The importance of ALCOA++ principles in Pharmaceutical Regulatory Affairs

It is well-established that researchers conducting clinical trials systematically collect, store, and process large volumes of data from diverse sources.

As a result, in recent years, computerized systems and electronic data have been used increasingly in clinical trials.

The EMA has released a revised guideline, EMA/INS/GCP/112288/2023, replacing the “Reflection Paper on Expectations for Electronic Source Data and Data Transcribed to Electronic Data Collection Tools in Clinical Trials (EMA/INS/GCP/454280/2010).”

This guideline has been in effect from October 2023 and provides a framework to help ensure the integrity, reliability, and regulatory compliance of systems and electronic data by describing applicable principles, key concepts, and requirements for computerized systems.

It serves as a comprehensive guide, covering everything related to the use of any type of computerized system in clinical trials. It also offers a holistic view of electronic data.

This blog focuses on the ALCOA++ principles, providing an overview of the general concepts that must be considered when managing clinical data. The guideline includes considerable detail on how to adhere to or achieve these principles within the clinical trial process.

The ALCOA++ principles consist of ten attributes that are universally important in data management - data should be attributable, legible, contemporaneous, original, accurate, complete, consistent, enduring, available when needed, and traceable.

These principles provide a straightforward set of rules to follow when managing data for clinical trials.

Attributable - it should be possible to trace it to the person or system that generated the data. Depending on the data's criticality, the guideline suggests that it should be possible to trace the data to the device used to generate it.

Crucially, information regarding this traceability, such as the system operator, data originator, and system used to generate the data, should be kept as part of the metadata. Metadata provides context for the generated data points.

The guidelines point out that loss of metadata may result in a lack of data integrity and may render the data unusable and unattributable. This focus on traceability goes beyond attributing data to a person or system, making it a highlighted principle.

It is important that data are traceable throughout their life cycle, meaning any changes to the data or metadata should be traceable, should not obscure the original information, and should be explained.

Changes should be documented as part of the metadata.

Legible, the information must be maintained in a readable form, allowing review in the original context. The guideline indicates that changes to the data, such as compression, encryption, and coding, should be 100% reversible.

Contemporaneous, the guideline states that data should be generated or captured at the time the observation is made. The time the observation was made and the time the data was stored should be kept as part of the metadata.

Recording the required time points should be automatic and linked to an external standard.

Originality is a simple principle, meaning that the data should be the first capture of the observation, and only certified copies should replace the original.

Accuracy is another self-explanatory principle. The guideline emphasizes that the use of computerized systems should ensure that the data are at least as accurate as those recorded on paper, and any data transfers between systems should be validated to maintain accuracy.

Maintaining accuracy relies on the maintenance of metadata, which should contain information to describe the observations.

Closely tied to accuracy, data should be complete and consistent so that a clear, full picture can be obtained to fully understand an observation.

This includes the associated metadata and audit trail. Processes should be in place to ensure consistency in the definition, capture, and management of data throughout its life cycle, so there are no contradictions and a clear picture of what was observed can be achieved.

Data should also be available when needed throughout the whole life cycle. To achieve this, data must be enduring and maintained appropriately to remain intact from the beginning to the end of the lifecycle. To aid in this, the guideline provides information on backing up and archiving data.

While discussed here in the context of the guideline on computerized systems and electronic data in clinical trials, ALCOA++ principles can be applied in all pharmaceutical regulatory affairs settings to ensure data integrity.

Ben Torrens is a Regulatory Executive at G&L Healthcare Advisors.