The advisory process for anticancer drug regulation: a global perspective.

PURPOSE: This paper summarizes the role of external advisors in oncology drug development and regulation from a global perspective. DESIGN: Recently, representatives from the United States Food and Drug Administration, European Medicines Agency, the Japanese Pharmaceuticals and Medical Devices Agency, the Australian Therapeutic Goods Administration and Health Canada held a meeting in conjunction with the American Society of Clinical Oncology meeting. The role of external advisors in oncology drug development and regulation in each of these jurisdictions was presented and discussed. RESULTS: All regulatory bodies described have experience with two forms of outside expertise: advice from individual experts and advice from a group of experts assembled as an advisory group. Regulatory jurisdictions use individual experts variably. In some regions, individual experts provide advice based on knowledge and experience during the drug development phase or in the planning phase for the submission of a drug registration package. In other regions, these individuals serve as external evaluators with the primary responsibility for the review of a clinical trials package submitted for drug registration. Advisory boards have been formalized in all jurisdictions discussed. Advisory boards have a role in discussing specific applications as well as broad policy issues. A common theme is a composition of a core panel of experts with augmentation by additional expertise as needed for consideration of specific scientific questions. In all jurisdictions, advisory board recommendations are not binding on the regulatory body. CONCLUSIONS: Global oncology drug development and registration involves the use of experts by regulatory authorities. The types of experts needed, the expert's role and the transparency of the advisory process reflect the individual needs in different regions.     

September 11th related stress and trauma in New Yorkers

Exposure to trauma and stress has been linked with poor health, while forgiveness appears to be positively associated with health outcomes. The current study investigates whether traits such as forgiveness and ruminative tendencies predict levels of trauma and stress experienced by New York City residents on the 1‐year anniversary of the September 11th terrorist attack. Seventy‐one students and staff members (57 females, 14 males) of a graduate school in New York City were administered the Impact of Events Scale, the Perceived Stress Scale, and questionnaires designed for the purpose of this study to measure ruminative tendencies and forgiveness on September 11, 2002. Rumination predicted levels of trauma (p < 0.05) and perceived stress (p < 0.01). Lower levels of forgiveness predicted perceived stress (p < 0.05), but not trauma. Rumination mediated the relationship between forgiveness and perceived stress. These findings suggest that individuals with higher levels of rumination have an elevated risk of experiencing trauma and stress‐related symptoms following a traumatic event. Forgiveness is associated with lower levels of stress, but not trauma, perhaps because trauma is an extreme form of stress. Forgiveness appears to serve as a buffer against stress more so in individuals with low levels of rumination than in individuals with high levels of rumination. Copyright © 2005 John Wiley & Sons, Ltd.     

Management of the pregnant opiate user

Increasing numbers of women are seeking help for drug misuse. In addition to problems associated with drug dependence, there are also problems concerning child care, pregnancy and women's health. In this paper we discuss the management of the pregnant opiate user, effects of opiate use in utero and postpartum and ways in which non-drug services can assist in the early identification and treatment of these women.     

Immunization-induced inflammatory infiltration of the central nervous system in transgenic mice expressing a microbial antigen in astrocytes

Transgenic mice expressing a defined microbial antigen from central nervous system (CNS) cell type-specific promoters can be utilized to investigate the consequences of induction of peripheral immune responses to foreign antigens produced by different CNS cell types. Immunization of mice expressing β-galactosidase (β-gal) in astrocytes with this protein resulted in antigen-dependent infiltration of the CNS by mononuclear cells, principally CD4⁺ T lymphocytes and monocyte/macrophages. The perivascular and intraparenchymal infiltrates, which were located predominantly in the hippocampal formation and cerebellum, the areas of highest β-gal expression, were associated with astrocytosis, microgliosis, and a generalized increase in blood-brain barrier permeability. The resemblance of these pathological changes to aspects of human immune inflammatory CNS disorders e.g. multiple sclerosis, suggests that an initiating step in the process by which such complex diseases are produced could be the induction of peripheral immune responses to antigens expressed in astrocytes.     

A semi-quantitative direct contact assay using fluorescein diacetate and L929 mouse fibroblasts in monolayer culture

Summary A semi-quantitative procedure is described for measuring cell viability after short-term exposure to a test substance using a monolayer culture. Test substances are placed in direct contact with cell monolayers for various time intervals. The substances are removed and the monolayers are incubated in the presence of fluorescein diacetate. Monolayers are viewed under a fluorescent microscope and the percentage of fluorescing (viable) cells is estimated. The method is suitable for examining cytotoxic effects at short times of exposure and for discriminating between test substances that give similar, low toxicity endpoints in standard 24-h assays.     

The Stafford outbreak of Legionnaires' disease

A large outbreak of Legionnaires' disease was associated with Stafford District General Hospital. A total of 68 confirmed cases was treated in hospital and 22 of these patients died. A further 35 patients, 14 of whom were treated at home, were suspected cases of Legionnaires' disease. All these patients had visited the hospital during April 1985. Epidemiological investigations demonstrated that there had been a high risk of acquiring the disease in the out patient department (OPD), but no risk in other parts of the hospital. The epidemic strain of Legionella pneumophila, serogroup 1, subgroup Pontiac 1a was isolated from the cooling water system of one of the air conditioning plants. This plant served several departments of the hospital including the OPD. The water in the cooling tower and a chiller unit which cooled the air entering the OPD were contaminated with legionellae. Bacteriological and engineering investigations showed how the chiller unit could have been contaminated and how an aerosol containing legionellae could have been generated in the U-trap below the chiller unit. These results, together with the epidemiological evidence, suggest that the chiller unit was most likely to have been the major source of the outbreak. Nearly one third of hospital staff had legionella antibodies. These staff were likely to have worked in areas of the hospital ventilated by the contaminated air conditioning plant, but not necessarily the OPD. There was evidence that a small proportion of these staff had a mild legionellosis and that these 'influenza-like' illnesses had been spread over a 5-month period. A possible explanation of this finding is that small amounts of aerosol from cooling tower sources could have entered the air-intake and been distributed throughout the areas of the hospital served by this ventilation system. Legionellae, subsequently found to be of the epidemic strain, had been found in the cooling tower pond in November 1984 and thus it is possible that staff were exposed to low doses of contaminated aerosol over several months. Control measures are described, but it was later apparent that the outbreak had ended before these interventions were introduced. The investigations revealed faults in the design of the ventilation system.     

An Interdisciplinary Clinical Advancement Program Within a Patient-Centered Care Model

Restructuring in health care does not have to compromise the pursuit of clinical excellence and quality patient care. The clinical advancement program (CAP) at the Hospital for Special Care is a newly developed multidisciplinary reward and recognition program for clinical staff. The program is integrated into the hospital's structure of service line management and, unlike traditional advancement programs, is open to all levels of care providers: professional personnel, technical staff, and aides. This article describes the basic features of the CAP model and how it was developed by a multidisciplinary task force.