Changing Times: New Thinking on

Prevention and Treatment

G. Caleb Alexander, MD, MS
galexand@jhsph.edu
February 23, 2018
Disclosures
• Chairman, FDA Peripheral and Central Nervous System
Advisory Committee
• Consultant: IQVIA; MesaRx Innovations
• Co-founder and equity holder: Monument Analytics, a
consultancy whose clients include the life science industry
as well as plaintiffs in opioid litigation
• Member, OptumRx National P&T Committee
• Funding: FDA, CDC, AHRQ, NHLBI, NIDA, AstraZeneca,
Department of Health and Human Services, Arnold
Foundation, Robert Wood Johnson Foundation

© 2015/2016, Johns Hopkins University. All rights reserved.

© 2015/2016, Johns Hopkins University. All rights reserved.
© 2015/2016, Johns Hopkins University. All rights reserved.
© 2015/2016, Johns Hopkins University. All rights reserved.
 onlinelearninginsights.wordpress.com

© 2015/2016, Johns Hopkins University. All rights reserved.

The next slide is important

© 2015/2016, Johns Hopkins University. All rights reserved.

 Volume of Prescription Opioid Use in
U.S. and Other Countries, 1990-2015

Sources: International Narcotics Board; World Health Organization population data.

By: Pain & Policy Studies Group, University of Wisconsin/WHO Collaborating Center, 2017

8 Slide from D. Dowell (2018)

 Sea change in clinical
standards (reversing the tide)

© 2015/2016, Johns Hopkins University. All rights reserved.

 CDC Guidelines: Twelve
Recommendations Including…
• Opioids not 1st line or routine therapy for
chronic pain
• Use caution when increasing dosages,
especially >50 mg*; avoid or justify escalating
to >90 mg
• No more than needed for acute pain; 3-7 days
usually enough
• Check Prescription Drug Monitoring Program
(PDMP) for other prescriptions, high total
dosages
• Avoid concurrent benzodiazepines and opioids
• Offer or arrange medication-assisted treatment
*in morphine equivalents for opioid use disorder

10 Slide from D. Dowell (2018)

 Lin et al. JAMA IM. 2017.

11
• Probability of long-term opioids increases based on initial length of use (MMWR.
2017;66:265–269.)
• Rates of long-term use increase among opioid naïve patients seeing high intensity
prescribers (Barnett et al. NEJM. 2017;376:663-73)
• High volume prescribers prescribe higher doses, durations and overall opioid volume
than their counterparts, holding patient factors constant (Chang et al. Addiction. 2017)

© 2015/2016, Johns Hopkins University. All rights reserved.

 Longer opioid duration and higher dose
associated with opioid use disorder

Edlund, MJ et al. The role of opioid prescription in incident opioid abuse and dependence
among individuals with chronic noncancer pain. Clin J Pain 2014; 30: 557-564.

13 Slide from D. Dowell (2018)

 Frequency of overdose among people
prescribed opioids for pain

Bohnert ASB et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA. 2011;305:1315-1321.
Dunn KM et al. Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Int Med, 2010; 152: 85-92.
Gomes T et al. Opioid dose and drug-related mortality in patients with non-malignant pain. Arch Intern Med 2011; 171: 686-91.
Kaplovitch E et al. Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study. PLOS ONE DOI:10.1371/journal.pone.0134550 August 20, 2015

14 Slide from D. Dowell (2018)

 Risk of opioid-related overdose death
correlates with prescribed opioid dose

Bohnert ASB et al. Association between opioid prescribing patterns and opioid
overdose-related deaths. JAMA 2011; 305: 1315-1321

15 Slide from D. Dowell (2018)

© 2015/2016, Johns Hopkins University. All rights reserved.
Case Study #1: Kaiser Permanente
• Between 2010 and 2015, Kaiser Permanente Southern California
implemented a “Safe and Appropriate Opioid Prescribing” program
• Prescribing and dispensing policies, follow-up and monitoring
processes, and organizational and clinical coordination through EHR
integration
• Significant decreases in opioid prescribing
• 30% reduction in high-dose opioid prescription
• 98% reduction in prescriptions of greater than 200 pill
• 90% reduction in opioids combined with benzos and carisoprodol
• 72% reduction in Extended Release/Long Acting (ER/LA) opioids
• 95% reduction in brand name opioid-acetaminophen prescriptions
• No change in methadone prescriptions

Losby JL, Hyatt JD, Kanter MH, Baldwin G, Matsuoka D. Safer and more appropriate opioid prescribing: a large healthcare
system's comprehensive approach. Journal of Evaluation in Clinical Practice. 2017;23:1173-1179.

© 2015/2016, Johns Hopkins University. All rights reserved.

Case Study #2: Veterans Affairs
• VA implemented Opioid Safety Initiative (OSI) during 2013, created a
dashboard tool aggregating EHR opioid prescribing data
• Each facility identified “Key leader” responsible for reviewing reports,
identifying prescribing variations, responding with appropriate actions
• Tool associated with 16% decrease in total high-dosage opioid
prescribing, including decreases of:
• 331 patients per month who received opioid dosages greater
than 100 morphine equivalents (MEQ)
• 164 patients per month receiving dosages greater than 200 MEQ
• 781 patients per month receiving concurrent benzos
• Tool designed to inform educational and quality improvement
practices to improve safe opioid prescribing
Lin LA, Bohnert AS, Kerns RD, Clay MA, Ganoczy D, Ilgen MA. Impact of the Opioid Safety Initiative on Opioid-related
Prescribing in Veterans. Pain. 2017;158:833-839.

© 2015/2016, Johns Hopkins University. All rights reserved.

Things I Wonder About
• Marijuana
• Best practices
• Coverage policies
• Regulatory action
• Safe storage and disposal
• Marketing and promotion
• Unintended consequences
• Abuse deterrent formulations
• Other risk mitigation measures

© 2015/2016, Johns Hopkins University. All rights reserved.

20 From Chris Jones (SAMHSA). 2018.
 From Chris Jones (SAMHSA). 2018.
© 2015/2016, Johns Hopkins University. All rights reserved.
 Case Study #3: Collaborative Care Model
• Office-based opioid treatment (OBOT) Collaborative Care Model implemented
in Community Health Centers in Massachusetts between 2007 and 2013
• Model consisted of four treatment stages:
• Initial screening by a nurse care manager (NCM) to determine whether
the patient is appropriate for treatment using this model
• Buprenorphine induction under the supervision of an NCM
• Treatment stabilization monitoring
• Maintenance with follow-ups
• Expansion of OBOT associated with the following outcomes:
• Nineteen CHCs enrolled in the OBOT-program
• An increase in admissions to OBOT programs from 178 in the last five
months of 2007 to 1210 during the entire year of 2012
• 375% increase in physicians with buprenorphine waivers
• Increase in 12-month treatment retention (32% in 2010 to 67% in 2013)
LaBelle CT, Han SC, Bergeron A, Samet JH. Office-based opioid treatment with buprenorphine (OBOT-B): statewide implementation of
the Massachusetts collaborative care model in community health centers. Journal of Substance Abuse Treatment. 2016;60:6-13.

© 2015/2016, Johns Hopkins University. All rights reserved.

Case Study #4: ED-Initiated Treatment
• ED of urban teaching hospital randomized patients to: (1) treatment referral; (2) brief
intervention and treatment referral; (3) brief intervention, initiation of BUP in ED,
and referral to follow-up treatment
• 30 days after randomization, engagement in addiction treatment
• 37% in referral only group
• 45% in brief intervention and referral group
• 78% in buprenorphine group
• Decreases in illicit opioid use (days per week)
• Referral only group: 5.4 days to 2.3 days
• Brief intervention and referral group: 5.6 days to 2.4
• Buprenorphine group: 5.4 days to 0.9
• No significant differences in urine samples negative for opioids, nor for HIV risk
• Inpatient addiction treatment service use
• Referral only group: 37%
• Brief intervention and referral group: 35%
• Buprenorphine group: 11%
D’Onofrio G, O’Connor PG, Pantalon MV, et al. Emergency Department–initiated Buprenorphine/naloxone Treatment for Opioid
Dependence: A Randomized Clinical Trial. JAMA. 2015;313:1636-1644.

© 2015/2016, Johns Hopkins University. All rights reserved.

Case Study #5: Treatment in Jails
• Most correctional facilities do not offer treatment for opioid use disorder
• New initiative to treat patients with MAT within RI Department of Corrections
• Community program engaged within corrections system, with community-based
centers of excellence established to facilitate referrals and maximize continuity
upon release
• Analysis of medical examiner data for unintentional overdoses from Jan-June 2016
compared with Jan-June 2017, focus on proportion of overdose decedents recently
incarcerated
• In 2016, 26 of 179 (14.5%) decedents were recently incarcerated, compared with 9 of
157 individuals (5.7%) in 2017, representing 60.5% reduction in mortality
• Number needed to treat to prevent one fatal overdoses was 11
• Large, clinically meaningful reductions in overdose mortality, consistent with other
studies, and without evidence of some of the main alternative explanations such as
changes in the use of naloxone or differences in the baseline population incarcerated
during these two time periods

Green TC, Clark J, Brinkley-Rubinstein L, et al. JAMA Psychiatry. 2018.

© 2015/2016, Johns Hopkins University. All rights reserved.

Things I Wonder About
• Ripple effects
• Best practices
• Harm reduction
• Special populations
• Adolescents
• Incarcerated
• Pregnant women . . .
• Taking down stigma
• From access to quality

© 2015/2016, Johns Hopkins University. All rights reserved.

• Informing Evidence with Action
– Scaling up evidence-based interventions;
rapidly implementing and evaluating
promising policies and programs
• Intervening Comprehensively
– All along supply chain; clinic, community
and addiction treatment settings; primary,
secondary and tertiary prevention; creating
synergies across different interventions
• Promoting appropriate & safe opioid use
– Reducing overuse; focus on safe use,
storage and disposal; optimizing use in
accordance with best practices

26
 Ten Pillars
1. Strengthening Prescription Drug Monitoring Programs
2. Implementing Clinical Guidelines
3. Engaging Pharmacy Benefits Managers & Pharmacies
4. Implementing Innovative Engineering Strategies
5. Engaging Patients and General Public
6. Improving Surveillance
7. Treating Opioid Use Disorder
8. Improving Naloxone Access & Use
9. Practicing Harm Reduction
10. Combatting Stigma

27
28
Glimmers of hope
• Reductions in prescription opioid volume
• Prescription opioid misuse declining among youth
• Plateauing of deaths from prescription opioids
• Some states seeing leveling of total opioid deaths
• Increased delivery of MAT from treatment facilities
• Increased rates of buprenorphine and naltrexone
dispensing from pharmacies
• Increased naloxone dispensing from pharmacies
• Increased harm reduction programs such as syringe
exchange

© 2015/2016, Johns Hopkins University. All rights reserved.

CDC MMWR. May 14, 1999/Vol. 48/No. 18.
 Conclusions
• Surging rates of opioid-related injuries
and deaths continue, including from
fentanyl and heroin
• Rapid changes in regulatory, clinical
and payment policies (as well as other
sectors, such as enforcement)
• Many lives will be saved through
strategic investments in prevention,
treatment and recovery services
• Good journalism plays a vital role –
thank you for shining a light on the
issues that matter
32