January 23, 2024

4 Questions to Ask When Developing a Monitoring Strategy for a Complex Clinical Trial

When it comes to clinical operations, one of the core functions of monitoring is to prevent research site compliance issues and quickly identify them when they do occur. ClinOps leaders bear primary responsibility for spearheading the monitoring plan for a trial, implementing new monitoring approaches, and more. 

But in today’s landscape of complex trial designs and biospecimen plans, monitoring can be a daunting task. Study complexity demands innovative monitoring solutions — but in order to determine what those solutions are, it’s important to evaluate what exactly makes monitoring today’s trials so difficult in the first place.

What Do ICH GCP Guidelines for Clinical Trials Say About Monitoring?

Clinical trial sponsors widely consider ICH GCP guidelines to be the gold standard for dictating study conduct. As such, clinical operations leads should consider their framework for clinical trial monitoring when formulating a robust monitoring plan.

Per ICH GCP guidelines, the purposes of trial monitoring are to verify that:

  1. The rights and well-being of human subjects are protected.
  2. The reported trial data are accurate, complete, and verifiable from source documents.
  3. The conduct of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and with the applicable regulatory requirement(s).

So what does this look like in practice? 

Protecting the rights and well-being of human subjects is about more than safeguarding patient confidentiality — it’s also about treating patients with the dignity they deserve. This means investing in monitoring solutions that minimize patient burden and treat patient samples as physical extensions of the patients themselves. Study stakeholders should be handling biospecimens with the utmost level of dignity, precision, and care, and proactively mitigating any sample mishandling risks that could jeopardize a patient’s experience on a trial.

Sponsors also care about data integrity, and understandably so — after all, poor data quality is a significant contributing factor to the 90% failure rate for drugs progressing through development phases to a launched product. When sponsors ensure that research sites and labs are abiding by the correct sample collection and sample handling procedures, they in turn safeguard the accuracy, completion, and verification of their trial data. When data integrity reaches its full potential, clinical trials are more nimble and successful.

A robust monitoring strategy should also facilitate compliance with current versions of study documents (including the protocol), with GCP, and with regulatory requirements. For sponsors, this not only means having a streamlined implementation strategy for protocol amendments and study modifications across various research sites, but it also means maintaining a real-time audit trail for every single sample. 

What do all of these principles have in common? All three of them tie back to research site activity, proper handling of patient samples, and the data tied to those samples. 

How Does Complex Clinical Trial Planning and Design Affect Centralized Monitoring?

If patients, data integrity, and regulatory compliance are critical to sponsors, then how do clinical operations personnel ensure that monitoring plans are up to snuff with the challenges of managing complex clinical trials? 

As a result of study complexity, site personnel become more susceptible to accidental oversights and delays when managing lab kits and patient samples on trials that involve high sample volume; complicated sampling schemes; frequent study modifications; multiple arms, cohorts, stages, and substudies; several vendors; and more. 

GCP guidelines now encourage sponsors to incorporate centralized monitoring into their monitoring plans, especially given the increase in scale and complexity of clinical trials. 

The guidelines state that reviewing and analyzing accumulating data from centralized monitoring can offer many benefits, including the ability to:

  1. identify missing data, inconsistent data, data outliers, unexpected lack of variability and protocol deviations.
  2. examine data trends such as the range, consistency, and variability of data within and across sites.
  3. evaluate for systematic or significant errors in data collection and reporting at a site or across sites; or potential data manipulation or data integrity problems.
  4. analyze site characteristics and performance metrics.
  5. select sites and/or processes for targeted on-site monitoring.

With today’s trials at a heightened risk for deviations, it’s even more important for sponsors to identify research site compliance issues as soon as they occur. Sponsors should also analyze site-specific and study-wide non-compliance trends that can be remedied with site retraining, study modifications, and more. 

Unfortunately, complex studies depend on multiple disparate systems and vendors, making real-time sample tracking incredibly challenging. Not only do sponsors have to manually piece together biospecimen data by communication with other study stakeholders and performing searches across various clinical systems, but access to this data is often delayed, making it nearly impossible to identify research site compliance issues that demand immediate attention until it’s too late.

How Does an Insufficient Risk-Based Monitoring Strategy Impact Research Site Compliance?

Monitoring encompasses more than just identifying issues once they have already occurred; it’s also about proactively preventing the conditions that can lead to protocol deviations. GCP guidelines state that the monitoring plan should be “tailored to…data integrity risks of the trial.”

But without a clinical trial execution strategy that guides clinical inventory management and sample management across research sites, and surfaces important data trends for samples that have already been collected, how can sponsors improve their approach to risk-based monitoring to minimize the occurrence of future compliance issues?

Sponsors should consider risk-based biospecimen monitoring approaches that directly mitigate the complex nuances of today’s clinical trials. For example, if research sites are relying on dense, static lab manual documents to determine how they should collect and manage patient samples, are there alternative solutions that sponsors can implement to ensure that research sites don’t miss a collection, mishandle a sample, or forget to collect an important data point? If a protocol states that sites should only collect a critical biospecimen for a subset of patients at a particular visit, are there mitigating strategies that sponsors can implement to ensure that this sample is collected for the patients that require it, and only these patients? These are the kinds of questions that clinical operations leaders should be asking themselves as they formulate their monitoring plans.

What Study Activities Should Sponsors Monitor to Ensure the Data They Receive Reflects the Trial They Designed?

Novel monitoring approaches should include a more robust strategy for managing the entire biospecimen lifecycle — from the moment a sample is collected, until it is discarded or stored at a biobank. 

To learn more about how Slope can augment your biospecimen monitoring strategy and enhance research site compliance with your protocol, check out our white paper on de-risking your clinical trial data by turning your static lab manuals into software-guided workflows.

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