Setting the Scene: Addressing the Increased Complexity of Phase I Clinical Trials with EDC Systems

This blog was authored by Katrina Weigold, Vice President of Global Partners at Medidata. Katrina has grown and cultivated global partnerships at Medidata for over a decade, expanding the reach of the company’s transformative platform for clinical development, commercial, and real-world data.

There are many factors that make early-phase clinical trials, including Phase I trials, particularly unique and complex. These factors can sometimes lead to additional challenges for sponsors and partners to navigate, including delays and increased trial costs.

The pandemic certainly added new barriers to tackle and forced companies to adapt and execute these early-phase clinical trials with greater agility and efficiency. The unprecedented environment the industry found itself in demonstrated the increased value of clinical trial technology to address some of these challenges. It also highlighted the importance of working with trusted partners, who bring extensive experience and a track record of adapting to changing circumstances without compromising data quality, security and privacy, and patient safety.

What Makes a Phase I Clinical Trial Unique?

Recruiting Healthy Volunteers

Phase I trials typically involve testing healthy volunteers (except in cancer trials), not patients suffering with the condition or disease that the new treatment is being investigated for. This is because the objective of Phase I trials is to test the safety of the drug, not if the drug works against the disease, as well as to determine the appropriate dosing. In a Phase I clinical trial, investigators are looking at two things—the pharmacodynamics (PD), which is the body’s biological response to the drug and what impact it actually has molecularly, and the pharmacokinetics (PK), which is the movement of the drug through the body. The focus here is on safety, whether the drug has any serious side effects, and what the safest dosing level is. 

Given this is the first in-human experiment of the drug, it can be difficult to recruit patients; there’s a certain amount of risk involved which could deter individuals, as well as a time commitment. In early-stage studies, patients are motivated by the desire to do good in the world and contribute to life-saving clinical research, and/or a financial incentive. Alongside financial reimbursement, patients might be asking themselves: how convenient is this for me? How intrusive is this going to be? How uncomfortable are the procedures going to be? This is why education and patient engagement are key at this early stage. 

In later-stage trials, patients are also incentivized by the fact that they have the condition or disease being tested and these trials could be a cure or even a ‘last resort.’ Key trial stakeholders need to think about how to lower the burden for patients and keep the focus on them at the center of decision-making; this is true at all phases of a clinical trial. Taking a patient-centric approach to clinical research has become an imperative. These mutually-beneficial partnerships with the patient community will transform both the future of research and development and the healthcare industry at-large.

Obviously recruiting and enrolling new patients into trials during the pandemic was one of the toughest barriers faced by the industry. Medidata was continuously tracking these numbers in its COVID-19 white paper and noted, in June 2020, a global 74% decrease in the average number of new patients entering trials per study-site in May 2020 compared to the same period the previous year. In Medidata’s survey of over 1,000 site personnel, the biggest impact of the pandemic was noted as ‘ability to enroll patients’ and ‘ability to recruit patients’. Using insights gained from this ongoing research, Medidata was able to advise and support sponsors and partners in their trial design and/or necessary trial protocol amendments. 

Small in Scale and Specialist

Phase I trials generally recruit 20-80 healthy patients. They are usually conducted in person since patients need to be monitored closely and remain on site to track any and all symptoms and regularly measure vitals, as this is the first time the drug is being tested in humans. These trials will often engage specialist Phase I clinical trial units, whereas Phase II and III studies can be moved out into more general clinical settings. These specialist units are typically private and may be attached to a hospital—it’s imperative to have access to emergency services, should anything go wrong. So there’s a need to carefully identify and negotiate with these sites, which can sometimes be an added challenge early on. 

During the pandemic, this was a major barrier for early-stage trials as most staff at hospitals were pulled from clinical trials and into treating COVID patients. Additionally, non-urgent cases and visitors were not allowed into hospitals at the peak of the pandemic and healthy volunteers in an early-stage trial would typically fall into that non-urgent category.

Most sponsors and partners were left with two options: delay or close the Phase I study, or adapt the study and tighten up the procedure. During this period, Medidata was helping its sponsors and partners adapt their trials in this new, difficult environment. Solutions like Rave EDC (electronic data capture) and Rave RTSM (randomization and trial supply management), for example, were able to support accelerated study start-up, direct-to-patient supply management, and any necessary site transfers. 

Low Budget, Short Timeline

Given the small scale, the budget for early-stage trials is inherently much lower than for later-stage trials, which involve more patients and endure longer timelines to meet their clinical objectives. The timelines are also shorter—usually weeks or months compared to years for the later stages.

However, when comparing the cost-per-patient during the conduct of the trial, early-stage trials are typically more expensive due to the close on-site monitoring. Usually, fewer virtual and/or remote solutions are available at these early stages. This is why it is crucial for pricing and configuration of the solutions and technologies that are available at this stage, like EDC, to match the needs and budget of the study. 

Why Are Phase I Clinical Trials Important?

Phase I clinical trials are important because they can set the tone for the rest of the drug development process. A successful and smooth (on time, on budget) Phase I trial means a sponsor and partner can move into Phase II with confidence in the safety profile and dosing level. It sets the study team up nicely to be able to start looking at the efficacy of the drug.

How Can EDC Systems Support Early-Phase Clinical Trials?

Digital tools, like EDC, can have a big impact in these early-stage trials. Leveraging these tools earlier will position successful drugs to rapidly move into the next phase, giving studies a head start compared to the competition.

Rather than manually or disparately monitoring a small group of healthy volunteers via paper or an Excel spreadsheet, EDC allows investigators to shift their focus to the patients rather than on managing data. This is key as patients need close monitoring at this stage. Even though these trials involve a smaller group of patients, the amount of data collected on each individual is still extensive.

EDC systems also enhance data quality through automatic validation checks and query workflows. And should any amendments be necessary, like dosing levels, EDC ensures an audit trail, traceable mid-study changes, and continuous data capture.

While low-tech approaches may have worked in the past for early-stage trials, they become much more cumbersome as more complexity is incorporated and the need for clinical trial technology becomes imperative. As such, sponsors and CROs need to partner with trusted technology providers that have deep expertise and a proven track record in running these early-stage trials.

Medidata delivers tailored, flexible, and cost-effective solutions for small to medium-sized CROs. Supporting over 4,000 Phase I studies for 400 clients over the past two decades, Medidata helps its partners attract and win more sponsor bids and execute them successfully with its proven, innovative technology and unmatched partnership experience. Read more about Medidata’s EDC offering here.