Study protocol

Based primarily on the study protocol of the 1995 NINDS rt-PA study.Many centers would also exclude patients with known documented endocarditis or aortic dissection, and those with CT hypoattenuation in more than one third of the middle cerebral artery territory. There are insufficient data to support the use of rt-PA for ischemic stroke in pregnancy or in the pediatric population (age <18 years). 

Clinical trials are costly to conduct, and results are often critical to the commercial viability of a phytochemical product. Seemingly minor decisions, such as which measurement tool to use or a single entry criterion, can produce thousands of dollars in additional costs. Likewise, a great deal of time, effort and money can be saved by having experts review the study protocol to provide feedback regarding ways to improve efficiency, reduce subject burden and insure that the objectives are being met in the most scientifically sound and cost-effective manner possible. In particular, I recommend that an expert statistician is consulted regarding sample size and power and that the assumptions used in these calculations are reviewed carefully with one or more clinicians. It is not uncommon to see two studies with very similar objectives, which vary by two-fold in the number of subjects under study. Often this can be explained by differences in the assumptions employed in the sample size calculations. 

When conducting a clinical trial, the well-being of the study subjects is primary. Subjects must be treated fairly and with respect. The two primary methods of ensuring fair treatment of study subjects are review of the study protocol by an Institutional Review Board (IRB) or Ethics Committee and... 

Once objectives have been defined, a study protocol including an appropriate QA/QC program is developed. Initially, both literature and information searches should be made. If possible, selected field measurements based on an assumed dispersion model can also be made. The objective of the exploratory study is to obtain the best possible answers to the following questions. 

In the SMMT process, draft protocols are reviewed, and guidance provided to the sponsor to help ensure that the format and specifications are adequate. The protocol should be approved by CVM prior to the initiation of the method trial. Once the protocol and method description are acceptable to CVM, the methods are sent to the participating laboratories for review, and a method demonstration is scheduled. The method demonstration, attended by all participating laboratory analysts, involves review of the study protocol and method SOP and a laboratory demonstration of the method. Ideally, all revisions are completed by the end of the demonstration and the study protocol is signed. 

Nevertheless, such special study protocols should be discussed with those regulatory authorities which are involved in the national registration and/or EU evaluation in advance. 

PHI for the crop (for early season applications this may need to be estimated in the protocol and then confirmed upon harvest of the crop for applications close to the harvest time for a specific RAC, the PHI must be in specific days/hours after the last application and be clearly described in the study protocol)... 

For studies involving test substance application to soil, there may be a requirement for more soil information than for studies where applications are made to foliage of established crops. The study protocol should describe any specific requirements relative to soil type selection and how to confirm the soil characteristics for the study. Most studies simply require that the soil be identified by its name (e.g., Keystone silt loam) and composition (e.g., percent sand, silt, and clay). This information can typically be acquired from farm records, a soil survey of the local area, or a typical soil analysis by a local soil analysis laboratory. In some instances, a GLP compliant soil analysis must be completed. The study protocol must clearly define what is needed and how it is to be obtained. Unless specified in the protocol, non-GLP sources are adequate to identify the soil and its characteristics. The source of the soil information should be identified in the field trial record. 

The study protocol determines the quantities of raw materials to be processed. The protocol should state the quantity of each fraction sample to be provided and whether multiple samples are to be drawn from each fraction sample. The wording of the protocol should allow for a range of quantities that is to be provided for each processes commodity to avoid having to prepare protocol deviations. For example, stating that a minimum of 1 lb of pur6e is to be provided avoids a protocol deviation if the processor provides 1.1 lb of purde. 

This article summarizes key items discovered or developed during the OPMBS, to illustrate (a) the design of an LSMBS study protocol and (b) specific practices found useful in the conduct of such a study. 

To be successful, an LSMBS requires a clear definition of the responsibilities of each participating individual or group. Preparation of an organization chart may be appropriate, as would its inclusion in the study protocol. Key study participants could include Study Directors, Principal Investigators in the sample collection and analytical phases, sponsor representatives, technical consultants, residue analytical laboratories, and QA specialists. 

Residue study protocols typically either include quality specifications for analytical procedures or refer to a written analytical method that includes such specifications. The protocol for an LSMBS should also include analytical quality specifications, either directly or by reference to a method. Analytical specifications usually include minimum and maximum recovery of analyte from fortified control samples, minimum number of such fortifications per set of samples, minimum linearity in calibration, minimum stability of response to injection of calibration solutions, and limits of quantitation and of detection. 

Study Prospective Ground-Water Monitoring Study Study Protocol No. 12345... 

Study Protocol (160.120) an approved written plan that clearly indicates the objectives and all methods for the conduct of the study. 

Most consent forms that have been developed have at some time been reviewed by standing ethical review boards, usually associated with a university. The format of the consent form described above has been reviewed over time by more than one ethical review board and would be acceptable in most States for the purpose of acquiring the consent of potential volunteers in a worker exposure or re-entry study. If performing worker exposure studies in California, the researcher is advised to contact the State regulatory agencies and submit the draft consent form and study protocol to the State-appointed ethical review board for review and approval prior to initiation of the field phase of the study. Of course, if the researcher has any doubt about the acceptability of the proposed consent form, he/she should contact the appropriate state agencies where they plan to perform the study. 

The establishment of performance criteria for a given tumor marker test is not a simple process because accuracy and precision are unique for each type of analyte and its application. Establishing methodological limits for accuracy, precision, sensitivity, and specificity often requires standard reference materials, quality control materials, comparative studies, and actual clinical specimens. Accuracy and precision must be measured over the analyte reportable range for which the device is intended to be used. Sensitivity and specificity must be considered with respect to the intended clinical use of the device. Also, the indications for use should be carefully considered in the design of the study protocol. The indications for class II should be to monitor residual tumor after surgery (or radiation), the recurrence of tumor, or response to therapy. A 510(k) must provide clear evidence that the device is accurate, safe, effective, and substantially equivalent to a device legally marketed in the United States. 

Model development is intimately linked to correctly assigning model parameters to avoid problems of identifiability and model misspecification [27-29], A full understanding of the objectives of the modeling exercise, combined with carefully planned study protocols, will limit errors in model identification. Compartmental models, as much as any other modeling technique, have been associated with overzealous interpretation of the model and parameters. 

The US EPA has been concerned with neurotoxicity and sensitivity of children to pyrethroids (Sect. 5.1.2), and demanded pyrethroid registrants in the US to conduct developmental neurotoxicity (DNT) studies. However, the EPA concluded that a DNT study was inadequate for the evaluation of age-dependent sensitivity for pyrethroids, and asked interested parties to submit study protocols voluntarily to understand better the age-dependent sensitivity for pyrethroids (February 2010). To deal with this issue, the pyrethroid registrants in US formed a task force group, and proposed a new study design including PBPK modeling to the US EPA. 

Common Study Protocols. The dog is the most commonly used nonrodent species in safety assessment testing (i.e., acute, subchronic, and chronic studies). The exception to this is its use in developmental toxicity and reproductive studies. For developmental toxicity studies, the dog does not appear to be as sensitive an indicator of teratogens as other nonrodent species such as the monkey (Earl et al., 1973) or the ferret (Gulamhusein et al., 1980), and, for reproductive studies, the dog is not the species of choice because fertility testing is difficult to conduct (due to prolonged anestrus and the unpredictability of the onset of proestrus) and there is no reliable procedure for induction of estrus or ovulation. 

Study Protocols. Historically, the ferret has been used more often in teratology (Hoar, 1984), reproductive (Hoar, 1984), and acute safety studies than in repeated dose studies (4-52 weeks in duration). More consideration, however, is now being given to the use of the ferret in pivotal repeated-dose safety assessment testing (Thornton et al., 1979 Hart, 1986 Haggerty et al., 1989). 

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