Medical Monitoring Risk Exposure in New Regulatory Climate


Applied Clinical Trials

In this article, we will discuss trends and challenges with medical monitoring clinical analytics, analyze the alignment of existing medical monitoring tools and technologies with ICH-E6 (R2) addendum guidelines, and discuss trends in medical monitoring insourcing and outsourcing models.

In a previous interview with medical monitors, we discussed how the lack of data aggregation and the use of manual processes in medical monitoring can introduce the potential for errors and missing safety signals. Additionally, this interview elaborated on how the lack of workflows with existing medical monitoring tools make the entire process highly inefficient. In this article, we will discuss trends and challenges with medical monitoring clinical analytics, analyze the alignment of existing medical monitoring tools and technologies with ICH-E6 (R2) addendum guidelines, and discuss trends in medical monitoring insourcing and outsourcing models.

Trends and Challenges in Medical Monitoring Clinical Analytics

1. Increase in Data Sources and Data Aggregation Requirements: Clinical trial data sources are growing in complexity and are becoming more discordant. For example, with increased trends in outsourcing, clinical data exists in a variety of databases and in differing formats, such as ePRO data, data in EDC, and now with the introduction of digital data programmed in wearables and eDROs

2. Expanding Complexity in Safety Data: In both clinical trial and post-marketing settings (especially with FDA’s active post-marketing surveillance programs), the complexity of safety signals is expanding, as safety data is arising from electronic medical records, claims data, and social media data.

3. Increased Regulatory Scrutiny: With the release and FDA’s adoption of the ICH-E6 (R2) addendum, sponsors are now encouraged to enhance patient safety through leveraging technologies and advanced analytics to track and execute clinical trials; for medical monitoring, this means detecting safety signals, tracking the resolution of those signals and generating an audit trail including which personnel reviewed the data and what actions have been taken.

4. Cost of Technology: Customizing internal technology infrastructures to comply with new ICH E6 (R2) addendum guidelines is an expensive feat. However, specialized medical-monitoring cloud-based technologies offer quick and cost-effective solutions.

How Medical Monitoring Fits in to ICH E6 (R2) Addendum’s Section 5.0 on Quality:

The ICH E6 (R2) addendum contains many sections that can apply towards medical monitoring; in this article, we will focus on section 5.0 (Quality), as much of this section applies towards enhancing quality and improving patient safety through efficient technologies. Table 1 details how section 5.0 can be applied towards medical monitoring.

Table 1: Interpretation of ICH E6 (R2) Addendum on Medical Monitoring in Section 5.0


ICH E6 (R2) Addendum Abbreviated Description

How Medical Monitoring Technology Complies with ICH E6 (R2) Addendum

5.0.1: Critical Process and Data Identification

Sponsor should identify processes and data that are critical to ensure subject protection and reliability of trial results.


Specific safety data points can be identified, and workflows can be defined using medical monitoring technology.  

5.0.2 Risk Identification


Sponsor should identify risks to critical trial processes and data. Risks should be considered at both the system level (e.g., standard operating procedures, computerized systems, and personnel)

On a systems level, medical monitoring technology incorporates workflows that define how safety signals are detected and resolved and contains user-specific information for tracking actions through the safety signal resolution process.

5.0.3 Risk Evaluation

Sponsor should evaluate the identified risks against existing risk controls by considering:

(a) The likelihood of errors occurring.

(b) The extent to which such errors would be detectable.

(c) The impact of such errors on human subject protection and reliability of trial results.



Using medical monitoring technology with pre-identified safety risks can help with easily identifying signals, which reduces signal detection oversight/errors.  Moreover, medical monitoring technology has visualizations that can assist medical monitors with efficiently detecting and resolving new and unexpected safety events.  This enhances subject safety and study data quality.

5.0.4 Risk Control


Sponsor should decide which risks to reduce and/or which risks to accept. Predefined quality tolerance limits should be established. Detection of deviations from the predefined quality tolerance limits should trigger an evaluation to determine if action is needed.


Medical monitoring technology can be incorporated in RBM plans to define KPIs/KRIs and set electronic triggers for safety events that deviate from risk tolerance limits, and customized workflows can address, track and resolve detected safety signals.

5.0.5 Risk Communication


Sponsor should communicate and document quality management activities.

Medical monitoring technologies can track the detection of safety signals through resolution (i.e., which users reviewed what data and their actions) and include an audit trail for efficient analysis during audits and safety report creation.

5.0.6 Risk Review


Sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience.


Sponsors can easily optimize risk triggers in medical monitoring technology based on accumulating study data.

5.0.7 Risk Reporting


Sponsor should describe the quality management approach implemented in the trial and summarize important deviations from the predefined quality tolerance limits and remedial actions taken in the clinical study report.


Through facile reporting, medical monitoring technology enables sponsors to describe the process of safety signal detection through resolution, and document all decisions and remedial actions for individual safety events, or events in aggregate.

Leveraging medical monitoring technology in clinical trials essentially enhances subject safety signals detection and efficiency by (a) facilitating safety signal detection through clinical analytics, (b) enabling sponsors to enhance oversight by understanding how safety events are tracked and processed, and (c) supporting metrics driven decision-making and risk-based monitoring in accordance with the ICH-E6 (R2) addendum.

Hybrid Outsourcing Models for Medical Monitoring

It is the norm for sponsors to outsource medical monitoring functions to CROs or medical monitoring partners. However, with the release of the ICH-E6 (R2) addendum, it is expected that regulators will be more stringent on sponsors to demonstrate sufficient oversight of safety events, and while current oversight plans are adequate, regulator expectations will change as technology continues to evolve. To elaborate, regulators will likely expect sponsors to demonstrate how sponsors are able to oversee safety signal data through technology-based workflows, and how the sponsor interacts with vendors to ensure safety signal detection and resolution. Some sponsors are moving towards hybrid models, where they are outsourcing clinical operational functions to CROs and vendors, but, are insourcing medical monitoring review through the use of medical monitoring technology. This hybrid approach enables sponsors to effectively collect data, while efficiently identifying and resolving safety signals from numerous clinical databases and demonstrate proper vendor oversight.


In summary, the complexity of safety signal detection is increasing with clinical analytics; numerous data sources create challenges with data aggregation, the incorporation of real-world evidence data makes it more challenging to detect safety signals, the changing regulatory environment is creating new expectations for oversight, and the cost of insourcing medical monitoring technology is rising compared to the cost of cloud-based solutions. The ICH-E6 (R2) addendum is encouraging the use of novel technologies, nonetheless, the biopharmaceutical industry is still struggling to find how to best implement medical monitoring technologies. Hybridizing the outsourcing model by insourcing medical monitoring and using cloud-based medical monitoring technology to detect and resolve safety signals is an optimal approach towards demonstrating proper vendor oversight, complying with ICH-E6 (R2) addendum recommendations, and efficiently enhancing subject safety and risk detection and resolution through clinical analytics.


Moe Alsumidaie, MBA, MSF is Chief Data Scientist at Annex Clinical, and Editorial Advisory Board member for and regular contributor to Applied Clinical Trials.

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