Experimental Design RCT

7/30/2019 Experimental Design RCT

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EXPERIMENTAL DESIGN

Anton B. Darmawan


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Experimental

Quasi

ExperimentalRCT

Cross-sectional

Study

Descriptive

Restropective

in time

Prospective

in time

Observational

No Comparison

Group

Comparison

Group

Analytic

Outcome Exposure

Cause Disease

Cohort StudyCase Control

Study

RESEARCH DESIGN

Determine exposure &outcome at time of study


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Deciding whether the basic methods used were strong or weak

Strength Method

Strongest Randomized Clinical Trial

Cohort Study

Case-Control Study

Weakest Descriptive study

Case series


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Why run an experiment?

We typically have a particular cause in mind, and want to know if it has an

effect on an outcome, and if so, to what degree.

to determinecauseand effectrelationships


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Definitions

Experimental group (EG)

The group that is exposed to some sort of

a change or manipulation

Control group (CG)

A group not exposed to changes or

manipulations that serves as a baseline

comparison to the experimental group


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Cause and effect

What has to happen to establish a cause and effect relationship?

The cause must precede the effect

The cause must be related to the effect

We can find no other plausible alternative explanation for the effectother than the cause


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KEY Features of Experimental Designs

at least two groups of individuals / participants

random assignment to groups

an independent variable manipulated by the experimenter

dependent variable being measured


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RCT (randomized controlled clinical trial)

Randomized Randomisation

Controlled

Inclusion

Procedure

Outcome

Clinical Trial

Intervention

Vs. control group


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RCT

InvestigatorParticipants

Clinical Manoeuvre


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RCT

Quantitative Comparative Control Experiment

Measuring outcome

quantitatively

Comparing 2 or more

intervention

All variables are

Closely controlled


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Objectives of RCT

RCT

Drug patient population

Efficacy Safety


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TYPES OF EXPERIMENTAL DESIGN

RCTs according to whether the investigators and participants know which

intervention is being assessed

RCTs according to the number of participants

RCTs according to how the participants are exposed to the interventions

RCTs according to the aspects of the interventions they evaluate


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Efficacy and effectiveness trials

Explanatory and pragmatic trials

Phase I, II, and III trials


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Explanatory trial

address whether or not an intervention works

strict inclusion criteria that will produce highly homogeneous

study groups

E.g.: only patients aged between 40 and 50 years, with no

coexisting diseases

to include participants with heterogeneous characteristics,

similar to those seen by clinicians in their daily practice

tend to use active controls (that is, the new antihypertensive

drug vs a b-blocker), flexible regimens

pragmatic trials


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Efficacy

trialseffectiveness

trials

Ideal setting Real settingAll variables which

might influenceoutcome are closely

controlled

e.g.Severity of illness,

Compliance,Takin with without meal


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(RCT-parallel design) (RCT cross-over design)

(RCT factorial design)

DESIGN

RCTs according to how the participants are exposed to the interventions


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RCT-parallel design

Patient

eligible Random

Treatment B

OU

T

C

O

M

E

treatment A


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RCT cross-over design

Treatment B

Treatment A

washed

out

eligible

Patient

Treatment A

Random

Treatment B

O

U

T

CO

M

E


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RCT-factorial design

Patient

Randomeligible

OU

T

C

O

M

E

Tx B

tx A

tx A + tx B


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RCTs according to whether the investigators and participants know which intervention

is being assessed

Open trials

Triple and quadruple-blind trials

Double blind trials

Single blind trials


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Review of Steps for RCT Design

1. Select sample from population

2. Measure baseline variables

3. Randomize

4. Apply interventions & placebo

5. Follow-up cohorts

6. Measure outcomes


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1. Appropriate to the study question

2. Generalizable

3. Consider the outcome of interest

4. Allow adequate recruitment (study

patients you have access to)

Inclusion Criteria

1. Exclude patients with conditions that will

compete with the outcomes (e.g. likely

early death from cancer)

2. Contradictions to interventions

3. Difficult to comply

Exclusion Criteria

1. Select sample from population


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Example of eligibility criteria

Male and female outpatients

Clinically diagnosed as CAP

Chest-X-ray: pulmonary infiltrate or consolidation Showing at least three of the following symptom/sign:

nonproductive cough,

new onset of purulent sputum (productive cough), or

change in the character of their sputum;

sputum culture positive for gram-positive diplococci;

body temperature of 38 7C or more at least twice within a 24 h period; and/or

elevated leukocyte count (10x10 9 /l).

RCT: azithromycin vs clarithromycin for adult with mild to moderate CAP


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Example of exclusion criteria

Terminal illness

Any condition that could interfere with the attendance schedule Patient with the followings:

1. Likely to affect gastrointestinal absorption of antimicrobial activity

2. significant hepatic disease with a serum transaminase level more than three times the

upper limit of the normal range [serum glutamic oxalacetic transaminase (SGOT)

0.020.90 mM/s/; serum glutamic pryruvic transaminase (SGPT) 0.150.95 mM/s/l].3. hypersensitive to azithromycin, clarithromycin, or other macrolide

4. cyclosporine, theophylline, astemizole, terfenadine, or antacids


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Define potential important variables

Compare between study groups

Account for differences in study design or

analysis of results

2. Measure baseline variables


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RCT helicobacter pylori eradication in

NSAID user


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MEASUREMENT

Measurable

Objective

Accurate

Consistent


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RANDOMISATION

Objective measures

Equal chance for treatment or control group

Both groups are balanced

To prevent bias

Simple

randomisation

Random

permuted block

Random

permuted block

within strata

metode

3. Randomize


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Treatment Control

Drug formulation

therapeutic class

dosage

drug administration, frequency

duration of treatment

standard drug (DOC)

placebo

non fatal outcome/ disease

Treatment & Control group

4. Apply interventions & placebo


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Requirements: Test and Control Groups

Distinguishable.

Medically justifiable

Ethical base for each treatment

Compatible with health care needs

Either treatment acceptable

Reasonable doubt about efficacy

Benefits outweigh risks

Similar to real-world use

5. Follow-up cohorts


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RCT helicobacter pylori eradication in NSAID user


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BLINDING

Single blind Double blind Triple blind

Patient Patientdoctor/rater

PatientDoctor/rater

Statistician


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BLINDING

To prevent bias To prevent prediction effect

Objective measures

Reducing risk of overwhelming examination

Aims:


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Outcome Measures

Easy to diagnose and observe

Free of measurement or ascertainment

errors

Can be observed independent of

treatment assignment

Chosen before the start of data collection

Clinically relevant


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Survival time: early treatment vs. dead

tumor response: reduction of tumor size

Duration of treatment vs. treatment response

Patients improvement

Toxicity

e.g: cytostatics

MEASURING RESPONSE


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Severity of Illness

1. Difficult to measure

2. Disease specific vs. general3. Use validated instruments

4. Applicability to study population

5. Acknowledge limitations


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Advantages :

1. Is the only effective method known to control

selection bias

2. Is statistically efficient since equal numbers of

exposed and unexposed are studied.

3. Is theoritically atractive

Disadvantages :

1. Design and implementation of RCTs may be complex

and expensive.

2. It may be lack of representativeness

3. The problem of ethics

4. Sometime is impractical


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KOMPONEN UJI KLINIK

1. Seleksi/ pemilihan subjek

2. Rancangan

3. Perlakuan pengobatan yg diteliti &pembandingnya

4. Pengacakan perlakuan5. Besar sampel

6. Penyamaran/ blinding

7. Penilaian respon

8. Analisis data

9. Protokol uji klinik

10. Etika uji klinik


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QUASY EXPERIMENTAL

Untuk mengatasi keterbatasan penelitian

RCT

Teknis & akademik tidak direkomendasikan

utk mencari jawaban definitif thd manfaat

suatu intervensi

Solusi sementara


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1. The One-Group Posttest-Only design

Thd subyek yg telah mendapat terapi/

perlakuan diamati

Contoh:

- Colonostomy :

- lama penyembuhan- komplikasi post colonostomy

- Infeksi post colonostomy

Kelemahan:

- Tdk ada info pre op (pretest observation)

- Tdk ada kontrol


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2. The Posttest-Only design with

Nonequivalent Groups

Lebih baik dr nomor 1 pembanding

Pembanding tdk mendapat perlakuan

Contoh: Appendisitis appendiktomi

non appendiktomi Masalah etis

3. The One-Group Pretest-posttest Design

Before and after Observasi sebelum perlakuan perlakuan

observasi setelah perlakuan

Predictable


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Experimental Design RCT

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