Review by Joseph Ross – 02/21/2018 – 8:26am

Data Request Number: 2017-2036 Is the scientific purpose of the research proposal clearly described?: Yes Will request create or materially enhance generalizable scientific and/or medical knowledge to inform science and public health?: Yes Can the proposed research be reasonably addressed using the requested data?: Yes, or it’s highly likely Please use this space to provide any comments, feedback or concerns (optional):

This is an interesting proposal to estimate tumor regression and growth rates, along with fractional cell kill and overall survival, among men with prostate cancer treated with abiraterone acetate in 2 clinical trials. While I think I understand the purpose of the analysis, it could have been written a bit more clearly. I would have preferred to see more explicit text describing how tumor regression and growth rates, along with fractional cells killed, would be estimated. The citations were not embedded in the article, so I presume the method is similar to the mathematical model described in citation 7 (Lancet Oncol. 2017; 18:143-154), but I was not certain.
In addition, I was confused by aim 2 – the application of these estimates to other data sources. This aspect of the proposal is not well described (no methods or statistical analysis plan is focused on the application of the estimates to other public data sources or the VA data). The work to calculate the growth rate estimates and correlate to observed survival from the shared abiraterone acetate clinical trial data is clearly described. I would advice focusing this proposal on that aspect of aim 2.
In addition, specific information about the mathematical model would be useful to provide. For instance, what % of missing data can be tolerated before a patient needs to be excluded from analysis (1%, 10%?); the first sentence of the statistical analysis plan was difficult to comprehend; can the time point for landmark analysis be pre-specified (the text says only that it will be pre-specified – but the purpose of the proposal is to pre-specify the methods).
Lastly, more information on how this proposal will establish the efficacy of abiraterone would be helpful. As I read it, I understood it as a more granular analysis, better understanding the correlation between the rate of growth and the overall survival. However, since all patients are receiving abiraterone, it was not clear how this work would evaluate drug efficacy.

Recommendation for this data request: Approve