TDMS Study 88122-07 Pathology Tables
NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus ELMIRON DATE: 04/23/01 EXPERIMENT: 88122 TEST: 07 TIME: 15:31:43 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE PAGE: 1 CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: C88122 PATHOLOGIST: GRUMBEIN, SONDRA CAS: 37319-17-8 ------------------------------------------------------------------------------------------------------------------------------------ final#1/Mice REASONS FOR REMOVAL: ALL REMOVAL DATE RANGE: ALL TREATMENT GROUPS: INCLUDE ALL NTP STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS REPORT: PEIRPT10 LAB: Battelle Columbus ELMIRON DATE: 04/23/01 EXPERIMENT: 88122 TEST: 07 TIME: 15:31:43 TEST TYPE: CHRONIC CAGES FROM 0000 TO LAST CAGE CONT: NO1-ES-55388 ROUTE: GAVAGE NTP C#: C88122 PATHOLOGIST: GRUMBEIN, SONDRA CAS: 37319-17-8 SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS IN THE ANALYSIS OF ELMIRON =============================================================== Male Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Hyperplasia Hypertrophy Intestine Large, Cecum Inflammation Chronic Intestine Large, Rectum Infiltration Cellular Histiocyte Inflammation Chronic Metaplasia Myxomatous Change Necrosis Kidney Nephropathy Liver Basophilic Focus Inflammation Chronic Liver: Centrilobular Degeneration Lymph Node, Mesenteric Infiltration Cellular Histiocyte Nose Inflammation Seminal Vesicle Dilatation Spleen Hematopoietic Cell Proliferation Infiltration Cellular Histiocyte Stomach, Forestomach Hyperplasia =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Adrenal Cortex Hypertrophy Intestine Large, Rectum Infiltration Cellular Histiocyte Inflammation Chronic Metaplasia Myxomatous Change Necrosis Kidney Metaplasia Osseous Nephropathy Liver Basophilic Focus Clear Cell Focus Eosinophilic Focus Fatty Change Lymph Node, Mandibular Infiltration Cellular Histiocyte Lymph Node, Mesenteric Hemorrhage Infiltration Cellular Histiocyte Spleen Hematopoietic Cell Proliferation Infiltration Cellular Histiocyte Metaplasia Osseous =============================================================== Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 1 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 8/50 (16%) 8/50 (16%) 13/49 (27%) |5/49 (10%) 3/49 (6%) 2/49 (4%) 2/48 (4%) | |POLY-3 RATE (b) | 5/45.56 8/44.27 8/45.36 13/41.34 |5/44.48 3/44.80 2/44.13 2/43.60 | |POLY-3 PERCENT (g) | 11.0% 18.1% 17.6% 31.5% |11.2% 6.7% 4.5% 4.6% | |TERMINAL (d) | 5/39 (13%) 7/40 (18%) 8/38 (21%) 9/30 (30%) |5/37 (14%) 2/38 (5%) 2/37 (5%) 2/34 (6%) | |FIRST INCIDENCE | 730 (T) 707 730 (T) 621 |729 (T) 555 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004 ** P=0.295 P=0.256 P=0.009 ** |P=0.255N P=0.344N P=0.215N P=0.250N | |POLY 3 | P=0.014 * P=0.256 P=0.272 P=0.016 * |P=0.230N P=0.352N P=0.219N P=0.224N | |POLY 1.5 | P=0.016 * P=0.254 P=0.275 P=0.019 * |P=0.227N P=0.357N P=0.216N P=0.222N | |POLY 6 | P=0.011 * P=0.270 P=0.267 P=0.014 * |P=0.236N P=0.347N P=0.224N P=0.228N | |LOGISTIC REGRESSION| P=0.007 ** P=0.292 P=0.256 P=0.014 * |P=0.228N P=0.359N P=0.215N P=0.250N | |COCH-ARM / FISHERS | P=0.024 * P=0.277 P=0.277 P=0.030 * |P=0.229N P=0.357N P=0.218N P=0.226N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Cortex | | Hypertrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 27/50 (54%) 27/50 (54%) 23/50 (46%) 15/49 (31%) |1/49 (2%) 3/49 (6%) 3/49 (6%) 12/48 (25%) | |POLY-3 RATE (b) | 27/45.83 27/45.01 23/46.13 15/40.86 |1/44.48 3/44.24 3/44.13 12/44.29 | |POLY-3 PERCENT (g) | 58.9% 60.0% 49.9% 36.7% |2.3% 6.8% 6.8% 27.1% | |TERMINAL (d) | 25/39 (64%) 24/40 (60%) 21/38 (55%) 13/30 (43%) |1/37 (3%) 3/38 (8%) 3/37 (8%) 10/34 (29%) | |FIRST INCIDENCE | 690 508 548 646 |729 (T) 729 (T) 729 (T) 517 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.073N P=0.526N P=0.310N P=0.109N |P<0.001 ** P=0.314 P=0.305 P<0.001 ** | |POLY 3 | P=0.011N* P=0.544 P=0.249N P=0.027N* |P<0.001 ** P=0.303 P=0.302 P<0.001 ** | |POLY 1.5 | P=0.009N** P=0.523 P=0.257N P=0.024N* |P<0.001 ** P=0.302 P=0.305 P<0.001 ** | |POLY 6 | P=0.018N* P=0.574N P=0.247N P=0.035N* |P<0.001 ** P=0.304 P=0.298 P<0.001 ** | |LOGISTIC REGRESSION| P=0.023N* P=0.547 P=0.288N P=0.060N |P<0.001 ** P=0.314 P=0.305 P<0.001 ** | |COCH-ARM / FISHERS | P=0.005N** P=0.579N P=0.274N P=0.015N* |P<0.001 ** P=0.309 P=0.309 P<0.001 ** | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 2 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Adrenal Medulla | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 0/50 (0%) 1/49 (2%) |0/49 (0%) 0/49 (0%) 0/47 (0%) 0/47 (0%) | |POLY-3 RATE (b) | 0/45.56 3/44.27 0/45.36 1/40.28 |0/44.48 0/44.24 0/42.51 0/42.86 | |POLY-3 PERCENT (g) | 0.0% 6.8% 0.0% 2.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 2/40 (5%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 707 --- 730 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.652 P=0.131 (e) P=0.448 |(e) (e) (e) (e) | |POLY 3 | P=0.647N P=0.114 (e) P=0.475 |(e) (e) (e) (e) | |POLY 1.5 | P=0.642N P=0.113 (e) P=0.481 |(e) (e) (e) (e) | |POLY 6 | P=0.652N P=0.117 (e) P=0.468 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.673 P=0.117 (e) P=0.448 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.621N P=0.121 (e) P=0.495 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Bone | | Fibrous Osteodystrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |4/50 (8%) 1/50 (2%) 5/50 (10%) 5/50 (10%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 0/40.88 |4/44.88 1/45.21 5/44.89 5/45.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |8.9% 2.2% 11.1% 11.1% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |4/37 (11%) 1/38 (3%) 4/37 (11%) 5/34 (15%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 677 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.190 P=0.171N P=0.497 P=0.446 | |POLY 3 | (e) (e) (e) (e) |P=0.239 P=0.176N P=0.500 P=0.505 | |POLY 1.5 | (e) (e) (e) (e) |P=0.245 P=0.179N P=0.503 P=0.507 | |POLY 6 | (e) (e) (e) (e) |P=0.229 P=0.173N P=0.495 P=0.497 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.217 P=0.171N P=0.484 P=0.446 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.238 P=0.181N P=0.500 P=0.500 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 3 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Eye: Cornea | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/0 (0%) 1/1 (100%) 2/2 (100%) 0/1 (0%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 1/2 (50%) | |POLY-3 RATE (b) | 0/0.00 1/1.00 2/2.00 0/0.51 |0/0.00 0/0.00 0/1.00 1/2.00 | |POLY-3 PERCENT (g) | 0.0% 100.0% 100.0% 0.0% |0.0% 0.0% 0.0% 50.0% | |TERMINAL (d) | 0/0 (0%) 1/1 (100%) 2/2 (100%) 0/0 (0%) |0/0 (0%) 0/0 (0%) 0/1 (0%) 1/2 (50%) | |FIRST INCIDENCE | --- 730 (T) 730 (T) --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=1.000 (e) (e) (e) |P=0.638 (e) (e) P=1.000N | |POLY 3 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 1.5 | (e) (e) (e) (e) |(e) (e) (e) (e) | |POLY 6 | (e) (e) (e) (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=1.000N | |COCH-ARM / FISHERS | P=0.221N (e) (e) (e) |P=0.667 (e) (e) P=1.000 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Gallbladder | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/40 (0%) 1/38 (3%) 1/39 (3%) 0/34 (0%) |0/39 (0%) 2/40 (5%) 1/38 (3%) 1/38 (3%) | |POLY-3 RATE (b) | 0/38.19 1/33.83 1/36.93 0/29.75 |0/36.77 2/37.97 1/35.38 1/35.22 | |POLY-3 PERCENT (g) | 0.0% 3.0% 2.7% 0.0% |0.0% 5.3% 2.8% 2.8% | |TERMINAL (d) | 0/35 (0%) 1/32 (3%) 1/33 (3%) 0/26 (0%) |0/34 (0%) 2/35 (6%) 0/33 (0%) 1/31 (3%) | |FIRST INCIDENCE | --- 730 (T) 730 (T) --- |--- 729 (T) 653 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.602N P=0.482 P=0.488 (e) |P=0.588 P=0.245 P=0.490 P=0.482 | |POLY 3 | P=0.595N P=0.476 P=0.493 (e) |P=0.596 P=0.244 P=0.492 P=0.491 | |POLY 1.5 | P=0.590N P=0.478 P=0.494 (e) |P=0.599 P=0.242 P=0.493 P=0.493 | |POLY 6 | P=0.601N P=0.476 P=0.492 (e) |P=0.591 P=0.245 P=0.493 P=0.489 | |LOGISTIC REGRESSION| (e) P=0.482 P=0.488 (e) |P=0.603 P=0.245 P=0.512 P=0.482 | |COCH-ARM / FISHERS | P=0.574N P=0.487 P=0.494 (e) |P=0.603 P=0.253 P=0.494 P=0.494 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 4 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Gallbladder | | Degeneration Hyaline | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/40 (8%) 1/38 (3%) 0/39 (0%) 1/34 (3%) |1/39 (3%) 1/40 (3%) 3/38 (8%) 2/38 (5%) | |POLY-3 RATE (b) | 3/38.43 1/33.83 0/36.93 1/29.75 |1/36.77 1/37.97 3/35.10 2/35.22 | |POLY-3 PERCENT (g) | 7.8% 3.0% 0.0% 3.4% |2.7% 2.6% 8.6% 5.7% | |TERMINAL (d) | 2/35 (6%) 1/32 (3%) 0/33 (0%) 1/26 (4%) |1/34 (3%) 1/35 (3%) 3/33 (9%) 2/31 (7%) | |FIRST INCIDENCE | 664 730 (T) --- 730 (T) |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.421N P=0.328N P=0.134N P=0.414N |P=0.356 P=0.755N P=0.294 P=0.468 | |POLY 3 | P=0.381N P=0.352N P=0.125N P=0.401N |P=0.376 P=0.753N P=0.288 P=0.485 | |POLY 1.5 | P=0.380N P=0.347N P=0.124N P=0.391N |P=0.382 P=0.755N P=0.290 P=0.488 | |POLY 6 | P=0.384N P=0.354N P=0.127N P=0.412N |P=0.368 P=0.752N P=0.286 P=0.481 | |LOGISTIC REGRESSION| P=0.396N P=0.339N P=0.123N P=0.385N |P=0.356 P=0.755N P=0.294 P=0.468 | |COCH-ARM / FISHERS | P=0.381N P=0.327N P=0.125N P=0.371N |P=0.386 P=0.747N P=0.298 P=0.490 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Harderian Gland | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 1/48 (2%) 1/49 (2%) 1/48 (2%) |3/48 (6%) 3/41 (7%) 2/50 (4%) 4/46 (9%) | |POLY-3 RATE (b) | 1/44.56 1/42.84 1/44.86 1/39.66 |3/43.37 3/36.80 2/44.70 4/41.57 | |POLY-3 PERCENT (g) | 2.2% 2.3% 2.2% 2.5% |6.9% 8.2% 4.5% 9.6% | |TERMINAL (d) | 1/38 (3%) 1/39 (3%) 1/38 (3%) 1/30 (3%) |2/35 (6%) 2/32 (6%) 2/37 (5%) 4/32 (13%) | |FIRST INCIDENCE | 730 (T) 730 (T) 730 (T) 730 (T) |583 703 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.601 P=0.756N P=0.762 P=0.708 |P=0.367 P=0.633 P=0.478N P=0.458 | |POLY 3 | P=0.633 P=0.752 P=0.759N P=0.734 |P=0.408 P=0.585 P=0.486N P=0.477 | |POLY 1.5 | P=0.642 P=0.750 P=0.759N P=0.740 |P=0.413 P=0.582 P=0.482N P=0.481 | |POLY 6 | P=0.618 P=0.758 P=0.759N P=0.726 |P=0.399 P=0.590 P=0.494N P=0.469 | |LOGISTIC REGRESSION| P=0.601 P=0.756N P=0.762 P=0.708 |P=0.411 P=0.587 P=0.480N P=0.482 | |COCH-ARM / FISHERS | P=0.665 P=0.747 P=0.753N P=0.747 |P=0.406 P=0.583 P=0.480N P=0.476 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 5 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Harderian Gland | | Inflammation Acute | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/48 (2%) 2/49 (4%) 0/48 (0%) |0/48 (0%) 0/41 (0%) 0/50 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/44.56 1/42.84 2/44.88 0/39.66 |0/42.88 0/36.70 0/44.70 0/41.57 | |POLY-3 PERCENT (g) | 0.0% 2.3% 4.5% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/38 (0%) 1/39 (3%) 1/38 (3%) 0/30 (0%) |0/35 (0%) 0/32 (0%) 0/37 (0%) 0/32 (0%) | |FIRST INCIDENCE | --- 730 (T) 725 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.590N P=0.505 P=0.240 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.556N P=0.492 P=0.239 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.546N P=0.490 P=0.238 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.571N P=0.497 P=0.239 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.579N P=0.505 P=0.239 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.520N P=0.495 P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Cardiomyopathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 3/45.56 0/44.17 1/45.36 2/40.88 |0/44.88 1/45.39 1/44.98 1/45.21 | |POLY-3 PERCENT (g) | 6.6% 0.0% 2.2% 4.9% |0.0% 2.2% 2.2% 2.2% | |TERMINAL (d) | 3/39 (8%) 0/40 (0%) 1/38 (3%) 2/30 (7%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) 730 (T) |--- 681 653 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.465 P=0.117N P=0.314N P=0.619N |P=0.472 P=0.514 P=0.490 P=0.483 | |POLY 3 | P=0.543 P=0.124N P=0.307N P=0.549N |P=0.486 P=0.502 P=0.500 P=0.501 | |POLY 1.5 | P=0.555 P=0.125N P=0.306N P=0.535N |P=0.488 P=0.500 P=0.501 P=0.502 | |POLY 6 | P=0.523 P=0.120N P=0.309N P=0.569N |P=0.480 P=0.505 P=0.499 P=0.499 | |LOGISTIC REGRESSION| P=0.465 (e) P=0.314N P=0.619N |P=0.481 P=0.501 P=0.492 P=0.483 | |COCH-ARM / FISHERS | P=0.571 P=0.121N P=0.309N P=0.500N |P=0.483 P=0.500 P=0.500 P=0.500 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 6 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 2/50 (4%) 1/50 (2%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 0/40.88 |1/45.63 2/45.31 1/44.70 0/45.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.2% 4.4% 2.2% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 1/38 (3%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- --- |456 703 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.249N P=0.509 P=0.758N P=0.496N | |POLY 3 | (e) (e) (e) (e) |P=0.237N P=0.498 P=0.756 P=0.502N | |POLY 1.5 | (e) (e) (e) (e) |P=0.235N P=0.496 P=0.759 P=0.500N | |POLY 6 | (e) (e) (e) (e) |P=0.241N P=0.500 P=0.752 P=0.505N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.247N P=0.515 P=0.739 P=0.664N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.235N P=0.500 P=0.753N P=0.500N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Heart | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 1/45.91 0/44.17 1/45.36 2/41.59 |1/45.21 1/45.21 1/45.08 1/45.32 | |POLY-3 PERCENT (g) | 2.2% 0.0% 2.2% 4.8% |2.2% 2.2% 2.2% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 1/38 (3%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 632 --- 730 (T) 617 |636 729 (T) 621 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.191 P=0.505N P=0.755 P=0.452 |P=0.658 P=0.757N P=0.758 P=0.757 | |POLY 3 | P=0.216 P=0.508N P=0.758 P=0.466 |P=0.666N P=0.761 P=0.760 P=0.760N | |POLY 1.5 | P=0.223 P=0.508N P=0.759 P=0.475 |P=0.664N P=0.759 P=0.760N P=0.759N | |POLY 6 | P=0.204 P=0.505N P=0.755 P=0.453 |P=0.662 P=0.760N P=0.757 P=0.758 | |LOGISTIC REGRESSION| P=0.256 P=0.469N P=0.761 P=0.555 |P=0.660 P=0.762N P=0.749 P=0.755 | |COCH-ARM / FISHERS | P=0.235 P=0.500N P=0.753N P=0.500 |P=0.668N P=0.753N P=0.753N P=0.753N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 7 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Heart: Artery | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 3/45.81 0/40.88 |0/44.88 0/45.21 0/44.70 0/45.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.6% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 2/38 (5%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 597 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.691 (e) P=0.119 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.686 (e) P=0.120 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.676N (e) P=0.120 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.655 (e) P=0.119 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.647N (e) P=0.119 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.646N (e) P=0.121 (e) |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Cecum | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 0/46 (0%) 2/39 (5%) |0/41 (0%) 0/43 (0%) 0/44 (0%) 0/43 (0%) | |POLY-3 RATE (b) | 0/44.72 0/42.17 0/43.31 2/35.39 |0/39.12 0/40.87 0/40.14 0/39.93 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 5.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 0/37 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 584 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.030 * (e) (e) P=0.200 |(e) (e) (e) (e) | |POLY 3 | P=0.026 * (e) (e) P=0.186 |(e) (e) (e) (e) | |POLY 1.5 | P=0.026 * (e) (e) P=0.185 |(e) (e) (e) (e) | |POLY 6 | P=0.026 * (e) (e) P=0.187 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.030 * (e) (e) P=0.201 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.027 * (e) (e) P=0.194 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 8 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 0/46 (0%) 6/44 (14%) |0/45 (0%) 0/45 (0%) 2/44 (5%) 10/46 (22%) | |POLY-3 RATE (b) | 0/44.56 0/42.17 0/43.31 6/38.29 |0/41.21 0/42.20 2/41.31 10/43.74 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 15.7% |0.0% 0.0% 4.8% 22.9% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 0/38 (0%) 3/30 (10%) |0/37 (0%) 0/37 (0%) 0/37 (0%) 7/34 (21%) | |FIRST INCIDENCE | --- --- --- 498 |--- --- 509 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P=0.011 * |P<0.001 ** (e) P=0.244 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.008 ** |P<0.001 ** (e) P=0.237 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.008 ** |P<0.001 ** (e) P=0.236 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.008 ** |P<0.001 ** (e) P=0.239 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.014 * |P<0.001 ** (e) P=0.185 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.009 ** |P<0.001 ** (e) P=0.242 P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 1/46 (2%) 8/44 (18%) |0/45 (0%) 0/45 (0%) 2/44 (5%) 32/46 (70%) | |POLY-3 RATE (b) | 0/44.56 0/42.17 1/43.31 8/37.93 |0/41.21 0/42.20 2/40.55 32/45.04 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.3% 21.1% |0.0% 0.0% 4.9% 71.1% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 1/38 (3%) 5/30 (17%) |0/37 (0%) 0/37 (0%) 1/37 (3%) 23/34 (68%) | |FIRST INCIDENCE | --- --- 730 (T) 584 |--- --- 653 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) P=0.500 P=0.002 ** |P<0.001 ** (e) P=0.235 P<0.001 ** | |POLY 3 | P<0.001 ** (e) P=0.494 P<0.001 ** |P<0.001 ** (e) P=0.233 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) P=0.492 P<0.001 ** |P<0.001 ** (e) P=0.234 P<0.001 ** | |POLY 6 | P<0.001 ** (e) P=0.497 P<0.001 ** |P<0.001 ** (e) P=0.233 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) P=0.500 P=0.002 ** |P<0.001 ** (e) P=0.231 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) P=0.484 P=0.002 ** |P<0.001 ** (e) P=0.242 P<0.001 ** | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 9 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 0/46 (0%) 5/44 (11%) |0/45 (0%) 0/45 (0%) 1/44 (2%) 26/46 (57%) | |POLY-3 RATE (b) | 0/44.56 0/42.17 0/43.31 5/37.45 |0/41.21 0/42.20 1/40.27 26/44.66 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.4% |0.0% 0.0% 2.5% 58.2% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 0/38 (0%) 3/30 (10%) |0/37 (0%) 0/37 (0%) 1/37 (3%) 18/34 (53%) | |FIRST INCIDENCE | --- --- --- 617 |--- --- 729 (T) 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P=0.020 * |P<0.001 ** (e) P=0.500 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.018 * |P<0.001 ** (e) P=0.495 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.018 * |P<0.001 ** (e) P=0.496 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.017 * |P<0.001 ** (e) P=0.494 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.021 * |P<0.001 ** (e) P=0.500 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.021 * |P<0.001 ** (e) P=0.494 P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Myxomatous Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 0/46 (0%) 13/44 (30%) |0/45 (0%) 3/45 (7%) 21/44 (48%) 31/46 (67%) | |POLY-3 RATE (b) | 0/44.56 0/42.17 0/43.31 13/39.27 |0/41.21 3/42.39 21/41.78 31/45.77 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 33.1% |0.0% 7.1% 50.3% 67.7% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 0/38 (0%) 8/30 (27%) |0/37 (0%) 2/37 (5%) 18/37 (49%) 21/34 (62%) | |FIRST INCIDENCE | --- --- --- 498 |--- 681 509 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.127 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.123 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.121 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.125 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.122 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P<0.001 ** |P<0.001 ** P=0.121 P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 10 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Intestine Large, Rectum | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/47 (0%) 0/46 (0%) 5/44 (11%) |0/45 (0%) 0/45 (0%) 1/44 (2%) 24/46 (52%) | |POLY-3 RATE (b) | 0/44.56 0/42.17 0/43.31 5/37.54 |0/41.21 0/42.20 1/40.55 24/44.94 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 13.3% |0.0% 0.0% 2.5% 53.4% | |TERMINAL (d) | 0/38 (0%) 0/40 (0%) 0/38 (0%) 3/30 (10%) |0/37 (0%) 0/37 (0%) 0/37 (0%) 16/34 (47%) | |FIRST INCIDENCE | --- --- --- 584 |--- --- 653 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** (e) (e) P=0.020 * |P<0.001 ** (e) P=0.490 P<0.001 ** | |POLY 3 | P<0.001 ** (e) (e) P=0.018 * |P<0.001 ** (e) P=0.497 P<0.001 ** | |POLY 1.5 | P<0.001 ** (e) (e) P=0.018 * |P<0.001 ** (e) P=0.497 P<0.001 ** | |POLY 6 | P<0.001 ** (e) (e) P=0.017 * |P<0.001 ** (e) P=0.496 P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** (e) (e) P=0.022 * |P<0.001 ** (e) P=0.487 P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** (e) (e) P=0.021 * |P<0.001 ** (e) P=0.494 P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 3/50 (6%) 1/49 (2%) |0/48 (0%) 1/49 (2%) 0/48 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 3/45.36 1/40.16 |0/44.46 1/44.91 0/43.18 0/41.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.6% 2.5% |0.0% 2.2% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 3/38 (8%) 1/30 (3%) |0/37 (0%) 1/38 (3%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 730 (T) 730 (T) |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.297 (e) P=0.116 P=0.448 |P=0.602N P=0.505 (e) (e) | |POLY 3 | P=0.327 (e) P=0.118 P=0.475 |P=0.596N P=0.502 (e) (e) | |POLY 1.5 | P=0.344 (e) P=0.119 P=0.481 |P=0.596N P=0.501 (e) (e) | |POLY 6 | P=0.302 (e) P=0.116 P=0.467 |P=0.595N P=0.504 (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.116 P=0.448 |(e) P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.379 (e) P=0.121 P=0.495 |P=0.594N P=0.505 (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 11 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Infarct | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 3/50 (6%) 4/50 (8%) 0/49 (0%) |0/48 (0%) 1/49 (2%) 1/48 (2%) 1/46 (2%) | |POLY-3 RATE (b) | 1/45.56 3/44.17 4/45.81 0/40.16 |0/44.46 1/45.02 1/43.46 1/41.91 | |POLY-3 PERCENT (g) | 2.2% 6.8% 8.7% 0.0% |0.0% 2.2% 2.3% 2.4% | |TERMINAL (d) | 1/39 (3%) 3/40 (8%) 3/38 (8%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | 730 (T) 730 (T) 597 --- |--- 703 653 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.282N P=0.314 P=0.174 P=0.552N |P=0.465 P=0.510 P=0.490 P=0.483 | |POLY 3 | P=0.255N P=0.294 P=0.180 P=0.525N |P=0.463 P=0.502 P=0.495 P=0.488 | |POLY 1.5 | P=0.240N P=0.293 P=0.180 P=0.519N |P=0.466 P=0.501 P=0.497 P=0.490 | |POLY 6 | P=0.277N P=0.301 P=0.180 P=0.533N |P=0.459 P=0.505 P=0.494 P=0.486 | |LOGISTIC REGRESSION| P=0.237N P=0.314 P=0.179 (e) |P=0.468 P=0.503 P=0.518 P=0.483 | |COCH-ARM / FISHERS | P=0.210N P=0.309 P=0.181 P=0.505N |P=0.469 P=0.505 P=0.500 P=0.489 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 3/50 (6%) 1/49 (2%) |0/48 (0%) 0/49 (0%) 0/48 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/45.56 3/44.27 3/46.84 1/40.75 |0/44.46 0/44.91 0/43.18 0/41.91 | |POLY-3 PERCENT (g) | 0.0% 6.8% 6.4% 2.5% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 1/40 (3%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 707 465 539 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.622N P=0.133 P=0.124 P=0.487 |(e) (e) (e) (e) | |POLY 3 | P=0.610N P=0.114 P=0.124 P=0.478 |(e) (e) (e) (e) | |POLY 1.5 | P=0.599N P=0.113 P=0.122 P=0.482 |(e) (e) (e) (e) | |POLY 6 | P=0.623 P=0.117 P=0.125 P=0.471 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.500N P=0.117 P=0.067 P=0.591 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.564N P=0.121 P=0.121 P=0.495 |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 12 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 1/50 (2%) 0/50 (0%) 0/49 (0%) |0/48 (0%) 0/49 (0%) 0/48 (0%) 3/46 (7%) | |POLY-3 RATE (b) | 1/45.56 1/44.17 0/45.36 0/40.16 |0/44.46 0/44.91 0/43.18 3/41.91 | |POLY-3 PERCENT (g) | 2.2% 2.3% 0.0% 0.0% |0.0% 0.0% 0.0% 7.2% | |TERMINAL (d) | 1/39 (3%) 1/40 (3%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 3/34 (9%) | |FIRST INCIDENCE | 730 (T) 730 (T) --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.351N P=0.756N P=0.505N P=0.552N |P=0.006 ** (e) (e) P=0.106 | |POLY 3 | P=0.316N P=0.754 P=0.501N P=0.525N |P=0.006 ** (e) (e) P=0.108 | |POLY 1.5 | P=0.315N P=0.753 P=0.500N P=0.519N |P=0.007 ** (e) (e) P=0.109 | |POLY 6 | P=0.319N P=0.758 P=0.502N P=0.533N |P=0.006 ** (e) (e) P=0.106 | |LOGISTIC REGRESSION| P=0.351N P=0.756N (e) (e) |(e) (e) (e) P=0.106 | |COCH-ARM / FISHERS | P=0.309N P=0.753N P=0.500N P=0.505N |P=0.007 ** (e) (e) P=0.113 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Mineralization | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |3/48 (6%) 2/49 (4%) 1/48 (2%) 1/46 (2%) | |POLY-3 RATE (b) | 1/46.28 0/44.17 0/45.36 0/40.16 |3/44.87 2/45.17 1/43.84 1/41.91 | |POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 0.0% |6.7% 4.4% 2.3% 2.4% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | 477 --- --- --- |661 681 509 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.471N P=0.513N P=0.500N P=0.504N |P=0.284N P=0.485N P=0.322N P=0.332N | |POLY 3 | P=0.464N P=0.509N P=0.504N P=0.528N |P=0.285N P=0.497N P=0.314N P=0.330N | |POLY 1.5 | P=0.466N P=0.509N P=0.502N P=0.521N |P=0.281N P=0.499N P=0.310N P=0.326N | |POLY 6 | P=0.463N P=0.506N P=0.506N P=0.537N |P=0.290N P=0.494N P=0.319N P=0.336N | |LOGISTIC REGRESSION| P=0.384N P=0.358N P=0.667N P=0.362N |P=0.284N P=0.488N P=0.267N P=0.320N | |COCH-ARM / FISHERS | P=0.475N P=0.500N P=0.500N P=0.505N |P=0.279N P=0.490N P=0.308N P=0.325N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 13 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney | | Nephropathy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 43/50 (86%) 41/50 (82%) 47/50 (94%) 41/49 (84%) |19/48 (40%) 17/49 (35%) 22/48 (46%) 27/46 (59%) | |POLY-3 RATE (b) | 43/49.04 41/46.92 47/48.34 41/44.83 |19/45.89 17/45.76 22/46.22 27/44.12 | |POLY-3 PERCENT (g) | 87.7% 87.4% 97.2% 91.5% |41.4% 37.2% 47.6% 61.2% | |TERMINAL (d) | 34/39 (87%) 37/40 (93%) 38/38 (100%) 29/30 (97%) |15/37 (41%) 14/38 (37%) 15/37 (41%) 20/34 (59%) | |FIRST INCIDENCE | 477 455 548 492 |456 555 481 509 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.020 * P=0.357N P=0.197 P=0.098 |P=0.016 * P=0.383N P=0.350 P=0.056 | |POLY 3 | P=0.298 P=0.605N P=0.067 P=0.393 |P=0.013 * P=0.420N P=0.349 P=0.045 * | |POLY 1.5 | P=0.380 P=0.577N P=0.099 P=0.470 |P=0.013 * P=0.423N P=0.342 P=0.045 * | |POLY 6 | P=0.184 P=0.621N P=0.039 * P=0.286 |P=0.012 * P=0.414N P=0.360 P=0.044 * | |LOGISTIC REGRESSION| P=0.378 P=0.562N P=0.155 P=0.447 |P=0.013 * P=0.403N P=0.355 P=0.049 * | |COCH-ARM / FISHERS | P=0.499N P=0.393N P=0.159 P=0.483N |P=0.013 * P=0.387N P=0.340 P=0.050 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Kidney: Renal Tubule | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 0/49 (0%) |0/48 (0%) 0/49 (0%) 0/48 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 2/45.36 0/40.16 |0/44.46 0/44.91 0/43.18 0/41.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 4.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 2/38 (5%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 730 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.725 (e) P=0.233 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.720 (e) P=0.236 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.720N (e) P=0.237 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.698 (e) P=0.235 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) P=0.233 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.700N (e) P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 14 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 10/50 (20%) 5/50 (10%) 10/50 (20%) |5/50 (10%) 6/49 (12%) 8/50 (16%) 12/49 (24%) | |POLY-3 RATE (b) | 14/47.07 10/45.26 5/45.36 10/40.88 |5/44.88 6/44.91 8/44.89 12/44.29 | |POLY-3 PERCENT (g) | 29.8% 22.1% 11.0% 24.5% |11.1% 13.4% 17.8% 27.1% | |TERMINAL (d) | 11/39 (28%) 8/40 (20%) 5/38 (13%) 10/30 (33%) |5/37 (14%) 6/38 (16%) 7/37 (19%) 12/34 (35%) | |FIRST INCIDENCE | 420 311 730 (T) 730 (T) |729 (T) 729 (T) 677 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.533 P=0.235N P=0.025N* P=0.490N |P=0.013 * P=0.519 P=0.272 P=0.032 * | |POLY 3 | P=0.426N P=0.274N P=0.022N* P=0.377N |P=0.023 * P=0.501 P=0.275 P=0.047 * | |POLY 1.5 | P=0.391N P=0.274N P=0.021N* P=0.332N |P=0.025 * P=0.491 P=0.279 P=0.049 * | |POLY 6 | P=0.481N P=0.263N P=0.025N* P=0.442N |P=0.020 * P=0.510 P=0.268 P=0.044 * | |LOGISTIC REGRESSION| P=0.390N P=0.238N P=0.021N* P=0.339N |P=0.016 * P=0.519 P=0.254 P=0.032 * | |COCH-ARM / FISHERS | P=0.327N P=0.241N P=0.020N* P=0.241N |P=0.025 * P=0.486 P=0.277 P=0.049 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Clear Cell Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 21/50 (42%) 23/50 (46%) 19/50 (38%) 15/50 (30%) |0/50 (0%) 4/49 (8%) 1/50 (2%) 21/49 (43%) | |POLY-3 RATE (b) | 21/45.81 23/44.17 19/45.78 15/40.88 |0/44.88 4/45.02 1/44.70 21/45.13 | |POLY-3 PERCENT (g) | 45.8% 52.1% 41.5% 36.7% |0.0% 8.9% 2.2% 46.5% | |TERMINAL (d) | 20/39 (51%) 23/40 (58%) 18/38 (47%) 15/30 (50%) |0/37 (0%) 3/38 (8%) 1/37 (3%) 20/34 (59%) | |FIRST INCIDENCE | 664 730 (T) 611 730 (T) |--- 703 729 (T) 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.361N P=0.461 P=0.459N P=0.469N |P<0.001 ** P=0.069 P=0.500 P<0.001 ** | |POLY 3 | P=0.138N P=0.351 P=0.417N P=0.256N |P<0.001 ** P=0.061 P=0.499 P<0.001 ** | |POLY 1.5 | P=0.111N P=0.351 P=0.416N P=0.221N |P<0.001 ** P=0.059 P=0.501 P<0.001 ** | |POLY 6 | P=0.195N P=0.377 P=0.424N P=0.319N |P<0.001 ** P=0.063 P=0.497 P<0.001 ** | |LOGISTIC REGRESSION| P=0.291N P=0.479 P=0.443N P=0.412N |P<0.001 ** P=0.064 P=0.500 P<0.001 ** | |COCH-ARM / FISHERS | P=0.070N P=0.420 P=0.419N P=0.149N |P<0.001 ** P=0.056 P=0.500 P<0.001 ** | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 15 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Eosinophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 13/50 (26%) 11/50 (22%) 9/50 (18%) 12/50 (24%) |10/50 (20%) 6/49 (12%) 7/50 (14%) 15/49 (31%) | |POLY-3 RATE (b) | 13/45.99 11/44.93 9/45.36 12/41.26 |10/45.26 6/44.91 7/44.70 15/44.45 | |POLY-3 PERCENT (g) | 28.3% 24.5% 19.8% 29.1% |22.1% 13.4% 15.7% 33.8% | |TERMINAL (d) | 12/39 (31%) 10/40 (25%) 9/38 (24%) 9/30 (30%) |7/37 (19%) 6/38 (16%) 7/37 (19%) 13/34 (38%) | |FIRST INCIDENCE | 606 455 730 (T) 676 |667 729 (T) 729 (T) 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.259 P=0.387N P=0.252N P=0.396 |P=0.017 * P=0.194N P=0.306N P=0.129 | |POLY 3 | P=0.450 P=0.432N P=0.242N P=0.561 |P=0.027 * P=0.209N P=0.305N P=0.158 | |POLY 1.5 | P=0.488 P=0.439N P=0.238N P=0.590N |P=0.029 * P=0.216N P=0.298N P=0.165 | |POLY 6 | P=0.395 P=0.410N P=0.251N P=0.512 |P=0.023 * P=0.204N P=0.321N P=0.145 | |LOGISTIC REGRESSION| P=0.396 P=0.440N P=0.242N P=0.486 |P=0.021 * P=0.194N P=0.314N P=0.146 | |COCH-ARM / FISHERS | P=0.553N P=0.408N P=0.235N P=0.500N |P=0.030 * P=0.220N P=0.298N P=0.163 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Fatty Change | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 9/50 (18%) 12/50 (24%) 8/50 (16%) 13/50 (26%) |4/50 (8%) 2/49 (4%) 1/50 (2%) 12/49 (24%) | |POLY-3 RATE (b) | 9/46.28 12/45.86 8/46.68 13/41.39 |4/46.57 2/45.23 1/44.70 12/46.98 | |POLY-3 PERCENT (g) | 19.5% 26.2% 17.1% 31.4% |8.6% 4.4% 2.2% 25.5% | |TERMINAL (d) | 8/39 (21%) 10/40 (25%) 6/38 (16%) 12/30 (40%) |0/37 (0%) 1/38 (3%) 1/37 (3%) 6/34 (18%) | |FIRST INCIDENCE | 477 311 465 576 |411 642 729 (T) 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.081 P=0.329 P=0.517N P=0.080 |P<0.001 ** P=0.341N P=0.187N P=0.033 * | |POLY 3 | P=0.161 P=0.302 P=0.492N P=0.147 |P<0.001 ** P=0.351N P=0.191N P=0.026 * | |POLY 1.5 | P=0.187 P=0.294 P=0.494N P=0.170 |P<0.001 ** P=0.352N P=0.185N P=0.026 * | |POLY 6 | P=0.129 P=0.321 P=0.493N P=0.119 |P<0.001 ** P=0.349N P=0.201N P=0.026 * | |LOGISTIC REGRESSION| P=0.228 P=0.322 P=0.502N P=0.145 |P<0.001 ** P=0.328N P=0.199N P=0.013 * | |COCH-ARM / FISHERS | P=0.251 P=0.312 P=0.500N P=0.235 |P<0.001 ** P=0.349N P=0.181N P=0.024 * | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 16 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |3/50 (6%) 7/49 (14%) 5/50 (10%) 7/49 (14%) | |POLY-3 RATE (b) | 0/45.56 1/45.10 1/45.36 0/40.88 |3/45.03 7/45.76 5/46.16 7/45.54 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.2% 0.0% |6.7% 15.3% 10.8% 15.4% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 0/30 (0%) |1/37 (3%) 4/38 (11%) 2/37 (5%) 2/34 (6%) | |FIRST INCIDENCE | --- 311 730 (T) --- |703 555 481 509 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.576N P=0.496 P=0.495 (e) |P=0.224 P=0.180 P=0.358 P=0.151 | |POLY 3 | P=0.568N P=0.498 P=0.499 (e) |P=0.254 P=0.164 P=0.370 P=0.162 | |POLY 1.5 | P=0.560N P=0.496 P=0.500 (e) |P=0.253 P=0.156 P=0.368 P=0.160 | |POLY 6 | P=0.578N P=0.503 P=0.498 (e) |P=0.251 P=0.173 P=0.370 P=0.162 | |LOGISTIC REGRESSION| P=0.438N P=0.798 P=0.495 (e) |P=0.227 P=0.151 P=0.345 P=0.146 | |COCH-ARM / FISHERS | P=0.541N P=0.500 P=0.500 (e) |P=0.240 P=0.151 P=0.357 P=0.151 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 15/50 (30%) 23/50 (46%) 33/50 (66%) |40/50 (80%) 37/49 (76%) 40/50 (80%) 38/49 (78%) | |POLY-3 RATE (b) | 10/45.56 15/44.93 23/46.99 33/43.21 |40/46.83 37/45.31 40/46.76 38/47.64 | |POLY-3 PERCENT (g) | 22.0% 33.4% 49.0% 76.4% |85.4% 81.7% 85.6% 79.8% | |TERMINAL (d) | 10/39 (26%) 14/40 (35%) 19/38 (50%) 28/30 (93%) |34/37 (92%) 34/38 (90%) 35/37 (95%) 30/34 (88%) | |FIRST INCIDENCE | 730 (T) 455 465 498 |456 681 313 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.190 P=0.004 ** P<0.001 ** |P=0.301 P=0.221N P=0.588 P=0.520 | |POLY 3 | P<0.001 ** P=0.162 P=0.005 ** P<0.001 ** |P=0.306N P=0.415N P=0.617 P=0.318N | |POLY 1.5 | P<0.001 ** P=0.157 P=0.005 ** P<0.001 ** |P=0.351N P=0.419N P=0.586N P=0.353N | |POLY 6 | P<0.001 ** P=0.180 P=0.005 ** P<0.001 ** |P=0.286N P=0.416N P=0.554 P=0.307N | |LOGISTIC REGRESSION| P<0.001 ** P=0.156 P=0.005 ** P<0.001 ** |P=0.480N P=0.272N P=0.593N P=0.426N | |COCH-ARM / FISHERS | P<0.001 ** P=0.178 P=0.005 ** P<0.001 ** |P=0.520N P=0.384N P=0.598N P=0.479N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 17 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 5/50 (10%) |0/50 (0%) 0/49 (0%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/46.28 2/44.18 2/45.94 5/42.68 |0/44.88 0/44.91 0/44.70 0/44.29 | |POLY-3 PERCENT (g) | 4.3% 4.5% 4.4% 11.7% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 1/40 (3%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 477 728 548 539 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.067 P=0.689N P=0.689 P=0.173 |(e) (e) (e) (e) | |POLY 3 | P=0.088 P=0.677 P=0.691 P=0.184 |(e) (e) (e) (e) | |POLY 1.5 | P=0.092 P=0.677 P=0.692 P=0.191 |(e) (e) (e) (e) | |POLY 6 | P=0.083 P=0.683 P=0.689 P=0.177 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.134 P=0.678N P=0.671 P=0.288 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.103 P=0.691N P=0.691N P=0.218 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver | | Tension Lipidosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 2/50 (4%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 2/49 (4%) 1/50 (2%) 0/49 (0%) | |POLY-3 RATE (b) | 2/45.91 2/45.10 2/45.36 0/40.88 |0/44.88 2/45.47 1/44.70 0/44.29 | |POLY-3 PERCENT (g) | 4.4% 4.4% 4.4% 0.0% |0.0% 4.4% 2.2% 0.0% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 2/38 (5%) 0/30 (0%) |0/37 (0%) 1/38 (3%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | 632 455 730 (T) --- |--- 555 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.202N P=0.691N P=0.684 P=0.289N |P=0.400N P=0.243 P=0.500 (e) | |POLY 3 | P=0.185N P=0.687 P=0.690 P=0.264N |P=0.384N P=0.240 P=0.499 (e) | |POLY 1.5 | P=0.175N P=0.684 P=0.692 P=0.256N |P=0.384N P=0.236 P=0.501 (e) | |POLY 6 | P=0.200N P=0.692N P=0.685 P=0.276N |P=0.386N P=0.245 P=0.497 (e) | |LOGISTIC REGRESSION| P=0.140N P=0.640N P=0.695 P=0.234N |P=0.396N P=0.237 P=0.500 (e) | |COCH-ARM / FISHERS | P=0.156N P=0.691N P=0.691N P=0.247N |P=0.388N P=0.242 P=0.500 (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 18 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Liver: Centrilobular | | Degeneration | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 3/50 (6%) 4/50 (8%) |0/50 (0%) 0/49 (0%) 1/50 (2%) 1/49 (2%) | |POLY-3 RATE (b) | 0/45.56 1/44.18 3/46.01 4/42.50 |0/44.88 0/44.91 1/45.03 1/44.47 | |POLY-3 PERCENT (g) | 0.0% 2.3% 6.5% 9.4% |0.0% 0.0% 2.2% 2.3% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 728 597 539 |--- --- 638 683 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.024 * P=0.510 P=0.120 P=0.053 |P=0.308 (e) P=0.500 P=0.500 | |POLY 3 | P=0.032 * P=0.494 P=0.120 P=0.052 |P=0.304 (e) P=0.501 P=0.498 | |POLY 1.5 | P=0.033 * P=0.493 P=0.120 P=0.053 |P=0.306 (e) P=0.501 P=0.499 | |POLY 6 | P=0.029 * P=0.498 P=0.121 P=0.050 |P=0.299 (e) P=0.499 P=0.497 | |LOGISTIC REGRESSION| P=0.051 P=0.505 P=0.116 P=0.081 |P=0.290 (e) P=0.488 P=0.493 | |COCH-ARM / FISHERS | P=0.039 * P=0.500 P=0.121 P=0.059 |P=0.302 (e) P=0.500 P=0.495 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Alveolar Epithelium | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/50 (6%) 7/50 (14%) 4/50 (8%) 4/50 (8%) |5/50 (10%) 3/50 (6%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 3/45.56 7/44.17 4/45.75 4/41.19 |5/44.93 3/45.21 1/44.70 1/45.26 | |POLY-3 PERCENT (g) | 6.6% 15.9% 8.7% 9.7% |11.1% 6.6% 2.2% 2.2% | |TERMINAL (d) | 3/39 (8%) 7/40 (18%) 3/38 (8%) 3/30 (10%) |4/37 (11%) 3/38 (8%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | 730 (T) 730 (T) 620 646 |717 729 (T) 729 (T) 717 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.509 P=0.167 P=0.486 P=0.368 |P=0.107N P=0.344N P=0.106N P=0.126N | |POLY 3 | P=0.553N P=0.144 P=0.502 P=0.445 |P=0.087N P=0.353N P=0.102N P=0.099N | |POLY 1.5 | P=0.534N P=0.143 P=0.502 P=0.460 |P=0.086N P=0.357N P=0.101N P=0.099N | |POLY 6 | P=0.580N P=0.152 P=0.502 P=0.424 |P=0.089N P=0.348N P=0.105N P=0.102N | |LOGISTIC REGRESSION| P=0.586N P=0.167 P=0.497 P=0.415 |P=0.097N P=0.339N P=0.109N P=0.108N | |COCH-ARM / FISHERS | P=0.486N P=0.159 P=0.500 P=0.500 |P=0.089N P=0.357N P=0.102N P=0.102N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 19 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lung: Alveolus | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 1/45.56 0/44.17 1/45.36 2/41.28 |0/44.88 0/45.21 2/44.70 2/45.31 | |POLY-3 PERCENT (g) | 2.2% 0.0% 2.2% 4.8% |0.0% 0.0% 4.5% 4.4% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 1/38 (3%) 1/30 (3%) |0/37 (0%) 0/38 (0%) 2/37 (5%) 1/34 (3%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) 617 |--- --- 729 (T) 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.174 P=0.495N P=0.756 P=0.429 |P=0.106 (e) P=0.238 P=0.225 | |POLY 3 | P=0.214 P=0.506N P=0.760 P=0.466 |P=0.125 (e) P=0.236 P=0.239 | |POLY 1.5 | P=0.222 P=0.507N P=0.760 P=0.475 |P=0.126 (e) P=0.238 P=0.240 | |POLY 6 | P=0.202 P=0.502N P=0.758 P=0.453 |P=0.121 (e) P=0.233 P=0.237 | |LOGISTIC REGRESSION| P=0.218 (e) P=0.756 P=0.486 |P=0.119 (e) P=0.238 P=0.238 | |COCH-ARM / FISHERS | P=0.235 P=0.500N P=0.753N P=0.500 |P=0.124 (e) P=0.247 P=0.247 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/28 (0%) 0/29 (0%) 0/30 (0%) 0/30 (0%) |1/33 (3%) 1/38 (3%) 3/37 (8%) 0/39 (0%) | |POLY-3 RATE (b) | 0/25.34 0/25.75 0/28.35 0/24.22 |1/29.96 1/34.28 3/33.58 0/35.17 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |3.3% 2.9% 8.9% 0.0% | |TERMINAL (d) | 0/20 (0%) 0/24 (0%) 0/26 (0%) 0/18 (0%) |1/25 (4%) 1/29 (3%) 3/29 (10%) 0/28 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.319N P=0.729N P=0.358 P=0.477N | |POLY 3 | (e) (e) (e) (e) |P=0.304N P=0.731N P=0.346 P=0.468N | |POLY 1.5 | (e) (e) (e) (e) |P=0.301N P=0.732N P=0.347 P=0.467N | |POLY 6 | (e) (e) (e) (e) |P=0.308N P=0.731N P=0.341 P=0.470N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.319N P=0.729N P=0.358 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.303N P=0.717N P=0.352 P=0.458N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 20 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/28 (0%) 0/29 (0%) 0/30 (0%) 0/30 (0%) |0/33 (0%) 0/38 (0%) 0/37 (0%) 3/39 (8%) | |POLY-3 RATE (b) | 0/25.34 0/25.75 0/28.35 0/24.22 |0/29.96 0/34.28 0/33.58 3/35.91 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 8.4% | |TERMINAL (d) | 0/20 (0%) 0/24 (0%) 0/26 (0%) 0/18 (0%) |0/25 (0%) 0/29 (0%) 0/29 (0%) 1/28 (4%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 517 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.009 ** (e) (e) P=0.129 | |POLY 3 | (e) (e) (e) (e) |P=0.010 * (e) (e) P=0.151 | |POLY 1.5 | (e) (e) (e) (e) |P=0.010 * (e) (e) P=0.151 | |POLY 6 | (e) (e) (e) (e) |P=0.010 * (e) (e) P=0.151 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.009 ** (e) (e) P=0.146 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.011 * (e) (e) P=0.153 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mandibular | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/28 (0%) 0/29 (0%) 0/30 (0%) 0/30 (0%) |0/33 (0%) 1/38 (3%) 1/37 (3%) 2/39 (5%) | |POLY-3 RATE (b) | 0/25.34 0/25.75 0/28.35 0/24.22 |0/29.96 1/34.28 1/33.58 2/35.17 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 2.9% 3.0% 5.7% | |TERMINAL (d) | 0/20 (0%) 0/24 (0%) 0/26 (0%) 0/18 (0%) |0/25 (0%) 1/29 (3%) 1/29 (3%) 2/28 (7%) | |FIRST INCIDENCE | --- --- --- --- |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.201 P=0.530 P=0.530 P=0.263 | |POLY 3 | (e) (e) (e) (e) |P=0.219 P=0.527 P=0.523 P=0.273 | |POLY 1.5 | (e) (e) (e) (e) |P=0.221 P=0.526 P=0.524 P=0.274 | |POLY 6 | (e) (e) (e) (e) |P=0.216 P=0.527 P=0.520 P=0.270 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.530 P=0.530 P=0.263 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.219 P=0.535 P=0.529 P=0.290 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 21 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/48 (6%) 0/46 (0%) 3/45 (7%) 0/41 (0%) |0/47 (0%) 0/44 (0%) 0/42 (0%) 0/45 (0%) | |POLY-3 RATE (b) | 3/44.28 0/40.27 3/41.99 0/35.23 |0/43.27 0/41.79 0/38.98 0/41.14 | |POLY-3 PERCENT (g) | 6.8% 0.0% 7.1% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/37 (5%) 0/37 (0%) 2/37 (5%) 0/30 (0%) |0/37 (0%) 0/37 (0%) 0/36 (0%) 0/34 (0%) | |FIRST INCIDENCE | 477 --- 725 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.231N P=0.127N P=0.661 P=0.150N |(e) (e) (e) (e) | |POLY 3 | P=0.229N P=0.136N P=0.638 P=0.163N |(e) (e) (e) (e) | |POLY 1.5 | P=0.223N P=0.136N P=0.635 P=0.159N |(e) (e) (e) (e) | |POLY 6 | P=0.239N P=0.133N P=0.642 P=0.167N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.219N P=0.102N P=0.614 P=0.120N |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.220N P=0.129N P=0.630 P=0.152N |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hemorrhage | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/46 (0%) 1/45 (2%) 0/41 (0%) |0/47 (0%) 0/44 (0%) 1/42 (2%) 3/45 (7%) | |POLY-3 RATE (b) | 0/43.56 0/40.27 1/41.97 0/35.23 |0/43.27 0/41.79 1/38.98 3/41.36 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.4% 0.0% |0.0% 0.0% 2.6% 7.3% | |TERMINAL (d) | 0/37 (0%) 0/37 (0%) 1/37 (3%) 0/30 (0%) |0/37 (0%) 0/37 (0%) 1/36 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- 730 (T) --- |--- --- 729 (T) 683 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.814 (e) P=0.500 (e) |P=0.019 * (e) P=0.495 P=0.116 | |POLY 3 | P=0.803 (e) P=0.493 (e) |P=0.020 * (e) P=0.479 P=0.110 | |POLY 1.5 | P=0.807 (e) P=0.490 (e) |P=0.021 * (e) P=0.478 P=0.111 | |POLY 6 | P=0.796 (e) P=0.495 (e) |P=0.020 * (e) P=0.481 P=0.110 | |LOGISTIC REGRESSION| (e) (e) P=0.500 (e) |P=0.021 * (e) P=0.495 P=0.112 | |COCH-ARM / FISHERS | P=0.807N (e) P=0.484 (e) |P=0.022 * (e) P=0.472 P=0.113 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 22 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/46 (0%) 0/45 (0%) 0/41 (0%) |3/47 (6%) 1/44 (2%) 3/42 (7%) 0/45 (0%) | |POLY-3 RATE (b) | 0/43.56 0/40.27 0/41.97 0/35.23 |3/43.27 1/41.79 3/39.28 0/41.14 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.9% 2.4% 7.6% 0.0% | |TERMINAL (d) | 0/37 (0%) 0/37 (0%) 0/37 (0%) 0/30 (0%) |3/37 (8%) 1/37 (3%) 2/36 (6%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) 647 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.157N P=0.305N P=0.648 P=0.136N | |POLY 3 | (e) (e) (e) (e) |P=0.153N P=0.318N P=0.617 P=0.127N | |POLY 1.5 | (e) (e) (e) (e) |P=0.149N P=0.325N P=0.613 P=0.127N | |POLY 6 | (e) (e) (e) (e) |P=0.158N P=0.311N P=0.624 P=0.128N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.149N P=0.305N P=0.613 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.146N P=0.334N P=0.606 P=0.129N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 15/46 (33%) 33/45 (73%) 34/41 (83%) |0/47 (0%) 23/44 (52%) 35/42 (83%) 25/45 (56%) | |POLY-3 RATE (b) | 0/43.56 15/41.59 33/44.27 34/38.95 |0/43.27 23/43.54 35/40.40 25/43.77 | |POLY-3 PERCENT (g) | 0.0% 36.1% 74.5% 87.3% |0.0% 52.8% 86.6% 57.1% | |TERMINAL (d) | 0/37 (0%) 13/37 (35%) 28/37 (76%) 26/30 (87%) |0/37 (0%) 20/37 (54%) 32/36 (89%) 19/34 (56%) | |FIRST INCIDENCE | --- 508 465 483 |--- 18 509 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** |P<0.001 ** P<0.001 ** P<0.001 ** P<0.001 ** | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 23 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Lymph Node, Mesenteric | | Infiltration Cellular Plasma Cell | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/48 (0%) 0/46 (0%) 0/45 (0%) 0/41 (0%) |1/47 (2%) 0/44 (0%) 1/42 (2%) 2/45 (4%) | |POLY-3 RATE (b) | 0/43.56 0/40.27 0/41.97 0/35.23 |1/43.27 0/41.79 1/38.98 2/41.24 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 0.0% 2.6% 4.9% | |TERMINAL (d) | 0/37 (0%) 0/37 (0%) 0/37 (0%) 0/30 (0%) |1/37 (3%) 0/37 (0%) 1/36 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) --- 729 (T) 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.211 P=0.500N P=0.756 P=0.471 | |POLY 3 | (e) (e) (e) (e) |P=0.227 P=0.507N P=0.737 P=0.483 | |POLY 1.5 | (e) (e) (e) (e) |P=0.231 P=0.511N P=0.736 P=0.484 | |POLY 6 | (e) (e) (e) (e) |P=0.223 P=0.503N P=0.739 P=0.482 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.223 (e) P=0.756 P=0.481 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.233 P=0.516N P=0.724 P=0.484 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Mesentery: Fat | | Necrosis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/10 (100%) 3/4 (75%) 19/20 (95%) 10/10 (100%)|29/30 (97%) 33/34 (97%) 31/32 (97%) 41/42 (98%) | |POLY-3 RATE (b) | 10/10.00 3/3.84 19/19.61 10/10.00 |29/29.25 33/33.41 31/31.67 41/42.00 | |POLY-3 PERCENT (g) | 100.0% 78.2% 96.9% 100.0% |99.2% 98.8% 97.9% 97.6% | |TERMINAL (d) | 9/9 (100%) 3/3 (100%) 18/18 (100%) 9/9 (100%) |21/21 (100%) 27/27 (100%) 25/25 (100%) 29/30 (97%) | |FIRST INCIDENCE | 477 730 (T) 680 631 |411 681 589 579 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.494 P=0.513N P=0.753 (e) |P=0.147 P=0.376N P=0.413N P=0.301 | |POLY 3 | P=0.580 P=0.385N P=0.840N (e) |P=0.520N P=0.965N P=0.801N P=0.677N | |POLY 1.5 | P=0.537 P=0.343N P=0.736N (e) |P=0.629N P=0.872N P=0.774N P=0.753N | |POLY 6 | P=0.681 P=0.485N P=0.979N (e) |P=0.381N P=1.000N P=0.915N P=0.601N | |LOGISTIC REGRESSION| P=0.626 P=0.290N P=0.440N (e) |P=0.481N P=0.354N P=0.517N P=0.669N | |COCH-ARM / FISHERS | P=0.500 P=0.286N P=0.667N (e) |P=0.570 P=0.722 P=0.738 P=0.663 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 24 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Nose | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 0/50 (0%) 11/50 (22%) 2/47 (4%) |2/50 (4%) 0/50 (0%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 5/46.47 0/44.17 11/46.23 2/39.33 |2/44.90 0/45.21 2/45.55 2/45.21 | |POLY-3 PERCENT (g) | 10.8% 0.0% 23.8% 5.1% |4.5% 0.0% 4.4% 4.4% | |TERMINAL (d) | 2/39 (5%) 0/40 (0%) 8/38 (21%) 2/30 (7%) |1/37 (3%) 0/38 (0%) 0/37 (0%) 2/34 (6%) | |FIRST INCIDENCE | 599 --- 620 730 (T) |723 --- 509 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.539N P=0.037N* P=0.088 P=0.322N |P=0.406 P=0.237N P=0.687 P=0.663 | |POLY 3 | P=0.489N P=0.035N* P=0.081 P=0.289N |P=0.430 P=0.236N P=0.689N P=0.691N | |POLY 1.5 | P=0.454N P=0.035N* P=0.083 P=0.272N |P=0.435 P=0.237N P=0.689N P=0.690N | |POLY 6 | P=0.545N P=0.034N* P=0.078 P=0.314N |P=0.422 P=0.234N P=0.690N P=0.692 | |LOGISTIC REGRESSION| P=0.440N P=0.030N* P=0.086 P=0.248N |P=0.424 P=0.231N P=0.686 P=0.678 | |COCH-ARM / FISHERS | P=0.417N P=0.028N* P=0.086 P=0.244N |P=0.429 P=0.247N P=0.691N P=0.691N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Atrophy | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 1/50 (2%) 0/47 (0%) |0/50 (0%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 3/44.17 1/45.36 0/39.33 |0/44.88 1/45.21 1/44.70 1/45.21 | |POLY-3 PERCENT (g) | 0.0% 6.8% 2.2% 0.0% |0.0% 2.2% 2.2% 2.2% | |TERMINAL (d) | 0/39 (0%) 3/40 (8%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 1/38 (3%) 1/37 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- 730 (T) 730 (T) --- |--- 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.348N P=0.126 P=0.495 (e) |P=0.456 P=0.505 P=0.500 P=0.483 | |POLY 3 | P=0.322N P=0.113 P=0.499 (e) |P=0.486 P=0.501 P=0.499 P=0.501 | |POLY 1.5 | P=0.315N P=0.113 P=0.500 (e) |P=0.488 P=0.500 P=0.501 P=0.502 | |POLY 6 | P=0.332N P=0.117 P=0.498 (e) |P=0.480 P=0.503 P=0.497 P=0.499 | |LOGISTIC REGRESSION| (e) P=0.126 P=0.495 (e) |(e) P=0.505 P=0.500 P=0.483 | |COCH-ARM / FISHERS | P=0.296N P=0.121 P=0.500 (e) |P=0.483 P=0.500 P=0.500 P=0.500 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 25 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Nose: Olfactory Epithelium | | Metaplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 3/50 (6%) 1/50 (2%) 1/47 (2%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 3/44.17 1/45.36 1/39.33 |0/44.88 2/45.21 0/44.70 1/45.21 | |POLY-3 PERCENT (g) | 0.0% 6.8% 2.2% 2.5% |0.0% 4.4% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 3/40 (8%) 1/38 (3%) 1/30 (3%) |0/37 (0%) 2/38 (5%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- 730 (T) 730 (T) 730 (T) |--- 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.631 P=0.126 P=0.495 P=0.448 |P=0.591 P=0.244 (e) P=0.483 | |POLY 3 | P=0.643N P=0.113 P=0.499 P=0.471 |P=0.617 P=0.239 (e) P=0.501 | |POLY 1.5 | P=0.634N P=0.113 P=0.500 P=0.476 |P=0.618 P=0.237 (e) P=0.502 | |POLY 6 | P=0.643 P=0.117 P=0.498 P=0.463 |P=0.615 P=0.241 (e) P=0.499 | |LOGISTIC REGRESSION| (e) P=0.126 P=0.495 P=0.448 |(e) P=0.244 (e) P=0.483 | |COCH-ARM / FISHERS | P=0.613N P=0.121 P=0.500 P=0.485 |P=0.615 P=0.247 (e) P=0.500 | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Angiectasis | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |1/47 (2%) 0/46 (0%) 0/47 (0%) 2/48 (4%) | |POLY-3 RATE (b) | |1/42.97 0/41.53 0/41.98 2/43.54 | |POLY-3 PERCENT (g) | |2.3% 0.0% 0.0% 4.6% | |TERMINAL (d) | |0/36 (0%) 0/35 (0%) 0/36 (0%) 2/34 (6%) | |FIRST INCIDENCE | |456 --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.186 P=0.500N P=0.496N P=0.489 | |POLY 3 | |P=0.199 P=0.507N P=0.505N P=0.505 | |POLY 1.5 | |P=0.200 P=0.507N P=0.502N P=0.508 | |POLY 6 | |P=0.195 P=0.506N P=0.509N P=0.499 | |LOGISTIC REGRESSION| |P=0.172 P=0.443N P=0.595N P=0.465 | |COCH-ARM / FISHERS | |P=0.198 P=0.505N P=0.500N P=0.508 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 26 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Ovary | | Cyst | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |10/47 (21%) 12/46 (26%) 8/47 (17%) 7/48 (15%) | |POLY-3 RATE (b) | |10/44.49 12/41.81 8/42.65 7/43.54 | |POLY-3 PERCENT (g) | |22.5% 28.7% 18.8% 16.1% | |TERMINAL (d) | |6/36 (17%) 10/35 (29%) 6/36 (17%) 7/34 (21%) | |FIRST INCIDENCE | |183 681 589 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.202N P=0.393 P=0.403N P=0.338N | |POLY 3 | |P=0.166N P=0.339 P=0.435N P=0.312N | |POLY 1.5 | |P=0.156N P=0.344 P=0.421N P=0.299N | |POLY 6 | |P=0.182N P=0.339 P=0.451N P=0.333N | |LOGISTIC REGRESSION| |P=0.148N P=0.384 P=0.410N P=0.306N | |COCH-ARM / FISHERS | |P=0.150N P=0.382 P=0.397N P=0.280N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Pancreas | | Basophilic Focus | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/49 (0%) 0/50 (0%) |0/46 (0%) 2/45 (4%) 0/46 (0%) 1/46 (2%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/44.86 0/40.88 |0/42.79 2/42.20 0/41.89 1/41.88 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 4.7% 0.0% 2.4% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 2/37 (5%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |--- 729 (T) --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.593 P=0.238 (e) P=0.483 | |POLY 3 | (e) (e) (e) (e) |P=0.612 P=0.234 (e) P=0.496 | |POLY 1.5 | (e) (e) (e) (e) |P=0.614 P=0.232 (e) P=0.498 | |POLY 6 | (e) (e) (e) (e) |P=0.608 P=0.236 (e) P=0.493 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) P=0.238 (e) P=0.483 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.617 P=0.242 (e) P=0.500 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 27 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Pituitary Gland: Pars Distalis | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 3/49 (6%) 2/48 (4%) |11/48 (23%) 8/47 (17%) 10/45 (22%) 11/48 (23%) | |POLY-3 RATE (b) | 0/43.37 0/42.17 3/44.36 2/39.13 |11/43.21 8/42.52 10/41.65 11/43.65 | |POLY-3 PERCENT (g) | 0.0% 0.0% 6.8% 5.1% |25.5% 18.8% 24.0% 25.2% | |TERMINAL (d) | 0/37 (0%) 0/38 (0%) 3/37 (8%) 2/30 (7%) |11/36 (31%) 7/37 (19%) 8/36 (22%) 10/34 (29%) | |FIRST INCIDENCE | --- --- 730 (T) 730 (T) |729 (T) 703 638 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.103 (e) P=0.121 P=0.193 |P=0.346 P=0.277N P=0.504N P=0.539 | |POLY 3 | P=0.125 (e) P=0.122 P=0.215 |P=0.440 P=0.316N P=0.539N P=0.587N | |POLY 1.5 | P=0.135 (e) P=0.124 P=0.222 |P=0.448 P=0.324N P=0.546N P=0.583N | |POLY 6 | P=0.110 (e) P=0.121 P=0.206 |P=0.422 P=0.306N P=0.531N P=0.597N | |LOGISTIC REGRESSION| (e) (e) P=0.121 P=0.193 |P=0.411 P=0.295N P=0.558N P=0.547 | |COCH-ARM / FISHERS | P=0.159 (e) P=0.129 P=0.253 |P=0.433 P=0.323N P=0.567N P=0.596N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Ectasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 3/49 (6%) 3/50 (6%) 5/49 (10%) 3/50 (6%) | | |POLY-3 RATE (b) | 3/45.04 3/44.34 5/44.84 3/41.44 | | |POLY-3 PERCENT (g) | 6.7% 6.8% 11.2% 7.2% | | |TERMINAL (d) | 2/38 (5%) 2/40 (5%) 4/38 (11%) 1/30 (3%) | | |FIRST INCIDENCE | 590 688 653 631 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.473 P=0.650N P=0.357 P=0.566 | | |POLY 3 | P=0.553 P=0.655 P=0.354 P=0.624 | | |POLY 1.5 | P=0.573 P=0.654 P=0.356 P=0.637 | | |POLY 6 | P=0.520 P=0.661N P=0.351 P=0.605 | | |LOGISTIC REGRESSION| P=0.590 P=0.661N P=0.356 P=0.658N | | |COCH-ARM / FISHERS | P=0.571N P=0.651N P=0.357 P=0.651N | | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 28 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Preputial Gland | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 1/49 (2%) 2/50 (4%) 2/49 (4%) 3/50 (6%) | | |POLY-3 RATE (b) | 1/44.56 2/44.17 2/44.55 3/40.88 | | |POLY-3 PERCENT (g) | 2.2% 4.5% 4.5% 7.3% | | |TERMINAL (d) | 1/38 (3%) 2/40 (5%) 2/38 (5%) 3/30 (10%) | | |FIRST INCIDENCE | 730 (T) 730 (T) 730 (T) 730 (T) | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.167 P=0.518 P=0.500 P=0.224 | | |POLY 3 | P=0.234 P=0.497 P=0.500 P=0.275 | | |POLY 1.5 | P=0.246 P=0.495 P=0.500 P=0.285 | | |POLY 6 | P=0.215 P=0.505 P=0.499 P=0.260 | | |LOGISTIC REGRESSION| P=0.167 P=0.518 P=0.500 P=0.224 | | |COCH-ARM / FISHERS | P=0.273 P=0.508 P=0.500 P=0.316 | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Salivary Glands | | Infiltration Cellular Lymphocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/49 (0%) |0/49 (0%) 0/49 (0%) 2/50 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 0/40.09 |0/44.21 0/44.24 2/45.36 0/43.60 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 4.4% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- --- |--- --- 509 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.700N (e) P=0.242 (e) | |POLY 3 | (e) (e) (e) (e) |P=0.699N (e) P=0.243 (e) | |POLY 1.5 | (e) (e) (e) (e) |P=0.697N (e) P=0.244 (e) | |POLY 6 | (e) (e) (e) (e) |P=0.704N (e) P=0.240 (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.735N (e) P=0.219 (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.700N (e) P=0.253 (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 29 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Seminal Vesicle | | Dilatation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 5/50 (10%) 0/49 (0%) | | |POLY-3 RATE (b) | 0/45.56 0/44.17 5/45.36 0/40.28 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 11.0% 0.0% | | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 5/38 (13%) 0/30 (0%) | | |FIRST INCIDENCE | --- --- 730 (T) --- | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.631 (e) P=0.031 * (e) | | |POLY 3 | P=0.646 (e) P=0.030 * (e) | | |POLY 1.5 | P=0.640N (e) P=0.031 * (e) | | |POLY 6 | P=0.610 (e) P=0.029 * (e) | | |LOGISTIC REGRESSION| (e) (e) P=0.031 * (e) | | |COCH-ARM / FISHERS | P=0.597N (e) P=0.028 * (e) | | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Seminal Vesicle | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/49 (4%) | | |POLY-3 RATE (b) | 0/45.56 0/44.17 1/45.36 2/40.51 | | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.9% | | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 1/30 (3%) | | |FIRST INCIDENCE | --- --- 730 (T) 668 | | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.052 (e) P=0.495 P=0.192 | | |POLY 3 | P=0.070 (e) P=0.499 P=0.212 | | |POLY 1.5 | P=0.074 (e) P=0.500 P=0.217 | | |POLY 6 | P=0.065 (e) P=0.498 P=0.205 | | |LOGISTIC REGRESSION| P=0.069 (e) P=0.495 P=0.218 | | |COCH-ARM / FISHERS | P=0.081 (e) P=0.500 P=0.242 | | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 30 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Hematopoietic Cell Proliferation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 10/49 (20%) 8/50 (16%) 15/49 (31%) 15/49 (31%) |10/47 (21%) 19/48 (40%) 15/47 (32%) 18/46 (39%) | |POLY-3 RATE (b) | 10/46.45 8/46.66 15/48.52 15/42.40 |10/45.28 19/45.25 15/44.02 18/43.75 | |POLY-3 PERCENT (g) | 21.5% 17.1% 30.9% 35.4% |22.1% 42.0% 34.1% 41.1% | |TERMINAL (d) | 6/39 (15%) 4/40 (10%) 6/38 (16%) 7/30 (23%) |5/37 (14%) 13/38 (34%) 10/37 (27%) 11/34 (32%) | |FIRST INCIDENCE | 590 311 465 590 |456 541 589 509 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.031 * P=0.409N P=0.191 P=0.081 |P=0.135 P=0.064 P=0.189 P=0.059 | |POLY 3 | P=0.042 * P=0.393N P=0.211 P=0.111 |P=0.130 P=0.034 * P=0.152 P=0.042 * | |POLY 1.5 | P=0.050 P=0.395N P=0.198 P=0.125 |P=0.136 P=0.033 * P=0.159 P=0.044 * | |POLY 6 | P=0.034 * P=0.388N P=0.224 P=0.097 |P=0.123 P=0.035 * P=0.147 P=0.039 * | |LOGISTIC REGRESSION| P=0.115 P=0.284N P=0.152 P=0.162 |P=0.140 P=0.044 * P=0.188 P=0.053 | |COCH-ARM / FISHERS | P=0.080 P=0.379N P=0.177 P=0.177 |P=0.140 P=0.043 * P=0.175 P=0.049 * | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Hyperplasia Lymphoid | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) |1/47 (2%) 3/48 (6%) 0/47 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/44.72 0/44.17 0/44.81 0/40.16 |1/43.70 3/43.55 0/42.46 0/41.88 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |2.3% 6.9% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |1/37 (3%) 3/38 (8%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.170N P=0.314 P=0.500N P=0.517N | |POLY 3 | (e) (e) (e) (e) |P=0.162N P=0.304 P=0.506N P=0.508N | |POLY 1.5 | (e) (e) (e) (e) |P=0.161N P=0.304 P=0.504N P=0.507N | |POLY 6 | (e) (e) (e) (e) |P=0.163N P=0.306 P=0.508N P=0.511N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.170N P=0.314 (e) (e) | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.160N P=0.316 P=0.500N P=0.505N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 31 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Infiltration Cellular Histiocyte | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 1/49 (2%) 22/49 (45%) |0/47 (0%) 3/48 (6%) 12/47 (26%) 28/46 (61%) | |POLY-3 RATE (b) | 0/44.72 1/44.84 1/45.28 22/42.62 |0/43.70 3/43.55 12/43.17 28/44.08 | |POLY-3 PERCENT (g) | 0.0% 2.2% 2.2% 51.6% |0.0% 6.9% 27.8% 63.5% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 18/30 (60%) |0/37 (0%) 3/38 (8%) 11/37 (30%) 23/34 (68%) | |FIRST INCIDENCE | --- 508 592 17 |--- 729 (T) 481 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.492 P=0.496 P<0.001 ** |P<0.001 ** P=0.126 P<0.001 ** P<0.001 ** | |POLY 3 | P<0.001 ** P=0.501 P=0.502 P<0.001 ** |P<0.001 ** P=0.118 P<0.001 ** P<0.001 ** | |POLY 1.5 | P<0.001 ** P=0.499 P=0.502 P<0.001 ** |P<0.001 ** P=0.118 P<0.001 ** P<0.001 ** | |POLY 6 | P<0.001 ** P=0.505 P=0.503 P<0.001 ** |P<0.001 ** P=0.119 P<0.001 ** P<0.001 ** | |LOGISTIC REGRESSION| P<0.001 ** P=0.621 P=0.454 P<0.001 ** |P<0.001 ** P=0.126 P<0.001 ** P<0.001 ** | |COCH-ARM / FISHERS | P<0.001 ** P=0.505 P=0.500 P<0.001 ** |P<0.001 ** P=0.125 P<0.001 ** P<0.001 ** | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Spleen | | Metaplasia Osseous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 0/49 (0%) 0/49 (0%) |0/47 (0%) 0/48 (0%) 0/47 (0%) 2/46 (4%) | |POLY-3 RATE (b) | 0/44.72 0/44.17 0/44.81 0/40.16 |0/43.70 0/43.55 0/42.46 2/41.88 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 4.8% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 2/34 (6%) | |FIRST INCIDENCE | --- --- --- --- |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.034 * (e) (e) P=0.220 | |POLY 3 | (e) (e) (e) (e) |P=0.038 * (e) (e) P=0.228 | |POLY 1.5 | (e) (e) (e) (e) |P=0.038 * (e) (e) P=0.230 | |POLY 6 | (e) (e) (e) (e) |P=0.037 * (e) (e) P=0.225 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) P=0.220 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.039 * (e) (e) P=0.242 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 32 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Hyperplasia | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/49 (12%) 0/50 (0%) 2/50 (4%) 3/50 (6%) |2/47 (4%) 2/48 (4%) 2/49 (4%) 0/48 (0%) | |POLY-3 RATE (b) | 6/47.48 0/44.17 2/45.65 3/41.73 |2/43.74 2/44.26 2/43.93 0/43.54 | |POLY-3 PERCENT (g) | 12.6% 0.0% 4.4% 7.2% |4.6% 4.5% 4.6% 0.0% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 1/38 (3%) 1/30 (3%) |1/37 (3%) 1/38 (3%) 2/37 (5%) 0/34 (0%) | |FIRST INCIDENCE | 477 --- 653 483 |661 642 729 (T) --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.596N P=0.023N* P=0.152N P=0.334N |P=0.173N P=0.683N P=0.687 P=0.252N | |POLY 3 | P=0.522N P=0.020N* P=0.146N P=0.310N |P=0.159N P=0.690N P=0.692N P=0.238N | |POLY 1.5 | P=0.512N P=0.018N* P=0.138N P=0.285N |P=0.156N P=0.692N P=0.687N P=0.236N | |POLY 6 | P=0.542N P=0.020N* P=0.156N P=0.345N |P=0.164N P=0.686N P=0.689 P=0.242N | |LOGISTIC REGRESSION| P=0.424N P=0.005N** P=0.075N P=0.135N |P=0.153N P=0.684N P=0.689N P=0.231N | |COCH-ARM / FISHERS | P=0.502N P=0.012N* P=0.128N P=0.233N |P=0.153N P=0.684N P=0.676N P=0.242N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Stomach, Forestomach | | Ulcer | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |3/47 (6%) 0/48 (0%) 0/49 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 0/45.37 1/44.17 0/45.36 1/40.88 |3/44.38 0/43.94 0/43.93 0/43.54 | |POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 2.5% |6.8% 0.0% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 1/40 (3%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 730 (T) --- 730 (T) |636 --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.395 P=0.505 (e) P=0.448 |P=0.134N P=0.123N P=0.133N P=0.125N | |POLY 3 | P=0.431 P=0.495 (e) P=0.479 |P=0.121N P=0.120N P=0.120N P=0.122N | |POLY 1.5 | P=0.440 P=0.495 (e) P=0.486 |P=0.121N P=0.120N P=0.117N P=0.119N | |POLY 6 | P=0.420 P=0.498 (e) P=0.470 |P=0.121N P=0.121N P=0.126N P=0.127N | |LOGISTIC REGRESSION| (e) P=0.505 (e) P=0.448 |P=0.131N P=0.095N P=0.094N P=0.108N | |COCH-ARM / FISHERS | P=0.462 P=0.505 (e) P=0.505 |P=0.128N P=0.117N P=0.113N P=0.117N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 33 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Tooth | | Inflammation Chronic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 6/33 (18%) 6/27 (22%) 5/30 (17%) 6/23 (26%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 6/32.23 6/26.99 5/29.52 6/22.31 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 18.6% 22.2% 16.9% 26.9% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 6/30 (20%) 6/26 (23%) 5/28 (18%) 6/20 (30%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 730 (T) 730 (T) 730 (T) 730 (T) |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.284 P=0.518 P=0.550N P=0.320 |(e) (e) (e) (e) | |POLY 3 | P=0.326 P=0.492 P=0.563N P=0.349 |(e) (e) (e) (e) | |POLY 1.5 | P=0.331 P=0.484 P=0.565N P=0.351 |(e) (e) (e) (e) | |POLY 6 | P=0.319 P=0.505 P=0.560N P=0.345 |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.284 P=0.518 P=0.550N P=0.320 |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.334 P=0.472 P=0.570N P=0.350 |(e) (e) (e) (e) | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Tooth | | Malformation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | 29/33 (88%) 22/27 (81%) 27/30 (90%) 20/23 (87%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |POLY-3 RATE (b) | 29/33.00 22/27.00 27/30.00 20/23.00 |0/0.00 0/0.00 0/0.00 0/0.00 | |POLY-3 PERCENT (g) | 87.9% 81.5% 90.0% 87.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 26/30 (87%) 21/26 (81%) 25/28 (89%) 17/20 (85%) |0/0 (0%) 0/0 (0%) 0/0 (0%) 0/0 (0%) | |FIRST INCIDENCE | 632 728 653 621 |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.366 P=0.217N P=0.596N P=0.592 |(e) (e) (e) (e) | |POLY 3 | P=0.533 P=0.373N P=0.552 P=0.619N |(e) (e) (e) (e) | |POLY 1.5 | P=0.533 P=0.373N P=0.552 P=0.619N |(e) (e) (e) (e) | |POLY 6 | P=0.533 P=0.373N P=0.552 P=0.619N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| (e) (e) (e) (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.533 P=0.370N P=0.555 P=0.613N |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 34 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Hydrometra | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |27/48 (56%) 21/49 (43%) 25/50 (50%) 20/50 (40%) | |POLY-3 RATE (b) | |27/44.27 21/44.63 25/46.24 20/45.54 | |POLY-3 PERCENT (g) | |61.0% 47.1% 54.1% 43.9% | |TERMINAL (d) | |24/37 (65%) 18/38 (47%) 19/37 (51%) 17/34 (50%) | |FIRST INCIDENCE | |667 681 621 683 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.312N P=0.126N P=0.435N P=0.197N | |POLY 3 | |P=0.126N P=0.130N P=0.323N P=0.074N | |POLY 1.5 | |P=0.120N P=0.142N P=0.333N P=0.074N | |POLY 6 | |P=0.143N P=0.116N P=0.307N P=0.078N | |LOGISTIC REGRESSION| |P=0.144N P=0.111N P=0.395N P=0.092N | |COCH-ARM / FISHERS | |P=0.132N P=0.132N P=0.338N P=0.079N | |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Hyperplasia Cystic | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |8/48 (17%) 9/49 (18%) 8/50 (16%) 10/50 (20%) | |POLY-3 RATE (b) | |8/44.48 9/44.24 8/44.93 10/45.46 | |POLY-3 PERCENT (g) | |18.0% 20.4% 17.8% 22.0% | |TERMINAL (d) | |6/37 (16%) 9/38 (24%) 7/37 (19%) 9/34 (27%) | |FIRST INCIDENCE | |636 729 (T) 667 661 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.283 P=0.522 P=0.598 P=0.334 | |POLY 3 | |P=0.392 P=0.495 P=0.600N P=0.417 | |POLY 1.5 | |P=0.402 P=0.495 P=0.588N P=0.426 | |POLY 6 | |P=0.375 P=0.494 P=0.602 P=0.400 | |LOGISTIC REGRESSION| |P=0.379 P=0.511 P=0.594N P=0.420 | |COCH-ARM / FISHERS | |P=0.401 P=0.519 P=0.572N P=0.435 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 35 Statistical Analysis of Non-neoplastic Lesions in Mice(B6C3F1) - ELMIRON Terminal Sacrifice at 105 weeks |=================================================================================================================================| | | | | | | Males | Females | |Dose | 0 MG/KG 56 MG/KG 168 504 |0 MG/KG 56 MG/KG 168 504 | | | MG/KG MG/KG | MG/KG MG/KG | |=================================================================================================================================| | | |Uterus | | Inflammation | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |LESION RATES | | | |----------- | | | |OVERALL (a) | |2/48 (4%) 0/49 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | |2/43.89 0/44.24 0/44.70 0/45.21 | |POLY-3 PERCENT (g) | |4.6% 0.0% 0.0% 0.0% | |TERMINAL (d) | |2/37 (5%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.251N P=0.232N P=0.238N P=0.257N | |POLY 3 | |P=0.229N P=0.235N P=0.233N P=0.230N | |POLY 1.5 | |P=0.228N P=0.237N P=0.231N P=0.229N | |POLY 6 | |P=0.231N P=0.233N P=0.236N P=0.233N | |LOGISTIC REGRESSION| |P=0.251N (e) (e) (e) | |COCH-ARM / FISHERS | |P=0.233N P=0.242N P=0.237N P=0.237N | |=================================================================================================================================| (a) Number of tumor-bearing animals / number of animals examined at site. (b) Number of tumor-bearing animals / Poly-3 number (d) Observed incidence at terminal kill. (f) Beneath the control incidence are the P-values associated with the trend test. Beneath the dosed group incidence are the P-values corresponding to pairwise comparisons between the controls and that dosed group. The life table analysis regards tumors in animals dying prior to terminal kill as being (directly or indirectly) the cause of death. Logistic regression is an alternative method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage and Fishers exact tests compare directly the overall incidence rates For all tests a negative trend is indicated by N (e) Value of Statistic cannot be computed. (g) Poly-3 adjusted lifetime tumor incidence. (I) Interim sacrifice (T) Terminal sacrifice # Tumor rates based on number of animals necropsied. * To the right of any statistical result, indicates significance at (P<=0.05). ** To the right of any statistical result, indicates significance at (P<=0.01).