After a multi-year gestation period (my notes on this project go back to 2012!!), a comment on the FDA draft HABP/VABP guidance document has now been submitted by the FNIH (Foundation for the NIH) Biomarkers Consortium HABP/VABP Project Team and posted online. Links to the docket and document are below my signature.
The document is substantial and you should plan to review it in detail if you are interested in studies of Noscomial Pneumonia. I have excerpted below my signature the summary recommendations.
At a high level, the key points are that (a) VABP and ventilated HABP may be studied together, (b) non-ventilated HABP is meaningfully different, (c) all-cause mortality at day 14-28 remains a valid endpoint but also (d) the Standardized MedDRA Query (SMQ) for Toxic/Septic Shock can be used to create a “mortality plus” endpoint that incorporates SAEs & AEs from that SMQ.
Interestingly, it turned out that non-ventilated HABP seems amenable to study with the same symptom-based tool that we use for CABP.
Frustratingly (and despite its obvious biological relevance), the available data on improvement in oxygenation were inadequate to support meaningful analysis. We were all eager for a way to validate this as an endpoint, but the required data were not collected in sufficient detail in the studies avaialble for analysis. The project team recommends that such data be gathered in future trials and perhaps this can be revisited.
Overall, this docket submission is expected to be a substantial boost to finalization by FDA of its guidance on conducting HABP-VABP trials. Establishing the acceptable performance of the “mortality plus” strategy is important as this helps ensure an event rate high enough to allow to allow use of the fixed 10% NI margin recommended for HABP-VABP trials.
It’s a work of many hands, but I would be remiss if I failed to say that the entire commmunity owes thanks to George Talbot for his exemplary leadership of this project. Thank you, George!!
All best wishes,
John H. Rex, MD | Chief Medical Officer, F2G Ltd. | Chief Strategy Officer, CARB-X | Expert-in-Residence, Wellcome Trust. Follow me on Twitter: @JohnRex_NewAbx
The FDA docket: https://www.regulations.gov/docket?rpp=10&po=0&D=FDA-2010-D-0589
FNIH’s submission in the docket: https://www.regulations.gov/document?D=FDA-2010-D-0589-0027
Summary of Recommendations
1. VABP and ventilated HABP appear to be similar syndromes that can readily be studied together. Patients with non-ventilated HABP have a lower mortality rate, and this difference should be anticipated if a study seeks to pool data across all three categories of nosocomial pneumonia.