Tutorial CRP Therapy 2

Kelompok B1
 Skenario
• Seorang dokter di IGD menerima pasien seorang laki-laki,
umur 40 tahun yang didiagnosa menderita pneumonia. Untuk
pilihan antibiotik yang diberikan dokter tersebut
mempertimbangkan pemberian Biapenem (obat baru yang
dianggap lebih unggul) dibandingkan pemberian meropenem
sebagai sebagai obat yang sudah digunakan selama ini.
• Bagaimana pendapat anda, apakah sudah tepat keputusan
tersebut?
• P : Pneumonia
• I : Biapenem
• C : Meropenem
• O : Clinical efficacy
 Critical Appraisal
Three main aspects to be appraised:

1. Validity :
Valid (Closeness to the truth)  in the methodology
section

2. Importance :
Important (usefulness)  in the results section

3. Applicability:
Applicable (can be applied in clinical practice)  in the
discussion section
Therapy Worksheet
Citation:

Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments
randomized?
Was the randomization list concealed?
Was follow-up of patients sufficiently long
and complete?

Were all patients analyzed in the groups to

which they were randomized?

Were patients, clinicians, and study personnel

kept “blind” to treatment?
Were the groups treated equally, apart from
the experimental treatment?

Were the groups similar at the start of the

trial apart from the experimental therapy?
Therapy Worksheet
Are the valid results of this randomized trial important?
What is the magnitude of the treatment
effect?
How precise is the estimate of the treatment
effect?
Sample calculation
Relative risk Absolute risk Number
reduction reduction needed to
(RRR) (ARR) treat (NNT)
CER EER CER − EER CER − EER 1/ARR

CER

95% CI
Therapy Worksheet
Can you apply this valid, important evidence about therapy in
caring for your patient?
Do these results apply to our patient?
Is our patient so different from those in the
study that its results cannot apply?
Is the treatment feasible in our setting?
What are our patient’s potential benefits and harms from the therapy?
Method I : f Risk of the outcome in our patient, relative to
patients in the trial.
Expressed as a decimal:______
NNT/f=______/______=______

(NNT for patients like ours)

Method II : 1/(PEER × RRR) Our patient’s expected event rate if they
received the control treatment (PEER)
=______
1/(PEER × RRR)=1/________=______

(NNT for patients like ours)

Are our patient’s values and preferences satisfied by the regimen and its consequences?

Do we and our patient have a clear

assessment of their values and preferences?

Are they met by this regimen and its

consequences?
Was the assignment of patients to treatments
randomized?
• Yes
• Page 996
• Material and methods
• A stratified block randomization method was used. A
computer generated randomization schedule was used to
provide randomization number and medication-kit number
for each patient. The patients were randomized to receive
biapenem or meropenem at a 1:1 ratio.
Was the randomization list concealed?

• Yes
• Page 996
• Mariterial and methods
• Patients were randomly assigned to receive biapenem or
meropenem as stratified by the Center, through consecutively
opening sealed computer-generated envelopes.
Was follow-up of patients sufficiently long and
complete?
• Yes
• Page 996
• Material and methods
• Duration of therapy was 7 to 14 days, according to their disease
severities.
• Page 997
• Results
• Only 132 cases in each group were included in the clinical efficacy
assessment because four patients in each group could not be assessed
due to various reasons.
• Lost to follow up = 8/272 = 0,029 or 2,9%
• The follow up of patients is complete,no more loss to follow up >20%
Were all patients analyzed in the groups to
which they were randomized?
• Yes, intetion to treat analysis
• Page 997
• Results
• All 136 cases in each group were included in the ITT analysis
Were patients, clinicians, and study personnel
kept “blind” to treatment?
• No
• The study was not double-blinded, due to the reason that
meropenem should be given three times daily while
biapenem administered twice daily.
• Page 996
• Material and methods
• Biapenem (300 mg, every 12 h) or meropenem (500 mg, every
8 h) was administrated intravenously and the infusion time
was 1 h.
Were the groups treated equally, apart from the
experimental treatment?
• Yes
• Page 996
• Material and methods
• Biapenem (300 mg, every 12 h) or meropenem (500 mg, every
8 h) was administrated intravenously and the infusion time
was 1 h. For severe infections, the dose was doubled. The
duration of therapy was 7 to 14 days, according to their
disease severities.
Were the groups similar at the start of the trial
apart from the experimental therapy?
• Yes, inclusion and exclusion criteria
• Page 996
• Material and methods
• Inclusion criteria : inpatients and a few outpatients aged 18 to
70 yr, regardless of their gender and ethnicity, who were
diagnosed of either lower respiratory tract infections or UTIs
caused by bacteria were eligible for the study and continue...
• Exclusion criteria : patients with any of the following
conditions were excluded: history of hypersensitivity to β-
lactams; serum creatinine level above the upper limit of the
normal range or creatinine clearance <50 ml/min and
continue...
Therapy Worksheet
Citation:

Are the results of this single preventive or therapeutic trial valid?

Was the assignment of patients to treatments Yes
randomized?
Was the randomization list concealed? Yes
Was follow-up of patients sufficiently long Yes
and complete?

Were all patients analyzed in the groups to Yes

which they were randomized?

Were patients, clinicians, and study personnel No

kept “blind” to treatment?
Were the groups treated equally, apart from Yes
the experimental treatment?

Were the groups similar at the start of the Yes

trial apart from the experimental therapy?
What is the magnitude of the treatment effect?
• CER, EER, RRR, ARR, NNT
Sample Calculation
• Outcome : Clinical efficacy
Outcome Yes No Total
Control drug
124 12 136
(Meropenem)
Experimental drug
125 11 136
(Biapenem)

• CER (Control Event Rate)

• CER = 12/136 = 0,088 or 8,8 %
• No clinical efficacy occurred among 8,8 % of patients
randomized to control group
• EER (Experimental Event Rate)
• EER = 11/136 = 0,08 or 8 %
• No clinical efficacy occurred among 8 % of patients
randomized to experimental group
Sample Calculation
• RRR (Relative Risk Reduction)
• RRR = CER – EER/CER = 0,088-0,08/0,088 = 0,09 or 9%
• Patients given the experimental treatment reducing risk in no
clinical efficacy up to 9% than control treatment
• ARR (Absolute Risk Reduction)
• ARR = CER – EER = 8,8% - 8% = 0,8%
• No clinical efficacy between control treatment and
experimental treatment up to 34%
• NNT (Number Need to Treat)
• NNT = 1/ARR = 1/0,8% = 125
• We need to treat 125 people with a experimental treatment
(rather than control) to prevent one additional person from
no clinical efficacy
Are the valid results of this randomized trial important?
What is the magnitude of the treatment effect? CER, EER, RRR, ARR and NNT

How precise is the estimate of the treatment CI

effect?

Sample calculation
Non-compliance in addiction Relative risk Absolute risk Number needed to
treatment reduction (RRR) reduction (ARR) treat (NNT)

CER − EER
CER EER CER − EER 1/ARR
CER

8,8% 8% 9% 0,8% 125

95% CI
Therapy Worksheet
Can you apply this valid, important evidence about therapy in
caring for your patient?
Do these results apply to our patient?
Is our patient so different from those in the No
study that its results cannot apply?
Is the treatment feasible in our setting? Yes

What are our patient’s potential benefits and harms from the therapy?
Method I : f Risk of the outcome in our patient, relative to
patients in the trial.
Expressed as a decimal:______
NNT/f=125/1=125

(NNT for patients like ours)

Method II : 1/(PEER × RRR) Our patient’s expected event rate if they
received the control treatment (PEER)
=______
1/(PEER × RRR)=1/________=______

(NNT for patients like ours)

Are our patient’s values and preferences satisfied by the regimen and its consequences?

Do we and our patient have a clear Yes

assessment of their values and preferences?

Are they met by this regimen and its Yes

consequences?
THANK YOU