While biostatistics does not get used very much in early human clinical trials, any regulatory changes can have an effect on the practice. The EMEA has published new guidelines (pdf - in draft form, to be finalized after public comment and consultation with industry) about the conduct of Phase I trials for "high-risk" compounds. This comes in the wake of the infamous TGN1412 trial, in which a monoclonal antibody caused severe adverse reactions in all of the six otherwise healthy trial participants. (All six participants suffered multiple organ failure, along with gangrene. They will all probably contract and die of cancer within a few short years.)
The EMEA concluded that the trial was conducted in accordance with current regulations. These new recommendations are changes to avoid another similar disaster.
Among the recommendations:
- stronger pre-clinical data, and a stronger association between pre-clinical data and choice of dosing in humans (e.g. using minimal dose for biological activity), as opposed to the no observed adverse-event dose
- the use of independent data safety monitoring boards, along with well-defined stopping rules for subjects, cohorts, and trials
- well-defined provisions for dose-escalation
- increasing follow-up length for safety monitoring
- use of sites with appropriate medical facilities
(via Thomson Centerwatch)
