By Missy Heidelberg, senior product development industry collaborations and bioethics leader, Roche, and TransCelerate Clinical Content & Reuse website steward
The clinical trial space is at an inflection point. Clinical trials have been run the same way for decades, but their design and implementation are now changing rapidly and becoming increasingly novel. The aim of these changes is to foster collaboration, streamline harmonized processes, and improve the ability to reuse data and content so that the biopharmaceutical community can leverage new and innovative opportunities in clinical trials.
For example, the FDA has encouraged clinical research sponsors to consider using master study protocols for their trials, enabling multiple research sponsors to collaborate while studying the efficacy of their respective therapies. Remote trials are also becoming increasingly common. Now, clinical research activities that have conventionally been done solely at on-site locations are becoming more decentralized, enabled by technology advances and fueled by the remote work environment that the COVID-19 pandemic has accelerated. As data infrastructure continues to improve, clinical trial data will increasingly be able to flow seamlessly from its point of collection into trial databases for reuse and to drive additional insights across the clinical research ecosystem.
Clinical Template Suite And Content Reuse And Digitization
For clinical trial transformation to achieve its full potential, the structure and content of clinical trial documents must change to facilitate data transfer, content reuse, and predictability of information flow to support more efficient trial conduct by sites and sponsors. In addition to the FDA’s work on master study protocols, for example, TransCelerate BioPharma’s Clinical Content and Reuse (CC&R) initiative has been supporting content reuse and harmonization of operations since 2014. The CC&R initiative produced an entire suite of templates for clinical trial documents that are intended to support the biopharmaceutical community. The templates include a common protocol template (CPT), common statistical analysis plan (SAP), and common clinical study report (CSR) that can be used by all stakeholders in clinical research across all phases of studies. These materials allow researchers and authors to extract and reuse relevant data and content for submissions and enable regulators and investigators to access important information within clinical trial documents with greater ease. These harmonized templates also allow sponsors to take an aligned approach to extraordinary events, such as the disruptions caused by COVID-19.
The CC&R team has also focused on identifying opportunities to reuse content across documents in the Clinical Template Suite without heavy manual rework, enabling automation of digitized content. Content reuse will support the digital transformation of clinical research data, but the task remains a tall order. Each biopharmaceutical company has its own set of practices and protocols for clinical research and how they report findings, creating wide variations in the formats used and the location of key information.
Digitizing clinical trial data is one of the CC&R team’s priorities, so the initiative has spent time to improve the clarity and completeness of key content areas within the CPT that are reused when registering clinical trials on ClinicialTrials.gov. With the latest updates to the CPT, SAP, and CSR templates, a subset of these elements can now be exported and directly uploaded into the Protocol Registration System of ClinicialTrials.gov, laying the foundation for more automation.
The CC&R initiative has also pursued collaborations to serve a more diverse set of stakeholders in the clinical research community. CC&R has collaborated with TransCelerate’s Clinical Research Access & Information Exchange (CRAIE) initiative to pursue several important updates to the Clinical Template Suite, such as making clinical trial registries more user-friendly and creating more meaningful exchanges between researchers and participants. The teams worked together to update the CPT, enabling CPT authors to write more patient-focused copy for the report.
The development of the Clinical Template Suite has been a critical step forward to facilitate consistency among and within clinical study documents, as well as digitization of clinical trial data. The team continues to fine-tune the documents to better serve the clinical research ecosystem. In 2020, the team reduced barriers to digital adoption of CPT, SAP, and CSR eTemplates by providing support and guidance on customizing libraries, automating quality registry submissions on ClinicalTrials.gov, and improving functionality to accommodate more complex trial designs.
Grappling With The Impact Of COVID-19 In CSRs
The COVID-19 pandemic is one of the most urgent challenges facing clinical trials and reporting and has brought about a unique set of hurdles for the biopharmaceutical research community. The pandemic brought unprecedented disruption to clinical research, amplifying existing clinical trial difficulties from patient enrollment in studies to collecting patient data.
Inspiringly, stakeholders throughout the biopharmaceutical research space have come together to collaborate on solutions to COVID-19 disruptions. Regulators around the globe issued guidance to help researchers and research sponsors to navigate the challenges and disruptions caused by COVID-19, but ambiguities remained. One challenge was how researchers and authors of CSRs should describe the pandemic’s impact on clinical trials in a way that was meaningful and clear for regulators, clinical research organizations (CROs), research sites, and others.
The CC&R initiative has used its well-established foundation in content reuse and medical writing and its deep familiarity with the Clinical Template Suite to support the community in managing the novel difficulties caused by the pandemic. Specifically, a diverse, cross-functional team led by the CC&R initiative developed Guiding Principles to support researchers as they describe how COVID-19 impacted their studies, to share key points that researchers should consider when they discuss the disruption of COVID-19 to their trials, and to provide sample text that can support researchers and authors to address key considerations in their clinical study reports.
The guiding principles offer a road map for describing how and to what degree a clinical trial was affected by COVID-19 and the level of emphasis it merits in the CSR. For example, a completed study with conclusions should cover the pandemic as an element affecting the trial, but it should not be a focal point. The CC&R team suggests that the most effective summaries highlight only the aspects of the study that were disrupted or changed as a result of COVID-19 and avoid mentioning tactics or findings that were part of the original study plan.
The CC&R team suggests that an impact summary of the pandemic should consider several key points:
- How the pandemic impacted the overall continuity of the trial, such as terminating or pausing and restarting trials at specific sites or in specific countries. The CSR should include an explanation of how the decision was made and factors that were considered.
- What, if any, pandemic-related amendments were made to the protocol or SAP. The CSR should describe the status of the trial at the time of the amendment(s). It should explain how trials may have been amended – for example, to allow for extended visit windows, modification of endpoints, or sensitivity analyses.
- Whether the trial met its objectives.
With regulators and statisticians keeping watchful eyes on potential biases, the CSR should thoroughly explain measures that were taken to minimize bias when mitigations were necessary and offer a rationale to explain why the data should be accepted as unbiased.
In pursuit of collaboration among relevant stakeholders, including regulators, health authorities and other stakeholders such as CDSIC, groups external to TransCelerate have been invited to share their perspectives to inform the guidance and recommendations that the CC&R team developed.
Advancing Digitization Of Content
While the pandemic monopolized attention in 2020, it has also underscored the need for a continued push to make content more digital and user-friendly.
Achieving the goals of content reuse and digitization, such as template harmonization, has required extensive effort from the CC&R team and is proving to be worthwhile. Over the course of 2020, the clinical research community has had to find new ways of working. The existence of industry-aligned templates has made it easier to move forward with many studies despite uncertainty. Rethinking how basic content is structured and created will enable everyone to extract greater value and help to accelerate clinical research. By taking steps to harmonize and simplify the flow of data and clinical content, clinical research and reporting are more efficient, and the community is well equipped to innovate and, ultimately, bring medicines to patients faster.
About the Author:
Missy Heidelberg is a product development industry collaboration and bioethics leader at Roche with nearly 20 years of experience in the clinical trial space. She represents Roche on numerous pre-competitive industry collaborations, including TransCelerate BioPharma Inc., and supports the internal realization of those efforts to improve the clinical trial process and experience. She also provides expertise on bioethics topics related to clinical research and drug development with a specific focus on data ethics.