Critical appraisal of research paper - impact of zinc supplementation on cases of ALRTI in children

1. A CRITICAL APPRAISAL
Anuradha Bansal – Veena R. Parmar – Srikant Basu – Jasbinder Kaur
– Suksham Jain – Abhijeet Saha – Deepak Chawla
Presented at
Workshop on RANDOMIZED CONTROL TRIALS- DESIGN,
ANALYSIS AND REPORTING
Indian Institute of Public Health (Delhi)

2. 1. Summary of the article
2. Basic Study Design
3. Section-wise critical appraisal
Title and abstract
Introduction
Material and Methods
Results
Discussion
Conclusion
4. Internal Validity and External Validity

3. Objectiv To evaluate the efficacy of zinc supplementation on
e duration of illness in children with severe ALRTI
Children age group 2-24 months with severe ALRTI (Inclusion
P criteria)
In a teaching referral hospital in North India
20mg of elemental zinc per day for 5 days
I
Control group received an equal amount of placebo with
C appropriate taste, smell, color and consistency similar to zinc
mixture
Primary - Time to be asymptomatic (Composite)
O Secondary – Duration on hospital stay,
Resolution of danger signs, respiratory distress, tachypnea
and hypoxia in room air
Superiority objective
T

4. Randomized Control Trial, prospective in nature

5. Assessed for
eligibility
N=120
14
excluded Enrollment
(parental refusal
or exclusion
Process
criteria)
106
Randomized
53 - zinc 53 -control
Randomization
group group
52 - zinc group
(1 left against medical 53 received Intervention
advice) placebo
Follow up
52 analyzed
52 analyzed (1 lost to follow
up)

6. ITT?
 The study claims to have followed an intention to
treat analysis whereas actually the trial profile
shows a minor inconsistency
 In the intervention arm, one patient left after being
randomized – the final result has EXCLUDED the
patient and considered n=52 in this arm
 In the control arm, the loss to follow up has been
INCLUDED in the size of the control group as n=53
here.
 (The n given in the baseline and outcome tables
is different)

8.  TITLE
 Mentions study design, intervention and population
 Does not mention the area from which the population
has been studied
 ABSTRACT
 Objectives, methods, findings and
conclusions have been well summarised
 No mention of the method of randomization
 INTRODUCTION
 Justification for the
 need for study and
 area mentioned (North India) has been clearly
outlined and reflects clinical equipoise

9. MATERIAL AND METHODS

10. Method Description Comment
RANDOMIZATION Simple Randomization through a random Suspicious as
TECHNIQUE number table exactly same size of
control and
intervention arm
has been achieved
ALLOCATION Achieved by dispensing the drug and placebo Justified- but no
CONCEALMENT in identically looking bottles mention of who
dispensed the drug
to the patient
PREPARATION OF Placebo prepared to give similar taste, smell, Mentioned sources
PLACEBO color and consistency compared to original and details
zinc mixture
BLINDING Repeated mention of the trial being of a No mention of
‘triple blind design’ ‘WHO’ exactly was
blinded
DISCHARGE Asymptomatic for at least 24 hours. Objective in nature
CRITERIA FOR
PATIENTS

11. SAMPLE SIZE Pilot study revealed that No detailed mention of
CALCULATION for 80% power and 0.05 way of arriving at sample
two sided alpha, a sample size
of 400 was needed which -effect size
was brought down to 106 -change in primary
due to time constraints outcome
SAMPLE SIZE OF THE N=106 Small to give any decisive
STUDY Identified by the study as a result, does not resolve
limitation the inconsistency of
results established by
studies before –
Precision compromised
therefore WIDE
CONFIDENCE INTERVAL
OBTAINED.

12.  Time to be asymptomatic
Median hours with IQR – range more or less same,
statistically insignificant
 No. of children symptomatic
Similar and statistically insignificant value
 Duration of hospital stay
Shorter by 9 hours in the zinc group – result insignificant
 Time to resolution of respiratory distress, tachypnea,
dangers signs and hypoxia
Similar in both the groups, results statistically insignificant.

13. Sub Group Analysis
 Post Hoc is questionable, should have been a
priori
 Multiplicity problem
 Secondary outcomes are correlated
 Primary and secondary also correlated
 Duration of stay- degree of subjectivity, not
mentioned about blinded also
 Components of composite endpoint have equal
importance in terms of relevance to the patient -
more or less the same, least important is duration of
stay

14.  Zinc supplementation did not reduce recovery
time and duration of hospital stay
 Not enough evidence found to reject null
hypothesis
The conclusions are plausible.

15. Internal Validity
 Selection bias – Doubtful since the number in both
the arms has been found to be equal despite simple
randomisation
 Performance bias – Triple blind claimed but no
mention of who all were blinded
 Attrition bias – no problem
 Detection bias – no mention of who assessed the
outcome and who did what?
 Reporting bias – inconclusive

16. External Validity
 Given the inclusion and exclusion criteria which is
generally applicable
 Inclusion of both wheezy and non wheezy
children
 Very less proportion of population of slum areas,
less even in intervention group -Pragmatism?
 Good proportion of anaemic patients,
confounding variable
 Small sample size

17. Group 2 :
Dr Sabyasachi Das, Aleesha Mary Joseph, Jalnidh
Kaur, Anjali Sinha, Mr Suraj Parab, Dr Sunny
Chaudhary, Dr Bhawna Shukla, Dr Rupal Shah