Some thoughts / notes on the topic of why so many drugs fail to get FDA approval:
- Efficacy-related failures
- Safety-related failures
- assess risk profile
- ex. systemic toxicity, tumorigenicity, arrhythmias, side effects
- Research, Manufacturing, & Commercial Processes
- optimized for one objective and not the other
- Suboptimal endpoints chosen
- clinical benefit difficult to measure
- disease progression
- overall survivability
- Control Group Problems
- Poorly-chosen Patient Populations
- broad vs. targeted
- Data Management
- Suboptimal data capture / entry
- Investigator bias
- Reporting bias
- Patient Enrollment
- Suboptimal inclusion / exclusion criteria
- Failure to meet enrollment goals
- Cannot recruit enough patients for clinical trial
- Although most patients do not have a problem with the drug; there is a need to redesign the trial
- ex. change the dosage, administration, or procedure
- Lack of money to redesign the trial and start the process over again
- Regulatory
- Key parameters must be clear
- establish criteria needed for safety
- Learning curve for both clinical operations and regulatory agencies
- Agencies fear bad press & litigation
- The framework is still evolving
caco-2 immortalized human epithelial colorectal adenocarcinoma cell line
is used to search for novel compounds to treat colorectal and other cancers
