Clinical studies/trials monitoring

Given the above preclinical observations, patients in a clinical study were monitored closely during treatment (including measurement of testosterone, luteinizing hormone, follicle-stimulating hormone levels, alkaline phosphatase, and serum vitamin A concentrations). This phase I clinical study of TAG-101 was conducted to determine the safety, toxicity, and pharmacokinetics of this agent in patients with advanced cancer. Currently, the drug is in a phase I/II clinical trial for advanced hepatocellular carcinoma. 

The Food Additives Amendment to the Federal Food, Drag, and Cosmetic Act of 1938, which was adopted in 1958, requires that proof of safety of a new food additive be furnished by the manufacturer based on extensive scientific research. Since it is impossible to conclusively prove the safety of a new food additive through animal and clinical trials, manufacturers routinely conduct postmarketing surveillance and long-term follow-up studies to monitor adverse events. 

The investigator should prepare an informed consent form for every study to be performed at the institute and should obtain an approval by the IRB that covers the institute. GCP listed a dozen points to be covered by the informed consent (1C) form (see Table 23.6). The new GCP allows a reasonable amoimt of pa)unent to the patient, such as transport cost. Patients should allow clinical trial monitors, auditors, IRB members and inspectors from the regulatory authority to verify the source documents. This new requirement of obligatory written 1C is regarded as a... 

This is not to say that cardiotoxicity is not seen with biopharmaceuticals. Cardiomyopathy is now a well-recognized complication of trastuzumab and and has been reported with bevacizumab treatment, in particular in combination with other cytotoxic cancer therapies [20]. Myocarditis and pericarditis are a well-documented complications of vaccinia immunization [21], and could also complicate use of a pox-virus vector for other therapeutics. In 1995 Genetics Institute suspended phase 2 cancer trials of Interleukin-12 for serious tox-icities including cardiac arrhythmia. However, such toxicities are best detected by incorporation of biomarkers for myocardial damage such as troponin-T into preclinical and early clinical studies, and continual ECG monitoring for arrhythmia in preclinical and early clinical studies, not by in vitro explorations of electrophysiology. 

In the ongoing Phase I clinical trials, the effects of NPI-0052 on proteasome activities in both packed whole blood and peripheral blood mononuclear cells are being monitored. In approximately 80 patients treated to date with NPI-0052, a dose-dependent inhibition of the whole blood 20V proteasome activity is observed, with increasing inhibition upon multiple administrations and partial recovery between consecutive doses (Figure 12.4). Nicely paralleling the pre-clinical studies, a more pronounced recovery of 20V proteasome CT-L activity is observed between consecutive NPI-0052 administrations in the peripheral mononuclear cell population of patients compared to packed whole blood. 

Outsourcing is now a common practice of almost all pharmaceutical companies. For example, the use of CSOs to support some aspect of clinical trial research has grown from approximately 30% of the clinical studies conducted in 1993 to over 60% in 1997. The processes that a client uses to select a CSO and how a client interacts with the CSO ensure contracted research studies are monitored appropriately and completed on time and within budget. 

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