The ALCOA+ Principles for Data Integrity In Clinical Trials

The ALCOA principles guide and model a company’s policies and procedures to help ensure that regulatory compliance is being maintained, and adheres to policies such as GCP and GMP. The ALCOA principles play a critical step in ensuring data integrity and compliance is of an excellent standard.

Data is of the upmost importance and its management is key, especially with the ever-expanding data collection tools available to companies running clinical trials. With these advances in technology and the emergence of AI (Artificial Intelligence) and ML (Machine Learning) and virtual trials, ensuring the integrity of the data is even more important. While the ALCOA principles are relevant due to the ever changing technological demands mentioned, the core requirements are still as applicable as they have always been on more traditional style clinical trials.

Importance of Data Integrity

In the modern era of clinical trials, data integrity and compliance are a vital part of regulatory reviews. Regulatory agencies such as the FDA (US Food and Drug Administration) and EMA (European Medicines Agencies) are always checking for any potential data integrity issues in a regulatory submission. Such issues can compromise the safety and efficacy of a new drug/device and can be a result of a number of reasons, including; human errors, technical issues or malicious acts. Data integrity issues are unlikely to be done on purpose but that does not mean that regulators will be sympathetic to any issues they detect.

A violation will result in receiving a warning letter and consent decrees. There has been an upward trend of warning letters being issued for data integrity reasons, since 2008, it is estimated 80% of the data integrity related warning letters were between 2014 to 2018, which demonstrates the growing focus regulators are looking into data integrity.

What is ALCOA and How It Fits with Data Compliance and Integrity?

ALCOA is a set of principles established by the FDA to ensure data integrity and good documentation practices in the pharmaceutical industry. Developed in the 1990s by Stan W. Wollen, these principles apply to both paper and electronic data. The ALCOA principles help avoid data integrity and compliance issues and provides an audit trail that records additions, deletions, and alterations without obscuring the original records. This audit trail enables the reconstruction of details related to the original electronic record.

ALCOA stands for Attributable, Legible, Contemporaneous, Original, and Accurate. In 2010, the principles evolved to include Complete, Consistent, Enduring, and Available, forming ALCOA+ (also known as ALCOA-C). These additional principles are particularly relevant to clinical data management electronic systems.

By following ALCOA+ principles, organisations can prevent common data integrity breaches such as intentional deletion or manipulation of records, accidental data loss, uncontrolled documentation or failure to record data in real-time. Using electronic data recording systems that restrict access to authorized and authenticated individuals further ensures data completeness, consistency, and security, while also preventing unauthorized disclosure of Protected Health Information (PHI). All data entries and changes are logged, time-stamped, and easily accessible to authorized users at any time and from any location.

Let’s explore each attribute of ALCOA+

The Original ALCOA:   

Attributable:

This refers to how any data that is entered should be easily traced/referred back to the individual who performed the data collection, and the date and time that this was performed.

A good example of this attribute would be clear password and user control settings that ensures everyone has unique credentials, and any electronic systems being utilized has a fully validated audit trail.

Legible:

This attribute ensures that the data in question can easily be read and there is no misunderstanding of the data, additionally this can also refer to the durability of the data, so if a person wishes to view that data in 15 years’ time will it still be legible?

Contemporaneous:

This dictates that the collection time of the data should correspond to the date of the recording of the data.

This is where the audit trails and meta data for all electronic systems are essential to ensure time and date stamps on the data. To ensure compliance you must ensure that time zones and systems clocks are recorded to remove any ambiguity i.e., 23:00 Eastern Standard time would be 04:00 GMT the following day which would cause issues when comparing the date and time of collection.

Original:

Records should be original as opposed to transcriptions or copies of the originals.

All analysis, calculations, summaries or reports based on data provided must be traceable back to the original source, this is why any electronic system being utilized must be fully validated with an audit trail.

All copies of original documentation must be formally verified as a true copy and must be distinguishable to the original, also having a copy does not mean that the original document can be discarded, the original must be preserved.

Accurate:

Records should be deemed as error free and represent the true nature of what has occurred. There should be no amending/modification of the original information that could result in data being discarded or lost.

If an amendment/modification is required, these changes must be documented clearly and concisely so tracing back to the original entry is possible.

When using an electronic system, the technology in question should have built in accuracy and discrepancy checks to assist with the entry, additionally devices being used to capture information must be calibrated.

The additional ALCOA+ principles:

Complete:

This refers to all data being present, nothing should ever be truly removed or deleted. There should always be a record of that data and the audit trail is essential to show all data changes and the time of the change.

Consistent:

Data should be arranged chronologically with clear time and date stamps for any additions to the original record.

Enduring:

Similar to legible, this principle of ALCOA+ is specifically aimed at the durability of data. For example data should be stored in a format that preserves its integrity, quality and readability so it can still be viewed the future regardless of time or determined by regulatory requirements.

While dealing with electronic data, you must ensure that the readability of the data or the hardware used is still relevant and that any system being used has back ups and a full disaster recovery policy in place.

Available:

Data should be accessible whenever needed over the lifecycle of the study.

All storage facilities utilized must be accessible and searchable with applicable indexing and labelling of the records.

Summary

The ALCOA and ALCOA+ principles are so entwined in how we operate in the Pharmaceutical industry with regards to regulatory compliance, quality of data and the integrity of the data. Given the importance of the above principles’ adoption and adherence to these guidelines should be pivotal for any company within the Pharmaceutical world. Quanticate understands this and the importance of adhering to the ALCOA principles and can help ensure that your clinical data and integrity is of the highest standard. By partnering with our Clinical Data Management team we ensure your clinical data is always clean, accurate, complete and following ALCOA+.

For more information about our Clinical Data Management services arrange a call with one of our data experts and avoid the risk of data integrity issues on your trial.