spicy debate - amersa
TRANSCRIPT
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