Study design sample size

In addition, it has become accepted (and even expected) that a cardiovascular safety outcome trial be conducted to accrue the number of cardiovascular events to discharge the 1.3 threshold. The approach utilized to discharge the 1.8 and 1.3 thresholds will determine the timing of when this trial will be initiated (during Phase III or post-submission), a topic discussed shortly. Typically, these cardiovascular safety outcome trials are event driven, i.e., they are designed to accrue a prespecified number of outcomes. The number of outcomes will determine the statistical power of the study. The sample size and cardiovascular event rate, contingent on the underlying risk of the population, will impact the duration of the trial, as shown in Table 13.2. 

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). 

Similarly, the number and types of tests completed will influence the cost in ways that can be very complex. Recently, the author was involved in designing a proof-of-principle study intended to assess the ability of a dietary supplement to enhance weight loss among subjects instructed to follow a reduced energy diet. Sample size calculations were run for two scenarios, the first using change in body weight as the primary outcome variable, the... 

LSMBSs are designed so that the types of data to be collected meet particular objectives regarding how the data will be used. For example, the number of exemplars collected in the LSMBS will depend on the use planned for the study results. Thus, if the levels of plasticizer in packaged foods will be determined to address an acute (i.e., short-term) dietary exposure and risk concern, the sample size (i.e., number of food packages to be collected) must be adequate to support the higher percentiles... 

Additional information regarding applicator-boom width, spray-tank capacity, and the wheelbase of any vehicle-mounted soil sampling equipment used during the study is also required to ensure that the field plot design accommodates size restrictions of field equipment. 

However, since the data used in this study are subject to the limitations and uncertainties cited above, the results of this analysis represent only a very rough approximation of the national frequency distribution of indoor radon levels. EPA s national survey will seek to more accurately characterize this distribution through use of a larger sample size, a statistically based survey design, and consistent, quality assured sample collection and measurement procedures. 

Discussion This was the first study involving volunteers - four members of the laboratory staff who, with minimal baselines, were observed for 48 hours, or until effects appeared to have subsided. No statistical analysis was done with the data, due to the small sample size and the fact that this was essentially a range-finding study, designed to indicate the approximate doses required to produce moderate to severe incapacitation. 

The impact of these considerations on study subject selection, sample size and endpoint measures will need to figure in future clinical trial designs. 

It is generally the case that when more complex statistical analysis strategies and designs are under consideration, standard sample size calculations are inadequate to cover them. In such circumstances simulation is often used to determine the t)rpe-I and type-II errors of the proposed studies for a given sample size. 

We decided to examine only one sample size for the design, 4096. Abt et al. (6) examined sample size, among other factors, when studying sequential screening. Yi et al. (20) also used a sample size of 4096 when studying the optimization of a statistical analysis method for this dataset. Both studies indicated that relatively small sample sizes of 5000 to 10,000 compounds could be used to produce useful trees. Clearly, large sample sizes should lead to better... 

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