Evidence Based
Medicine: A Critical
Appraisal on
Therapeutics
BY: JOSE EDUARDO P. BELTRAN
FAMED RESIDENT, MENDERO MEDICAL CENTER
General Objective
To appraise a journal on the efficacy of Recombinant Influenza Vaccine
in Adults 50 Years of Age or Older.
CASE SCENARIO
A 55/M male patient come in to your clinic for his regular check-up and follow up.
Patient is heavily into health and is heavily invested in his wellness.
Patient is living alone and independently, with no co-morbids and contraindications
to vaccines.
Patient has been taking/having his annual flu vaccines c/o your clinic but he has
recently read an article regarding this new kind of flu vaccine, the recombinant
influenza vaccine.
He asks your opinion as his doctor regarding the benefits, efficacy and safety of the
recombinant vaccine compared to the inactivated influenza vaccines that you
normally use.
As a five-star/diamond physician, you decided to investigate/research on the matter.
EBM REVIEW:
ASK
FORMULATION OF PICOM
Adults 50 yrs old and older with no co-morbidities
P and contraindications to vaccines.
I
Recombinant influenza vaccine
C
Inactivated influenza vaccine
O
Preventing influenza – like illnesses
M
Randomized Clinical Trial
RESEARCH QUESTION
Are recombinant influenza vaccines better than inactivated influenza
vaccines in preventing influenza-like illnesses in adults 50 years old and
older?
Are recombinant influenza vaccines more effective than inactivated
influenza vaccines in preventing influenza-like illnesses in adults 50
years old and older?
Are recombinant influenza vaccines safer than inactivated influenza
vaccines in terms of adverse effects in adults 50 years old and older?
Acquire
ACQUISITION OF JOURNAL MATERIAL
ACQUISITION OF JOURNAL MATERIAL
RELEVANCE
Is the objective of the article similar to the clinical dilemma?
Yes
P- 50 yo adults and older with no co-
P- 55/M with no comorbids morbids and contraindications to
vaccines
I- recombinant influenza vaccine I- recombinant influenza vaccine
C- inactivated influenza vaccine C- ated influenza vaccine
O- effectiveness of recombinant
O- efficacy of the recombinant vaccine
influenza vaccine in preventing
vs influenza vaccine
influenza-like illnesses
M- Randomized Control Trial M- randomized Control Trial
RELEVANCE
Inclusion Criteria:
Adults 50 years of age or older who were living independently
without clinically significant acute illness
who were not receiving ongoing immunosuppressive therapy,
and who had no contraindications to trial vaccines
RELEVANCE
Exclusion Criteria:
Patients under 50 years old
Patients with comorbids
Patients with allergies to previous influenza vaccines.
Patient who showed signs of adverse effects after
getting the vaccine.
Appraisal
Was the assignment of patients to
treatment randomized?
Yes, the study proponents applied randomization via computer block
randomization in assigning patients to the treatment and placebo group
to avoid biases.
Was the follow up complete
Yes, all participants were accounted for at the end of the study
Intention to treat analysis was done
RIV4 IIV4
Drop-out 246/4474 253/4489
5.5% 5.64%
Were the patients analyzed in the group to which they were
randomized?
Yes
There was no crossing over treatment modalities
Were patients, their clinicians, and
study personnel “blind” to
treatment?
Yes, both groups chosen by random to receive their
respected vaccines and monitored for influenza like
illnesses. 25 participants were excluded from the
study due to the vaccines given cannot be verified.
Were the groups similar at the start
of the trial?
Yes, groups were similar at the start of the trial
except for the vaccines to be given. All participants
are 50 years old and above, living independently,
without clinically significant illnesses and
contraindications to the vaccines.
Applicability
Are the results applicable to my patient?
YES, the patient meets the inclusion criteria done in the study and he
also does not have anything that can include him on the exclusion list.
Is my treatment available in my setting?
YES, the recombinant influenza vaccine can be purchased (alongside a
prescription note) in some pharmacies in the Philippines.
Results and Conclusion
RESULTS
9003 patients were assessed to be eligible to join the study
4498 subjects were assigned to the experimental group
4505 subjects were assigned to the control group
Only 4303 subjects assigned to the experimental group were included
in the primary efficacy modified per protocol group. 195 subjects were
excluded for various reasons.
Only 4301 subjects assigned to the control group were included in the
primary efficacy modified per protocol group. 143 subjects were
excluded for various reasons.
In the experimental group, 96 patients developed influenza-like
illnesses during the course of the study accounting for 2.2% of the
population vaccinated with the Recombinant influenza virus vaccine.
In the control group, 138 patients developed influenza-like illnesses
during the course of the study accounting for 3.2% of the population
vaccinated with the inactivated influenza virus vaccine.
Terms & Definition
Relative Risk (RR) = risk of the outcome in the treatment group / risk
of the outcome in the control group.
Absolute Risk Reduction (ARR) = Absolute difference between the
proportion of control compared to the proportion treatment
Terms & Definition
Relative Risk Reduction (RRR) = risk of the outcome in the control
group - risk of the outcome in the treatment group.
Number Needed to Treat (NNT) = inverse of the ARR and is
calculated as 1 / ARR.
Validity of the study
2x2 table:
Yes No Total
Control 138 4163 4301
Treatment 96 4207 4303
N = 8604
How large is the treatment effect?
Rt = 96/4303 = 0.022
Rc = 138/4301 = 0.032
RR = Rt/Rc
0.022/0.032 = 0.6875
What is the relative risk reduction?
RRR = 1-RR
RRR = 1-0.6875 = .3125 or 31.25%
What is the absolute risk reduction?
ARR = Rc-Rt
0.032-0.022 = 0.01 or 1%
How precise is the estimate of the treatment
effect?
What were the confidence intervals or p values?
The researchers claimed confidence intervals of 95% and p values of p
= 0.006
What is the number needed to treat to prevent one adverse outcome or
produce one positive outcome?
NNT = 1/ARR
1/0.01 = 100
You need to inject 100 patients with the recombinant influenza vaccine to
produce 1 adverse effect/1 patient to present with influenza-like illness
CONCLUSION
In conclusion, this trial showed that RIV4, as compared with
IIV4, improved protection against laboratory-confirmed
influenza-like illness in adults 50 years of age or older. These
results occurred during an influenza season characterized by
widespread circulation of antigenically mismatched strains of
influenza A/H3N2.
Thank you!