Problems (Session 4) 1.

To investigate the effects of different regimens on the age at which children walk, newborn children were randomly assigned to one of four treatment groups (>2 groups = ANOVA, not t-test; the groups are independent (different patients)): active exercise; passive exercise; no exercise; or an 8-week control group. Infants in the active- exercise group received walking and placing stimulation four times a day for eight weeks, infants in the passive-exercise group received an equal amount of gross motor stimulation, infants in the no-exercise group were tested along with the first two groups at weekly intervals, and the eight-week control group consisted of infants observed only at 8 weeks of age to control for possible effects of repeated examination. The response variable was age (in months) at which the infant first walked. The data is as follows: One factor (treatment regimen) = one-way ANOVA test required.
Distribution of Ages (in Months) at which Infants First Walked Alone
Active Group Passive Group No-Exercise Group Eight-Week Control Group

9.00 9.50 9.75 10.00 10.00 9.50

11.00 12.00 10.00 11.75 10.50 15.00

11.50 12.00 10.00 11.50 13.25 13.00

13.25 11.50 12.00 13.50 11.50 13.35

Is there evidence to suggest that certain regimens are better than others? Yes, active group shows infants walked at a significantly earlier age than the other groups; the other groups were statistically the same for age at which they walked. 1. Select Analyze General Linear Model Univariate. Univariate because we have only 1 dependent variable. The dependent variable is the outcome which is the age

2. 3. 4. 5. 6. 7.

The dependent variable is the outcome so we select age. Select Group for the Fixed Factor (we wont use the others in the course random factor, covariate, WLS weight. Select Model leave it on Full factorial (you dont always want that but OK for this problem). Continue. Contrasts button wont be used in this course. Plots may be used at some point Select Post Hoc this will tell us which of the 4 groups is/are different. Move Group over to the right (Post Hoc Tests for). Then check Tukey. **Always choose Tukey.** 8. Save wont use this 9. Select Options. Select Descriptive Statistics (always run this) and keep significance interval at .05. (do not have to display estimated marginal means) 10. Click OK Between-Subjects Factors Value Label 1 Active Group 2 Passive Group 3 No-Exercise Group 4 Eight-Week Control Group

N 6 6 6 6

Group

Descriptive Statistics Dependent Variable:Age Group Mean Std. Deviation Active Group 9.6250 .37914 Passive Group 11.7083 1.77776 No-Exercise Group 11.8750 1.18057 Eight-Week Control Group 12.5167 .95219 Total 11.4312 1.56468

N 6 6 6 6 24

Tests of Between-Subjects Effects Dependent Variable:Age Source Type III Sum of Squares df Mean Square a Corrected Model 28.286 3 9.429 Intercept 3136.163 1 3136.163 Group 28.286 3 9.429 Error 28.023 20 1.401 Total 3192.473 24 Corrected Total 56.309 23 a. R Squared = .502 (Adjusted R Squared = .428)

F 6.729 2238.285 6.729

Sig. .003 .000 .003

Tests of Between Subjects Effects Intercept not interested in this Group look at Sig. for the hypothesis test it is .003 which is less than 0.05 and therefore, we reject the null hypothesis. At least 1 group is significantly different but which one? Post Hoc table needed: (NOTE: do not run Post Hoc if there is no significance between the group.) looking for * in Mean Difference column. Shows Active Group has * by each of the other 3 groups which means there was a sig. difference between active and the other groups.

Multiple Comparisons Age Tukey HSD (I) Group Active Group

(J) Group

Passive Group No-Exercise Group Eight-Week Control Group Passive Group Active Group No-Exercise Group Eight-Week Control Group No-Exercise Group Active Group Passive Group Eight-Week Control Group Eight-Week Control Group Active Group Passive Group No-Exercise Group Based on observed means. The error term is Mean Square(Error) = 1.401. *. The mean difference is significant at the Homogenous Subset:

Mean Difference (I-J) -2.0833* -2.2500* -2.8917* 2.0833* -.1667 -.8083 2.2500* .1667 -.6417 2.8917* .8083 .6417

Std. Error .68341 .68341 .68341 .68341 .68341 .68341 .68341 .68341 .68341 .68341 .68341 .68341

Sig. .030 .018 .002 .030 .995 .644 .018 .995 .785 .002 .644 .785

95% Confidence Interval Lower Bound Upper Bound -3.9962 -.1705 -4.1628 -.3372 -4.8045 -.9788 .1705 3.9962 -2.0795 1.7462 -2.7212 1.1045 .3372 4.1628 -1.7462 2.0795 -2.5545 1.2712 .9788 4.8045 -1.1045 2.7212 -1.2712 2.5545

Age Tukey HSD Group

a,b

Subset N 1 9.6250 2

Active Group 6 Passive Group 6 11.7083 No-Exercise Group 6 11.8750 Eight-Week Control Group 6 12.5167 Sig. 1.000 .644 Means for groups in homogeneous subsets are displayed. Based on observed means. The error term is Mean Square(Error) = 1.401. a. Uses Harmonic Mean Sample Size = 6.000. b. Alpha = This last table puts the groups into subsets by which groups each is equivalent to. Active group is by itself but the other are grouped together meaning that those 3 are equivalent. The active group is statistically significant. The infants walked at an earlier age in the active group.

2. Aspirin is known to induce microbleeding in the gastrointestinal system, as evidence by minute amounts of blood in the stool. Arsenault et al. (1976) reported on a new agent, R-803, studying its effect in comparison to placebo and aspirin (900 mg, q.i.d.) on blood loss. The study design was a crossover design where each subject received all three treatments. Each subject was placed on each drug for one week, with a washout week between treatments. The order in which the drugs were administered to each patient was random. The following table shows the average amount of blood lost per day (ml) over a week. The data is as follows: Subject 1 Placebo 0.45 R-803 0.82 Aspirin 18.00 2 0.54 0.39 6.46 3 0.69 0.67 6.19 4 0.53 1.19 6.52 5 3.03 1.18 7.18 Mean Blood Loss (ml/day) 6 7 8 9 0.78 0.14 0.82 0.96 1.07 0.49 0.14 0.80 9.39 6.93 1.57 4.03

Is there a difference in the amount of blood loss among the treatments? Yes, aspirin has significantly higher blood loss than either R803 and placebo. Reject the null hypothesis. R803 and aspirin are statistically equivalent to each other. Notes: This is a crossover design each subject received all treatments the groups are dependent, have to parameterize GLM. Because they are dependent, have to keep track of subject. Crossover design almost always has higher power and is preferable; removes a lot of variability by running on the same patient. Have to keep track of subject so create a variable for it. Continuous dependent variable = GLM. Will use GLM univariate (cant use one-way ANOVA). This is a randomized block design. There are 3 groups ANOVA Steps: 1. 2. 3. 4. 5. 6. Select Analysis GLM Univariate. Dependent variable is blood loss. Fixed factors = drug and subject. Model cant use full factorial (cant compare subject against each drug). Choose Custom and move Subject and Drug over. Post Hoc dont need to do this for subjects but do need it for drug. Choose Tukey. Options select descriptive statistics; display means for drug (at top)

Tests of Between-Subjects Effects Dependent Variable:BloodLoss Source Type III Sum of Squares df Mean Square a Corrected Model 315.846 10 31.585 Intercept 242.760 1 242.760 Subject 58.571 8 7.321 Drug 257.275 2 128.638 Error 113.187 16 7.074 Total 671.794 27 Corrected Total 429.034 26 a. R Squared = .736 (Adjusted R Squared = .571) Multiple Comparisons BloodLoss Tukey HSD (I) (J) Drug Drug

F 4.465 34.316 1.035 18.184

Sig. .004 .000 .451 .000

Mean Difference Std. (I-J) Error Sig. Placeb R-803 .1322 1.25381 .994 * o Aspirin -6.4811 1.25381 .000 R-803 Placeb -.1322 1.25381 .994 o Aspirin -6.6133* 1.25381 .000 * Aspirin Placeb 6.4811 1.25381 .000 o R-803 6.6133* 1.25381 .000 Based on observed means. The error term is Mean Square(Error) = 7.074. *. The mean difference is significant at the Homogeneous subsets

95% Confidence Interval Lower Upper Bound Bound -3.1030 3.3675 -9.7164 -3.2459 -3.3675 3.1030 -9.8486 3.2459 3.3781 -3.3781 9.7164 9.8486

BloodLoss Tukey HSD Drug

a,b

Subset N 1 .7500 .8822 .994 7.3633 1.000 2

R-803 9 Placebo 9 Aspirin 9 Sig. Means for groups in homogeneous subsets are displayed. Based on observed means. The error term is Mean Square(Error) = 7.074. a. Uses Harmonic Mean Sample Size = 9.000. b. Alpha =

3. To investigate the effect of different drugs to relieve itching, 3 drugs were compared to both placebo and no drug. The study design was a crossover design where each participant underwent one treatment per day. Thus, individuals served as blocks. The subjects were given the therapy intravenously, and then itching was induced on their forearms with an effective itch stimulus. The subjects recorded the durations of the itching in seconds. The following data were obtained: Patient 1 2 3 4 5 6 7 8 9 10
NO DRUG PLACEBO PAPA VERINE MORPHINE PENTOBARBITAL

174 224 260 255 165 237 191 100 115 189

263 213 231 291 168 121 137 102 89 433

105 103 145 103 144 94 35 133 83 237

199 143 113 225 176 144 87 120 100 173

108 341 159 135 239 136 140 134 185 198

Is there evidence to suggest that certain therapies are better than others? Yes, Papaverine significantly reduces itch duration when compared to placebo. Reject H0.

Tests of Between-Subjects Effects Dependent Variable:ItchDuration Source Type III Sum of Squares df Mean Square Corrected Model 1.347E5 13 10362.869 Intercept 1.410E6 1 1.410E6 Patient 86182.500 9 9575.833 Drug 48534.800 4 12133.700 Error 127607.200 36 3544.644 Total 1.672E6 50 Corrected Total 262324.500 49 a. R Squared = .514 (Adjusted R Squared = .338)

F 2.924 397.648 2.701 3.423

Sig. .005 .000 .016 .018

Multiple Comparisons ItchDuration Tukey HSD (I) Drug

(J) Drug

Placebo Papaverine Morphine Pentobarbital Placebo No drug Papaverine Morphine Pentobarbital Papaverine No drug Placebo Morphine Pentobarbital Morphine No drug Placebo Papaverine Pentobarbital Pentobarbital No drug Placebo Papaverine Morphine Based on observed means. The error term is Mean Square(Error) = 3544.644. *. The mean difference is significant at the Estimated Marginal Means

No drug

Mean Difference (IJ) -13.8000 72.8000 43.0000 13.5000 13.8000 86.6000* 56.8000 27.3000 -72.8000 -86.6000* -29.8000 -59.3000 -43.0000 -56.8000 29.8000 -29.5000 -13.5000 -27.3000 59.3000 29.5000

95% Confidence Interval Std. Error 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 26.62572 Sig. Lower Bound Upper Bound .985 -90.2379 62.6379 .068 -3.6379 149.2379 .498 -33.4379 119.4379 .986 -62.9379 89.9379 .985 -62.6379 90.2379 .020 10.1621 163.0379 .229 -19.6379 133.2379 .842 -49.1379 103.7379 .068 -149.2379 3.6379 .020 -163.0379 -10.1621 .795 -106.2379 46.6379 .193 -135.7379 17.1379 .498 -119.4379 33.4379 .229 -133.2379 19.6379 .795 -46.6379 106.2379 .801 -105.9379 46.9379 .986 -89.9379 62.9379 .842 -103.7379 49.1379 .193 -17.1379 135.7379 .801 -46.9379 105.9379

Drug Dependent Variable:ItchDuration Drug 95% Confidence Interval Mean Std. Error Lower Bound Upper Bound No drug 191.000 18.827 152.817 229.183 Placebo 204.800 18.827 166.617 242.983 Papaverine 118.200 18.827 80.017 156.383 Morphine 148.000 18.827 109.817 186.183 Pentobarbital 177.500 18.827 139.317 215.683 Placebo has highest itch duration; Papaverine has lowest. But need post-hoc to determine actual variances (above). Only placebo and Papaverine show a significant difference.

4. To investigate the effects of three different anesthesia therapies on concentrations of plasma epinephrine, 30 dogs were randomly selected to participate in a controlled study. The 30 dogs were randomly assigned to one of the following treatment conditions: Isofluorane; Halothane; or Cyclopropoane. For each dog, the concentrations of plasma epinephrine were measured in nanograms per milliliter. The following data were obtained: Anestheia Isofluorane .28 Halothane .30 Cyclopropoane 1.07 .51 .39 1.35 1.00 .63 .69 .39 .68 .28 .29 .38 1.24 .36 .21 1.53 .32 .88 .49 .69 .39 .56 .17 .51 1.02 .33 .32 .30

Is there a difference in the treatment effects? Yes (.011 < 0.05; reject null hypothesis). Cyclopropane increases levels of plasma epinephrine.

Descriptive Statistics Dependent Variable:PlasmaConc Anesthesia Mean Std. Deviation Isofluorane .4340 .24428 Halothane .4690 .20529 Cyclopropoane .8530 .44826 Total .5853 .36225

N 10 10 10 30

Tests of Between-Subjects Effects Dependent Variable:PlasmaConc Source Type III Sum of Squares df Mean Square a Corrected Model 1.081 2 .540 Intercept 10.278 1 10.278 Anesthesia 1.081 2 .540 Error 2.725 27 .101 Total 14.084 30 Corrected Total 3.806 29 a. R Squared = .284 (Adjusted R Squared = .231)

F 5.355 101.851 5.355

Sig. .011 .000 .011

PostHoc Multiple Comparisons PlasmaConc Tukey HSD (I) Anesthesia Isofluorane

(J) Anesthesia

Halothane Cyclopropoane Halothane Isofluorane Cyclopropoane Cyclopropoane Isofluorane Halothane Based on observed means. The error term is Mean Square(Error) = .101. *. The mean difference is significant at the PlasmaConc a,b Tukey HSD Anesthesia Subset N 1 2 Isofluorane 10 .4340 Halothane 10 .4690 Cyclopropoane 10 .8530 Sig. .967 1.000 Means for groups in homogeneous subsets are displayed. Based on observed means. The error term is Mean Square(Error) = .101. a. Uses Harmonic Mean Sample Size = 10.000. b. Alpha =

Mean Difference (I-J) -.0350 -.4190* .0350 -.3840* .4190* .3840*

Std. Error .14207 .14207 .14207 .14207 .14207 .14207

Sig. .967 .017 .967 .031 .017 .031

95% Confidence Interval Lower Bound Upper Bound -.3872 .3172 -.7712 -.0668 -.3172 .3872 -.7362 -.0318 .0668 .7712 .0318 .7362

5. To investigate the effect of time on a new medical therapy for the treatment of pain, 7 patients were followed over a 3-hour period. Patients were asked to indicate the amount of pain they were experiencing on a scale from 1-20 (20 being worst pain). Baseline data was collected just before the administration of the therapy. Patient 1 2 3 4 5 6 7 Baseline 17 14 11 10 9 7 5 Hour 1 16 13 11 9 9 7 6 Hour 2 15 13 10 8 7 5 4 Hour 3 8 6 5 4 3 2 2

HINT: This is a within-subjects design that requires blocking on the patient. What does the data above suggests about the effectiveness of the new therapy? What effect does time have? Pain level decreases over time. Dependent groups (repeated measures on same patient) Variables tracked for patient, hour, and pain level. Tests of Between-Subjects Effects Dependent Variable:PainLevel Source Type III Sum of Squares df Mean Square a Corrected Model 454.857 9 50.540 Intercept 1989.143 1 1989.143 Patient 284.857 6 47.476 Hour 170.000 3 56.667 Error 16.000 18 .889 Total 2460.000 28 Corrected Total 470.857 27 a. R Squared = .966 (Adjusted R Squared = .949)

F 56.857 2237.786 53.411 63.750

Sig. .000 .000 .000 .000

Estimated marginal means Hour Dependent Variable:PainLevel Hour 95% Confidence Interval Mean Std. Error Lower Bound Upper Bound Baseline 10.429 .356 9.680 11.177 Hour1 10.143 .356 9.394 10.892 Hour 2 8.857 .356 8.108 9.606 Hour 3 4.286 .356 3.537 5.034 Homogeneous subsets PainLevel Tukey HSD Hour
a,b

Hour 3 7 Hour 2 7 8.8571 Hour1 7 10.1429 10.1429 Baseline 7 10.4286 Sig. 1.000 .085 .941 Means for groups in homogeneous subsets are displayed. Based on observed means. The error term is Mean Square(Error) = .889. a. Uses Harmonic Mean Sample Size = 7.000. b. Alpha =

1 4.2857

Subset 2

Larges decrease in pain level occurs between hours 2 and 3.