In the realm of clinical research, adherence to ALCOA-C principles is paramount to ensure the integrity and reliability of trial data. Originally established for paper-based records, ALCOA-C stands for these principles—Attributable, Legible, Contemporaneous, Original, Accurate, and Complete—remain crucial even in an era dominated by electronic systems.
Despite the shift to electronic Trial Master File (eTMF) platforms, meeting ALCOA-C requirements remains a challenge. Clinical trial site documentation serves multifaceted purposes, including maintaining medical records, confirming participant eligibility, and providing a communication basis for physicians. Ensuring these documents are clear, complete, and accurate is essential for generating high-quality data, ultimately streamlining drug development processes and reducing time-to-market.
Ongoing Challenges in Clinical Trial Site Documentation
“The most important purpose of source documentation in a clinical trial is to reconstruct the trial as it happened,” writes Chitra Bargaje in an article in Perspectives on Clinical Research. An outside party should be able to reconstruct the trial and confirm the data from the documentation alone, with no other information about the clinical trial.
Other essential functions of clinical trial site documentation include:
- Maintaining medical records of clinical trial participants.
- Confirming each participant’s eligibility for participation in the trial.
- Documenting the entire trial participation of each subject, from initial consent through study completion.
- Tracking medications, medical devices, and other items dispensed to participants.
- Providing a basis of communication for physicians treating participants.
- Serving as the foundational data source for compliance, clinical study reports, and publications.
Clinical trial documentation is thus called upon to serve many purposes at once. To meet these needs, the documentation must be clear, complete, and accurate.
High-quality clinical trial data, in turn, “helps to produce a drastic reduction in time from drug development to marketing,” write Binny Krishnankutty, Shantala Bellary, Naveen B.R. Kumar, and Latha S. Moodahadu in the Indian Journal of Pharmacology. By ensuring all interested parties have complete, reliable data, clinical trial teams reduce delays both among team members and in responding to information demands from regulatory authorities and stakeholders.
ALCOA-C Standards as a Response to Documentation Challenges
“If it is not documented, it did not happen,” warns a University Hospitals Clinical Research Center handout on data quality. Effective documentation demands attention to whether an event is documented and to how accurate and complete the documentation is.
The ALCOA-C standards seek to achieve high-quality data. The standards call for data that is:
- Attributable. Who did what when? Attributable data is easily connected to a person, date, and time.
- Legible. Legible data is easy to read. Signatures are readable, or printed names are included with signatures.
- Contemporaneous. Contemporaneous records are made during the event they record. When this is not possible, the information should include statements about when it was recorded and the reason for the delay.
- Original. An original is the record made first. Certified copies may serve as originals for some uses. Clinical trial investigators are expected to maintain the originals of all trial-related records.
- Accurate. Data recorded should consistently reflect actual readings taken, correct spelling of names, or other information gathered.
In a March 2018 guidance document, the U.S. Food and Drug Administration (FDA) called for the addition of “Complete” to the ALCOA standards, creating the ALCOA-C model:
- Complete. Complete data answers the six standard questions: Who, what, when, where, why, and how.
One aspect of complete documentation is to document not only what was done but also what was not done, writes Karen K. Carter, associate director of the Center for Clinical and Translational Science at The Ohio State University. Documenting the gaps — what wasn’t done or didn’t happen — makes these gaps visible, placing surrounding information in context.
Data that meets ALCOA-C standards is of higher quality than data that falls short of these standards. This data can more easily be used by the clinical trial team that collects it and by future researchers seeking insight into similar scientific questions.
By contrast, “[e]rrors in long-term data storage and sharing can render findings nonconfirmable because data are not available to be analyzed,” write Andrew W. Brown, Kathryn A. Kaiser, and David B. Allison.
Using an eTMF to Meet or Exceed ALCOA-C Standards
While the ALCOA-C requirements anticipate paper-based recordkeeping, each element also applies in an electronic environment, writes Carter. Electronic Trial Master Files (eTMF) recordkeeping must:
- Preserve a data trail that tracks changes and attributes them to specific users.
- Record data queries and corrections.
- Meet applicable compliance standards.
Applied correctly, an eTMF can help clinical trial teams meet or exceed ALCOA-C standards.
Attributable
eTMF systems typically use role-based access controls (RBAC) to maintain security. Access to particular documents is connected to the user’s predefined role within the system.
RBAC systems log users’ activity within the eTMF as well. Records are automatically generated whenever a user logs in or performs any task, including viewing, editing, or creating files within the eTMF. These automatically-generated records allow any particular action in the system to be attributed to a particular person at any time.
Legible
ALCOA’s original legibility concerns arose at a time when many clinical trial records were handwritten. An eTMF reduces legibility issues by storing data in standardized typed formats, using easy-to-read fonts. When data is maintained in a digital format, handwriting idiosyncrasies and printer artifacts are eliminated, boosting legibility.
Contemporaneous
In addition to logging which user performs which tasks within the eTMF, the system also logs the time and date specific events occur. A record of contemporaneous activities is therefore more easily generated. When a user’s attempt to record data does not occur contemporaneously with the event that generated the data, the system can be customized to flag the discrepancy and require the user to indicate a reason for the gap between the time of the event and the time of data recording.
Original
Electronic records are a form of original clinical trial records when the electronic record is the first logging of information, rather than the result of data entry from a paper source.
By tracking exactly when documents are created or edited, an eTMF establishes the originality of data creation and entry. Robust security features help ensure that the data is protected and remains accessible to trial teams and future researchers.
Accurate and Complete
Many digital platforms today use autocorrect, required-field flags, and other tools to help human users submit more accurate entries, and eTMF systems are no exception. These tools help improve the accuracy of data by serving as an extra screening for data entry errors, information inserted into the wrong field, or information that is omitted. While they cannot stand in for human attention to detail, these tools help eTMF users remember to provide accurate information.
The past decade has seen significant advances in the use of digital technologies to improve clinical trial recordkeeping and communication.
In 2013, Meredith Mealer and fellow researchers attempted to use remote electronic monitoring to perform source document verification (SDV) across clinical trials at five hospitals. The researchers found, however, that “[b]ecause each site had different policies, requirements, and technologies, a common approach to assimilating monitors into the access management system could not be implemented.” While the researchers had some success monitoring data remotely, they struggled to collect consistent, high-quality data across all five trial sites.
Today, the struggle is significantly reduced. The use of eTMFs and similar tools eliminate barriers to collaboration, monitoring, and data-sharing across clinical trial sites while also boosting the quality of data collected.
One example of electronic recordkeeping in action is using electronic means to create case report forms (CRFs), write Shantala Bellary, Binny Krishnankutty, and M.S. Latha in Perspectives in Clinical Research. An electronic CRF, based on an eTMF, can:
- Be standardized for use by investigators, site coordinators, and other trial team members.
- Organize data in ways that facilitate data analysis.
- Promote completeness by prompting users to supply all required information.
An eTMF allows clinical trial teams to access templates for CRFs and other trial-related documentation. These templates save time in the trial setup process and standardize processes. As clinical trial team members familiarize themselves with the eTMF and its templates, they spend less time puzzling over the documents and documentation process and more time collecting high-quality data.
ALCOA-C requirements remain relevant regardless of the format of clinical trial records. Whether on paper or created electronically, clinical trial data requires rigorous attention to quality. A tool like Anju’s eTMF Master can improve the quality of trial data by helping teams adhere to ALCOA-C demands within the context of their daily work.
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