Source Data Verification (SDV) demands a large part of the work of clinical monitors. An inherent philosophy that has indoctrinated the belief that clinical data should be transcribed onto the CRF from source documentation remains normal practice. Ideas are changing and it is now proposed that all trial data are entered in the CRF, which is the source document during the course of the trial. Only pre-screening data that testify the patient’s existence, medical history and concomitant medication, should be recorded elsewhere. It may be necessary to put aside inherent philosophies and comfortable practices in order to become more efficient in our development of monitoring strategies and more effective in our use of modern technologies.
Does Source Data Verification need a revolution?
Philosophy and Status quo
For years, clinical trial philosophy has indoctrinated a popular belief that most clinical trial data reside in the patient’s chart, which is kept in the physician’s office. Some “non-standard” data are recorded directly onto trial-specific forms, but the majority of “standard” data are transcribed from the physician’s file (e.g. laboratory test results, medical history and adverse event data) into trial notes.
Even today this inherent belief leads to situations whereby investigators record everything on the Patient Chart first and then transcribe it elsewhere. This process introduces countless transcription errors, which lead to queries and audit findings. Conversely, some investigators use the Case Record Form (CRF) to record their findings and then transcribe the data onto the Patient Chart because this is more convenient for them. In all fairness, even the International Conference on Harmonisation (ICH) guidelines are unclear about the process of source data verification (SDV) and the frequency of its conduct. The guidelines stipulate that the goal of SDV is to ensure that the data recorded in the CRF are accurate. One way to check this is to compare the CRF with the “source data” recorded on the patient’s chart and in the physician’s notes.
Arguments againt SDV
Source data verification can be considered an exceptionally expensive way of ensuring that two sets of data are congruent. This does not mean that both sets of data are a true representation of the findings; rather that they are identical. From this perspective, a more sober look at SDV is possible. Most trialists concede that verification of the patient’s identity, medical history, and concomitant medication is an essential prerequisite to patient enrolment. Documentation of all other information could be recorded in the CRF. Thus, the CRF should be the source document on which all patient data are entered. Any additional information not required by the trial protocol, could be entered on the Patient Chart provided that a note is placed on the chart linking the two sets of databases to each other.
It is my opinion that technology has already enabled this process to develop a stage further. Electronic data capture (EDC) makes it possible to type data directly onto a CRF without the need for paper. The data then flow directly into a database. Some regulatory agencies have formed draft guidelines, which stipulate conditions under which such systems and processes can be used. Nevertheless, most companies are hesitant to withdraw the use of pen and paper entirely.
If SDV was a simple and straightforward procedure no one would be trying to “simplify” the process with other technologies. However, the philosophy behind SDV is questionable – which elevates its already high cost. A key reason for periodic monitoring visits is to verify the CRF with the source data. The cost for a periodic monitoring visit, including all expenses, can be between $500 – 1000. Most companies only have the resource to conduct one monitoring visit per day (although there is still some room for improving productivity). In addition to inflated monitoring costs for sponsors, data transcription necessitates additional time and effort on the part of the physician. In turn, this has an effect on investigator remuneration, as the trial demands more of his or her time and resources.
A brief survey conducted by telephone to sample regulatory opinion has shown that regulatory personnel do not wish to be seen to be being too “liberal”. Some of the agency representatives maintained that SDV is “necessary” but were not prepared to endorse the 100% SDV initiatives that some companies are aiming for. Others felt that it was up to the industry to come up with proposals that would liberalise the process whilst maintaining the integrity of the data and adhering to data protection laws.
In an attempt to quantify the “value added” by SDV, GlaxoWellcome screened 20 of its internal site audits to determine the number of audit findings that related to SDV. In addition, monitors at GlaxoWellcome completed an internal questionnaire about the effectiveness of periodic monitoring visits in uncovering discrepancies between the source data and the CRF.
The results of this survey showed that although SDV improves the accuracy of data it adds little value to the trial and, at best, may be considered costly. On the other hand, it could be concluded that a significant reduction in SDV would lead investigators to believe that a reduction in transcription accuracy was acceptable. This clearly is not the case and here statistical quality control could be of benefit. A quality control strategy that introduces a “sliding scale” i.e. number of spot checks increases in proportion to the number of discrepancies found, would be an efficient and effective way of conducting site audits and would compensate for the reduction in monitoring visits.
The conduct of SDV is in need of a revolution. Paperless offices and electronic digital data exchanges are becoming more common. Nethertheless, most of us are still collecting the majority of our clinical trial data on NCR paper and comparing the data to entries in the patient files from which they have been transcribed. In the face of escalating drug costs and static time-to-market periods, we must work together as an industry to revolutionise data capture. It may be necessary to put aside inherent philosophies and comfortable practices in order to become more efficient in our strategy development and more effective in our use of modern technologies. Radical changes to the way in which we conduct SDV would be a significant step in the right direction.
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