Data Integrity Challenges in the Scope of Clinical Trials – Part 1

Global collaboration between regulatory agencies and health authorities became of paramount importance during the COVID-19 pandemic. Not only allowed it regulators to continue their inspections and surveillance function, but the cooperation also enabled the rapid development and approval of treatments and vaccines against the coronavirus SARS-CoV-2.

Although the level of international collaborations increased greatly over this period, it is not a new subject and will definitely remain to enable regulators to adapt to evolving technologies in drug development, but also to streamline inspections worldwide, as Peter Marks, director of FDA’s CBER, stated in the lead-up to RAPS Convergence 2021.

Amongst a plethora of such international joint efforts, the bilateral FDA-MHRA GCP collaboration established that it will discuss, in the form of annual workshops, the agencies’ perspectives in respect to Data Integrity (DI) in clinical trials. The first workshop took place in 2018 and the latest one, held in February 2020, just had its summary article published. The main topics during this workshop were revolving around Data Governance and Data Integrity with a focus on novel trial paradigms, usage of eSource and Electronic Health Records (EHRs), protocol deviation management, and sponsor oversight. The agencies also shared their collective experiences from clinical trial inspections in the form of case studies with findings on these topics.

With the aim of focusing on key DI challenges from a computerized systems compliance perspective, we summarize below the main topics discussed during this meeting and how they align with current regulations and guidance.

Ensuring Data Quality and Integrity in novel Clinical Trial Designs

Decentralized Trials

The COVID-19 pandemic has accelerated the adoption of decentralized trial (DCT) components into ongoing clinical trial protocols to mitigate disruption to clinical trial conduct. When deciding to conduct a DCT or hybrid trial, the regulators advise the trial sponsors to consider the following points:

  1. The study population
  2. The disease state of the study population: Is the study population stable enough to participate in a trial with remote components?
  3. Suitability of the study endpoints for remote data collection
  4. Suitability of the Investigational Product (IP) for direct shipment to trial participants, after considering the risk, logistics, and local legislation parameters

To ensure DI during the conduct of the trial, especially for DCTs, it is important to establish proper procedures. These should pertain to robust data collection, handling and management, and having a good understanding of the data flow when using eSystems. Sponsors should proactively monitor the usage of eSystems and address DI issues as they, and not the vendors, are ultimately responsible for collecting, maintaining, and retaining the patient-generated data. To that end, it is deemed critical to establish good technical support for the eSystems in use, as it can support the DI monitoring efforts as the first line of defense in the technical bug, validation issues, or error detection. Furthermore, sponsors but also investigators should be able to demonstrate trial oversight at all times, which can be achieved by effectively retaining all records and communication regarding the study.

Adaptive Design Trials

For trials that are designed upfront to be adaptive (i.e. frequent modifications to the trial’s course in accordance with pre-specified rules), one major challenge to both DI and patient safety is to ensure that the study personnel is always informed and up to date in respect to the changes but also to effectively manage the changes within the given timeframe, which could require additional resources.

The regulators point out that in this context, the main pillars for ensuring DI are robust change control processes and a well-documented risk assessment for the pre-specified protocol changes, with regular updates on key safety and efficacy data. Processes and procedures should be established to document key decisions regarding modifications in the design of the trial, to an extent that will allow reconstruction of the trial conduct by inspectors.

Stay tuned because Part 2 will include the topics of eSource Data and EHRs.

Remember, if you need any support on dealing with the topics mentioned in this article, please reach us today for a conversation.

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