The latest FDA guidelines on using data monitoring committees (DMCs) in clinical trials call for greater accountability and transparency, whereby sponsors and contract research organizations (CROs) are responsible for establishing strong DMCs and promoting openness and responsibility in operations and oversight. Drug safety monitoring of clinical trials needs to evolve throughout the year to remain effective. Strategic adjustments based on emerging data are required as trials progress into the later quarters (Q3 and Q4). TFS HealthScience (TFS) offers insights on anticipating and addressing the shifts in drug safety monitoring and maintaining the highest data quality for decision-making. 

 

Leveraging Decentralized Clinical Trials for Drug Safety Monitoring 

The U.S. Food and Drug Administration (FDA) defines decentralized clinical trials (DCTs) as “trials where some or all of the trial-related activities occur at locations other than traditional clinical trial sites” and supports decentralization to improve clinical trial participation. While traditional clinical trials rely on a physical site for trial-related activities, some or all DCT activities take place closer to the participant, e.g., at home or a community healthcare facility, to improve participation and retention. The burdens of participating in a traditional clinical trial, such as personal, physical, cognitive, and economic burdens, reduce the likelihood that willing individuals participate. These burdens are compounded for underrepresented communities of lower socioeconomic status. 

Both traditional clinical trials and DCTs must report study-related safety events. The FDA draft guidance on DCTs for drugs, biological products, and devices released in May 2023 includes recommendations on the design of DCTs, the conduct of remote trial activities, roles of sponsors and investigators, investigational product (IP) considerations in DCTs, and safety monitoring in DCTs. Together with the FDA draft guidance on digital health technologies (DHTs) for remote data acquisition in clinical investigations published in December 2023, these documents facilitate the decentralization of trial-related activities and allow data acquisition directly from participants.

A recent study on the opportunities and challenges for DCT from a health technology assessment (HTA) perspective interviewed representatives from European HTA bodies. Respondents recognized the opportunity of DCTs to reduce recall bias as patient-reported outcome data is collected more frequently and in a setting reflective of everyday life (potentially from a more diverse participant population) and its potential to increase the generalizability of results. 

 

TFS Insights on DCT & Safety Monitoring 

A comprehensive DCT solution built from an ecosystem of tools, people, and processes allows patients, sites, and sponsors to participate, contribute, and monitor DCTs. Programs like Medidata’s DCT program provide for the remote capture and monitoring of participant data, which is particularly beneficial as trials progress and expand geographically or need to adapt due to external factors like public health concerns or regulatory changes. This technology supports a flexible trial structure, enabling sponsors and contract research organizations (CROs) like TFS HealthScience (TFS) to manage trials more efficiently by reducing the need for on-site visits.

Sponsors and CROs may face varying recruitment rates or regulatory requirements as trials progress into Q3 and Q4. The FDA DEPICT Act requires diversity action plans to improve enrollment of participants from underrepresented populations. As envisaged by the FDA, DCTs can improve diversity by enhancing trial participant convenience, reducing caregiver burden, expanding access to diverse populations, and improving trial efficiencies. Using Medidata’s DCT program, TFS ensures continuous trial progress even when in-person visits are restricted, thus maintaining momentum towards end-of-year regulatory or study deadlines​.

In DCTs, an advantage of using DHTs is the continuous monitoring of participants, which enables the flagging of safety issues and adverse events (AEs) in real-time and a timely response. Clinical trials are evolving to integrate real-world data (RWD) sources like wearables, medical devices, and electronic health records (EHR). Incorporating RWD presents a level of complexity that relies heavily on a robust data science infrastructure6, such as the Medidata DCT program. 

 

Safety data management 

Regulatory submissions and safety monitoring require accurate and reliable data, made possible by robust clinical trial data management systems. TFS has the added advantage of access to a comprehensive data surveillance and risk monitoring tool that improves data quality and promotes patient safety.  

 

TFS Insights on Automated Safety Data Management 

Medidata’s Rave Safety Gateway automates the collection, tracking, and transmission of AE and Serious Adverse Event (SAE) data using the industry-standard E2B file format, which expedites the receipt of clean, timely data by safety teams. By integrating this tool, TFS streamlines the safety data management process and enhances the efficiency of safety data collection and reporting. Towards the later stages of a trial, the volume of safety data often increases as more participants are enrolled and more prolonged exposure to the IP has taken place. The automated collection and transmission of safety data ensures timely and accurate safety reporting, which is crucial in Q3 and Q4 when sponsors and CROs prepare for year-end regulatory submissions and analyses. 

 

Oversight and risk management 

Clinical monitoring solutions help keep clinical trials on track and mitigate risk. Strategic monitoring plans include on-site monitoring, while remote monitoring includes remote monitoring visits, off-site data review, teleconferences, and electronic document collection.  

 

TFS Commitment to Data Surveillance & Patient Safety 

In November 2023, TFS announced its strategic investment in Medidata Detect, a comprehensive data surveillance and risk monitoring solution that improves data quality and promotes patient safety in clinical trials. TFS is the first and only CRO to adopt Medidata Detect technology for its clients.

Medidata Detect allows cross-functional teams to perform detailed surveillance of trial data and manage risks proactively. Meanwhile, Rave CTMS is bolstered by Visual Analytics, which enables faster and more intuitive navigation and analysis of trial data, leading to quicker decision-making for patient safety and trial adjustments.

Understanding that drug safety monitoring needs to evolve throughout the year, TFS ensures that strategic, evidence-based adjustments can be made as trials progress. Medidata Detect and Rave CTMS offer robust data oversight and visualization capabilities and help identify trends and anomalies quickly as data accumulates. In Q3 and Q4, when decisions about continuing, modifying, or stopping certain trial arms are critical, TFS provides sponsors immediate access to clear, actionable data visualizations to support timely strategic decisions. 

 

Adaptive Trial Designs 

Global clinical trials constantly evolve as traditional clinical trial designs have constraints in accommodating complex emerging research questions. Adaptive trials allow for prospective modifications, e.g., adaptation of endpoint selection based on the accumulating data in a trial. The FDA, observing the increasing adoption of adaptive trial designs, acknowledges that trial designs are becoming more flexible. The 2024 FDA draft guidance on data monitoring committees provides advice for integrating data monitoring committees into these changing clinical trial structures. 

Adaptive trial designs require changes as the trial progresses, especially in response to safety data collected. With growing interest in such trial designs, Pang et al. observe that challenges to drug supply chain management may offset the benefit of adaptive designs. The authors call for developing a tool to facilitate decision-making and analysis of drug supply chain planning. The automation of supply and logistics management has enabled studies to include more diverse participants worldwide. 

 

TFS on Leveraging Adaptive Trial Designs 

A Randomization and Trial Supply Management (RTSM) system regulates patient randomization, automates IP supply and resupply to sites and direct-to-patient (DTP), and manages medication dosage and dispensing. Medidata’s RTSM systems allow for rapid treatment assignments and dosing modifications based on emerging data. Rave RTSM is the only fully pre-validated RTSM solution that can be configured in minutes and enables mid-study changes with minimal downtime. RTSM is built on Rave EDC (electronic data capture), so there is no double data entry and minimal reconciliation expediting study start-up and study close-out.

Adaptive trial designs and RTSM systems are particularly beneficial as they allow for dynamic adjustments to the trial based on interim data. For example, if initial results in Q3 suggest modifications to dosing or participant allocation are necessary, Medidata’s RTSM systems can facilitate these changes swiftly and compliantly. This flexibility is critical to optimizing trial outcomes and ensuring robust data collection as the trial nears completion. 

 

Drug Safety Monitoring & Strategic Adjustments in Clinical Trials 

By leveraging the advanced technologies described, TFS can ensure that our customers’ clinical trials are conducted with the highest safety and efficiency standards, adapting in real-time to changes and maintaining robust data integrity and participant protection throughout the trial’s lifecycle.

At TFS HealthScience, we understand the key trends shaping our shared future as partners in clinical research. Would you like more information on our related services and resources? Contact us today to start the conversation!