- Full participation across all stakeholders — clinical trial sponsors, sites, investigators, patients and their healthcare providers
- Information is fully used to improve the overall quality, design and development process. We protect patients through shared, proactive safety science
- Improving the execution of research and development through greater harmonization with the potential to conduct collaborative trials
Newest Resources and Company Milestones
- In June, BioCelerate announced the release of its first set of solutions as part of its Public Private Partnership (PPP) with the U.S. Food & Drug Administration’s Center for Drug Evaluation and Research (CDER) Office of Computational Science (OCS). One of the goals of this PPP is to help optimize the implementation of the Clinical Data Interchange Standards Consortium’s (CDISC) Standard for Exchange of Nonclinical Data (SEND) so nonclinical data is presented in a harmonized format across the ecosystem to facilitate cross-study analysis.
- DIA Global 2021 finished on July 1 after four days of TransCelerate and Member Company sessions. At the conference, TransCelerate received DIA’s Global Inspire Award for Author of the Year for the paper “Utilizing Advanced Technologies to Augment Pharmacovigilance Systems: Challenges and Opportunities.” To read the full recap of our sessions, click here.
- We welcomed Rob Lenz, M.D., Ph.D. of Amgen to our Board of Directors. He will assume the role for Elliott Levy (Amgen), who will be stepping down. Rob currently serves as Senior Vice President, Global Development, responsible for the clinical development of Amgen’s pipeline. We look forward to Rob bringing his immense industry experience to TransCelerate’s collaborative Board of Directors members.
- We welcomed Karin Kramer Nielsen (Novo Nordisk) who will be assuming the role of Oversight Committee Chair for Simon Trowell (GSK). Karin currently serves as Corporate Vice President, Data Management and has been with Novo Nordisk since 1994. We look forward to Karin’s global industry experience and leadership in this new role.
Pulse On Progress Updates
Information Sharing & Harmonization
Enable the industry to move toward greater harmonization of process and facilitate the sharing of information amongst industry stakeholders to enable the industry to capture, optimize and experience efficiencies.
- The Clinical Content & Reuse (CC&R) Initiative released Japanese (日本語) translations of the Common Protocol Template (CPT) and Patient Library. Translations are available on CC&R’s Solutions page, at Clinical Content & Reuse Assets – Clinical Studies, and under Solutions Available in Additional Languages.
- In mid-2018 and into 2019, the TransCelerate eSource team engaged with a Site Advocacy Group (SAG) in collaboration with the Society for Clinical Research Sites (SCRS) for an information gathering exercise via voluntary site survey to discuss challenges and areas for improvement in conjunction with technology use in clinical trials. The eSource Informatics Continuum and Reference Guide for Clinical Research Sites provides information on clinical research informatics, the basics of informatics, and possible resources to expand capabilities around interoperability and data exchange for clinical sites.
Improve the Patient & Site Experience
Improve the patient and site experience by decreasing burden, enabling a better-informed patient and improving clinical research awareness, participation & engagement.
- Throughout the COVID-19 pandemic, our Patient Technology Initiative was one of the teams recognized as having produced valuable solutions with applicability to the changing industry landscape. To modernize key solutions for use in the “new normal,” the Patients Considerations Guide and Patient Technology Site Feedback Questionnaire (PTSFQ) were updated to include considerations around decentralized trials and virtual environments. The full list of Patient Technology assets are available on its Solutions page.
- TransCelerate’s Privacy Methodology for Data Sharing initiative recently completed its first-ever Initiative poster, which is now live on the DataCelerate® webpage. The Privacy Methodology Initiative supports TransCelerate’s greater Information Sharing strategic program and the DataCelerate® platform. This initiative aims to identify a model approach to implement privacy safeguards that will provide increased transparency and enable simpler utilization of clinical trial data reuse within the DataCelerate® modules.
- The newly launched Diversity of Participants in Clinical Trials Initiative seeks to move beyond our prior awareness building activities and begin to equip sponsors and ecosystem stakeholders with the actionable tools and resources needed to improve outcomes for diversification of participants in clinical trials. As part of the first phase of the initiative, the following efforts are underway: a Member Company clinical research diversity collaboration hub, race and ethnicity enrollment data benchmarking, leveraging existing solutions, and best practices for sponsors and clinical trial sites.
Enhance Sponsor Efficiencies
Facilitate the advancement of innovative healthcare and clinical research through improved technologies, advanced data collection systems and simplified processes.
- CDISC published its CDASH SAE V2.0 Supplement, which captures how to structure serious adverse events (SAE) concepts for regulated clinical trials. This supplement aligns with E2B (R3) Electronic Transmission of Individual Case Safety Reports Implementation Guide—Data Elements and Message Specification. This standard issuance would not be possible without TransCelerate’s hard work in 2019 through our Common SAE Fields Initiative and the gathering of input from both our clinical and pharmacovigilance sides of our portfolio. In only four months, the Common SAE team conducted a comprehensive landscape assessment to understand the applicable current industry regulations. They identified the common core fields collected and reported following a serious adverse event. The proposed list contained 833 unique fields and through the team’s analysis, the list was pared down to approximately 130 unique fields spread across nine sections of data. The result was the “Common SAE Fields Project Overview & Outputs” slide deck and methodology. Once complete, TransCelerate transitioned this deliverable to CDISC’s CDASH SAE Standard team in Q4 2019. CDISC has worked for the past year to develop this new industry standard surrounding SAE data collection.
- TransCelerate’s Modernizing Clinical Trial Conduct (MCTC) Initiative, in collaboration with the Risk Based Monitoring (RBM) Initiative, released a new publicly-available report that organizations can use to help benchmark their RBM activities pre-COVID-19. Key findings from a voluntary 2020 survey conducted in TransCelerate Member Companies pre-COVID, regarding their Risk Based Monitoring practices related to Source Data Verification (SDV) and Source Data Review (SDR), are summarized in “Results of RBM SDV/SDR Survey: 2020 Pre-COVID-19 Pandemic Practices.” This report serves as the final deliverable of the recently completed RBM Initiative.
- Modernization of Statistical Analytics launched its Foundational Framework along with many supporting resources to aid in awareness and adoption. The framework seeks to explore a product agnostic approach to build trustworthiness in modern statistical software tools which includes principles that can be used across the industry to establish a high level of accuracy, traceability, and reproducibility. The team developed an infographic and case for adoption to help socialize these concepts.
- TransCelerate’s Protocol Deviations (PD) initiative team published a peer-reviewed article, “Protocol Deviations: A Holistic Approach from Defining to Reporting.” Protocol Deviation Management processes can be complex and varied, making it difficult to navigate the clinical trial landscape in R&D. Especially with COVID-19 altering many clinical trial operations, protocol modifications will be necessary to ensure sponsors conducting clinical research can improve their PD classification, collection, analysis and reporting processes.
Check Out Our Blog
Learn about what we’ve been up to this past quarter:
A Framework for Evolving Analytics and Modernizing Software Technologies in Clinical Development
We spoke with Daniel Woodie, Merck, Senior Scientist Statistical Programming, TransCelerate Modernization of Statistical Analytics Team Co-Lead and Min Lee, Amgen, Director of Biostatistical Programming, TransCelerate Modernization of Statistical Analytics Team Co-Lead about this new initiative and the need for technology to support regulatory filings.
Biopharmaceutical companies operate in a highly regulated environment. As such, it is important that the software systems used to analyze data, as part of the clinical R&D development process, can be relied upon to produce accurate and consistent results. At the same time, the pharmaceutical ecosystem has seen a slow evolution in analytics capabilities, causing challenges and failure to leverage modern technologies.
“The increasing amount of data sources collected as part of drug development and commercialization has vastly increased the amount and types of data biopharmaceutical companies collect. This has increased the need and urgency for technology that can process large amounts of structured and unstructured data and can be used to support regulatory filings,” notes Daniel.
Companies need to modernize their statistical offerings through non-traditional (e.g., open source) software to meet the increasing complexity of data analysis now required. To springboard innovation in analytics, TransCelerate BioPharma recently produced a “Modernization of Statistical Analytics (MSA) Framework” with the goal of building confidence in cutting-edge analytical programs, which will ultimately help bring new medical breakthrough products to patients more quickly.
Historically, regulatory agencies have offered limited guidance on what constitutes reliable software causing the actual breadth of software used in the biopharmaceutical space to be constrained. This Framework provides a methodology that stakeholders across the ecosystem can use to demonstrate to Health Authorities the reliability of software – whether traditional or non-traditional – and thereby build confidence in analytical programs even if they are newer.
While biopharmaceutical companies and their clinical research organizations (CRO) partners have well-established standard operating procedures for assessing the suitability of traditional software for inclusion as a component of a modern statistical analytics environment, many do not have practical procedures in place to enable a similar assessment for non-traditional software.
“Our goal is to build confidence in cutting-edge analytical programs and eliminate inefficiencies in bringing new medical breakthrough products to patients more quickly. This framework provides practical guidance on how to demonstrate that an analytics solution produces credible results and is suitable for use in the regulatory process,” says Min.
Additionally, with the emergence of electronic and digital data sources (e.g., wearable tech data, electronic health records) and the mass quantities of data collected, there is a strong desire and need to implement algorithmic capabilities (automation, advanced statistical methods, machine learning algorithms, and other artificial intelligence techniques) that requires multiple solution providers (whether traditional, non-traditional, or both) to take advantage of that data for generating new insights, decision making, and evidence generation for clinical trials. Moreover, the programmers, statisticians, and data scientists leveraging these technologies are just as well versed.
This Framework proposes approaches for developing an MSA environment, regardless of whether it supports relatively traditional or less traditional software, that will give regulatory bodies, and thus ecosystem, confidence in the reliability of the results generated from such an environment, even when the agencies heavily scrutinize the results.
The MSA Framework comprises a set of principles that can be adhered to build and maintain a modern computing environment that we believe Health Authorities will find reliable and output of which can be used with confidence to support regulatory filings (i.e., marketing applications for clinical trials novel treatments or therapies). Additionally, the Framework includes discussing requirements for programming infrastructure and processes, including risk-assessment and mitigation practices to execute to demonstrate reliability of an MSA environment.
While the concepts specified within the MSA Framework can be basic in principle, they may prove challenging in practice to implement. The legacy infrastructure and processes upon which current environments in biopharmaceutical companies often rely upon provide a basis for how analytical programming environments can and cannot evolve. However, when attempting to implement a new type of environment without the guidance and constraints of legacy, a set of best practices and explorations of use cases can be invaluable.
Excitingly, this Framework is part of a bigger culture shift happening within analytics across the biopharmaceutical ecosystem, and within analysis and reporting competencies for these companies. We are seeing innovations happening at an accelerated pace with software used for statistical analysis. While risk-averse companies may choose to avoid using these software capabilities, there is an opportunity cost which ultimately impacts the ability to bring drugs to market faster. The MSA and accompanying Best Practices give the R&D ecosystem an approach for demonstrating to the regulatory bodies the reliability of analytical software, including newly developed software. By working together to build the Health Authorities’ confidence in these software and technology solutions, we will facilitate the modernization of our statistical tools. We only stand to gain from accelerating this digital transformation.
While each organization will have to decide its own desire for change and willingness to balance any risks, embracing a culture shift towards modernizing statistical analysis will be crucial for the ability to bring medicines to patients more quickly. As data sources will continue to expand in the coming years and decades, TransCelerate’s MSA framework will allow stakeholders to stay ahead of that trend.
The team further shares seven tips that can be used to help implement a modernized statistical analytics environment in August’s Clinical Leader.
For additional information, visit TransCelerate’s Modernization of Statistical Analytics Initiative solutions page.
BioCelerate’s SEND Implementation for Cross-Study Analysis Initiative
Historically, nonclinical study toxicology data has been reported in text files and proved difficult to analyze using current digital based tools. As flat text files do not lend themselves to automation (e.g., searches, find specific data, categorize data, etc.), the need to digitize nonclinical data has become a priority over the last 10 years.
To address this inefficiency, the Standard for Exchange of Nonclinical Data (SEND) data sets was developed by the Clinical Data Interchange Standards Consortium (CDISC) to provide an opportunity to put data in an electronic format that’s categorized, searchable, and applies standards to how data is entered, improving efficiency in nonclinical data input. Not only do SEND data sets improve efficiency in nonclinical data input but also help expedite the evaluation process as well.
We spoke with Mark Carfagna, Senior Research Advisor at Eli Lilly, about BioCelerate’s published paper, Leveraging the Value of CDISC SEND Data Sets for Cross-Study Analysis: Incidence of Microscopic Findings in Control Animals, who also took a deep dive into BioCelerate’s role in automating and improving the utilization of CDISC SEND data.
Q: How are BioCelerate and the FDA’s Center for Drug Evaluation and Research working together to provide solutions that make cross-study analysis more efficient?
A: Before SEND, Pharmacology/Toxicology Reviewers at FDA CDER used their own manual procedures to extract data from submitted reports. With an increase in electronic tools that enable automated analyses and the standardization of data, data analysis has evolved and enabled us to leverage data in ways that we were unable to do previously. In addition to meeting the FDA SEND requirement, sponsors have a desire to build their own internal databases to perform evaluations to better understand their own portfolios. BioCelerate’s biggest role here is to facilitate the use of that data among member companies and to work through the consortium to help create recommendations for harmonization of SEND data.
The collaboration and engagement of this integrated consortium – crossing from the FDA to BioCelerate to PHUSE to CDISC – are unique. It has truly been a team effort with engagement from all parties. As the keeper of the most comprehensive database of SEND data, the FDA has been a crucial partner in enabling a lot of collaborative work – analyzing a repository of aggregated data sets and sharing in our mutual interest in using and applying electronic SEND data to interpret and understand differences between studies. The collaboration allowed the group to ask questions of the data that were previously very time consuming (e.g., background control incidence of specific findings). With the data in a digital format that can be categorized and analyzed systematically, we can now apply processes that allow for better evaluation of the data sets with the goal of improving overall drug development.
Q: How does the manuscript that was just released build on the foundation that the first manuscript, SEND harmonization & cross-study analysis: A proposal to better harvest the value from SEND data (2020), set for this Initiative?
A: The BioCelerate SEND Initiative was started to explore ways to leverage SEND data. For the last three to four years, there was a lot of emphasis by pharmaceutical companies and CROs on how to put data in SEND structure for it to be acceptable for submission to the FDA. We were curious if we could use these SEND data sets that the FDA requires to improve our internal drug development outcomes. There is a lot of focus on the process and IT component of getting toxicology data from laboratory data systems into the SEND format and has been the emphasis for the past few years.
The SEND implementation guide was developed to accommodate very broad data formats so that it could handle a multitude of study data entry situations. This has led to variability in how data is entered into SEND. Our efforts are focused on proposing recommendations for entering data in such a way that helps us compare studies more reliably. With a system to accept those different styles, we’re able to get toxicology data into the SEND format, meet the FDA requirement, and evolve from just providing data sets to using the data sets.
The second manuscript also discusses some of the limitations and room for additional work to further improve the SEND structure. There are approximately five topics we brought forward from that manuscript that are being addressed by PHUSE and CDISC to change the SEND structure to better enable cross-study analysis.
Ultimately, we hope scientists can leverage the technology and use it to extract and compare data across multiple studies. The ability to do this with toxicology data is a big step forward from text files.
Q: What are the biggest areas of opportunities and/or challenges in leveraging SEND data for cross-study analysis?
A: The biggest challenges are harmonization of SEND data entry to enable cross study analysis. Something as simple as identifying studies that used the same vehicle is a challenge due to variability in data entry. The goal is to harmonize how data are recorded and put in SEND format, but it remains a challenge. For example, when you look at 10 different SEND data sets in which the same vehicle was used, the recording of vehicle components will vary greatly between studies thus making it difficult to confidently analyze the data. As for controlled terminology, we’re working on taking the current broad scope platform and honing in on what data needs controlled terminology to decrease variability. There’s been a lot of progress in these areas recently, providing optimism that solutions can be implemented.
Another challenge and opportunity is to get toxicologist’s comfortable with transitioning from the evaluation of text reports to the use of electronic tools. Many scientists are comfortable with the way it’s been done in the past and are hesitant to use new technologies. Using something new that has the potential for questions and leaves room for concern on the quality of the data makes people less inclined to adopt it quickly. Currently the use of SEND data for study interpretation is not widely implemented within CROs and pharmaceutical companies, however the value and increased efficiency it offers is resulting in increased adoption.
All of the support for these projects comes from individuals providing time and resources outside of their day to day responsibilities within their own organization. The progress accomplished by collaborating over the past three years shows the dedication of the FDA, sponsors, CDISC, PHUSE, BioCelerate, and TransCelerate. There’s a strong passion to get this right.
Q: As SEND dataset requirements constantly shift, what changes do you foresee?
A: The SEND data requirements will continue to evolve from a broader, catch-all digital system to focusing on changes in areas related to study interpretation. Instances where there’s ambiguity in the data will continue to be addressed resulting in changes to the requirements while also improving the utility of the data. Scientists who use electronic data want to ensure search result confidence and a lot of changes are now in place to help increase confidence. Instead of shifting, we see this as focusing.
Mark Your Calendars
TransCelerate leaders and Member Companies are invited to participate and present at many biopharmaceutical research industry conferences and meetings across the globe to provide a perspective on industry challenges and clinical trial issues. Take a peek at a few places we will be presenting in the coming months. For detailed information on speaker presentations, visit the events page on the TransCelerate website.