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the MCV was observed while the platelet count fell by 15%. A white cell differential count was reported for every sample up to day 4 but the instrument failed to give a valid result for 10 five-day-old samples and 26 samples 6 days old. When the H*3 provided a valid result, the values for WBC and the white cell differentialfor all but basophilswere similar to the day-2 results, even when the samples were 5 or 6 days old. |
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V. Clinical Pathology Support of Phase I: Safety and Tolerance Trials |
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Phase I trials tend to be of a limited nature and usually each trial is performed at a single center. A few pharmaceutical companies run their own Phase I trials in house while the majority contract these to CROs that specialize in these types of trials. At this stage the volunteers are intensively monitored and it is essential that the investigator receives the laboratory results as soon as possible after dosing and certainly before the volunteer is administered a further dose of the new drug. |
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Consistency of tests results between laboratories is less critical for these trials and only becomes an issue if a trial is performed at multiple centers, each using their own local laboratory. The critical issue is the turnaround time between the sample being taken and the investigator receiving the laboratory results for review. |
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Phase I clinical trials often deal with novel therapeutic agents and novel therapeutic targets, therefore non-routine laboratory support is often required. Surrogate marker data, as an indicator of drug efficacy, is becoming more widely accepted by regulatory authorities. Some of these surrogate markers are commercially available (e.g., prostate specific antigen [PSA] for monitoring prostate cancer patients) while others, such as urinary 3-methyl-histidine for monitoring muscle breakdown, require a more specialized approach. For a novel surrogate marker, the credibility of the laboratory to perform the analysis is very important and the sponsor should seek reassurance, possibly by means of published papers, that the individual assigned to the assay is competent. Local laboratories, while comfortable in providing routine safety testing data, may not be the right choice to analyze these markers. |
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At Zeneca, the majority of Phase I trials are performed in the Clinical Pharmacology Unit on site using a volunteer population of Zeneca employees. Sample transport to the laboratory is not a problem and all analyses are reported on the day samples are received. Recently more Phase I trials are being contracted to specialized CRO Clinical Units, sometimes at more than one location. All these samples are also analysed by the Zeneca laboratory but special transport arrangements are necessary to ensure that the samples are |
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