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ABSTRACT: The global experiments in the presence of repeated measurements are represented in the case
of three overlapping factors and the third factor is represented by experimental units (Subjects). Repeated
measurements or treatments are taken for experimental units and these treatments are treated as a fourth factor.
This type of experiment has been analyzed by the parameterized methods represented by the F test. If the
conditions for variance analysis are available for repeated measurement experiments, and if the conditions are
not met, we use the non-parametric methods of converting to the ranks.
The purpose of this research is an analytical study of this type of experiment by non-parametric and non-
parametric methods and the application of this experiment to thalassemia in DhiQar
x
D B
C
(الشكل1. ) مخطط لتجربة عامليه متداخلة بوجود قياسات متكررة
Factor D
Factor A Factor B Factor C
𝐝𝟏 𝐝𝟐 . . . 𝐝𝐫
1 Y1111 Y1112 . . . Y111r
2 Y1121 Y1122 . . . Y112r
. . . .
𝐛𝟏 . . . .
. . . .
𝐧𝟏 Y11n11 Y11n12 . . . Y11n1r
1 Y1211 Y1212 . . . Y121r
𝐚𝟏 2 Y1221 Y1222 . . . Y122r
𝐛𝟐 . . . .
. . . .
. . . .
𝐧𝟐 Y12n21 Y12n22 . . . Y12n2r
1 Y1q′11 Y1q′12 . . . Y1q′ 1r
2 Y1q′21 Y1q′22 . . . Y1q′ 2r
𝐛𝐪′ . . . .
. . . .
. . . .
Y1q′n ′ 1 Y1q′n ′ 2 . . . Y1q′n ′ r
𝐧𝐛𝐪′ bq bq bq
. . . . .
. . . . .
. . . . .
ANOVA Table
The methods or mathematical formulas appropriate for calculating the sums of squares are obtained as follows:
p q n r
2
= ∑ ∑ ∑ ∑(YijkL – ̅
Y…. )
SST
i=1 j=1 k=1 L=1
p q n r
2
= ∑ ∑ ∑ ∑(YijkL – ̅
Yijk. + ̅
Yijk. – ̅
Y…. )
i=1 j=1 k=1 L=1
p q n r p q n
2
̅…. )2
̅ijk. ) + r ∑ ∑ ∑( ̅Yijk. − Y
= ∑ ∑ ∑ ∑(YijkL − Y
i=1 j=1 k=1 L=1 i=1 j=1 k=1
p q n r
̅ijk. )( ̅Yijk. − Y
+ 2 ∑ ∑ ∑ ∑(YijkL − Y ̅…. )
i=1 j=1 k=1 L=1
= ∑ ∑ ∑( ̅Yijk. − Y
̅…. ) [∑(YijkL − Y
̅ijk. )] = 0
i=1 j=1 k=1 L=1
p q n r
̅ijk. )2
SSW = ∑ ∑ ∑ ∑(YijkL − Y
i=1 j=1 k=1 L=1
p q n r
= ∑ ∑ ∑ ∑(YijkL − ̅
Yijk. − ̅
Y…. + ̅
Y…. − ̅
Yi..L + ̅
Yi..L − ̅
Yij.L + ̅
Yij.L − ̅
Yij.. + ̅
Yij.. − ̅
Y…L
i=1 j=1 k=1 L=1
2
+̅
Y…L − ̅
Yi… + ̅
Yi… )
p q n r
2
= ∑ ∑ ∑ ∑(YijkL − ̅
Yijk. − ̅
Yij.L + ̅
Yij.. )
i=1 j=1 k=1 L=1
p q n r
2
̅ij.L − ̅Yij.. − ̅
+ ∑ ∑ ∑ ∑(Y Yi..L + ̅
Yi… )
i=1 j=1 k=1 L=1
p q n r p q n r
̅i..L − Y
+ ∑ ∑ ∑ ∑(Y ̅i… − Y
̅…L + Y
̅…. )2 + ∑ ∑ ∑ ∑( ̅Y…L − Y
̅…. )2
i=1 j=1 k=1 L=1 i=1 j=1 k=1 L=1
= SSD + SSAD + SSDB(A) + SSDC(AB)
p q n p q n
2 2
SSB = r ∑ ∑ ∑( ̅Yijk. − ̅
Y…. ) = r ∑ ∑ ∑( ̅Yijk. − ̅
Y…. − ̅
Yi… + ̅
Yi… − ̅Yij.. + ̅Yij.. )
i=1 j=1 k=1 i=1 j=1 k=1
p q n p q n p q n
2
= r ∑ ∑ ∑( ̅Yi… − Y
̅…. )2 + r ∑ ∑ ∑( ̅Yij.. − Y
̅i… ) ̅ij.. )2
+ r ∑ ∑ ∑( ̅Yijk. − Y
i=1 j=1 k=1 i=1 j=1 k=1 i=1 j=1 k=1
+ 2 ( 0 ) = SSA + SSB(A) + SSC(AB)
p q n r
Y2
[1] = …. = C. F 2
[2] = ∑ ∑ ∑ ∑ YijkL
pqnr
i=1 j=1 k=1 L=1
∑pi=1 Yi…
2 ∑qj=1 Y.j..
2
[3] = [4] =
nqr npr
∑nk=1 Y..k.
2 ∑r Y 2
[5] = [6] = L=1 ...L
pqr npq
∑pi=1 ∑qj=1 Yij..
2
∑pi=1 ∑nk=1 Yi.k.
2
[7] = [8] =
nr qr
∑pi=1 ∑rL=1 Yi..L
2 ∑qj=1 ∑nk=1 Y.jk.
2
[9] = [10] =
nq pr
∑qj=1 ∑rL=1 Y.j.L
2
∑nk=1 ∑rL=1 Y..kL
2
[11] = [12] =
np pq
∑pi=1 ∑qj=1 ∑nk=1 Yijk.
2 ∑pi=1 ∑qj=1 ∑rL=1 Yij.L
2
[13] = [14] =
r n
∑qj=1 ∑nk=1 ∑rL=1 Y.jkL
2
∑pi=1 ∑nk=1 ∑rL=1 Yi.kL
2
[15] = [16] =
p q
The table of variance analysis for the following design is shown in the table below:
The sum of the total squares will be:
SST = 2− 1 = SSB + SSW… (2)
|Volume 2| Issue 1 | www.ijmcer.com Page 12
Analysis of variance of global experiments with repeated measurements with practical application
∑nk Y..k.
2
Y….2 ∑pi ∑nk Yi.k.
2 ∑pi Yi…2 ∑nk Y..k.
2 2
Y…. ∑qj ∑nk Y.jk.
2 ∑qj Y.j..
2
∑nk Y..k.
2
∴ SSC(AB) = − + − − + + − −
pqr pqnr qr qnr pqr pqnr pr pnr pqr
2
Y…. ∑pi ∑qj ∑nk Yijk.
2
∑pi Yi…2 ∑qj Y.j..
2
∑nk Y..k.
2
+ + + + +
pqnr r qnr pnr pqr
p q 2 q
∑i ∑j Yij.. ∑pi ∑nk Yi.k.
2 ∑j ∑nk Y.jk.
2
Y…. 2
− – – –
nr qr pr pqnr
= [5] − [1] + [8] − [3] − [5] + [1] + [10] − [4] − [5] + [1] + [13] + [3] + [4]
+ [5] − [7] − [8] − [10] − [1]
∑pi ∑qj ∑nk Yijk.2 ∑pi ∑qj Yij..
2
= − = [13] − [7]
r nr
𝟑 − SSDB(A) = SSDB + SSDBA … (14)
∑qj ∑rL Y.j.L
2 ∑qj Y.j..2 r 2
∑L Y...L Y….2
∗ SSDB = − − +
np pnr npq pqnr
= [11] − [4] – [6] + [1]
∑pi ∑qj ∑rL Yij.L
2
∑pi Yi…
2 ∑qj Y.j..
2
∑rL Y…L2 ∑pi ∑qj Yij..2
∑pi ∑rL Yi..L
2 ∑qj ∑rL Y.j.L
2 2
Y….
∗ SSDBA = + + + − − − –
n qnr pnr npq nr nq np pqnr
= [14] + [3] + [4] + [6] − [7] − [9] − [11] − [1]
∑qj ∑rL Y.j.L
2 ∑qj Y.j..
2
∑rL Y...L
2 2
Y…. ∑pi ∑qj ∑rL Yij.L 2
∑p Yi… 2 ∑qj Y.j..
2
∑rL Y...L
2 ∑pi ∑qj Yij..
2
∴ SSDB(A) = − − + + + i + + −
np pnr npq pqnr n qnr pnr npq nr
∑pi ∑rL Yi..L 2 ∑qj ∑rL Y.j.L2 2
Y….
− − −
nq np pqnr
= [11] − [4] − [6] + [1] + [14] + [3] + [4] + [6] − [7] − [9] − [11] − [1]
∑pi ∑qj ∑rL Yij.L 2
∑p Yi… 2 ∑pi ∑qj Yij..
2
∑p ∑rL Yi..L 2
= + i − − i
n qnr nr nq
= [14] + [3] − [7] − [9]
𝟒 − SSDC(AB) = SSDC + SSACD + SSBCD + SSABCD … (15)
∑n ∑rL Y..kL
2 ∑n Y 2 ∑rL Y...L
2 2
Y….
∗ SSDC = k − k ..k. − +
pq pqr npq pqnr
= [12] − [5] − [6] + [1]
∑pi ∑nk ∑rL Yi.kL
2 ∑pi Yi…
2 ∑nk Y..k.
2 ∑rL Y...L
2 ∑pi ∑nk Yi.k. 2 ∑pi ∑rL Yi..L
2 ∑n ∑rL Y..kL
2 2
Y….
∗ SSACD = + + + − − − k −
q qnr pqr npq qr nq pq pqnr
= [16] + [3] + [5] + [6] − [8] − [9] − [12] − [1]
∑qj ∑nk ∑rL Y.jkL
2 ∑qj Y.j..
2
∑nk Y..k.
2 ∑rL Y...L
2 ∑qj ∑nk Y.jk.2 ∑qj ∑rL Y.j.L
2
∑n ∑rL Y..kL
2 2
Y….
∗ SSBCD = + + + – − − k −
p pnr pqr npq pr np pq pqnr
= [15] + [4] + [5] + [6] − [10] − [11] − [12] − [1]
p q n r
∑pi ∑qj ∑nk Yijk.
2 ∑pi ∑qj ∑rL Yij.L2
∑p ∑n ∑rL Yi.kL2 ∑qj ∑nk ∑rL Y.jkL
2
∑p Yi…
2
∗ SSABCD = ∑ ∑ ∑ ∑ YijkL 2
− − − i k − − i
r n q p qnr
i j k L
∑qj Y.j..
2
∑nk Y..k.
2 ∑rL Y...L
2 ∑pi ∑qj Yij..
2
∑p ∑n Y 2 ∑p ∑rL Yi..L
2 ∑qj ∑nk Y.jk.
2 ∑qj ∑rL Y.j.L
2
− − − + + i k i.k. + i + +
pnr pqr npq nr qr nq pr np
∑nk ∑rL Y..kL
2
Y….2
+ +
pq pqnr
= [2] − [13] − [14] − [16] − [15] − [3] − [4] – [5] − [6] + [7] + [8] + [9] + [10]
+ [11] + [12] + [1]
S .O . V dF S .S M.S EMS F
Between(sub. pq(i) n(ij) − 1 SSB
) p−1 SSA SSA
A P−1 rσ2c +
MSA
P(q(i) – 1) SSB(A) qnr∅A
MSE(B)
B(A)
SSE(B) SSB(A)
Error(Bet.) q(i) (n(ij) − 1) P(q(i) – 1)
= C(AB) SSW MSB(A)
pq(i) n(ij) (r−1) SSD rσ2c MSE(B)
SSE(B) + nr∅B
Within(sub.) r−1
SSAD pq(i) (n(ij) − 1)
D
(p−1)(r − 1)
SSDB(A) rσ2c
AD
P(r−1)(q(i) − SSError
DB(A)
1)
pq(i) (r − SSD
Error(Within
) 1)(nij − 1) r−1 σ2DC
= C(AB + pqn∅D
MSD
MSE(W)
Total pq(i) n(ij) r−1 SST SSAD
(p − 1)(r − 1)
σ2DC
+ qn∅AD MSAD
MSE(W)
SSDB(A)
P(r − 1)(q(i) − 1)
σ2DC
+ n∅DB
SSE(W) MSDB(A)
MSE(W)
pq(i) (r − 1)(n(ij) − 1)
σ2DC
Table (2) shows ANOVA for its experiments with the presence of repeated measurementsThis analysis is used
to test the hypothesis:
H_0 = T_1 = T_2 = ... = T_r ... (16)
Analysis of variance for repeated measurement experiments requires the following conditions to be met:
The main influences are aggregate: It means that the factors influence add to each other to determine the values
of observations
The random and independent random distribution of the experimental error: This condition assumes that the
errors are randomly and independently distributed with an average of zero and its value varies (σ ^ 2), meaning
that:
e_ij ~ NID (0, σ ^ 2) ... (17)
Homogeneity of variance: This condition means that random differences are equal within groups homogeneous
and therefore random differences are equal for different samples, which helps to obtain a reduced variance of all
groups.
There is no correlation between the mean and the contrast
Sphericality: This condition means the order of the experimental units does not change in the results of the
experiment as well as the association of any two treatments is the same for each pair of treatments and the
spherical condition indicates that there is no interaction between the factor of the experimental units and the
treatments (repeated measurements).
Analytical methods for this experiment
There are several statistical methods for analyzing the designs of repeated measurements, including parameter
and non-parametric methods and multivariate methods and each of the mentioned methods is implemented
according to certain conditions. In this research we will use the parameter methods represented by testing F and
nonparametric methods by means of Rank Transformation.
The practical side:
This study was applied to data collected from Al-Hussein Hospital _ Thalassemia Center in DhiQar from
patients with beta anemia of the Mediterranean type of beta or the so-called Thalassemia major, and the number
of observations (160) was represented by two groups (two medications) and each group included (20) Patient
(10 males, 10 females) and given treatment at four equal time periods each 30-day time period
Box-and-Whisker Plot
0 2 4 6 8
(X 1000)
Col_5
Figure (2) Box-and-Whisker Plot plot of Thalassemia data, where no abnormal values are shown
The hypothesis that errors are distributed naturally is tested with an average (0) and a variance (σ2) that are:
H_0 = ε_ij ~ N (0, σ_ε ^ 2). . . (18)
H_1 = ε_ij≁ N (0, σ_ε ^ 2). . . (19)
First, we find the error values (ε_ij) according to the linear model of the design:
Y_ijkL = μ + A_i + B_j (i) + C_ (k (ij)) + D_L + AD_iL + DB_Lj (i) + 〖E〗 _kL (ij) ... (20)
ε_ (Lk (ij)) = Y_ijkL- μ_ (ijk.) - μ_ (ij.L) + μ_ (ij ..). . . (21)
Test Test Value
P-Value
S .O . V dF S .S M.S FC Ftable
Between(su 39 681492955
b.) 1 161885522.9 161885522.9 14.368
A 2 113997336.1 56998668.05 5.058 F(0.01,1,36) = 7.31
B(A) 36 405610096 11266947.11 F(0.01,2,36) = 5.18
Error(Bet.)
= C(AB) 120 98061199
3 19081539 6360513 10.064
Within(sub. 3 3122776 1040925.333 1.647 F(0.01,3,104) = 3.95
) 6 7601402 1266900.333 2.005
F(0.01,3,104) = 3.95
D 108 68255482 631995.203
AD F(0.01,6,104) = 2.96
DB(A)
Error(With
in)
= C(AB)
Table (7) Table of analysis of variance of the global experiment in the presence of repeated
measurementsThrough the results of the ANOVA table, we note that:
There are significant differences in levels between factor A (pharmacists.)
There were no significant differences between levels of factor II B (gender) within factor I (pharmacists.)
There are significant differences between factor D levels (repeated measurements.)
There were no significant differences for interaction between factor A (pharmacokinetics) and factor III D
(repeated measurements.)
-There were no significant differences for interaction between factor II B (gender) and factor IIID (repeated
measurements) within factor IA (pharmacokinetics.)
We are now taking the data rank, finding the table of variance analysis and studying the conditions of variance
analysis for repeated measurements experiments.
-5Test of Normality for errors
To test the hypothesis that errors are naturally distributed (18) using the Chi-Squared test after taking error
estimates(21)
Test value
Test P-Value
S .O . V dF S .S M.S FC Ftable
Between(sub. 39 297801.375
) 1 62805.625 62805.625 12.447
A 2 53354.925 26677.4625 5.287 F(0.01,1,36) = 7.31
B(A) 36 181640.825 5045.57847 F(0.01,2,36) = 5.18
Error(Bet.)
= C(AB) 120 43517.125
3 10087.7125 3362.5708 12.306
Within(sub.) 3 1018.587 339.529 1.242 F(0.01,3,108) = 3.95
D 6 2901 483.5 1.769
F(0.01,3,108) = 3.95
AD 108 29509.825 273.23912
DB(A) F(0.01,6,108) = 2.96
Error(Withi
n)
= C(AB)
There are significant differences between levels of factor II B (gender) within factor I (pharmacists).
There are significant differences between factor D levels (repeated measurements).
There were no significant differences for interaction between factor A (pharmacokinetics) and factor III D
(repeated measurements).
There were no significant differences for interaction between factor B (sex) and factor D (repeated
measurements) within factor I (pharmacokinetics).
• Conclusions
1- It was found that converting data from parameterized to non-parametric methods by grade resulted in
providing conditions for variance analysis for repeated measurements experiments such as normal distribution
of errors, homogeneity of variations, correlation between mean and variance, as well as the spherical condition.
2- Where it was observed that the conditions for normal distribution and homogeneity of variations, as well as
the condition for the absence of correlation between the mean and variance, were achieved and after a transfer
to the ranks, it improved the value of value - P for the condition of normal distribution from (0.0229) to
(0.2210) as well as for homogeneity of variance for Bartlett's test ( 0.688) to (0.935) and likewise for the
Cochran test, it changed from (0.505) to (1.0), and the correlation condition was a value equal to (0.532) and
changed to (0.588). As for the spherical condition, unfulfilled by the value of the test (18.465), which led to
adjusting the degrees of freedom for the F test From (3,108) to (3,104), after a conversion to the data levels, the
spherical condition was met and the test value was equal to (11.343). As for the results of the F test, it may
change. It ranges for the first factor (A) from (14.368) to (12.447), for the second factor (B) from (5.058) to
(5.287) and the fourth factor (D) from (10.069) to (12.306) and for the interaction between the first factor and
the fourth factor (AD From (1.647) to (1.212), and also with regard to the interaction between the second factor
and the fourth factor (DB), it has changed from (2.05) to (1.769).
3- In the practical application of overlapping factor experiments with the presence of repeated measurements
and there were no alternative methods for unparalleled parameters such as Friedman or others so the method we
used was the alternative method for these cases.
4- Among the medical conclusions, the majority of patients with blood types (A +) and (B +), as well as the
majority of patients from his parents who carry the disease and are relatives and it was also observed with poor
or uneducated academic achievement for one of the spouses (housewives, earners) and it was found that the
majority of patients have His residence is rural.
5- Through the four applications, we see that giving the dose of the first drug to patients led to an increase in the
amounts of iron for patients over time, and this type of treatment is used when the amounts of iron are high.
Likewise, when administering the dose of the second medication to patients, it led to increased amounts of iron
for patients over time, but with lower proportions than the first treatment, and this type of treatment is used
when the iron is weak in the patient’s blood.
• Recommendation
Through this research, we reached the following recommendations that they should be taken into consideration
and serve the scientific and human aspect and preserve the life of the individual, we recommend the following:
1. Applying the conditions of variance analysis for repeated measurements in the case of three or more factors,
and in their different situations and experiments.
2. Application of unbalanced overlapping globalization experiments with repeated measurements. Or missing
values.
3. Transferring data to non-parametric methods by converting ranks as one of the solutions in the absence of
conditions for variance analysis for repeated measurements experiments.
4. The use of multivariate methods for analyzing experiments, repeated measurements, and clarifying the
conditions for this type of analysis.
5. Applying repeated measurements in the case of medical data of all kinds in the service of the scientific
process, including psychological data and time-dependent psychology.
.6Giving the dose to patients resulted in increasing the amounts of iron for patients over time, so it is necessary
to carry out a study on different drugs or doses in order to lead to reducing the amounts of iron as well as
reducing complications for patients.
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