Each year, records related issues, inadequate and inaccurate records represent the second most commonly cited deficiency in CDER’s (Center for Drug Evaluation and Research’s) GCP (Good Clinical Practice) compliance inspections of clinical trial investigators and sites. The first one is failure to adhere to clinical protocol.

In FY 2006 23% of clinical sites investigated by CDER were cited for records related issues. If one looks at the serious non compliance, 60% were cited for records related issues second only to failure to adhere to the protocol at 81%. Why are there so many problems with source documentation? It is not clear what records are to be maintained and it is not clear how records are to be completed.

ICH GCP states the following information that will help clarify these issues.

1. Glossary

Section 1.51. Source Data is all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in source documents (original records or certified copies).
Section 1.52. Source Documents are original documents, data, and records (e.g., hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ dairies or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate copies, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files and records kept at the pharmacy, at the laboratories and at medico-technical departments involved in the clinical trial).

Good Clinical Practice Principle 2.10 states “All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation and verification.”

Good Clinical Practice requires that the investigator be responsible for the following practice with respect to clinical research records.

4.9 Records and Reports

Section 4.9.1 The investigator should ensure the accuracy, completeness, legibility, and timeliness of the data reported to the sponsor in the CRFs and in all required reports.
Section 4.9.2 Data reported on the CRF, which are derived from source documents, should be consistent with the source documents or the discrepancies should be
explained.
Section 4.9.3 Any change or correction to a CRF should be dated, initialed, and explained
(if necessary) and should not obscure the original entry (i.e., an audit trail should
be maintained); this applies to both written and electronic changes or corrections
(see section 5.18.4(n)). Sponsors should provide guidance to investigators and/or
the investigators' designated representatives on making such corrections. Sponsors should have written procedures to assure that changes or corrections in CRFs made by sponsors’ designated representatives are documented, are necessary, and are endorsed by the investigator. The investigator should retain records of the changes and corrections.

The acronym ALCOA stands for a set of standards that are often cited by FDA and GCP compliance officials. Though this standard has no official standing under FDA regulations, the standard has been often quoted by GCP experts to identify the essential characteristics of data recording practices. It is mentioned in FDA draft guidance on Computerized Systems Used in Clinical Trials.
Attributable – The data is attributable to the person collecting and recording the data.
Legible – The data must be readable.
Contemporaneous – The data must be complete, dated and signed and/or initialed at the same time the data was recorded. Additional information may be added as addendums with new date and signatures and/or intials.
Original – The data must be the first recording, and not copied.
Accurate – The data must reflect the record and be an accurate accounting of the events.

As neatly summarized by the National Institute of Allergies and Infectious Diseases (NIAID) guidance on source documentation requirements:

• Keep handwritten notes and signatures legible
• Sign and date all entries
• Make error corrections in the right way
• Don’t obliterate entries that require correction
• Don’t destroy original if they require correction
• Don’t alter past-dated notes, chart notes / progress notes
• Use only dark ink
• Never use whiteout
• Never use pencils
• Maintain records chronologically

Understanding and complying with these GCP principles will ensure proper source documentation and record keeping that will contribute to the integrity and success of your clinical trial. Taking some extra time when collecting and recording data on the front end will also save more time on the back end when the monitor comes!