(by Andrew Gelman)
Following our discussion of Avastin, a drug that some have argued doesn’t work for one of its Medicare-approved uses, an anonymous source who has worked with a foreign regulatory review agency, speculated that at least there, in similar situations, the lack of observed OS advantage would not have been a large concern (for the statistical reasons that Don Berry raised in his thoughtful post). However, there is uncertainty about a PS advantage always leading to OS survival. This can be fairly well contained from the context in many cancers, as Don Berry also indicates, but it remains extra uncertainty above what is usual in the evaluation of RCT based evidence.
The larger concerns more likely would have been:
1. Is the benefit of the uncertain increase in PFS worth the risk of uncertain harms observed in the trials?
2. How does one properly discount what was “reported” about the trials/research program by the sponsor, given as Sander Greenland nicely put it is his short post “the influences of vested interests” that almost surely exaggerated those reports?
For 1, it needs to be kept in mind that the consideration of costs and whether to provide the approved products to which patients (i.e. consider cost-effectiveness) might be best left for others to decide later. That is, an initial focus to strictly decide if benefits exceed (justify) the harms might be better. In this initial focus, note that the increases in PFS are often small, harms often include fatal ones, and the observed harms in the trials usually considerably under estimate the harms in the less well controlled practice settings.
For 2, one should not blame the drug companies or expect otherwise from their employees/consultants. It is in partly human nature and also what business is about (when within reason such as when the “answer” is not obvious to most and there is enough uncertainty for judgments to vary widely.) See this paper by Sander Greenland.