A new study, conducted collaboratively by the Tufts Center for the Study of Drug Development (Tufts CSDD), the FDA, and sponsor companies, illuminates the intricacies of clinical trial protocols, particularly focusing on Non-Core procedures. Non-core procedures, though not directly supporting primary or key secondary endpoints, have long been a point of contention and confusion within clinical research. They are often included in trial protocols for various reasons, from regulatory safety nets to exploratory ambitions. However, they come with a cost—not just in monetary terms but also in trial duration and participant burden.
The Heart of the Matter: Non-Core Complexity
The Tufts CSDD study involved a deep dive into 700 distinct procedures from 19 pivotal trials, painting a vivid picture of the current landscape. For instance, sponsors reported that patient-reported outcomes and lab results, comprising 18.5% and 16% of Non-Core data, respectively, were collected with the intention of enriching the trial data set.
But at what point does the pursuit of comprehensive data infringe upon the efficacy and efficiency of a trial? The study addressed this by comparing sponsor classifications with those of FDA reviewers. While sponsors considered 48.1% of procedures as Core, the FDA only agreed to 18.2% (Figure 1). It is also critical to note the significant discrepancy in interpreting ‘Required or Standard Classification’ procedures, demonstrating a disparity in the perceived necessity of certain procedures, which could be a gateway for protocol optimization.
Cost vs. Benefit: The Price of Redundancy
The financial implications are stark. With Non-Core procedures accounting for an estimated $3.7 billion annually in direct costs, as reported by Tufts CSDD, the incentive to streamline is clear. Yet, the study found that a sizeable 21% of Non-Core data was an assorted mix, labeled as ‘other data’, suggesting a catch-all approach that might benefit from more discerning scrutiny (Figure 2). Moreover, many non-core procedures, such as Labs, Biomarkers, and other bloodwork, increase patient burden.
Harmonizing Objectives for Progressive Clinical Trials
The study brings to the forefront a pivotal challenge in clinical trials: synchronizing the objectives of sponsors and regulatory bodies. Sponsors often regard Non-Core data as a treasure trove of insight, not just serving the immediate trial but as a valuable asset for future explorations and interpretations. This data might not be critical for a study’s primary outcomes, yet it is seen as a strategic reserve, potentially illuminating future pathways or bolstering supplementary findings that could be crucial in a drug’s lifecycle.
In contrast, regulators, with a mandate to safeguard public health, prioritize the direct impact of trial data on demonstrating safety and efficacy. Their primary concern is the robustness of evidence that directly supports the therapeutic claims made by a drug. In its gatekeeper role, the FDA seeks to streamline the process, focusing sharply on what is necessary to reach decisive conclusions about a new treatment’s approval.
Bridging the Divide: A Call for Synchronicity in Clinical Trial Design
This perspective dichotomy necessitates deeper engagement and dialogue between sponsors and the FDA. It’s not merely about achieving a consensus on the relevance of data but fostering an understanding of the differing imperatives that drive each entity. For sponsors, the value of Non-Core data may lie in its potential to mitigate risks or provide a competitive edge. For regulators, the emphasis is on minimizing patient burden and ensuring that the volume of data does not obscure the clarity and relevance of trial outcomes.
The study advocates for enhanced communication strategies and collaborative planning stages of clinical trials. The goal is establishing a shared understanding early in the trial design process. By doing so, sponsors can tailor their data collection strategies to align more closely with regulatory standards, potentially facilitating a smoother review process. For regulators, offering clear guidance on the data that will inform their decision-making can lead to more efficient trials optimized to deliver conclusive results without extraneous data collection.
Such alignment could lead to a paradigm shift in clinical trial design, where every procedure and endpoint is purposeful and mutually understood by all stakeholders involved. The result would be a clinical trial ecosystem that is more efficient and more responsive to the evolving landscape of drug development and regulation.
Looking Ahead: Simplicity as the North Star
In conclusion, there’s an opportunity to simplify the clinical trial process. Reducing the Non-Core clutter could lead to leaner, more participant-friendly, and cost-effective protocols. This could accelerate the development timeline, bringing vital medications to market faster.
This study is a clarion call to the industry, highlighting the need for introspection and evolution in clinical trial design and better communication between sponsors and the FDA. By embracing a shared vision of simplicity and relevance, we can streamline the path to discovery, ensuring that every procedure and every data point serves a purpose that resonates with both sponsors and regulators alike.
Reference: Smith, Z., Getz, K. A Case Study Assessment on the Rationale for, and Relevance of, Non-Core Protocol Data. Ther Innov Regul Sci (2023). https://doi.org/10.1007/s43441-023-00595-1