Protocols, clinical

There are several areas of study that will help you understand the research topic. As a first step you will want to read the clinical protocol. The protocol describes the device or medication to be used, the patient populations under study, the statistical plan of the clinical trial, and the details of the disease state. If you want to understand the disease state or indication further, you may want to seek out a clinical investigator of the clinical trial or do some further reading about the disease. Understanding the patient population is a good way to understand the data that you will see and whether there is reason for concern when viewing the data. For example, if you were studying a medication to reduce hypertension, you would not be as worried if patient blood pressure data were elevated at baseline. You would expect to see this because you understand that hypertensive patients have high blood pressure. 

In order to reduce unnecessary data queries, the statistics group should be consulted early in the clinical database development process to identify variables critical for data analysis. Optimally, the statistical analysis plan would already be written by the time of database development so that the queries could be designed based on the critical variables indicated in the analysis plan. However, at the database development stage, usually only the clinical protocol exists to guide the statistics and clinical data management departments in developing the query or data management plan. 

Tjelle TE, Rabussay D, Ottensmeier C, Mathiesen I, Kjeken R (2008) Taking electroporation-based delivery of DNA vaccination into humans a generic clinical protocol. Methods Mol Biol 423 497-507... 

Figure 14.7 Large-scale manufacture of adenoviral vectors for use for gene-therapy-based clinical protocols. Refer to text for details...

Division of Clinical Trial Design and Analysis Preclinical pharmacology and toxicology Clinical trial design, safety and efficacy 20% of CBER clinical protocols are now for gene therapy. 

The formulations that are developed and used for preclinical studies are sometimes specific for the test species to be employed, but their development always starts with consideration of the route of exposure that is to be used clinically and, if possible, in accordance with a specified regimen of treatment (mirroring the intended clinical protocol, as much as possible). One aspect of both nonclinical and clinical formulation and testing which presents an important but often overlooked aspect of pharmaceutical safety assessment is the special field of excipients. These will be considered at the end of this chapter... 

Such a meeting will help the Sponsor to organize animal research, gather data, and design the clinical protocol based on suggestions by the FDA. 

Clinical Trial Application (CTA) has to be submitted to Health Canada seeking permission to conduct clinical trials. The submission should include information regarding drug characteristics, test data, animal studies, and clinical protocol. A clinical trial may be stopped when either it is shown to be unsafe or dramatic benefits are obtained. The approval process may be fast-tracked if a drug is shown to have substantial benefits, such as for treatment of life-threatening or severely debilitating conditions. 

In the future, studies testing co-administration of HDAC inhibitor and an activator such as IL7 or prostratin-like agent, together with intensified HAART, could offer a new hope for HIV-1-infected patients. This type of clinical protocol could provoke a drastic HIV-1 activation leading to a strong decline of HIV-1 reservoir level, sufficiently to allow HIV-1 remission. 

Sixth, clinical protocols may offer patients additional resources that are not routinely available in clinical practice. These additional resources may provide health benefits to patients. For example, protocols offering extensive home care services may affect the observed benefits of a therapy if the nursing intervention improves the management of the patient s illness. This could result in a bias in the study design if there are differences in the amount of home care services provided to patients in the treatment and control arms of a trial, or may result in additional health benefits to all study patients. 

Seventh, patients in trials often are carefully selected. If a study sample has a mean patient age of 45 years, the result of the trial may not be readily generalizable to substantially older or younger populations. Similarly, exclusion criteria in clinical protocols may rule out patients with specific clinical syndromes (e.g., diabetes mellitus), women of childbearing potential, or patients of advanced age. These patients may require additional resources or may receive less benefit from therapy because their life span is shorter. These exclusions further limit the generalizability of the findings of efficacy studies. 

In summary, due to their focus on efficacy and their use of clinical protocols, economic assessments of pharmaceutical products based upon phase III clinical trials are not without their problems. However, these issues can be developed in pharmacoeco-nomic analysis plans or through supplemental data collection activities conducted concurrently with the clinical trial. 

For women who are of childbearing potential, the risks can be evaluated in reproductive toxicology studies and steps taken to minimize those risks. Alternatively, stringent contraceptive requirements can be incorporated into the clinical protocol to prevent the occurrence of pregnancy in the participants, although in practice, contraception is usually specified in all cases. Any risks should be... 

Some of the above-mentioned methods have limitations. Southern blot analysis requires a large amount of high-quality DNA, and the results are unreliable if the sample has a low percentage of tumor cells (Ross and Fletcher, 1998). For these and other drawbacks, this method is precluded from becoming a routine clinical protocol to determine HER-2 status. 

G.F. Whalen, Lipid coated microbubble (LCM)-facilitated ultrasonic treatment of liver tumors, Clinical Protocol No. 99-235 filed with Office of Clinical Research, Institutional Review Board (IRB), Univ. of Connecticut Health Ctr. (IRB Approval by full Board for first phase granted 5-13-99) in conjunction with Critical Technologies Funding Competition (G.F. Whalen and J.S. D Arrigo, Co-P.I. s), 1999 (limited distribution reports). 

In the following section, the current clinical methodologies to detect EMPs and MPs as they pertain to EMPs are discussed. In addition, a summary of the most widely used clinical methods can be found in Table 1. The protocols described are circumscribed to clinical protocols, as they are representative of in vitro assays as well. 

Adhere to the clinical protocol s inclusion and exclusion criteria. 

Principal investigator—The individual responsible for conducting the study at the clinical site and selecting additional investigators when needed. The investigator must adhere to the clinical protocol and comply with inclusion and exclusion criteria. Clinical QA must ensure that monitors know how to identify principal investigator noncompliance. 

Janson, C. et al. (2002). Clinical protocol. Gene therapy of Canavan disease AAV-2 vector for neurosurgical delivery of aspartoacylase gene (ASPA) to the human brain. Hum. Gene Ther. 13, 1391-1412. 

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