EXPERIMENTAL DESIGN IN
CLINICAL TRIALS
SUBMITTED TO SUBMITTED BY
Dr. S. AWASTHI ARUN Kr. MISHRA
DEPTT. OF MANAGEMENT M.PHARM IST SEM.
IFTM, MORADABAD IFTM MORADABAD
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WHAT IS CLINICAL TRIALS ?
INTRODUCTION
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FDA GUIDELINES FOR CLINICAL EVALUATION
6. CHOICE OF PATIENTS
Age, sex, bodyweight, disease condition are necessraily to
be considered while selecting patients.
9. ADEQUATE PRECISION
More the no. of patients more precise results but ethics and
expense are to be considered.
Blocking boost up the precision. 5
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).
6 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
7 4 2B 4 1 2
8 2 4B 5 8 5
4 3 1A 6 3 6
1 5 6B 3 2 7
2 8 8B 1 7 8
3 1 5A 8 6 1
6 7 3A 7 5 4
5 6 7A 2 4 3
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PARELLEL DESIGN
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PLACEBO NEW From Table
DRUG 4 5 6 7
SUBSET 1 1,5,6,7,9 2,3,4,8,10
1P 3 4 1
SUBSET 2 11,13,15,1 12,14,16,1 8N 2 7 4
7,18 9,20
4N 7 8 5
SUBSET 3 22,24,27,2 21,23,25,2 10 P 8 9 8
8,29 6,30
9P 1 6 6
5P 6 2 9
SUBSET 4 31,33,36,3 32,34,35,3
7N 9 3 10
8,39 7,40
2P 5 1 7
3N 10 5 3
P= Placebo 6N 4 10 2
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
Sp = (S12+S22/2)1/2
= [(102)2+(83)2/2]1/2 = 93
t = X1-X2 / Sd.(1/N1+1/N2)1/2
t0.05/38 = 2.03
Source d.f SS MS
Between 1 59213 59213
Groups
Within 38 383787 10099.7
Groups
Total 39 443000
F1,38 =5.86
F tabulated=4.10
Interpretation:- “Rejection of Null Hypothesis” 12
CROSS OVER DESIGN & BIOAVLABILITY STUDIES
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PATIENT FIRST SECOND
1 A B
2 B A
2 X 2 Table
4 X 4 Table 14
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
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REFERENCES:--
• Bolton.S, “Pharmaceutical Statistics”,- 3rd edition,
New York, Mrcel Dekker, P.P-384-442.
• Remington,”The Science & Practical of Pharmacy”
Volume 1st , P.P-146-147.
• Lachman.L& Liberman “The Theory & Practical of
Industrial Pharmacy” 2nd P.P-276-279.
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