Guideline for Opioid Therapy and Chronic Noncancer Pain

GUIDELINE CPD

Guideline for opioid therapy and chronic noncancer pain

Jason W. Busse DC PhD, Samantha Craigie MSc, David N. Juurlink MD PhD, D. Norman Buckley MD, Li Wang PhD, Rachel J. Couban MA MISt, Thomas Agoritsas MD PhD, Elie A. Akl MD PhD, Alonso Carrasco-Labra DDS MSc, Lynn Cooper BES, Chris Cull, Bruno R. da Costa PT PhD, Joseph W. Frank MD MPH, Gus Grant AB LLB MD, Alfonso Iorio MD PhD, Navindra Persaud MD MSc, Sol Stern MD, Peter Tugwell MD MSc, Per Olav Vandvik MD PhD, Gordon H. Guyatt MD MSc n Cite as: CMAJ 2017 May 8;189:E659-66. doi: 10.1503/cmaj.170363

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hronic noncancer pain includes any painful condition that persists for at least three months and is not associated KEY POINTS with malignant disease.1 According to seven national sur- • We recommend optimization of nonopioid pharmacotherapy Cveys conducted between 1994 and 2008, 15%–19% of Canadian and nonpharmacologic therapy, rather than a trial of opioids, adults live with chronic noncancer pain.2 Chronic noncancer pain for patients with chronic noncancer pain. interferes with activities of daily living, has a major negative • Patients with chronic noncancer pain may be offered a trial of impact on quality of life and physical function,3 and is the leading opioids only after they have been optimized on nonopioid cause of health resource utilization and disability among working- therapy, including nondrug measures. age adults.4,5 • We suggest avoiding opioid therapy for patients with a history of In North America, clinicians commonly prescribe opioids for substance use disorder (including alcohol) or active mental illness, and opioid therapy should be avoided in cases of active substance acute pain, palliative care (in particular, for patients with cancer) use disorder. and chronic noncancer pain. Canada has the second highest rate • For patients beginning opioid therapy, we recommend per capita of opioid prescribing in the world when measured using restricting to less than 90 mg morphine equivalents daily (MED) defined daily doses, and the highest when defined using morphine and suggest restricting the maximum prescribed dose to less equivalents dispensed, with more than 800 morphine equivalents than 50 mg MED. 6,7 per capita in 2011. • Patients already receiving high-dose opioid therapy (≥ 90 mg Substantial risks accompany the use of opioids in chronic non- MED) should be encouraged to embark on a gradual dose taper, cancer pain. In Ontario, admissions to publicly funded treatment and multidisciplinary support should be offered where available programs for opioid-related problems doubled from 2004 to 2013, to those who experience challenges. from 8799 to 18 232.8,9 Among Ontarians receiving social assis- tance, 1 of every 550 patients started on chronic opioid therapy died of opioid-related causes at a median of 2.6 years from the first prescribing, but no change in rates of fatal opioid overdose and opioid prescription, while 1 in 32 of those receiving 200 mg mor- increases in both high-dose opioid prescribing and opioid-related phine equivalents daily (MED) or more died of opioid-related hospital visits. Moreover, 40% of recipients of long-acting opioids causes.10 An estimated 2000 Canadians died from opioid-related received > 200 mg MED, and 20% received > 400 mg MED.14 poisonings in 201511 and initial numbers for 2016 are higher, with This updated guideline incorporates all new evidence pub- most deaths attributed to fentanyl.12 lished subsequent to the literature search that was used to In 2010, the National Opioid Use Guideline Group offered rec- inform the 2010 guideline. It adheres to standards for trustwor- ommendations for safe and effective use of opioids.13 Many of the thy guidelines15 and aspires to promote evidence-based prescrib- recommendations were nonspecific and almost all supported the ing of opioids for chronic noncancer pain. The full guideline is prescribing of opioids; the guideline provided few suggestions available in Appendix 1 (at www.cmaj.ca/lookup/suppl/ about when not to prescribe.11 A time-series analysis in Ontario, doi:10.1503/cmaj.170363/-/DC1) and at http://nationalpaincentre. Canada, from 2003 to 2014, found a slight decline in overall opioid mcmaster.ca/guidelines.html.

© 2017 Joule Inc. or its licensors CMAJ | MAY 8, 2017 | VOLUME 189 | ISSUE 18 E659 GUIDELINE dation development. system tomeetstandardsofevidenceassessmentandrecommen- ommendations Assessment,DevelopmentandEvaluation(GRADE) We performedsystematicreviewsandappliedtheGradingofRec- and committee composition, and competing interest management. approaches forkeystandardssuchaspatientinvolvement,panel E660 the useofopioids inthemanagementofchronic pain.Fourteen patients fromacrossCanadawith avarietyofopinionsregarding panel andcreateda16-member patientadvisorycommitteeof committee includedtwopatient representativesonourguideline or limited,andreviewedthefinal guideline. vided clinicalpracticeguidanceinareaswhereevidencewasabsent informed theselectionofguidelinerecommendationtopics,pro - oids inthissettingwithextremeskepticism.Thiscommittee an importantrole and others who viewedthe practice of using opi- ment ofchronicpain,includingthosewhoviewedopioidsashaving experts witharangeofviewsontheroleopioidsinmanage - tions weredeveloped.Theclinicalexpertcommitteecomprised ing panelmembersandwerenotpresentwhentherecommenda - serve onaclinicalexpertcommittee.Theseindividualswerenotvot - oids, thesteeringcommitteeenlisted13experiencedclinicians to necessary expertiseinmanagementofchronicpainanduseopi - mately responsiblefortherecommendationsandtheirpresentation. of therecommendations,votedonallrecommendationsandisulti- The panel had extensive input into the development and presentation cle andathttp://nationalpaincentre.mcmaster.ca/guidelines.html). conflicts ofinterest(seecompetingstatementsatendarti- representatives. Mostpanelmembershadnofinancialorintellectual methodological training;oneisamedicalregulator)andtwopatient ducted thesystematicreviewsandotherliteraturesearches. line development.Additionally,anevidencesynthesisteamcon- mittee (GHG,JWB,DNJandDNB)oversawallaspectsofguide- and patientadvisorycommittee.Thefour-membersteeringcom- a steeringcommittee,guidelinepanel,clinicalexpertcommittee The developmentofourguidelinewassupportedbyfourgroups: Guideline developmentgroup dards fortrustworthyguidelines. In developingthisguideline,thesteeringcommitteefollowedstan- Methods of opioidaddictionorusedisorder. ment ofacuteorsubacutepain,careattheendlifetreatment regarding thisissue.Thisguidelinedoesnotaddressthemanage- get audienceincludesthosewhoprescribeopioidsorcreatepolicy scribing ofopioidsforadultswithchronicnoncancerpain.Thetar- The purpose of this clinical practice guideline is to inform the pre- Scope Health Researchprovidedfundingforthisguideline. Appendix 1andwww.magicapp.org/public/guideline/8nyb0E. To optimize patient involvement in our guideline, the steering To optimizepatientinvolvement inourguideline,thesteering To ensurethattheguidelinedevelopmentwasinformedby The guidelinepanelconsistedof13clinicians(mostwithextensive Health CanadaandagrantfromtheCanadianInstitutesof 16,17 For complete details on our methods, see Forcompletedetailsonourmethods,see 15 Weincludedinnovative CMAJ | MAY 8,2017 | VOLUME 189 ca/lookup/suppl/doi:10.1503/cmaj.170363/-/DC1). patient advisory committee (Appendix 2, available at www.cmaj. preferences foropioidtherapy, andthroughdiscussionswiththe by asystematicreviewofthe literatureofpatientvaluesand values andpreferencesstatement. Thisstatementwasinformed panel’s recommendations,the steeringcommitteedevelopeda To complementtheresearchfindingsandtoguideguideline Values andpreferences models wereoptimallyadjusted. outcome assessment,losstofollow-upandwhetherpredictive sentativeness ofthestudypopulation,validityexposureand and informedourvaluespreferencesstatement. reviews thatsummarizedtheevidenceforourrecommendations, approved theoutcomesconstitutingfocusofsystematic on prescriptionopioids.Thepatientadvisorycommittee another representedafamilymemberwhohadfatallyoverdosed scription opioids,onehadexperiencewithopioidaddictionand patients werelivingwithchronicpainandused(orhadused)pre- from theUsers’GuidestoMedicalLiterature, Pain, line for Safe and Effective use of Opioids for Chronic Non-Cancer The evidence synthesis team reviewed the 2010 Canadian Guide- Research questions Guideline development ing theuseofopioidsforchronicnoncancerpain, bias instrument, of biasfromrandomizedtrialsusingamodifiedCochranerisk of outcome-by- harms, alongwitharatingofthecertaintyevidenceonan the GRADE system to provide a clear description of benefits and The evidencesynthesisteamcreatedsummariesusing the systematicreviews,anddevelopmentofrecommendations. larly toensureharmonizationofthescope,approachandoutput guideline panelandtheevidencesynthesisteaminteractedregu- ized trialsandobservationalstudies(excludingcasereports).The PsycINFO, and PubMed through October 2016, including random evidence in AMED, CINAHL, Cochrane Library, Embase, MEDLINE, - erSR, Evidence Partners, Ottawa,Canada; https://systematic standardized forms in an online data abstraction program (Distill The evidencesynthesisteamconductedsystematicreviewsusing Systematic reviews Technologies inHealth(CADTH)andCanada. Centre onSubstanceAbuse,theCanadianAgencyforDrugsand oners, nursing,Workers’CompensationBoards,theCanadian groups, family medicine, pain medicine, addiction medicine, cor- enforcement, pharmacy,medicalregulation,patientadvocacy recommendations. Attendeesincludedrepresentativesfromlaw previous recommendationsandidentifyotherrelevanttopicsfor held anationalstakeholdermeetingonJuly17,2015,todiscuss marized all prior recommendations. The steering committee review.ca) to inform our recommendations. The team searched for review.ca) toinformourrecommendations.Theteamsearchedfor Reviewers fromtheevidencesynthesisteamassessedrisk 13 aswellsixotherrecentlypublishedguidelinesaddress- | ISSUE 18 outcome basis(Box1). 23 and from observational studies using criteria 24 includingrepre- 18–22,53 andsum- - - GUIDELINE E661 Input from medical 27 28 ISSUE 18 ISSUE Box 2 and multilayered formats in MAGICapp (www. | Members of the guideline panel, along with two Health Canada Health two with along panel, guideline the of Members also endorsed three good practice state- The guideline panel The steering committee reviewed and summarized more thanThe steering committee reviewed and summarized observers, attended a second in-person meeting on Jan. 6, 2017. meeting on attended a second in-person observers, and for each recommendation relevant evidence Panellists reviewed (https://ietd.epistemonikos online voting software used anonymous, weak in strong in favour, their recommendation: .org) to select by We required endorsement against, or strong against. favour, weak for acceptance of a recommendation. 80% of panel members with interventions guidance for actionable offer to intended ments of large net benefits (www.magicapp. compelling indirect evidence org/goto/guideline/8nyb0E/section/jmA7Mj). Maximizing nonopioid treatment When considering therapy for patients with chronic noncancer pain, we recommend optimization of nonopioid pharmacotherapy and nonpharmacologic therapy, rather than a trial of opioids (strong recommendation). See www.magicapp.org/goto/ guideline/8nyb0E/rec/LqqP6L for details. Recommendations We developed 10 recommendations, 7 of which focus on harm reduction. magicapp.org/public/guideline/8nyb0E) provide our 10 recommendations and associated remarks. Here we describe five key recommendations in greater detail. - of Physicians and Surgeons of Ontario, Col regulators (the College of Surgeons of British Columbia, College lege of Physicians and of Nova Scotia and Federation of MedicalPhysicians & Surgeons of Canada) guided our selection of good Regulatory Authorities practice statements. External review on the National PainWe posted the draft guideline recommendations for publicCentre website (http://nationalpaincentre.mcmaster.ca/) encouraged participa- consultation, from Jan. 30 to Feb. 28, 2017. We announced the oppor- tion by inviting 429 stakeholders by email and and on social media. tunity for review through a national press release when drafting the 500 comments, which it carefully considered strength of any recom- final guideline. Neither the direction nor however, the steeringmendations changed because of feedback; added details to clarifycommittee did make wording changes and was reviewed by anareas of concern. Finally, the draft guideline to the “Clinical Practiceexternal review committee for adherence Health and MedicineGuidelines We Can Trust” checklist from the Engineering, and Medi- Division, National Academies of Sciences, cine (www.nationalacademies.org/hmd/Reports/2011/Clinical -Practice-Guidelines-We-Can-Trust.aspx). Guideline format the Irresistible Choice We partnered with the Making GRADE presentation of the (MAGIC) nonprofit initiative to optimize guidelines, in digitally structured and multilayered formats available on all devices, and to develop decision aids for clinicians to use in shared decision-making. VOLUME 189 VOLUME | om MAY 8, 2017 MAY 15–17 | CMAJ Our guideline panel and clinical expert committee expert clinical and panel guideline Our 25,26 The guideline also contains best practice statements and clinical Statements about qualifying remarks and values andStatements about qualifying remarks and values Strong recommendations indicate that all or almost all fully course ofinformed patients would choose the recommended isaction, and indicate to clinicians that the recommendation appropriate for all or almost all individuals. Strong recommendations represent candidates for quality of care criteria or performance indicators. Weak recommendations indicate that the majority of informed patients would choose the suggested course of action, but an appreciable minority would not. With weak recommendations, clinicians should recognize that different choices will be appropriate for individual patients, and they should help patients arrive at a decision consistent with their values and preferences. Weak recommendations should not be used as a basis for standards of practice (other than to mandate shared decision-making). expert guidance, which are distinct from recommendations that have been formally categorized using GRADE. Good practice statements represent common-sense practice, are supported by indirect evidence, and are associated with assumed large net benefit. Clinical expert guidance provides direction in areas for which there is either no published evidence or insufficient evidence to justify a formal recommendation. These do not have the force of either recommendations that have been categorized using GRADE or good practice statements. Box 1: How to use and understand this guideline Box 1: How to use and understand this guideline a basis forThis guideline provides prescribers and patients with noncancer pain.decisions about using opioids to manage chronic regulatoryPrescribers, patients and other stakeholders — particularly in thisagencies or the courts — should not view the recommendations the uniqueguideline as absolute. No guideline can account for this guideline isfeatures of patients and their clinical circumstances; not meant to replace clinical judgment. and arepreferences are integral parts of the recommendations guideline. Thesemeant to facilitate accurate interpretation of the should never be omitted when quoting or translating in thisrecommendations from this guideline. Recommendations ofguideline are categorized according to the Grading EvaluationRecommendations Assessment, Development and (GRADE) system as strong or weak recommendations. We applied the GRADE system to move from evidence to recom- We applied the GRADE

mendations (supported by evidence from randomized controlled from randomized (supported by evidence mendations good practice studies), trials or observational statements (supported and expert guidance by indirect evidence), (supported no published evidence). by little or mendations. Development of recommendations of Development rec categories of guidance: includes three The guideline - meeting on Jan. 5, 2017, as did representa attended an in-person The primary purpose was to discuss tives from Health Canada. was no — or very limited — research evidenceissues for which there - expert guidance. These included restric in order to develop clinical of the quantity of opioids prescribed, use tions with respect to sed- coprescribing of controlled-release opioids, versus immediate- - opioid-induced sleep apnea or hypogonad atives, management of mitigating risk (i.e., treatment agreements,ism, and strategies for tamper-resistant formulations, fentanyl patchurine drug screening, exchange and coprescribing of naloxone). GUIDELINE E662 quent addiction(SupplementaryTables3a–einAppendix3,avail- unintentional overdose, very frequent physical dependence and fre- ments atthecostofasmallbutimportantrisknonfatalandfatal est improvementsinpainandfunctionrelativetoothertreat- When addedtononopioids,opioidsmayachieve,onaverage,mod- Rationale *Available atwww.magicapp.org/public/guideline/8nyb0E. • recommend aformalmultidisciplinaryprogram(strongrecommendation) (www.magicapp.org/goto/guideline/8nyb0E/rec/ERX6WL). Recommendation 10:Forpatientswithchronicnoncancerpainwhoareusingopioidsandexperiencing seriouschallengesintapering,we • (weak recommendation)(www.magicapp.org/goto/guideline/8nyb0E/rec/L4BypE). we suggesttaperingopioidstothelowesteffectivedose,potentiallyincluding discontinuation,ratherthanmakingnochangeinopioidtherapy Recommendation 9:Forpatientswithchronicnoncancerpainwhoarecurrentlyusing90mg morphineequivalentsofopioidsperdayormore, • magicapp.org/goto/guideline/8nyb0E/rec/nJM4bL). problematic adverseeffects,wesuggestrotationtootheropioidsrather thankeepingtheopioidsame(weakrecommendation)(www. Recommendation 8:Forpatientswithchronicnoncancerpainwhoarecurrentlyusingopioids, andhavepersistentproblematicpainand/or • less than50mgmorphineequivalentsdaily(weakrecommendation)(www.magicapp.org/goto/guideline/8nyb0E/rec/noAgMj). Recommendation 7:Forpatientswithchronicnoncancerpainwhoarebeginningopioidtherapy,wesuggestrestrictingtheprescribeddoseto • magicapp.org/goto/guideline/8nyb0E/rec/jmJ0VL). to lessthan90mgmorphineequivalentsdaily,ratherhavingnoupperlimitorahigherondosing(strongrecommendation)(www. Recommendation 6:Forpatientswithchronicnoncancerpainwhoarebeginningopioidtherapy,werecommendrestrictingtheprescribeddose • recommendation) (www.magicapp.org/goto/guideline/8nyb0E/rec/j79BGn). optimized, andwhohavepersistentproblematicpain,wesuggestcontinuingnonopioidtherapyratherthanatrialofopioids(weak Recommendation 5:Forpatientswithchronicnoncancerpainahistoryofsubstanceusedisorder,whosenonopioidtherapyhasbeen recommendation) (www.magicapp.org/goto/guideline/8nyb0E/rec/jzPK1n). and whohavepersistentproblematicpain,wesuggeststabilizingthepsychiatricdisorderbeforeatrialofopioidsisconsidered(weak Recommendation 4:Forpatientswithchronicnoncancerpainanactivepsychiatricdisorderwhosenonopioidtherapyhasbeenoptimized, • (strong recommendation)(www.magicapp.org/goto/guideline/8nyb0E/rec/jxZ7Dn). Recommendation 3:Forpatientswithchronicnoncancerpainanactivesubstanceusedisorder,werecommendagainsttheofopioids • continued therapywithoutopioids(weakrecommendation)(www.magicapp.org/goto/guideline/8nyb0E/rec/j91boj). psychiatric disorders,whohavepersistentproblematicpaindespiteoptimizednonopioidtherapy,wesuggestaddingatrialofopioidsratherthan Recommendation 2:Forpatientswithchronicnoncancerpain,withoutcurrentorpastsubstanceusedisorderandotheractive and nonpharmacologictherapy,ratherthanatrialofopioids(strongrecommendation)(www.magicapp.org/goto/guideline/8nyb0E/rec/LqqP6L). Recommendation 1:Whenconsideringtherapyforpatientswithchronicnoncancerpain,werecommendoptimizationofnonopioidpharmacotherapy Box 2:Summaryofrecommendationsforopioidtherapyandchronicnoncancerpain* kinesiologist, anoccupationaltherapist, anaddictionmedicinespecialist,apsychiatristandpsychologist). availability (possibilitiesinclude,but arenotlimitedto,aprimarycarephysician,nurse,pharmacist,physical therapist,achiropractor, a coordinatedmultidisciplinarycollaboration thatincludesseveralhealthprofessionalswhomphysicians can accessaccordingtotheir In recognitionofthecostformalmultidisciplinary opioidreductionprogramsandtheircurrentlimitedavailability/capacit y, analternativeis reduction; taperingmaybepausedorpotentiallyabandonedinsuchpatients. Some patientsmayhaveasubstantialincreaseinpainordecreasefunction thatpersistsformorethanonemonthafterasmalldose Rotation insuchpatientsmaybedoneparallelwith,andasawayof facilitating, dosereduction. pain control. some patientswhowouldbereadytoaccepttheincreasedrisksassociatedwithadosehigherthan50mginorderpotentiallyachieveimproved The weakrecommendationtorestricttheprescribeddoselessthan50mgmorphineequivalentsdailyacknowledgesthattherearelikelybe regarding thepossibilityofincreasingdosetomorethan90mgmorphineequivalentsdailymaythereforebewarrantedinsomeindividuals. Some patientsmaygainimportantbenefitatadoseofmorethan90mgmorphineequivalentsdaily.Referraltocolleagueforsecondopinion abuse anddependence,narcoticsometimesreferredtoICD-9diagnoses. The studiesthatidentifiedahistoryofsubstanceusedisorderasriskfactorforadverseoutcomescharacterizedtheconditionsalcohol and sometimesreferredtoICD-9diagnoses. disorder asariskfactorforadverseoutcomescharacterizedtheconditionsalcoholabuseanddependence,narcotic Clinicians shouldfacilitatetreatmentoftheunderlyingsubstanceusedisorders,ifnotyetaddressed.Thestudiesthatidentified and depression,includingICD-9definitions,aswell“psychiatricdiagnosis,”“mooddisorder”post-traumaticstressdisorder. Diseases, 9threvision(ICD-9)diagnoses.Thementalillnessesidentifiedinstudiesasriskfactorsforadverseoutcomesweregenerallyanxiety conditions asalcoholabuseanddependence,narcoticsometimesreferredtoInternationalClassificationof or functionisnotachieved.Thestudiesthatidentifiedsubstanceusedisorderasariskfactorforadverseoutcomescharacterizedthe By atrialofopioids,wemeaninitiation,titrationandmonitoringresponse,withdiscontinuationopioidsifimportantimprovementinpain CMAJ | MAY 8,2017 | VOLUME 189 but withouttheharmsofdependence,addictionandoverdose. drugs [NSAIDs],graduatedexercise,cognitivebehaviouraltherapy), ment inpainandfunction(e.g.,nonsteroidalanti-inflammatory eral nonopioidtherapiesmayachieveasimilardegreeofimprove- As first-linetreatmentforpatientswithchronicnoncancerpain,sev- able at www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.170363/-/DC1). | ISSUE 18 GUIDELINE

10 35–40 E663 34 Moreover, = 0.22). 41 Data from popula- 33 100 mg MED/day. 100 mg MED/day. = 0.49) or functional recovery (p or more, we suggest tapering opioids to the the to opioids tapering suggest we more, or

ISSUE 18 ISSUE | The weak recommendation to restrict the prescribed dose toThe weak recommendation to restrict the Chronic opioid therapy (treatment for more than three months) for more than three therapy (treatment Chronic opioid Tapering For patients with chronic noncancer pain who are currently using day per MED mg 90 lowest effective dose, potentially including discontinuation, rather than making no change in opioid therapy (weak recommendation). See www.magicapp.org/goto/guideline/8nyb0E/rec/ L4BypE for details. Dosing noncancer pain who are beginning opioidFor patients with chronic restricting the prescribed dose to less thantherapy, we recommend on having no upper limit or a higher limit 90 mg MED, rather than - We suggest restricting the pre dosing (strong recommendation). 50 mg MED (weak recommendation). Seescribed dose to less than and www. www.magicapp.org/goto/guideline/8nyb0E/rec/jmJ0VL for details. magicapp.org/goto/guideline/8nyb0E/rec/noAgMj patients will be will- less than 50 mg MED acknowledges that some with doses exceedinging to accept the increased risks associated pain control. Fur- 50 mg in order to potentially achieve improved at a dose of morether, some patients may gain important benefit a pain special- than 90 mg. Referral to a colleague (not necessarily of increasing theist) for a second opinion regarding the possibility be warranted in dose to more than 90 mg MED may therefore some individuals. Rationale evidence of a Observational studies provide moderate-quality unintentional nonfatal progressive increase in the likelihood of of opioids increases. overdose or death as the prescribed dose in patients pre- These serious outcomes are very uncommon in those prescribed scribed less than 50 mg MED, but increase uncommon, are fur- doses of 50 mg to 90 mg, and although still more than 90 mg MED. ther increased in those prescribed doses of Evidence summary Meta-regression of within-trial comparisons of different doses of opioids found moderate-quality evidence against a dose–response effect for pain relief (p tion surveys suggest similar rates among Canadian adults. tion surveys suggest similar However, there is likely a dose-dependent increase in the risk of nonfatal opioid overdose: 0.2% for < 20 mg MED/day; 0.7% for 50–99 mg MED/day; and 1.8% for ≥ there is an increased risk of fatal opioid overdose with higher there is an increased risk of fatal opioid overdose with higher doses: 0.1% for < 20 mg MED/day; 0.14% for 20–49 mg MED/day; 0.18% for 50–99 mg MED/day; and 0.23% for ≥ increases the risk of gastrointestinal adverse events, including vom- including events, adverse of gastrointestinal the risk increases adverse more gastrointestinal and constipation (5.8% iting, nausea Appendix 3). Table 3f, events) (Supplementary doses low very at and, addiction of risk 5.5% a with associated is (< 20 of and a 0.1% risk risk of nonfatal overdose MED/day), a 0.2% - of overdose increases at higher doses (Sup fatal overdose; the risk - 3). In 2013, 4.9% of Americans admit plementary Table 3f, Appendix of prescription opioids. ted to nonmedical use VOLUME 189 VOLUME | MAY 8, 2017 MAY | CMAJ The mental illnesses identified in the studies as risk factors The mental illnesses identified in the studies 29–32 By a trial of opioids, we mean initiation, titration and monitoringBy a trial of opioids, we mean initiation, titration as a risk fac- The studies that identified substance use disorder

For patients with chronic noncancer pain, without current or pastFor patients with chronic noncancer pain, - disor psychiatric active other without and disorder use substance despite optimized non- ders, who have persistent problematic pain of opioids rather than opioid therapy, we suggest adding a trial recommendation). See continued therapy without opioids (weak for details. www.magicapp.org/goto/guideline/8nyb0E/rec/j91boj if important improve- of response, with discontinuation of opioids reasonable trial of ther- ment in pain or function is not achieved. A to six months; opioidsapy should be accomplished within three may patients some and months three after relief pain less provide symptoms. continue use to address inter-dose withdrawal conditions as alcoholtor for adverse outcomes characterized the and dependence, andabuse and dependence, and narcotic abuse of Diseases, 9thsometimes referred to International Classification evidence did not sup- revision (ICD-9) diagnoses. Moderate-quality and opioid misuse port an association between smoking status 0.97– [CI] interval confidence 95% 1.29, [OR] ratio odds (adjusted 1.7). Trial of opioids Evidence summary similar effects opioids may have evidence that We found low-quality (a nabilone or antidepressants, tricyclic NSAIDs, as relief pain on - and similar improvements in physical func synthetic cannabinoid), - tricyclic antidepressants or nabi tion as NSAIDs, anticonvulsants, evi- 3). High-quality Tables 3a–e, Appendix lone (Supplementary gastrointestinal of rate the increase opioids that shows dence with NSAIDs, and low-quality evidenceadverse events compared increase the rate of gastrointestinal adverseshows that they may anticonvulsants and tricyclic antidepressantsevents compared with 3a–e, Appendix 3). (Supplementary Tables CADTH has compiled the evidence supporting nonopioid therapies nonopioid supporting evidence the compiled has CADTH noncancer pain (www.cadth.ca/evidence-bundles/ for chronic opioid-evidence-bundle/browse-category#alternatives). Evidence summary We found moderate-quality evidence that opioid add-on therapy versus no opioid add-on therapy has, on average, a modest effect on pain reduction (best estimate of percentage of patients achieving a reduction in pain greater than the minimally important difference is 11.1%), and on functional improvement (best estimate for achieving an important improvement in function is 10.0%), but also Rationale When added to nonopioids, opioids achieve, on average, modest improvements in pain and function. Adverse effects include relatively frequent constipation, nausea and vomiting, sedation and addiction, and a small but important risk of unintentional overdose, which can be fatal. The risk of unintentional overdose increases progressively with the daily dose prescribed (Supplementary Table 3f, Appendix 3). for adverse outcomes were most typically anxiety and depression,for adverse outcomes were most typically diagnosis,”“psychiatric as well as definitions, ICD-9 of use including “mood disorder” and post-traumatic stress disorder. GUIDELINE E664 is uncertainwhethertaperinghasaneffectonpain(Table1). gether. Thismayreducetheriskofopioid-relatedharms,althoughit a substantialreductioninopioiddose,orcessationofopioidsalto- We foundlow-qualityevidencethattaperingmayeventuallyresultin Evidence summary symptoms ofopioidwithdrawal. cause increasedpain,decreasedfunctionorhighlyaversive tentional overdose.Ifnotdonegradually,dosereductionmay cognitive impairmentandthelikelihoodofnonfatalorfatalunin- Reduction inopioiddosemayreduceadverseeffects,including Rationale tially abandonedinsuchpatients. after asmalldosereduction;taperingmaybepausedandpoten- or decreaseinfunctionthatpersistsformorethanonemonth Hydromorphone Codeine opioid taper at aUS Veterans Affairs medical centre. A taper was considered successful ifthe patient’s dose at 12months was lessthanthe baseline dose. Source: Modifiedfrom Nielsenandcolleagues. †The maximumrecommended dailydoseoftramadol is300mgto 400mg,dependingontheformulation. *Conversion ratios for opioidsare subject to variations inkinetics governed by genetics andother drugs. Morphine Opioids* Table 2:Conversion ratios for opioids ¶These 2studies defined“success oftapering” differently. Baron andMcDonald § Smallnumberofpatients. ‡Neither study enrolled acomparison group. †Minimally important difference for pain onan11-pointNRS isa reduction of2points. *Available at www.magicapp.org/SoF9. Note: NRS =NumericPain Rating Scale, SD=standard deviation. 6–12 mo lower isbetter)† Pain (11-pointNRS; Outcome follow-up morphine equivalents of opioidsperdayormore* Table 1:Theeffect of opioid tapering versus maintaining thedose for adult patients withchronic noncancer pain using90mg addiction to opioids.Thegoal oftheprogram was to taper patients completely offopioids.Harden and colleagues prescription opioidsifthepatient orphysicianfelt that thepatient was not getting benefitfrom highdosesofopioids.Nopatient was referred for diversion, overuse, abuse or 6–12 mo Success oftapering Oxycodone Tramadol Tapentadol Some patientsarelikelytohaveasubstantialincreaseinpain 2 studies (73patients) 2 studies (73patients) morphine equivalent, No. of studies To convert to oral multiply by: 52 0.1–0.2 0.1–0.2 0.3–0.4 5.0 1.0 1.5 CMAJ 42,43 42,43 | MAY 8,2017 In onestudy, In onestudy, patients successfully tapered opioids and 33%reported more pain after tapering reported lesspain, 28%reported nochange In theother study, successfully tapered opioids. In theother study, at baseline to 3.35(0.33)at 6mo. 11-point NRS from mean (SD)of8.00(0.30) morphine, multiplyby: To convert from oral 42 Absolute effect estimates enrolled patients into avoluntaryinpatient detoxification program intended to taper themoff 42 42 | 0.667 pain was reduced onan 6.67 3.33 100%ofpatients VOLUME 189 0.2 1.0 6.0 43 43 consultation decisionaidsavailablethroughtheMAGICapplica- guideline. Clinicianscanfacilitateshareddecision-makingusing length ofguidelines)toguidedesignandformatthecurrent barriers toimplementation age chronicpainhavebeenlimited. Canadian guidelinerecommendationsforuseofopioidstoman- based therapiesforpatientswithchronicnoncancerpain. should exploreopportunitiestofacilitateaccessevidence- deliver servicesthatareunavailable.Rather,policy-makers ject toresourceavailability:physicianscannotberequired dose formultidisciplinarycare.Bothrecommendationsaresub- of opioids,andtoreferpatientsstrugglingreducetheiropioid therapy (includingnondrugtherapies)beforeconsideringatrial We havemadestrongrecommendationstooptimizenonopioid Implementation 40%ofpatients 47of50(94%) Canadian physicians’ awareness of and adherence to the 2010 Canadian physicians’awarenessofandadherencetothe2010 | ISSUE 18 43 equivalent dose, mg/d includedindividualsdrawn from alist ofpatients initiated onan 50 mgmorphine 334 160 300 10 50 33 serious imprecision§ indirectness¶ and Low, dueto serious imprecision§ and serious serious riskofbias‡ low,Very dueto Quality of evidence 45 and used the findings (e.g., excessive andusedthefindings(e.g.,excessive 44 We have formally explored Wehaveformallyexplored equivalent dose, mg/d 90 mgmorphine population high inthispatient tapering maybe Success of pain of tapering on about theeffect We are uncertain Plain language 540† 600 300 18 90 60 summary GUIDELINE

. 80. E665 Global 77- Chronic . 9 16: J Clin Epi- Ann Intern Ann Intern 381- e0167479. 2011; 11: 144: Acta Anaesthesiol Acta Anaesthesiol J Occup Environ Med Preventing misuse of 2016; 2013; Guideline panels should Guideline panels should Chest GRADE guidelines: 15. Going GRADE guidelines: 15. Going Pain Res Manag PLoS One et al. Opioid use behaviors, mental Opioid use behaviors, mental . Olympia (WA): Washington State The prevalence of chronic pain and chronic pain of prevalence The Creating clinical practice guidelines HJ, et al. Sex differences in dose escalation Sex differences in dose escalation et al. ACOEM practice guidelines: opioids for Automated prediction of risk for prob- GRADE guidelines: 14. Going from evi- AD, High-dose opioid prescribing and opioid- et al. Going from evidence to recommenda- Narcotic drugs: estimated world require- Narcotic drugs: estimated world et al. American Society of Interventional Pain Pain Interventional of Society American Changes in and characteristics of admis- Changes in and characteristics et al.

, GRADE: an emerging consensus on rating on consensus emerging an GRADE: SR, , P et al. Trustworthy clinical guidelines. Health utilities in people with chronic pain chronic with people in utilities Health et al. X DM, , et al. et al. . Prescription opioid use, harms and interven- Prescription opioid use, harms , et al. K K, C et al. Specific instructions for estimating unclearly Specific instructions for estimating unclearly et al. et D , Oxman al. et B. Effective Canadian policy to reduce harms from R Doyle AD, B, , S, Schunemann et al. et

, GE, HJ, M. J, P et al. JO, Camacho Buchanan Kunz Bowden Rush Mulrow Atluri , Fischer Vist Juurlink Saunders 64. , Oxman T , JW, Katz Alonso-Coello N, JE, , S, , D .

AD, MS, DB, M, L 7 Tyndall AD, G, A, EM, Merrill 157- J, Abdi 31: 262- Busse Gomes CJ, Weiss , , Schunemann , L, 59. Martins , X

Brandt Tranmer 65: Oxman , Alonso-Coello of pain management. Economic implications Guyatt E Oxman Taddio K Goldner Rehm www.va.gov/painmanagement/docs/cpg_opioidtherapy_fulltext.pdf Nakamura The need for a Canadian pain strategy. The need for a Canadian pain KT, 2011; Von Korff Von JC, ISSUE 18 ISSUE J, Taichman | ML, PO, Y, e143- Sun B, B, JD. , GH, GH, GH, ME, 2012; ME. TR, C BMJ 2008;336:1049-51. 56: , EA, population from 1994 to 2008. in the Canadian pain-related interference Dis Inj Can Hogan Availability of internationally controlled Board. Availability of internationally International Narcotics Control for medical and scientific purposes. New York:drugs: ensuring adequate access United Nations; 2016. Murphy International Narcotics Control Board. Control Narcotics International 2004. 2002. New York: United Nations; ments for 2004, statistics for Reitsma :957-9. Scand 1999;43 Lynch Hylan Guyatt using a population-level survey and linked health care administrative data. health care administrative survey and linked using a population-level :408-16. Pain 2017;158 Loeser update of new developments and findings since tions in Canada: a review :E605-14. 2010. Pain Physician 2015;18 Fischer we can trust, use, and share: a new era is imminent. treatment of acute, subacute, chronic, and postoperative pain. treatment of acute, subacute, chronic, and postoperative 2014; Manchikanti Laine fentanyl/ (accessed 2017-by-province-look-at-opioid-overdose-stats-including- Apr. 7). for chronic non-cancer Canadian guideline for safe and effective use of opioids 2010. pain Canada. Canada: National Opioid Use Guideline Group (NOUGG); Fernandes and overdose death during chronic opioid therapy: a population-based cohort and overdose death during study. PLoS One 2015;10:e0134550. Fischer 2016;188:1240-4. prescription opioids: learning from past failures. CMAJ fentanyl. stats, including at opioid-overdose look province-by-province A /a-province News 2016 Nov. 17. Available: http://globalnews.ca/news/3072316 sions to treatment related to problematic prescription opioid use in Ontario, Ontario, in use opioid prescription problematic to related treatment to sions 2010;109:257-60. 2004–2009. Drug Alcohol Depend Kaplovitch lem opioid use in a primary care setting. J Pain 2015;16:380-7. Banta-Green Med 2011;154:774-5. Guyatt related hospitalization: a population-based study. tions. seldom make good practice statements: guidance from the GRADE Working seldom make good practice statements: guidance from the GRADE Working Group. J Clin Epidemiol 2016;80:3-7. Vandvik from evidence to recommendation-determinants of a recommendation’s from evidence to recommendation-determinants of a recommendation’s direction and strength. J Clin Epidemiol 2013;66:726-35. Guyatt dence to recommendations: the significance and presentation of recommendations. J Clin Epidemiol 2013;66:719-25. Andrews BMJ 2008;336:924-6. quality of evidence and strength of recommendations. Hegmann demiol Randolph AG, Cook DJ, Guyatt G. Prognosis. In: Guyatt G, Rennie D, Meade MO, et al., editors. Users’ guides to the medical literature: a manual for evidence-based clinical practice. 3rd ed. New York: American Medical Association; 2015:421-9. Andrews reported blinding status in randomized trials were reliable and valid. Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic prescribing in chronic Physicians (ASIPP) guidelines for responsible opioid ;15(Suppl):S67-116. non-cancer pain: Part 2–guidance. Pain Physician 2012 pain: an education aidInteragency guideline on opioid dosing for chronic noncancer therapy opioid with safety and care improve to agencymeddirectors.wa. Agency Medical Directors Group; 2010. Available: www. gov/Files/OpioidGdline.pdf (accessed 2017 Mar. 9). . New York City Department of Health and Mental Hygiene (accessed 2017 Mar. 9). Akl ;30:23-30. prescription opioid drugs. City Health Information 2011 pain chronic for therapy opioid of management guideline: practice clinical VA/DoD 2010. Defense; of Affairs/Department Veterans of Department (DC): Washington Available:

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VOLUME 189 VOLUME | 52 MAY 8, 2017 MAY | CMAJ and no risk mitigation strategy in Canada. Our recommenda- 51 48,49 has been endorsed by selected provincial col- selected by endorsed been has 47 The current guideline addresses these limitations. 50 Having all the content digitally structured and published in published and structured digitally content the all Having We are seeking funds to support the development, delivery development, the funds to support seeking We are 46 46 Merskey H, Bogduk N; Task Force on Taxonomy of the International Associa- Classification of chronic pain, second edition Pain. of Study the for tion (revised). Seattle (WA): International Association for the Study of Pain; 1994. The National Pain Centre (http://nationalpaincentre.mcmaster. The National

and measurement of a national knowledge translation strategy. knowledge translation of a national and measurement by dynami- review of new evidence provide an ongoing ca/) aims to “living guide- as needed, yielding a recommendations cally updating line.” leges of physicians and surgeons has convincingly shown reduced harm for patients prescribed opioidhas convincingly shown reduced harm for patients therapy. Research addressing these issues would be valuable. MAGICapp facilitates dynamic updating from a technical perspective;MAGICapp facilitates dynamic cen- the which for resources requires guidelines of updating however, If we are unable to implement the dynamictre is seeking funds. minimum) (at guideline this update to plan we process, updating (estimated 2022). within five years of publication

References 1. Conclusion noncancerchronic for therapy opioid for base evidence limited The pain supports offering a trial of opioids to selected patients with chronic noncancer pain who have not found sufficient relief with optimized nonopioid therapy (see Table 2 for opioid conversions). Clinical trials of opioids for chronic noncancer pain failed to followClinical trials of opioids for chronic noncancer patient populationspatients for more than one year, enrolled limited of outcomes. Noneand did not provide a comprehensive assessment patients for high risk ofof the instruments designed for screening predict to shown been have use opiate with outcomes adverse patients unsuitable for opioid therapy, Gaps in knowledge Several guidelines for prescribing of opioids for chronic pain have pain chronic for opioids of prescribing for guidelines Several www. at available 4, (Appendix years five last the in published been however,cmaj.ca/lookup/suppl/doi:10.1503/cmaj.170363/-/DC1); Control and Preven- only the 2016 United States Centers for Disease tion (CDC) guideline Other guidelines tion. tions regarding dose escalation for patients initiating opioid therapypatients initiating opioid for escalation dose tions regarding of the CDC guide- are consistent with the CDC guideline. Limitations critical of opioid use forline include the heavy involvement of experts of patients, excessivechronic noncancer pain, limited involvement application ofrestrictions on the selection of evidence, suboptimal recommendationsthe GRADE rating system, excessive use of strong in some recom- in the face of low-quality evidence and vagueness mendations. The harms associated with opioid therapy are substantial; indeed, 7 of our 10 recommendations focus on harm prevention. Although the evidence supports dose limits for patients beginning opioid therapy, - dis a constitute therapy opioid high-dose receiving currently those tinct population, and tapering efforts should be individualized and should consider patients’ values and preferences. GUIDELINE 31. E666 38. 37. 34. 40. 39. 36. 42. 35. 33. 32. 41. (da Costa), University of Bern, Bern, Switzerland; (da Costa),University ofBern,Switzerland; Canada (Cull);InstituteofPrimaryHealth Care of Chile,Santiago,Chile;Inspireby Example, Faculty ofDentistry(Carrasco-Labra), University Department of Oral and Maxillofacial Surgery, Canadian PainCoalition(Cooper),Oshawa, Ont.; can UniversityofBeirut(Akl),Beirut, Lebanon; Geneva (Agoritsas),Geneva,Switzerland;Ameri- versity, Hamilton,Ont.;UniversityHospitalsof Carrasco-Labra, Iorio and Guyatt), McMaster Uni- Research Methods,Evidence,andImpact(Busse, sia (BusseandBuckley),DepartmentofHealth ban, CraigieandWang),DepartmentofAnesthe- for PainResearchandCare(Busse,Buckley,Cou- Affiliations: This articlehasbeenpeerreviewed. ests weredeclared. Pharma andPaladin.Noothercompetinginter- Medical EducationpresentationsfromPurdue Courses; andreceivedhonorariaforContinuing from mdBriefCase.com,EthypharmandSea Protective Association;receivedconsultingfees for expertopinionsfromtheCanadianMedical Squibb andJohnsonJohnson;receivedfees sory boardsforAstraZeneca,Bristol-Myers submitted work.SolSternwasamemberofadvi- Long-Term Care,andpersonalfeesoutsidethe CIHR andfromtheOntarioMinistryofHealth from Indivior.DavidJuurlinkreportsgrants submitted work.ChrisCullreceivedpersonalfees due PharmaandJanssenInc.outsidethe study. D. Norm Buckley reports grants from Pur- Health Research(CIHR)duringtheconductof ceived grantsfromtheCanadianInstitutesof during theconductofstudy.JasonBussere- Jason BussereportgrantsfromHealthCanada Competing interests:D.NormBuckleyand Colburn Alcohol Depend2009;104:34-42. health andpain—developmentofatypologychronicpatients. DeLemos ER) inthetreatmentofchroniclowbackpain.JOpioidManag2008;4:87-97. 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Dapoigny interventions inCanada:areview.PainPhysician2012;15(Suppl3):ES191-203. Han patients withchronicpain:aprospectivecohortstudy. Ives Dunn TJ, B, KM, TJ, MJ, R Compton AW, B, Chelminski JL, , Rapoport Pascual M, Saunders Argento BP, GJ, McDonald Bornstein Jasinski The Michael G. DeGroote Institute Abitbol Xiang Xiang WM, E. ML, PR, DR, KW, R JD, JL, J J Prescription opioid relatedmisuse, harms, diversionand Jones , PW. , , Hammett-Stabler Fleming Thipphawong Rastegar Benson Gana Hamm Fraitag Rutter Significant painreductioninchronicpatients CM, TJ, LR, CM, B. C RR, et al. DA. et al. , et al. Efficacy ofperipheralkappaagonistfedoto- et al. et al. Long-term opioidtherapy,aberrantbehav- et al. Nonmedical prescriptionopioiduseand J Aliment PharmacolTher Clinical trial: asimadoline in the treatment Clinical trial:asimadolineinthetreatment Extended-release tramadol(tramadol . CA, Results ofadouble-blind,placebo- Opioid prescriptionsforchronicpain Tramadol hydrochlorideextended- Extended-release tramadolinthe et al. J OpioidManag Predictors of opioid misuse in Predictors ofopioidmisusein BMC HealthServRes CMAJ decision-making process for this article. decision-making process forthisarticle. for Disclaimer: NavPersaudisanassociateeditor the guidelinesteeringcommittee. ment processweresolelytheresponsibility of issues thataroseduringtheguideline develop- line. Finaldecisionsregardingtheprotocol and or preparation,reviewapprovaloftheguide- lection, analysis and interpretation of the data; role inthedesignorconductofstudy;col- tion oftheguideline.Thefundershadnoother vided non-binding feedback duringthe prepara- Health Canada.Canadapersonnelpro- Canadian Institutes of Health Research and initiated study,supportedbygrantsfromthe Funding: Thisguidelinewasaninvestigator- endorsement ofguidelinerecommendations. advisory committee in no way constitutes pation intheclinicalexpertcommitteeorpatient agreed toactasguarantorsofthework.Partici- final approvaloftheversiontobepublishedand and towritingthearticle.Allofauthorsgave substantially totheinterpretationoffindings Contributors: Alloftheauthorscontributed Gjøvik (Vandvik),Norway Ottawa, Ont.;InnlandetHospitalTrust-Division Medicine (Tugwell),UniversityofOttawa, cal Centre(Stern),Oakville,Ont.;Departmentof St. Michael’s Hospital, Toronto, Ont.; Argus Medi- Ont.; LiKaShingKnowledgeInstitute(Persaud), atrics (Juurlink),UniversityofToronto, Halifax, NS;DepartmentsofMedicineandPedi- Physicians andSurgeonsofNovaScotia(Grant), of Medicine(Frank),Aurora,Colo.;College Denver, Colo.andUniversityofColoradoSchool VA EasternColoradoHealthCareSystem(Frank), and was not involved in the editorial CMAJ and was not involved in the editorial | MAY 8,2017 2012; 2008; 28: 8 : 153- 2006; 239- 60. 49. Drug 6 : 46. | VOLUME 189 45. 43. 46. 44. 47. 48. 49. 50. 51. 53. 52.

Chang cians. PainResManag2013;18:177-84. management ofchronicnoncancerpain:asurveyCanadianfamilyphysi- Harden Agoritsas study. JOpioidManag2016;12:377-87. safe andeffectiveuseofopioidsforchronicnon-cancerpain:aqualitative Allen oids inaveteranpopulation.PainMed2015;16:1975-81. Dowell decision making:thepacequickens.BMJ2015;350:g7624. chronic pain—UnitedStates,2016.MMWRRecommRep2016;65:1-49. dard-on-Safe-Prescribing.pdf (accessed2017Feb.11). 1. Available:www.cpsbc.ca/files/pdf/2016-06-01-Board-Adopts-New-Stan- Vancouver: CollegeofPhysiciansandSurgeonsBritishColumbia;2016June address publichealthemergencyrelatedtoopioidoverdoses[mediarelease]. College Boardadoptsnewprofessionalstandardonsafeprescribingto Busse -for-Prescribing-Opioids-for-Chronic-Pain (accessed2017Mar.11). ca/News/Press-Releases/Details/ArticleId/266/College-Endorses-CDC-Guidelines lege ofPhysicians&SurgeonsNovaScotia;2016.Available:www.cpsns.ns. lines forprescribingopioidschronicpain[mediarelease].Halifax(NS):Col- College endorses the US Centers for Disease Control and Prevention’s guide 2010; scribing opioidsfortreatmentofpain. Kaye line forprescribingopioidschronicnoncancerpain.CMAJ2016;188:1210-1. Rolfs Available: (OME) foropioidutilisationstudies. Nielsen abuse (part2).PainPhysician2017;20(2S):S111-S133. an updatedreviewofopioidabusepredictorsandstrategiestocurb 24( RT, AD, MJ, JW, Y, S D P, 3 | , ):219- Johnson ISSUE 18 , http://onlinelibrary.wiley.com/doi/10.1002/pds.3945/full. Zhu Jones Degenhardt Asbridge T, Ahmed Juurlink Haegerich Heen KL, 35. MR, Florez AF, S, E MM D, , Kaye Ang Williams L Brandt TM, Guyatt , , [email protected] Correspondence to:JasonW.Busse, (Chair), PabloAlonsoCoello,MirandaLangendam External reviewcommittee:PaulGlasziou Vogel, RaadYameen,MadisonZhang Rehman, JohnJ.Riva,StephanieRoss,Nicole Regina Li,VeenaManja,CurtisMay,Yasir hua, JustinHo,PatrickHong,AlkaKaushal, Chang, KayliCulig,KyleDeOliveria,AnnaGos- Vahid Ashoorion,MahmoodAmniLari,Yaping Jason W.Busse,LiWang,RachelJ.Couban, Evidence synthesisteam:SamanthaCraigie, sent tobelisted. *Three members did not provide written con cer, KyleNeilsen,IanTregunna,JenWatson. Kane, AndrewKoster,SueMace,TracyL.Mer- Deborah Ironbow,PamelaJessen,Mechelle Lynn Cooper,ChrisCull,AdaGiudice- Patient advisorycommittee:*BartBennett, ley-Forster, DwightMoulin,MarkSullivan Jovey, David N. Juurlink, Priya Manjoo, Pat Mor- Harris, LydiaHatcher,KurtHegmann,Roman Donna Buna,GaryFranklin,ChrisGiorshev,Jeff Clinical expertcommittee:D.NormBuckley, Sol Stern,PeterTugwell,PerOlavVandvik don H.Guyatt,AlfonsoIorio,NavindraPersaud, R. daCosta,JosephW.Frank,GusGrant,Gor- Carrasco-Labra, LynnCooper,ChrisCull,Bruno (Chair), ThomasAgoritsas,ElieA.Akl,Alonso Guideline panel members: Busse, DavidN.Juurlink Guyatt (Chair),D.NormBuckley,JasonW. Guideline steeringcommittee:GordonH. Hoban Macdougall ID, K, AM, Chou et al. et al. L, GH. NJ, B et al. , et al. Gisev R Clinical implicationsoftaperingchronicopi- Sundwall Attitudes towardtheCanadianguideline for Addressing thelimitationsofCDCguide- . Pharmacoepidemiol DrugSaf.2016; CDC guidelineforprescribingopioids Prescription opioid abuse in chronic pain: PC, Decision aidsthatreallypromoteshared N . et al. A synthesis of oral morphine equivalents A synthesisoforalmorphineequivalents J PainPalliatCarePharmacother. DN. Self-reported practices in opioid Utah clinicalguidelinesonpre- Jason W. Busse Tompson, Tompson, 25( 6 ):733- - 7 - .