EXPERIMENTAL STUDIES

RECAP:
Types of study designs:

- Affords the most control over the study situation

1. Observational: observing participants. You cannot

control participants.

- Enables the researcher to isolate the observed effect

of the exposure or intervention.

A. Descriptive
1. A .1. Case report/study
- 1 case/disease
1. A .2.case series
-many patients but same cases. If you are
Looking for the commonalities and differences of
Cases.
1. A .3. Ecologic study
1. A .4. Cross sectional

- Researcher chooses a study population without the

outcome (like cohort) usually the outcome is that the
disease will diminished or the patient will have no
disease.
- eg. Occurrence of COPD with the smokers and nonsmokers. The characteristics of each group study are
equal. And the only difference is that other group are
smokers and the other is not.

B. Analytic-observational:
b. 1 case control:
- Case: patients who have the disease
Control: patients without the disease
Put back in time for the exposure. It is how many
Case and control patients are exposed to the
Diseases.
b. 2 cohort: 2 groups of people (exposed and
Unexposed, with factor or without factor)

- Assigns the subjects into two groups by scientific

technique.
- introduces the intervention to one group and
withhold it from the other.
- sabihin natin 2 groups of people may hypertension. 1
group is given an intervention and the other group not
given intervention. When you assigned participants to
the groups you do it by a scientific technique
(randomization)
two types:

eg. Smokers and non-smokers. Without COPD then

follow-up over period of time. Then identifying
incidence of COPD among smokers and non-smokers
sample.
We compare the incidence of the disease among the
smokers vs the non-smokers and then look at the risk
ratio (risk of acquiring disease of smokers vs nonsmokers)
2. Experimental
Experimental studies
- Called interventional study because we give an
intervention. You intervene.
- involves intentional change with some characteristics
of the study participants.
- eg. Introduction of a drug. You give an intervention.
- Provides the strongest evidence of causal relationship
of all the study designs compared to observational
studies.

True experiments scientific technique, there is

randomization in the allocation of treatment (assign the
treatment to study part at random)
Quasi- experiments- no randomization
*random sampling and randomization is different.
Randomization is random allocation of treatment. You
assign treatment to participants at random. Like for
example kayong lahat may sakit, HD. Each of you are
assigned to take drugs by picking from the box with 2
different kinds of drugs. Random sampling means
pagkuha ng sample at random. For example 100 kayo I
will pick only 70 from you at random.
1. True experiments:
+ Randomized controlled trials
- Participants are randomly assigned to two groups,
usually 1 study grp (receive treatment) and 1 control
grp (no treatment).
- The study group receives a treatment, the control grp
does not.
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EXPERIMENTAL STUDIES
Before the control group receives placebo for the
treatment but now a days it is not given anymore
because it is unethical to give a medicine that will not
cure the patient. Only those disease that are less conflict
or less extensive could have the placebo. Give a drug to
the study group and give placebo to the control group
with both groups having same lifestyle modification.
Giving of placebo is justified.

- More commonly known as randomized clinical trial

- normally conducted in 4 phases (1-4)
- each phase is treated as separate clinical trial
- drug discovery, drug development.
Drug-development process will normally
proceed through all four phases over many
years.
Phases of clinical trial:

- Treatment can be an experimental preventive or

therapeutic procedure, maneuver or intervention.
- Results are assessed by comparison of the outcome in
the study group and in the control group.
- With randomization you ensure the characteristics of
the two groups are equal. When you assign participants
at randomization you ensure that the participants in the
2 groups are of equal characteristics. That will only
happened if the sample size is very large.
Example: effect of a drug VS placebo
Divide the study participants into two groups (1 group
with placebo and the other is the experimental drug)
suppose that people given with the drug are younger
than people receiving the placebo. The result shows that
the study group receiving the drug has more number of
cured patients as to the group of placebo who has no
one or less number of cured patients. Will you say that
the drug is effective? No, because the participants who
took the drug are younger than that of those who took
the placebo. For us to say that the drug is effective over
the placebo then the characteristics of the participants
of the 2 groups should equal.
Randomized controlled trials:
1. Preventive clinical trial: used to test the
effectiveness of a preventive measure. Eg. Vaccines
2. Intervention clinical trial: manages risk factors to
prevent occurrence of disease for which a factor is
known to cause. Eg. Smoking cessation program.
3. Therapeutic clinical trial: used to test the
effectiveness of treatment drugs and procedures to
arrest the disease problem. Eg. Drugs to cure the
disease.
Therapeutic clinical trial:

Phase1:
- A single sub therapeutic doses of the study drug are
given to a small no subjects (10-15)
-normally given to normal or healthy subjects/patients.
Usually males are the subject.
- Gathers preliminary data on the drugs
pharmacodynamics (what the drugs does to the body)
and pharmacokinetics (what the body does to the
drugs)
- documents the absorption, distribution, metabolism,
and excretion (ADME) of the drug.
-not randomized controlled
Phase 2:
- tested with as small group of people 20-80 grp of
people to evaluate the safety of drug.
- determine safe dosage ranges and identifies side
effects of drug.
- A drugs side effects could be subtle or long term or
may only happen with a few of people.
-thus phase 2 trials are not expected to identify all side
effects. Because it has only small group of people.
-not randomized controlled
Phase 3:
-aimed to establishing the efficacy of the drug. Usually
against placebo
- tested with a large group of people (100-300) to see if
it is effective and to further evaluate its safety.
-the gradual increase in sample size allows for less
common side to be progressively sought. (In larger
subjects, the former few seen side effects will be shown
in much larger side effects).
- More commonly studied as a Randomized Controlled
Clinical Trial
-Randomization is done in phase 3. The study group
receives the new treatment or the drug. The control
group receives an alternative treatment more
commonly a placebo.
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EXPERIMENTAL STUDIES
-The control group may also receive a standard
treatment
- blinding is usually done to prevent bias in the
reporting of outcome
Single blind: only the subject are unaware of the
treatment they receive.
*if the signs and symptoms of the subject is subjective.
*in the informed consent, it should be indicated that
they can either receive the placebo or the treatment
drug. Except that the subjects do not know the
treatment that they will be having.

Double blind: both the subject and the

investigators or unaware of the treatment the subject
are getting.
*done when the examinations of the outcome is
subjective, then that is the time that you blind the
investigators.
Phase 4:
-PMS post marketing surveillance/studies
- serves as final confirmation of safety and efficacy
- tested with large groups of people (1,000-3,000) to
confirm is effectiveness, monitor SE, Compare it to
commonly used treatments and collect information that
will allow it to be used safely.
*involve drugs that already in the market. Drugs
approved in the country. We collect information about
the marketed drugs and its efficacy.

2. Quasi-experimental design:
- No randomization in allocation of treatment
-most community trials are done using this type of
study design. (you cannot do randomization in
community trial study).
Example: community trial
- Test of efficacy of fluoridation of drinking water in
preventing tooth decay

-Two comparable cities in New York State in 1940s

(Newburgh and Kingston) were compared for the
occurrence of tooth decay and related dental problems
in children
-Newburgh received fluoride for about one decade and
Kingston did not.
-In Newburgh the incidence of dental problems
decreased by about a half compared to the period prior
to fluoridation
-In Kingston dental problems slightly increased
-This particular study utilized a quasi-experimental
study since subjects (cities) were assigned the
treatment arbitrarily and not randomly.
Other classification of clinical trials
A. by the study design:
Parallel group- each participants is randomly assigned
to a group, a d all the participants in the grp either
receive or do not receive intervention. (Very much the
same with the randomized controlled trial)
Cross over- over time, each participant receives (or
does not receive) an intervention in a random
sequence. In exchange.
*1 group will receive the study drug, that randomized
and the other group will receive placebo. Then you look
out at the outcome. Compare the outcome. Wash out
period (wash out the drug that are given para mawala
sa effect sa system ng subject. Normally 5-7x the halflife of the drug). Then you crossover meaning you have
grp A that receive the study drug ngayon receives the
placebo. The group B that receives the placebo now will
receive the study drug.
B. by outcome:
Explanatory or pragmatic
Explanatory RCTs - test efficacy (strict inclusion and
exclusion criteria) in a research setting with highly
selected participants and under highly controlled
conditions.
Pragmantic RCTs - test effectiveness in everyday
practice with relatively unselected participants and
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EXPERIMENTAL STUDIES
under flexible conditions; in this way, pragmatic RCTs
can "inform decisions about practice.
*not much strict rules in inclusion and exclusion criteria.
C. by hypothesis:
- Categorized as Superior trials or noninferiorty trials
Superiority trials experimental drug is superior to
the placebo. *if you want to test a drug over a placebo
more often than not it is a superiority trial.
-Most RCTs are superiority trials, in which one
intervention is hypothesized to be superior to another
Non-inferiority Trials - which determines whether a
new treatment is no worse than a reference treatment
(Standard drug).
*if you want to test an experimental drug (less
expensive than the standard drug) whether it is a
comparable with the standard drug.
Clinical trials (Randomized):
- can be likened to a cohort study (2grps of people. 1 is
exposed and other 1 unexposed. Both no
outcome/disease. Follow up ilan sa mga groups ang may
sakit and ilan ang wala. And compare.)
*unlike in cohort both groups have outcome/disease.
Giving 2 different intervention (placebo or study drug)
then follow up. Ilan ang may sakin parin with the groups
then that is youre RISK RATIO.
- Measures called risk ration (RR), absolute risk
reduction (ARR), relative risk reduction (RRR) and
numbers needed to treat (NTT)
- Calculation for RR is the same as that for the cohort
study.
Disease

No Disease

Exposed

Unexposed

a- with intervention still with disease

b- with intervention, did not have the disease

(gumaling)
c- placebo, with disease
d- placebo no disease
EER experimental event rate: no of events/disease in
the experimental grp
EER = A/A+B
EER = with intervention but with disease/binigyan ng
study drug

CER control event rate: no of events /dse crisk in the

control grp
CER= C/C+D
CER= with placebo but with disease/total with placebo
or no intervention

RR risk ratio of the disease in the experimental grp

(EER) and the risk in the control grp (CER)
RR= EER/CER
If RR is 1 means that the treatment has no effect.
If RR is less than 1: effective
If RR is greater than 1: mas lumala yung sakit. For
cohort study. E.g. in smoking (smoker vs non-smoker).
*example:
With drug= 100
With disease= 40
EER = 40/100
= .4
With placebo = 100
With disease = 40
CER= 40/100
=.4
RR= EER/CER
= 1 (not effective)

Absolute Risk reduction ARR: risk difference is the

difference in the event rates for the EER and CER.
ARR= CER-EER
*reduction in the risk of the disease.
Example:
EER = .2
CER=.4
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ARR= .4 - .2
= .2 (20% reduction of disease by the drug)

Relative risk reduction RRR:

Relative Risk Reduction - the difference in event
rates expressed in a proportional or relative
manner, in relation to the control event rate.
Often more impressive than the risk difference.
The lower the event rate in the control group,
the larger the difference between relative risk
reduction and risk difference.
RRR= CER-EER/CER
= ARR/CER
RRR= .2/.4
= .5 X 100
RRR = 50%
Number needed to treat NNT;
- the number of patients who would have to receive the
treatment for one of them to benefit.
- Calculated as 1 divided by the absolute risk
reduction.
*no. of people that will have to have the treatment in
order to one of them will benefit.
*If the number to treat is high, the drug is not good.
1/ARR
* The lower the number the better the drug is.
*Ideal number
Acne
needed to treat: 1.
Treatment
Yes
No
Example:
Oxygenated
A study was
Water
40
60
made comparing
the efficacy of an
Placebo
50
50
oxygenated water
in treating moderate to severe acne. Results of
the study are shown in the table below.
The control event rate is
The experimental event rate is

The relative risk = 0.80

The Absolute risk reduction = 0.10
The numbers needed to treat (NNT) = 10

INTERPRETATION:
If the EER is lower than the CER, the ratio is < 1,
the treatment favors the disease.
If the 95% Confidence Interval of the measure
excludes the null value, (1), the relationship is
statistically significant.
If the numerator (EER) is equal to the
denominator (CER) the RR is equal to 1, no
relatiohnsip or no effect/ NULL.
If EER is higher then CER and the RR is greater
than 1, the treament is dangerous to the
disease.
In cohort study:the exposure is the risk factor of
the disease.
If the EER is lower than the CER, RR is less than
1 treatment favors the disease or beneficial
treatment.
Not all beneficial are significant. To know
whether it is significantly benefical you look at
the 95% confidence interval (lower limit and
upper limit). If the upper limit and the lower
limit excludes 1 (null value) then it is
significantly lower than 1, and is significantly
beneficial. If 95% confidence interval excludes 1
or the null value then it is significantly highers
than 1.
Example: lower limit = .2 upper limit is .8
It excludes 1 so it is significantly lower
than 1.
Null value/ line of unity

CER = 0.50
EER = 0.40
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EXPERIMENTAL STUDIES

RISK RATIO / Sample size

95% CONFIDENCE INTERVAL
Does not significantly favor treatment because it
crossed the line of unity.

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