Three Easy Mistakes That Will Wreck Your AdComm Preparations
by Nancie Poppema
CCA has been helping clients in the pharmaceutical industry prepare for advisory committees for more than 25 years. During this time in the trenches, we’ve created what has proven to be a very effective step-by-step process for prepping sponsor teams for these high-stakes interactions. We’ve also developed some pretty strong insight into what doesn’t work during AdComm preparation.
Over the years, I have seen sponsor teams make many of the same mistakes over and over. When these mistakes aren’t addressed, they can lead to disastrous advisory committee presentations. And even if they are caught and resolved before the AdComm meeting, they still result in wasted resources, lost time, frustration, and angst for team members.
The good news is that while the universe of potential problems is large, I have identified the top three most devastating potential mistakes. If not caught early and corrected, these critical mistakes won’t diminish just one aspect of the AdComm experience. Instead, their impact will be felt throughout the effort, creating a cascading effect that will hinder the entire regulatory approval process.
The fundamental nature of these mistakes means that avoiding them can pay big dividends. Going into AdComm preparations with an eye out for these three traps will increase the value of your committee feedback, improve your chances of an eventual approval, and remove chaos and uncertainty from the preparation process.
Mistake #1: Thinking Someone Else Can Do It for You
Time pressures clearly create incentives to take shortcuts in preparing for advisory committee. Everyone is busy, after all. Sponsors’ teams may be on several projects at once, pulled in multiple directions and with ever-increasing workloads.
This pressure creates a strong temptation to believe that subject matter experts (SMEs) and regulatory staff can handle much of the presentation and back-up slide prep with only minimal input from the primary team, who are the people who will be at the microphone presenting or responding to critical questions and concerns from the committee. It also makes it easy to be seduced by outside consultants who pitch the promise of doing all of the prep work for you and delivering a ready-to-go presentation.
The belief that these hands-off approaches will work, however, is based on the false assumption that the advisory committee meeting will be a straightforward conversation about the safety and efficacy of a drug, biologic, or device.
In reality, advisory committees are more like a hearing or a trial than a discussion with peers. The sponsor’s presentation is its case-in-chief, the team stands for “cross examination” by the committee, and then the committee deliberates and votes publicly to deliver its “verdict” by recommending or not recommending approval.
To address this reality, you must do more than just clearly present the facts. Approach interactions with regulators with the focus and intensity of an attorney preparing for trial. Understand the data inside and out, build a team that can work together under pressure, and have a plan for making a compelling scientific argument.
The primary team should “take destiny in their own hands,” by rolling up their sleeves early and being involved in every aspect of the preparation. They should lead the process, and not just respond to drafts prepared by support staff. The support staff won’t be the ones standing at the microphone, after all. If the primary team isn’t involved in developing the strategy, data, science, and medical story from the very beginning of presentation prep, they won’t have the deep understanding needed to make these elements their own, and it will show during the presentation and Q&A.
When you include the full primary team in the very earliest stages of the preparation process, and start the process six months in advance, you see some important benefits. First, the sponsor’s presentation will be tightly integrated and guided by one strategy. Similarly, the team members themselves will be better prepared to respond as a unit to the tough questions that will be fired at them during the meeting.
Just as importantly, this approach ensures that the presentation fully reflects the thoughts, style, and expertise of the team. Embedding these qualities at the very core of the presentation and responses will make the team’s case more persuasive, increase their credibility with regulators, and give them greater control over the meeting’s direction and outcome.
I know that this level of time commitment can be a difficult pill to swallow (sorry, couldn’t resist). Advisory committee, however, is a critical milestone for product approval. It has implications that extend into every aspect of your company. If your product isn’t on the market, it impacts research, development, your company’s ability to continue operating, and, by extension, your job. It even impacts the lives of patients who could benefit from the product. So yes, it’s worth a significant investment of time.
In the long run, these time-saving shortcuts rarely even accomplish the goal of saving time. When we see cases where the primary team is too busy to get involved from the beginning, we almost always identify wasted time, effort, and resources, with work that needs to be undone and redone under difficult, last-minute circumstances.
Mistake #2: Assuming Q&A Will Be Linear
We believe that in most cases the sponsor wins or loses the vote in Q&A. Because of this, we suggest that the team spend more time preparing for Q&A, and less time perfecting the presentation. This Q&A prep needs to include drill downs, issue resolution practice, and exercises to develop skills for building effective responses, all with an emphasis on developing the nimbleness to stay up with the committee.
We have watched many teams employ a very linear approach when they practice for the question-and-answer component of the AdComm meeting. They develop a list of anticipated questions, and then practice their answers.
Unfortunately, this rarely results in a great outcome. The actual questions may be phrased differently or take a different direction than anticipated, leading the carefully rehearsed answers to come across a little “off” and/or stilted.
The bigger problem, however, is that it assumes that the delivery of a rehearsed answer concludes the discussion. In reality, an answer may trigger another question from a slightly different angle, or a request for more detail. If your team has been practicing linear Q&A, you may not be ready to adjust to the demands of questioners as they go in different directions.
We prepare and drill teams for what many people call “trench warfare” or “mud wrestling.” This readies responders to be mentally present during Q&A, listen critically, and be ready to answer effectively by moving from one thought to another on the same issue. It gives them the ability to think strategically about where arguments are going, and be able to keep up. That takes more than just rote practicing of canned answers. That is a skill that needs to be honed.
To meet this challenge, replace Q&A memorization with a more robust approach that includes the following activities.
- Identify issues as opposed to questions – Questions about an issue might be phrased hundreds of different ways, but it’s still the same issue. That’s why it makes sense to focus on the responses and approaches to issues, and allow the responders to use their own words to form the specific answer. For each issue, every responder should know the team’s bottom line, and be fluent in describing the team’s position.
- Develop proof points – Whatever position you take, you have to prove it. That means developing supporting data for each issue, and giving the members of the sponsor team a working knowledge of this data. Team members also have to access this factual backup quickly, and clearly connect it back to the issue at hand. Creating 5-6 options for each issue allows a responder to pick the most compelling response for the situation, and gives them room to maneuver.
- Consider the entire committee – When identifying issues and creating proof points, consider the unique concerns of each member of the committee and the diverse disciplines they represent. By creating proof points tailored to specific concerns, you give responders the tools to directly address a broad range of questions. A responder will have the nimbleness and flexibility to craft a highly targeted and relevant answer, regardless of whether the question is coming from a statistician, clinician, or patient advocate.
- Engage in realistic practice – Before they’re used in front of the committee, your responses need to be vetted, flight tested, and strengthened to make sure they are concise and compelling. This means they need to be practiced orally. A team can sit around a conference table or speaker phone for hours discussing responses to issues. Until these responses are flight tested orally, however, you can’t be sure of the strength of the argument.
It’s important to remember the earlier warning about thinking someone else can do it for you. While Q&A prep may require extensive input from the support team, the primary responders should be heavily involved in the process. This is the only way to ensure that all responses will be defensible before the committee, and that they will be delivered with maximum clarity, consistency, and conviction.
Mistake #3: Ignoring the Big Picture
Another mistake I see regularly is sponsor teams taking a very narrow focus during their preparations, and failing to think about the broader regulatory environment that surrounds their upcoming presentation. This is most often the result of team members not being aware of ongoing changes that are taking place at the FDA and in individual advisory committees.
For example, it used to be that the p-value ruled, and we would often see the statistician telling the clinician how to vote. It made sense for teams to prepare to showcase their p-value.
Over time, however, the medical and scientific factors have become more balanced, and today the medical story continues to gain influence. In a sense, the U.S. environment is looking more like the E.U., where regulators have long given heavy consideration to medical and public health issues during the approval process.
Knowing this, you can see how preparing a team to focus solely on scientific issues would be a mistake. It would miss the opportunity to take advantage of the growing importance of key opinion leaders, as well as the rapidly emerging influence of patient advocates and consumers themselves.
Stepping back even further, it’s critical that sponsors are aware of the noise that is happening beyond the data. This means considering the current media environment, recent events, hot topics in the medical community, and the growing influence of highly vocal patients, families, and advocacy organizations. The FDA is also finding it harder to identify non-conflicted members for some advisory committees, which can significantly impact both how you prepare and the feedback the committee gives the FDA.
Another source of “noise” to consider are the forces impacting the way the FDA operates at the highest levels. The agency is being simultaneously criticized for being too slow and too fast to grant approvals, and for being both too hard and too easy on sponsors. Now the new 21st Century Cures Act has the potential to increase the pace of change as it eases requirements for some approvals.
The ultimate outcome of these changes, however, is still very much uncertain. In the meantime, sponsors are still seeking approvals, and those that do so with an eye on these ongoing changes will have the best chance of avoiding unpleasant surprises.
Regardless of changes to the big picture, however, there is one thing you can always count on. Even if the FDA has been helpful and cooperative in the months leading up to the AdComm, it will still be sharply critical of your application and fulfill its official role before the committee.
Avoid these three mistakes and you’ll be on your way to creating a well-prepared team with the nimbleness to respond to almost any question or concern from committee members. You’ll also be positioning your team to maximize the value of its advisory committee feedback and increase its chances for eventual approval. And you will have done this without the false starts, headaches, and wasted resources that so often accompany the preparation process.
In addition to FDA advisory committees, avoiding these mistakes is equally important for other agency-related interactions – ranging from EOP1 to label negotiations – as well as other regulatory environments, including the EU approval process.
Nancie Poppema is the President and CEO of CCA.
If you need guidance in putting these recommendations to work during your own preparations, CCA can help. We have been active in the industry since 1989, and have helped clients prepare for advisory committee in pursuing approval of over 100 indications, covering drugs, biologics, and devices. This diverse experience gives us a remarkably expansive view of how conditions are evolving, and what sponsors must do to succeed.