The automation of clinical trial serious adverse event reporting workflow.

BACKGROUND: The reporting of serious adverse events is a requirement when conducting a clinical trial involving human subjects, necessary for the protection of the participants. The reporting process is a multi-step procedure, involving a number of individuals from initiation to final review, and must be completed in a timely fashion. PURPOSE: The purpose of this project was to automate the adverse event reporting process, replacing paper-based processes with computer-based processes, so that personnel effort and time required for serious adverse event reporting was reduced, and the monitoring of reporting performance and adverse event characteristics was facilitated. METHODS: Use case analysis was employed to understand the reporting workflow and generate software requirements. The automation of the workflow was then implemented, employing computer databases, web-based forms, electronic signatures, and email communication. RESULTS: In the initial year (2007) of full deployment, 588 SAE reports were processed by the automated system, eSAEy. The median time from initiation to Principal Investigator electronic signature was <2 days (mean 7 +/- 0.7 days). This was a significant reduction from the prior paper-based system, which had a median time for signature of 24 days (mean of 45 +/- 5.7 days). With eSAEy, reports on adverse event characteristics (type, grade, etc.) were easily obtained and had consistent values based on standard terminologies.Limitation The automated system described was designed specifically for the workflow at Thomas Jefferson University. While the methodology for system design, and the system requirements derived from common clinical trials adverse reporting procedures are applicable in general, specific workflow details may not be relevant at other institutions. CONCLUSION: The system facilitated analysis of individual investigator reporting performance, as well as the aggregation and analysis of the nature of reported adverse events.

Institutional review board approval: why it matters.

The modern institutional review boards originated in the 1970s. They exist to protect human subjects participating in research from potential harm. The Belmont Report provided the ethical principles (respect for persons, beneficence, and justice) that should be observed while conducting research on human subjects. Compliance with the ethical principles of the Belmont Report is a first step in successful submissions to an institutional review board. Regulations regarding conflict of interest represent an attempt to ensure that research is not biased by financial or other interest and to maintain public trust.

Phenotypic characterization of inflammatory cells from osteoarthritic synovium and synovial fluids.

Osteoarthritis (OA) is considered a degenerative joint disorder caused by mechanical wear to the articular surface. However, while joint injury, obesity, and mutations in collagen increase the risk of developing OA, evidence implicates inflammatory mechanisms in disease progression and chronicity. To address this question we used FACS analysis, immunohistochemistry, and in vitro cell culture to evaluate inflammatory mechanisms in synovial fluids and joint tissues obtained after arthrocentesis or knee replacement surgery. Immunohistochemistry revealed a significant T cell infiltrate in six of nine tissue specimens. T cells were present throughout the synovial membrane and were particularly localized around vasculature and in large cellular aggregates. Cells within the aggregates expressed markers associated with immune activation and antigen presentation. T cells from OA synovial fluids expressed an activated phenotype and synthesized interferon-gamma following in vitro stimulation. These data support the hypothesis that inflammatory cells play a significant role in OA disease progression and chronicity.

Increased microchimeric CD4+ T lymphocytes in peripheral blood from women with systemic sclerosis.

Recent studies have demonstrated the presence of microchimeric cells in peripheral blood and skin lesions from patients with systemic sclerosis (SSc). In a previous study we found that some peripheral blood CD3+ cells from female patients with SSc contained male DNA. Here, peripheral blood samples from 47 patients with SSc (30 with diffuse cutaneous SSc and 17 with limited cutaneous SSc) and 22 healthy controls were sorted for CD4+ and CD8+ T cells. Both positively and negatively selected populations were analyzed for male DNA by quantitative PCR. Analysis of Y chromosome sequences in the sorted cells demonstrated the presence of microchimerism in 82.9% of SSc patients compared to 63.6% of controls. The numbers of CD4+ and CD8+ T cells were found to be significantly higher in the SSc patients than in controls. Furthermore, patients with dcSSc were observed to have significantly more CD4+ microchimeric T cells than the controls. In the CD8+ T-cell population, there was a trend toward more microchimeric cells in the patients but this did not reach significance. These results support the hypothesis that microchimeric CD4+ T cells may be involved in the pathogenesis of SSc.

Rheumatoid arthritis--a molecular understanding.

The application of molecular immunology techniques in the study of rheumatoid arthritis has resulted in an explosion of knowledge on the risk factors for the disease, predictors of disease severity, the molecular mechanisms of inflammatory responses, and mechanisms of tissue destruction. We know, for example, that inheriting certain genes in the major histocompatibility complex partly dictates susceptibility and severity of rheumatoid arthritis. These genes and others in the major histocompatibility complex are critical for the occurrence of immune responses both constructive (prevention of infection, surveillance for malignant cells) and destructive (development of autoimmune diseases). We also now understand mechanisms of cell communication, regulation of immune responses, how the cells that mediate immune responses and tissue injury accumulate in tissues, and how the injury occurs. The knowledge itself is satisfying, but more important, based on this knowledge, effective and reasonably safe treatments that address basic mechanisms of the disease process have been developed and are now widely used. In fact, the newer treatments represent the "tip of the iceberg," and as our basic knowledge increases, so too will the armamentarium with which we can fight rheumatoid arthritis and other similar autoimmune diseases.