Clinical Researcher—August 2025 (Volume 39, Issue 4)
OPINIONS & INNOVATIONS
Jeff Kingsley, DO, MBA, MS, FACRP; Laura O’Donnell; Brad Hightower; Denali Stahlke; Lou Sanquini; April Lewis; Denise Bronner
The clinical trial industry has a problem. If it isn’t proactively addressed, too many patient populations will continue to suffer the loss of access to live-changing or life-saving therapies because of poor research trial design and the incomplete and inconsistent data currently being relied upon to test life-saving drugs and treatments.
The problem is exacerbated by flawed protocol designs, unrealistic inclusion/exclusion criteria, and other factors.
Put simply, the clinical trial industry must finally design trials around real-world patients and stop extrapolating narrow clinical trial data to wider patient populations.
Fortunately, there is a new approach called P3, which we believe will alleviate this problem by improving clinical trial relevance to more patient populations.
The Problem We Face
Our research protocols are looking for unicorns when we enroll patients because our inclusion/exclusion criteria are designed to enroll only the very rare, perfect patient in the absence of any robust understanding of what real-world patients look like. Further, our participation requirements make it next to impossible for most people to even consider participating in a clinical trial. This is inefficiency by design.
We are putting unrealistic expectations on wide swaths of the patient population. Potential participants don’t have enough time to consider engagement in clinical trials, they aren’t always able to travel even when they do enroll, and our medical requirements serve to overly restrict the involvement of the vast majority of the population. It is an untenable situation and patients deserve better.
For example, in a recent trial enrolling type 2 diabetics, we were told to only recruit those who have not had a heart attack in the last five years, who’ve not had cancer in the last five years, and who’ve not been on an antipsychotic in the past five years.
In other words, we were told to recruit unicorns.
The problem becomes more serious after we get U.S. Food and Drug Administration (FDA) approval to market a product after its clinical trials. What do we do next? Too often, we extrapolate the data captured by our narrow, non-representative studies and use them on real-world patients outside the original trial parameters.
Let us be clear: It is neither scientifically sound nor ethically viable to do research on one patient population and extrapolate to another.
A New Approach
Taking an integrated, collaborative approach, we’ve developed a new way to design protocols and recruit and retain patients based on our extensive experience. It’s called P3, a new non-profit organization which will work to address and correct this dangerous imbalance.
Our vision is to provide the tools and services that create protocols to actually and accurately reflect and accommodate real patients and amplify the patient voice in the process.
At its core, P3 is about people powering protocols. Engaging a larger pool of patients will promote vital diversity in clinical trials.
How Does P3 Work?
The P3 process is designed to incorporate input from a wide variety of those in the clinical trial ecosystem and make trials more effective and realistic.
First, we look at a sponsor’s previous protocol packages along with the historical data around it. This large amount of data is fed into our artificial intelligence (AI) system, which in turn generates insights reflecting the strengths and weaknesses of how well prior protocols have been written. With the sponsor’s permission, our AI system can additionally compare these results with the strengths and weaknesses of protocol packages and historical data from other institutions in a blinded fashion. This AI analysis of protocols provides an unbiased, unemotional analysis of what has really worked or not worked regarding this particular therapeutic area and the surrounding nuances.
Second, we add in a current draft protocol of choice to gain insights from AI into areas for improvement.
What’s further unique about P3 is the combined outputs are then sent to patients, and from their responses we can provide specific and real-world information about their insights, zeroing in on what they liked and didn’t like about the original protocol design. This adds the current emotional and reality-based viewpoints that may be shifting based upon current financial, environmental, and healthcare trends.
We also review the protocol with sponsors, focusing their attention on the most impactful areas of change, considering the pros and cons of these changes, and citing any areas of unique opportunity with other potential patients.
Distilling and analyzing this targeted and valuable data, we are able to learn in a real-world way from AI and genuine patients what people liked best and least about the study design, as well as what has worked and not worked from prior data consumed by the P3 AI.
Based on this information from disparate, representative, and vital sources, we will then provide insights on how best to adapt the protocol to be more effective and inclusive. (See Figure 1 for more details.)
Figure 1: A Closer Look at the P3 Process
The P3 approach is straightforward and effective and involves three basic steps:
- A sponsor provides a protocol package that includes a recruitment plan, considers relevant historical protocols, highlights relevant feedback, etc.
- P3 uses AI and human intelligence to summarize the protocol package and shares it with relevant audiences.
- The sponsor receives participant reports and partnership reports with insights and suggestions for improving the protocol package based on real-world input previously not considered.
New Vistas, New Patients
Key to the P3 approach is embracing new ways to better inform protocol design.
Common sense strongly suggests that clinical trial design featuring human participants will benefit from human input from the very outset. It’s akin to political focus groups, or marketers testing a new product. In both of those cases, the people most impacted are directly involved in assessing approaches and tactics. It is vital from an ethical and scientific point of view to engage human clinical trial patients in the design, development, and conduct of trials.
Today, industry relies on a somewhat stale suite of approaches in its attempt to capture the patient voice. Tactics include ad boards, steering committees, outreach to non-naïve populations, and working with patient advocacy groups.
Those tactics can be helpful, but they clearly aren’t getting the real job done. They aren’t connecting with enough patients, and they aren’t producing trials with relevance for wide enough portions of the patient population.
P3 will build on existing tools and significantly enhance them by reaching out to experienced and naïve patients; the general public; site staff including investigators, coordinators, and others; as well as industry and retail partners within the clinical trial ecosystem to widen the tent of clinical trial inclusion by finding and listening to more patients and professionals. This will be accomplished via simple, low-impact social media and app-based interactions with users and superusers who have demonstrated their interest in providing input into the future of clinical trial design.
This approach will also reduce preventable protocol amendments, speed recruitment, improve retention, and raise the bar on the very data and science underpinning successful clinical trials.
When asked about customer input in the development of the Ford Model T, Henry Ford famously said, “If I had asked people what they wanted, they would have said faster horses.” As the P3 AI engine ingests prior protocol designs, industry input, and study outcomes, P3 will become capable of designing the V1 of future protocols. Not solely based upon asking people (patients, investigators, statisticians, experienced industry professionals), but also based upon what P3 can see in the relationship between design and outcomes. That sight will transcend the blinders we have based upon what we currently know and do.
Conclusion
The clinical trial industry is at a crossroads. We must find new ways to reach out to more patients in order to better serve more people with ethically and scientifically sound clinical trials. It starts with a more robust and effective protocol development process.
P3 offers a new way to approach patients and clinical trial professionals. Together, we will advance important drugs and treatments for patients with stronger and more inclusive clinical trials.
This opinion piece is based on a presentation delivered at the 2024 Innovation Network Gathering in West Chester, Pa., an annual symposium dedicated to anticipating and shaping the future of human-centric clinical trials, by:
Jeff Kingsley, DO, MBA, MS, FACRP, Chief Development Officer of Centricity Research and a former Chair of the ACRP Board of Trustees (2017)
Laura O’Donnell, Senior Director and Head, Global Site Engagement, at GlaxoSmithKline
Brad Hightower, CEO of Hightower Clinical
Denali Stahlke, Head of Strategic Partnerships for Haystack Health
Lou Sanquini, President of TribecaOutcomes
April Lewis, in the Innovative Health sector of Johnson & Johnson Innovative Medicine
Denise Bronner, Founder and CEO of Empactful Ventures
