Control and Blinding

Kamalia Layal
 Control
• Control group
No active treatment
placebo
Blinded

• No cointervention (medication, therapies,

behaviour) reduce outcome of interest
 Purpose of Control Group

To allow discrimination of patient outcomes

caused by experimental intervention from
those caused by other factors
 Considerations in Choice of
Control Group
• Available standard therapies

• Methodological consideration

• Ethical considerations
 Type of Controls
Classified based on:
• Type of treatment used
• Method of determining who will be in the
control group
Type of controls:
1. Placebo concurrent control
2. No treatment concurrent control
3. Dose response concurrent control
4. Active (positive) concurrent control
5. External control (historical control)
6. Multiple control group

Can use more than one type of control, each type of control
group is appropiate in some sircumstances but non is
adequate in every situation
 Placebo concurrent control
 Subject
 Active treatment
 Treatment doesn’t cotain test drug
 Almost double blind placebo effect,
investigator expectation
 Showing a difference of efectiveness and
safety
 The use of a placebo doesn’t imply that the
control group untreated (placebo or a
common standard therapy)
 No treatment concurrent control
 Subject
 Test treatment
 No treatment
 Unblinded
 Suitable only when it’s difficult or impossible
to double blind
 Dose response concurrent control
 Subjects are randomly assigned to two or
more dosage groups, with or without placebo
group
 To establish the relation between dose and
efficacy or adverse effect
 Advantages to use a placebo (zero-dose)
 Avoid interpretable study
 Can estimate of the total pharmacologically
mediated effect of treatment
 Permite to use smaller sample size
Active (positive) concurrent control
 Comparing new drug with a known active drug
(new drug is believed to be a good alternative to
standard care)
 Usually double blind
 To show a difference between the two
treatments or to show noninferiority or
equivalence
 Should be: drug acceptable, using fixed-dose,
and has same indication
External control (historical control)
• Compares a group of subjects receiving the
test treatment with a group of patients
external to the study
• External group can be a group of patients
treated an earlier time (historical control) or a
group treated during the same time period
but in another setting
Con’t…

Rapid, inexpensive, good for initial testing of

new treatments
Two sources of historical control data:
 Literature
 Data base
Vulnerable to bias
Con’t…

Changes in outcome over time may come from

change in:
 underlying patient populations
 criteria for selecting patients
 patient care and management peripheral
to treatment
 diagnostic or evaluating criteria
 quality of data available
Con’t…
 Tend to exaggerate the value of a new
treatment
 Literature controls particularly poor
 Multiple control group
Both an Active and Placebo
Multiple doses of test drug and of an active
control
 Blinding
• Keeping the identity of treatment
assignments (subject, investigator, and
other)
• Purpose: bias reduction
Prevents bias due to use of
cointervention, biased ascertainment and
adjudication of outcome
 ICH Guidelines
Blinding can prevent/minimize source of bias:
– Patients may be more likely to report benefit on
active drug.
– Observers may be more likely to report favorable
outcomes and adverse on active drug.
– Knowledge of treatment may affect vigor of follow-
up.
– Knowledge of treatment could affect decision to
leave in the analysis.
– Knowledge of treatment could affect choice of
statistical analysis.
Type of blinding
1. Open label study

2. Single-blind study

3. Double-blind study

4. Double-dummy design
 Unintentional Ublinding
• Efek suatu obat yg diteliti diket--digunakan
plasebo yg dapat menghasilkan efek samping
yg sama  plasebo aktif

• Obat yg diteliti memerlukan penyesuaian

dosis--- penyesuaian plasebo
 Plasebo
Syarat:
• Belum ada terapi standar untuk penyakit yang
sedang diteliti
• Lebih aman pada penyakit yang tidak parah
• Hasil pengobatan bersifat subjektif (subjective
outcome)– suggestion
pada objective outcome menghindari
perlakuan berbeda pada subjek
Tujuan
• Peneliti: menghindari perlakuan/penilaian yg
menguntungkan terhadap kel yang diberi obat
yg diteliti
• Subjek: menghindarkan efek plasebo,
diharapkan terjadi seimabang antara
kelompok
Efek plasebo: perasaan mengalami suatu efek
padahal efek tersebut tidak ada
Terima Kasih