Medical Cannabis for NonCancer Chronic Pain: Systematic
Review
Mary Butler, PhD, MBA
Co-Director, Minnesota EPC
Assistant Professor, UMN SPH HP&M
Review Team
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Mary Butler
Erin Krebs, MD, MPH
Michelle Brasure, PhD, MLIS
Ben Sunderlin, MPH
Victoria Nelson, MS
Robert Kane, MD
Minnesota EPC
• Collaborative venture between the UMN and
Minneapolis VA Health Care System since 2002
• Funded by Agency for Healthcare Research and
Quality, 1 of 13 centers in Northern America
• Also VA Evidence Synthesis Program (1 of 4
centers) and professional guideline groups.
• Members of Cochrane Collaborative, GRADE,
other International/Interorganizational methods
groups
Hierarchy of Evidence
Systematic
Reviews/metaanalysis
Lowest risk of bias
RCTs
Controlled Clinical Trials
and Observational Studies
Applicability?
Uncontrolled Observational Studies
Case reports and case series
Expert Opinions
RCT = randomized controlled trial
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Systematic Review Elements
• Systematic search processes avoid
introducing bias through exhaustive searches
and pre-decided selection criteria
• Techniques for data collection quality control
to avoid error and introducing additional bias
SR Elements: Risk of Bias
Assessment
• Systematic deviation of study results from
the true results because of the study design.
• Systematic Reviews assess risk of bias of
each individual study by examining the
extent to which a study’s design, conduct,
and analysis have minimized potential
sources of bias.
Bias Sources
• Selection
(Confounding)
• Attrition
• Observation
• Ascertainment
• Measurement
• Reporting
SR Elements: Strength of Evidence
Assessment
• Assess strength of the body of evidence for
each particular outcome examined.
• Strength refers to the confidence the
reviewers have in the findings.
Strength of Evidence
The Holy Grail
• Bias of overall body
• Direct or indirect
answer to the
question
• Consistency of
results
• Precision of estimate
Research Questions:
• What are the benefits (short-term and longterm) of medical cannabis use for the
treatment of non-cancer pain?
• What are the harms (short-term and longterm) of medical cannabis use for the
treatment of non-cancer pain?
PICOS
PICOS
Populations
Inclusion
Children or adults experiencing
chronic non-cancer pain
Interventions Unmodifed whole plant material
Whole Plant Extracts
Nabiximols (Sativex®)
Dronabinol (Marinol®)
Nabilone (Cesamet®) (synthetic)
Comparators Placebo
Active pain treatment (1)
Outcomes
Exclusion
Acute pain
Animal studies
Studies will not be
excluded for type of
comparator; however, a
comparator arm must be
present to assess
benefits
Pain measures (ex: visual analog Intermediate outcomes
scales, McGill Pain Scale)
such as lab values
PICOS (cont.)
PICOS
Settings
Inclusion
Outpatient
Study
Designs
Benefits: Randomized controlled
trials, controlled trials, prospective
or retrospective cohort with
comparators
Other
limitations
Harms: case control, case series
(at least 10 participants) for
potential serious harms
(hospitalizable events)
No date limitations
Exclusion
Inpatient (hospital
treatment in response
to acute episode)
Applicability of Findings
• Interpreting the results will be impacted by
– How study populations compare to expected
program patients
– How study treatment arms compare to expected
MN-produced products
– Match of study follow-up periods to expected use
periods by program patients