain a low profile nationally,and to commit to scientifically based messaging.Due to these evolving issues the need to bring a Commu-nications consultant on board was identified in order tohelp define a response and to respond to media. This per-son was charged with putting together the text for a studywebsite http://www.naomistudy.ca, writing press releases,responding to basic media queries and arranging inter-views which became a huge part of the overall NAOMIstudy. While some journalists presented thoughtful andengaging perspectives on heroin therapy, incomplete andintended-to-shock media reports, not only within Canadabut also internationally, continued to stir emotions andincrease anxiety among local communities, police, vari-ous levels of government, and our neighbours to thesouth. Having someone on the team to help manage andrespond to these types of issues was very beneficial.The NAOMI team's media strategy continues to be torespond to media whilst committing to an unwaveringfocus on the scientific aspects of the study. As discussedearlier, the team also conducted community consultationmeetings and made numerous presentations to local serv-ices organizations such as the Vancouver Area Network ofDrug Users (VANDU), and to local community organiza-tions, the Provincial Government and the Federal Govern-ment. In addition, Community Advisory Boards/Committees (CABs) were established in Vancouver andMontréal. The Vancouver CAB included representatives oflocal community groups such as Grief to Action andVANDU, the Provincial Health Officer, and also repre-sentatives from the Royal Canadian Mounted Police, Van-couver Police Department, British Columbia Ministries ofHealth and Attorney General, British Columbia Centre forDisease Control, and the City of Vancouver. The MontréalCAB had a similar make-up comprising of representativesfrom municipal, provincial and federal governments andpolice, health authorities, pharmacists and physicians,public security, ex-injection drug users, as well as repre-sentatives from addiction treatment centres and the Uni-versité de Montréal.Over time, headlines and attitudes shifted from "Clinicaldisorder on our northern border" (The Hoya, GeorgetownUniversity) to "Why it makes sense to give them heroin"(The Globe & Mail, Canada). More recently, the Vancou-ver Courier published an article on NAOMI entitled "Endof NAOMI wastes research" (April 2, 2008) describingPage 10 of 14(page number not for citation purposes)Injection Site (an important local harm reduction initia-tive).that the study was due to finish this year and the chancesHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2of HAT being turned into a government supported pro-gram were unlikely.NAOMI – status reportThe last of NAOMI's 251 participants completed the clin-ical portion of the study in June 2008. While the Montréalclinic is now closed, part of the Vancouver clinic remainsopen and is now functioning as a small MMT clinic.At the end of the 12-month period of active treatment,participants were transitioned to available therapies in thecommunity, primarily MMT. Thus, even those who wereresponding to HAT had to stop this treatment and go backto the same options that had not worked for them in thepast because the study team could not legally continue toprescribe DAM outside of the clinical trial treatmentperiod. Retention in treatment at the 12-month point wassignificantly higher in the injection arm than the oral arm.Results of the primary outcomes were released publicly onOctober 17, 2008 and are available on the study websiteat http://www.naomistudy.ca (scientific publicationpending).Compassionate access to DAM for a small sample ofNAOMI participants who were retained, responding, andhad benefited from HAT, was sought through Health Can-ada's Special Access Programme. However, the requestswere denied as the Programme felt that 'there are otheroptions (i.e. marketed drugs) that we would consideralternatives to diamorphine at this time'. The results of theprimary end points demonstrate that, like in other coun-tries, HAT can attract, retain, and benefit this sub-popula-tion. However, as the Federal Government, throughHealth Canada, has denied compassionate access use toDAM, HAT treatment is unavailable in Canada. Canada isthe only country where diamorphine has been tested foraddiction treatment and has been denied compassionateuse [62].On a separate but related issue, recently the SupremeCourt of British Columbia ruled that Section 4(1) and5(1) of the Canadian Controlled Drug and Substances Act(CDSA) are inconsistent with section 7 of the CanadianCharter of Rights, thus meaning that those sections of theCDSA are of no force or effect. This translates to Vancou-ver's Supervised Injection Site being able to remain opendespite Federal Government. Specifically, the judgementgrants "users and staff at the Supervised Injection Site, act-ing in conformity with the operating protocol now ineffect, a constitutional exemption form the application ofss. 4(1) and 5(1) of the CDSA." However, the CanadianFederal Government is appealing this ruling [63].results of these interviews are not expected to be dissemi-nated until summer 2009, it appears that after the treat-ment endpoint participants generally either havereturned, or are returning to, where they were at baseline.In a few cases the treatment participants accessed throughthe study acted as a springboard to more long-term stabil-ity. However, it appears that a much larger proportion ofparticipants have returned, or are returning to, where theywere at when they first entered the study.As previously mentioned, the Vancouver clinic is partiallyopen and is providing MMT to some NAOMI participants,as well as other patients from the community. The studyteam hopes that the clinic will also be prescribing hydro-morphone in the future. While details have not been final-ized, and funding remains an issue that needs to beresolved, the team is hopeful that this opportunity willpan out. However, the possibility of providing herointreatment seems less likely given the conservative natureof those that would need to provide approval and giventhe response to-date from Health Canada's Special AccessProgram. Notwithstanding, the NAOMI team continuesto work to try and make access to heroin and/or hydro-morphone available to NAOMI participants and hope-fully others who are in need of, and want, treatment, andwho would be good candidates for a form of HAT therapy.ConclusionDespite the challenges surrounding NAOMI, the authorsfirmly believe that the study was worth doing. Given thepolitical issues still surrounding HAT, the authors feel thatit was important to conduct a HAT RCT in Canada andlook at HAT in the Canadian context. Although HAT is notapproved it Canada at this time, the authors hope that thiswill change one day given the NAOMI results, in combi-nation with the other HAT trial results already published.If any of the authors, or anyone else associated with thestudy, were to ever doubt whether NAOMI was worthdoing, or the profound affect it had on some participants,we need only to remember the words recently written tothe Principal Investigator of NAOMI by one of theNAOMI participants:"...I want to tell you what being a participant in this studydid for me. Initially it meant "free heroin". But over time itbecame more, much more. NAOMI took much of the stressout of my life and allowed me to think more clearly aboutmy life and future. It exposed me to new ideas, people (staffand clients) that in my street life (read: stressful existence)there was no time for.After NAOMI, I was offered oral methadone, which IPage 11 of 14(page number not for citation purposes)While not all of the 18 month and 24 month follow-upresearch interviews have been conducted as of yet, and therefused. After going quickly downhill, I ended up hopelessand homeless. I went into detox in April 2007, abstainedHarm Reduction Journal 2009, 6:2 http://www.harmreductionjournal.com/content/6/1/2from using for two months, then relapsed. In July 2008 Iagain went to detox and I am presently in a treatmentcenter...I am definitely not "out of the woods" yet, but I feel I am onthe right path. And this path started for me at the corner ofAbbott and Hastings in Vancouver...Thank you and all who were involved in making NAOMIhappen. Without NAOMI, I wouldn't be where I am today.I am sure I would be in a much worse place."AbbreviationsAll abbreviations used in the text were defined in the textwhere first used.Competing interestsThe authors declare that they have no competing interests.Authors' contributionsCCG has been involved with the study since late 2002.The case study submitted is an account of events prior to2002, and the majority of the case study focuses on eventsafter 2002, which CCG was directly involved with. CCGdrafted the article, coordinated the study, chronicled theevents, and researched many of the references.EOJ researched the references listed in the case study andadded intellectual content for the case study.NL was also involved with the study in the early days andadded intellectual content for the case study.MTS is the principal investigator of the study, wasinvolved in revising the case study, and gave finalapproval of the version submitted.Authors' informationCCG is the National Coordinator for the Study. CCG isalso the Chief Operating Officer for the CIHR CanadianHIV Trials Network. EOJ is a researcher and analyst for theStudy. She was also a lead investigator in the Spanish HATTrial. NL became involved with the study shortly after itwas approved by CIHR and was the Vancouver ClinicCoordinator for the study. MTS was an initial member ofthe first working group and is the Principal Investigator ofthe Study.ConsentWritten informed consent was obtained from all personswho participated in this study. A copy of the written con-sent in available for review by the Editor-in-Chief of thisjournal.AcknowledgementsThe authors wish to acknowledge the contributions of Julie Schneiderman, who was the Communications Consultant for the study. Also, she and CCG initially developed an abstract, which inspired this manuscript, in relation to Media and NAOMI. The authors also whish to acknowledge the work and commitment of all of the NAOMI staff and participants.The NAOMI study is primarily funded by the Canadian Institutes of Health Research. It is also supported by the Centre for Health Evaluation & Out-come Sciences at St. Paul's Hospital in Vancouver – Canada, the University of British Columbia – Canada, and the Hôpital Saint-Luc du Centre Hospi-talier de l'Université de Montréal – Canada.References1. 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