From Paper to Digital to Virtual: The Past, Present, and Future of Clinical Research

Heraclytus of Ephesus (fl.c. 500 BCE) said, “The only constant in life is change.” But throughout history, there have been periods when that change has been momentous. In just thirty years, we’ve seen unprecedented technological, societal, and business transformations; and we’re about to take another giant leap forward.

An example of transformative change is the evolution of communication methods and technology, from cuneiform clay tablets and papyrus scrolls to letters delivered by Pony Express, telegrams, telephones, telexes, fax machines, and smartphones. Since the 1990s, we’ve seen the Internet—email, social media, messaging apps, and video conferencing—change how we live and work beyond recognition. For the future, 3D holographic communication and medical imaging have already been developed, ready for the advances in technological infrastructures that will enable common adoption.

Learning from the Past

James Lind, known as the ‘Father of Clinical Trials,’ was a Royal Navy surgeon who ran one of the first controlled clinical trials, a study for scurvy in 1747. His study was successful and he published his findings in the “Treatise of the Scurvy” in 1753.¹

Despite discovering a cure for scurvy, he faced significant barriers to gaining acceptance and adoption. At that time, the Four Humors theory was central to medical practices, so his approach was as transformational to eighteenth-century medicine as artificial intelligence (AI) has been to clinical trials today. The Royal Navy did not sanction the simple remedy, lemon or lime juice, until forty-two years later in 1795. By 1797, no cases of scurvy existed at the Haslar Hospital, one of the largest Naval hospitals of its time. In 1815, only two cases of scurvy were reported over the final four years of the Napoleonic Wars.² To put this into context, scurvy typically killed most sailors on any ship making a long voyage. An estimated two million sailors died from it between the 16th and 18th Century.³

Once treated, full recovery from scurvy is possible, so if the cure had been adopted immediately after it was discovered and tested, how many people could have been saved?

Lind did not have the clinical trial infrastructure and support we have today. But against all odds, he managed to usher in change at a time when the medical profession and Admiralty were resistant to his evidence and convictions.

Another practice that has remained the same since Lind’s time, right up to the 1990s and to some extent today, is using paper-based record-keeping and manual processes.

During the 1990s, paper case report forms, manual data entry, and physical storage systems were standard. Data managers worked with stacks of paper that were thousands of pages high, and their tool kit would typically include Post-It notes, pens, and a ruler. Regulatory guidelines from the time were based on paper-based processes and were only updated in recent years to include digital processes.

The entire process was slow, error-prone, inefficient, and not scalable.

The Transformation from Paper to Digital

By the mid-1990s, the transformation from paper to digital systems began, followed by web-based solutions a few years later. In the late 1990s, the first sophisticated electronic data capture (EDC) systems from Medidata and Oracle were launched, bringing efficiency, accuracy, and scalability to clinical data management.

Global technology infrastructures and hardware capabilities advanced, and new technology, such as smartphones and tablets, became widely adopted. This meant additional data acquisition technologies—eCOA, ePRO, sensors, imaging, and other eClinical solutions—thrived in the new technology-enhanced world we recognize today.

More recently, AI and machine learning (ML) solutions have been enabled by increasing advances in hardware, leading to advanced automation of study builds, data reviews, and data quality workflows. 

Today, the ability to scale, be efficient, and process at speed has new meaning as more studies are adopting complex methodologies and processing an ever-increasing volume/velocity of data.

Virtualization—The Dawn of a New Era

The clinical trial industry is witnessing a historic moment as we enter the dawn of another new era—the virtualization of clinical research.

Virtualization will redefine how clinical trials are designed, conducted, and analyzed, promising to make clinical research more efficient, cost-effective, and patient-centric as treatments become more personalized. As a result, the clinical data manager’s role will evolve from data custodian to pivotal strategist in leveraging virtual data by employing:

• Virtual assistants: Human-in-the-loop AI virtual assistants to streamline trial processes
• Digital twins: Simulated patients for more precise predictions and exposing fewer real patients to risk
• In-silico clinical trials:  The use of advanced multi-scale modeling and generative AI simulations to run studies that reduce the need for physical trials

Medidata already provides Synthetic Control Arm^® (SCA) and simulant (simulated patients) technologies that meet rigorous regulatory and privacy constraints. In collaboration with the FDA, our parent company, Dassault Systèmes, developed and released a playbook in 2024 that will set the standard for how the FDA evaluates in-silico trial data.

Much as James Lind defined clinical trial practices and changed the future of clinical research, Medidata and Dassault Systèmes are shaping the next generation of clinical trial technology to build a future that eclipses the industry's current advancements.

Learn more about how Medidata has been consistently leading innovation in clinical trial technologies for the past 25 years with our story timeline.

References 

• • 1. 1. Tröhler U (2003). James Lind and scurvy: 1747 to 1795. JLL Bulletin: Commentaries on the history of treatment evaluation
       2. Ibid.
       3. Finding the Cure for Scurvy | Naval History Magazine - February 2021 Volume 35, Number 1