Posted by: Karen E. Woodin, PhD
Source document review, sometimes called source document verification, involves checking the data recorded in the case report forms against data found in available source documents, including the patient chart, laboratory reports and other supporting documents. (A source document is any document where the data are first recorded.)
The purpose of source documentation is twofold: first, to verify that the subjects exist and, second, to verify that data in the CRF are consistent with the information found in the source documents, which verifies the integrity of the data.
For example, one would expect to see basic demographic information in an office chart for a patient, including name, address, phone number, insurance information and a social security number. The usual office chart will also contain lab reports or reports of other tests. This information is indicative that the person entered in the trial actually exists.
When the data in the case report forms are in agreement with data contained in source documents, it is an indicator of the quality and veracity of the information being gathered for the study. It is not necessary for every entry in a CRF to have a matching entry in a source document, but where the data do appear in both, they should agree.
Neither ICH GCPs nor FDA regulations require that source documents be kept for all entries on case report forms. Under 21 CFR 312.62(b), “An investigator is required to prepare and maintain adequate and accurate case histories that record all observations and other data pertinent to the investigation…Case histories include the case report forms and supporting data including, for example, signed and dated consent forms, progress notes of the physician,…hospital chart(s) and nurse’s notes.” (21 CFR 312.62 (b)). ICH GCPs say only that the study monitor shall verify that “the data required by the protocol are reported accurately on the CRFs and are consistent with the source data/documents.” (ICH Guideline for Good Clinical Practice 5.18.4(m)).
Despite the lack of any regulatory requirement, many companies are currently insisting on a matching source document for every case report form entry, in which case they may provide the site with source document templates to use, or the study coordinator may be charged with developing source documents to use during the trial. So in this case, what happens is the study coordinator fills in the provided “source documents”, then has to copy the same information onto the case report forms – where have we gone wrong? Not only is this redundant, but recopying material leads to additional errors.
There are significant differences among sponsors with respect to the amount of source document review that a CRA must do, and there are no guidelines in the regulations. Some companies require “100% source document review,” but the definitions of 100% also vary, from the expectation of a source document for every data point for every subject to 100% verification of the data insofar as it exists in source documents. Other sponsors have sampling schemes, and these also vary considerably.
Maybe it’s time for us all to stand back and think about what makes sense to do. What is really important for verifying the subjects actually exist, and that the data we are collecting are valid? We are expending enormous amounts of time and energy (which equal money, of course) on an activity that may not need to be done.
What’s really important to review and verify? We probably should check source documents for critical information, such as the inclusion and exclusion criteria (especially the diagnosis), a signed informed consent form, adverse events and critical study-specific parameters. Perhaps it would be wise to check the first two subjects at each site completely, insofar as the information exists, to ensure that the site understands their responsibilities for data collection and is doing things correctly. If there are problems, continue with more aggressive review; otherwise, checking only the important items listed above is probably sufficient.
The cost of SDR
Let’s look at a hypothetical study. There are 6 sites, and each site requires 12 visits over the course of one year. Let’s assume an average CRA salary of $50/hour, which, with fringe benefits, would be about $90/hour. That means a CRA cost of $51,840 to monitor the study, not including travel time and costs, which are also significant.
CRAs tell me that doing SDR takes about twice as long as doing case report form review. Since some SDR will still be done, let’s say we can cut half the SDR time by not doing 100% verification. So, on our hypothetical study, a company could save about $26,000 by modifying their SDR policy. Now consider what else the CRA could do with that time – monitoring another study, for example. Or maybe the CRA would need to travel only six times to the site, rather than twelve, saving significantly on travel costs and general wear and tear.
Look at one of your own company’s studies and do the math. How much could you save, and how could you better utilize your CRAs? Is the payback for doing “100% source document review” worth it? Does it make the study better? Are the data more meaningful?
It’s probably time to reassess the purpose and need for 100% source document review.
Karen E. Woodin, PhD, is an independent consultant for the pharmaceutical industry, specializing in the areas of clinical operations, Good Clinical Practice (GCP), and Standard Operating Procedures (SOPs). Dr. Woodin worked for The Upjohn Company/Pharmacia for over twenty years in the areas of biostatistics, clinical trial monitoring, and drug safety. She also teaches courses in the area of clinical trial operations and is the author of The CRC’s Guide to Coordinating Clinical Research and co-author of The CRA’s Guide to Monitoring Clinical Research and The Investigator’s Guide to Clinical Research.