All Monitoring is Risk Based

Contributed by:

Michael Brooks, Senior VP and Head Product Registration, Americas, PRA Health Sciences

NOTE: The content below contains the first few paragraphs of the printed article and the titles of the sidebars and boxes, if applicable.

PV0615_MichaelBrooksDrug developers must introduce innovation across the entire life cycle of product development to more effectively bring new therapies to markets. The innovations will be recognized by the use of smarter and faster methods for discovery of new drug entities and companion diagnostics, use of flexible trial designs, implementation of an end-to-end clinical trial platform, and the successful leverage of business intelligence tools. In particular, clinical trial monitoring will benefit through the design of higher quality protocols and processes, and more effective management of risks to patients, trial endpoints, data integrity, and commercial objectives. Often, risk-based monitoring is recognized as a potential point of innovation within overall trial monitoring.

Evaluation of Risk

Risk-based monitoring is a popular buzz term in our industry, however, all monitoring has been, and will continue to be, fundamentally risk based in nature, regardless of the type of strategy or percentage of source documentation review required. Ultimately, all aspects of clinical trial monitoring begin with the end in mind — protecting patients; delivering high-quality, reliable data; overall compliance with good clinical practice and regulations; and maximizing the value of the drug development investment. Therefore, an adaptive approach to all aspects of the clinical trial process — starting with early protocol development through the entire life of the product development — is the most effective foundation for a risk-based monitoring and trial management strategy.

Beginning with the End in Mind

We believe a data-driven, adaptive approach to risk management and decision making should be applied to all trials, regardless of the source document percentage, monitoring frequency, or use of centralized resources. It is critical to develop the adaptive monitoring approach with the end in mind and then develop a comprehensive risk assessment and data-driven strategy for delivery of the program or trial. Each clinical trial should be evaluated and optimized by adaptive monitoring techniques during, or even before, completion of the final protocol. A variety of factors can influence the overall approach, including:
Study phase and design
Primary and secondary study objectives
Safety profile of product/device
Treatment paradigm and standard of care
Complexity of study-specific requirements
Number of subjects as well as statistical methodologies to reduce sample size
Patient-centric approach for determining country and site placement
Site profile (ie, research naïve, patient care pathways)
Study duration
Geographic regions
Availability of real-time data from the
patient or site
Number of vendors contributing data

Considering the possible combinations of complex factors, it is obvious that risk-based monitoring is not a one-size-fits-all strategy. Therefore, an effective risk-based strategy would encompass a near constant cycle of risk assessment, real-time analytics to detect signals of risk and determine root cause, and adaptive decision making and strategy.

Taking an Adaptive Approach

Through the integration of systems, data, processes, and clinical trial expertise, a clinical trial platform is able to manage the significant volume of trial data and protocol complexity required for effective decision making and timely risk mitigation, yet still provides each client the flexibility to configure the clinical monitoring strategy according to the risk profile of their asset, protocol, or individual company requirements. Specifically, the concept of adaptive monitoring would apply to all services, not just site monitoring — the site monitoring plan would be derived based on quality requirements and statistical methodologies, rather than random sampling or estimated percentages of source document verification; the use of centralized (remote) monitoring for risk/issue detection and resolution would be considered based on a careful assessment of value and the alignment with investigator relations; risks and issues for all sites and services would be managed within global work flows to ensure timely, complete resolution and regulatory documentation.

With an end-in-mind approach to quality, a clinical trial platform should ensure that all clinical trials benefit from use of a wide range of data sources for trial optimization, powerful analytics, and agile decision making, while maintaining flexibility for the overall monitoring frequency, source document verification percentage, or to accommodate a customer’s comfort with less traditional monitoring methodologies.(PV)


PRA Health Sciences is one of the world’s leading global contract research organizations, providing outsourced clinical development services to the biotechnology and pharmaceutical industries.
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