CTSA PROGRAM STEERING COMMITTEE [OPEN SESSION]...Jul 10, 2017 · New Generation Of Pain...
Transcript of CTSA PROGRAM STEERING COMMITTEE [OPEN SESSION]...Jul 10, 2017 · New Generation Of Pain...
CTSA PROGRAM STEERING COMMITTEE [OPEN SESSION]
JULY 10, 2017 2:30 – 4:00 ET
Agenda
2
2:30 Welcome Kathleen Brady
Redonna Chandler
2:35 – 3:30 NIH Opioid Crisis Presentation and
Discussion
Chris Austin (NCATS Director)
Nora Volkov (NIDA Director)
3:30 - 4:00 NCATS CTSA Program Policy and Procedure
for Surveys
Governance for the Clinical and
Translational Science Awards (CTSA) Program
Erica Rosemond
Discussion by SC Members
NIH’s Efforts to Reduce the Opioid Epidemic
Nora D. Volkow, M.D.Director
@NIDAnews
National Instituteon Drug Abuse
Numbers in Millions
Source: SAMHSA, 2015 National Survey on Drug Use and Health, 2016.
Current Drug Use Rates in Persons Ages 12+
Past Year Nonmedical Use of Psychotherapeutic Drugs
Persons Ages 12+
0.3
0.5
1.2
1.9
6.4
22.2
27.1
0 10 20 30
Heroin
Inhalants
Hallucinogens
Cocaine
Psychotherapeutics
Marijuana
Any Illicit Drug
Prescription Drug Misuse/Abuse is a Major Problem in the US
4.74.9
5.1 54.84.94.8
4.3
4.8
4.2
3.9
4.7
2.12.22.12.1 22.22.2
22.3
2 2 2.3
1.21.11.4
1.21.11.21.1 11.31.31.4
2
0.30.30.40.30.20.30.40.20.20.20.30.6
0
1
2
3
4
5
6
Trendline break due to questionnaire change in 2015
Overdose Death Rates
Designed by L. Rossen, B. Bastian & Y. Chong. SOURCE: CDC/NCHS, National Vital Statistics System
1999 2015
2015 Overdose Deaths:
52,404 Any Drug
33,091 Any Opioid
Opioid OD Deaths US, 2000-2015
266 260 253242 234
222
0
50
100
150
200
250
300
201020112012201320142015
OP
IOID
MM
E IN
BIL
LIO
NS
Source: IMS Health, U.S. Outpatient Retail Setting
Opioid morphine milligram
equivalents (MME) dispensed fell by over 15% from 2010-2015
Opioid Prescriptions have started to Decrease
but Opioids Fatalities are still Increasing
Heroin Price Has Decreasedin Recent Years
$-
$500
$1,000
$1,500
$2,000
$2,500
$3,000
$3,500
"Retail" Price Per PureGram
National Drug Control Strategy--Data Supplement 2014. https://www.whitehouse.gov/sites/default/files/ondcp/policy-and-research/ndcs_data_supplement_2 014.pdf
Emerging Illicit Synthetic Opioids
• Increasing reports of fentanyl laced-heroin
and prescription pills
• Other synthetic opioids emerging i.e.,
Carfentanil
PAIN MANAGEMENT
Safe, more effective strategies
OPIOID ADDICTION
TREATMENT
New and innovative
medications and
technologies
OVERDOSE REVERSAL
Interventions to reduce
mortality and link to
treatment
Using Research to End the Opioid Crisis
NIH OPIOID RESEARCH INITIATIVE
Safe, More Effective Strategies for Pain Management
Non-pharmacological treatmentNeural stimulation;
Surgical interventions; Meditation
Non-Opioid AnalgesicsCannabinoids;Inflammatory mediators; Ion channel blockers
Targeted Opioid Analgesics
with reduced potential for addiction and overdose
Biologics
e.g. antibodies that bind to pain producing cytokines
Soergel DG et al., Pain 2014; 155(9):1829–1835.
Biased Mu-Opioid Receptor Ligands:
New Generation Of Pain Therapeutics
Knowledge of Pain Pathways –
New Biomarkers for Pain?New study assess glial role in human pain
• Patients with low back pain (LBP) versus controls
– Uses PET to detect levels of glial protein (TSPO)
– Demonstrates role of glial activation in human pain
– Possible biomarker
– May suggest new treatments for chronic pain
Loggia et al., Brain 2015;138.
Limiting Abuse by Predicting Addiction
• OPRM1 encodes for the target of
opioids
• Can variants predict likelihood
addiction?
• OPRM1 variant
– Affects receptor levels in brain
– Associated with increased risk
for addiction, overdose severity
Hancock et al., Biol Psychiatry 2015; 78.
Manini et al., J Med Toxicol 2013; 9.
Peciña et al., Neuropsychopharmacology 2015; 40.
Variant Common Type
Mapping the differences
Intravenous
User Friendly Naloxone
NARCAN® Nasal Spray device-- $37.50 per 4mgApproved by FDA November 2015
2,000
4,000
6,000
8,000
10,000
12,000
14,000
02/16 05/16 08/16 11/16 02/17
IMS
Mo
nth
ly P
resc
ript
ions
Narcan Nasal Spray All other naloxone products
• Naloxone Px increased 3.5X in past year
• NARCAN® Nasal Spray is the most prescribed
naloxone
• 900,000 NARCAN® Nasal Spray doses
distributed since launch in 2/16
Opioid Overdose Reversal
By tNarcan® Nasal Spray
N=245
Avetian GE et al., Current Medial Research and Opinion, 23 May 2017.
Overdose Treatment: Saving
Lives for Future Recovery
• New stronger, longer acting
formulations to address more
potent opioids (e.g. fentanyl)
• Stimulation devices to prevent
respiratory depression
• Overdose detection and alert
technologies
• Post-overdose interventions to
ensure engagement in treatment
Medications Assisted Therapies for OUD
effect
no effect
agonist antagonist
Op
ioid
Eff
ec
t
Full Agonist(Methadone: Daily Dosing)
Partial Agonist(Buprenorphine: 3-4X week)
Antagonist(Naltrexone: ER 1 month)
Log Dose
DECREASES:
• Opioid use
• Opioid-related OD deaths
• Criminal activity
• Infectious disease
transmission
And INCREASES
• Social functioning
• Retention in treatment
• Outcomes in NAS
MAT is highly underutilized
Sigmon SC et al. N Engl J Med 2016.
Abstinence from Illicit Opioids over 12 Weeks with
Interim Buprenorphine
5.4 5.4 5.6
0.9
2.3 2.4
0
1
2
3
4
5
6
Buprenorphine Referral Brief Intervention
Baseline 30 days
Emergency Department-Initiated
Buprenorphine – Reduced self-reported, illicit opioid use
– Increased engagement in addiction
treatment
– Decreased use of inpatient addiction
treatment services
Da
ys
Self-Reported Illicit Opioid Use in the Past 7 Days
D’Onofrio G et al., JAMA April 28, 2015.
Overdoses in 78 weeks:
Control: 7
Naltrexone: 0
Naltrexone Trial in CJ Populations
• Participants: parolees/probationers with opioid addiction – all
volunteers – received either
– Monthly injections of extended release naltrexone for 6 months
– Community treatment, including methadone or Suboxone
(encouraged)
O’Brien et al., Poster presentation at the Annual Meeting of the College on Problems of Drug Dependence, June 2015.
Relapse Frequency
Pro
ba
bilit
y o
f No
Rel
apse
Weeks
Treatment as usual
Naltrexone
Lee et al. NEJM March 31, 2016.
Improving Treatments for Addiction:
Rosenthal et al., Addiction 2013;105.
PROBUPHINE®
FDA approval – May 26, 2016
Extended Release Formulations
Vivitrol®
Krupitzky et al., Lancet 2011
Placebo: N=124
XR-NTX: N=126
IM Injection q 4 weeks for 24 weeks
Median % Opioid-Negative Urines
Pe
rce
nt
of W
ee
kly
Uri
ne
Te
sts
100%
80%
60%
40%
20%
0%
PLACEBO XR-NTX
Innovative Opioid Addiction Treatments:
Fentanyl Vaccine • 2016: First vaccine for fentanyl and fentanyl
analogs reported in a mouse model
• Successfully stimulated antibody production
• Reduced fentanyl reaching the brain
• Reduced analgesia and protected against overdose
Bremer et al, 2016;
Janda and Treweek, 2012.
Cutting Edge Science Meeting Series
to End the Opioid Crisis
Medications Development for Opioid Use Disorders and
for Overdose Prevention and Reversal -- June 5, 20171
Development of Safe, Effective, Non-Addictive
Pain Treatments -- June 16, 2017 2
3 Understanding the Neurobiological Mechanisms
of Pain -- July 7, 2017
CTSA’s Potential Role
ED Network
• Testing new MAT ER formulations in OD patients with OUD
• Epidemiological studies to characterize OD patients (ie., pain patients vs OUD patients;
symptomatology, doses of naloxone required, rate of response).
• Implementation research for after care models for treatment of OUD
Primary Care Physicians Network• Implementation research for initiation and follow up of ER MAT formulations
• Clinical trials for testing new analgesics or other pain therapeutics
• Research on development of biomarkers for pain with predictive clinical validity
Neonatal Unit Network• Implementation research for models of after care for mothers with OUD
• Clinical research on treatment of NAS
PAIN
ORWH
OBSSRNIDA
NIDCR
NINDS
NIA
NINRNICHD
NIAMS
NCCIH
NIH Pain Consortium Centers of Excellence in Pain Education
Goal: Improve pain treatment through education
Education
SUD
Goal: Prevent SUD and improve outcomes in addiction through education of health care providers
SCIENTIFIC STRATEGIES FOR COMBATING THE OPIOID EPIDEMICSHORT-TERM STRATEGIES INTERMEDIATE STRATEGIES LONG-TERM STRATEGIES
TREATMENT
OF OPIOID-USE
DISORDERS
TREATMENT
OF CHRONIC PAIN
New formulations of existing medications
Repurposing approved therapies (e.g., lorcaserin)
Novel medications targeting neurobiology (e.g., lofexidine)
*Vaccines and monoclonal antibodies
Brain-stimulation technologies
Opioid formulations with abuse-deterrent properties
M OR-biased agonists
Cannabinoids
Novel or repurposed medications targeting pathophysiology (e.g., sodium-channel blockers)
M onoclonal antibodies
Brain-stimulation technologies
*Gene therapies
*Progenitor cell therapies
Precision medicine
BiomarkersAdapted from Volkow & Collins,
NEJM , 2017.
OVERDOSE
PREVENTION
& REVERSAL
Stronger opioid antagonist formulations
Novel medications (e.g., 5-HT1A agonists, ampakines)
Phrenic-nerve stimulation devices
Technologies to detect overdose & alert help or autoinject naloxone
ERICA ROSEMOND, PHD, PROGRAM DIRECTOR
SAM JONSON, M.P.S, OPERATIONS MANAGER
DIVISION OF CLINICAL INNOVATION
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
STEERING COMMITTEE MEETING 7.10.2017
Governance and Surveys
for the CTSA Program
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Governance for the CTSA Program
Surveys
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Surveys are generated from different groups and/or sources and will be processed in different ways:
A. DTF Survey - generated from one or more DTFs or their working groups▪ Within DTFs: Approvals and distribution managed within and across DTFs
▪ External to DTFs: SC and DCI leadership reviews
B. CTSA Program Grantee Survey - generated from NCATS-funded grants (e.g. TIN, CCIAs, admin supplement, coordinating center) ▪ If peer reviewed already: SC informed for feedback
▪ If not peer reviewed: SC and DCI leadership reviews
C. CTSA Program Partner Survey - generated from a hub and/or an affiliated partner institution▪ SC and DCI leadership reviews
D. External Survey - generated by a group not affiliated(is external to the CTSA Program) ▪ DCI leadership reviews and SC reviews
REQUESTING FEEDBACK BY COB AUGUST 11 TO:[email protected]
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