It is often necessary to pool safety data from late phase studies, in preparation for regulatory submission. Some of our clients have also begun to add Phase 1 safety data to this pool. On some occasions this is required by regulators. In many cases, however, these Phase 1 data simply provide further evidence that a new therapeutic lives up to the promise of safety across patient populations.
When adding early phase data to data pooling for safety, the challenges of data pooling in late phase studies quickly amplify. If data are not stored and streamlined using common standards like CDISC, pooling early phase data (or indeed any datasets) across studies can become a nightmare. Cytel once had a client that wanted to pool data from more than ten Phase 1 studies, where most of the data were collected using no common forms or standards. This meant that we had to dispatch a team of data managers with the statistical savvy to interpret and collate the data supplied to us.
Adding to the challenge was that these studies, like many early phase studies, had several clinical trial designs, often constructed with varying objectives in mind. Understanding the objectives of the trial designs became critical for data interpretation. Thankfully our team of data managers also contained statisticians, clinical trial designers, and early phase experts, in addition to individuals with regulatory expertise.
Finally, the small sample sizes of Phase 1 trials needed careful attention from our statisticians. Taken together, the sample size was large enough to add significant evidence to safety. However, once again, as the studies often tested different doses or focused on different populations, advanced statistical techniques were necessary to streamline them.