Recent guidance on safety monitoring during drug development, issued by regulatory authorities in the US and EU, indicate a shift in focus toward aggregate safety monitoring and scientific evaluation of integrated safety data earlier in the development program. This shift in emphasis provides an opportunity for sponsors to engage in the advancement of cross disciplinary procedures for aggregate safety analysis to further improve identification and characterization of risks for a medicine on a program level. Expectations are for a more systematic approach to identify and evaluate important safety information during clinical development.
One of the greatest challenges in the biopharma industry, but at the same time, one of the greatest opportunities for growth and collaboration; as different region-specific regulatory initiatives go beyond ICH technical requirements, changes in emphasis develop. For postmarketing safety surveillance, aligned with CIOMS VIII, the EMA/HMA have developed numerous and diverse GVP modules that implement the 2010 EU PV legislation. Progress has been made in harmonization across regions. For clinical trial safety monitoring, aligned with CIOMS VI, the FDA has issued the IND Safety Reporting final rule.
Sponsors should have a systematic approach to safety surveillance; where an aggregate analysis of specific events could indicate whether those events occur more frequently in the drug treatment group than in a concurrent or historical control group. After each review of accumulating safety data collected across completed and ongoing studies in the program, the SPONSOR should make a judgment about the likelihood that the drug caused any SAEs. An effective systematic approach by sponsors to safety surveillance, along with limiting IND safety reports to suspected adverse reactions that are both serious and unexpected, allows all involved to focus on important safety issues and take necessary actions to minimize the risks of participation in a clinical trial.
The US FDA has placed responsibility squarely on sponsors to send a safety report only after they have judged there to be a reasonable possibility that the study drug caused the event. For other regional regulatory agencies (including in the EU), assessment of causality considers the opinion of the investigator as well as the sponsor and all individual SUSARs are required to be reported in an expedited manner. Consequently, it can be challenging to apply a single global approach to report handling. Regulators in different regions could be examining different SUSAR data as trials progress, which can introduce additional challenges.
Regaining Global Alignment on Safety Reporting from Clinical Trials.