Clinical studies sites

The new GCP requires clinical study sites to have enough facilities to conduct clinical trials and be able to cope in the case of emergency. Adequately trained staff should be available. The sites must prepare SOPs for accepting, reviewing and operating clinical trial. Additional SOPs are required for the operation of the Institutional Review Board (IRB). A clinical trial office and an office for IRB operation must be established in the study site. These requirements have been defined as the minimum requirements for any clinical trial to be conducted in hospitals equipped with ample resources, to manage many SOPs, and office staff for clinical trial and IRB. 

Prior to selection of a clinical study site, the sponsor/CRO must confirm and document, in the pre-study assessment visit report, that the investigator has access to a local ethics committee/IRB. Local committees cannot be bypassed the only... 

It was customary for Phase III studies that study centres were chosen on marketing grounds as well as from the scientific aspect. Because many similar products were developed and launched, hospitals decided to list in their formularies only those drugs in whose development they had participated. A vital issue for sponsoring companies is that their product be listed in the formularies of major hospitals, such as university hospitals or main regional hospitals. Therefore, the Phase III clinical study sites tend to... 

Prior to selection of a clinical study site, the sponsor/CRO must confirm and document, in the prestudy assessment visit report, that the investigator has access to a local ethics committee/ IRB. Local committees cannot be bypassed the only official exception to this requirement is in France, where, by regulation, a central committee may rule for all sites in a multicentre study. However, in the USA, it appears to be common practice for a central IRB to rule for the widely geographically separated areas in the country, and researchers may not inform the local IRB. 

When the product development program has been completed and the NDA has been submitted for review, the FDA will likely perform routine inspections of the manufacturing facilities to verify GMP compliance and a sample of the clinical study sites to verify GCP compliance. 

Fused Pellets. Another form of an implant is a fused pellet. The pellets may be composed of either the dmg alone, or the dmg fused with cholesterol (29,36), and are formed as small cylinders by melting the dmg and then soHdifying it under pressure. Clinical studies with norethindrone pellets have been in progress for a number of years. Effective rates of release of the dmg from the implantation site were originally difficult to achieve. 

Design validation, on the other hand, is focussed on assessing if the device in its totality meets the user s needs and intended uses and functions correctly under the intended use conditions. Thus, evaluation will usually be carried out at field sites/(i-sites (hospitals) or, at a minimum, under simulated use conditions. In the case of high-risk devices this will normally involve actual clinical studies. Validation should be performed using initial production lots of the device or their equivalents. 

In contrast to the wide range of phenotypic susceptibility of viruses to enfuvirtide, analyses of gp41 sequences at entry into clinical studies show relatively little variation within the gp41 aa 36 5 region representing the binding site of enfuvirtide (described later). The most common polymorphism, N42S ( 16% prevalence... 

An overall osteoprotective effect is associated with soy diets, the major active component being the isoflavones although the contribution (if any) of soy protein has to be clarified. The spine, rather than the femur, appears to be the most consistently protected bone site. The average daily intake in Japanese women is around 50 mg/day and appears to be sufficient to have a long-term protective effect on the spine. In non-Asian, postmenopausal women, the demonstrated effective dose is 80-90 mg/day. In future clinical studies, investigating the effect of isoflavones on bone metabolism, larger scale, randomized, controlled, intervention trials for longer time periods (1-3 years) will be necessary with a standardized source of soy protein/isoflavones and... 

The number of study sites to be used for a clinical trial depends on the characteristics and number of subjects that need to be recruited. Often, a sufficient number of participants cannot be enrolled from a single site, especially if the study inclusion criteria are restrictive and the timeframe for recruitment is limited. In order to complete the study within a reasonable period of time, an inclusion of multiple research centers is often necessary (Chow and Liu, 1998). The selection of study sites depends on several factors including ... 

As indicated, a progressively larger portion of activities in a clinical trial matrix is controlled by function-specific software, provided by IT vendors, CROs, or sponsors. This may be problemahc in study sites that execute multiple studies for different sponsors simultaneously, all having different SOPs, data collection procedures and payment policies. Standardized site-specific software is being developed and refined to accommodate this problem, but currently busy study sites can find this accommodation challenging. 

CRAs achieve these tasks through frequent visits to the clinical trial site. During these visits, the monitor will verify source data, audit regulatory documents for accuracy and completion, perform drug accountability assessments, and communicate any concerns, problems, or new information with the study staff. 

Normally, the study subject is informed both verbally and in the ICF that certain other individuals besides the investigator site staff wiU view his or her medical records. In clinical studies sponsored by pharmaceutical companies or institutions, the monitoring and quality assurance (QA) personnel from the sponsors and CROs, and inspectors from a regulatory agency wiU review the medical records of the study subject. 

Inspectors will visit the investigator site and may possibly wish to visit the sponsor s office. They will review the documentation of the study file (see Box 7.1). Approval documents of the lEC will be compared with any amendments made to the protocol or to the subject s information sheet/ICR Consent forms for the study subjects will be inspected to establish who actually gave consent and whether this was before entry into the clinical study. A thorough source data verification of the CRF with the source documents, including the medical records, will be undertaken. Documentation relating to drug accormtability wiU be matched with each subject s CRF The facilities wiU be reviewed and the site staff interviewed. Further information can be obtained from... 

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