Ensure the Integrity of Your Clinical Research Data

It may be no surprise that during a sponsor audit, data management and source documentation rank among the top ten most common categories for critical inspection findings. According to a report on behalf of the European Medicines Agency (EMA), out of 398 GCP inspections over a 12-year period, a total of 5,685 findings were recorded; 532 of these findings were critical – 48 directly related to data management and 32 to source documentation. Needless to say, the quality of a study’s documentation ultimately impacts the validity and usability of your data.

With increasing trends in outsourcing and globalization, the number and diversity of stakeholders involved in most studies continues to grow. Investigator sites, clinical research organizations (CROs) and service providers are spread across geographies, and each stakeholder has their own organizational culture as well, often not aligned with yours. This complexity makes the likelihood great that Good Documentation Practices (GDP) are not standardized.

Good Documentation Practices (GDP)

While much has been written about GDP, there is no definitive regulatory guidance on the topic. The International Conference on Harmonization (ICH) recently released a revision of the so-called Gold Standard for Good Clinical Practice (GCP). This ICH E6 (R2) guideline introduces new requirements that directly impact the way you manage your trial master file (TMF).

Source data, source documents and essential documents

Your source data are the data contained in any given study’s source documents. These are the original records (or certified copies) which can enable reconstruction and evaluation of the clinical trial per se.

Sponsors running multi-site, global trials face a major challenge regarding what constitutes an “essential document” – without guidance, each site could operate under distinct definitions of what they believe to be essential.

Some questions to ask yourself:

  • How do I currently define my studies’ essential documents?
  • Do I have study-specific definitions or do I define this unilaterally across all trials?
  • If I use an electronic trial master file (eTMF), is it flexible enough to support my approach?

For sponsors deploying eTMF systems, all documents are classified as essential, and thus, captured within the system, enabling easy retrieval at any point in time. An eTMF provides the tools to ensure accurate planning and preparedness.

How well does your clinical research rank? ALCOA, ALCOAC or ALCOACCEA?

The quality of your source documentation is a strong measure from which to assess how well your clinical research ranks. Whether your essential documents are paper or electronic, a number of attributes known as ALCOA (Accurate, Legible, Contemporaneous, Original and Attributable) are considered of universal importance.


  • Accurate – Information is captured in the data record so that it is uniquely identified as executed by the originator of the data (g., a person, a date, a computer system). eTMF systems provide quality control (QC) processes guaranteeing accuracy of data records in both the metadata and the content itself. The eTMF also classifies the record by assigning it to the correct document type.
  • Legible – Legible, traceable and permanent (signatures must be identifiable). An eTMF system offers features like quality checks for scanned documents, ensuring high quality images.
  • Contemporaneous – Data are recorded at the time they are generated or observed. An acceptable amount of delay should be defined and justified. To comply with inspection readiness, eTMF supports tracking of document due dates, any time and everywhere, and reports on upcoming due or overdue documents to support your decision-making.
  • Original – The earliest record or the first source capture of data and all subsequent data required to fully reconstruct the conduct of the good practice (GxP) activity. A robust QC process on the destruction of paper after the required retention period allows for the replacement of paper originals within an eTMF.
  • Attributable – Correct, truthful, valid and reliable. eTMF systems introduce the perspective of the audit trail; in other words, any modification and activity in the system can be tracked and linked to a username at a certain point in time.


With the increasing use of information technology in clinical development, in 2010, the EMA added four additional attributes (and hence additional acronym letters) to the quality measure – Complete, Consistent, Enduring and Available, forming the ALCOACCEA acronym. These additional attributes are particularly targeted at electronic documentation.

The newer ICH E6 (R2) guideline also introduces the “Complete” attribute, creating the  ALCOAC acronym, but does not adopt the EMA requirement for source data to be “Consistent, Enduring and Available”.

  • Complete – The eTMF tracks and informs you of received, expected, overdue and missing documents. Computers can check data and records for completeness in a fraction of seconds several times per day.
  • Consistent – Edit checks can be designed to check for consistency of data and document trails and would have the ability to send electronic notifications to the responsible stakeholder.
  • Enduring – Electronic records can be stored indefinitely in multiple places as long as steps are taken to migrate them forward as underlying technology changes.
  • Available – A cloud-based eTMF is an ideal solution to ensure that documents are “globally and remotely accessible when needed” to support decision-making and to prepare for site monitoring visits and audits.

As a result of the variations in guidance, are you sure that your TMF is truly compliant? The ALCOACCEA principles, combined with an appropriate study design and the implementation of an eTMF solution, can ensure you have the necessary tools and documentation for a robust and compliant TMF.


As a popular quote, which is often attributed to Confucius, states, “Life is really simple, but we insist on making it complicated.” At HighPoint, we navigate those complicated landscapes to guide our clients along the most practical path forward.