Journal Club Alcohol, Other Drugs, and Health: Current Evidence July–August 2011 Featured Article Association between Opioid Prescribing Patterns and Opioid Overdose-Related Deaths Bohnert AS, et al.

Report
Journal Club
Alcohol, Other Drugs, and Health: Current Evidence
July–August 2011
1
Featured Article
Association between
Opioid Prescribing Patterns
and Opioid Overdose-Related
Deaths
Bohnert AS, et al. JAMA. 2011;305(13):1315-21.
2
Study Objective
• To examine the association between prescribed
daily opioid dose and dosing schedule and risk
of opioid overdose death among patients with
cancer, chronic pain, acute pain, or substance
use disorders.
3
Study Design
• Case cohort study comparing Department of
Veterans Affairs (VA) prescription and
diagnosis data in a random sample of
patients who received opioids for pain in
2004 or 2005 (N=155,434).
• Seven hundred fifty patients in the sample
had died from unintentional prescription
opioid overdose by 2008.
4
Assessing Validity of an
Article About Harm
• Are the results valid?
• What are the results?
• How can I apply the results to
patient care?
5
Are the Results Valid?
• Did the investigators demonstrate similarity in all
known determinants of outcomes? Did they
adjust for differences in the analysis?
• Were exposed patients equally likely to be
identified in the two groups?
• Were the outcomes measured in the same way in
the groups being compared?
• Was follow-up sufficiently complete?
6
Did the investigators demonstrate similarity in
all known determinants of outcomes? Did they
adjust for differences in the analysis?
• Cox proportional hazards models were used to
examine the relationship of opioid dose
(expressed as milligrams of morphine
equivalents per day) and risk of opioid
overdose death adjusting for age group, sex,
race, ethnicity, and comorbid conditions.
• Multivariable modeling was restricted to
periods when individuals were prescribed at
least 1 opioid.
7
Were exposed patients equally likely
to be identified in the groups?
 Yes.
 For each patient, observation time began on the
date of the first opioid fill that occurred after the
first medical visit.
 Prescription medication data came from the VA
Pharmacy Benefits Management Services.
8
Were the outcomes measured in the
same way in the groups being compared?

Opioid overdose death was determined
using National Death Index files and
defined using underlying-cause-of-death
codes from the International Statistical
Classification of Diseases (10th Rev.)
−
−
Included all opioid-related deaths that were
ruled unintentional or indeterminant.
Deaths coded as intentional ovedoses were
not included.
9
Was follow-up sufficiently complete?
• Yes.
– Death certificates and cause-of-death codes
were obtained for >99% of known deaths in
the sample.
10
What are the Results?
• How strong is the association between
exposure and outcomes?
• How precise is the estimate of the risk?
11
How strong is the association between
exposure and outcome?
How precise is the estimate of the risk?
• Adjusted hazard ratios (HRs) associated with a
prescribed dose of ≥100 mg/d, compared with
the dose category 1–<20 mg/d, were as follows:
– 4.54 among patients with substance use disorders
(95% confidence interval [CI], 2.46–8.37; absolute risk
difference approximation [ARDA]=0.14%).
– 7.18 among those with chronic pain (95% CI, 4.85–
10.65; ARDA=0.25%)
– 6.64 among those with acute pain (95% CI, 3.31–
13.31; ARDA=0.23%).
– 11.99 among those with cancer (95%CI, 4.42–32.56;
ARDA=0.45%).
How Can I Apply the Results to
Patient Care?
• Were the study patients similar to the patients
in my practice?
• Was the duration of follow-up adequate?
• What was the magnitude of the risk?
• Should I attempt to stop the exposure?
13
Were the study patients similar to the
patients in my practice?
• The sample was comprised of VA patients from
across the US. More than 93% were men; the
majority were white and over age 40.
14
Was the duration of follow-up adequate?
• Observation time began in 2004 and
ended on the day of death or the end of
2008 (whichever came first).
15
What was the magnitude of the risk?
• The frequency of unintentional fatal overdose
over the study period among individuals
treated with opioids was 0.04%.
16
Should I attempt to stop the exposure?
• This study adds to others that demonstrate
increasing morbidity and mortality with
increasing doses of opioids after adjusting
for confounders.
• Prescribers should appreciate that doses of
opioids >100 mg morphine equivalents per
day appear to be associated with increased
mortality.
17

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