Episode 33: Ana Palijan – Beyond Safety: The Evolving Complexity of Early Phase Studies
Resources:
- [email protected]: Use this email to let us know what you want to hear about.
- Innovative Approaches to Study Design in Early Phase Dermatology Trials
- Dr. Robert Bissonnette and Dr. Kim Papp on the Intricacies of Dermatology Early Phase Clinical Research
- 3 Tips for Collecting Samples with Tape Stripping
- Investigating Transdermal Analysis Patch (TAP) as a Non-Invasive Option for Biomarkers Studies
- Leveraging Technology in Phase I Clinical Trials
In this episode of Phase Forward, Dr. Ana Palijan, Director of Early Phase and Translational Research at Indero, returns to the podcast to share insight into how early phase clinical trials have evolved far beyond their traditional focus on safety. With more than 25 years of experience in translational and early phase research, Dr. Palijan unpacks the drivers of increased trial complexity—from advances in biology to technology integration—and the importance of context-specific strategies in early drug development.
Redefining the Boundaries of Early Phase Research
Historically, early phase trials have focused on first-in-human studies using healthy volunteers—commonly referred to as single ascending dose (SAD) or multiple ascending dose (MAD) designs. These represent a compound’s first introduction into the clinical space.
However, the early phase stage also extends beyond these usual settings. It also includes Phase 1b and 2a studies, often described as proof-of-concept trials, which are typically the first studies conducted in patient populations. While the study designs and objectives may differ, one element remains consistent across early phase work: safety is always the primary endpoint.
The Evolution of Safety in Early Phase Trials
Over the past decade, the approach to assessing safety in early phase research has undergone a significant transformation. A key driver of this shift is the evolution of biological science. With decades of investment in omics technologies, researchers now have a more granular understanding of signaling pathways, targets, and disease mechanisms. This expanded knowledge base has paved the way for the development of novel therapies—including biologics and bispecific antibodies—that introduce new dimensions of safety risk.
For example, whereas legacy dermatologic therapies were mostly topical, today’s treatments are systemic, requiring investigators to evaluate safety on a broader scale.
These scientific advancements demand more sophisticated study designs and more nuanced inclusion and exclusion criteria. Investigators must have a deep understanding of disease physiology to ensure appropriate patient selection and risk mitigation. As a result, early phase protocols have become more complex, and trial execution requires closer oversight and scientific alignment than ever before.
Technology’s Double Edge
The rise of technology has both facilitated and complicated the operational aspects of early phase studies. On the positive side, modern clinical systems now allow for better oversight and more efficient data capture. Tools such as electronic trial master files (eTMF), clinical trial management systems (CTMS), and electronic data capture (EDC) platforms are often integrated to form digital ecosystems. These connected systems improve the traceability of information and allow teams to respond in real time to emerging safety or operational issues.
However, technology also introduces challenges. Integrated systems require careful setup, validation, and ongoing maintenance. Breaks in communication between platforms—such as through system updates or misaligned application programming interfaces (APIs)—can compromise data integrity and delay timelines. User acceptance testing (UAT), script validation, and interface customization all add to the operational burden.
While off-the-shelf platforms may be easier to deploy, they often lack the flexibility required for trials with unique requirements. In contrast, highly customized systems provide precision but come with higher implementation costs and greater complexity. As a result, trial managers must not only be scientifically fluent but also technologically savvy, understanding how each system contributes to the overall clinical workflow.
While these ecosystems promise efficiency, their practical implementation still has a way to go. This dynamic is exemplified by multi-function office machines: while an all-in-one printer, scanner, and fax machine may be convenient, it may not perform any one function at the highest possible quality. Similarly, clinical platforms that promise everything may not deliver the same performance as best-in-class single-function tools. When using individual best-in-breed systems, integration becomes the challenge—and often the cost.
Nonetheless, technology is essential, especially in a landscape where early phase trials are now conducted across multiple countries and regions. Centralized systems enable global oversight, support remote monitoring, and help ensure data consistency regardless of site location. Despite the growing pains, the adoption of technology is necessary to meet the evolving demands of early clinical development.
The Value of Niche CROs
The conversation next turns to outsourcing trends and the growing recognition that early phase trials require tailored execution strategies. In recent years, many large pharmaceutical sponsors have shifted from a one-size-fits-all model to more targeted collaborations with niche CROs. This move reflects a broader understanding that early phase studies—particularly those in specialized therapeutic areas—benefit from operational partners with deep, indication-specific expertise.
Rather than relying on standardized, internalized models, sponsors are seeking CROs that understand the nuances of disease-specific trial design, regulatory requirements, and patient populations. This is especially important in smaller studies—such as early dermatology trials—that may include as few as 30 to 40 participants. In such settings, every patient and every data point carries disproportionate weight. Poor data quality, missed visits, or delayed lab results can prevent detection of critical safety or efficacy signals.
Outsourcing to specialized CROs allows sponsors to maintain data integrity while managing costs. It also enables them to focus internal resources on core research and development functions or on advancing assets closer to commercialization. When outsourcing is executed strategically, it becomes a mutually beneficial model—offering both quality and efficiency in early development.
Biotech and the Complexity Gap
Beyond scientific and technological complexity, another important driver: the human factor. Today, a large portion of early phase trials are being conducted by small or virtual biotech companies. These organizations often operate with lean teams, relying on external consultants with deep pharmaceutical experience. While this model allows companies to scale quickly, it can also introduce operational mismatches.
Consultants who have spent their careers running large-scale Phase III trials may struggle to adapt to the unique needs of a 40-patient early phase study. The infrastructure, expectations, and timelines for late-phase studies are vastly different from those in early development. Attempting to apply large-scale systems or practices to a small-scale proof-of-concept study can lead to inefficiencies and budget overruns.
Aligning the operational approach to the scope and intent of the study is essential. Early phase trials are fundamentally about learning: understanding safety, exploring early signals of efficacy, and informing downstream development decisions. They are not miniaturized versions of registrational studies; they require their own mindset, tools, and operational agility.
Complexity as the New Normal
Taken together, these trends point to one clear conclusion: early phase clinical research has grown markedly more complex. Scientific advancements have introduced new targets, mechanisms, and modalities. Technology has created opportunities for better oversight but demands technical expertise and system integration. Operational models are evolving to favor customized strategies over standardization. And the growing role of small biotech sponsors is reshaping how early phase studies are conducted.
Despite these challenges, the early phase space remains one of the most innovative and rewarding areas in drug development. It is where foundational decisions are made, and where the first human insights into a new therapy emerge. For researchers, the complexity is not a deterrent—it is what makes the work meaningful. Early development is no longer just about safety; it is about strategy, precision, and the successful translation of science into patient-focused outcomes.
As we conclude another illuminating episode of Phase Forward, we find ourselves at the crossroads of science and progress. Remember that behind the jargon and statistics, lies stories of unwavering commitment, meticulous observation, and the pursuit of evidence that shapes our understanding of health and disease. Stay at the forefront of knowledge and innovation and follow Phase Forward on your preferred platform. My name is Valerie Coveney. Thank you for joining us. Until next time.
Let’s shape the future of research and make a difference in the industry, gain Indero’s support in your upcoming trial and propel your study to new heights.
