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Development of the CDCOpioid Prescribing Guidelines

for Chronic Pain in Primary CarePresenters:

• Tamara Haegerich, PhD, Deputy Associate Director for Science, Division of Unintentional Injury Prevention, CDC

• Deborah Dowell, MD, MPH, Senior Medical Advisor, Division of Unintentional Injury Prevention, CDC

Clinical Track

Moderator: Mark D. Birdwhistell, MPA, Vice President for Administration and External Affairs, University of Kentucky HealthCare

Disclosures

• Deborah Dowell, MD, MPH, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services.

• Tamara Haegerich, PhD, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services.

• Mark D. Birdwhistell, MPA, has disclosed no relevant, real or apparent personal or professional financial relationships with proprietary entities that produce health care goods and services.

Disclosures

• All planners/managers hereby state that they or their spouse/life partner do not have any financial relationships or relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months.

• The following planners/managers have the following to disclose:– John J. Dreyzehner, MD, MPH, FACOEM – Ownership interest:

Starfish Health (spouse)– Robert DuPont – Employment: Bensinger, DuPont &

Associates-Prescription Drug Research Center

Learning Objectives

1. Outline the new CDC guideline for prescribing opioid pain relievers for chronic pain in primary care settings.

2. Describe the evidence and development process behind the CDC guideline.

3. Explain the potential benefits of implementing CDC’s recommendations to promote safer use of opioids in clinical practice and improve patient outcomes and public health.

4. Provide accurate and appropriate counsel as part of the treatment team.

Development of the CDC Opioid Prescribing Guideline for Chronic Pain in Primary Care

Deborah Dowell, MD, MPHTamara Haegerich, PhD

Division of Unintentional Injury PreventionNational Center for Injury Prevention and Control

Centers for Disease Control and Prevention

BACKGROUND AND METHODS

Background and need

• 11% of Americans experience daily (chronic) pain• Opioids frequently prescribed for chronic pain• Primary care clinicians

account for ~50% of opioid pain medications dispensed report concern about opioids and insufficient training

• >165,000 rx opioid-related overdose deaths since 1999• About 2 million people abused or were dependent in 2013• Existing national guidelines were published in 2010 or earlier

and do not incorporate new evidence published since 2010

Primary audience

• Primary care clinicians (e.g., family physicians, internists) treating patients > 18 years with chronic pain (i.e., lasting > 3 months or past time of normal tissue healing) in outpatient settings outside of active cancer treatment, palliative care, and end- of-life care

CDC Draft Recommendations

Core Expert Group Consultation

Constituent Input(Webinar)

NCIPC Advisory Committee

CDC Draft Guideline

FRN Public Comment

Federal Partner Review

Peer Review

Core Expert and Stakeholder Review

Systematic Literature Review

CDC Revised Guideline

Overview of the development process

GRADE Methodology• Updated 2014 AHRQ-sponsored review• Identified key clinical questions

– KQ1: Effectiveness of long-term opioid therapy– KQ2: Harms and adverse events– KQ3: Effectiveness of methods for initiation, titration, dosing– KQ4: Accuracy of risk prediction instruments and effectiveness of risk mitigation

strategies– KQ5: Effects of prescribing for acute pain on long-term use

• Categorized type (quality) of evidence– Type 1: RCTs; overwhelming observational studies– Type 2: RCTs (limitations); strong observational– Type 3: RCTs (notable limitations); observational– Type 4: RCTs (major limitations); observational (notable limitations) clinical

experience

GRADE Methodology

• Conducted supplemental contextual evidence review– Benefits and harms– Provider and patient values and preferences– Resource allocation (cost)– Effectiveness of alternative treatments

• Drafted recommendations• Applied strength of recommendation categories

– A: applies to all patients; most patients should receive recommended course of action

– B: individual decision making required; providers help patients arrive at decision consistent with values/preferences and clinical situation

CLINICAL EVIDENCE REVIEW

KQ1: Effectiveness

• No study of opioid therapy vs. placebo, no opioid therapy, or non-opioid therapy for chronic pain evaluated long-term (>1 year) outcomes related to pain, function, or quality of life

• Most placebo-controlled trials < 6 weeks*– Opioids more effective than placebo for nociceptive and

neuropathic pain– Small to moderate effect sizes– High percentage discontinued long-term use because of

lack of efficacy and adverse events

* short-term studies not re-reviewed

KQ2: Abuse, addiction, misuse

• 10 non-comparative studies; Variations in definitions and methods for assessment

• Primary care: dependence 3% to 26%• Pain clinics: addiction 2% to 14%

KQ2: Overdose

• 1 retrospective cohort study: chronic pain patients in US health system; recent opioid use associated with increased risk of:– Any overdose event (adjusted HR 5.2, 95% CI 2.1 to 2.5) – Serious overdose event (adjusted HR 8.4, 95% CI 2.5 to 2.8)– Dose-dependent association

• 1 case-control study: dose-dependent association with risk of overdose (relative to 1 to 19 MME/day . . .)– 20 to 49 MME/day: 1.92– 50 to 99 MME/day: 2.04– 100 to 199 MME/day: 2.88– > 200 MME/day: 2.88

KQ2: Dose-dependent effects

• Higher doses associated with– Overdose (2 studies)– Abuse or dependence diagnosis (1 study)– Fractures (2 studies)– Cardiovascular events (2 studies)– Endocrinologic adverse events (2 studies)– Motor vehicle crashes (1 study)

• No evidence on dose-dependent effects on pain or function

KQ3: Initiation and titration

• 4 studies (RCTs and cohort): Inconsistent results and differences in dosing protocols and opioid doses

• New large VA cohort study– Initiation with long-acting opioid vs short-acting

associated with increased risk of overdose (adjusted HR 2.33, 95% CI 1.26 to 4.32)

– Greatest risk in first 2 weeks

KQ3: Comparative effectiveness and harms of long-acting opioids

• 6 studies (RCTs and cohort): Inconsistent results regarding differences between long-acting opioids– Risks may vary in different settings as a function of

monitoring and management protocols• New TN Medicaid cohort study – Methadone associated with higher mortality risk

compared to sustained-release morphine (HR 1.46, 95% CI 1.17 to 1.83)

K3: Dose escalation vs maintenance

• 1 RCT in VA patients with musculoskeletal pain• No differences in pain, function, or use of nonopioid

medications or physical therapy after 12 months– Limited separation between groups in doses (mean 52

MME/day vs 40 MME/day)

KQ4: Accuracy of risk prediction

• 5 studies with inconsistent estimates and methodological shortcomings– Opioid Risk Tool (ORT)– Screener and Opioid Assessment for Patients with

Pain-Revised (SOAPP-R)– Brief Risk Interview

• Based on sensitivity and specificity, insufficient accuracy for classification of patients

KQ5: Effects of opioid therapy for acute pain on long-term use

• 2 retrospective cohort studies– Low risk surgery: use of opioids within 7 days associated

with increased likelihood of use at 1 year (adjusted OR 1.44, 95% CI 1.39 to 1.50)

– Lower back pain: opioid use within 15 days of onset associated with increased likelihood of receiving 5 or more prescriptions from 30-730 days following onset

Versus no opioid use:• 1 to 140 mg morphine equivalents: adjusted OR 2.08 (95% CI 1.55

to 2.78)• >=450 mg morphine equivalents: adjusted OR 6.14 (95% CI 4.92

to 7.66)

CONTEXTUAL EVIDENCE REVIEW

Effectiveness of nonpharmacologic therapy

• CBT– Helps patients understand and modify factors and

processes that exacerbate pain– Has been shown to have small, positive effects on disability

and catastrophizing, and an improvement in symptoms• Exercise– Helps to restore the normal range of motion and muscle

conditioning– Demonstrated effectiveness in improving pain and function

in CLBP and reduced pain in other conditions such as OA and fibromyalgia

* Findings from systematic reviews

Effectiveness of nonopioid pharmacologic therapy

• Acetaminophen and NSAIDs (e.g., first-line pharmacotherapy for OA and low back pain)– Potential harms: GI, renal, and cardiovascular risks

• Anticonvulsants and antidepressants (e.g., neuropathic pain)– Pregabalin, gabapentin– TCAs, SNRIs

• Useful in patients with concurrent pain and depression• Limited comparative effectiveness data, but some

suggestion that opioids do not differ from non-opioids in pain reduction

* Findings from systematic reviews

Benefits and harms: overdose risk

Benefits and harms:Overdose risk

• Opioid-related overdose risk is dose-dependent– 5 additional case control and cohort studies on the association

of opioid dosage and overdose risk excluded from clinical review– Compared to doses < 20 MME, odds of overdose increased:

• 1.3 –1.9 at dosages of 20 to <50 MME• 1.9 –4.6 at dosages of 50 to <100 MME• 2.0 –8.9 at dosages of <= 100 MME

– Overdose risk significantly elevated >1830 MME total over 6 months

– 58-62% of fatal overdoses >50 MME– 19% of controls (no overdose) prescribed daily doses >60 MME

vs. 48% fatal OD

Benefits and harms:Factors that increase risk

• Pregnancy• Older age• Mental health disorder• Substance use disorder• Sleep-disordered breathing

• Note: Sensitivity and specificity of risk stratification instruments are poor

Values and preferences:Clinician perspective

• Lack confidence in their ability to prescribe opioids safely, predict or detect prescription drug abuse, and discuss abuse with their patients

• Feel pressured to treat with opioids• Have difficulties interpreting patients' reports of pain• Worry about secondary gain/diversion, and "abusive" or

"difficult" patients • Feel frustrated, ungratified, and guilty when providing

chronic pain care

Values and preferences:Patient perspective

• Many patients do not have an opinion about “opioids,” or know what this term means

• One in three associate “narcotics” with addiction or abuse

• Half fear “addiction” from long-term “narcotic” use• Patients with chronic conditions: – Ambivalent about risks and benefits– Continue taking opioids even while recognizing them

to be ineffective in controlling pain

Resource allocation:Costs and cost-effectiveness

• Direct medical costs: opioids vs pharmacologic vs non-pharmacologic (OA; CLBP, 2012)– Acetaminophen, NSAIDs, TCAs, and massage therapy

were associated with lower mean and median annual costs relative to opioid therapy

– COX-2 inhibitors, SNRIs, anticonvulsants, topical analgesics, PT, and CBT also associated with lower median costs

• Cost-benefit for opioid therapy difficult to estimate due to a lack of available evidence on benefits

RECOMMENDATIONS

Organization of Recommendations

12 recommendations grouped into three conceptual areas: • Determining when to initiate or continue opioids

for chronic pain • Opioid selection, dosage, duration, follow-up, and

discontinuation• Assessing risk and addressing harms of opioid use

DETERMINING WHEN TO INITIATE OR CONTINUE OPIOIDS FOR CHRONIC PAIN

Recommendation 1

• Nonpharmacologic therapy and nonopioid pharmacologic therapy are preferred for chronic pain. Clinicians should consider opioid therapy only if expected benefits for both pain and function are anticipated to outweigh risks to the patient. If opioids are used, they should be combined with nonpharmacologic therapy and nonopioid pharmacologic therapy, as appropriate.

Recommendation category: A, Evidence type: 3

Opioids not first-line or routine therapy for chronic pain

• Use nonpharmacologic therapy (e.g., exercise therapy, CBT) to reduce pain and improve function

• Use nonopioid pharmacologic therapy (e.g., NSAIDS, acetaminophen, anticonvulsants, SNRIs) when benefits outweigh risks, combined with nonpharmacologic therapy

• When opioids used, combine with nonpharmacologic therapy and nonopioid pharmacologic therapy to provide greater benefits

Recommendation 2

• Before starting opioid therapy for chronic pain, clinicians should establish treatment goals with all patients, including realistic goals for pain and function, and should consider how therapy will be discontinued if benefits do not outweigh risks. Clinicians should continue opioid therapy only if there is clinically meaningful improvement in pain and function that outweighs risks to patient safety.


Establish and measure progress toward goals

• Before initiating opioid therapy for chronic pain, – determine how effectiveness will be evaluated – establish treatment goals with patients

• pain relief • function

• Assess progress using 3-item PEG Assessment Scale* – Pain average (0-10)– interference with Enjoyment of life (0-10)– interference with General activity (0-10)

*30% = clinically meaningful improvement

Recommendation 3

• Before starting and periodically during opioid therapy, clinicians should discuss with patients known risks and realistic benefits of opioid therapy and patient and clinician responsibilities for managing therapy.


Ensure patients are aware of potential benefits, harms, and alternatives to opioids

• Be explicit and realistic about expected benefits • Emphasize improvement in function as a primary goal • Discuss– serious and common adverse effects – increased risks of overdose• at higher dosages• when opioids are taken with other drugs or alcohol

– periodic reassessment, PDMP and UDT checks– risks to family members and individuals in the community

OPIOID SELECTION, DOSAGE, DURATION, FOLLOW-UP, AND DISCONTINUATION

Recommendation 4

• When starting opioid therapy for chronic pain, clinicians should prescribe immediate-release opioids instead of extended-release/long-acting (ER/LA) opioids.


Choose predictable pharmacokinetics and pharmacodynamics to minimize overdose risk

• In general, avoid the use of immediate-release opioids in combination with ER/LA opioids

• Methadone should not be the first choice for an ER/LA opioid; Only clinicians who are familiar with methadone’s unique risk profile and who are prepared to educate and closely monitor their patients should consider prescribing it for pain

• Only consider prescribing transdermal fentanyl if familiar with the dosing and absorption properties and prepared to educate their patients about its use

Recommendation 5

• When opioids are started, clinicians should prescribe the lowest effective dosage. Clinicians should use caution when prescribing opioids at any dosage, should carefully reassess evidence of individual benefits and risks when increasing dosage to ≥50 morphine milligram equivalents (MME)/day, and should avoid increasing dosage to ≥90 MME/day or carefully justify a decision to titrate dosage to >90 MME/day.


Start low and go slow

• Start opioids at the lowest effective dosage • Increase dosage by the smallest practical amount• If total opioid dosage >50 MME/day

– reassess pain, function, and treatment – increase frequency of follow-up– consider offering naloxone

• Avoid increasing opioid dosages to >90 MME/day• If escalating dosage requirements

– discuss other pain therapies with the patient – consider working with the patient to taper opioids down or

off – consider consulting a pain specialist

When patients are already receiving high dosages

• Offer established patients already taking > 90 MME/day the opportunity to re-evaluate their continued use of high opioid dosages in light of recent evidence regarding the association of opioid dosage and overdose risk

• For patients who agree to taper opioids to lower dosages, collaborate with the patient on a tapering plan (see Recommendation 7)

Recommendation 6

• Long-term opioid use often begins with treatment of acute pain. When opioids are used for acute pain, clinicians should prescribe the lowest effective dose of immediate-release opioids and should prescribe no greater quantity than needed for the expected duration of pain severe enough to require opioids. Three days or less will often be sufficient; more than seven days will rarely be needed.


When opioids are needed for acute pain

• Prescribe the lowest effective dose • Prescribe amount to match the expected duration

of pain severe enough to require opioids • Often <3 days and rarely more than 7 days needed • Do not prescribe additional opioids “just in case” • Re-evaluate patients with severe acute pain that

continues longer than expected to confirm or revise the initial diagnosis and adjust management

• Do not prescribe ER/LA opioids for acute pain

Recommendation 7

• Clinicians should evaluate benefits and harms with patients within 1 to 4 weeks of starting opioid therapy for chronic pain or of dose escalation. Clinicians should evaluate benefits and harms of continued therapy with patients every 3 months or more frequently. If benefits do not outweigh harms of continued opioid therapy, clinicians should optimize other therapies and work with patients to taper opioids to lower dosages or to taper and discontinue opioids.


Follow-up

Re-evaluate patients• within 1 - 4 weeks of starting long-term therapy or of dosage

increase • at least every 3 months or more frequently

At follow up, determine whether• opioids continue to meet treatment goals• there are common or serious adverse events or early warning

signs• benefits of opioids continue to outweigh risks• opioid dosage can be reduced or opioids can be discontinued

Tapering opioids

• Offer to work with patients to taper opioids down or off when – no sustained clinically meaningful improvement in pain and function – opioid dosages >50 MME/day without evidence of benefit– concurrent benzodiazepines that can’t be tapered off– patients request dosage reduction or discontinuation – patients experience overdose, other serious events, warning signs

• Taper slowly enough to minimize opioid withdrawal – a decrease of 10% of per week is a reasonable starting point

• Access appropriate expertise for tapering during pregnancy • Optimize nonopioid pain management, psychosocial support

ASSESSING RISK AND ADDRESSING HARMS OF OPIOID USE

Recommendation 8

• Before starting and periodically during continuation of opioid therapy, clinicians should evaluate risk factors for opioid-related harms. Clinicians should incorporate into the management plan strategies to mitigate risk, including considering offering naloxone when factors that increase risk for opioid overdose, such as history of overdose, history of substance use disorder, higher opioid dosages (≥50 MME/day), or concurrent benzodiazepine use, are present.


Risk factors increase susceptibility to opioid-associated harms

• Avoid prescribing opioids to patients with moderate or severe sleep-disordered breathing when possible

• Carefully weigh risks and benefits with pregnant patients• Additional caution with renal or hepatic insufficiency, >65• Ensure treatment for depression is optimized • Consider offering naloxone when patients – have a history of overdose– have a history of substance use disorder– are taking central nervous system depressants with opioids – are on higher dosages of opioids (> 50 MME/day)

Recommendation 9

• Clinicians should review the patient’s history of controlled substance prescriptions using state prescription drug monitoring program (PDMP) data to determine whether the patient is receiving opioid dosages or dangerous combinations that put him or her at high risk for overdose. Clinicians should review PDMP data when starting opioid therapy for chronic pain and periodically during opioid therapy for chronic pain, ranging from every prescription to every 3 months.


If prescriptions from multiple sources, high dosages, or dangerous combinations

• Discuss safety concerns, increased risk of overdose with patient• For patients receiving high total opioid dosages, consider tapering

to a safer dosage, consider offering naloxone• Discuss safety concerns with others prescribing to your patient • Consider opioid use disorder and discuss concerns with your patient• If you suspect your patient might be sharing or selling opioids and

not taking them, consider urine drug testing to assist in determining whether opioids can be discontinued without causing withdrawal

• Do not dismiss patients from care—use the opportunity to provide potentially lifesaving information and interventions

Recommendation 10

• When prescribing opioids for chronic pain, clinicians should use urine drug testing before starting opioid therapy and consider urine drug testing at least annually to assess for prescribed medications as well as other controlled prescription drugs and illicit drugs.

Recommendation category: B, Evidence type: 4

Use UDT to assess for prescribed opioids and other drugs that increase risk

• Be familiar with drug testing panels and how to interpret results• Do not test for drugs that would not affect patient management • Before ordering urine drug testing

– explain to patients that testing is intended to improve their safety – explain expected results – ask patients whether there might be unexpected results

• Discuss unexpected results with local lab or toxicologist and patients

• Verify unexpected, unexplained results using specific test • Do not dismiss patients from care based on a urine drug test

Recommendation 11

• Clinicians should avoid prescribing opioid pain medication and benzodiazepines concurrently whenever possible.


Avoid concurrent opioids and benzodiazepines whenever possible

• Taper benzodiazepines gradually • Offer evidence-based psychotherapies for anxiety– cognitive behavioral therapy– specific anti-depressants approved for anxiety – other non-benzodiazepine medications approved for

anxiety • Coordinate care with mental health professionals

Recommendation 12

• Clinicians should offer or arrange evidence-based treatment (usually medication-assisted treatment with buprenorphine or methadone in combination with behavioral therapies) for patients with opioid use disorder.


If you suspect opioid use disorder• Discuss with your patient, provide opportunity to disclose concerns • Assess for OUD using DSM-5 criteria. If present, offer or arrange MAT

– buprenorphine through an office-based buprenorphine treatment provider* or an opioid treatment program specialist**

– methadone maintenance therapy from an opioid treatment program specialist**

– oral or long-acting injectable formulations of naltrexone (for highly motivated non-pregnant adults)

Consider obtaining a waiver to prescribe buprenorphine for OUD (see http://www.samhsa.gov/medication-assisted-treatment/buprenorphine-waiver-management)

*SAMHSA’s buprenorphine physician locator: http://buprenorphine.samhsa.gov/bwns_locator **SAMHSA’s Opioid Treatment Program Directory: http://dpt2.samhsa.gov/treatment/directory.aspx

http://www.samhsa.gov/medication-assisted-treatment/buprenorphine-waiver-management

http://buprenorphine.samhsa.gov/bwns_locator

http://dpt2.samhsa.gov/treatment/directory.aspx

TRANSLATION AND IMPLEMENTATION

Translation materials

• Website• Checklist/algorithm• Mobile application (including MME calculator)• Fact sheets– assessing benefit and harm– MME conversions– nonpharmacologic and nonopioid pharmacologic tx

options– checking the prescription drug monitoring program– use of opioid therapy in pregnant women

• Poster

Complementary activities for consideration

• EHR clinical decision support and defaults• Clinician education• Insurance and pharmacy benefit manager mechanisms• Clinical quality improvement measures and initiatives • Policy initiatives to address barriers– improving PDMP accessibility and interoperability– improving access to medication-assisted treatment– coverage for nonpharmacologic therapies and risk

mitigation strategies (e.g., urine drug testing)• Research

Thank you

For more information see:http://www.cdc.gov/drugoverdose/prescribing/guideline.html

The recommendations presented herein were in draft form upon submission of the presentation and had not yet been formally disseminated by the Centers for Disease Control

and Prevention. At the time of submission, the content within the presentation did not represent and should not be construed to represent any agency determination or policy.

http://www.cdc.gov/drugoverdose/prescribing/guideline.html

http://www.cdc.gov/drugoverdose/prescribing/guideline.html

Development of the CDCOpioid Prescribing Guidelines

for Chronic Pain in Primary CarePresenters:

• Tamara Haegerich, PhD, Deputy Associate Director for Science, Division of Unintentional Injury Prevention, CDC

• Deborah Dowell, MD, MPH, Senior Medical Advisor, Division of Unintentional Injury Prevention, CDC

Clinical Track

Moderator: Mark D. Birdwhistell, MPA, Vice President for Administration and External Affairs, University of Kentucky HealthCare

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