Title: How to Analyze Therapy in the Medical Literature (part 1)
1How to Analyze Therapy in the Medical
Literature(part 1)
Akbar Soltani. MD. Tehran University of Medical
Sciences (TUMS) Shariati Hospital www.soltaniebm.c
om
2 The hierarchy of evidence
- Systematic reviews and meta-analyses
- Randomised controlled trials
- Cohort studies
- Case-control studies
- Cross sectional surveys
- Case reports
- Expert opinion
3Three Step Guide in Using an Article to Assess
Therapy
- Are the results of the study valid?
- What are the results? What measures of precision
of effects were reported (CIs, p-values)? - How can I apply these results to patient care?
-
4Randomized control trial design
5Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
6Benefits of Random Allocation (Randomization)
- 1.Reduces bias in those selected for treatment
- guarantees treatment assignment will not be based
on patients prognosis - 2.Prevents confounding
- known and unknown potential confounders are
evenly distributed
7Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
8Ensuring Allocation Concealment
- NOT RANDOMIZED
- Date of birth, alternate days, etc
9Do Not Confuse Allocation Concealment with
Blinding
- Allocation concealment seeks to prevent selection
bias, protects assignment sequence before and
until allocation, and can always be successfully
implemented
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11Do Not Confuse Allocation Concealment with
Blinding (Contd)
- Blinding seeks to prevent information bias,
protects sequence after allocation, and cannot
always be successfully implemented
12Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
13Placebo effect Trial in patients with chronic
severe itching
No treatment
Trimeprazine tartrate
Cyproheptadine HCL
Treatment vs no treatment for itching
14Placebo effect Trial in patients with chronic
severe itching
No treatment
Trimeprazine tartrate
Cyproheptadine HCL
Placebo
Treatment vs no treatment vs placebo for itching
Placebo effect - attributable to the expectation
that the treatment will have an effect
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16Blinding and Reporting
- Usually reduces differential assessment of
outcomes (information bias) - Authors should explicitly state who was blinded
and how. - Many investigators and readers consider a
randomized trial as high quality simply because
it is double-blind, as if double-blinding is
the sine qua non of an RCT. - Trials not double-blinded should not
automatically be deemed inferior trials.
17Blinding in randomised trials hiding who got
what
- Double blinding prevents bias but is less
important, than adequate allocation concealment. - open studies are more likely to favour
experimental interventions over the controls and
that studies that are not double-blinded can
exaggerate effect estimates by 17 - Furthermore, in some trials, blinding cannot be
successfully implemented, whereas allocation
concealment can always be successfully
implemented.
18Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
19Significance tests for baseline differences
20Baseline data
Effect of azathioprine on the survival of
patients with primary biliary cirrhosis
Azathioprine Placebo
Mean age 54.7 54.9
Serum bilirubin (?mol/L) 37.2 30.9
Stage I disease 14 12
Stage II disease 44 43
Stage III disease 15 15
Stage IV disease 27 30
Christensen et al. Gastro 1985
21Baseline data
Effect of azathioprine on the survival of
patients with primary biliary cirrhosis
Azathioprine Placebo
Mean age 54.7 54.9
Serum bilirubin (?mol/L) 37.2 30.9
Stage I disease 14 12
Stage II disease 44 43
Stage III disease 15 15
Stage IV disease 27 30
Christensen et al. Gastro 1985
22Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
23How complete was the follow up? How many dropouts
were there?
- Conventionally, a 20 drop out rate is regarded
as acceptable, but this depends on the study
question. - Some regard should be paid to why participants
dropped out, as well as how many. - It should be noted that the drop out rate may be
expected to be higher in studies conducted over a
long period of time. - A higher drop out rate will normally lead to
downgrading, rather than rejection of a study.
24Bias a one-sided inclination of the mind
- Not random 40
- Not double-blind 17
- Duplicate information 20
- Small trials 30
- Poor reporting quality 25
Over-estimation of treatment effect
25Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
26Intention to treat
Montorri V, Guyatt G. CMAJ 2001 165(10) p1340
27Intention to treat
Montorri V, Guyatt G. CMAJ 2001 165(10) p1340
28Intention to treat
High risk?
Montorri V, Guyatt G. CMAJ 2001 165(10) p1340
29Assess Validity and Applicability to my practice
setting
- 1.Is the study a randomized control trial (RCT)?
- Yes (go on) No (stop)
- 2.Were the patients properly selected for the
trial and randomized with concealed assignment? - Yes (go on) No (stop)
- 3.Were patients and study personnel blind to
treatment? - Yes (go on) No (pause)
- 4.Were the intervention and control groups
similar at the start? (Check Table 1 of most
studies) - Yes (go on) No (stop)
- 5.Was follow-up complete?
- ii. Were patients analyzed in the groups to which
they were randomized (intention-to-treat
analysis)?
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