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and compliance. They should ensure that standard operating procedures (SOPs) are in place and that equipment, staff training records, service records, and maintenance contracts are adequate to ensure the integrity of the trial. They should also ensure that all samples are identified throughout the process, that all documents are dated and signed, and that all raw data is archived. For the analytical procedures, the QA personnel should ensure frequent calibration of all methods, daily testing of precision and accuracy prior to sample analysis, and a demonstration of quality control checks throughout the day to detect any drift in methodology. Validated methods and procedures should be used at all times and particular attention should be paid to investigators or laboratories that are running specialised or novel tests to ensure that the method is fully documented, validated, and acceptable to regulatory authorities. |
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It is also appropriate that the sponsor receive quarterly quality-control reports on key laboratory parameters throughout the course of the trial. These reports allow the sponsor to monitor that the laboratory remains in control and that the patient data will remain consistent from one month to the next. This consistency is especially important if the analysis being performed is used as a measure of drug efficacy. In such cases, examining trend analysis reports may be appropriate to guard against any drift or bias in the results. Similarly, laboratories should be actively discouraged from using cheaper generic reagents for in house assays since this is not in the best interest of the sponsor. Proprietary reagents should always be used so that any variation in a patient's laboratory results are due to a treatment effect and not to an artifact associated with a methodological imbalance over time. |
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Diligent monitoring of key laboratory results can also avoid surprises, such as a laboratory changing its methodology without the consent of the sponsor. Changes to testing methods mid-trial can leave the sponsor guessing which tests were run with which methodology and whether the data can be combined. The laboratory should always inform both the sponsor and the investigator of any intended change in methodology or reference range and, prior to any such decision, the laboratory should have validated the new method and have clearly demonstrated that there was no significant bias in the results derived from the old and new method. In an extreme illustration, Hill [3] described how a central laboratory involved in monitoring an antiretroviral drug trial changed its methodology for evaluating viruses between visit 1 and the end of the trial. The new method only detected 20% of the viruses present compared to a 100% detection with the original method. |
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Probably the most difficult task related to Good Clinical Practice is protecting source documentation against destruction. As mentioned above, the European Union directive (91/507/EEC) not only indicates that clinical trials must be conducted in compliance with GCP but also that patient files and other source data should be kept for the maximum period of time permitted by the |
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