How One CRO Uses RBQM in DCT Implementation

Marina Acosta Enslen

Due to the timing of the industry’s gradual shift towards more decentralized clinical trial (DCT) models, when COVID pushed trials outside of the sites, Rho was already positioned to quickly adapt and narrow its focus towards the development of technological solutions that capture efficient and high-quality data in a virtual setting.

To seize the right opportunities, we have had to remain flexible in our approach. This adaptability is the driving force behind Rho’s development of a robust Risk-based Quality Management framework (RBQM). The customized framework has allowed many sponsors to navigate and implement decentralized solutions for their clinical trials and programs. While focusing on potentially critical risks, the framework helps you identify the right monitoring strategies for your trial. Rather than spending more time and money on-site, the streamlined approach provides the most value without sacrificing data quality.

Due to the ICH E6r2 requirement of sponsors (or CRO delegates) to implement quality risk management of clinical trials, it is more important than ever to direct our attention towards highly effective technology advancements. A federally registered revision to ICH E6 (R2) makes explicit the responsibility of the sponsor to understand and actively manage the risks to quality in clinical trials using a Quality Risk Management (QRM) approach.

Based on our experience helping sponsors navigate and implement decentralized solutions for their clinical trials and programs, we believe that the best decentralized solutions are patient-centric, customized and rooted in a robust Risk-Based Quality Management (RBQM) framework. Rho’s methodology was developed in partnership with a consultant from PharmaInitiatives and is derived directly from ICH E6R2. Other tools Rho used to develop its RBQM framework included resources and tools available from Transcelerate and the Metrics Champion Consortium, now part of the WCG Avoca Group.

The following are considerations for successfully implementing effective decentralized solutions:

1. Risk Analysis
2. Patient Centricity and Study Logistics
3. Technology
4. Continuous Assessment
5. Updating Study Plans/Protocols

Risk Analysis—A formal risk analysis is the foundation for implementing a decentralized solution. A data driven RBQM process that allows you to identify and evaluate risks early, monitor those risks and provide insights to adjust throughout your trial is essential. A robust RBQM process led by an experienced CRO will help determine the type of decentralized solution needed for your clinical trial (e.g., fully virtual or hybrid). It will also help you make decisions around the most appropriate use of monitoring strategies, including risk-based monitoring, central monitoring, off-site monitoring, and targeted source data verification (TSDV), as well as provide insight into other critical considerations for subject safety and data integrity.

Patient Centricity and Study Logistics—The patient must be the central focus of any decentralized solution. This includes considerations for safety, engagement, and study logistics. When clinical sites are closed and/or travel to sites is a burden to patients, it’s important to consider the following:

1. Telemedicine Visits—Many of our sites have implemented telemedicine visits to evaluate subject safety throughout a decentralized trial. In a telemedicine visit, the clinical site staff connect with the patient via phone or web conference to assess new and/or ongoing adverse events and any changes to the patient’s medications.
2. Lab Draws—It is important not to overlook a local laboratory as an option for certain blood collections. Allowing a patient to have blood draws done at a lab closer to his or her home, can reduce patient burden. We have also partnered with a vendor that provides the patient with the ability to collect blood, urine, saliva and stool samples in their own home and send it directly to the lab for analysis.
3. Direct to patient (DTP) Investigational Product (IP) shipments—We have developed strategies for the dispensation of IP, such as home delivery or use of courier services for shipment of IP directly to patients’ homes. To ensure IP maintains a specific temperature in transit, our shipping partners use a controlled temperature shipper and a temperature tracking device.
4. Off-Site Monitoring—We have implemented many types of off-site monitoring processes to meet the needs of specific decentralized clinical trials. These solutions have included customized approaches to and levels of risk-based monitoring, off-site monitoring and targeted site data verification (TSDV). The right combination of these solutions for your clinical trial will depend on the risks identified in the RBQM process, along with the status of your clinical trial or program (e.g., a new study that has not begun yet versus a study that has been on-going and needs to implement a decentralized solution partway through), and the level of access to your clinical sites.
5. Centralized Monitoring and Data Visualization—Remote evaluation of clinical data (e.g., centralized monitoring) is a critical component of any decentralized solution, and it becomes more important as direct access to clinical sites and patients is reduced. Centralized monitoring is used to identify trends in the clinical data, including information pertinent to site management activities and data related to safety events. Our teams have centralized monitoring tools to identify key quality and risk indicators early and monitor them throughout the study to provide actionable and timely insights that will help manage your decentralized clinical trial.

Technology—Technology is a key component of most decentralized solutions. At Rho, we have implemented eCOA and ePRO solutions, along with devices and wearables that capture data directly from patients. Technology solutions have the potential to significantly reduce patient burden and increase patient engagement if implemented properly. It’s important to map out a strategy early in the process, which includes robust plans for site and patient training. It’s also important to ensure that the CRO you are working with has developed strong partnerships with any technology vendors they bring to the table.

Continuous Assessment—The conditions at research sites and patient availability have rapidly shifted over the last few years. Therefore, it is even more important to have a decentralized approach that is grounded in a robust RBQM framework, which can provide data and triggers to determine when a shift in approach is necessary.

Updating Study Plans/Protocols—To document potential changes to your decentralized strategy, make sure to update study plans and protocols throughout your trial or program. Study plans include the project management plan, clinical monitoring plan, and the statistical analysis and data management plans, among others. Updating plans and protocols will ensure compliance and result in reliable data that supports endpoints.

Looking forward, DCTs are here to stay. However, these decentralized solutions are not one-size-fits-all. The right solution for your trial or program should be determined and managed using a robust risk-assessment process, which will identify risks upfront and monitor them throughout to let you know when changes need to be made.

To fully realize all the advantages and benefits of a truly decentralized approach, partnering with a reliable and experienced CRO to implement and execute your decentralized solution is critical. While there are no set guidelines to define the future of clinical trials, our industry is at a unique point with boundless opportunities to craft adaptable solutions that best serve our patients.

Marina Acosta Enslen, Director, Clinical Management, Rho