Clinical investigator responsibilities

PARHAMI F, FANG Z T, FOGELMAN A M, ANDALIBI A, TERRITO M C and BERLINER J A (1993) Minimally modified low density lipoprotein-induced inflammatory responses in endothelial cells are mediated by cyclic adenosine monophosphate /owmaZ of Clinical Investigation 92, 471-8. 

Jung, H.C., Eckmann, L., Yang, S.K, Panja, A., Fierer, J., Morzyckawroblewska, E. and Kagnoff, M.F. (1995) A distinct array of proinflammatory cytokines is expressed in human colon epithelial cells in response to bacterial invasion. Journal of Clinical Investigation 95, 55-65. 

Wang, H.W., Tedla, N., Lloyd, A.R., Wakefield, D. and McNeil, P.H. (1998) Mast cell activation and migration to lymph nodes during induction of an immune response in mice. Journal of Clinical Investigation 102, 1617-1626. 

Further studies have shown additional cancer types, most notably ovarian and bladder cancer, non-Hodgkin s lymphoma and acute myeloid leukaemia, to be at least partially responsive to IL-2 treatment. However, a persistent feature of clinical investigations assessing IL-2 effects on various cancer types is variability of response. Several trials have yielded conflicting results, and no reliable predictor of clinical response is available. 

However, native antisense oligonucleotides also suffer from a number of disadvantages, which are ultimately responsible for numerous disappointing trial results, and the fact that, after almost two decades of clinical investigation, only a single product has gained approval to date. Disadvantages include ... 

Name and address of Sponsor and Monitor Name of authorized person Name of Sponsor s medical expert Name of Investigator responsible for the trial Name of physician responsible for trial-related medical decisions Name of clinical laboratory and other institutions involved in the trial... 

Soon, my adventures in the Clinical Investigation Division began. I spent the first few days learning the names and responsibilities of staff members and observing tests with EA 2277. Before long, however, I became impatient to get off the bench and onto the playing field. 

The introduction of GCP has accelerated the need for quality control and quality assurance, particularly in the field of clinical research. Quality control is carried out by the staff who are responsible for the particular activity, working to SOPs that cover all the tasks under scrutiny. SOPs not only need to be written but must also be updated regularly. Quality assurance is the process which seeks to confirm that SOPs have been observed this is accomplished by the process of auditing. Internal audit departments should be under a separate management from the medical department. Regular audits can not only assure external bodies, such as regulatory authorities, that proper procedures have been followed, but also serve to deter those rare attempts at fraud on the part of clinical investigators, which occasionally become evident. ... 

Those siderophores with low molecular weight, nonpeptidal structures are anticipated to be stable to proteolytic enzymatic degradation, and less likely to evoke an immune response. The antibiotic can be selected from commercial sources or from a large arsenal of potential antibiotics with low solubility that were overlooked, or never underwent extensive clinical investigations. 

Cytokines have been under clinical investigation as adjuvants to vaccines, and IFNs and IL-2 have shown some positive effects in the response of human subjects to hepatitis vaccine. IL-12 and GM-CSF have also shown adjuvant effects with vaccines. GM-CSF is of particular interest because it promotes recruitment of professional antigen-presenting cells such as the dendritic cells required for priming naive antigen-specific T-lymphocyte responses. There are some claims that GM-CSF can itself stimulate an antitumor immune response, resulting in tumor regression in melanoma and prostate cancer. 

Rowland-Jones, S. L., T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. 1998. Cytotoxic T Cell Responses to Multiple Conserved HIV Epitopes in HIV-Resistant Prostitutes in Nairobi. Journal of Clinical Investigation 102 1758-1765. 

In clinical investigations, the use of drugs with known mechanisms of action to provoke biological or behavioral responses that would provide clues where abnormalities in brain functioning may exist in specific psychiatric disorders... 

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