February 28, 2012
Rodney L. Lemery, MPH, PhD, Vice President of Safety and Pharmacovigilance, BioPharm Systems, Inc
Where does data stop and information begin? I believe this question directly lead to the Food and Drug Administration’s (FDA) recent change to the existing rules governing the reporting of individual case safety reports (ICSR) collected in clinical trials under Investigational New Drug (IND) licenses. These changes, made effective last year on March 28, 2011, contain the following highlights (Sherman, Woodcock, Norden, Grandinetti, & Temple):
1. Reported cases must contain unexpected events. These are event terms not present in the investigational brochure.
2. Reported cases must contain serious events. These are events meeting seriousness criteria defined by the ICH:
a. Events resulting in death, or a threat to life
b. Events resulting in the initialization or prolongation of hospitalization
c. Events resulting in the persistent or clinically significant incapacitation of the patient
d. Events resulting in substantial disruption of the ability to conduct normal life functions
e. Events resulting in a congenital anomaly or birth defect.
3. The event must be a suspected adverse reaction, meaning that there must be a “reasonable possibility” (i.e., evidence to suggest) that the product caused it
While none of the above modifications are new to those of us in product safety, the regulation now provides guidance on how the “causal” assessment should be conducted (item three above). This modification means that a company should ensure they are reporting only serious, unexpected adverse product reactions. Prior to this, the agency noted that many times serious events were being reported to the program regardless of relationship to study product. This can lead to overwhelming amounts of data that detract from the meaningful information required to protect the public health. For example, the causal relationship to study product in a report of osteoporosis in an elderly female would be very difficult to ascertain. However, a report of anaphylaxis in a clinical trial might have a stronger causal assessment of “reasonable possibility.”
Additionally, sponsors should not include study end points except in unusual situations. Recognizing that events common in the study population or representing study endpoints could be study product related, the regulation requires periodic assessment of all serious events reported in a clinical trial. These changes should bring the FDA in better alignment with wording already in place with the rest of the International Conference on Harmonisation (ICH).
References
Sherman, R., Woodcock, J., Norden J., Grandinetti, C., and Temple, R.. (2011). New FDA Regulation to Improve Safety Reporting in Clinical Trials. Retrieved on January 31, 2012 from http://www.nejm.org/doi/full/10.1056/NEJMp1103464
Note: This post was edited by Adam Kaus.
