Experimental Designs

Dwi Indria Anggraini Medical Faculty Lampung University

RESEARCH DESIGN
OBSERVATIONAL EXPERIMENTAL

Descriptive
Exposures & outcomes are measured at the same time

Analytic
Outcome Cause

RCT
Exposure Disease

Quasi experimental

Case report Case series

Crosssectional
Cohort Study

Case Control Study

Why run an experiment?

to determine cause and effect relationships

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.

Definitions
Independent Variables (IVs)
What is being manipulated or changed by the researcher, e.g., hypertension, hyperlipidemia, smoking, life style

Dependent Variables (DVs)

The outcome variable the researcher is interested in, e.g., stroke, lung cancer, cured, controlled blood pressure

Definitions
All variables other than the IVs that may have caused the DVs that the researcher didnt take into consideration in the design E.g.: age, income, geographic location, competitors actions, weather conditions, world events, time of day, consumers mood, etc.

Extraneous Variables

Terminology: Experiment
An investigation in which

the investigator applies some treatments to experimental units and

then observes the effect of the treatments on the experimental units by measuring one or more response variables.

Experimental Study

Definitions
Experimental group (EG) Control group (CG)

The group that is exposed to some sort of a change or manipulation in the IV

A group not exposed to changes or manipulations that serves as a baseline comparison to the experimental group

Definitions
Internal validity Extent to which change in the DV is due to manipulation or changes made in IVs and not extraneous variables External validity

Extent to which results of the experiment are generalizable to the real world

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 effect other than the cause

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

RCT (randomized controlled clinical trial)

Randomized Randomisation Inclusion Controlled Procedure Outcome Intervention Clinical Trial Vs. control group

RCT

Investigator

Participants

Clinical Manoeuvre

RCT

Quantitative

Comparative

Control Experiment

Measuring outcome quantitatively

Comparing 2 or more intervention

All variables are Closely controlled

Objectives of RCT

RCT
Drug patient population

Efficacy

Safety

Hierarch of Research Methods

Kategori Evidence

Ia Ib IIA IIb

evidence dari meta analisis pada RCT evidence dari minimal 1 RCT evidence dgn kelompok kontrol, tanpa randomisasi evidence dari suatu quasi experimental evidence dari nonexperimental/descriptive study evidence dari laporan Expert Committee/pendapat ahli

III IV

TYPES OF EXPERIMENTAL DESIGN

RCTs according to the aspects of the interventions they evaluate RCTs according to how the participants are exposed to the interventions RCTs according to the number of participants RCTs according to whether the investigators and participants know which intervention is being assessed

Explanatory and pragmatic trials

RCT according to the aspects of intervention they evaluate

Efficacy and effectiveness trials Phase I, II, and III trials

RCTs according to the aspects of the interventions they evaluate

Explanatory Trial

inclusion criteria sangat ketat highly homogeneous study groups Mis. Hanya pasien usia 40 50 tahun, tanpa penyakit penyerta

Pragmatic Trials

Memasukkan subyek dengan karakteristik yang heterogen Sesuai dengan pasien yang ditemui di ruang praktek Menggunakan kontrol aktif (mis antihypertensive vs. b-blocker), flexible regimens

RCTs according to the aspects of the interventions they evaluate

Efficacy trials

Effectiveness trials

Ideal setting
Semua variabel yang berpengaruh thd outcome dikendalikan e.g. Keparahan penyakit Ketaatan minum obat, Setelah/sebelum makan

Real setting

Fase I

sukarelawan sehat efek samping & toleransi hubungan dosis-efek farmakokinetika uncontrolled subyek terbatas kemungkinan efek tx controlled trial efek terapi definitif pms efek samping yg jarang

Fase II Fase III Fase IV

DESIGN

(RCT-parallel design)

(RCT cross-over design)

(RCT factorial design)

RCT-parallel design

Patient treatment A eligible

O U T C O M E

Random

Treatment B

RCT cross-over design

Patient
washed out

eligible

Treatment A Random
Treatment B

O U T C O M E

Treatment B

Treatment A

O U T C O M E

RCT-factorial design

Patient

tx A
eligible Random Tx B

tx A + tx B

O U T C O M E

RCTs according to the number of participants From n-of-1 to mega-trials

Fixed size Sequential trials

RCTs according to whether the investigators and participants know which intervention is being assessed

Open trials Single blind trials

Double blind trials

Triple and quadruple-blind trials

Non-random selections

Non-random assignments

Dwi Indria Anggraini Pharmacology Deptartment Medical Faculty of Lampung University

PRECLINICAL TRIALS :
Experimental research
In vivo & in vitro research Utilize animal models

Consist of :
Pharmacodynamic studies Toxicological studies

Potency Very high High Intermediate Less toxic Nearly toxic Relative nontoxic

LD50 value (Pure compound) < 1 mg / kg. BW 1-50 mg / kg. BW 50-500 mg / kg. BW 500-5000 mg/ kg. BW 5-15 g/ kg. BW > 15 g/ kg. BW

The most common measure of acute toxicity is the LD50 LD50 and/or ED50 value, depends on the route of administration

Appropriate animals : Mice Rats Guinea pigs

Characteristics : Strains Sex

- Rabbits - Cats - Dogs

- Age - Holding conditions

In vivo

Whole animals

In vitro

Isolated organs and tissues Blood and its components Cell culture, etc.

Methods
-In vivo

Advantages
-Biochemical and physiolo gical function are normal -May predict effect in human -Least expensive -Mechanistic effects -Molecular level

Disadvantages
-May not provide mechanistic effects -May not provide metabolic activati on ( e.g. prodrug)

-In vitro

ANIMALS :
Rodent or nonrodent (may depend on desired effect) Healthy or diseasedanimal model Sex : male and/or female Number : adequate for statistical analysis

Route of administration :
Per Oral- similar to human use

Dose :

Based on Dose-Response Relationship One or more doses that provide a desired effect Dose conversion from human to animal Calculation of ED50

Control group :

Negative control Positive control

To validate that a method works

To obtain Relative Potency of drug candidate or herbal medicines

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