You’ve Got Issues

BOLDAPPROVED Newsletter Issue 3:

You’ve Got Issues

Every product, every data set, every submission, every communication, and every message has issues.

This is especially true at the intersection of drug development, clinical data, and regulatory science. Failure to identify and address issues represents the biggest threat to success in achieving regulatory approval for a new therapeutic.

“Issues” are any gaps, weaknesses, or concerns that may detract from the persuasiveness of your data or its communication. The data may be lacking, conflicting, or ambiguous; there could be uncertainty in the regulatory environment for your product, or the issues could arise from the preconceptions or biases of your audience.

When issues are not adequately addressed, they are more likely to develop into setbacks for your product, such as unanticipated information requests from FDA or being caught off-guard by a crucial question in a meeting. However, it is not always easy to spot issues. It can also be difficult to address issues once you have them identified. This BOLDAPPROVED newsletter will discuss our best practices for identifying and addressing your issues.

You will have some level of issue blindness

After being deeply involved in a project for months or years, it is highly likely that you have developed some level of “issue blindness”. This is when you are so deep in the weeds that you lose the ability to see your own data as others may see them.

To identify the issues, you need to set aside your own in-depth knowledge and systematically examine your data from your audience’s perspective. Most audiences are not as familiar with your data as you are and, for some, this may be the first time they have seen your content.

For example, a serious safety issue may be identified early in your clinical development program, and your team has since thoroughly investigated and developed risk mitigation to address it. Since you see the issue as resolved, it has effectively become invisible to you. But remember how concerned you were the first time you became aware of this issue? Perhaps you even feared that this issue might sink your entire clinical program. Those are likely the same thoughts and emotions your audience will feel when they see this issue for the first time, especially if they are skeptical of your claims that you have already addressed it.

In addition, your audience will see your data through the lens of their expertise, training, experience, and biases. It is important to analyze your audience to uncover every factor that might influence how they perceive your data, identify the issues that will be most important to them, and tailor your messages accordingly.

Identify issues in your messages

We have previously written about how to maximize the impact of your messages based on an audience-focused communication strategy. With your audience analysis in mind, analyze each message to identify issues that could reduce its impact. A message may be associated with any number of issues.

Scrutinizing your messages for weaknesses, concerns, and gaps requires a high level of equipoise and even some devil’s advocacy so you’re not stuck in your own internal view.

Analyze each message objectively and as different audience members may perceive it—what would run through their minds? — a clinician who is concerned about safety, a statistician who disagrees with your handling of missing data, a regulator who lacks a strong precedent for your product, a CEO, CMO, or CFO, a patient, an advocate, and so on. By putting yourself into each person’s shoes, one at a time, you will better identify a wider range of issues and help overcome any issue blindness you may have developed.

Adjust your messages to mitigate issues

Failing to address the issues can lead your audience to questions and concerns you cannot resolve. We’ve all seen the death spiral when one unaddressed issue fuels a cascade of additional issues, all with unanswerable questions, which leaves you in a puddle in the middle of the floor.

As much as possible, face the issues head-on and address them in advance. To address a message’s issues, you may need to rethink or reword the message. Tempering the message to make it less vulnerable to the issue should also make it more compelling to the audience.

An issue elegantly addressed through your messages can transform into a potential asset. For example, there may be concern about a novel primary endpoint that has never been used previously to support regulatory approval. Your audience may be skeptical that the novel endpoint can demonstrate a clinically meaningful benefit. Messages that offer a data-backed rationale for the endpoint validation and the importance of the clinical outcome to the patient will not only address the issue but are more likely to persuade your audience to act in your favor.

Anticipate questions that could arise from issues

Even if you think you have addressed an issue with your messages, this doesn’t mean you are immune to related questions. By anticipating questions that arise from your issues, you can test to see if your strategy to address that issue will hold up under expert scrutiny.

Inadequately addressed issues are often the ones that can generate the “killer” questions that lead to a downward spiral.

For each issue, generate a list of questions that could arise from that underlying issue. Again, consider your audience analysis while anticipating questions—the same issue may inspire different questions depending on the questioner’s perspective and what matters most to them.

For example, perhaps one of your issues is that more patients in the experimental treatment group dropped out of your pivotal clinical trial compared with the placebo group. You can anticipate that there will be questions about why this imbalance occurred and how this might have affected your results. A clinician may ask, “What percentage of patients discontinued treatment because of a serious adverse event?”. In contrast, a statistician might ask, “Have you evaluated the data using every possible alternate assumption for missing data?” While these two questions seem very different, they arise from the same underlying issue.

Develop responses to the questions that address the underlying issues

Once you’ve identified your list of questions, generate responses that align with your communication strategy.  Your response should directly address the question and the underlying issue, supported by just as much data as is necessary. Using this approach, you can manage concerns transparently and directly without opening yourself up to a death spiral of follow-ups.

Going back to our example above, with the issue of an imbalance in patient drop-out, the multiple questions that arise from that issue will have different direct responses and supporting data but may address the underlying issue similarly.

When preparing for live Q&A (particularly for a high-pressure setting like an FDA Advisory Committee meeting), iterative rehearsal is key. The questions are not usually worded exactly as you have prepared, and no two rehearsals will ever be the same; however, the underlying issues will likely remain much more constant. Your team needs to practice listening to identify the specific question and the underlying issue in real time to respond agilely and in line with your strategy.

Conclusion

We’ve all got issues—what sets you apart is how you handle them.

In our experience with hundreds of client teams, we have seen a wide range of issues and developed effective approaches to address them. Overcoming issues is crucial to implementing an effective communication strategy, generating compelling messages, and preparing effective responses to questions. Identifying your issues and facing them head-on will help you reach your goals.

About the Authors

Angela W. Corona, PhD, is a Senior Scientific Director with BOLDAPPROVALS where she supports teams approaching new drug or biologics approvals. With 10 years of broad medical and regulatory communications experience across a range of therapeutic areas including neurology/neurodegenerative disease, oncology, and immunology, she has played a key role in preparing teams for AdComms, strategic submission messaging, and other complex regulatory communication challenges. Her PhD training was in neuroscience at The Ohio State University, and she performed post-doctoral research in Alzheimer’s disease at Case Western Reserve University.

Steven C. Cohen is the Managing Director of BOLDAPPROVALS, the division of BOLDSCIENCE that prepares clients for AdComms, regulatory submissions for the approval of new therapeutics (NDAs/BLAs), FDA meetings, and label development. Steven has 33 years of leadership in communication consulting, strategy, and delivery coaching, including 117 AdComm preparations. He has supported numerous health authority interactions at key milestones and led submission messaging workshops. He has trained and coached over 1000 scientists, clinicians, and other leaders across disciplines. Steven earned a bachelor’s degree in French Literature from Wesleyan University. He studied medical science at NY Medical College and marketing, communication, and the internet at Columbia University.

About BOLDAPPROVALS

BOLDAPPROVALS blends science, communication, and technology to support product approvals. We deliver comprehensive support for FDA Advisory Committee meetings (AdComms), submission messaging, labeling strategy, and health authority interactions.

Our proven methodology integrates in-house scientific expertise with communication consulting to develop compelling, data-driven arguments for persuasive presentations, responses to questions, and briefing materials.

Our highly experienced team has supported over 250 AdComm preparations and aligned teams on messages for regulatory submissions and interactions with health authorities. Our team can address the unique needs of your people, products, and circumstances.

To learn more about how BOLDAPPROVALS can help your team identify and overcome issues, please visit boldapprovals.com, email info@boldapprovals.com, or call Steven Cohen at +1 (646) 930-0453.