Critical Appraisal for Therapy

Using the worksheet (page ....)

Critical appraisal for therapy articles

Three day versus five day treatment with

amoxicillin for non severe pneumonia in
young children: a multicentre randomised
controlled trial
CONSORT
 CONSORT
CONSORT = Consolidated Standards
Of Reporting Trial
25 items à
•  Title & abstract
•  Background & objectives
•  Methods
•  Results
•  Discussion
•  Other information
http://www.consort-statement.org
TITLE  AND  ABSTRACT  
 
1a.  Identi5ication  as  a  randomised  trial  in  the  title  
1b.  Structured  summary  of  trial  design,  methods,  
results,  and  conclusions  
1. Title &Abstract
BACKGROUND  &  OBJECTIVE  
 
2a.  Scienti'ic  background  and  explanation  of  rationale  
2b.  Speci'ic  objectives  or  hypotheses  
2. BACKGROUND & OBJECTIVE
METHODS  
Trial  Design  
 
3a.  Description of trial design (such as parallel, factorial)
including allocation ratio  
3b.  Important changes to methods after trial
commencement (such as eligibility criteria), with reasons  
3. METHODS – Trial design
METHODS  
Participants  
 
4a.  Eligibility  criteria  for  participants    
4b.  Settings  and  locations  where  the  data  were  
collected  
4. METHODS – participants
METHODS  
Interventions  
 
5.  The  interventions  for  each  group  with  suf'icient  
details  to  allow  replication,  including  how  and  when  
they  were  actually  administered  
5. METHODS – Interventions
METHODS  
Outcomes  
 
6a.  Completely  de'ined  pre-­‐speci'ied  primary  and  
secondary  outcome  measures,  including  how  and  when  
they  were  assessed  
6b.  Any  changes  to  trial  outcomes  after  the  trial  
commenced,  with  reasons  
6. METHODS – Outcomes
METHODS  
Sample  Size  
 
7a.  How  sample  size  was  determined  
7b.  When  applicable,  explanation  of  any  interim  
analyses  and  stopping  guidelines  
7. METHODS – sample size
METHODS  
Randomisation  –  sequence  
generation  
 
8a.  Method  used  to  generate  the  random  allocation  
sequence  
8b.  Type  of  randomisation;  details  of  any  restriction  
(such  as  blocking  and  block  size)  
8. METHODS – randomization generation
METHODS  
Randomisation  –  Allocation  
concealment  mechanism  
 
9.  Mechanism  used  to  implement  the  random  
allocation  sequence  (such  as  sequentially  numbered  
containers),  describing  any  steps  taken  to  conceal  the  
sequence  until  interventions  were  assigned  
9. METHODS – randomization allocation
METHODS  
Randomisation  –  Implementation  
 
10.  Who generated the random allocation sequence, who
enrolled participants, and who assigned participants to
interventions  
METHODS  
Blinding  
 
11a.  If  done,  who  was  blinded  after  assignment  to  
interventions  (for  example,  participants,  care  
providers,  those  assessing  outcomes)  and  how  
11b.  If  relevant,  description  of  the  similarity  of  
interventions  
11. METHODS – Blinding
 11 doses amoxicillin
for 3 days
5 days of
treatment
(control) 8 doses amoxicillin
for next 2 days
Treatment
11 doses amoxicillin
for 3 days
5 days of
treatment
(experimental) 8 doses placebo
for next 2 days
METHODS  
Statistical  Method  
 
12a.  Statistical  methods  used  to  compare  groups  for  
primary  and  secondary  outcomes  
12b.  Methods  for  additional  analyses,  such  as  subgroup  
analyses  and  adjusted  analyses  
12. METHODS – Statistical Methods
RESULTS  
Participant  5low    
 
13a.  For  each  group,  the  numbers  of  participants  who  
were  randomly  assigned,  received  intended  treatment,  
and  were  analysed  for  the  primary  outcome  
 13b.  For  each  group,  losses  and  exclusions  after  
randomisation,  together  with  reasons  
13. RESULTS – Participant flow
RESULTS  
Recruitment  
 
14a.  Dates  de'ining  the  periods  of  recruitment  and  
follow-­‐up    
14b.  Why  the  trial  ended  or  was  stopped  
14. RESULTS – recruitment
RESULTS  
Baseline  data  
 
15.  A  table  showing  baseline  demographic  and  clinical  
characteristics  for  each  group  
15. RESULTS –
Baseline data
RESULTS  
Number  analysed  
 
16.  For  each  group,  number  of  participants  
(denominator)  included  in  each  analysis  and  whether  
the  analysis  was  by  original  assigned  groups  
16. RESULTS – Number analyzed
16. RESULTS – Number analyzed
INTENTION TO TREAT ANALYSIS

a type of analysis of clinical trial data in

which all patients are included in the
analysis based on their original assignment
to intervention or control groups,
regardless of whether patients failed to
fully participate in the trial for any reason,
including whether they actually received
their allocated treatment, dropped out of
the trial, or crossed over to another group.
RESULTS  
Outcomes  and  estimation  
 
17a.  For  each  primary  and  secondary  outcome,  results  
for  each  group,  and  the  estimated  effect  size  and  its  
precision  (such  as  95%  con'idence  interval)  
17b.  For  binary  outcomes,  presentation  of  both  
absolute  and  relative  effect  sizes  is  recommended  
17. RESULTS – Outcomes
RESULTS  
Ancillary  analysis  
 
18.  Results  of  any  other  analyses  performed,  including  
subgroup  analyses  and  adjusted  analyses,  
distinguishing  pre-­‐speci'ied  from  exploratory  
18.
RESULTS –
Ancillary
analysis
RESULTS  
Harm  
 
19.  All  important  harms  or  unintended  effects  in  each  
group    
19. RESULTS – Harm
DISCUSSION  
Limitations  
 
20.  Trial  limitations,  addressing  sources  of  potential  
bias,  imprecision,  and,  if  relevant,  multiplicity  of  
analyses  
20. DISCUSSION – Limitations
RESULTS  
Generalisability  
 
21.  Generalisability  (external  validity,  applicability)  of  
the  trial  'indings  
21. DISCUSSION – generalisability
RESULTS  
Interpretation    
 
22.  Interpretation consistent with results, balancing
benefits and harms, and considering other relevant
evidence  
22. DISCUSSION – Interpretation
OTHER  INFORMATION  
Registration,  protocol,  funding  
 
23.  Registration  number  and  name  of  trial  registry    
24.  Where  the  full  trial  protocol  can  be  accessed,  if  
available    
25.  Sources  of  funding  and  other  support  (such  as  
supply  of  drugs),  role  of  funders  
23-25. OTHER INFORMATION
CRITICAL APPRAISAL
 Methods-1
Randomized, placebo controlled trial, multicentre,
double blind

2188 children 2-59 months

cough, rapid respiration or

Subjects : difficulty in breathing

Non severe pneumonia:

respiratory rate ≥ 50/min
(2-11) or ≥ 40/min (12-59)

Interventions:
Oral amoxicillin 31-54mg/kg/day in 3 divided dose.
1095 subject given 3 days and 1093 subjects given
five days
Methods-2
Severe pneumonia

Condition requiring AB

Excluded Congenital heart disease

Chronic systemic disorder

Using AB and allergy penicillin

Asthma & measles

Methods-3
OUTCOMES : treatment failure

development chest indrawing, convulsions,

drowsiness, or inability to drink, respiratory
rate above age specific cut points on day-3 or
later, or oxygen saturation by pulse oximetry <
90% on day 3

3 and 5 days after enrollment

FOLLOW UP
12 and 14 days after enrolment
EBM Therapy
Worksheet
 Are the results of the trial valid? (Internal
Validity) What question did the study ask?

1a. Was the assignment of patients to treatments

randomised?
1b. Were the groups similar at the start of the trial?
2a. Aside from the allocated treatment, were groups
treated equally?

2b. Were all patients who entered the trial accounted for? –
and were they analysed in the groups to which they were
randomised?

3. Were measures objective or were the patients and

clinicians kept “blind” to which treatment was being
received?
What were the results?

1.  How large was the treatment effect?

Relative Risk (RR),
Absolute Risk Reduction (ARR),
Relative Risk Reduction (ARR)
Number Needed to Treat

2.  How large was the treatment effect?

95% CI
Are  the  results  of  the  trial  valid?  (Internal  
Validity)  What  question  did  the  study  ask?  

P I C O
Patient Intervention Comparison Outcomes
Or Problem

Non severe Antibiotic Cure rate

Antibiotics
pneumonia for 3 for 5 days
in children days
1a. Was the assignment of patients
to treatments randomized?

Block randomization with variable

sized block, to avoid unblinding

11 doses of 8 doses amoxicillin

amoxicillin for 3 or placebo for next
days 2 days
1b. Were
the groups
similar at
the start of
the trial ?
 2a. Aside from the allocated treatment, were the
groups treated equally?

11 doses amoxicillin
for 3 days
5 days of
treatment
(control) 8 doses amoxicillin
for next 2 days
Treatment
11 doses amoxicillin
for 3 days
5 days of
treatment
(experimental) 8 doses placebo
for next 2 days
2b. Were all
patients who
entered the trial
accounted for?
And were they
analyzed in the
groups to which
they were
randomized?

Lost to follow
up no more
than 20%
2b. Were all patients who entered the trial accounted
for? And were they analyzed in the groups to which
they were randomized?
 INTENTION TO TREAT ANALYSIS

a type of analysis of clinical trial data in

which all patients are included in the
analysis based on their original assignment
to intervention or control groups,
regardless of whether patients failed to
fully participate in the trial for any reason,
including whether they actually received
their allocated treatment, dropped out of
the trial, or crossed over to another group.
3. Were patients measure objective or
were the patients and clinicians and kept
"blind" to which treatment was being
received?

Double blind (participants and

researcher)
What were the results?

1. How large was the treatment effect

2. How precise is the estimate of the

treatment effect?
 Risiko relatif (RR = Relative Risk)

Disease a
------
+ - a+b
RR = --------------
A a b c
Treatment
------
B c d
c+d
 (RR = Relative Risk)

Cure EER 89.5

RR = --------------
+ - CER 89.9
3 days 980 115
RR = 0.996 = 1.00
5 days 983 110
 Control Event Rate (CER)
CER : the proportion of outcome in the
control group
(5 days treatment)

Experimental Event Rate (EER)

EER : the proportion of outcome in the
experimental group
(3 days treatment)
EER CER
Absolute Risk Reduction (ARR)

ARR = (|CER – EER|)

ARR = (89.90-89.50)

ARR = 0.40
Relative Risk Reduction (RRR)

RRR = (|CER – EER|/CER)

RRR = (89.9-89.5/89.9)

RRR = 0.005
Number Needed to Treat (NNT)

NNT = 1/ARR

NNT = 1/0.4%
ARR = 0.40
NNT = 250
Confidence Interval (CI) ARR

CER × (1 − CER) EER × (1 − EER)

± 1.96 +
Ncontrol Nexp
Confidence Interval (CI) ARR

CER × (1 − CER) EER × (1 − EER)

± 1.96 +
Ncontrol Nexp

95% CI = ± (1.96 x 1.30)

95% CI = ± 2.26
95% CI ARR

95% CI ARR = 0.40 ± 2.26

95% CI ARR = -1.86 - 2.66