By Todd Page, director of toxicology, Eli Lilly & Company
Clinical research organizations (CROs) are often required to adhere to a variety of sponsor-specific protocol and/or reporting templates, often presenting the same information in various places or in different ways, depending on sponsor-specific requests. Maintaining multiple templates requires a significant amount of time and resources. Once these templates are developed into study protocols, managing different formats introduces variability, which can lead to mistakes during the live phase of a study. This can result in drug development delays and impacts the quality and efficiency of a study. Considering this, there is a clear unmet need to help facilitate operational efficiencies for all stakeholders involved in the interpretation and execution of studies.
To address these mounting complexities, BioCelerate is pursuing the development of a Nonclinical Protocol Template. A common template will increase efficiency for both CROs and sponsors, resulting in toxicology study execution and review with fewer errors. It could be integral in driving quality, reducing costs, and decreasing the time it takes to deliver new and innovative therapies to patients. Furthermore, the adoption of a nonclinical common protocol template will help to promote data integrity, as well as simplify the interpretation and reuse of historical data.
To inform Version 0.1 of the Protocol Template for Repeat-Dose Toxicology Studies, the Common Templates for Nonclinical Studies Initiative team leveraged TransCelerate member company and laboratory partner insights, as well as feedback from those involved in non-clinical protocol authoring/review and health authorities. Throughout the development phase, there was a clear understanding that too much specificity in the template’s design would make it difficult to adopt. Therefore, four guiding principles were selected to serve as the north star during the template’s design: Purpose, Scalability, Process, and Structure.
Our purpose is to simplify sponsor and CRO expectations, eliminating content better suited for inclusion in contracts and focus on increasing efficiency and quality during study execution and conduct. We then determined a need to provide scalability to the template to minimize the need for major customizations, allow for evolution based on stakeholder needs, enable flexibility across stakeholder types or geographies, and create linkages to future templates or available standards like CDISC’s Standard for Exchange of Nonclinical Data (SEND).
Effectively aiding processes was a huge driver as well. We wanted a template design that was fundamentally prescriptive where it counts, referencing the Organisation for Economic Cooperation and Development’s (OECD) Principles of Good Laboratory Practice (GLP) as a minimum baseline. We avoided process instructions where large variations in preferences exist and embraced the concept of a living protocol. To tie it all together, we built a structure that would allow us to focus on layout and format, use of consistent terminology through sections ordered to intentionally ease reference, and navigation through an electronic common technical document (eCTD) format and ensured OECD GLP-compliance.
We expect that the template will be beneficial for a wide variety of stakeholders across the drug development continuum, with occasional areas of shared value. One opportunity that could benefit both sponsors and CROs would be the development of more automation and reuse of content in downstream processes.
On a more granular level, though, sponsors could potentially identify opportunities to condense existing templates, streamline protocol authoring and review, improve quality, and reduce errors during study conduct. CROs might find more consistent expectations across clients, the ability to streamline protocol authoring and review, fewer protocol templates to manage, and greater efficiency in study start-up and conduct.
Lastly, health authorities could even see an increased consistency and ease of review around sponsor protocols due to streamlined data interpretation, greater ability to compare protocols, and increased use of data standards, enabling end-to-end traceability.
To help make these benefits tangible for our stakeholders, we are actively seeking input to further improve future versions of the protocol template. Earlier in 2019, we held two separate public webinar sessions and fielded a handful of poll questions to understand the challenges and opportunities associated with the use of nonclinical templates. The audience included CROs, health authorities and regulatory agencies, industry groups, research sponsors, and service providers. Representatives from nine of TransCelerate’s member companies were in attendance, as well.
Based on the results calculated across both webinar sessions, a majority of respondents (43 percent) are using six or more nonclinical protocol templates in their organization. When asked about the most problematic issues with using multiple protocol templates across different sponsors or studies, participants cited process or time inefficiencies (31 percent) and quality of study execution (27 percent) as the top challenges. This was closely followed by inconsistent review or interpretation of studies (19 percent) and difficulty compiling SEND data sets (17 percent). These concerns are ultimately what our version of the nonclinical template is working to address.
Additionally, most respondents agreed (83 percent) that the OECD GLP should be used as a baseline for a global common protocol template, rather than other options such as the FDA GLP. Finally, in terms of implementing CDISC SEND information into the protocol template, attendees were relatively divided on the best course of action. Most said it should be included as a separate section identifying key variables (39 percent), but others felt the information should be included throughout the template in relevant sections (29 percent) or not included at all (32 percent). Overall, these insights are helping us refine and enhance the template so we can continue to decrease study errors, improve data quality, and lead to more rapid protocol development.
As of today, a draft document of the nonclinical protocol template is available for review and feedback by the public. All interested stakeholders are welcome to submit comments and input on the first draft to help us improve, tailor, and revise the template for its official release by the end of the year. Looking ahead, our hope is that we can continue to help facilitate and streamline the toxicology study process for CROs, sponsors, and other industry partners — and have a positive impact on building better, more efficient clinical trials.
About The Author:
Todd Page is director of toxicology at Eli Lilly and Company. At Eli Lilly, Todd focuses on ensuring that the non-clinical toxicology studies conducted to support clinical development are done with the highest quality and in the most efficient manner to speed medicines to patients. He also leads the BioCelerate Common Templates for Nonclinical Studies Initiative, aiming to develop open-source documents for nonclinical study protocols and study reports for sponsors, CROs, and other stakeholders. Todd received his Ph.D in pharmacology/toxicology from the University of Nebraska Medical Center and did post-doctoral work at the University of Wisconsin, focusing on Immunotoxicology.