#23 Practical RWE – Monitoring


Clinical trial regulations and ICH GCP require that clinical trials be monitored at an intensity proportionate to the risks (and potential risks) posed to the research participants.

The purpose of the monitoring in the context of clinical trials?

  1. Verify that the rights, safety and well-being of subjects are protected
  2. Verify that the data generated in the clinical trial are accurate, complete, and verifiable from source documents (= reliable and robust).
  3. Verify that the conduct of the trial is in compliance with the currently approved protocol/ amendment(s), with GCP, and with the applicable regulatory requirement(s).

[as per §5.18 of ICH GCP (R2), Article 48 of Regulation EU/536/2014, and 21 CFR §312.53]

What about the monitoring requirements for non-interventional (observational) studies?

Very few countries provide guidance on the expectations and standards for monitoring of non-interventional studies. However, according to the 2023 FDA Guidance, study monitoring is one of the principal quality control activities critical to ensuring that:

  1. The study is conducted according to the protocol
  2. Data submitted to FDA are reliable
  3. Data are appropriately protected

For non-interventional studies, monitoring should begin at the data extraction from RWD sources and focus on the protection of human subjects, as applicable, and on maintaining data integrity (= the completeness, consistency, and accuracy of data).

As part of study monitoring of a non-interventional study, sponsors should, at a


  1. Ensure that the RWD required by the protocol are accurate and consistent with the

source records

  1. Ensure that prespecified plans (e.g., SAP), protocol, and study procedures (e.g., for

curation and transformation and reporting of results) were followed

  1. Ensure that deviations from the prespecified plans and protocol and study procedures are identified and documented, and when necessary, promptly evaluated and remediated according to the significance of the deviations that have been identified

[FDA Guidance – Considerations for the Use of RWD and RWE To Support Regulatory Decision-Making (Aug 2023): https://www.fda.gov/media/171667/download]

In conclusion, monitoring in non-interventional studies involves verifying that appropriate consent has been given, verifying the consistency of RWD with source records, ensuring adherence to predetermined plans and study protocols, and effectively managing deviations. This approach reflects an overarching commitment to the protection of research participants and the integrity of the data in research, irrespective of the study design.

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