Monitoring of clinical trials is a federally mandated responsibility of trial sponsors and a core offering of contract research
organizations (CROs) that is crucial to the validity of clinical research. Source document verification (SDV)—the comparison
of reported trial data with information from primary health records of trial subjects—is an important component of trial monitoring
intended to ensure the integrity of trial data. Sponsors and project managers should develop SDV strategies for each trial
that comply with regulatory requirements and accommodate the size, complexity, design, and purpose of the trial.
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One hundred percent SDV, the comparison of each data point on every case report form (CRF) to subject medical records, may
not be appropriate for most large, multi-center trials. Targeted SDV—the verification of critical trial data, including study
endpoints—has the potential to improve safety oversight, data quality, regulatory compliance, protocol adherence, and overall
trial validity while reducing costs and the time to database lock for large, multi-center trials.
Regulatory requirements and SDV
The Guidance on Good Clinical Practices (GCP), developed by the International Conference on Harmonization (ICH), requires
that trial monitors have access to and can review source documents. This guidance, ICH E6, has been adopted by both the Food
and Drug Administration (FDA) in the US Code of Federal Regulations (CFR) under Title 21 and by the European Union (EU) as
part of the EU directive on clinical trials. Guidance ICH E6 and the regulatory authorities that have adopted it, refer to
source documents (i.e., primary health records, in the sections on investigators, sponsors, trial protocols, and essential
documents).
According to the E6 guidance, source documents must be kept in good order and investigators must make source documents available
to the sponsor and monitors working on behalf of the sponsor. Investigators are responsible for ensuring that the data reported
on CRFs is consistent with source documents,1 and the sponsor is responsible for ensuring that each subject has provided written consent to direct access to his or her
medical records.2 Sponsors must also ensure that the trial protocol or other written agreement specifies that investigator(s)/institution(s)
will allow trial-related monitoring3 and that the monitors verify the source documents are accurate, complete, up-to-date, and maintained.4
Source documents are used to achieve two explicit regulatory objectives: to document the existence of the subjects and to
substantiate the integrity of trial data.5 Both objectives depend on effective SDV by monitors. The most effective strategies for SDV depend on the particulars of
each clinical trial. While 100 percent SDV is not required by law, industry standards maintain 100 percent SDV as the most
straightforward approach to regulatory compliance. However, the FDA guidelines for monitoring clinical trials states, "...the
monitor should compare a representative number of subject records and other supporting documents to the investigator's report..."6
FDA guidelines explicitly refer to a representative number of subject records, not all subject records. The Department of
Health and the Medical Research Council in the United Kingdom announced, "verifiable...does not imply that every item of data
recorded must be supported by a source document or checked."7 The number of subjects, the experience of the clinical site, the clinical endpoints, and the nature of ancillary data are
several of the factors that should be considered when developing a strategy and protocol for a project-specific SDV plan.
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