Kritisi Artikel Randomized Control Trial dengan jurnal

Pembrolizumab versus docetaxel for previously treated,

PD-L1-positive, advanced non-small-cell lung cancer
(KEYNOTE-010): a randomised controlled trial

Kelompok 9
Sudarmanto T.B.P. (1720343863)
Vianda Ekta Putri (1720343864)
Widyaningrum (1720343865)
Yesika Dwiastuti Kurniawan (1720343866)
Yoga Adi Sunaryo (1720343867)
1a. R- Was the assignment of patients to treatments randomised?
What is best? Where do I find the information?
Centralised computer randomisation is ideal and The Methods should tell you how patients were
often used in multi-centred trials. Smaller trials allocated to groups and whether or not
may use an independent person (e.g, the hospital randomisation was concealed.
pharmacy) to “police” the randomization.

This paper: Yes √ No Unclear

Comment:
From Method :
Pada jurnal hal. 3 bab Metode sub bab Randomisation and Masking paragraf 1.
Pasien secara di tugaskan secara acak (1:1:1) dengan sistem pusat suara interaktif untuk
menerima pemvrolizumab 2 mg/kg secara intravena lebih dari 30 menit selama 3 minggu, 10
mg/kg secara intravena lebih dari 30 menit selama 3 minggu, atau docetaxel 75 mg/m2 secara
intravena lebih dari 1 jam selama 3 minggu. Pembagian jadwal diperoleh dari sistem vendor
menggunakan generator daftar acak terkomputerisasi

Patients were randomly assigned (1:1:1) with a central interactive voice-response system to
receive pembrolizumab 2 mg/kg intravenously over 30 min every 3 weeks, 10 mg/kg
intravenously over 30 min every 3 weeks, or docetaxel 75 mg/m² intravenously over 1 h every 3
weeks. The allocation schedule was generated by the system vendor using a computerised
randomised list generator.
 1b. R- Were the groups similar at the start of the trial?
What is best?
If the randomisation process worked (that is, achieved comparable groups) the
groups should be similar. The more similar the groups the better it is.
There should be some indication of whether differences between groups are
statistically significant (ie. p values).

This paper: Yes √ No Unclear

Comment:
Pada jurnal hal. 7 bab Results paragraf 2.
Karakteristik dasar yang diharapkan untuk pasien dengan sel kanker paru-paru non-
small-cell tingak lanjut dan diseimbangkan antara kelompok (tabel 1). Karakteristik
awal serupa di 442 pasien yang memiliki PD-L1 dengan proporsi tumor 50% atau lebih
besar (Tabel 1)

Baseline characteristics were as expected for patients with advanced non-small-cell

lung cancer and were balanced between groups. Baseline characteristics were similar
in the 442 patients who had a PD-L1 tumour proportion score of 50% or greater (Table
1)
2a. A – Aside from the allocated treatment, were groups treated
equally?
What is best?
Apart from the intervention the patients in the different groups should be treated the same,
eg., additional treatments or tests.
This paper: Yes √ No  Unclear 
Comment:
Pada tabel 1 hal. 4 dan bab Results hal. 6 paragraf 1
 2b. A – Were all patients who entered the trial accounted for? – and were
they analysed in the groups to which they were randomised?
What is best? Where do I find the information?
Losses to follow-up should be minimal – The Results section should say how many
preferably less than 20%. However, if few patients were randomised (eg., Baseline
patients have the outcome of interest, then even Characteristics table) and how many patients
small losses to follow-up can bias the results. were actually included in the analysis. You will
Patients should also be analysed in the groups need to read the results section to clarify the
to which they were randomised – ‘intention-to- number and reason for losses to follow-up.
treat analysis’.

This paper: Yes √ No  Unclear 

Pada bab Results hal. 6 paragraf 1

2699-2222 = 477

x 100% = 17,67% < 20%

3. M - Were measures objective or were the patients and
clinicians kept “blind” to which treatment was being received?
What is best?
It is ideal if the study is ‘double-blinded’ – that is, both patients and investigators are
unaware of treatment allocation. If the outcome is objective (eg., death) then blinding
is less critical. If the outcome is subjective (eg., symptoms or function) then blinding
of the outcome assessor is critical.

This paper: Yes  No  Unclear 

Comment: the measurement were objective
Pada jurnal bab Methods sub bab Randomisation and masking paragaraf 2 dan bagian Abstrak bab
Methods
 Perhitungan RR
• All patient
– Jumlah awal pasien : 1034
• Pasien meninggal : 521
• Pembrolizumab 2 mg/kg = 172 (50%) dari 344
172/344 = 0.5/0.5 = 1

• Pembrolizumab 10 mg/kg = 156 (45%) dari 346

156/346 = 0.45/0.55 = 0.82

• Docetaxel = 193 (56%) dari 343

193/343 = 0.56/0.44 = 1.27

• Patient PD-L1 50%

– Jumlah awal pasien = 442
• Pasien meninggal : 204
• Pembrolizumab 2 mg/kg = 58 (42%) dari 139
58/139 = 0.42/0.58 = 0.72

• Pembrolizumab 10 mg/kg = 60 (40%) dari 151

60/151 = 0.4/0.6 = 0.67

• Docetaxel = 86 (57%) dari 152

86/152 = 0.57/0.43 = 1.32

KESIMPULAN : Pembrolizumab 10 mg/kg memiliki nilai RR 0.82 dan 0.67 < 1 sehingga menurunkan resiko dari outcome/
hasil
Perhitungan ARR

• All patient
• Pembrolizumab 2 mg/kg = 0.5 – 0.5 = 0
• Pembrolizumab 10 mg/kg = 0.55 – 0.45 = 0.1
• Docetaxel = 0.44 – 0.56 = -0.12

• Patient PD-L1 50%

• Pembrolizumab 2 mg/kg = 0.58 – 0.42 = 0.16
• Pembrolizumab 10 mg/kg = 0.6 – 0.4 = 0.2
• Docetaxel = 0.43 – 0.57 = -0.14

KESIMPULAN = Pembrolizumab 10 mg/kg untuk All Patient memiliki nilai

ARR terebsar 0.1 sehingga memiliki keuntungan pengobatan sebesar
0.1 atau 10% yang dapat menurunkan resiko kematian, dan untuk
Patient PD-L1 50% nilai ARR terbesar 0.2 sehingga memiliki keuntungan
pengobatan sebesar 20%
 Perhitungan
RRR

All patient

• Pembrolizumab 2 mg/kg = 1 – 1 = 0; 0%
• Pembrolizumab 10 mg/kg = 1 – 0.82 = 0.18 x 100% = 18%
• Docetaxel = 1 – 1.27 = -0.27

Patient PD-L1 50%

• Pembrolizumab 2 mg/kg = 1 – 0.72 = 0.28 x 100% = 28%
• Pembrolizumab 10 mg/kg = 1 – 0.67 =0.33 X 100% = 33%
• Docetaxel = 1 – 1.32 = -0.32

KESIMPULAN = Pembrolizumab 10 mg/kg memiliki nilai RRR paling

tinggi 18% dan 33%. Pada All patient, menurunkan resiko kematian
18%, pada Patient PD-L1 50%, menurunkan resiko kematian 33%
Perhitungan NNT

All patient
• Pembrolizumab 2 mg/kg = 1 /0 = 0
• Pembrolizumab 10 mg/kg = 1 / 0.1 = 10
• Docetaxel = 1/ -0.12 = -8.33

Patient PD-L1 50%

• Pembrolizumab 2 mg/kg = 1 / 0.16 = 6.25
• Pembrolizumab 10 mg/kg =1 / 0.2 = 5
• Docetaxel = 1 / -0.14 = -7.14

KESIMPULAN = Pada All Patient, digunakan pembrolizumab 10 mg/kg untuk

pengobatan 10 orang selama 2 tahun untuk mencegah 1 kematian.
Pada Patient PD-L1 50%, digunakan pembrolizumab 2 mg/kg untuk
pengobatan 6 orang selama 2 tahun untuk mencegah 1 kematian.
Jawaban :
Pasien tidak berbeda dibandingkan dengan pasien dalam penelitian.
Berdasarkan table diatas sampling pasien pada penelitian memiliki
karakteristik yang sama dengan pasiensaya, hal ini dibuktikan dengan hasil
base line karakteristik yang menunjukkan adanya ras Asia.
 Penelitian ini layak diaplikasikan ke dalam terapi pengobatan pasien di
Indonesia karena didasarkan pada status perokok (smoking status) yang sama.
Pengobatan ini mempunyai potensi manfaat pengobatan yang lebih
besar dibandingkan dengan potensi kerugiannya. Hal ini dibuktikan dari nilai
RR, ARR, RRR, dan NNT,dan juga dilihat dari efek merugikan yang lebih
kecil/minimal.