600 - Regarding Code s3.1.1, does PAAB distinguish between different types of "pooled data"? For example a post-hoc pooled analyses of unrelated trials (low evidence), vs. a pre-specified pooled analyses of replicate trials (higher evidence)? Such pre-specified pooled analyses are commonly used in registration trials for certain therapeutic categories, and therefore interpretation of s3.1.1 could potentially be biased.

  • I’ll begin by paraphrasing s3.1.1 in saying that pooled analysis are generally not considered high-level evidence. Now, onto your question. There is a difference in the sense that, post-hoc, I may select which studies to include/exclude in a pooled analysis based on how each potential combination will impact the outcome. Pre-specifying the pooling protocol & studies eliminates that risk. But there is more to this than the simple fact that pre-specifying commits me to the studies I’ll eventually be pooling. Pre-specifying may also enable me to consider my intention to eventually pool the data while I am designing those individual studies. This way, I am more likely to design the studies such that the endpoints are defined & measured the same way, the drugs are dosed the same way, identical inclusion/exclusion criteria are used… etc. These all impact the validity of the pooled analysis. I should stress that this is not always the case. I’ve seen pre-specified analysis where important aspects of the methodologies conflicted (thus calling into question the pooling). Also, note that a pooled analysis cannot be considered if the individual studies do not meet the rigors of the PAAB Code and guidances. It is also important to note that a pooled analysis cannot be used to convey an outcome which differs from individual trials in the TMA (i.e. advertising must be consistent with the TMA). As you can see, there is a lot to consider here and it’s impossible to capture it all in a general answer to a general question. For an answer more specific to your situation, you’ll need to submit a written (see fee schedule on our site).