At an FDA Advisory Committee (ADCOM) meeting – one of the most important days in a product’s development – sponsors typically have no more than 75 minutes to credibly and persuasively explain their entire development program. The stakes are high because the committee plays a key role in influencing the fate of the product. Since every minute counts, every word must be chosen carefully. Fortunately, a sponsor’s briefing documents, which ADCOM members receive in advance of the meeting, are an opportunity to elaborate on key issues and set the tone for the day.
Similar to the sponsor’s presentation, no two briefing documents are exactly alike. Based on 3D Communications’ work on hundreds of briefing documents, we put together some tips on what ADCOM members want to see.
Before starting to write, here are a few things to consider.
First, the document will be available to the public (with the exception of briefing documents for closed sessions). As a result, sponsors must be very deliberate about what information – particularly proprietary information – they choose to share.
Second, it is important to keep in mind that the intended audience for this document is not the FDA, but rather a committee of physicians, academicians, and nonvoting industry and consumer representatives. While some members of the committee may be experts in the product’s indication, the group is heterogeneous; therefore, the briefing document needs to be geared toward a diverse audience.
One of the hardest parts of writing a briefing document is deciding what to include without making it 300 pages. The goal is to lead the readers through the logical and usually chronological development of the product without overloading them with unnecessary details. In addition to the general overview of the development program, the briefing document should also highlight specific topics or key issues on which the ADCOM will likely be asked to discuss or vote.
In general, a briefing document for a new chemical entity will include an executive summary, disease background, unmet medical need, product background, clinical pharmacology, overview of clinical development including regulatory history, efficacy from key studies, safety including topics of special interest, risk management plan, and benefit-risk conclusion. The executive summary is arguably the most important section of this entire document, in part because it may be the only section that is read from start to finish.
In 2015, 3D Communications polled 340 former ADCOM members from the Center for Drug Evaluation and Research (CDER). Results showed that 26% read beyond the executive summary only for key data sections or specific data, and 30% spend four hours or less reviewing both the FDA and sponsor’s briefing documents. The vast majority (86%) prefer documents under 100 pages, with summaries for each section.
Based on these practices, 3D recommends starting the briefing document with a relatively long executive summary (10-15 pages). We also suggest structuring the body of the document so it is easy to navigate with a detailed table of contents, cross-links, and clear headings.
In terms of content, rule number one is to make sure no data are in the briefing document that the FDA has not yet seen. Otherwise, all other data are fair game, including new analyses of data that’s already been submitted. ADCOM members who were surveyed also reported that they prefer text supported by tables and graphs (as opposed to mostly text or mostly tables and graphs).
While the briefing document is due approximately one month (22 business days) before ADCOM members will hear the sponsor’s presentation, it is essential that key messages are aligned between the document and presentation. The repetition is important for consistency and retention: the more times messages are delivered, the more likely they are to stick.
A few final points: be transparent. Get ahead of any major issues likely to be brought up by the FDA or ADCOM members. It is better to acknowledge shortcomings and use the opportunity to explain them, rather than to appear to be hiding things. 3D Communications’ general rule of thumb is to include data that most of the committee members will want to see, use the appendices for things that one or two members may want to see, and leave the rest for Q&A.
Once a draft of the briefing document is complete, test it. 3D Communications recommends two mock meetings to test the briefing document strategy before the final version is due to the FDA. Getting feedback to determine the best order in which to present the studies, how much detail to include on a topic of special interest, or whether the document sets up the presentation appropriately is invaluable in being able to refine both content and structure. The process of writing a briefing document can be overwhelming, but if done properly, it can improve the clarity and relevance of a sponsor’s message and ultimately boost their chances of a favorable ADCOM meeting recommendation.