Spicy Debate Tapering Opioids: Compassionate Care or Punitive Policy

Moderator: Joanna L. Starrels, MD, MS Associate Professor of Medicine Division of General Internal Medicine

Dr. Starrels’ disclosures • Research support from FDA-mandated Industry

Post-marketing Requirement Consortium • Consulting fees from Venebio Group LLC • SCOPE of Pain speaker • Expert consultant for CDC Guideline

Introduction to today’s debate • What is opioid tapering and why the tension? • Intro to our speakers • Intro to the format

What is opioid tapering?

• Reduction in dose or discontinuation of opioids prescribed for chronic pain

• General goal is to reduce risks or harms

How did we get here?

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Source: Automation of Reports and Consolidated Orders System, US DEA, slide adapted from A Gilson

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CDC guideline for prescribing opioids for chronic pain 1. Non-pharmacologic and non-opioid therapies first 2. Establish functional treatment goals 3. Discuss risks/benefits and responsibilities 4. Prescribe lowest effective dose 5. For acute pain, no more than 7day supply 6. Reassess and taper if benefits do not exceed risks 7. Evaluate and mitigate harms (give naloxone) 8. Use PMP and urine drug testing 9. Avoid concurrent benzodiazepines 10.Offer buprenorphine or methadone for OUD

Dowell 2016 - http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

CDC guideline for prescribing opioids for chronic pain 1. Non-pharmacologic and non-opioid therapies first 2. Establish functional treatment goals 3. Discuss risks/benefits and responsibilities 4. Prescribe lowest effective dose 5. For acute pain, no more than 7day supply 6. Reassess and taper if benefits do not exceed risks 7. Evaluate and mitigate harms (give naloxone) 8. Use PMP and urine drug testing 9. Avoid concurrent benzodiazepines 10.Offer buprenorphine or methadone for OUD

Dowell 2016 - http://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm

Points of tension • Many are already taking high dose opioids • Many tapers are occurring

– Sometimes with harms – Sometimes with benefits

• Who should decide? – Prescriber, patient, institution, insurer, legislators,

regulators, pharmacies, distributors…

Positions and perspectives founded in evidence

Tapering is good Tapering is bad

Introduction to today’s debate • What is opioid tapering and why the tension? • Intro to our speakers • Intro to the format

Anna Lembke, MD • Associate Professor of Psychiatry and

Medical Director of Addiction Medicine at Stanford University

• Author of Drug Dealer, MD – How Doctors were Duped, Patients Got Hooked, and Why It’s So Hard to Stop

• Speaking “for” tapering

Stefan Kertesz, MD, MSc

• Professor of Preventive Medicine at University of Alabama at Birmingham

• Author of the letter calling on the CDC to address misapplication of its guideline through clarification and impact evaluation

• Speaking “against” tapering

Introduction to today’s debate • What is opioid tapering and why the tension? • Intro to our speakers • Intro to the format

Today’s spicy debate • Proposition 1

– For patients taking high-dose opioids for chronic pain, reducing the dose or discontinuing opioids promotes safety and well-being

• 5 minutes per speaker, 3 minute rebuttals

• Proposition 2 – Policies that strongly incentivize or mandate opioid dose

reduction or discontinuation promote safety and wellbeing of patients and public health

• 7 minutes per speaker, 3 minute rebuttals

• Coda: Consider the other’s perspective • Q/A

Proposition 1

For patients taking high-dose opioids for chronic pain, reducing the dose or discontinuing opioids promotes safety and well-being

Tapering Opioids: Compassionate Care or Punitive

Policy? Anna Lembke, MD

Stanford University School of Medicine AMERSA “Spicy Debate”

November 7, 2019

Disclosures ●I have been retained as a medical expert witness in federal and state opioid litigation against the opioid pharmaceutical industry.

Proposition #1

●Opioids don’t work for chronic pain.

●High dose and/or long duration opioids are harmful for patients.

●Patients who taper long-term opioids have less pain.

●Patients who taper long-term opioids have less depression and decreased risk of suicide.

●Tapering is not equivalent to abrupt opioid discontinuation.

Krebs et al, SPACE RCT, JAMA, 2018 ●Studied opioid-naïve patients for 12 months in a primary care setting, including patients with severe depression and post-traumatic stress disorder

●Bottom line: Opioids no better than acetaminophen, with fewer side effects

Busse et al, JAMA, 2018 ● This metanalysis defined “Minimally Important Difference” (MID) as at least 1 cm

on the 10 cm Visual Analog Scale (VAS).

● Analysis shows no clinically significant difference between opioids and placebo in the treatment of chronic pain. (The difference between opioid therapy and placebo was 0.79 cm. )

● Conclusion: “In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning.”

Chou et al, Annals of Internal Medicine, 2015 “Evidence supports a dose dependent risk for

serious harm” ● Tolerance, dependence, withdrawal

● Constipation ● Opioid induced hyperalgesia ● Hormonal imbalance ● Cardiac arrhythmias ● Cognitive impairment ● Depression and suicide ● Addiction ● Death

Edlund et al, Pain, 2014 >120 MEDs = 122 x odds of new onset OUD ● Compared to those not prescribed opioids, those on high dose

opioids (> 120 MEDs per day) for 90 or more days, the odds ratio of developing OUD was 122.45 (95% CI = 72.79, 205.99).

● Odd ratios for mental health diagnosis (3.12); multiple mental health diagnoses (5.71); prior alcohol use disorder (3.22); and prior non-opioid use disorder (8.26)

Darchuck et al, Pain Medicine, 2010 Tapering opioids plus other pain treatment

reduces depression ●3 week individualized opioid taper

●Interdisciplinary Pain Rehabilitation Program

●“Patients reported reduced depression, catastrophizing, pain severity, and pain interference (P < 0.001) at discharge and 6 months follow-up.”

Ilgen et al, Pain, 2016 Dose-dependent risk of suicide in

patients on opioids

“Increased dose of opioids was found to be a marker of increased suicide risk, even when relevant demographic and clinical factors were statistically

controlled …. There was no significant association between acetaminophen dose and regimen and suicide risk, suggesting that the observed effects

may be specific to opioids.”

The BRAVO Protocol

Oregon Pain Guidance Flowchart adapted for HHS

James, J Gen Intern Med, 2019

●20% of patients died!

●There was no statistically significant difference in death between “discontinued” and “maintained” patients.

Tapering Opioids: Compassionate Care or Punitive Policy The case for skepticism

STEFAN G. KERTESZ, MD, MSC PROFESSOR, UNIVERSITY OF ALABAMA AT BIRMINGHAM OPIOID SAFETY, RISK MITIGATION, OPIOID ADVICE TEAM: BIRMINGHAM VA MEDICAL CENTER

Disclosures and my background

I do not represent the US Government

No pharmaceutical grants, honoraria,

Past owned stock (Abbot, Merck <3%), sold in 2017.

My wife owns stock in Abbot, Merck+ J&J (<15% of her private assets)

A caveat: to make this a debate, I have “leaned into” and somewhat overemphasized my skepticism on taper per se.

Proposition 1: For patients taking high-dose opioids for chronic pain, reducing the dose or discontinuing opioids promotes safety and well-being

BUT FIRST, A CAVEAT

A taper story

45 year old woman with anasarca and sedation from opioids + benzos past heroin use, HIV, chronic pain, anxiety

methadone at >120 MME from OTP

oxycodone at 40mg/day

benzodiazepines

Involuntary taper was unavoidable and helped

2014

Cases like that clarify

Our question is not: “is any person ever helped by taper?” The proposition is general,

that taper promotes safety and well being generally such that we must regard it as care to propose and advance for all

We should want strong evidence before pushing this to 10 million patients

And if we intended to do it by force, the standard should be even more stringent

40 studies with patient outcomes 5 were RCTs (total N=261 patients) Most observational Most short-term & voluntary None rated as “good quality” 8 were “fair”, 32 “poor” Improvements in “fair” quality studies

Pain: 8/8 Pain related function: 5/5

Frank et al. Annals of Internal Medicine. August 1, 2017

Frank et al cautioned:

“no prospective studies of mandatory, involuntary opioid dose reduction among otherwise stable patients”

“insufficient evidence on adverse events related to opioid tapering, such as accidental overdose …or suicidality or other mental health symptoms”

An updated lit review by Mackey et al (Evidence Synthesis Program, 2019)

VA data on outcomes Changes in Prescribing VA long-term opioid recipients:

2011: 425,203

2018 : 203,837

From 2012 to 2018: High-dose Rx’s fell 68%

What do VA results show?

1. Handlandsmyth. 2. WhiteHouse 10/26/18 link 2. Meyer & Sandbrink. NAM. 1/10/19. link

VA: Rx declines and OD trends

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Opioid OD death rate (all)Opioid OD death rate (natural/semisynthetic)% of OD decdents with Rx in 3 months before death

1. Lin. Am J Prev Med 2019;57(1):106−110.

Success in getting our fingerprints off the deaths

Opioid reduction, in the real world Stoppage a/w suicidal ideation and action (11.4%) (Demidenko, 2017)

Dose variation associated with increased OD risk (Glanz, 2019)

Cessation from high dose (>120 MME) typically rapid and followed by emergency care (Mark, 2019)

Cessation associated with 3x risk of OD death (James, 2019)

Associated with termination of outpatient care (Perez, 2019)

Observational data don’t prove cause and effect, but they are not reassuring do show discrepancy between what’s typical and what might be ideal

So what do we know re: “promotes safety and well-being” Some tapered patients are helped!

A safety benefit has not been found yet

Five real-world studies show harms after stoppage Not that each is cause-and-effect!

The benefits are far too elusive (putting it kindly) to support a broad proposition

And remember our history of medical reversals: Estrogen post-menopause

We must not lower our evidentiary standards based on moral sentiment

Dr. Lembke rebuttal

Dr. Kertesz rebuttal

Introduction to Proposition 2 • Tapering can be beneficial or harmful • Given the complexity, how should decisions be

scaled? Who should be making these decisions?

Maybe you noticed • State laws and regulations • Practice policies • Prescription drug plans denying coverage • Lawsuits • Patients being turned away

Proposition 2 Policies that strongly incentivize or mandate opioid dose reduction or discontinuation promote safety and wellbeing of patients and public health

– By policies, we are broadly speaking about: Policies from payers (insurance companies, prescription benefit managers), regulators (e.g., states), employers, health systems and licensing boards

Dr. Kertesz

Proposition 2

Mandates

Incentives

Metrics

Legal threats

An interdependency of Part 1 & 2

If the thing you are incentivizing is not always helpful… Then mandating or incentivizing could turn out poorly

But, we can and should still discuss how mandates and

incentives have already worked out so poorly

Let’s acknowledge how health policy is devised and carried out

The scholarship that applies here: Implementation Science

Policy Analysis Scholarship

Policy scholarship insights 1. Policy isn’t ever entirely rational Leaders commit to solving before they understand

Overwhelming complexity shortcuts

This likely will recur

2. Policy made not by one but many: Competing actors and agencies all act simultaneously to

change care

Consequences of these two facts is that policies are

often jarring, inconsistent and risky for health care where individualization should be our watchword

Governmental • Congress (SUPPORT Act,

etc) • HHS FDA • Dept of Justice & DEA • CMS Medicare D policies • State laws & regs • Medical boards

Framing Voices • Leading Journalists • Advocates • Government speakers • Litigation language • Medical journals

Guidances & Metrics • CDC • VA/DoD & Canadian

Guidelines • NCQA, National Quality

Providers & Payors • Pharmacy chains • Pharmacy Benefit

Managers • Hospital Administration

POLICY ACTORS

Governmental • Congress (SUPPORT Act,

etc) • HHS FDA • Dept of Justice & DEA • CMS Medicare D policies • State laws & regs • Medical boards

Framing Voices • Leading Journalists • Advocates • Government speakers • Litigation language • Medical journals

Guidances & Metrics • CDC • VA/DoD & Canadian

Guidelines • NCQA, National Quality

Providers & Payors • Pharmacy chains • Pharmacy Benefit

Managers • Hospital Administration

POLICY ACTORS

Governmental • Congress (SUPPORT Act,

etc) • HHS FDA • Dept of Justice & DEA • CMS Medicare D policies • State laws & regs • Medical boards

Framing Voices • Leading Journalists • Advocates • Government speakers • Litigation language • Medical journals

Guidances & Metrics • CDC • VA/DoD & Canadian

Guidelines • NCQA, National Quality

Providers & Payors • Pharmacy chains • Pharmacy Benefit

Managers • Hospital Administration

POLICY ACTORS

Governmental • Congress (SUPPORT Act,

etc) • HHS FDA • Dept of Justice & DEA • CMS Medicare D policies • State laws & regs • Medical boards

Framing Voices • Leading Journalists • Advocates • Government speakers • Litigation language • Medical journals

Guidances & Metrics • CDC • VA/DoD & Canadian

Guidelines • NCQA, National Quality

Providers & Payors • Pharmacy chains • Pharmacy Benefit

Managers • Hospital Administration

POLICY ACTORS

Governmental • Congress (SUPPORT Act,

etc) • HHS FDA • Dept of Justice & DEA • CMS Medicare D policies • State laws & regs • Medical boards

Framing Voices • Leading Journalists • Advocates • Government speakers • Litigation language • Medical journals

Guidances & Metrics • CDC • VA/DoD & Canadian

Guidelines • NCQA, National Quality

Providers & Payors • Pharmacy chains • Pharmacy Benefit

Managers • Hospital Administration

POLICY ACTORS

VA/DOD Guideline, 2017 (p.14)

Point 1 in my case is : if one likes mandates & incentives… We have them Because this is the real world and not a fantasy:

There are many they’re inconsistent

Policies transmit liabilities to prescribers without any support There is no accountability for patient outcomes by any agency making the

mandates and incentives

Do you favor that?

Point 2: outcomes are not reassuring

Prescriptions have fallen Prescription volume has

fallen most heavily for the high-dose patients

That means most of the burden or benefit of our “success” is born by this group

Something else also happened, a lot “Due to insurance and dosage

changes…Adam no longer had regular access to the pain medication he needed” (ABC News)

“The night before he left, he

gave us all hugs and told us how much he loved us…I’m glad he’s not in pain anymore, even though we do miss him.” Kelcee Palmer, age 19

Point 3: A key feature of institutional mandates is they resist revision

Mandates embody political “stakes” for agencies

To favor them, you have to acknowledge that resistance to adjustment is part of the bargain

Case in point: Oregon

2018: Oregon Medicaid Plan

Proposal: use the state’s payment power to mandate taper (to ZERO) all non-cancer Medicaid patients on opioids

We sent a private letter to Medicaid Med. Director for “HERC” (7/28/18) after direct discussion with Medicaid staff (who confirmed and assured receipt) Signed by 3 opioid/addiction faculty (Manhapra, Gordon, me) 4 pages, 18 links 3 peer-reviewed articles We offered a private briefing

What response does one expect in these situations?

Oregon denouement

Then ensued high-publicity events, briefings, letters, news articles, all the way to briefing the Governor

Hundreds of hours from dozens of volunteers across the US regarding ONE payer in ONE state

This plan was “paused” in spring, 2019 Who will speak to all the other payers and agencies?

“Totally support this cautionary letter” Barry R McCaffrey General USA, Ret White House Drug ”Czar”, 1996-2001

March 19, 2019 With Kate Nicholson, JD, after our meeting at the CDC FYI: vacation day

Point 4: what’s missing 8 years into Rx downturn

Clarifications from FDA, CDC and HHS

What’s missing No organization tracks outcomes after opioid stoppage

No systematic follow-up after patient deaths

No change from any agency that pays for or measures health care

Note the inequity of attention: 29 Vaping deaths: daily news coverage, immediate CDC task force

94 publicly reported suicides related to pain, 46 with explicit opioid reduction mention. Highly stigmatized, but announced publicly by grieving families.

…..Crickets

Summary of the argument against Taper may still be helpful if done well with some patients, with strong resource

supports, after careful negotiation

Mandating and incentivizing is problematic if There is no evidence that it’s broadly protective for all *

There is no accountability for safety of patients *

There is no matching resource investment to address the original issue (pain!) that the opioids were started for*

Asterisks*** = Nope

You better be 100% confident in the thing you are mandating

Dr. Lembke

Proposition #2 Policies that strongly incentivize or mandate opioid dose reduction or

discontinuation promote safety and wellbeing of patients and public health

● Top-down policies to incentivize patient-centered tapers are necessary to combat the many invisible forces inside and outside of medicine that promote and incentivize opioid prescribing.

● Reducing the prescription opioid supply is a public health emergency (not just the purview of individual patients).

Invisible forces driving overprescribing

#1 Big Pharma Co-Opts Big Medicine … Trojan Horse

This risk too is dose dependent

“We now know that many patients with chronic, nonmalignant pain respond very well to opioids and that, contrary to our

teaching, addiction is very rare and possibly nonexistent as a result of treating such patients with opioids. The barriers to

vastly improved treatment for hundreds of thousands of people in pain, are simply the misinformation and prejudice of

doctors, pharmacists and regulatory bodies.”

-Purdue Physicians’ Pain Management Speaker Training Program, April 1997

#2 The Toyota-ization of Medicine

#3 The Medicalization of Poverty

2016 opioid prescriptions per 100 persons (county)

U.S. unemployment by county

#4 Prescriber Narcissism

Heinz Kohut, The Kohut Seminars, 1987

Motivated by mutually affectionate relationships

Denial

Clark et al, Pain Medicine, 2018 Prescreening is “no better than chance”

● Re-assessment of the Opioid Risk Tool. A total of 225 consecutive new patients, aged 18 years or older.

● “In this population, we were not able to replicate the findings of the initial ORT study. Self-report was no better than chance in predicting those who would have an opioid aberrant behavior. The ORT risk variables did not predict aberrant behaviors in either gender group. There was significant disparity in the scores between self-reported ORT and the ORT supplemented with medical record data (enhanced ORT).”

#5 Addiction

Neuroadaptation

Fleming et al, Pain, 2007 “Eighty-four of 185 (46%) patients with positive toxicology testing denied

illicit drug use during the research interview, even when they were guaranteed anonymity. This finding confirms clinical observations that patients

with chronic pain often mislead their physicians about illicit drug use….Minimization of drug use and drug problems by patients is a major concern

in all studies that try to estimate rates of addiction, especially for illegal drugs.”

This is a public health problem

Ruhm, C., Journal of Health Economics, 2019

● Higher opioid analgesic prescriptions explain 85% of rise in associated deaths from 2000-2011.

● Evidence consistent with importance of drug environment

● 1999-2011: opioid analgesic deaths ↑

● 2010-2015: illicit opioid deaths ⇑, opioid analgesics flat

NSDUH, 2018

Cicero et al, JAMA, 2014 Prescription opioids are the gateway to

heroin ● In the 1960s, 80% of opioid users reported that their first exposure to opioids

was in the form of heroin.

● In the 2000s, 75% of opioid users reported that their first exposure to opioids was in the form of prescription painkillers.

CDC data opioid prescriptions/100 persons

●U.S. average in 2012 = 81 opioid Rx’s/100 persons

●U.S. average in 2017 = 59 opioid Rx’s/100 persons

●Highest state average in 2017 = Alabama at 107 opioid Rx’s/100 persons

●“While the overall opioid prescribing rate in 2017 was 58.7 prescriptions per 100 people, some counties had rates that were seven times higher than that.”

CDC data opioid prescriptions/100 persons (2012 state)

CDC data opioid prescriptions/100 persons (2017 state)

CDC data opioid prescriptions/100 persons (2017 county)

Guy et al, JAMA Internal Med, 2019

While the amount of opioids prescribed, prescribing rates, high dose prescribing rates, and average daily MME per prescription all declined from 2015-2017, “the average and median duration of opioid prescriptions increased by 3.4% and

33.3% respectively.”

U.S. continues to outstrip other rich nations in opioid prescribing

Vaughn, Federal Practitioner, 2019

Hedberg et al, J Pub Health Mgmt Pract, 2019 Oregon reduced opioid deaths by mandating

reductions in opioid prescribing ●Oregon Health Authority 2015 Opioid Initiative to reduce opioid prescribing

●37% decline in Oregonians on > 90 or more MEDs

●27% decline in Oregonian Medicaid patients on > 120 MEDs

●2015-2016: Oregon had the sharpest decline (17 %) in prescription opioid overdose death rates of any state in the U.S.

●“Oregon data do not show an increase in heroin overdose deaths”p. 218

●During same period, prescription opioid deaths nationally increased 10%

Dr. Kertesz rebuttal

Dr. Lembke rebuttal

Coda

What element of the other's argument could resonate most strongly for you and lead you to see things 'the other way' at some point in the future?

Why Stefan Kertesz of 2019 was sadly

mistaken “SMASHING GOOD LOOKS AND WORDPLAY DON’T MAKE UP FOR

WELL-INTENTIONED MISTAKES”

1. It was unfair to hold opioid taper to such a high evidentiary standard; no one demanded such evidence when we put 10 million on opioids!

2. The evidence that the average opioid-recipient is functioning better was never that strong. Your “heart” for subjective reports didn’t reflect “the truth”

3. You pivoted your arguments on OD death; that was myopic

4. Over time we saw how dependence harms, maybe not all, but more patients than you were willing to admit

5. The fact that there were bad outcomes after stoppage in retrospective observational comparisons may well have reflected two things:

1. Doctors “stop” the most risky patients

2. Lack of supports that we can proudly say we have now built!

6. Your concern on systems implementation was not misplaced. But you underestimated how well those concerns could be addressed

Dr. Lembke

What might change my mind? • Evidence showing opioids work for chronic pain: e.g. 12-

month RCT showing robust effectiveness of opioids compared to placebo in the treatment of chronic pain … at a clinically meaningful level that justifies the known harms of long-term opioids.

• Evidence showing more harm than benefit, both for individuals and the public good, of a slow, patient-centered ‘BRAVO-style’ taper in patients on chronic opioid therapy.

Q/A • State your name and where you’re from • State your succinct question • Wrestle with ideas not individuals