TDMS Study 88122-07 Pathology Tables
NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ELMIRON DATE: 04/23/01 EXPERIMENT: 88122 TEST: 07 TIME: 15:18:43 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 PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ELMIRON DATE: 04/23/01 EXPERIMENT: 88122 TEST: 07 TIME: 15:18:43 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 Mice(B6C3F1) ----------------------------- FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED. IN OTHER TISSUES/ORGANS RATES ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED. --------------- Adrenal Cortex Adrenal Medulla Bone Marrow Brain Clitoral/Preputial Gland Heart Islets, Pancreatic Kidney Liver Lung Ovary Pituitary Gland Spleen Testes Thyroid Gland Urinary Bladder NTP STATISTICAL ANALYSIS OF PRIMARY TUMORS REPORT: PEIRPT08 LAB: Battelle Columbus ELMIRON DATE: 04/23/01 EXPERIMENT: 88122 TEST: 07 TIME: 15:18:43 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 ----- ---------- Liver Hemangiosarcoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Lung Alveolar/Bronchiolar Adenoma Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma All Organs Hemangiosarcoma Hemangiosarcoma or Hemangioma Histiocytic Sarcoma Malignant Tumors Malignant and Benign Tumors =============================================================== Female Mice ------------ Organ Morphology ----- ---------- Liver Hemangiosarcoma Hepatocellular Adenoma Hepatocellular Carcinoma or Hepatocellular Adenoma Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma Ovary Hemangioma All Organs Hemangioma Hemangiosarcoma or Hemangioma Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated Cell Type Benign Tumors Malignant Tumors Malignant and Benign Tumors =============================================================== Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 1 Statistical Analysis of Primary Tumors 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 | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 1/50 (2%) 0/49 (0%) |0/49 (0%) 0/49 (0%) 0/49 (0%) 0/48 (0%) | |POLY-3 RATE (b) | 2/45.56 0/44.17 1/45.36 0/40.28 |0/44.48 0/44.24 0/44.13 0/43.60 | |POLY-3 PERCENT (g) | 4.4% 0.0% 2.2% 0.0% |0.0% 0.0% 0.0% 0.0% | |TERMINAL (d) | 2/39 (5%) 0/40 (0%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 730 (T) --- 730 (T) --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.319N P=0.233N P=0.509N P=0.298N |(e) (e) (e) (e) | |POLY 3 | P=0.281N P=0.244N P=0.502N P=0.265N |(e) (e) (e) (e) | |POLY 1.5 | P=0.276N P=0.245N P=0.500N P=0.259N |(e) (e) (e) (e) | |POLY 6 | P=0.291N P=0.239N P=0.504N P=0.275N |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.319N (e) P=0.509N (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.270N P=0.247N P=0.500N P=0.253N |(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 Marrow | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 2/49 (4%) 1/50 (2%) |0/50 (0%) 1/48 (2%) 0/50 (0%) 0/49 (0%) | |POLY-3 RATE (b) | 2/46.04 0/44.17 2/45.38 1/40.88 |0/44.88 1/44.18 0/44.70 0/44.52 | |POLY-3 PERCENT (g) | 4.3% 0.0% 4.4% 2.5% |0.0% 2.3% 0.0% 0.0% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 1/38 (3%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 590 --- 653 730 (T) |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.653 P=0.249N P=0.688 P=0.576N |P=0.602N P=0.505 (e) (e) | |POLY 3 | P=0.618N P=0.246N P=0.689 P=0.541N |P=0.582N P=0.497 (e) (e) | |POLY 1.5 | P=0.607N P=0.247N P=0.688 P=0.529N |P=0.583N P=0.495 (e) (e) | |POLY 6 | P=0.637N P=0.243N P=0.690 P=0.559N |P=0.580N P=0.499 (e) (e) | |LOGISTIC REGRESSION| P=0.575N P=0.217N P=0.671 P=0.504N |(e) P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.589N P=0.247N P=0.684 P=0.500N |P=0.586N P=0.490 (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 2 Statistical Analysis of Primary Tumors 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 | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 9/50 (18%) 5/50 (10%) 6/50 (12%) |4/50 (8%) 3/50 (6%) 4/50 (8%) 3/50 (6%) | |POLY-3 RATE (b) | 6/45.99 9/44.35 5/45.36 6/42.08 |4/44.88 3/45.21 4/44.70 3/46.04 | |POLY-3 PERCENT (g) | 13.1% 20.3% 11.0% 14.3% |8.9% 6.6% 9.0% 6.5% | |TERMINAL (d) | 5/39 (13%) 7/40 (18%) 5/38 (13%) 3/30 (10%) |4/37 (11%) 3/38 (8%) 4/37 (11%) 2/34 (6%) | |FIRST INCIDENCE | 606 688 730 (T) 539 |729 (T) 729 (T) 729 (T) 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.522 P=0.308 P=0.518N P=0.465 |P=0.539N P=0.485N P=0.645 P=0.538N | |POLY 3 | P=0.480N P=0.261 P=0.510N P=0.557 |P=0.470N P=0.496N P=0.641 P=0.486N | |POLY 1.5 | P=0.462N P=0.260 P=0.504N P=0.573 |P=0.469N P=0.500N P=0.642N P=0.487N | |POLY 6 | P=0.509N P=0.273 P=0.519N P=0.535 |P=0.477N P=0.491N P=0.635 P=0.490N | |LOGISTIC REGRESSION| P=0.487N P=0.269 P=0.506N P=0.600 |P=0.480N P=0.485N P=0.645 P=0.510N | |COCH-ARM / FISHERS | P=0.417N P=0.288 P=0.500N P=0.620N |P=0.484N P=0.500N P=0.643N 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 | |=================================================================================================================================| | | |Harderian Gland | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 1/50 (2%) 2/50 (4%) |0/50 (0%) 2/50 (4%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 1/45.36 2/41.37 |0/44.88 2/45.21 2/44.89 2/45.21 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.8% |0.0% 4.4% 4.5% 4.4% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 1/30 (3%) |0/37 (0%) 2/38 (5%) 1/37 (3%) 2/34 (6%) | |FIRST INCIDENCE | --- --- 730 (T) 584 |--- 729 (T) 677 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.058 (e) P=0.495 P=0.200 |P=0.306 P=0.244 P=0.234 P=0.220 | |POLY 3 | P=0.073 (e) P=0.499 P=0.216 |P=0.342 P=0.239 P=0.237 P=0.239 | |POLY 1.5 | P=0.077 (e) P=0.500 P=0.222 |P=0.345 P=0.237 P=0.238 P=0.240 | |POLY 6 | P=0.068 (e) P=0.498 P=0.209 |P=0.336 P=0.241 P=0.235 P=0.236 | |LOGISTIC REGRESSION| P=0.084 (e) P=0.495 P=0.247 |P=0.334 P=0.244 P=0.238 P=0.220 | |COCH-ARM / FISHERS | P=0.085 (e) P=0.500 P=0.247 |P=0.339 P=0.247 P=0.247 P=0.247 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 3 Statistical Analysis of Primary Tumors 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 | | Carcinoma or Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 9/50 (18%) 6/50 (12%) 8/50 (16%) |4/50 (8%) 5/50 (10%) 6/50 (12%) 5/50 (10%) | |POLY-3 RATE (b) | 6/45.99 9/44.35 6/45.36 8/42.57 |4/44.88 5/45.21 6/44.89 5/46.04 | |POLY-3 PERCENT (g) | 13.1% 20.3% 13.2% 18.8% |8.9% 11.1% 13.4% 10.9% | |TERMINAL (d) | 5/39 (13%) 7/40 (18%) 6/38 (16%) 4/30 (13%) |4/37 (11%) 5/38 (13%) 5/37 (14%) 4/34 (12%) | |FIRST INCIDENCE | 606 688 730 (T) 539 |729 (T) 729 (T) 677 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.253 P=0.308 P=0.603 P=0.245 |P=0.434 P=0.517 P=0.366 P=0.454 | |POLY 3 | P=0.398 P=0.261 P=0.611 P=0.327 |P=0.520 P=0.505 P=0.369 P=0.516 | |POLY 1.5 | P=0.414 P=0.260 P=0.616 P=0.341 |P=0.521 P=0.500 P=0.373 P=0.515 | |POLY 6 | P=0.372 P=0.273 P=0.603 P=0.309 |P=0.510 P=0.511 P=0.364 P=0.511 | |LOGISTIC REGRESSION| P=0.394 P=0.269 P=0.615 P=0.372 |P=0.505 P=0.517 P=0.352 P=0.498 | |COCH-ARM / FISHERS | P=0.460 P=0.288 P=0.620N P=0.387 |P=0.500 P=0.500 P=0.370 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 | |=================================================================================================================================| | | |Intestine Small: Duodenum | | Polyp Adenomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 1/40.88 |0/44.88 2/45.21 0/44.70 1/45.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% |0.0% 4.4% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 2/38 (5%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 730 (T) |--- 729 (T) --- 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.172 (e) (e) P=0.448 |P=0.594 P=0.244 (e) P=0.495 | |POLY 3 | P=0.201 (e) (e) P=0.478 |P=0.618 P=0.239 (e) P=0.502 | |POLY 1.5 | P=0.206 (e) (e) P=0.485 |P=0.618 P=0.237 (e) P=0.503 | |POLY 6 | P=0.194 (e) (e) P=0.470 |P=0.616 P=0.241 (e) P=0.500 | |LOGISTIC REGRESSION| (e) (e) (e) P=0.448 |P=0.612 P=0.244 (e) P=0.501 | |COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.615 P=0.247 (e) P=0.500 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 4 Statistical Analysis of Primary Tumors 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 Small: Jejunum | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 0/50 (0%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 4/46.04 1/44.17 0/45.36 0/40.88 |1/44.88 0/45.21 0/44.70 0/45.21 | |POLY-3 PERCENT (g) | 8.7% 2.3% 0.0% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/39 (8%) 1/40 (3%) 0/38 (0%) 0/30 (0%) |1/37 (3%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 590 730 (T) --- --- |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.074N P=0.182N P=0.068N P=0.098N |P=0.486N P=0.495N P=0.500N P=0.517N | |POLY 3 | P=0.056N P=0.191N P=0.062N P=0.077N |P=0.472N P=0.499N P=0.501N P=0.499N | |POLY 1.5 | P=0.054N P=0.192N P=0.061N P=0.072N |P=0.472N P=0.500N P=0.499N P=0.498N | |POLY 6 | P=0.058N P=0.187N P=0.064N P=0.085N |P=0.473N P=0.497N P=0.503N P=0.501N | |LOGISTIC REGRESSION| P=0.058N P=0.185N P=0.063N P=0.067N |P=0.486N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.056N P=0.181N P=0.059N P=0.059N |P=0.471N P=0.500N P=0.500N 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 | |=================================================================================================================================| | | |Intestine Small: Site Unspecified | | Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 4/50 (8%) 1/50 (2%) 1/50 (2%) 0/50 (0%) |1/50 (2%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 4/46.04 1/44.17 1/45.36 0/40.88 |1/44.88 0/45.21 0/44.70 0/45.21 | |POLY-3 PERCENT (g) | 8.7% 2.3% 2.2% 0.0% |2.2% 0.0% 0.0% 0.0% | |TERMINAL (d) | 3/39 (8%) 1/40 (3%) 1/38 (3%) 0/30 (0%) |1/37 (3%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | 590 730 (T) 730 (T) --- |729 (T) --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.094N P=0.182N P=0.189N P=0.098N |P=0.486N P=0.495N P=0.500N P=0.517N | |POLY 3 | P=0.074N P=0.191N P=0.183N P=0.077N |P=0.472N P=0.499N P=0.501N P=0.499N | |POLY 1.5 | P=0.071N P=0.192N P=0.181N P=0.072N |P=0.472N P=0.500N P=0.499N P=0.498N | |POLY 6 | P=0.080N P=0.187N P=0.187N P=0.085N |P=0.473N P=0.497N P=0.503N P=0.501N | |LOGISTIC REGRESSION| P=0.074N P=0.185N P=0.179N P=0.067N |P=0.486N (e) (e) (e) | |COCH-ARM / FISHERS | P=0.069N P=0.181N P=0.181N P=0.059N |P=0.471N P=0.500N P=0.500N P=0.500N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 5 Statistical Analysis of Primary Tumors 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 Small: Site Unspecified | | Polyp Adenomatous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 0/50 (0%) 1/50 (2%) |0/50 (0%) 2/50 (4%) 0/50 (0%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 1/44.17 0/45.36 1/40.88 |0/44.88 2/45.21 0/44.70 1/45.32 | |POLY-3 PERCENT (g) | 0.0% 2.3% 0.0% 2.5% |0.0% 4.4% 0.0% 2.2% | |TERMINAL (d) | 0/39 (0%) 1/40 (3%) 0/38 (0%) 1/30 (3%) |0/37 (0%) 2/38 (5%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- 730 (T) --- 730 (T) |--- 729 (T) --- 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.395 P=0.505 (e) P=0.448 |P=0.594 P=0.244 (e) P=0.495 | |POLY 3 | P=0.432 P=0.494 (e) P=0.478 |P=0.618 P=0.239 (e) P=0.502 | |POLY 1.5 | P=0.440 P=0.493 (e) P=0.485 |P=0.618 P=0.237 (e) P=0.503 | |POLY 6 | P=0.422 P=0.498 (e) P=0.470 |P=0.616 P=0.241 (e) P=0.500 | |LOGISTIC REGRESSION| (e) P=0.505 (e) P=0.448 |P=0.612 P=0.244 (e) P=0.501 | |COCH-ARM / FISHERS | P=0.459 P=0.500 (e) P=0.500 |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 | |=================================================================================================================================| | | |Islets, Pancreatic | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/49 (4%) 0/50 (0%) |0/46 (0%) 0/45 (0%) 0/45 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 2/45.14 0/40.88 |0/42.79 0/42.20 0/40.94 0/41.88 | |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%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 0/37 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 653 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.732 (e) P=0.237 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.722 (e) P=0.235 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.715N (e) P=0.234 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.697 (e) P=0.236 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.699N (e) P=0.231 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.694N (e) P=0.242 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 6 Statistical Analysis of Primary Tumors 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 | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 2/50 (4%) 0/50 (0%) 4/50 (8%) 9/50 (18%) |1/50 (2%) 1/49 (2%) 1/50 (2%) 4/49 (8%) | |POLY-3 RATE (b) | 2/45.87 0/44.17 4/45.36 9/42.54 |1/44.88 1/44.91 1/44.70 4/44.72 | |POLY-3 PERCENT (g) | 4.4% 0.0% 8.8% 21.2% |2.2% 2.2% 2.2% 8.9% | |TERMINAL (d) | 1/39 (3%) 0/40 (0%) 4/38 (11%) 5/30 (17%) |1/37 (3%) 1/38 (3%) 1/37 (3%) 2/34 (6%) | |FIRST INCIDENCE | 646 --- 730 (T) 539 |729 (T) 729 (T) 729 (T) 645 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P<0.001 ** P=0.237N P=0.327 P=0.014 * |P=0.049 * P=0.756N P=0.762 P=0.170 | |POLY 3 | P<0.001 ** P=0.246N P=0.332 P=0.017 * |P=0.056 P=0.760N P=0.760 P=0.177 | |POLY 1.5 | P<0.001 ** P=0.246N P=0.335 P=0.019 * |P=0.057 P=0.758 P=0.760N P=0.178 | |POLY 6 | P<0.001 ** P=0.242N P=0.326 P=0.015 * |P=0.055 P=0.757N P=0.757 P=0.176 | |LOGISTIC REGRESSION| P<0.001 ** P=0.235N P=0.334 P=0.026 * |P=0.056 P=0.756N P=0.762 P=0.175 | |COCH-ARM / FISHERS | P<0.001 ** P=0.247N P=0.339 P=0.026 * |P=0.056 P=0.747 P=0.753N P=0.175 | |=================================================================================================================================| | | | | | | 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 | | Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 19/50 (38%) 15/50 (30%) 15/50 (30%) 20/50 (40%) |7/50 (14%) 5/49 (10%) 4/50 (8%) 15/49 (31%) | |POLY-3 RATE (b) | 19/47.46 15/44.93 15/46.67 20/43.05 |7/45.48 5/44.91 4/45.00 15/45.68 | |POLY-3 PERCENT (g) | 40.0% 33.4% 32.1% 46.5% |15.4% 11.1% 8.9% 32.8% | |TERMINAL (d) | 15/39 (39%) 14/40 (35%) 12/38 (32%) 15/30 (50%) |6/37 (16%) 5/38 (13%) 3/37 (8%) 11/34 (32%) | |FIRST INCIDENCE | 420 455 592 483 |536 729 (T) 647 517 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.064 P=0.251N P=0.303N P=0.191 |P=0.002 ** P=0.362N P=0.266N P=0.035 * | |POLY 3 | P=0.195 P=0.328N P=0.280N P=0.342 |P=0.003 ** P=0.388N P=0.267N P=0.042 * | |POLY 1.5 | P=0.223 P=0.321N P=0.273N P=0.383 |P=0.003 ** P=0.394N P=0.262N P=0.042 * | |POLY 6 | P=0.157 P=0.319N P=0.288N P=0.290 |P=0.003 ** P=0.382N P=0.274N P=0.041 * | |LOGISTIC REGRESSION| P=0.223 P=0.289N P=0.263N P=0.409 |P=0.003 ** P=0.384N P=0.261N P=0.041 * | |COCH-ARM / FISHERS | P=0.293 P=0.263N P=0.263N P=0.500 |P=0.003 ** P=0.394N P=0.262N P=0.040 * | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 7 Statistical Analysis of Primary Tumors 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 | | Hepatocellular Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 11/50 (22%) 13/50 (26%) 15/50 (30%) 13/50 (26%) |3/50 (6%) 3/49 (6%) 5/50 (10%) 3/49 (6%) | |POLY-3 RATE (b) | 11/46.87 13/45.09 15/48.23 13/45.10 |3/45.05 3/44.94 5/44.70 3/44.70 | |POLY-3 PERCENT (g) | 23.5% 28.8% 31.1% 28.8% |6.7% 6.7% 11.2% 6.7% | |TERMINAL (d) | 8/39 (21%) 10/40 (25%) 7/38 (18%) 4/30 (13%) |2/37 (5%) 2/38 (5%) 5/37 (14%) 0/34 (0%) | |FIRST INCIDENCE | 590 508 548 483 |685 722 729 (T) 660 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.223 P=0.424 P=0.251 P=0.245 |P=0.562 P=0.649N P=0.352 P=0.638 | |POLY 3 | P=0.407 P=0.365 P=0.273 P=0.365 |P=0.583N P=0.661 P=0.352 P=0.659 | |POLY 1.5 | P=0.411 P=0.365 P=0.263 P=0.367 |P=0.579N P=0.656 P=0.357 P=0.659 | |POLY 6 | P=0.390 P=0.379 P=0.286 P=0.356 |P=0.590N P=0.658N P=0.343 P=0.656 | |LOGISTIC REGRESSION| P=0.482 P=0.385 P=0.243 P=0.481 |P=0.593N P=0.660N P=0.341 P=0.657 | |COCH-ARM / FISHERS | P=0.445 P=0.408 P=0.247 P=0.408 |P=0.587N P=0.651 P=0.357 P=0.651 | |=================================================================================================================================| | | | | | | 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 | | Hepatocellular Carcinoma or Hepatoblastoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 12/50 (24%) 14/50 (28%) 15/50 (30%) 13/50 (26%) |3/50 (6%) 3/49 (6%) 5/50 (10%) 3/49 (6%) | |POLY-3 RATE (b) | 12/46.87 14/45.99 15/48.23 13/45.10 |3/45.05 3/44.94 5/44.70 3/44.70 | |POLY-3 PERCENT (g) | 25.6% 30.4% 31.1% 28.8% |6.7% 6.7% 11.2% 6.7% | |TERMINAL (d) | 9/39 (23%) 10/40 (25%) 7/38 (18%) 4/30 (13%) |2/37 (5%) 2/38 (5%) 5/37 (14%) 0/34 (0%) | |FIRST INCIDENCE | 590 346 548 483 |685 722 729 (T) 660 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.299 P=0.426 P=0.323 P=0.310 |P=0.562 P=0.649N P=0.352 P=0.638 | |POLY 3 | P=0.498 P=0.387 P=0.357 P=0.455 |P=0.583N P=0.661 P=0.352 P=0.659 | |POLY 1.5 | P=0.504 P=0.381 P=0.345 P=0.458 |P=0.579N P=0.656 P=0.357 P=0.659 | |POLY 6 | P=0.478 P=0.405 P=0.373 P=0.446 |P=0.590N P=0.658N P=0.343 P=0.656 | |LOGISTIC REGRESSION| P=0.505N P=0.412 P=0.323 P=0.569 |P=0.593N P=0.660N P=0.341 P=0.657 | |COCH-ARM / FISHERS | P=0.545 P=0.410 P=0.326 P=0.500 |P=0.587N P=0.651 P=0.357 P=0.651 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 8 Statistical Analysis of Primary Tumors 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 | | Hepatocellular Carcinoma or Hepatocellular Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 23/50 (46%) 23/50 (46%) 26/50 (52%) 31/50 (62%) |10/50 (20%) 8/49 (16%) 9/50 (18%) 18/49 (37%) | |POLY-3 RATE (b) | 23/47.93 23/45.85 26/49.07 31/46.55 |10/45.65 8/44.94 9/45.00 18/46.09 | |POLY-3 PERCENT (g) | 48.0% 50.2% 53.0% 66.6% |21.9% 17.8% 20.0% 39.1% | |TERMINAL (d) | 18/39 (46%) 19/40 (48%) 16/38 (42%) 18/30 (60%) |8/37 (22%) 7/38 (18%) 8/37 (22%) 11/34 (32%) | |FIRST INCIDENCE | 420 455 548 483 |536 722 647 517 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.004 ** P=0.548N P=0.333 P=0.016 * |P=0.006 ** P=0.377N P=0.506N P=0.051 | |POLY 3 | P=0.031 * P=0.498 P=0.386 P=0.049 * |P=0.010 * P=0.411N P=0.514N P=0.057 | |POLY 1.5 | P=0.030 * P=0.502 P=0.367 P=0.049 * |P=0.010 * P=0.417N P=0.503N P=0.056 | |POLY 6 | P=0.030 * P=0.517 P=0.417 P=0.050 |P=0.010 * P=0.406N P=0.531N P=0.058 | |LOGISTIC REGRESSION| P=0.036 * P=0.544 P=0.346 P=0.068 |P=0.009 ** P=0.400N P=0.503N P=0.054 | |COCH-ARM / FISHERS | P=0.043 * P=0.579N P=0.345 P=0.080 |P=0.009 ** P=0.416N P=0.500N P=0.052 | |=================================================================================================================================| | | | | | | 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 | | Hepatocellular Carcinoma, Hepatocellular Adenoma, | | or Hepatoblastoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 24/50 (48%) 24/50 (48%) 26/50 (52%) 31/50 (62%) |10/50 (20%) 8/49 (16%) 9/50 (18%) 18/49 (37%) | |POLY-3 RATE (b) | 24/47.93 24/46.74 26/49.07 31/46.55 |10/45.65 8/44.94 9/45.00 18/46.09 | |POLY-3 PERCENT (g) | 50.1% 51.3% 53.0% 66.6% |21.9% 17.8% 20.0% 39.1% | |TERMINAL (d) | 19/39 (49%) 19/40 (48%) 16/38 (42%) 18/30 (60%) |8/37 (22%) 7/38 (18%) 8/37 (22%) 11/34 (32%) | |FIRST INCIDENCE | 420 346 548 483 |536 722 647 517 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.007 ** P=0.548N P=0.397 P=0.022 * |P=0.006 ** P=0.377N P=0.506N P=0.051 | |POLY 3 | P=0.047 * P=0.533 P=0.467 P=0.074 |P=0.010 * P=0.411N P=0.514N P=0.057 | |POLY 1.5 | P=0.047 * P=0.527 P=0.445 P=0.074 |P=0.010 * P=0.417N P=0.503N P=0.056 | |POLY 6 | P=0.046 * P=0.557 P=0.500 P=0.075 |P=0.010 * P=0.406N P=0.531N P=0.058 | |LOGISTIC REGRESSION| P=0.063 P=0.566 P=0.423 P=0.095 |P=0.009 ** P=0.400N P=0.503N P=0.054 | |COCH-ARM / FISHERS | P=0.068 P=0.579N P=0.421 P=0.114 |P=0.009 ** P=0.416N P=0.500N P=0.052 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 9 Statistical Analysis of Primary Tumors 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 | | Alveolar/Bronchiolar Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 10/50 (20%) 3/50 (6%) 8/50 (16%) 5/50 (10%) |2/50 (4%) 3/50 (6%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 10/46.26 3/44.17 8/45.86 5/42.08 |2/44.88 3/45.80 2/44.70 1/45.21 | |POLY-3 PERCENT (g) | 21.6% 6.8% 17.5% 11.9% |4.5% 6.6% 4.5% 2.2% | |TERMINAL (d) | 8/39 (21%) 3/40 (8%) 7/38 (18%) 1/30 (3%) |2/37 (5%) 2/38 (5%) 2/37 (5%) 1/34 (3%) | |FIRST INCIDENCE | 599 730 (T) 581 631 |729 (T) 541 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.472N P=0.036N* P=0.423N P=0.264N |P=0.334N P=0.512 P=0.695 P=0.530N | |POLY 3 | P=0.331N P=0.042N* P=0.405N P=0.175N |P=0.303N P=0.509 P=0.692 P=0.497N | |POLY 1.5 | P=0.315N P=0.042N* P=0.400N P=0.163N |P=0.300N P=0.503 P=0.693N P=0.496N | |POLY 6 | P=0.359N P=0.040N* P=0.414N P=0.192N |P=0.308N P=0.516 P=0.688 P=0.502N | |LOGISTIC REGRESSION| P=0.326N P=0.041N* P=0.399N P=0.151N |P=0.300N P=0.500 P=0.695 P=0.530N | |COCH-ARM / FISHERS | P=0.284N P=0.036N* P=0.398N P=0.131N |P=0.303N P=0.500 P=0.691N 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 | |=================================================================================================================================| | | |Lung | | Alveolar/Bronchiolar Carcinoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 5/50 (10%) 3/50 (6%) 5/50 (10%) 4/50 (8%) |1/50 (2%) 1/50 (2%) 1/50 (2%) 1/50 (2%) | |POLY-3 RATE (b) | 5/45.99 3/44.17 5/45.75 4/41.32 |1/44.88 1/45.24 1/45.41 1/45.21 | |POLY-3 PERCENT (g) | 10.9% 6.8% 10.9% 9.7% |2.2% 2.2% 2.2% 2.2% | |TERMINAL (d) | 4/39 (10%) 3/40 (8%) 4/38 (11%) 2/30 (7%) |1/37 (3%) 0/38 (0%) 0/37 (0%) 1/34 (3%) | |FIRST INCIDENCE | 606 730 (T) 620 668 |729 (T) 722 481 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.459 P=0.350N P=0.613 P=0.629 |P=0.650 P=0.754N P=0.756N P=0.743 | |POLY 3 | P=0.559 P=0.379N P=0.627 P=0.567N |P=0.666N P=0.759N P=0.758N P=0.759N | |POLY 1.5 | P=0.580 P=0.379N P=0.629 P=0.548N |P=0.664N P=0.760 P=0.758N P=0.758N | |POLY 6 | P=0.526 P=0.370N P=0.623 P=0.592N |P=0.663 P=0.757N P=0.760N P=0.760 | |LOGISTIC REGRESSION| P=0.569 P=0.371N P=0.630 P=0.551N |P=0.657 P=0.757N P=0.742 P=0.743 | |COCH-ARM / FISHERS | P=0.551N P=0.357N P=0.630N P=0.500N |P=0.668N P=0.753N P=0.753N P=0.753N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 10 Statistical Analysis of Primary Tumors 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 | | Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar | | Adenoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 14/50 (28%) 5/50 (10%) 13/50 (26%) 9/50 (18%) |3/50 (6%) 4/50 (8%) 3/50 (6%) 2/50 (4%) | |POLY-3 RATE (b) | 14/46.69 5/44.17 13/46.25 9/42.52 |3/44.88 4/45.83 3/45.41 2/45.21 | |POLY-3 PERCENT (g) | 30.0% 11.3% 28.1% 21.2% |6.7% 8.7% 6.6% 4.4% | |TERMINAL (d) | 11/39 (28%) 5/40 (13%) 11/38 (29%) 3/30 (10%) |3/37 (8%) 2/38 (5%) 2/37 (5%) 2/34 (6%) | |FIRST INCIDENCE | 599 730 (T) 581 631 |729 (T) 541 481 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.459 P=0.021N* P=0.531N P=0.375N |P=0.374N P=0.514 P=0.659N P=0.539N | |POLY 3 | P=0.466N P=0.025N* P=0.512N P=0.239N |P=0.335N P=0.511 P=0.657N P=0.497N | |POLY 1.5 | P=0.444N P=0.024N* P=0.504N P=0.221N |P=0.331N P=0.504 P=0.656N P=0.495N | |POLY 6 | P=0.500N P=0.024N* P=0.525N P=0.262N |P=0.344N P=0.520 P=0.660N P=0.502N | |LOGISTIC REGRESSION| P=0.465N P=0.024N* P=0.501N P=0.209N |P=0.335N P=0.499 P=0.662 P=0.539N | |COCH-ARM / FISHERS | P=0.396N P=0.020N* P=0.500N P=0.171N |P=0.335N P=0.500 P=0.661N 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 | |=================================================================================================================================| | | |Ovary | | Cystadenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |1/47 (2%) 1/46 (2%) 2/47 (4%) 0/48 (0%) | |POLY-3 RATE (b) | |1/42.21 1/41.53 2/42.26 0/43.54 | |POLY-3 PERCENT (g) | |2.4% 2.4% 4.7% 0.0% | |TERMINAL (d) | |1/36 (3%) 1/35 (3%) 1/36 (3%) 0/34 (0%) | |FIRST INCIDENCE | |729 (T) 729 (T) 653 --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.343N P=0.756 P=0.494 P=0.511N | |POLY 3 | |P=0.322N P=0.757 P=0.500 P=0.494N | |POLY 1.5 | |P=0.320N P=0.755 P=0.502 P=0.493N | |POLY 6 | |P=0.327N P=0.759 P=0.497 P=0.496N | |LOGISTIC REGRESSION| |P=0.322N P=0.756 P=0.500 (e) | |COCH-ARM / FISHERS | |P=0.324N P=0.747 P=0.500 P=0.495N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 11 Statistical Analysis of Primary Tumors 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 | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | |0/47 (0%) 0/46 (0%) 0/47 (0%) 2/48 (4%) | |POLY-3 RATE (b) | |0/42.21 0/41.53 0/41.98 2/43.54 | |POLY-3 PERCENT (g) | |0.0% 0.0% 0.0% 4.6% | |TERMINAL (d) | |0/36 (0%) 0/35 (0%) 0/36 (0%) 2/34 (6%) | |FIRST INCIDENCE | |--- --- --- 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.038 * (e) (e) P=0.226 | |POLY 3 | |P=0.044 * (e) (e) P=0.244 | |POLY 1.5 | |P=0.044 * (e) (e) P=0.245 | |POLY 6 | |P=0.043 * (e) (e) P=0.241 | |LOGISTIC REGRESSION| |(e) (e) (e) P=0.226 | |COCH-ARM / FISHERS | |P=0.044 * (e) (e) P=0.253 | |=================================================================================================================================| | | | | | | 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 or Unspecified Site | | Adenoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/47 (0%) 0/48 (0%) 0/49 (0%) 0/48 (0%) |2/48 (4%) 3/47 (6%) 4/45 (9%) 2/48 (4%) | |POLY-3 RATE (b) | 0/43.37 0/42.17 0/44.36 0/39.13 |2/43.21 3/42.52 4/41.03 2/43.72 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |4.6% 7.1% 9.8% 4.6% | |TERMINAL (d) | 0/37 (0%) 0/38 (0%) 0/37 (0%) 0/30 (0%) |2/36 (6%) 2/37 (5%) 4/36 (11%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- --- |729 (T) 703 729 (T) 683 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.544N P=0.514 P=0.336 P=0.678 | |POLY 3 | (e) (e) (e) (e) |P=0.497N P=0.493 P=0.313 P=0.690N | |POLY 1.5 | (e) (e) (e) (e) |P=0.494N P=0.489 P=0.313 P=0.689N | |POLY 6 | (e) (e) (e) (e) |P=0.504N P=0.497 P=0.311 P=0.693N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.510N P=0.496 P=0.336 P=0.695N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.503N P=0.490 P=0.308 P=0.692N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 12 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |Skin | | Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, | | or Fibrous Histiocytoma | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |3/50 (6%) 4/50 (8%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 1/40.88 |3/45.18 4/46.06 2/44.74 2/45.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% |6.6% 8.7% 4.5% 4.4% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 1/30 (3%) |1/37 (3%) 1/38 (3%) 1/37 (3%) 1/34 (3%) | |FIRST INCIDENCE | --- --- --- 730 (T) |661 555 717 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.172 (e) (e) P=0.448 |P=0.370N P=0.515 P=0.511N P=0.527N | |POLY 3 | P=0.201 (e) (e) P=0.478 |P=0.338N P=0.510 P=0.504N P=0.499N | |POLY 1.5 | P=0.206 (e) (e) P=0.485 |P=0.334N P=0.503 P=0.500N P=0.496N | |POLY 6 | P=0.194 (e) (e) P=0.470 |P=0.346N P=0.519 P=0.512N P=0.506N | |LOGISTIC REGRESSION| (e) (e) (e) P=0.448 |P=0.335N P=0.501 P=0.501N P=0.497N | |COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.337N P=0.500 P=0.500N 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 | |=================================================================================================================================| | | |Skin | | Fibrosarcoma, Sarcoma, Myxosarcoma, or Fibrous Histiocytoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 1/50 (2%) |3/50 (6%) 4/50 (8%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 1/40.88 |3/45.18 4/46.06 2/44.74 1/45.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 2.5% |6.6% 8.7% 4.5% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 1/30 (3%) |1/37 (3%) 1/38 (3%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- 730 (T) |661 555 717 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.172 (e) (e) P=0.448 |P=0.188N P=0.515 P=0.511N P=0.327N | |POLY 3 | P=0.201 (e) (e) P=0.478 |P=0.165N P=0.510 P=0.504N P=0.304N | |POLY 1.5 | P=0.206 (e) (e) P=0.485 |P=0.163N P=0.503 P=0.500N P=0.302N | |POLY 6 | P=0.194 (e) (e) P=0.470 |P=0.171N P=0.519 P=0.512N P=0.309N | |LOGISTIC REGRESSION| (e) (e) (e) P=0.448 |P=0.165N P=0.501 P=0.501N P=0.303N | |COCH-ARM / FISHERS | P=0.215 (e) (e) P=0.500 |P=0.165N P=0.500 P=0.500N P=0.309N | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 13 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |Skin | | Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |3/50 (6%) 4/50 (8%) 2/50 (4%) 1/50 (2%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 0/40.88 |3/45.18 4/46.06 2/44.74 1/45.32 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |6.6% 8.7% 4.5% 2.2% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |1/37 (3%) 1/38 (3%) 1/37 (3%) 0/34 (0%) | |FIRST INCIDENCE | --- --- --- --- |661 555 717 701 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.188N P=0.515 P=0.511N P=0.327N | |POLY 3 | (e) (e) (e) (e) |P=0.165N P=0.510 P=0.504N P=0.304N | |POLY 1.5 | (e) (e) (e) (e) |P=0.163N P=0.503 P=0.500N P=0.302N | |POLY 6 | (e) (e) (e) (e) |P=0.171N P=0.519 P=0.512N P=0.309N | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.165N P=0.501 P=0.501N P=0.303N | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.165N P=0.500 P=0.500N P=0.309N | |=================================================================================================================================| | | | | | | 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 | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | | | |----------- | | | |OVERALL (a) | 0/49 (0%) 0/50 (0%) 1/49 (2%) 2/49 (4%) |0/47 (0%) 1/48 (2%) 0/47 (0%) 0/46 (0%) | |POLY-3 RATE (b) | 0/44.72 0/44.17 1/44.81 2/40.75 |0/43.70 1/43.55 0/42.46 0/41.88 | |POLY-3 PERCENT (g) | 0.0% 0.0% 2.2% 4.9% |0.0% 2.3% 0.0% 0.0% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 1/38 (3%) 1/30 (3%) |0/37 (0%) 1/38 (3%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 730 (T) 539 |--- 729 (T) --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.060 (e) P=0.495 P=0.204 |P=0.602N P=0.505 (e) (e) | |POLY 3 | P=0.073 (e) P=0.500 P=0.217 |P=0.594N P=0.499 (e) (e) | |POLY 1.5 | P=0.076 (e) P=0.501 P=0.222 |P=0.594N P=0.499 (e) (e) | |POLY 6 | P=0.067 (e) P=0.500 P=0.210 |P=0.594N P=0.500 (e) (e) | |LOGISTIC REGRESSION| P=0.089 (e) P=0.495 P=0.260 |(e) P=0.505 (e) (e) | |COCH-ARM / FISHERS | P=0.083 (e) P=0.500 P=0.247 |P=0.591N P=0.505 (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 14 Statistical Analysis of Primary Tumors 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 | | Squamous Cell Carcinoma or Papilloma Squamous | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 1/50 (2%) 2/50 (4%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) | |POLY-3 RATE (b) | 0/45.56 1/45.10 2/45.75 0/40.88 |0/44.88 0/45.21 0/44.70 0/45.21 | |POLY-3 PERCENT (g) | 0.0% 2.2% 4.4% 0.0% |0.0% 0.0% 0.0% 0.0% | |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 | --- 311 620 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.554N P=0.496 P=0.234 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.558N P=0.498 P=0.238 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.545N P=0.496 P=0.238 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.577N P=0.503 P=0.238 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.417N P=0.798 P=0.234 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.517N P=0.500 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 | |=================================================================================================================================| | | |Stomach, Forestomach | | Squamous Cell Papilloma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 2/50 (4%) 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 2/45.75 0/40.88 |0/44.88 0/45.21 0/44.70 0/45.21 | |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%) 1/38 (3%) 0/30 (0%) |0/37 (0%) 0/38 (0%) 0/37 (0%) 0/34 (0%) | |FIRST INCIDENCE | --- --- 620 --- |--- --- --- --- | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.736 (e) P=0.234 (e) |(e) (e) (e) (e) | |POLY 3 | P=0.722 (e) P=0.238 (e) |(e) (e) (e) (e) | |POLY 1.5 | P=0.716N (e) P=0.238 (e) |(e) (e) (e) (e) | |POLY 6 | P=0.698 (e) P=0.238 (e) |(e) (e) (e) (e) | |LOGISTIC REGRESSION| P=0.689N (e) P=0.234 (e) |(e) (e) (e) (e) | |COCH-ARM / FISHERS | P=0.695N (e) P=0.247 (e) |(e) (e) (e) (e) | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 15 Statistical Analysis of Primary Tumors 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 | | Polyp Stromal | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | |3/50 (6%) 1/50 (2%) 2/50 (4%) 2/50 (4%) | |POLY-3 RATE (b) | |3/44.88 1/45.21 2/44.70 2/45.21 | |POLY-3 PERCENT (g) | |6.7% 2.2% 4.5% 4.4% | |TERMINAL (d) | |3/37 (8%) 1/38 (3%) 2/37 (5%) 2/34 (6%) | |FIRST INCIDENCE | |729 (T) 729 (T) 729 (T) 729 (T) | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | |P=0.622 P=0.295N P=0.500N P=0.539N | |POLY 3 | |P=0.580N P=0.303N P=0.502N P=0.497N | |POLY 1.5 | |P=0.577N P=0.306N P=0.499N P=0.495N | |POLY 6 | |P=0.588N P=0.299N P=0.508N P=0.502N | |LOGISTIC REGRESSION| |P=0.622 P=0.295N P=0.500N P=0.539N | |COCH-ARM / FISHERS | |P=0.582N P=0.309N P=0.500N 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 | |=================================================================================================================================| | | |All Organs | | Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 0/50 (0%) 0/50 (0%) 0/50 (0%) 0/50 (0%) |0/50 (0%) 0/50 (0%) 0/50 (0%) 3/50 (6%) | |POLY-3 RATE (b) | 0/45.56 0/44.17 0/45.36 0/40.88 |0/44.88 0/45.21 0/44.70 3/45.47 | |POLY-3 PERCENT (g) | 0.0% 0.0% 0.0% 0.0% |0.0% 0.0% 0.0% 6.6% | |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 | --- --- --- --- |--- --- --- 660 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | (e) (e) (e) (e) |P=0.007 ** (e) (e) P=0.113 | |POLY 3 | (e) (e) (e) (e) |P=0.008 ** (e) (e) P=0.121 | |POLY 1.5 | (e) (e) (e) (e) |P=0.008 ** (e) (e) P=0.121 | |POLY 6 | (e) (e) (e) (e) |P=0.008 ** (e) (e) P=0.119 | |LOGISTIC REGRESSION| (e) (e) (e) (e) |P=0.009 ** (e) (e) P=0.122 | |COCH-ARM / FISHERS | (e) (e) (e) (e) |P=0.009 ** (e) (e) P=0.121 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 16 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 0/50 (0%) 7/50 (14%) 9/50 (18%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 4/50 (8%) | |POLY-3 RATE (b) | 6/46.34 0/44.17 7/45.93 9/42.54 |1/44.88 1/45.21 3/45.36 4/45.64 | |POLY-3 PERCENT (g) | 13.0% 0.0% 15.2% 21.2% |2.2% 2.2% 6.6% 8.8% | |TERMINAL (d) | 4/39 (10%) 0/40 (0%) 5/38 (13%) 5/30 (17%) |1/37 (3%) 1/38 (3%) 2/37 (5%) 2/34 (6%) | |FIRST INCIDENCE | 590 --- 653 539 |729 (T) 729 (T) 509 645 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.013 * P=0.019N* P=0.484 P=0.171 |P=0.079 P=0.756N P=0.309 P=0.170 | |POLY 3 | P=0.026 * P=0.018N* P=0.493 P=0.227 |P=0.093 P=0.759N P=0.309 P=0.184 | |POLY 1.5 | P=0.029 * P=0.018N* P=0.497 P=0.242 |P=0.094 P=0.760 P=0.310 P=0.184 | |POLY 6 | P=0.022 * P=0.017N* P=0.487 P=0.208 |P=0.090 P=0.757N P=0.306 P=0.182 | |LOGISTIC REGRESSION| P=0.034 * P=0.017N* P=0.500 P=0.279 |P=0.089 P=0.756N P=0.300 P=0.182 | |COCH-ARM / FISHERS | P=0.038 * P=0.013N* P=0.500 P=0.288 |P=0.090 P=0.753N P=0.309 P=0.181 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |All Organs | | Hemangiosarcoma or Hemangioma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 6/50 (12%) 0/50 (0%) 7/50 (14%) 9/50 (18%) |1/50 (2%) 1/50 (2%) 3/50 (6%) 6/50 (12%) | |POLY-3 RATE (b) | 6/46.34 0/44.17 7/45.93 9/42.54 |1/44.88 1/45.21 3/45.36 6/45.90 | |POLY-3 PERCENT (g) | 13.0% 0.0% 15.2% 21.2% |2.2% 2.2% 6.6% 13.1% | |TERMINAL (d) | 4/39 (10%) 0/40 (0%) 5/38 (13%) 5/30 (17%) |1/37 (3%) 1/38 (3%) 2/37 (5%) 3/34 (9%) | |FIRST INCIDENCE | 590 --- 653 539 |729 (T) 729 (T) 509 645 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.013 * P=0.019N* P=0.484 P=0.171 |P=0.010 * P=0.756N P=0.309 P=0.056 | |POLY 3 | P=0.026 * P=0.018N* P=0.493 P=0.227 |P=0.013 * P=0.759N P=0.309 P=0.059 | |POLY 1.5 | P=0.029 * P=0.018N* P=0.497 P=0.242 |P=0.013 * P=0.760 P=0.310 P=0.059 | |POLY 6 | P=0.022 * P=0.017N* P=0.487 P=0.208 |P=0.012 * P=0.757N P=0.306 P=0.059 | |LOGISTIC REGRESSION| P=0.034 * P=0.017N* P=0.500 P=0.279 |P=0.012 * P=0.756N P=0.300 P=0.059 | |COCH-ARM / FISHERS | P=0.038 * P=0.013N* P=0.500 P=0.288 |P=0.012 * P=0.753N P=0.309 P=0.056 | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 17 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |All Organs | | Histiocytic Sarcoma | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 1/50 (2%) 0/50 (0%) 0/50 (0%) 3/50 (6%) |0/50 (0%) 4/50 (8%) 1/50 (2%) 3/50 (6%) | |POLY-3 RATE (b) | 1/45.72 0/44.17 0/45.36 3/41.37 |0/44.88 4/46.01 1/44.70 3/45.39 | |POLY-3 PERCENT (g) | 2.2% 0.0% 0.0% 7.3% |0.0% 8.7% 2.2% 6.6% | |TERMINAL (d) | 0/39 (0%) 0/40 (0%) 0/38 (0%) 0/30 (0%) |0/37 (0%) 1/38 (3%) 1/37 (3%) 1/34 (3%) | |FIRST INCIDENCE | 690 --- --- 646 |--- 541 729 (T) 703 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.033 * P=0.495N P=0.510N P=0.237 |P=0.278 P=0.072 P=0.500 P=0.113 | |POLY 3 | P=0.049 * P=0.507N P=0.502N P=0.270 |P=0.307 P=0.064 P=0.499 P=0.121 | |POLY 1.5 | P=0.051 P=0.507N P=0.501N P=0.280 |P=0.308 P=0.062 P=0.501 P=0.121 | |POLY 6 | P=0.046 * P=0.503N P=0.504N P=0.258 |P=0.304 P=0.066 P=0.497 P=0.119 | |LOGISTIC REGRESSION| P=0.053 P=0.500N P=0.501N P=0.293 |P=0.302 P=0.064 P=0.500 P=0.121 | |COCH-ARM / FISHERS | P=0.056 P=0.500N P=0.500N P=0.309 |P=0.303 P=0.059 P=0.500 P=0.121 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |All Organs | | Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, | | NOS, or Undifferentiated Cell Type | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 3/50 (6%) 1/50 (2%) 2/50 (4%) 4/50 (8%) |7/50 (14%) 8/50 (16%) 6/50 (12%) 16/50 (32%) | |POLY-3 RATE (b) | 3/45.56 1/44.17 2/45.36 4/40.88 |7/44.90 8/46.93 6/45.97 16/45.85 | |POLY-3 PERCENT (g) | 6.6% 2.3% 4.4% 9.8% |15.6% 17.1% 13.1% 34.9% | |TERMINAL (d) | 3/39 (8%) 1/40 (3%) 2/38 (5%) 4/30 (13%) |6/37 (16%) 5/38 (13%) 3/37 (8%) 14/34 (41%) | |FIRST INCIDENCE | 730 (T) 730 (T) 730 (T) 730 (T) |723 281 509 621 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.134 P=0.296N P=0.512N P=0.358 |P=0.005 ** P=0.518 P=0.503N P=0.017 * | |POLY 3 | P=0.210 P=0.316N P=0.502N P=0.441 |P=0.006 ** P=0.537 P=0.482N P=0.028 * | |POLY 1.5 | P=0.222 P=0.318N P=0.500N P=0.458 |P=0.007 ** P=0.521 P=0.486N P=0.029 * | |POLY 6 | P=0.191 P=0.309N P=0.505N P=0.417 |P=0.006 ** P=0.552 P=0.479N P=0.027 * | |LOGISTIC REGRESSION| P=0.134 P=0.296N P=0.512N P=0.358 |P=0.007 ** P=0.502 P=0.499N P=0.025 * | |COCH-ARM / FISHERS | P=0.243 P=0.309N P=0.500N P=0.500 |P=0.007 ** P=0.500 P=0.500N P=0.028 * | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 18 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |All Organs | | Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 29/50 (58%) 24/50 (48%) 29/50 (58%) 27/50 (54%) |17/50 (34%) 16/50 (32%) 14/50 (28%) 26/50 (52%) | |POLY-3 RATE (b) | 29/47.88 24/45.10 29/47.45 27/44.89 |17/45.82 16/45.90 14/45.28 26/47.87 | |POLY-3 PERCENT (g) | 60.6% 53.2% 61.1% 60.2% |37.1% 34.9% 30.9% 54.3% | |TERMINAL (d) | 24/39 (62%) 21/40 (53%) 24/38 (63%) 17/30 (57%) |15/37 (41%) 14/38 (37%) 12/37 (32%) 19/34 (56%) | |FIRST INCIDENCE | 420 455 581 483 |536 541 647 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.106 P=0.197N P=0.521 P=0.281 |P=0.006 ** P=0.464N P=0.337N P=0.035 * | |POLY 3 | P=0.450 P=0.305N P=0.562 P=0.569N |P=0.019 * P=0.497N P=0.344N P=0.068 | |POLY 1.5 | P=0.467 P=0.292N P=0.569 P=0.545N |P=0.018 * P=0.505N P=0.333N P=0.065 | |POLY 6 | P=0.418 P=0.297N P=0.554 P=0.579 |P=0.019 * P=0.488N P=0.360N P=0.070 | |LOGISTIC REGRESSION| P=0.419 P=0.261N P=0.580 P=0.532N |P=0.016 * P=0.494N P=0.337N P=0.056 | |COCH-ARM / FISHERS | P=0.545N P=0.212N P=0.580N P=0.420N |P=0.015 * P=0.500N P=0.333N P=0.053 | |=================================================================================================================================| | | | | | | 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 | |=================================================================================================================================| | | |All Organs | | Malignant Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 24/50 (48%) 20/50 (40%) 27/50 (54%) 30/50 (60%) |17/50 (34%) 22/50 (44%) 20/50 (40%) 28/50 (56%) | |POLY-3 RATE (b) | 24/47.76 20/46.91 27/48.81 30/47.14 |17/45.68 22/48.58 20/47.73 28/47.15 | |POLY-3 PERCENT (g) | 50.3% 42.6% 55.3% 63.6% |37.2% 45.3% 41.9% 59.4% | |TERMINAL (d) | 18/39 (46%) 15/40 (38%) 17/38 (45%) 14/30 (47%) |12/37 (32%) 13/38 (34%) 12/37 (32%) 18/34 (53%) | |FIRST INCIDENCE | 590 311 548 483 |647 281 481 579 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.007 ** P=0.276N P=0.333 P=0.044 * |P=0.022 * P=0.264 P=0.347 P=0.022 * | |POLY 3 | P=0.044 * P=0.296N P=0.384 P=0.132 |P=0.023 * P=0.279 P=0.401 P=0.024 * | |POLY 1.5 | P=0.041 * P=0.299N P=0.369 P=0.123 |P=0.024 * P=0.247 P=0.383 P=0.023 * | |POLY 6 | P=0.047 * P=0.288N P=0.402 P=0.140 |P=0.021 * P=0.311 P=0.415 P=0.024 * | |LOGISTIC REGRESSION| P=0.054 P=0.272N P=0.345 P=0.142 |P=0.025 * P=0.205 P=0.341 P=0.023 * | |COCH-ARM / FISHERS | P=0.054 P=0.273N P=0.345 P=0.158 |P=0.024 * P=0.206 P=0.339 P=0.022 * | |=================================================================================================================================| Date: 04/23/01 EXPERIMENT: 88122 TEST: 07 Page 19 Statistical Analysis of Primary Tumors 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 | |=================================================================================================================================| | | |All Organs | | Malignant and Benign Tumors | | | | | |---------------------------------------------------------------------------------------------------------------------------------| |TUMOR RATES | # # # # |# # # # | |----------- | | | |OVERALL (a) | 38/50 (76%) 32/50 (64%) 41/50 (82%) 42/50 (84%) |29/50 (58%) 34/50 (68%) 30/50 (60%) 40/50 (80%) | |POLY-3 RATE (b) | 38/48.82 32/47.67 41/49.26 42/48.00 |29/46.61 34/48.68 30/48.32 40/49.06 | |POLY-3 PERCENT (g) | 77.8% 67.1% 83.2% 87.5% |62.2% 69.8% 62.1% 81.5% | |TERMINAL (d) | 30/39 (77%) 25/40 (63%) 30/38 (79%) 24/30 (80%) |22/37 (60%) 24/38 (63%) 20/37 (54%) 26/34 (77%) | |FIRST INCIDENCE | 420 311 548 483 |536 281 481 401 | |-------------------| | | |STATISTICAL TESTS | | | |-------------------| | | |LIFE TABLE | P=0.002 ** P=0.163N P=0.304 P=0.028 * |P=0.019 * P=0.294 P=0.487 P=0.022 * | |POLY 3 | P=0.039 * P=0.168N P=0.336 P=0.159 |P=0.027 * P=0.284 P=0.579N P=0.026 * | |POLY 1.5 | P=0.032 * P=0.170N P=0.323 P=0.139 |P=0.025 * P=0.247 P=0.565 P=0.022 * | |POLY 6 | P=0.048 * P=0.163N P=0.361 P=0.187 |P=0.028 * P=0.316 P=0.561N P=0.030 * | |LOGISTIC REGRESSION| P=0.036 * P=0.154N P=0.312 P=0.133 |P=0.020 * P=0.197 P=0.507 P=0.017 * | |COCH-ARM / FISHERS | P=0.059 P=0.138N P=0.312 P=0.227 |P=0.018 * P=0.204 P=0.500 P=0.015 * | |=================================================================================================================================| (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).