Timing is critical in clinical trials, especially when it comes risk assessment. Earlier risk detection and intervention can prevent significant issues associated with data quality and patient safety, as well as spiraling costs and study delays – a shared understanding that drove the industry’s shift to risk-based monitoring (RBM). The approach’s success, along with advances in clinical trial technology, has led to the adoption of risk-based quality management (RBQM), a methodology that enables clinical trial sponsors and their CRO partners to extend RBM to every aspect of study execution by “focusing on what matters.” But how does RBQM work in practice and what differentiates it from RBM?
RBM is an approach designed to increase the efficiency, safety, and quality of clinical trials by enabling data-driven decisions. In traditional monitoring, clinical research associates (CRAs) check every data point reported by a study investigator against source records, with the goal of achieving 100% source data verification (SDV). However, studies have shown that SDV, a time- and cost-intensive process, does not necessarily ensure data quality. RBM takes a different approach, employing a combination of monitoring strategies, namely a greater reliance on centralized monitoring and statistical assessments, as well as technical capabilities, to guide site monitoring visits. These strategies allow sponsors and CROs to reduce the number of data points CRAs must check against source data on site, which reduces workload and saves time.
The growing complexity, size, and volume of clinical trials, as well as an understanding of the inefficiencies associated with traditional monitoring, led the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) to issue guidance on this topic in 2013. TransCelerate BioPharma followed suit, releasing a position paper followed by an update in early 2014, confirming the limited value of full source data verification (SDV) and outlining an approach for RBM that can be adopted for any type, phase, and stage of a clinical trial. The framework provided tools and triggers to help the industry identify and categorize risks. In 2015, EMA also released ICH Guideline Q9 on Quality Risk Management, offering clear guidance on how to manage a trial from a risk management perspective.
As a process, RBM calls for risk identification BEFORE a study team begins conducing a clinical trial. However, it’s also important to remember that: (1) RBM is a continuous process throughout the trial execution period, used to identify new risks and manage known risks; (2) when thresholds or limits are reached indicating risk activation, changes in the approach to monitoring must be demonstrated.
RBQM, adopted in recent years, takes this a step further, applying the principles of RBM to the entirety of a clinical trial. The methodology uses technology, analytics, and statistics to detect data quality issues in real time, allowing sponsors and CROs to take corrective action before potential issues can impact the integrity of study data. Endorsed by the FDA, the EMA, and the International Committee on Harmonization (ICH), RBQM can be used to help ensure patient safety and the likelihood of a study’s success. By helping researchers identify and focus on data that really matter, RBQM provides a safety net as catalyst to risk management.
RBQM Today: Where Are We Now & What’s Ahead?
Taking a risk-based approach to clinical trial monitoring is, for the most part, well established today. What’s changing is the focus on leveraging this approach for other areas of [clinical trial management such as data management?].. Regulatory authorities are, once again, taking the lead in regard to the change in thinking. In October 2023, the EMA released ICH E8 General Considerations for Clinical Studies, addressing a range of topics, including:
- Ethical considerations, such as informed consent and protection of human subjects
- General principles of good clinical practice (GCP)
- Study design, including randomization and blinding
- Data management and reporting
- Statistical considerations, such as sample size calculations
- Quality control and assurance
ICH E8 emphasizes the need to identify “critical-to-quality-factors,” stressing the importance of each functionality within the study team contributing to this list of factors and helping to manage the risks around them. The paper also points to the need for data surveillance and a focus on issues that could compromise data integrity and/or quality.
For sponsors and CROs, the challenge remains bringing all data sources together and, assuming they can be combined, finding a way to quickly and efficiently assess the data holistically. This is incredibly complex when data is received in different formats and requires some level of standardization.
Additionally, the industry is awaiting the release of ICH E6 (R3). The guidelines cover a range of topics, including:
- Ethical considerations, such as informed consent and protection of human subjects
- General principles of good clinical practice (GCP)
- Study design, including randomization, blinding and allocation concealment
- Data management and reporting
- Statistical considerations, such as sample size calculations
- Quality control and assurance
- Risk-based monitoring
- Electronic and hybrid clinical trial design
- Data integrity
Intended to promote consistency in the conduct and quality of clinical trials, the guidelines facilitate the acceptance of clinical trial data by regulatory authorities around the world. The latest version includes a number of new considerations for the use of electronic data capture and an increased focus on risk-based monitoring, remote and hybrid clinical trial design, and data integrity. Furthermore, the guideline provide more detailed guidance on the role of the sponsor and the study team, as well as the responsibilities of institutional review boards and other ethics committees. Alongside ICH E8, ICH E6 (R3) promises to not only change the way clinical trial data is collected, collated and cleaned, but also the was it is reviewed.
As the guidelines are put into practices, what’s clear is that research teams will need proven analytics tools, which can easily digest data to meet several different needs ranging from RBQM to data surveillance. Let the Bioforum team show you how this can be done effectively without sleepless nights or exorbitant costs.
Contact us to schedule a demo and learn more about the BioGRID platform!
Tali Rahinstein
VP Business Development
New regulations to keep an eye on:
CH E6(R2) is a guideline developed by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) titled “Guideline for Good Clinical Practice.” It provides guidance on the design, conduct, and reporting of clinical trials for the development of pharmaceutical products.
The guideline covers a range of topics, including:
- Ethical considerations, such as informed consent and protection of human subjects
- General principles of good clinical practice (GCP)
- Study design, including randomization, blinding and allocation concealment
- Data management and reporting
- Statistical considerations, such as sample size calculations
- Quality control and assurance
- Risk-Based Monitoring
- Electronic and Hybrid Clinical Trial Design
- Data integrity
The guideline is intended to promote consistency and quality in the conduct of clinical trials, and to facilitate the acceptance of clinical trial data by regulatory authorities around the world. The guideline was first published in 1996 and was updated in 2018, the new version includes a number of new considerations for the use of electronic data capture and an increased focus on risk-based monitoring, Electronic and Hybrid Clinical Trial Design, and Data integrity. The guideline also provides more detailed guidance on the role of the sponsor and the study team, as well as the responsibilities of institutional review boards and other ethics committees.