EXPERIMENTAL DESIGN IN

CLINICAL TRIALS

Presented by
ARUN Kr. MISHRA
Lecturer
Pharmacy College Azamgarh
UP INDIA 223223

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WHAT IS CLINICAL TRIALS ?

Clinical trials are performed to find out efficacy, safety,

bioavalibility and bioequivalance studies in animals. Data
outcome of experimentation is statistically treated.

INTRODUCTION

Clinical trials are to be done under proper control, adequate

proper control group(placebo and active) and preplanned
design of experimentation must be there.

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FDA GUIDELINES FOR CLINICAL EVALUATION

3. Proper planning, design and clinical analysis of investigation

of clinical pharmacology must be there to efficacy and
safety parameters.
5. Protocols must be framed including criteria for subjects how
patients are to be selected and important parameters.
3. Planning removes the inprocess problems.

GENERAL GUIDE LINES

•Objective of clinical study must be clear

•Documentation of every step is essential
•Suitable number of patients must be available
•Control group considerations
•Avoid the bias
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PRINCIPLES OF DESIGN AND DATA ANALYSIS:--
2. SIMPLICITY AND SYMMETRY
As simplicity is available in design, lesser restriction, lesser
the expense and less time consumption will be there.
It must be having equal no. of patients, equal no. of visits
per patients, balance order of administration.

7. CHOICE OF PATIENTS
Age, sex, bodyweight, disease condition are necessraily to
be considered while selecting patients.

11. ADEQUATE PRECISION

More the no. of patients more precise results but ethics and
expense are to be considered.
Blocking boost up the precision.

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4. INTENT TO TREAT
The drug given should improve the diseases status. When
discontinuation of medication, in proper withdrawal of
blood samples, irregular dose frequency- efficacy is not
considered(such patient are not considered).
10 RANDOMIZATION
Randomly selection of data is randomization.
Mean outcome of two test must be similar.
Eg. 48 patients are to be randomly selected?
From block of 8, up to 6th column
OR
From block of 6, up to 8th column
A = odd no., B= even no.
Eg. 3rd column of 8th block is selected,
2,4,1,6,8,5,3,7
then random assignment is BBABBAAA

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BLOCK OF 8

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PARELLEL DESIGN

•Two or more drug are considered

•Every patient is given a single drug
•Drug is given to randomly assigned patients
•Objective – To test in increase in exercise time after giving
placebo and drug to angina patients
Eg. 40 patients to be selected, odd no. for placebo and even
for new drug.
Sol. The selection may be done from block of 10 from
column 4 to 7

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 From Table

P= Placebo
N=New drug
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 PLACEBO ACTIVE DRUG
Exercise time Exercise time
Patient Pre Post Post-Pre Patient Pre Post Post-Pre
1 377 345 -32 02 232 372 140
6 272 310 38 03 133 120 -13
7 348 347 -01 04 206 294 088
8 348 300 -48 05 140 358 118
12 133 150 17 09 240 340 100
13 102 129 27 10 246 393 147
14 156 110 -46 11 226 315 089
15 205 251 46 16 123 180 057
18 296 262 -34 17 166 334 168
20 328 297 -31 19 264 381 117
21 315 278 -37 23 241 376 135
22 133 124 -09 24 074 264 190
26 223 289 66 25 400 541 141
27 256 303 47 29 320 410 090
28 493 487 -06 30 216 301 085
32 336 309 -27 31 153 143 -010
34 299 281 -18 33 193 348 155
35 140 186 46 38 330 440 110
36 161 125 -36 39 258 365 107
37 259 236 -23 40 353 483 130

MEAN 259 256 -3.05 226 333 107.2

s.d. 102 95 36.3 083 106 51.5

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RESULT OF EXERCISE TEST COMPARING PLACEBO TO
ACTIVE DRUG
Qu.:- Is there a significant difference between active and placebo.
Hypothesis – There is no significant difference between two treatment
in pre of placebo and active drug

Sp = (S12+S22/2)1/2

= [(102)2+(83)2/2]1/2 = 93

t = X1-X2 / Sd.(1/N1+1/N2)1/2

= 259-226 / 93 (0.1)1/2 = 1.12

t0.05/38 = 2.03

INTERPRETATION- Cal. Value of t=1.12 which falls under range t0.05/38

Hence there is no significant difference and hypothesis is accepted.10
ANOVA for the Posttreatment Readings:-
H0; “No significance difference”

F1,38 =5.86
F tabulated=4.10
Interpretation:- “Rejection of Null Hypothesis”
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CROSS OVER DESIGN & BIOAVLABILITY STUDIES

In crossover half of the subjects are randomly chosen to take either

One or other of two formulations on experimental occasion and
Remaining formulation on second occasion.
A sufficient time is given to washout drug so that all of drug is
eliminated before second dose administration.
It is a type of Latin square.
•No. of treatment is equal to no. of patients
•Order of treatment is included in experiment
Eg. Patient 1st and 2nd . 1st is given treatment firstly by A then after
Wash period B.
And in other case 2nd is given treatment B then after wash period
A.
That is 2 X 2 Latin square.

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2 X 2 Table

4 X 4 Table 13
 High plasma conc.
Due to pcd X not
C eliminated yet
O
N X
C. Y

TIME

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 Long washout
Period provided

CMAX
C
O
N
AUC
C. X Y

tP
TIME

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ADVANTAGE AND DISADVANTAGE OF CROSSOVER DESIGN

•Random comparison of two treatment is done

A ----> B & B ----> A
•Intrasubject variability is considered
•Crossover is economical and less time is consumed
•Smaller chances of variation

•Data missing imposes a great problem

•Possibility of interaction of the drug
•Residual effect
•Extra time for the wash period
•In acute diseases patient may be cured up so much improved after
first treatment that the different state of illness is treated in 2nd dose
of crossover

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REFERENCES:--
2. Bolton.S, “Pharmaceutical Statistics”,- 3rd edition,
New York, Mrcel Dekker, P.P-384-442.
3. Remington,”The Science & Practical of Pharmacy”
Volume 1st , P.P-146-147.
4. Lachman.L& Liberman “The Theory & Practical of
Industrial Pharmacy” 2nd P.P-276-279.

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