Researchers Want A Design Shake-Up In 2026
As told to Clinical Leader Executive Editor Abby Proch
When asked what clinical research professionals should leave behind in 2025, quite a few lamented the stale, even problematic, approach to clinical trial design. With increasing attention on adaptive trial design, growth in precision medicine, and the inclusion of biomarkers (for better science and better patient outcomes), many are asking one another to leave legacy approaches behind.
Less Rigidity, More Patient Centricity
“As we head into 2026, the clinical research field needs to let go of legacy trial structures that no longer match the complexity of modern drug development. We continue to see an overreliance on antiquated rigid study designs that don’t incorporate newer adaptive methodologies or real-world evidence or tools that can generate more meaningful insights earlier and reduce both cost and risk.
“Early-phase trials must evolve to include more meaningful patient-reported outcomes. Despite their proven ability to predict real-world performance, patient-centered measures are still too often overlooked in the initial stages of development. Embedding these insights earlier can help ensure that programs advance with a clearer understanding of both clinical and practical impact.” — Joel Latham, president and CEO, Incannex Healthcare Inc.
Some Sectors Should Not Study In Isolation
“The scientific method has greatly benefited humanity by providing a structured and reliable way to investigate the world and build confidence in our discoveries. However, at some point, parts of the healthcare industry began to misinterpret the scientific method. They reduced ‘real science’ to isolated variables and double-blind, placebo-controlled trials, treating these as the only valid ways to gain knowledge. While this approach is well-intentioned, it limits our ability to make valid, meaningful clinical decisions for real, complex human beings.
“As we approach 2026, it is crucial for the health, wellness, and longevity sectors to move away from this outdated reductionist mindset. This shift is necessary both in how we study interventions and how we design trials to evaluate them. Two persistent blind spots continue to hinder our progress: studying physiological interventions in isolation and relying on small, homogeneous research cohorts that do not accurately represent the complexity of real-world human biology.”
“For decades, research has been built on the idea that we should test one variable at a time. While this makes sense for mechanical systems, and maybe even single-action drug trials, it rarely reflects how human healing actually works. The body is not a single-input/single-output machine; it is an interconnected ecosystem of systems, signaling networks, and adaptive responses.”
“By studying modalities in isolation, we create a distorted understanding of what actually drives healing. We overestimate some effects, underestimate others, miss synergistic relationships, and fail to see how multiple small inputs can produce exponential benefits when combined. This reductionist approach is not just outdated; in many cases, it leads to misleading conclusions that limit clinical progress and patient outcomes.” — Jason Sonners, DC, DIBAK, DCBCN, clinician researcher, University of Miami Department of Molecular Biology
Treat The Cause, Not The Symptom
“As an industry, we need to leave behind clinical strategies that chase symptoms instead of targeting the root causes of disease. Too many programs still focus on downstream effects, particularly in neurodegeneration, where chronic innate immune dysfunction and neuroinflammation are clear mechanistic drivers. If we want true disease modification, we must design trials that focus on upstream biology and the patients most likely to benefit.
“Our neuroinflammation-enriched Alzheimer’s Phase 2 trial framework demonstrates that you can run efficient, precise studies with smaller, well-defined patient groups and more sensitive, biology-driven endpoints. The field should move toward adaptive designs, external control data, and smarter trial architectures that respect both the science and the patients.” — David Moss, CEO and cofounder, INmune Bio
“Medical science is shifting from symptom management to treating the root cause of disease and the discovery of breakthrough cures through gene therapy, cell-based treatments, and some small-molecule drugs that are showing promise in correcting basic biology and treating the underlying cause of a disease. Symptom-only approaches may relieve symptoms, making patients feel better temporarily, but can delay diagnosis or hide disease progression and rarely improve actual health outcomes.
“Additionally, biology is not uniform across populations. Differences exist in drug metabolism, immune response, genetics, disease presentation, and side effect profiles. “It’s becoming increasingly important to examine and fully understand the safety and efficacy profile and optimal dosing of a product within subgroups. As science is moving toward treating the root cause of diseases, it’s becoming clear that products that may be efficacious and/or well-tolerated by some subgroups may not have the same profile in others – particularly based on key biological differences such as sex, age, race, etc.” — Kelly Abernathy, vice president, clinical development, Arrivo Bio
Bigger Isn’t Better; Failure Isn’t Final
“What clinical research needs to leave behind in 2025 is the illusion that scale, tradition, and inertia are substitutes for thoughtful design. For too long, we’ve treated large, multinational Phase 3 trials as the unquestioned gold standard, even when feasibility signals, investigator capability, patient availability, and regulatory realities tell a different story. Bigger isn’t better if the wrong patients are enrolled, the wrong geographies are chosen, or variability drowns out meaningful biological signal.
“We also need to abandon the fatalistic view that trial failure is the end of the road. Recent years have shown that when teams interrogate the data, rather than discard it, they often uncover responsive subgroups or operational misalignments that can redirect a program toward success. Failure is information, not a verdict.” — Eyal Shoshani, vice president, clinical affairs, PolyPid
“Sometimes not hitting the main endpoint, particularly when developing products with a novel mechanism of action, uncovers key insights that guide the next breakthrough. Progress comes from following the data, not just the headline results.” — Kelly Abernathy
Enroll The Right Patient Population
“The FDA's November 2025 decision to remove black box warnings from hormone replacement therapy provides clinical researchers with an excellent case study in how flawed trial design can derail an entire therapeutic category and delay patient access to effective treatments for over two decades. This long-awaited and overdue regulatory shift offers valuable insights into clinical trial design and highlights significant opportunities in an underserved market.
“The 2002 Women's Health Initiative study represents a cautionary tale for drug developers. The trial enrolled predominantly older, post-menopausal women with an average age of 63, rather than symptomatic perimenopausal women who would actually use these therapies to manage menopause symptoms.
“Successful clinical development in women's health requires enrolling age-appropriate patient populations that match intended treatment demographics, conducting multiple formulation studies, and incorporating patient-reported outcomes that reflect quality of life improvements.
“Companies that maintained research programs throughout the regulatory uncertainty have demonstrated meaningful clinical outcomes, including improvements in vasomotor symptoms, bone density, cardiovascular markers in younger women, and quality of life metrics. These results show that well-designed trials addressing specific patient populations can generate compelling evidence even in challenging regulatory environments.” — Bruce Dorr, MD, senior medical advisor, Biote.