Integrated Evidence Systems: Digital Trials Work, When Everything Works Together

COVID-19, and the negative impact the pandemic wrought on in-flight trials and new trial initiations, accelerated work on digital clinical trial solutions that was underway.  

First, eSource 

The concept of electronic source (eSource) is not new. eSource is defined as capturing data from their source where that source is available in an electronic, digital, or an otherwise machine-retrievable format. As the definition implies, eSource entails capturing data in their original, electronic format versus adding a paper transcription to an electronic system or manually entering information later into a new electronic system – avoiding the double or triple entry of data.

Concepts for it appeared formally in 2006 when the Electronic Source Data Interchange (eSDI) Group within the Clinical Data Interchange Standards Consortium (CDISC) issued a paper entitled “Leveraging the CDISC Standards to Facilitate the use of Electronic Source Data within Clinical Trials.” eSource guidance began to emerge from the U.S. Food and Drug Administration and European Medicines Agency (EMA) in 2013 with a set of webinars and other forums to further the goals of eSource throughout 2014. Formally, this was an active period wherein the FDA issued “Guidance for Industry: Electronic Source Data in Clinical Investigations” in September 2013, directions that were largely consistent with the EMA’s 2010 “Reflection Paper on Expectations for Electronic Source Data and Data Transcribed to Electronic Data Collection Tools in Clinical Trials.” 

Now, a clear path 

While our definition of digital clinical trials is broader than the original definitions of eSource – e.g., inclusive of clinical trial design, digital and artificial intelligence-augmented site identification, AI-assisted patient identification for study eligibility, unstructured data processing into electronic case report forms (eCRFs) – it is the foundation from earlier guidance, plus some of the more recent additions to this guidance for Software as a Medical Device (SaMD) applications, that now create a clear path for a wholesale and accelerated move to integrated digital clinical trial solutions.   

The pandemic 

For the better part of the last decade, limited progress was made and only a few aspects of the eSource model predominated clinical development technologies – until the pandemic. A broader move of clinical development processes to the cloud and digital-only solutions met barriers of new digital investment scale versus legacy costs and complex organizational structures slowing its pace. Costs of legacy infrastructure and processes range from tens to hundreds of millions of dollars per organization. Clinical operations organizations were often defined by subfunctions that aligned to specific phases of the process and sets of technologies, reducing incentives for a group to eliminate the need for their expertise. Biopharma partners mirrored much of the same construct and therefore had a comparable structural and functional “lock-in.” Furthering the inertia was that the legacy system worked, furnished critical deliverables, and generally met its timetables. Guidance existed, but was thin, and had very limited use-cases supporting a hard pivot to a pure eSource-centered approach.   

Then came COVID-19 and the effective shut-down of traditional clinical trials. Sites limited patients joining trials. Some moved trial participants back to standard of care therapies. Many new studies were unable to open. Access to physical sites was limited to local clinical personnel (essential at that) and patients. Even supportive caregivers and family members were not allowed into facilities. Traditional technologies and ways of working showed their limitations in this new access-, time-, and technology-constrained world. 

Digital, eSource, decentralized and other remote and electronic solutions have existed for years but not at scale. These solutions always seemed at the margins of CRO and biopharma practices, belonging to special innovation and feasibility groups versus serving as a core standard of how work should be done for study design, set-up, conduct, and close-out. But now the role of these solutions is shifting at an accelerating pace. In one narrow category – decentralized trial solutions used for COVID-19 vaccines and therapeutics studies – some company revenues have grown almost 300 percent this year alone and even higher over the entire pandemic.  

The paradigm shifts 

What is important to understand is that digital clinical trials represent a paradigm shift that implies a set of aligned changes that are creating the elements of a new system. One-off or partial digital capabilities aimed at only the currently urgent bottlenecks provide relief at best. When the entire system is redesigned is when performance and new functionalities emerge that can ‘bend’ clinical trial quality, cost, and speed curves.

Oncology-related clinical trials are the largest area of biomedical innovation – estimated at 40 percent or more of the total number of sponsored clinical trials. It is also a very unique area within clinical development. Patients often undergo quite complex therapies, sometimes as combinations of medicines, pre-treatment with chemotherapeutic agents or radiation oncological therapy, and ongoing monitoring of response or progression using imaging studies and serial biopsies – all taking place within highly specialized facilities.  

Running these studies requires four things....... [CONTINUE READING AT CONCERTAI BY CLICKING HERE]

Paradigm Shift: Jeff Elton, PhD describes one way data as a service contributes to the paradigm shift underway.