Noel R.

Juban, MD, MSc

UP College of Medicine

Blinding
Matching
Random Sampling
Treatment Allocation
Randomization
Contamination
Co-Intervention
Withdrawals
Compliance/Adherence

Refers to a lack of knowledge of the identity of the study

treatment.
1.
2.
3.
4.

Open Label = no blind is used

Single Blind= the patient is unaware of which treatment is
being received, but the investigator has this information.
Double Blind = neither the patient nor the investigator is
aware of which treatment the patient is receiving.
Triple Blind

Refers to the pairing of one

or more controls to each
case on the basis of their
similarity with respect to
selected variables.

1.
2.

3.

Controls for confounding or confusing

variables.
Rule out some particular mechanism in
a postulated causal pathway between
exposure and disease.
Removal of bias; reduction of variance

1.

Stratified sampling
formation of subgroups by strata according
to a specified variable(s) and sampling
predetermined number of cases and a
predetermined number of controls within
each stratum prior to start of the study.

2. Frequency Matching= selection of

cases at random, with controls being
taken from corresponding subgroups in
proportion to the number of cases
prior start of the study.
Ex: If 30% of the cases were males of Northern European extraction
aged 60-64 years, then 30% of the controls would be taken to have similar
characteristics.

3. Post-stratification
4. Regression analysis

Technique whereby each sampling unit has the same probability of

being selected.
Basic Procedure:
1. Prepare a sampling frame or a list showing all the units from
which the sample is to be selected, arranged in any order (i.e,
obtain an up-to-date list of elderly people admitted in your
hospital)
2. Decide on the size of the sample.
3. Select the required number of units at random, by drawing lots
or (more conveniently) using a table of random numbers.

 the process of deciding

who (patient, subject,
unit) should get which
treatment.

The process of allocating patients (subjects,

units) to treatment or exposure of interest
according to an auditable random process,
wherein each unit has an equal probability of
being included.
This avoids bias, allows for blinding and provides
basis for standard methods of statistical
analysis.

1.
2.

3.

4.

Begin at any haphazardly chosen point.

Proceed in any predetermined direction and follow
this direction faithfully until your sample size is not
completed
Select sampling units by reading numbers off the
table until required numbers of units have been
selected.
Number not appearing in the list and numbers which
reappear are ignored.

Contamination = when the control subject

takes the test drug inadvertently (or vice
versa)
Co-intervention = when the study subject
takes another active drug inadvertently in
addition to the test or control drug.

The process of removing

a subject (patient,
etc.) from the
remaining portion of
the treatment
allocation.

Ineligibility
2. Non-compliance dropouts; still included in the
analysis
1.

a. Patient moved from area

b. Withdrawal of patients informed consent
c. Failure of patient to continue to meet criteria for

continuation in protocol
d. Decreased patient cooperation

3.

4.
5.

Losses to follow-up failure of patient to

return for an appointment or for a
specified number of appointments.
Competing events includes contamination
and co-intervention
Outliers extreme value significantly
different from remaining values; analyze
with and without

Inflate sample size

Example: drop-outs = 10%
n = n/(1-0.1) = n/0.9
e.g., n = 42, n = 46.6 = 47
2. Measure them anyway
3. Keep them in the group of original
allocation
1.

Adherence to dose and

dosing schedule, follow-up
schedule and restriction
from partaking/
participating in competing
events

1.

Simplify the demands of the protocol on

patients.

2.

Minimize the number and duration of

unpleasant or painful tests.

3.

Maintain relatively frequent contact with

patients, especially at emotionally or physically
difficult periods for the patient; contact the
patient prior to scheduled visits.

4.

Allow for flexible dosing regimens to deal with

adverse reactions, toxicity, and unanticipated
situations.

5.

Provide the patient with appropriate information

on the study.

6.

Avoid making the patient feel guilty about poor

compliance and provide positive physician-patient
relationship.

7.

Establish a therapeutic goal in conjunction with the

patient and assess the patients progress towards the
goal.

8.

Plan patient visits at a mutually convenient time and

insure that the patient has a minimal delay in waiting
to see the physician or staff.

9.

Allow for and encourage patients to participate in

their own care (e.g., with self-monitoring of their
disease and treatment).

10. Involve the patients spouse, family, or support

group in the clinical study.

Blinding
Matching
Random Sampling
Treatment Allocation
Randomization
Contamination
Co-Intervention
Withdrawals
Compliance/Adherence