March 26 2018 Stephen Cropper, MS

In recent years, much has been said about Source Document Verification (SDV), the comparison of information reported by an investigator to original source records to confirm its completeness, accuracy, and validity. The term SDV seems to mean different things to a lot of people. Some suggest that SDV is only the simplest form of transcription checking, with a goal of simply ensuring that the eCRF matches the patient’s medical records.

The accepted norm for assuring clinical trial quality had been 100% SDV, but there is no evidence that suggests it improves overall data quality, and FDA & ICH regulations do not require it. A process that includes 100% SDV review can be very time-consuming and expensive. Has the time come to change how we approach SDV in clinical research?

The ICH E6 (R2) addendum, which encourages more efficient oversight of clinical trials, drives the evolution in SDV. ICH 5.18.3 (Extent and Nature of Monitoring) permits flexibility in the monitoring approach, such as a combination of onsite, off-site (remote) monitoring and centralized monitoring; off-site monitoring combined with meetings, investigator trainings, and extensive written guidelines; and centralized, statistically controlled sampling of data for verification.

One approach to improving data quality begins before data is even generated through a quality by design approach. For example, thorough vetting and design of a protocol often helps to reduce the number of amendments and deviations. Those identified risks that cannot be eradicated should determine the monitoring approach, including the level of SDV and centralized monitoring to be utilized to look for recurring patterns that suggest data quality issues.

More than just a blind consistency check between the source and eCRF, source data review (SDR) should focus  on ensuring that sites follow the protocol and comply with regulatory requirements that cannot be checked centrally (ie IMP storage or calibration of equipment). The most practical monitoring strategy mixes activities like onsite monitoring and off-site data review to focus on the key risks; targeted SDV/ SDR can be used to focus on a controlled sample of the data for verification based on these key risks and linked to critical data and processes.

In order for Targeted SDV to be performed correctly, key data points must be identified, easily assigned to a CRA, and then tracked. The monitor’s data assignments should be able to be adjusted based upon the site’s risk. Risk does not necessarily mean a track record of poor performance, but outcomes that are more likely to occur. Risk can be identified onsite at an initiation visit or from an observation discovered though centralized monitoring.

ICH E6 (R2) requires risk assessment but does not specify how it is to be performed. How can a sponsor feel satisfied about whether or not they have calculated the risks correctly if the available guidelines do not clearly document the requirements? A sponsor must be able to identify critical data and processes. What is the best available method to do this?

Risk assessment tools can be very expensive, but the regulations do not require any expenditures. There is a non-profit organization named TransCelerate BioPharma Inc. whose mission is to collaborate with the biopharmaceutical research community and help create health solutions. They offer a Risk Assessment and Categorization Tool free of charge that can be used to assess risks. Cyntegrity offers a free cloud version of that Risk Assessment and Categorization Tool called @RACT, which can be used to define high, medium and low risk indicators and to develop a study specific adaptive trial monitoring plan. An account can be established at There are many companies that have developed other tools that can be used or modified as needed. Risk assessments should be repeated as often as necessary and the monitoring strategy adjusted accordingly.

As an industry of health professionals, we need to be striving toward ways where we work smarter and more efficiently. Shouldn’t the level of SDV that occurs be based entirely on a full assessment of a study’s risks? By reviewing anything less than everything, a sponsor stands to reduce cost and time, so they can focus their available resources on more critical clinical trial activities.

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