Experimental Design 210211

7/30/2019 Experimental Design 210211

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Experimental Design

s

Dwi Indria Anggraini

Medical Faculty Lampung University


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Cross-

sectional

Case Control Study

Cause

Cohort Study

DiseaseCase reportCase series

Exposures &

outcomes are

measured at

the same time

Descriptive

Outcome Exposure

RCT

Quasi

experi

-

mental

Analytic

OBSERVATIONAL

RESEARCH DESIGN

EXPERIMENTAL


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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 determine cause and effectrelationships


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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


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Definitions

ExtraneousVariables

All variables otherthan the IVs thatmay have causedthe DVs that theresearcher didnt

take intoconsideration in thedesign

E.g.: age, income,geographic location,

competitorsactions, weatherconditions, worldevents, time of day,consumers mood,etc.


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6

Terminology: Experiment

by measuring one or more response

variables.

then observes the effect of the treatments on

the experimental units

the investigator applies some treatments toexperimental units and

An investigation in which


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Definitions

Experimental group (EG)

The group that is exposed to some sort of

a change or manipulation in the IV

Control group (CG)

A group not exposed to changes or

manipulations that serves as a baseline

comparison to the experimental group

Experimental Study


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Internal validity

Extent to which change in the DV is due to

manipulation or changes made in IVs and notextraneous variables

External validity

Extent to which results of the experiment are

generalizable to the real world

Definitions


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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 effect

other 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 bythe 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

Investigator Participants

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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Hierarch of Research Methods


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Kategori Evidence

evidence dari meta analisis pada RCT

Ia evidence dari minimal 1 RCTIb

evidence dgn kelompok kontrol, tanparandomisasiIIA

evidence dari suatu quasi experimentalIIb

evidence dari non-experimental/descriptive studyIII

evidence dari laporan ExpertCommittee/pendapat ahliIV


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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 theinterventions they evaluate


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RCT according to theaspects of intervention

they evaluate

Explanatory andpragmatic trials

Efficacy andeffectiveness trials

Phase I, II, and IIItrials


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RCTs according to the aspects of the interventions they evaluate

Explanatory Trial

inclusion criteria sangat ketat

highly homogeneous study groups Mis. Hanya pasien usia 4050

tahun, tanpa penyakit penyerta

Memasukkan subyek dengan

karakteristik yang heterogen

Sesuai dengan pasien yangditemui di ruang praktek

Menggunakan kontrol aktif(mis

antihypertensive vs. b-blocker),

flexible regimens

Pragmatic Trials


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RCTs according to the aspects of the interventions they evaluate

Efficacy trials Effectiveness trials

Ideal setting Real setting

Semua variabel yang

berpengaruh thd outcome

dikendalikan

e.g.

Keparahan penyakit

Ketaatan minum obat,

Setelah/sebelum makan


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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 I

Fase II

Fase III

Fase IV


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

(RCT factorial design)

DESIGN


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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

eligible

Patient

Random

Treatment B

Treatment AO

U

TC

O

M

E

washed

out

Treatment B

Treatment A

O

U

TC

O

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 the number of participants

From n-of-1 to mega-trials

Sequential trials

Fixed size


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

Open trials

Triple and quadruple-blind trials

Double blind trials

Single blind trials


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Non-random selections

Non-random assignments


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Dwi Indria Anggraini

Pharmacology Deptartment

Medical Faculty of Lampung University


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PRECLINICAL TRIALS :

Experimental research

In vivo & in vitro research

Utilize animal models

Consist of :

Pharmacodynamic studies

Toxicological studies


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

Potency LD50 value (Pure compound)Very high

High

Intermediate

Less toxic

Nearly toxic

Relative nontoxic

< 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


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Appropriate animals :

Mice - Rabbits

Rats - Cats Guinea pigs - Dogs

Characteristics :

Strains - Age

Sex - Holding conditions


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Whole animalsIn vivo

Isolated organs and tissues

Blood and its components

Cell culture, etc.In vitro


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Methods Advantages Disadvantages-In vivo

-In vitro

-Biochemical and physiolo

gical function are normal

-May predict effect in

human

-Least expensive

-Mechanistic effects-Molecular level

-May not provide

mechanistic

effects

-May not provide

metabolic activation ( e.g. prodrug)


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Route of administration :

Per Oral- similar to human use

ANIMALS :

Rodent or non-rodent (may depend

on desired effect)

Healthy or diseased-animal model

Sex : male and/orfemale

Number : adequatefor statistical

analysis


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Dose :

Based on Dose-Response Relationship One or more doses that provide a desired effect

Dose conversion from human to animal

Calculation of ED50

Controlgroup :

Negative control

Positive control


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To validate that a method

works

To obtain Relative Potency

of drug candidate or herbalmedicines


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Persiapan

Pengumpulan

Data

PengolahanData

Penulisan danPublikasi


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Experimental Design 210211

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