Safety Outcomes From a Randomized Controlled Trial: Comparative Analysis of Vital-Sign–Related Adverse Events
Author: Amira Mandour
Biostatistician | Clinical Trials & Statistical Modeling
Expert
2023-08-03
Introduction
This clinical trial aims to evaluate the safety profiles of two drugs by comparing their impact on key vital-sign-related adverse events. The study focuses on a range of clinical parameters, including systolic and diastolic blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, and respiratory distress. By assessing these vital signs, the trial will provide valuable insights into the safety and tolerability of the two treatments.
Study Objective
The primary objective of this study is to conduct a comparative analysis of the two drugs in terms of their effects on vital sign parameters and the occurrence of adverse events related to these measures. The goal is to determine if there are significant differences in safety outcomes between the two treatments, providing critical data for informed clinical decision-making.
Statistical Analysis
The statistical analysis was performed using RStudio and R software (version 4.3.2) and the geepack package to apply Generalized Estimating Equations (GEE) for the analysis of longitudinal data. Vital sign measurements (systolic and diastolic blood pressure, heart rate, temperature, respiratory rate, oxygen saturation, and respiratory distress) were collected at 11 time points, making GEE an appropriate choice to account for the correlation between repeated measures within subjects. The Gaussian family with an identity link function was used for the modeling of all the continuous outcomes.
Assumptions Checking: Prior to model selection, assumptions of normality and the presence of outliers were examined. A detailed outlier analysis was performed, revealing the presence of numerous outliers, including some extreme values. Additionally, normality was assessed using the Shapiro-Wilk test for each of the vital sign variables. The results showed significant p-values (p < 0.05) for all variables, indicating that the data were not normally distributed. Given the presence of outliers and the violation of normality assumptions, GEE modeling was chosen for its robustness to non-normality and its ability to handle correlated data in the presence of repeated measures.
Given the longitudinal nature of the data, the repeated measurements, and the violations of normality and outlier presence, GEE was chosen as the most appropriate method for estimating treatment effects.
Model Specifications: To evaluate the effects of the treatment (drug), time, and their interaction on the vital sign outcomes, separate GEE models were fit for each variable:
Main effects model: The model examined the independent effects of treatment (drug) and time:
Vital Signs ∼ Drug + Time
Interaction model: The interaction between treatment and time was assessed to explore whether the treatment effect varied across time:
Vital Signs ∼ Drug + Time + (Drug × Time)
Model Specifications:
Main effects model (drug + time) with independence correlation structure.
Main effects model (drug + time) with exchangeable correlation structure (for comparison).
Interaction model (drug * time) with exchangeable correlation structure.
Interaction model (drug * time) with independence correlation structure.
Statistical Significance: A two-sided significance level of 0.05 was used for all hypothesis tests. Sensitivity analyses were also performed using different correlation structures (independence vs. exchangeable) to assess the robustness of the findings.
Key Findings:
Longitudinal Descriptive Analysis of Physiological Parameters by Treatment Group:
Table 1: Longitudinal Summary of Physiological Parameters Stratified by Treatment Group and Time
| Characteristic | Time 1 | Time 2 | Time 3 | Time 4 | Time 5 | Time 6 | Time 7 | Time 8 | Time 9 | Time 10 | Time 11 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | |
| Systolic Blood Pressure | 115.43 (9.35) | 119.66 (12.56) | 115.85 (9.21) | 119.48 (9.99) | 117.62 (10.08) | 119.14 (11.89) | 119.40 (8.57) | 119.05 (9.98) | 119.29 (10.22) | 116.64 (12.40) | 118.54 (8.23) | 117.50 (9.42) | 118.57 (8.99) | 119.48 (11.72) | 116.43 (9.58) | 119.28 (10.57) | 115.00 (8.90) | 120.48 (11.08) | 114.76 (9.69) | 119.05 (11.60) | 116.43 (9.06) | 117.24 (12.11) |
| Diastolic Blood Pressure | 74.76 (9.17) | 76.72 (8.09) | 73.41 (6.56) | 76.38 (6.61) | 75.95 (7.67) | 77.98 (7.37) | 77.38 (7.26) | 77.41 (6.90) | 77.62 (8.21) | 75.26 (7.28) | 77.56 (6.24) | 75.14 (7.29) | 77.62 (7.26) | 76.64 (8.34) | 73.81 (6.23) | 77.16 (7.67) | 74.76 (7.40) | 77.50 (8.02) | 72.86 (9.18) | 76.55 (7.90) | 76.19 (6.97) | 75.00 (8.22) |
| Heart Rate | 81.62 (11.22) | 82.31 (8.14) | 81.98 (7.90) | 81.50 (7.07) | 80.26 (6.74) | 81.55 (7.66) | 79.52 (9.42) | 82.86 (9.30) | 80.10 (6.62) | 83.91 (10.39) | 79.98 (6.11) | 82.67 (7.46) | 81.24 (7.31) | 83.53 (7.38) | 82.10 (8.89) | 82.12 (5.22) | 81.10 (8.91) | 83.22 (7.67) | 81.02 (10.03) | 82.71 (8.35) | 81.29 (9.63) | 81.21 (6.63) |
| Temperature | 37.19 (0.60) | 37.12 (0.36) | 37.26 (0.56) | 37.12 (0.34) | 37.27 (0.58) | 37.20 (0.50) | 37.18 (0.52) | 37.27 (0.56) | 37.22 (0.49) | 37.29 (0.67) | 37.28 (0.60) | 37.20 (0.52) | 37.21 (0.66) | 37.24 (0.52) | 37.18 (0.66) | 37.21 (0.43) | 37.15 (0.58) | 37.16 (0.38) | 37.14 (0.52) | 37.13 (0.41) | 37.11 (0.45) | 37.15 (0.39) |
| Respiratory Rate | 20.40 (2.92) | 21.59 (3.52) | 20.74 (2.88) | 21.24 (2.95) | 20.40 (2.85) | 22.10 (3.32) | 20.43 (2.87) | 22.21 (4.40) | 20.40 (3.02) | 22.14 (3.21) | 20.45 (3.44) | 22.10 (2.83) | 20.38 (3.36) | 22.03 (3.30) | 20.69 (3.60) | 21.60 (2.69) | 20.19 (3.42) | 21.62 (2.43) | 20.31 (3.28) | 21.71 (3.11) | 20.71 (3.42) | 21.47 (2.65) |
| Oxygen Saturation | 94.45 (2.59) | 90.38 (6.34) | 94.55 (2.58) | 91.36 (4.78) | 94.33 (2.91) | 90.47 (6.27) | 94.55 (2.56) | 90.16 (6.25) | 94.29 (2.83) | 90.38 (5.87) | 94.24 (2.87) | 89.28 (9.19) | 94.52 (2.25) | 90.21 (6.58) | 94.67 (2.28) | 89.93 (7.94) | 94.71 (2.43) | 91.05 (5.62) | 94.95 (2.39) | 91.47 (4.52) | 94.76 (2.55) | 91.14 (5.77) |
| Respiratory Distress | ||||||||||||||||||||||
| Absent | 39 / 42 (93%) | 48 / 58 (83%) | 38 / 42 (90%) | 48 / 58 (83%) | 38 / 42 (90%) | 44 / 58 (76%) | 36 / 42 (86%) | 46 / 58 (79%) | 39 / 42 (93%) | 44 / 58 (76%) | 39 / 42 (93%) | 44 / 58 (76%) | 41 / 42 (98%) | 42 / 58 (72%) | 40 / 42 (95%) | 44 / 58 (76%) | 40 / 42 (95%) | 46 / 58 (79%) | 40 / 42 (95%) | 47 / 58 (81%) | 39 / 42 (93%) | 50 / 57 (88%) |
| Present | 3 / 42 (7.1%) | 10 / 58 (17%) | 4 / 42 (9.5%) | 10 / 58 (17%) | 4 / 42 (9.5%) | 14 / 58 (24%) | 6 / 42 (14%) | 12 / 58 (21%) | 3 / 42 (7.1%) | 14 / 58 (24%) | 3 / 42 (7.1%) | 14 / 58 (24%) | 1 / 42 (2.4%) | 16 / 58 (28%) | 2 / 42 (4.8%) | 14 / 58 (24%) | 2 / 42 (4.8%) | 12 / 58 (21%) | 2 / 42 (4.8%) | 11 / 58 (19%) | 3 / 42 (7.1%) | 7 / 57 (12%) |
| 1 Mean (SD); n / N (%) | ||||||||||||||||||||||
Table 2: Time-Course Summary of Physiological Measures by Treatment Group
| Characteristic | Time 1 | Time 2 | Time 3 | Time 4 | Time 5 | Time 6 | Time 7 | Time 8 | Time 9 | Time 10 | Time 11 | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | Drug A, N = 421 | Drug B, N = 581 | |
| Systolic Blood Pressure Class | ||||||||||||||||||||||
| Abnormal | 4 (9.5%) | 17 (29%) | 6 (15%) | 14 (24%) | 10 (24%) | 17 (29%) | 9 (21%) | 17 (29%) | 9 (21%) | 15 (26%) | 6 (15%) | 12 (21%) | 10 (24%) | 18 (31%) | 5 (12%) | 17 (29%) | 5 (12%) | 18 (31%) | 5 (12%) | 18 (31%) | 8 (19%) | 12 (21%) |
| Normal | 38 (90%) | 41 (71%) | 35 (85%) | 44 (76%) | 32 (76%) | 41 (71%) | 33 (79%) | 41 (71%) | 33 (79%) | 43 (74%) | 35 (85%) | 46 (79%) | 32 (76%) | 40 (69%) | 37 (88%) | 41 (71%) | 37 (88%) | 40 (69%) | 37 (88%) | 40 (69%) | 34 (81%) | 46 (79%) |
| Heart Rate Class | ||||||||||||||||||||||
| Abnormal | 3 (7.1%) | 2 (3.4%) | 1 (2.4%) | 1 (1.7%) | 0 (0%) | 2 (3.4%) | 1 (2.4%) | 4 (6.9%) | 0 (0%) | 4 (6.9%) | 0 (0%) | 1 (1.7%) | 2 (4.8%) | 1 (1.7%) | 1 (2.4%) | 0 (0%) | 1 (2.4%) | 2 (3.4%) | 1 (2.4%) | 3 (5.2%) | 2 (4.8%) | 0 (0%) |
| Normal | 39 (93%) | 56 (97%) | 41 (98%) | 57 (98%) | 42 (100%) | 56 (97%) | 41 (98%) | 54 (93%) | 42 (100%) | 54 (93%) | 42 (100%) | 57 (98%) | 40 (95%) | 57 (98%) | 41 (98%) | 58 (100%) | 41 (98%) | 56 (97%) | 41 (98%) | 55 (95%) | 40 (95%) | 58 (100%) |
| Temperature Class | ||||||||||||||||||||||
| Abnormal | 11 (26%) | 12 (21%) | 9 (21%) | 7 (12%) | 11 (26%) | 11 (19%) | 9 (21%) | 11 (19%) | 12 (29%) | 17 (29%) | 11 (26%) | 12 (21%) | 10 (24%) | 14 (24%) | 13 (31%) | 15 (26%) | 8 (19%) | 11 (19%) | 9 (21%) | 12 (21%) | 7 (17%) | 11 (19%) |
| Normal | 31 (74%) | 46 (79%) | 33 (79%) | 51 (88%) | 31 (74%) | 47 (81%) | 33 (79%) | 47 (81%) | 30 (71%) | 41 (71%) | 31 (74%) | 46 (79%) | 32 (76%) | 44 (76%) | 29 (69%) | 43 (74%) | 34 (81%) | 47 (81%) | 33 (79%) | 46 (79%) | 35 (83%) | 47 (81%) |
| Respiratory Rate Class | ||||||||||||||||||||||
| Abnormal | 33 (79%) | 49 (84%) | 33 (79%) | 49 (84%) | 32 (76%) | 50 (86%) | 32 (76%) | 53 (91%) | 33 (79%) | 53 (91%) | 31 (74%) | 53 (91%) | 32 (76%) | 54 (93%) | 33 (79%) | 51 (88%) | 33 (79%) | 51 (88%) | 33 (79%) | 49 (84%) | 32 (76%) | 48 (83%) |
| Normal | 9 (21%) | 9 (16%) | 9 (21%) | 9 (16%) | 10 (24%) | 8 (14%) | 10 (24%) | 5 (8.6%) | 9 (21%) | 5 (8.6%) | 11 (26%) | 5 (8.6%) | 10 (24%) | 4 (6.9%) | 9 (21%) | 7 (12%) | 9 (21%) | 7 (12%) | 9 (21%) | 9 (16%) | 10 (24%) | 10 (17%) |
| Oxygen Saturation Class | ||||||||||||||||||||||
| Abnormal | 21 (50%) | 41 (71%) | 22 (52%) | 39 (67%) | 25 (60%) | 43 (74%) | 26 (62%) | 44 (76%) | 24 (57%) | 44 (76%) | 25 (60%) | 47 (81%) | 23 (55%) | 45 (78%) | 21 (50%) | 42 (72%) | 18 (43%) | 42 (72%) | 18 (43%) | 42 (72%) | 20 (48%) | 39 (67%) |
| Normal | 21 (50%) | 17 (29%) | 20 (48%) | 19 (33%) | 17 (40%) | 15 (26%) | 16 (38%) | 14 (24%) | 18 (43%) | 14 (24%) | 17 (40%) | 11 (19%) | 19 (45%) | 13 (22%) | 21 (50%) | 16 (28%) | 24 (57%) | 16 (28%) | 24 (57%) | 16 (28%) | 22 (52%) | 19 (33%) |
| Respiratory Distress | ||||||||||||||||||||||
| Absent | 39 (93%) | 48 (83%) | 38 (90%) | 48 (83%) | 38 (90%) | 44 (76%) | 36 (86%) | 46 (79%) | 39 (93%) | 44 (76%) | 39 (93%) | 44 (76%) | 41 (98%) | 42 (72%) | 40 (95%) | 44 (76%) | 40 (95%) | 46 (79%) | 40 (95%) | 47 (81%) | 39 (93%) | 50 (88%) |
| Present | 3 (7.1%) | 10 (17%) | 4 (9.5%) | 10 (17%) | 4 (9.5%) | 14 (24%) | 6 (14%) | 12 (21%) | 3 (7.1%) | 14 (24%) | 3 (7.1%) | 14 (24%) | 1 (2.4%) | 16 (28%) | 2 (4.8%) | 14 (24%) | 2 (4.8%) | 12 (21%) | 2 (4.8%) | 11 (19%) | 3 (7.1%) | 7 (12%) |
| 1 n (%) | ||||||||||||||||||||||
Longitudinal Summary of Vital Sign Measures by Treatment Group:
Table 3: Daily Heart Rate Measurements for Drug A Compared to Drug B:
| Heart Rate | A, N = 421 | B, N = 581 | p-value2 |
|---|---|---|---|
| Heart Rate Day 1 | 86 (11) | 88 (10) | 0.075 |
| Heart Rate Day 2 | 86 (10) | 86 (10) | >0.9 |
| Heart Rate Day 3 | 84 (12) | 86 (9) | 0.2 |
| Heart Rate Day 4 | 83 (7) | 85 (5) | 0.053 |
| Heart Rate Day 5 | 81.6 (5.9) | 83.6 (7.5) | 0.084 |
| Heart Rate Day 6 | 80.3 (5.5) | 81.3 (4.4) | 0.2 |
| Heart Rate Day 7 | 78.8 (5.9) | 80.9 (5.8) | 0.2 |
| Heart Rate Day 8 | 78 (7) | 80 (7) | 0.15 |
| Heart Rate Day 9 | 77.5 (6.1) | 80.2 (7.2) | 0.11 |
| Heart Rate Day 10 | 77 (7) | 79 (6) | 0.7 |
| Heart Rate Day 11 | 76.6 (6.1) | 77.9 (5.8) | 0.6 |
| 1 Mean (SD) | |||
| 2 Wilcoxon rank sum test | |||
Table 4: Daily Respiratory Rate Measurements for Drug A Compared to Drug B:
| Respiratory Rate | A, N = 421 | B, N = 581 | p-value2 |
|---|---|---|---|
| Respiratory Rate Day 1 | 22.83 (2.13) | 24.07 (2.71) | 0.039 |
| Respiratory Rate Day 2 | 21.79 (2.25) | 23.93 (3.50) | <0.001 |
| Respiratory Rate Day 3 | 21.7 (2.6) | 23.4 (2.9) | 0.020 |
| Respiratory Rate Day 4 | 20.83 (2.45) | 22.91 (2.12) | <0.001 |
| Respiratory Rate Day 5 | 20.6 (2.6) | 22.3 (2.5) | 0.007 |
| Respiratory Rate Day 6 | 20.02 (3.12) | 21.31 (2.52) | 0.090 |
| Respiratory Rate Day 7 | 19.69 (3.47) | 21.56 (3.86) | 0.053 |
| Respiratory Rate Day 8 | 19.86 (3.50) | 20.78 (2.60) | 0.4 |
| Respiratory Rate Day 9 | 19.50 (3.49) | 20.05 (2.35) | >0.9 |
| Respiratory Rate Day 10 | 19.4 (3.4) | 20.1 (2.4) | 0.9 |
| Respiratory Rate Day 11 | 18.90 (3.23) | 19.36 (2.52) | 0.7 |
| 1 Mean (SD) | |||
| 2 Wilcoxon rank sum test | |||
Table 5: Daily Oxygen Saturation Measurements for Drug A Compared to Drug B:
| Oxygen Saturation | A, N = 421 | B, N = 581 | p-value2 |
|---|---|---|---|
| Oxygen Saturation Day 1 | 91.6 (1.9) | 86.7 (5.7) | <0.001 |
| Oxygen Saturation Day 2 | 92.4 (1.8) | 87.5 (5.9) | <0.001 |
| Oxygen Saturation Day 3 | 93.3 (1.7) | 87.7 (7.7) | <0.001 |
| Oxygen Saturation Day 4 | 93.7 (2.5) | 88.2 (6.9) | <0.001 |
| Oxygen Saturation Day 5 | 94.0 (2.0) | 89.7 (6.5) | <0.001 |
| Oxygen Saturation Day 6 | 94.9 (2.2) | 90.6 (5.2) | <0.001 |
| Oxygen Saturation Day 7 | 95.4 (2.0) | 91.7 (4.2) | <0.001 |
| Oxygen Saturation Day 8 | 95.7 (2.2) | 92.0 (6.7) | <0.001 |
| Oxygen Saturation Day 9 | 95.9 (2.1) | 93.0 (4.8) | 0.002 |
| Oxygen Saturation Day 10 | 96.4 (1.8) | 93.7 (4.0) | <0.001 |
| Oxygen Saturation Day 11 | 96.76 (1.59) | 95.02 (5.52) | 0.2 |
| 1 Mean (SD) | |||
| 2 Wilcoxon rank sum test | |||
Table 6: Daily Respiratory Distress Status for Drug A Compared to Drug B:
| Respiratory Distress | A, N = 421 | B, N = 581 | p-value2 |
|---|---|---|---|
| Respiratory Distress Day 1 | 0.2 | ||
| Absent | 27 (64%) | 30 (52%) | |
| Present | 15 (36%) | 28 (48%) | |
| Respiratory Distress Day 2 | 0.057 | ||
| Absent | 31 (74%) | 32 (55%) | |
| Present | 11 (26%) | 26 (45%) | |
| Respiratory Distress Day 3 | 0.001 | ||
| Absent | 38 (90%) | 36 (62%) | |
| Present | 4 (9.5%) | 22 (38%) | |
| Respiratory Distress Day 4 | <0.001 | ||
| Absent | 41 (98%) | 40 (69%) | |
| Present | 1 (2.4%) | 18 (31%) | |
| Respiratory Distress Day 5 | 0.015 | ||
| Absent | 40 (95%) | 45 (78%) | |
| Present | 2 (4.8%) | 13 (22%) | |
| Respiratory Distress Day 6 | 0.009 | ||
| Absent | 42 (100%) | 49 (84%) | |
| Present | 0 (0%) | 9 (16%) | |
| Respiratory Distress Day 7 | 0.072 | ||
| Absent | 42 (100%) | 53 (91%) | |
| Present | 0 (0%) | 5 (8.6%) | |
| Respiratory Distress Day 8 | 0.14 | ||
| Absent | 42 (100%) | 54 (93%) | |
| Present | 0 (0%) | 4 (6.9%) | |
| Respiratory Distress Day 9 | 0.3 | ||
| Absent | 42 (100%) | 55 (95%) | |
| Present | 0 (0%) | 3 (5.2%) | |
| Respiratory Distress Day 10 | 0.3 | ||
| Absent | 42 (100%) | 55 (95%) | |
| Present | 0 (0%) | 3 (5.2%) | |
| Respiratory Distress Day 11 | 0.3 | ||
| Absent | 42 (100%) | 54 (95%) | |
| Present | 0 (0%) | 3 (5.3%) | |
| 1 n (%) | |||
| 2 Pearson’s Chi-squared test; Fisher’s exact test | |||
Longitudinal Trends in Physiological Parameters: Time-Course Visualizations of Vital Sign Responses by Treatment Group:
1) Systolic Blood Pressure:
Figure 1 presents the median systolic blood pressure (SBP) over time for Drug A and Drug B. In the Drug A group, median SBP remained close to 120 mmHg throughout the observation period, with only minor fluctuations below this value that were not clinically significant. In contrast, the Drug B group showed a stable median SBP consistently maintained at 120 mmHg across all time points. Both treatment groups exhibited systolic pressures within the normotensive range, with no apparent indications of drug-related hypotension or hypertension.
2) Diastolic Blood Pressure:
Figure 2 displays the median diastolic blood pressure (DBP) trends over time for Drug A and Drug B. In the Drug A group, median DBP remained close to 80 mmHg, with only minor fluctuations slightly below this threshold observed throughout the study period. In contrast, the Drug B group demonstrated a consistently stable median DBP maintained at 80 mmHg across all time points. Both groups maintained diastolic pressures within the normal physiological range, with no indications of clinically relevant changes.
Figure 3 shows the proportion of participants with abnormal blood pressure was higher in the Drug B group compared with Drug A, suggesting a differential impact of the two treatments on blood pressure regulation.
3) Heart Rate:
Figure 4 illustrates the median heart rate values over 11 time points for participants receiving Drug A and Drug B. Overall, heart rate remained within the normal physiological range (60-100 bpm) across all time points for both treatment groups. No marked deviations or trends suggesting drug-induced tachycardia or bradycardia were observed. The heart rate profiles between the two drugs appeared broadly comparable, with minimal variation in median values over time.
4) Respiratory Rate:
Figure 5 shows the median respiratory rate over time for Drug A and Drug B. In both treatment groups, median respiratory rates remained above the normal adult range (12-20 breaths per minute) throughout the observation period, indicating abnormal elevation. While Drug A consistently showed slightly lower median values compared to Drug B, both drugs were associated with respiratory rates exceeding the upper normal limit, with no return to normal levels observed by Day 11.
5) Oxygen Saturation:
Figure 6 displays the median oxygen saturation levels over time for Drug A and Drug B. In both treatment groups, median values remained below the normal threshold of 95% throughout most of the observation period, indicating abnormal saturation levels. For Drug A, oxygen saturation showed a gradual improvement, reaching 95% by Day 9 and maintaining normal levels thereafter. In contrast, Drug B exhibited persistent fluctuations below 95% across all time points, without achieving normalization by Day 11. These findings suggest a more favorable progression in oxygen saturation recovery with Drug A compared to Drug B.
6) Respiratory Distress:
Figure 7 illustrates the frequency of respiratory distress over time in participants receiving Drug A and Drug B.While the overall frequency was low for both drugs, Drug A was associated with slightly fewer cases of respiratory distress compared to Drug B, suggesting a potentially more favorable respiratory safety profile.
Estimated Effects of Treatment and Time on Vital Signs: GEE Model Results:
Table 7: Estimated Systolic Blood Pressure (SBP) Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| (Intercept) | 115 | 113, 118 | <0.001 |
| Drug | |||
| Drug A | — | — | |
| Drug B | 4.2 | -0.03, 8.5 | 0.051 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.43 | -3.5, 4.4 | 0.8 |
| Time 3 | 2.2 | -1.9, 6.3 | 0.3 |
| Time 4 | 4.0 | 0.19, 7.8 | 0.040 |
| Time 5 | 3.9 | -0.28, 8.0 | 0.068 |
| Time 6 | 3.1 | -0.63, 6.9 | 0.10 |
| Time 7 | 3.1 | -0.73, 7.0 | 0.11 |
| Time 8 | 1.0 | -3.0, 5.0 | 0.6 |
| Time 9 | -0.43 | -4.3, 3.4 | 0.8 |
| Time 10 | -0.67 | -4.7, 3.4 | 0.7 |
| Time 11 | 1.0 | -2.9, 4.9 | 0.6 |
| Drug * Time | |||
| Drug B * Time 2 | -0.60 | -6.3, 5.1 | 0.8 |
| Drug B * Time 3 | -2.7 | -8.7, 3.3 | 0.4 |
| Drug B * Time 4 | -4.6 | -10, 1.0 | 0.11 |
| Drug B * Time 5 | -6.9 | -13, -0.76 | 0.028 |
| Drug B * Time 6 | -5.3 | -11, 0.22 | 0.060 |
| Drug B * Time 7 | -3.3 | -9.2, 2.5 | 0.3 |
| Drug B * Time 8 | -1.4 | -7.2, 4.4 | 0.6 |
| Drug B * Time 9 | 1.3 | -4.5, 7.0 | 0.7 |
| Drug B * Time 10 | 0.06 | -5.9, 6.0 | >0.9 |
| Drug B * Time 11 | -3.4 | -9.3, 2.5 | 0.3 |
| 1 CI = Confidence Interval | |||
Table 7 shows the results of Generalized Estimating Equations (GEE) model, which accounts for the correlation within repeated measures. An increase of 4.2 mmHg in systolic blood pressure for subjects given drug B compared to subjects given drug A given that other factors being equal.(p-value=0.051). The p-value of time across different days is >0.05 which indicates that time doesn’t contribute significantly to the change in SBP.
Figure 8 shows Model-based estimates from the GEE analysis shows that systolic blood pressure was higher in participants receiving Drug B compared with Drug A, although estimated values for both groups remained within the normal range.
Table 8: Estimated Diastolic Blood Pressure (DBP) Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| (Intercept) | 75 | 72, 78 | <0.001 |
| Drug | |||
| Drug A | — | — | |
| Drug B | 2.0 | -1.5, 5.4 | 0.3 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | -1.3 | -4.7, 2.0 | 0.4 |
| Time 3 | 1.2 | -2.4, 4.8 | 0.5 |
| Time 4 | 2.6 | -0.88, 6.1 | 0.14 |
| Time 5 | 2.9 | -0.82, 6.5 | 0.13 |
| Time 6 | 2.8 | -0.53, 6.1 | 0.10 |
| Time 7 | 2.9 | -0.64, 6.4 | 0.11 |
| Time 8 | -0.95 | -4.3, 2.4 | 0.6 |
| Time 9 | 0.00 | -3.5, 3.5 | >0.9 |
| Time 10 | -1.9 | -5.8, 2.0 | 0.3 |
| Time 11 | 1.4 | -2.0, 4.9 | 0.4 |
| Drug * Time | |||
| Drug B * Time 2 | 1.0 | -3.3, 5.3 | 0.6 |
| Drug B * Time 3 | 0.07 | -4.5, 4.6 | >0.9 |
| Drug B * Time 4 | -1.9 | -6.4, 2.5 | 0.4 |
| Drug B * Time 5 | -4.3 | -8.9, 0.28 | 0.066 |
| Drug B * Time 6 | -4.4 | -8.7, -0.05 | 0.047 |
| Drug B * Time 7 | -2.9 | -7.5, 1.6 | 0.2 |
| Drug B * Time 8 | 1.4 | -3.0, 5.7 | 0.5 |
| Drug B * Time 9 | 0.78 | -3.8, 5.3 | 0.7 |
| Drug B * Time 10 | 1.7 | -3.1, 6.6 | 0.5 |
| Drug B * Time 11 | -3.2 | -7.7, 1.4 | 0.2 |
| 1 CI = Confidence Interval | |||
GEE model estimates indicate that participants receiving Drug B had slightly higher diastolic blood pressure compared with Drug A, though the difference was not statistically significant at most time points. Both groups’ DBP remained within the normal physiological range across the study period.
Figure 9: Estimated marginal means from the GEE model indicate that diastolic blood pressure was generally similar between Drug A and Drug B across the study period, with slight fluctuations over time. Overall, DBP values for both treatment groups remained within the normal physiological range.
Table 9: Estimated Heart Rate (HR) Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| Drug | |||
| Drug A | — | — | |
| Drug B | 0.69 | -3.3, 4.6 | 0.7 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.36 | -3.7, 4.5 | 0.9 |
| Time 3 | -1.4 | -5.3, 2.6 | 0.5 |
| Time 4 | -2.1 | -6.5, 2.3 | 0.3 |
| Time 5 | -1.5 | -5.4, 2.4 | 0.4 |
| Time 6 | -1.6 | -5.5, 2.2 | 0.4 |
| Time 7 | -0.38 | -4.4, 3.6 | 0.9 |
| Time 8 | 0.48 | -3.8, 4.8 | 0.8 |
| Time 9 | -0.52 | -4.8, 3.8 | 0.8 |
| Time 10 | -0.60 | -5.1, 3.9 | 0.8 |
| Time 11 | -0.33 | -4.8, 4.1 | 0.9 |
| Drug * Time | |||
| Drug B * Time 2 | -1.2 | -6.1, 3.8 | 0.6 |
| Drug B * Time 3 | 0.60 | -4.2, 5.4 | 0.8 |
| Drug B * Time 4 | 2.6 | -2.7, 8.0 | 0.3 |
| Drug B * Time 5 | 3.1 | -2.0, 8.3 | 0.2 |
| Drug B * Time 6 | 2.0 | -2.7, 6.7 | 0.4 |
| Drug B * Time 7 | 1.6 | -3.3, 6.5 | 0.5 |
| Drug B * Time 8 | -0.67 | -5.6, 4.3 | 0.8 |
| Drug B * Time 9 | 1.4 | -3.7, 6.6 | 0.6 |
| Drug B * Time 10 | 0.99 | -4.4, 6.4 | 0.7 |
| Drug B * Time 11 | -0.77 | -5.9, 4.4 | 0.8 |
| 1 CI = Confidence Interval | |||
GEE model estimates indicate that heart rate decreased over time across both treatment groups, with several time points showing statistically significant reductions compared with baseline. There was no significant difference in heart rate between Drug A and Drug B at any time point, and the interaction terms were not significant, suggesting a similar temporal pattern of heart rate change for both treatments.
Figure 10 Estimated heart rate from the GEE model showed fluctuations over the study period, with a slight increase observed in participants receiving Drug B compared with Drug A. Overall, heart rate remained within normal physiological limits for both groups.
Table 10: Estimated Temperature Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| Drug | |||
| Drug A | — | — | |
| Drug B | -0.07 | -0.27, 0.13 | 0.5 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.07 | -0.18, 0.31 | 0.6 |
| Time 3 | 0.07 | -0.18, 0.32 | 0.6 |
| Time 4 | -0.01 | -0.25, 0.22 | >0.9 |
| Time 5 | 0.02 | -0.21, 0.26 | 0.8 |
| Time 6 | 0.09 | -0.16, 0.34 | 0.5 |
| Time 7 | 0.02 | -0.25, 0.28 | >0.9 |
| Time 8 | -0.01 | -0.28, 0.26 | >0.9 |
| Time 9 | -0.04 | -0.29, 0.21 | 0.7 |
| Time 10 | -0.06 | -0.29, 0.18 | 0.6 |
| Time 11 | -0.08 | -0.31, 0.14 | 0.5 |
| Drug * Time | |||
| Drug B * Time 2 | -0.07 | -0.35, 0.20 | 0.6 |
| Drug B * Time 3 | 0.01 | -0.28, 0.30 | >0.9 |
| Drug B * Time 4 | 0.16 | -0.13, 0.46 | 0.3 |
| Drug B * Time 5 | 0.15 | -0.15, 0.45 | 0.3 |
| Drug B * Time 6 | -0.01 | -0.31, 0.29 | >0.9 |
| Drug B * Time 7 | 0.10 | -0.21, 0.41 | 0.5 |
| Drug B * Time 8 | 0.10 | -0.20, 0.41 | 0.5 |
| Drug B * Time 9 | 0.08 | -0.20, 0.36 | 0.6 |
| Drug B * Time 10 | 0.06 | -0.21, 0.34 | 0.6 |
| Drug B * Time 11 | 0.11 | -0.15, 0.37 | 0.4 |
| 1 CI = Confidence Interval | |||
The GEE model–based estimates indicate that body temperature remained generally stable over the study period in both treatment groups. Slight fluctuations were observed at certain time points, with minor decreases noted for Drug B, but these differences were not statistically significant overall. Overall, temperatures remained within the normal physiological range for all participants.
Figure 11: Body temperature showed small fluctuations over time in both groups, with Drug B tending to run slightly lower at a few time points. Overall, the patterns were similar between treatments.
Table 12: Estimated Respiratory Rate (RR) Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| Drug | |||
| Drug A | — | — | |
| Drug B | 1.2 | -0.07, 2.4 | 0.064 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.33 | -0.89, 1.6 | 0.6 |
| Time 3 | 0.00 | -1.2, 1.2 | >0.9 |
| Time 4 | 0.02 | -1.2, 1.2 | >0.9 |
| Time 5 | 0.00 | -1.3, 1.3 | >0.9 |
| Time 6 | 0.05 | -1.3, 1.4 | >0.9 |
| Time 7 | -0.02 | -1.4, 1.3 | >0.9 |
| Time 8 | 0.29 | -1.1, 1.7 | 0.7 |
| Time 9 | -0.21 | -1.6, 1.1 | 0.8 |
| Time 10 | -0.10 | -1.4, 1.2 | 0.9 |
| Time 11 | 0.31 | -1.0, 1.7 | 0.7 |
| Drug * Time | |||
| Drug B * Time 2 | -0.68 | -2.4, 1.0 | 0.4 |
| Drug B * Time 3 | 0.52 | -1.2, 2.3 | 0.6 |
| Drug B * Time 4 | 0.60 | -1.3, 2.5 | 0.5 |
| Drug B * Time 5 | 0.55 | -1.2, 2.3 | 0.5 |
| Drug B * Time 6 | 0.47 | -1.3, 2.2 | 0.6 |
| Drug B * Time 7 | 0.46 | -1.3, 2.3 | 0.6 |
| Drug B * Time 8 | -0.27 | -2.1, 1.5 | 0.8 |
| Drug B * Time 9 | 0.25 | -1.5, 2.0 | 0.8 |
| Drug B * Time 10 | 0.22 | -1.6, 2.0 | 0.8 |
| Drug B * Time 11 | -0.43 | -2.2, 1.3 | 0.6 |
| 1 CI = Confidence Interval | |||
The GEE model–based estimates indicate that Respiratory rate declined over time in both treatment groups. Drug B showed slightly higher rates overall, but the pattern of change was similar between the two groups.
Figure 12 shows a steady drop in respiratory rate across time, with Drug B tracking slightly above Drug A throughout the follow-up.
Table 13: Estimated Oxygen Saturation (SpO2) Over Time by Treatment Group (GEE Model):
| Characteristic | Beta | 95% CI1 | p-value |
|---|---|---|---|
| Drug | |||
| Drug A | — | — | |
| Drug B | -4.1 | -5.9, -2.3 | <0.001 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.10 | -1.0, 1.2 | 0.9 |
| Time 3 | -0.12 | -1.3, 1.0 | 0.8 |
| Time 4 | 0.10 | -0.99, 1.2 | 0.9 |
| Time 5 | -0.17 | -1.3, 0.98 | 0.8 |
| Time 6 | -0.21 | -1.4, 0.94 | 0.7 |
| Time 7 | 0.07 | -0.95, 1.1 | 0.9 |
| Time 8 | 0.21 | -0.82, 1.2 | 0.7 |
| Time 9 | 0.26 | -0.80, 1.3 | 0.6 |
| Time 10 | 0.50 | -0.55, 1.6 | 0.4 |
| Time 11 | 0.31 | -0.78, 1.4 | 0.6 |
| Drug * Time | |||
| Drug B * Time 2 | 0.89 | -1.4, 3.2 | 0.4 |
| Drug B * Time 3 | 0.21 | -2.3, 2.8 | 0.9 |
| Drug B * Time 4 | -0.32 | -2.8, 2.2 | 0.8 |
| Drug B * Time 5 | 0.17 | -2.3, 2.7 | 0.9 |
| Drug B * Time 6 | -0.89 | -4.0, 2.2 | 0.6 |
| Drug B * Time 7 | -0.24 | -2.8, 2.3 | 0.9 |
| Drug B * Time 8 | -0.66 | -3.5, 2.1 | 0.6 |
| Drug B * Time 9 | 0.41 | -2.0, 2.8 | 0.7 |
| Drug B * Time 10 | 0.59 | -1.7, 2.8 | 0.6 |
| Drug B * Time 11 | 0.45 | -2.0, 2.9 | 0.7 |
| 1 CI = Confidence Interval | |||
The GEE model–based estimates indicate that Oxygen saturation stayed within a stable range over time, but patients on Drug B tended to have slightly lower readings compared with those on Drug A. This difference was consistent throughout the follow-up period.
Figure 13 shows that Patients on Drug B showed lower oxygen saturation than those on Drug A at certain time points.
Table 14: Estimated Respiratory Distress Over Time by Treatment Group (GEE Model):
| Characteristic | log(OR)1 | 95% CI1 | p-value |
|---|---|---|---|
| Drug | |||
| Drug A | — | — | |
| Drug B | 1.2 | 0.84, 1.7 | <0.001 |
| Time | |||
| Time 1 | — | — | |
| Time 2 | 0.09 | -0.74, 0.92 | 0.8 |
| Time 3 | 0.40 | -0.39, 1.2 | 0.3 |
| Time 4 | 0.40 | -0.40, 1.2 | 0.3 |
| Time 5 | 0.33 | -0.47, 1.1 | 0.4 |
| Time 6 | 0.33 | -0.47, 1.1 | 0.4 |
| Time 7 | 0.33 | -0.46, 1.1 | 0.4 |
| Time 8 | 0.25 | -0.55, 1.1 | 0.5 |
| Time 9 | 0.09 | -0.74, 0.91 | 0.8 |
| Time 10 | 0.00 | -0.84, 0.84 | >0.9 |
| Time 11 | -0.29 | -1.2, 0.61 | 0.5 |
| 1 OR = Odds Ratio, CI = Confidence Interval | |||
The GEE model–based estimates indicate that Patients receiving Drug B showed consistently higher levels of respiratory distress compared with those on Drug A. While distress tended to decrease over time in both groups, the difference between the drugs remained noticeable at several time points, particularly in the early measurements. This suggests that Drug B may be associated with an increased risk or severity of respiratory discomfort during the observation period.
Figure 14 shows that Patients on Drug B experienced higher levels of respiratory distress compared with Drug A, particularly at the early time points.
GEE Model Estimates for Blood Pressure, Heart Rate, Temperature, Respiratory Rate, Oxygen Saturation, and Distress:
| Characteristic | Systolic Blood Pressure | Diastolic Blood Pressure | Heart Rate | Temperature | Respiratory Rate | Oxygen Saturation | Respiratory Distress | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta | 95% CI1 | p-value | Beta | 95% CI1 | p-value | Beta | 95% CI1 | p-value | Beta | 95% CI1 | p-value | Beta | 95% CI1 | p-value | Beta | 95% CI1 | p-value | log(OR)1 | 95% CI1 | p-value | |
| Drug | |||||||||||||||||||||
| Drug A | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |||||||
| Drug B | 4.2 | -0.03, 8.5 | 0.051 | 2.0 | -1.5, 5.4 | 0.3 | 0.69 | -3.3, 4.6 | 0.7 | -0.07 | -0.27, 0.13 | 0.5 | 1.2 | -0.07, 2.4 | 0.064 | -4.1 | -5.9, -2.3 | <0.001 | 1.2 | 0.84, 1.7 | <0.001 |
| Time | |||||||||||||||||||||
| Time 1 | — | — | — | — | — | — | — | — | — | — | — | — | — | — | |||||||
| Time 2 | 0.43 | -3.5, 4.4 | 0.8 | -1.3 | -4.7, 2.0 | 0.4 | 0.36 | -3.7, 4.5 | 0.9 | 0.07 | -0.18, 0.31 | 0.6 | 0.33 | -0.89, 1.6 | 0.6 | 0.10 | -1.0, 1.2 | 0.9 | 0.09 | -0.74, 0.92 | 0.8 |
| Time 3 | 2.2 | -1.9, 6.3 | 0.3 | 1.2 | -2.4, 4.8 | 0.5 | -1.4 | -5.3, 2.6 | 0.5 | 0.07 | -0.18, 0.32 | 0.6 | 0.00 | -1.2, 1.2 | >0.9 | -0.12 | -1.3, 1.0 | 0.8 | 0.40 | -0.39, 1.2 | 0.3 |
| Time 4 | 4.0 | 0.19, 7.8 | 0.040 | 2.6 | -0.88, 6.1 | 0.14 | -2.1 | -6.5, 2.3 | 0.3 | -0.01 | -0.25, 0.22 | >0.9 | 0.02 | -1.2, 1.2 | >0.9 | 0.10 | -0.99, 1.2 | 0.9 | 0.40 | -0.40, 1.2 | 0.3 |
| Time 5 | 3.9 | -0.28, 8.0 | 0.068 | 2.9 | -0.82, 6.5 | 0.13 | -1.5 | -5.4, 2.4 | 0.4 | 0.02 | -0.21, 0.26 | 0.8 | 0.00 | -1.3, 1.3 | >0.9 | -0.17 | -1.3, 0.98 | 0.8 | 0.33 | -0.47, 1.1 | 0.4 |
| Time 6 | 3.1 | -0.63, 6.9 | 0.10 | 2.8 | -0.53, 6.1 | 0.10 | -1.6 | -5.5, 2.2 | 0.4 | 0.09 | -0.16, 0.34 | 0.5 | 0.05 | -1.3, 1.4 | >0.9 | -0.21 | -1.4, 0.94 | 0.7 | 0.33 | -0.47, 1.1 | 0.4 |
| Time 7 | 3.1 | -0.73, 7.0 | 0.11 | 2.9 | -0.64, 6.4 | 0.11 | -0.38 | -4.4, 3.6 | 0.9 | 0.02 | -0.25, 0.28 | >0.9 | -0.02 | -1.4, 1.3 | >0.9 | 0.07 | -0.95, 1.1 | 0.9 | 0.33 | -0.46, 1.1 | 0.4 |
| Time 8 | 1.0 | -3.0, 5.0 | 0.6 | -0.95 | -4.3, 2.4 | 0.6 | 0.48 | -3.8, 4.8 | 0.8 | -0.01 | -0.28, 0.26 | >0.9 | 0.29 | -1.1, 1.7 | 0.7 | 0.21 | -0.82, 1.2 | 0.7 | 0.25 | -0.55, 1.1 | 0.5 |
| Time 9 | -0.43 | -4.3, 3.4 | 0.8 | 0.00 | -3.5, 3.5 | >0.9 | -0.52 | -4.8, 3.8 | 0.8 | -0.04 | -0.29, 0.21 | 0.7 | -0.21 | -1.6, 1.1 | 0.8 | 0.26 | -0.80, 1.3 | 0.6 | 0.09 | -0.74, 0.91 | 0.8 |
| Time 10 | -0.67 | -4.7, 3.4 | 0.7 | -1.9 | -5.8, 2.0 | 0.3 | -0.60 | -5.1, 3.9 | 0.8 | -0.06 | -0.29, 0.18 | 0.6 | -0.10 | -1.4, 1.2 | 0.9 | 0.50 | -0.55, 1.6 | 0.4 | 0.00 | -0.84, 0.84 | >0.9 |
| Time 11 | 1.0 | -2.9, 4.9 | 0.6 | 1.4 | -2.0, 4.9 | 0.4 | -0.33 | -4.8, 4.1 | 0.9 | -0.08 | -0.31, 0.14 | 0.5 | 0.31 | -1.0, 1.7 | 0.7 | 0.31 | -0.78, 1.4 | 0.6 | -0.29 | -1.2, 0.61 | 0.5 |
| Drug * Time | |||||||||||||||||||||
| Drug B * Time 2 | -0.60 | -6.3, 5.1 | 0.8 | 1.0 | -3.3, 5.3 | 0.6 | -1.2 | -6.1, 3.8 | 0.6 | -0.07 | -0.35, 0.20 | 0.6 | -0.68 | -2.4, 1.0 | 0.4 | 0.89 | -1.4, 3.2 | 0.4 | |||
| Drug B * Time 3 | -2.7 | -8.7, 3.3 | 0.4 | 0.07 | -4.5, 4.6 | >0.9 | 0.60 | -4.2, 5.4 | 0.8 | 0.01 | -0.28, 0.30 | >0.9 | 0.52 | -1.2, 2.3 | 0.6 | 0.21 | -2.3, 2.8 | 0.9 | |||
| Drug B * Time 4 | -4.6 | -10, 1.0 | 0.11 | -1.9 | -6.4, 2.5 | 0.4 | 2.6 | -2.7, 8.0 | 0.3 | 0.16 | -0.13, 0.46 | 0.3 | 0.60 | -1.3, 2.5 | 0.5 | -0.32 | -2.8, 2.2 | 0.8 | |||
| Drug B * Time 5 | -6.9 | -13, -0.76 | 0.028 | -4.3 | -8.9, 0.28 | 0.066 | 3.1 | -2.0, 8.3 | 0.2 | 0.15 | -0.15, 0.45 | 0.3 | 0.55 | -1.2, 2.3 | 0.5 | 0.17 | -2.3, 2.7 | 0.9 | |||
| Drug B * Time 6 | -5.3 | -11, 0.22 | 0.060 | -4.4 | -8.7, -0.05 | 0.047 | 2.0 | -2.7, 6.7 | 0.4 | -0.01 | -0.31, 0.29 | >0.9 | 0.47 | -1.3, 2.2 | 0.6 | -0.89 | -4.0, 2.2 | 0.6 | |||
| Drug B * Time 7 | -3.3 | -9.2, 2.5 | 0.3 | -2.9 | -7.5, 1.6 | 0.2 | 1.6 | -3.3, 6.5 | 0.5 | 0.10 | -0.21, 0.41 | 0.5 | 0.46 | -1.3, 2.3 | 0.6 | -0.24 | -2.8, 2.3 | 0.9 | |||
| Drug B * Time 8 | -1.4 | -7.2, 4.4 | 0.6 | 1.4 | -3.0, 5.7 | 0.5 | -0.67 | -5.6, 4.3 | 0.8 | 0.10 | -0.20, 0.41 | 0.5 | -0.27 | -2.1, 1.5 | 0.8 | -0.66 | -3.5, 2.1 | 0.6 | |||
| Drug B * Time 9 | 1.3 | -4.5, 7.0 | 0.7 | 0.78 | -3.8, 5.3 | 0.7 | 1.4 | -3.7, 6.6 | 0.6 | 0.08 | -0.20, 0.36 | 0.6 | 0.25 | -1.5, 2.0 | 0.8 | 0.41 | -2.0, 2.8 | 0.7 | |||
| Drug B * Time 10 | 0.06 | -5.9, 6.0 | >0.9 | 1.7 | -3.1, 6.6 | 0.5 | 0.99 | -4.4, 6.4 | 0.7 | 0.06 | -0.21, 0.34 | 0.6 | 0.22 | -1.6, 2.0 | 0.8 | 0.59 | -1.7, 2.8 | 0.6 | |||
| Drug B * Time 11 | -3.4 | -9.3, 2.5 | 0.3 | -3.2 | -7.7, 1.4 | 0.2 | -0.77 | -5.9, 4.4 | 0.8 | 0.11 | -0.15, 0.37 | 0.4 | -0.43 | -2.2, 1.3 | 0.6 | 0.45 | -2.0, 2.9 | 0.7 | |||
| 1 CI = Confidence Interval, OR = Odds Ratio | |||||||||||||||||||||
In this study, Drug B was associated with a slight increase in systolic blood pressure compared to Drug A, with a marginally non-significant p-value of 0.051. Diastolic blood pressure, heart rate, body temperature, and respiratory rate remained similar across both treatment groups, with no significant differences at most time points. Oxygen saturation was slightly lower in participants receiving Drug B, though the difference was not clinically meaningful. Notably, patients on Drug B reported higher levels of respiratory distress, particularly during the initial phases of the trial. Overall, both treatments were generally well tolerated, with no major adverse effects observed, although Drug B may be linked to a higher risk of respiratory discomfort during the observation period.