Risk Management Principles for Devices and Pharmaceuticals
vii
Table 7-7. Example Acceptability Legend. .......................................................................................108
Table 8-1. Traditional Quality Management vs. QRM Approach....................................................129
Table 10-1. Examples of Risk Mitigation and Monitoring.................................................................160
Table 11-1. Clinical Evidence Premarket Documentation Requirements...........................................167
Table 11-2. Clinical Evidence Postmarket Documentation Requirements. ........................................167
Table 11-3. Clinical Evidence Element General Safety and Performance Requirements...................167
Table 11-4. Clinical Evidence Element not in General Safety and Performance Requirements. .......172
Table 11-5. Clinical Evidence Elements for Medical Device Software. .............................................173
Table 11-6. Clinical Development Plan with R-IDEAL Endpoints..................................................176
Table 12-1. Categories of PASS..........................................................................................................184
Table 12-2. Summary of Applicable Regulatory Requirements for PASS Conducted in the EU.......184
Table 12-3. Regulatory Requirements for Noninterventional PASS...................................................187
Table 12-4. GVP Module I: Purpose and Applicability to PASS. ......................................................190
Table 12-5. GVP Modules II, IV, V and VI: Purposes and Applicability to PASS.............................191
Table 12-6. Management of Adverse Events for NI PAS with a Design Based on Primary Data
Collection........................................................................................................................194
Table 12-7. Obligations to Consider for Conduct of US PMS ..........................................................195
Table 15-1. Medical Device Clinical Evidence Requirements............................................................228
Table 15-2. Medical Device Software Clinical Evidence Requirements.............................................229
Table 15-3. Medical Device Clinical Evidence Requirements for Quality and Quantity. ..................230
Table 19-1. Adverse Drug Event Detection and Reporting Methods. ...............................................271
Table 19-2. Comparison of Current and Proposed Programs. ............................................................278
Table 20-1. Combined Osteoporosis Treatment and Prevention Trials including Hip Fracture
Trials. ...............................................................................................................................284
Table 20-2. Lung Cancer in Risedronate Phase III PMO/CIO and HIP Fracture Trials..................285
Table 20-3. Distribution of Cancer Cases by COSTART: Ten Combined Risedronate Trials. ..........286
Table 20-4. GI Cancer in Combined Risedronate Phase III PMO/CIO and Hip Fracture Trials.....287
Table 20-5. FDA Statistical Analysis of Lung Cancer by Smoking History, Age, and Risedronate
Dose in Risedronate Clinical Studies...............................................................................287
Table 20-6. Observed to Expected Lung Cancer Cases in Combined Risedronate Studies Based
on the SEER Database (1988-1992) for US White Women...........................................288
Table 20-7. Distribution of Lung Cancer Based on Best Available Evidence.....................................289
Table 20-8. Categorization of Lung Cancer Data..............................................................................290
Table 20-9. Lung Cancers Excluding Cases 6 Months After Dosing..............................................290
Table 20-10. Time of Diagnosis for 59 Cases of Lung Cancer.............................................................291
Table 20-11. Incidence of Lung Cancer Based on 1,000 Person-Years of Observation. .......................292
Table 20-12. Cancer Cases by Site........................................................................................................294
Table 20-13. Anticipated Deaths Due to Lung Cancer in Mortality Follow-Up Studies RVN,
RON, and RHN. .............................................................................................................295
Table 20-14. Patient-Years of Follow-up for RON009393, RVN008993, and RHN009193................296
Table 20-15. “On-Study” Mortality Studies RON009393, RVN008993, and RHN009193................297
Table 20-16. Estimated Mortality Due to Lung Cancer (Assumes RR* of 1.0 During “Off-Study”
Follow-up of Non-incident Lung Cancer Cases, Studies RON009393, RVN008993,
and RHN009193)............................................................................................................298
Table 20-17. Estimated Mortality Due to Lung Cancer (Assumes RR* of 2.0 during “Off-Study”
Follow-up of Non-incident Lung Cancer Cases, Studies RON009393, RVN008993,
and RHN009193)............................................................................................................298
Table 20-18. Mortality Comparisons Across Treatment Groups -All Cause through
December 31, 1997 (Intent-to-treat)................................................................................299
vii
Table 7-7. Example Acceptability Legend. .......................................................................................108
Table 8-1. Traditional Quality Management vs. QRM Approach....................................................129
Table 10-1. Examples of Risk Mitigation and Monitoring.................................................................160
Table 11-1. Clinical Evidence Premarket Documentation Requirements...........................................167
Table 11-2. Clinical Evidence Postmarket Documentation Requirements. ........................................167
Table 11-3. Clinical Evidence Element General Safety and Performance Requirements...................167
Table 11-4. Clinical Evidence Element not in General Safety and Performance Requirements. .......172
Table 11-5. Clinical Evidence Elements for Medical Device Software. .............................................173
Table 11-6. Clinical Development Plan with R-IDEAL Endpoints..................................................176
Table 12-1. Categories of PASS..........................................................................................................184
Table 12-2. Summary of Applicable Regulatory Requirements for PASS Conducted in the EU.......184
Table 12-3. Regulatory Requirements for Noninterventional PASS...................................................187
Table 12-4. GVP Module I: Purpose and Applicability to PASS. ......................................................190
Table 12-5. GVP Modules II, IV, V and VI: Purposes and Applicability to PASS.............................191
Table 12-6. Management of Adverse Events for NI PAS with a Design Based on Primary Data
Collection........................................................................................................................194
Table 12-7. Obligations to Consider for Conduct of US PMS ..........................................................195
Table 15-1. Medical Device Clinical Evidence Requirements............................................................228
Table 15-2. Medical Device Software Clinical Evidence Requirements.............................................229
Table 15-3. Medical Device Clinical Evidence Requirements for Quality and Quantity. ..................230
Table 19-1. Adverse Drug Event Detection and Reporting Methods. ...............................................271
Table 19-2. Comparison of Current and Proposed Programs. ............................................................278
Table 20-1. Combined Osteoporosis Treatment and Prevention Trials including Hip Fracture
Trials. ...............................................................................................................................284
Table 20-2. Lung Cancer in Risedronate Phase III PMO/CIO and HIP Fracture Trials..................285
Table 20-3. Distribution of Cancer Cases by COSTART: Ten Combined Risedronate Trials. ..........286
Table 20-4. GI Cancer in Combined Risedronate Phase III PMO/CIO and Hip Fracture Trials.....287
Table 20-5. FDA Statistical Analysis of Lung Cancer by Smoking History, Age, and Risedronate
Dose in Risedronate Clinical Studies...............................................................................287
Table 20-6. Observed to Expected Lung Cancer Cases in Combined Risedronate Studies Based
on the SEER Database (1988-1992) for US White Women...........................................288
Table 20-7. Distribution of Lung Cancer Based on Best Available Evidence.....................................289
Table 20-8. Categorization of Lung Cancer Data..............................................................................290
Table 20-9. Lung Cancers Excluding Cases 6 Months After Dosing..............................................290
Table 20-10. Time of Diagnosis for 59 Cases of Lung Cancer.............................................................291
Table 20-11. Incidence of Lung Cancer Based on 1,000 Person-Years of Observation. .......................292
Table 20-12. Cancer Cases by Site........................................................................................................294
Table 20-13. Anticipated Deaths Due to Lung Cancer in Mortality Follow-Up Studies RVN,
RON, and RHN. .............................................................................................................295
Table 20-14. Patient-Years of Follow-up for RON009393, RVN008993, and RHN009193................296
Table 20-15. “On-Study” Mortality Studies RON009393, RVN008993, and RHN009193................297
Table 20-16. Estimated Mortality Due to Lung Cancer (Assumes RR* of 1.0 During “Off-Study”
Follow-up of Non-incident Lung Cancer Cases, Studies RON009393, RVN008993,
and RHN009193)............................................................................................................298
Table 20-17. Estimated Mortality Due to Lung Cancer (Assumes RR* of 2.0 during “Off-Study”
Follow-up of Non-incident Lung Cancer Cases, Studies RON009393, RVN008993,
and RHN009193)............................................................................................................298
Table 20-18. Mortality Comparisons Across Treatment Groups -All Cause through
December 31, 1997 (Intent-to-treat)................................................................................299