In order to increase the likelihood that drug efficacy signals can be detected during clinical trials, pharmaceutical developers purposefully enroll subjects who are expected to help achieve the best possible results. Potential clinical trial participants are subjected to rigorous inclusion and exclusion criteria. Subjects that pass these selection processes and are ultimately enrolled in the trial, therefore, end up being a relatively homogenous group.

The selection process is vital for determining a compound’s efficacy and is also usually necessary for both financial and logistic reasons. The downside of such methods, however, is that this homogeneous group of subjects may react in similar ways to a test drug. The clinical trial process, therefore, cannot uncover many of the side effects that occur once the drug is introduced to real-word, heterogeneous, patient populations.


Related Read: Post Approval Adverse Events... What's the Real World Impact? [INFOGRAPHIC]


A member of the FDA’s Office of Drug Safety summed up the issue by stating: 1) “the complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials” and, 2) “since most trials exclude the elderly, children, pregnant women, patients with multiple diseases, and those on medications suspected of interaction with the study drug, the studies’ participants may not be representative of the real world where the drug is eventually used.”

Accordingly, clinical testing typically uncovers common side effects such as gastrointestinal discomfort, flu-like illnesses, nausea, etc. Oftentimes, however, serious and life-threatening side effects that were not exposed during the screening programs become evident only after the drug wins FDA approval.

The gradual evolution of side effect profiles across numerous drug classes after they were approved serves to underscore the preceding points. Examples include: life-threatening birth defects caused by the immunomodulator thalidomide, severe cardiac complications from the weight management drug Meirida, a fatal muscle-wasting syndrome from the cholesterol management drug Baycol, and increased heart attack and stroke rates in patients taking Vioxx prescribed for osteoarthritis and joint pain, etc.).

Healthcare professionals routinely obtain safety information from drug label “inserts” that are often times based predominately on pre-approval clinical trial results. It is this reliance on incomplete safety data derived from limited clinical trial systems that creates a significant gap in knowledge for the industry.


Careful and continuous post-approval monitoring of ADEs therefore plays a key role in the on-going evaluation of a drug’s true safety profile.

Learn more by reading our comprehensive guide to FAERS. 


Freedom of Information Act Request - FAERS Report download

Keith Hoffman

Keith Hoffman, PhD

Vice President, Scientific Affairs

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Topics: Drug Safety, FDA, Clinical Evidence

Dr. Keith Hoffman

Written by Dr. Keith Hoffman