Sponsors are generally aware of the commonly held Type B FDA meetings, from pre-IND to End of Phase 2 (EOP2) to pre-NDA/BLA, but how often do you take advantage of additional Type C meetings for agency feedback? Continued discussion and input from the agency can be very beneficial, even outside of the milestones that allow for a Type B Meeting. 

At times, the agency even encourages this. You may notice in the minutes from your latest FDA meetings, a “General Comments” section, with a mess of remarks that may or may not be relevant to your current program. But take note of one sub-heading in those comments, titled “Discussion of Safety Analysis Strategy for the ISS”.  After your EOP2 and before your pre-NDA/BLA, FDA offers sponsors an opportunity to meet and discuss plans for the Integrated Summary of Safety. This can help expedite the time to filing, by allowing programming of integrated analyses to move forward with minimal risk well ahead of the pre-NDA/BLA meeting.

In fact, this meeting can be used as a broad planning tool for many statistical aspects of the submission, from ISS/ISE analyses, to clinical data standardization, to SEND nonclinical data. We generally recommend submitting three documents for feedback at this Type C Meeting. Questions asked in the meeting request should aim to gain alignment on any components of these documents that are non-standard or critical to key messaging.

(1)  Statistical Analysis Plan for the Integrated Summary of Safety

• Specify how studies will be grouped for pooled safety analyses 
• Provide rationale for studies to be excluded from pooled analyses 
• Detail meta-analytical procedures to be used in combining data across studies 
• Identify methods to be used in summarization of known safety issues (e.g., SMQs) 

(2)  Statistical Analysis Plan for the Integrated Summary of Efficacy 

• Identify which studies will be included in pooled efficacy analyses
• Discuss analysis methods to be utilized for primary and secondary endpoints
• Include list of subgroups to be analyzed in accordance with 21 CFR 314.50
• Describe how study-level data will be utilized in conjunction with pooled analyses to support an integrated discussion of efficacy

(3)  Study Data Standardization Plan

• List all clinical and nonclinical studies under the IND 
• Identify the data format to be used for each study (SDTM, ADaM, SEND, etc.) 
• Justify any instance of non-conformance with FDA data standards requirements 

It’s never too early to start planning! Once you pass your EOP2 milestone, contact us to speak with one of our Biometrics Regulatory Experts about NDA/BLA planning.

Evan Zucker, Principal Biostatistician, has 9 years of experience providing statistical support for clinical trials, with a specific focus on late-stage regulatory submissions. Mr. Zucker has supported upwards of twenty marketing applications and over a dozen FDA meetings, often working as the primary author of integrated statistical analysis plans and CDISC-compliant integrated analysis dataset (ADaM) specifications for the ISS and ISE. In supporting marketing application submissions, he also acts as a data standards expert, reviewing and updating study data packages to ensure compliance with the latest FDA requirements, technical rejection criteria, and CDISC/legacy guidelines. Mr. Zucker has collaborated with clinical researchers and medical authors across various therapeutic areas, including pain/anesthesia, psychiatry, otolaryngology, oncology, ophthalmology, rare/genetic diseases, and vaccines/infectious diseases.