Dosage trials design

Protocol The detailed plan for a clinical trial that states the trial s rationale, purpose, drug or vacdne dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH]... 

In conclusion, robust population pharmacokinetic models may contribute to the mechanistic understanding of the fate of mAbs in the body. Factors that may influence the pharmacokinetics of mAbs should be investigated for their potential influence on dosage regimen design in clinical trials and therapeutic use. 

Phase I trials are the first-stage of testing in human subjects. These tests take about a year and involve about 20 to 80 normal, healthy volunteers. This phase includes trials designed to assess the safety profile, including the safe dosage range and tolerability. The studies also determine how a drug is absorbed, distributed, metabolised and excreted, and the duration of its action. 

Kenna and Sheiner (41) used a simulation study to show that the MPML method— which uses an aU compliance data-dosage history questionnaire, Cq, available from all subjects and combines that with dosing history obtained with MEMS, C, from a random fraction of subjects, effectively calibrating Cq to C—is superior to other methods that use only one compliance measure, or both, or neither where neither was intention-to-treat. The authors showed that the MPML approach yielded efficient dose-response estimates over a wide range of clinical trial designs, effect sizes, and varying quality and quantity of compliance information. The method was shown to maintain good performance even when its key assumptions were violated and compliance data were sparse. 

In pharmaceutical and medical device development, clinical trials are classified into four main phases designated with Roman numerals 1,11, III and lY The various phases of development trials differ in purpose, length and number of subjects involved. Phase I trials are conducted to determine safe dose levels of a medication, treatment or product (National Institutes of Health, 2002). The main purpose is often to determine an acceptable single dosage - how much can be given without causing serious side-effects. Phase I trials will also involve studies of metabolism and bioavailabity (Pocock, 1983). The sample size of a Phase 1 clinical trial is usually small, ranging from 10-80 subjects (National Institutes of Health, 2002 Pocock, 1983). 

A prospective, randomized, placebo-controlled trial of paroxetine in adults with chronic post-traumatic stress disorder (PTSD) was recently conducted (Marshall etal., 2007). The subjects were New Yorkers, predominantly female (67%) and Hispanic (65.4%). Seventy subjects entered the study and after a one week placebo lead-in, 52 subjects were randomized to placebo or paroxetine for ten weeks. The subjects were treated with a flexible dosage design (mean dosage, 40.4 mg/day). Dropout rates were 32% for paroxetine and 51.9% for placebo. There were no differences in rates of adverse effects between treatment arms. Paroxetine was superior to placebo in ameliorating the primary symptoms of PTSD (56% vs. 22.2%). 

Therapeutic exploratory (Phase lb/II) Explore use for the targeted indication Estimate dosage for subsequent studies Provide basis for confirmatory study design, endpoints, methodologies Earliest trials of relatively short duration in well-defined narrow patient populations, using surrogate or pharmacological endpoints or clinical measures Dose-response exploration studies... 

Statistics plays a major role in the design of the clinical trial. The groups or subgroups to be studied, the frequencies, dosages, and the markers used to monitor drug efficacy are all important factors to consider. Statistical analysis provides the means to demonstrate, at a certain confidence level, whether the... 

Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, and the clinical trial dose administration schedule was designed to account for this adsorption. Clinical trials were conducted using PVC tubing therefore its use is recommended. The concentrations and rates of infusion provided in Administration and Dosage reflect doses identified in these studies. It is important that the recommended infusion regimen be followed closely. 

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