Transcript PICO question

Using evidence for patient care
“Half of what you'll learn in medical school will
be shown to be either dead wrong or out of date
within five years of your graduation; the trouble
is that nobody can tell you which half.
So the most important thing to learn is how to
learn on your own.”
--- David Sacket (widely regarded as the father of
evidenced-based medicine)
Using evidence for patient care
About 40 percent of what we consider stateof-the-art health care is likely to turn out to be
unhelpful or actually harmful.
Vinayak K. Prasad and Adam S. Cifu. Ending
Medical Reversal: Improving Outcomes and Saving
Lives. September 2015
CASE #1: Treatment of resistant hypertension
A 68 year old male has had hypertension for many
years. No known CV disease. Renal function
normal. He has been taking HCTZ 25 mg daily,
lisinopril 40 mg daily, and his amlodipine was
increased last month to 10 mg daily because of a
persistently high BP. Today his BP is 168/96. No
symptoms. Exam normal. LVH on ECG.
You confirm as best you can that he is taking his
meds as directed.
What do you do now?
CASE #1: Treatment of resistant hypertension
The diagnosis is resistant hypertension.
A renal vascular study ruled out renal artery
stenosis, aldosterone/renin testing ruled out
hyperaldosteronism, and there were no signs or
symptoms of other secondary causes.
Treatment options could include adding a 4th
medication class, e.g. beta blocker or alpha2adrenergic agonist (clonidine), or adding a
mineralocorticoid receptor antagonist (e.g.
spironolactone)
CASE #1: Treatment of resistant hypertension
PICO question:
Patient
Intervention
Comparison intervention (e.g. placebo, another med)
Outcome
For a 68 year old male with resistant HTN, is adding
a beta blocker or clonidine more or less effective for
lowering BP than adding spironolactone to an
existing 3-drug regimen?
Does this intervention help?
Levels of evidence
Level 1: Systematic review of randomized trials or
n-of-1 trials [if high quality RCTs]
Level 2: Randomized trial or observational study
with dramatic effect
Level 3: Non-randomized controlled
cohort/follow-up study
Level 4: Case-series, case-control studies, or
historically controlled studies
Level 5: Mechanism-based reasoning
---Oxford Centre for Evidence-Based Medicine: www.cebm.net
CASE #1: Treatment of resistant hypertension
To find systematic reviews and RCTs (using free
UNM sources):
Cochrane Library: click on the “Databases” button,
then choose “Cochrane library.”
PubMed: from the UNM Health Sciences Library
site, click on the PubMed button, then the PubMed
link. Under “PubMed Tools” click on “Clinical
Queries.”
CASE #1: Treatment of resistant hypertension
Williams B, Macdonald TM, Morant S.
Spironolactone versus placebo, bisoprolol, and
doxazosin to determine the optimal treatment for
drug-resistant hypertension (PATHWAY-2): a
randomised, double-blind crossover trial. Lancet.
2015 Sep 18.
CASE #1: Treatment of resistant hypertension
Double-blind, placebo-controlled, crossover trial,
enrolled 335 patients aged 18–79 years with seated
clinic systolic blood pressure 140 mm Hg or greater
and home systolic blood pressure (18 readings over
4 days) 130 mm Hg or greater, despite treatment for
at least 3 months with maximally tolerated doses of
three drugs. They were randomly assigned to
spironolactone, doxazosin, bisoprolol, or placebo.
CASE #1: Treatment of resistant hypertension
The average reduction in home systolic blood
pressure by spironolactone [25-50 mg/day] was
superior to placebo (–8.70 mm Hg p<0.0001),
superior to the mean of the other two active
treatments (doxazosin and bisoprolol; -4.26;
p<0.0001), and superior when compared with the
individual treatments; versus doxazosin (–4.03;
p<0.0001) and versus bisoprolol (p<0.0001).
CASE #2: Treatment of fibromyalgia
A 56 year old female has had fibromyalgia for
“many years.” She is here today to establish care
with you. She states she has persistent pain that is
incapacitating at times, without much relief from
the amitriptyline that she has been taking. An
exercise program has been recommended (“I’m too
tired to do exercise”) and CBT helped “a little.”
She had depressive symptoms but does nor meet
criteria for a depressive disorder. She wants to
know if another medication would help.
CASE #2: Treatment of fibromyalgia
You recall that duloxetine has been a recommended
treatment for fibromyalgia, but when you try to
prescribe it, the pharmacist tell you that prescriptions
for duloxetine are restricted to patients who have first
tried at least two other meds. The pharmacist
suggests baclofen. You were unaware of any
evidence for efficacy of baclofen, so you decide to
check.
CASE #2: Treatment of fibromyalgia
PICO question:
Patient: 56 year old female with chronic pain from
fibromyalgia
Intervention: Baclofen
Comparison intervention (placebo or another med)
Outcome: pain relief
CASE #2: Treatment of fibromyalgia
Searching for systematic reviews and RCTs:
PubMed Clinical Queries search finds 0 systematic
reviews and 0 RCTs, and further PubMed search
finds no case control or cohort studies. Evidence is
level 5: Mechanism-based reasoning.
Probably not a good choice.
CASE #2: Treatment of fibromyalgia
UpToDate:
First line drug is amitriptyline.
If inadequate response or not tolerated:
Cyclobenzaprine
Pregabalin
Duloxetine
Milnacipran
Gabapentin
CASE #2: Treatment of fibromyalgia
To find systematic reviews:
PubMed: Clinical Queries search finds 466
systematic reviews
Cochrane Library has 41 systematic reviews,
including pregabalin, duloxetine, milnacipran,
gabapentin, and amitriptyline, but not
cyclobenzaprine.
CASE #2: Treatment of fibromyalgia
Cochrane systematic reviews: Pregabalin
Pregabalin has “proven efficacy” for fibromyalgia.
4 RCTs with 1,374 patients.
The best NNT for at least 50% pain relief over
baseline (substantial benefit) was 11 (for the 450
mg dose). Quality of the studies was considered
adequate for valid conclusions (though fairly low
quality in my assessment, and all studies were
sponsored by the manufacturer).
CASE #2: Treatment of fibromyalgia
Cochrane systematic reviews: Duloxetine
6 RCTs of 2,249 patients
“Duloxetine at 60 mg daily is effective for
fibromyalgia over 12 weeks (NNTB 8) and over 28
weeks as well as for painful physical symptoms in
depression (NNTB 8).”
Studies were “low to moderate quality” (most were
low quality, and nearly all were drug company
sponsored)
CASE #2: Treatment of fibromyalgia
Cochrane systematic reviews: Milnacipran
“… milnacipran 100 mg or 200 mg is effective for a
minority in the treatment of pain due to fibromyalgia,
providing moderate levels of pain relief (at least 30%)
to about 40% of participants, compared with about
30% with placebo. There were insufficient data to
assess substantial levels of pain relief (at least 50%).
Using stricter criteria for “responder” and a more
conservative method of analysis gave lower response
rates (about 26% with milnacipran versus 17% with
placebo).
CASE #2: Treatment of fibromyalgia
Cochrane systematic reviews: Gabapentin
The amount and quality of evidence were
insufficient to reach any reliable conclusion.
CASE #2: Treatment of fibromyalgia
Cochrane systematic reviews: Amitriptyline
There was no first or second tier evidence for
amitriptyline in the treatment of fibromyalgia. Using
third tier evidence the risk ratio (RR) for at least 50%
pain relief, or equivalent, with amitriptyline compared
with placebo was 3.0, with an NNT of 4.1 (very low
quality evidence). There were no consistent differences
between amitriptyline and placebo or other active
comparators for relief of symptoms such as fatigue,
poor sleep, quality of life, or tender points.
CASE #2: Treatment of fibromyalgia
PubMed systematic review (2004):
Cyclobenzaprine
5 RCTs of 312 patients
“Cyclobenzaprine-treated patients were 3 times as
likely to report overall improvement and to report
moderate reductions in individual symptoms,
particularly sleep” (NNT=5 for global improvement).
Pain was significantly relieved only at week 4.
Studies were judged to be of “fair” quality (most
appeared to be of low quality to me)
CASE #2: Treatment of fibromyalgia
Conclusion based on the evidence:
Best evidence is for pregabalin and duloxetine.
Consider amitriptyline (very low quality evidence
but extensive experience) or cyclobenzaprine (low
quality evidence, especially for pain.
There is a paucity of head-to-head comparative
studies. Cost becomes an important consideration.
Reading (and using) the medical
literature to improve patient care
“Just in time” : Searching for evidence to
answer a clinical question that arises during
patient care encounters
“Just in case” : Reading the literature
“prospectively” to keep up on evidence-based
health care practice
Reading (and using) the medical
literature to improve patient care
“Just in case” :
Evidence-based Medicine online journal, one issue
every 2 mo., available through UNM Library
BMJ EvidenceUpdates: free service of BMJ. Sign up
and receive regular updates by email