This article is taken from PharmaPhorum August 2021, "From start to finish – digitising clinical trials" [digital edition available here]
Over the past two years, the pharma industry’s demand for automated research solutions has increased significantly and, particularly when it comes to clinical trial design, the need has never been greater.
This shift to digitised approaches has been triggered by some persistent challenges faced by those companies still reliant on applying manual processes.
“A few common challenges appear time and time again when we speak with organisations about clinical trials,” Kevin Burges, head of product management at Formedix, explains.
“The first is a lack of standardization in trial design, which leads to delays in study setup. Metadata is often not stored centrally or controlled effectively. And because it’s not standardized it can’t be reused, which means that each trial needs to be set up manually from individual specifications. Not only does this introduce the risk of errors and inconsistencies, but it also extends timelines due to the manual work needed.”
The length of time required for data mapping and conversions is another common challenge. Manual data mapping can be complex and time consuming, and provides difficulties in the early viewing of a trial’s efficacy and safety so trials can be adapted accordingly.
This issue arises either when the source data has not been standardized, or those standards don’t include the mappings to downstream data formats, such as Study Data Tabulation Model (SDTM). If the standards are truly end-to-end and include mappings, data conversions can be run as soon as patient data starts coming in.
“COVID-19 has demonstrated that trials can be run much more efficiently, to everyone’s benefit. Nearly every element of the clinical trial design, data collection, analysis and approvals has been shortened and this helped ensure the swift rollout of safe and effective vaccines.”
“Thankfully, paper-based studies are becoming a thing of the past, but spreadsheets and Word documents are still commonly used to design and build trials. This gives great risk for human error and misinterpretation. It can also lead to difficulties in finding information, as it is often stored in disparate systems each with their own access rights and permissions.”
These formats also provide limited change history, so users are unable to see the downstream impact of making changes or view if they are working on the most up-to-date version of a particular document.
However, if metadata is standardized throughout the trial design process and submission-ready standards are embedded in the design, less manual time and effort is needed, and conversions can be automated.
The future is automation
Recognising the need for automated, harmonised solutions, Formedix developed the ryze platform which produces near-real time safety and efficacy readouts as soon as data is collected, allowing for rapid trial adaptations.
“This is an area where technology plays a critical role. By embedding end-to-end standards throughout the clinical trial design, data collection and analysis stages, submission-ready datasets can be generated as soon as data starts rolling in,” said Burges.
A central, single source for metadata in the form of a clinical metadata repository (CMDR) also encourages a collaborative approach, rather than a silo mentality. Stakeholders can access one system and view the most current versions of the relevant metadata and know that it is controlled and standardised.
“This approach encourages collaboration and removes silos, where people have access to fragments of the overall picture. By using a CMDR, reviews and approvals take place centrally, rather than through multiple spreadsheets and buried email chains, so the full history of a standard can be traced throughout the system, with every sign-off and change documented,” said Burges.
Additionally, the electronic data capture (EDC) automation allows teams to preview exactly how their forms will look for their chosen EDC system. By standardizing data and allowing team members to collaborate in one system, human error and miscommunication are reduced. And, with clear protocols for change control, impacts can be studied before a change is made, which reduces complications downstream too.
“The best part is once your team has approved your study metadata, the automation software automatically builds the study and converts your data as it is collected.”
In 2019, Formedix collaborated with a UK-based consortium interested in observing early safety data. To this end, ryze has been used extensively in several COVID-19 vaccine trials, to reduce the lag time for SDTM conversions. Raw data was quickly converted to SDTM formats and visualised, allowing early assessments of vaccine safety and efficacy.
“When companies suddenly needed to condense years of clinical trials into just a few months, technology facilitating automation and reuse were immediately appealing. Automation simply makes sense to so many trial designers and biostatisticians and that’s why we’re seeing an increase in adoption. A CMDR and study automation platform, such as ryze, can be used to design standards and then automatically generate the downstream EDC study from within the platform.”
Compliance is key
There has been huge progress in recent years in standardising data for clinical trial submissions, including the development of the Clinical Data Interchange Standards Consortium (CDISC) standards. These are now used by several regulatory bodies, including the Food and Drug Administration (FDA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) for submission packages.
Therefore, developing a platform that had CDISC at its core was essential for Formedix, both in terms of the non-regulatory elements of data planning and capturing the regulatory requirements of models such as the Standard for Exchange of Nonclinical Data (SEND) and the SDTM.
“Our relationship with CDISC has been established over many years,” said Burges. “We helped develop many of the features in the ODM and Define-XML models and our team still works with the CDISC Data Exchange Standards teams. With this close working relationship, we are fully aware of changes to all regulations and our platform reflects this up-to-date view.
‘’ryze is compliant with past and current versions of CDISC, but it is also future-proofed to incorporate further updates so that compliance is effortless,” he added.
As the platform provides a single hub built on the CDISC framework, the risks of using out-of-date or non-compliant structures when defining or reusing metadata are removed. “The user simply selects the relevant version of the CDISC metadata template and creates submittable deliverables with just a click. Metadata can also be uploaded into ryze and validated against relevant CDISC standards to ensure compliance.”
It marks an exciting revolution for the life sciences industry, where all-in-one cloud-based platforms are simplifying end-to-end metadata management and enabling cross-collaboration between stakeholders. Ultimately, all companies are benefiting from significant time and cost savings, resulting in the faster delivery of new therapies to patients.
“COVID-19 has demonstrated that trials can be run much more efficiently, to everyone’s benefit,” concluded Burges. “Nearly every element of the clinical trial design, data collection, analysis and approvals has been shortened and this helped ensure the swift rollout of safe and effective vaccines.”
“I can’t imagine that pharmaceutical companies will return to the ways of the past. COVID-19 has taught us too much and brought our expectations to a new level.”
About the interviewee
Kevin Burges, head of product management, Formedix – In his 20 years at Formedix, CDISC has been a core focus for Kevin. He was a founding member of the CDISC XML Technologies Governance team and helped drive the future technical direction of CDISC standards. Today, Kevin is a member of the Data Exchange Standards team, which includes ODM, Dataset XML and Define XML, and he works closely with customers to enhance the ryze platform and develop new features.