Rob Woolson, Chief Strategist-Biostatistics and Data Standards for Regulatory Submissions,  has led SDTM/ADaM dataset conversion projects in multiple therapeutic areas. He has held a leadership role in six CDISC-compliant regulatory submissions, having guided the creation of ISS/ISE statistical analysis plans; integrated analysis dataset design and production; integrated display design and production; and submission-related documentation development. 

Bridging the Gap between Technical/Data Standards and Regulatory/Medical Writing in NDA Submissions

Many CROs currently offer two categories of services to sponsor companies preparing for an NDA or marketing application submission. The first category contains technical data standards services. These services include converting existing clinical datasets to CDISC compliant formats and generating the datasets for the integrated summary of safety (ISS) and integrated summary of efficacy (ISE). The second category includes regulatory and medical writing services associated with the marketing application submission.

There are a number of activities that need to take place that fall in between these two categories to ensure a successful marketing application submission. While some CROs offer these services on an ad-hoc basis, and some sponsors have the internal expertise and capacity to fill these gaps, there remains an unmet need to define and consistently deliver these services. We see these late-stage biostatistics submission services falling into two sub-categories—marketing application services and regulatory interaction support.

Marketing applications services include activities like analysis plan development; data standards plan development; supporting regulatory and medical writing during the submission process; pooled data assessment; and analyses to support key messages. For example, an analysis development plan would help a sponsor devise an analysis strategy to support the key messages in their submission, such as:

• Defining the safety parameters of interest based on FDA expectations, a priori special interests/concerns, and safety concerns identified during data review.
• Determining an analysis and presentation approach that gets at the true value of parameters of interest and allows for meaningful comparisons between the active and placebo/comparator groups.
• Developing a strategy for combining and pooling data.  (For example, while you have a regulatory obligation to present all safety data, there is no requirement to pool all studies for analysis into a single group.)
• Determining which subgroups should be explored for consistency of effect.

Regulatory interaction support includes providing biostatistics input and analysis for both face-to-face meetings and written communications with FDA. In the period leading up to your submission and following the submission, it is likely you will have increasing interaction with FDA. These services prepare you to have the biostatistics and data standards expertise on-hand that you’ll need to effectively respond to FDA communications, and to recommend when you should initiate conversations with FDA over your data.

So, as you approach the end of your development program, make sure you have the statistical support in place that you need.