Sharing information and insights internally from either regulatory agencies or Notified Bodies is healthy behavior. Knowledge is power, several believe. It can change the world, your company, and your personal leadership behavior, but only when it is communicated in a timely manner and shared in the right ways. Break out of your self-imposed jail today.
Medical device and in vitro diagnostic manufacturers are struggling to create viable post-market surveillance (PMS) plans. In this fictional story, I’ll present a process that provides a framework to organize thinking to craft a robust PMS plan. I will be addressing relevant topics and providing simple, practical solutions that can be implemented globally.
The Product Approval Email
There was a thrill of anticipation in the air. Kai-Lin, an employee and manager at Mythical Medical (see previous articles), received the approval email from their recent product submission. Corporate announcements went out, informing that there were desserts in the conference room, but her efforts were not acknowledged. In the whole grand scheme of things, that’s fine. But to her, today, it wasn’t. She would learn that life is cruel. It gives you the test first and the lesson later.
There was that delicious “eight treasure rice pudding” (also known as “ba bao fan”), chocolate sugar cookies, and assorted ice creams awaiting the swarm of bodies heading that way. She was disappointed and tried to resist being seduced to celebrate with her colleagues. The announcement hurt mainly because the final issue preventing approval was addressing a weak PMS plan. It needed to be overhauled. Jae, the hero of the benefit-to-risk section, moved to another therapeutic area. The rest of the team was inexperienced. It fell on Kai-Lin’s shoulders to immediately re-write that section to meet an internal product approval company milestone, which she did.
It’s Time for a Break
The product approval celebration event was almost over. However, before Kai-Lin went back to work, she needed to get away and go to lunch. She needed “Kai-Lin” time. Grabbing some of her friends, they headed toward several of the local, popular lunch spots. As they walked toward a favored restaurant, En Thai Sing, known for their quick buffet, she froze as she saw another “colleague.” Trouble gathered on her forehead. Instead, they went next door to the Peking Inn café and joined several other co-workers. After casual introductions, they ordered.
Little did she know, amazing, remarkable things were evolving that would eventually become part of her heritage and legacy. That timeline, however, was not in her control. Hard work goes unrecognized, but not today during lunch.
Post-Market Surveillance Expectations
Wrapped in a sudden intensity of reflection and inward contemplation, Kai-Lin hesitated to participate in the lunch conversation as it turned to pain points they were experiencing on their projects. Then, the piercing question came directed like a laser to her heart, “How did you address the PMS issue? We are all getting that question.” A fiery exclamation of anger and contempt almost came out; however, a calmness settled on her spirit. She had to choose, “Do I want to make a point, or do I want to make a difference?” Sharing clinical, regulatory, and quality insights did not come naturally.
With the quiet inner strength of an emerging leader, she methodically went through the importance of ensuring they mapped out potential sources of data. Flipping over a napkin, she drew a circle with arrows pointing to several key sources. She kept using the words “living system,” “change in culture,” and “increasing expectations.”
She wrote on another napkin several PMS components that required internal investigation and further analyses. Then, without recognizing she now had their laser interest, and even the curiosity of another restaurant customer’s at the next table, she listed potential action items and communications that needed to be considered. In her mind, it was all so obvious. A post-market clinical follow-up (PMCF) plan was typically expected for all their products.
Clinical Investigation Process
Since some at the table were not experienced in running clinical trials, they asked her to walk them through that process. Some moderate to higher-risk products might require a post-approval investigation (or clinical trial or clinical registry) that would need to be documented in the PMCF plan. Local geographic clinical investigation regulations need to be considered, as well, along with personal data protection and data integrity laws. Before any official work occurs on structuring the investigation, there needs to be a clear, agreed-upon clinical question(s) of what is being asked about either the device or patient population and then justify why this approach is necessary.
A Detailed Clinical Investigation Surveillance Approach
A more detailed approach is shown below. The following is a method to use initially to develop a clinical surveillance trial that would answer the question(s). This process leverages experience with approval-based clinical investigations and could be modified depending on the specific device. A 3-phase framework is presented to consider (a) pre-site activation, (b) first subject (or patient) enrolled until the scheduled interim analysis or primary endpoint is reached, and (c) follow-up to eventual study close-out. Depending on the nature of the clinical surveillance investigation (or clinical trial or clinical registry), each phase could be modified, but not at the risk of inhibiting the proactive collecting and evaluating clinical data. This should be shared and discussed with regulatory agencies or notified bodies before pre-site activation formally begins.
As you modify this first template, ensure that the end result continues to (a) confirm the safety and performance throughout its product lifetime, (b) identify previously unknown side-effects and monitor for them, (c) identify and analyze emerging risks based on factual evidence, (d) ensure the continued acceptability of the benefit-to-risk analysis, and (e) identify possible systematic misuse, errors, or off-label use, with a view of verifying that the intended purpose (or use) is correct. Then, move to modify the next template.
Not all clinical surveillance trials are built the same. Factors affecting this phase (and budgets) would be the (a) question(s) being asked, (b) risk class of the device, (c) numbers of subjects (or patients), (d) number of sites involved, (e) countries where the sites are located, and (f) degree of monitoring. Depending on the inclusion criteria for subject (or patient) selection, it is valuable to regularly review site screen failure logs, if available, and their site protocol deviations. Insights into those two activities could be used, in part, to modify the protocol and downstream processes to ensure successful enrollment.
As the data is being analyzed, confidence intervals and standard error bars are an excellent way to show uncertainties with the clinical data. These data could be used, in part, to update the PMS plan strategy and subsequent PMCF plan, for example. These results are also beneficial because they can be used, in part, to develop future questions to be answered and serve as the basis to test new hypotheses in the future. It’s okay to say, “This is what we thought initially. This is what we know now.”
The decision to close out a clinical investigation (clinical trial or clinical study), should be discussed with the regulatory body or notified body. Be prepared to justify the rationale with evidence (data). Four potential justifications are provided below; however, others exist, too.
A Curious Customer Peeks In
Several at lunch today wanted Kay-Lin to attend their product team meetings and share her PMS Plan experience, having worked with several regulatory agencies and notified bodies. After briefly exchanging business cards, they paid and left the restaurant. “We need to do this more often. I appreciate you, Kai-Lin.” A few moments later, that previous curious customer walked out imperceptibly, too, momentarily pausing to survey, peeking in on the scribbled napkins left at their table. A business card also was discarded and left behind. “Hmm.” The customer quietly left the Peking Inn café.
Conclusion
Kai-Lin learned how to accept disappointment without being defeated. She did attend several product team meetings and assisted others in writing up robust PMS plans, most requiring PMCF plans, many of which required a clinical surveillance investigation, too.
The world does not end at the city limits of an email. Others have this same challenge, opportunity, or dilemma. It is not the time to be known as a hoarder of knowledge. Instead, embrace transparency and share. There naturally will come additional opportunities to learn and grow your experience that would have escaped you had you not been open to communicating. This behavior will inspire positive change in both your company and your leadership style. It has the potential to have a positive ripple effect that, in some cases, is unimaginable.
Sometimes, all you need to hear is, “I appreciate you.” Three straightforward, unsophisticated words that motivate, replenish, and encourage, even when your name doesn’t make the approval announcement email. Given enough time, wounds would diminish as your reputation and influence grow in unforeseen, astonishing ways. Hmm.
David R Rutledge, Pharm.D., FCCP, FAHA, President & CEO, Global Strategic Solutions, LLC, Silicon Valley in California. david.rutledge@globalstrategicsolutions.com . +1 (630) 846-0350 cell. The homepage is www.globalstrategicsolutions.com.
If you need help creating PMS or PMCF plans, contact me today.