Abstract: The objective of a long-term stability experiment is to confirm analyte stability in a given biological matrix, encompassing the duration of time from sample collection to sample analysis for a clinical or preclinical study. While long-term analyte stability has been identified as a key component of bioanalytical method validation, current regulatory guidance provides no specific recommendations regarding the design and analysis of such experiments. This paper reviews and evaluates various experimental designs, data analysis methods, and acceptance criteria for the assessment of long-term analyte stability. Statistical equivalence tests based on linear regression techniques are advocated. Both a nested errors and bivariate mixed model regression approach are suitable for application to long-term stability assessment, and control the risk of falsely concluding stability.
Abstract: BACKGROUND: Effective treatments for adolescent schizophrenia are needed. AIMS: To compare efficacy and safety of two dosing regimens of risperidone. METHOD: Double-blind, 8-week study. Patients, 13-17 years, with an acute episode of schizophrenia, randomised 1:1 to risperidone 1.5-6.0 mg/day (regimen A; n=125) or 0.15-0.6 mg/day (regimen B; n=132). Trial registration number: NCT00034749. RESULTS: Mean total Positive and Negative Syndrome Scale (PANSS) score improved significantly (P<0.001; effect size=0.49) from baseline to end-point for regimen A (mean=96.4 (s.d.=15.39) to mean=72.8 (s.d.=22.52)) compared with regimen B (mean=93.3 (s.d.=14.14) to mean=80.8 (s.d.=24.33)). Treatment-emergent adverse events occurred in 74% (regimen A) and 65% (regimen B) of patients; 4% of patients overall discontinued for adverse events. Mean change in body weight was 3.2 kg (s.d.=3.49) for regimen A and 1.7 kg (s.d.=3.29) for regimen B. CONCLUSIONS: Adolescent patients in the regimen A group showed greater improvement in total PANSS compared with the regimen B group. Treatment was well tolerated.
Abstract: Two diagnostic procedures with binary outcomes are usually compared by Cohen's kappa coefficient of agreement. If the results of the two procedures are completely identical on a sample and so kappa equals to 1, the precision of the estimate can not be computed with the usual formulae and statistical softwares. A formula for variance which is valid in this particular case is presented together with a real example.
Abstract: The usual methods of sample size determination which assume the homogeneity of within-group variances are not sufficiently robust against the violation of this assumption. A method using Satterthwaite's correction for unequal variances is given. It is shown that in the case of unequal variances the minimum total sample size is attained when the allocation ratio is equal to the proportion of the standard deviations.
Abstract: A simple table is derived to facilitate the rapid estimation of the number of dose administrations needed to achieve a certain fraction of the steady-state plasma concentration in the case of one-compartment model with uniform multiple oral dosing and equal absorption and elimination constants.
Abstract: This paper contains a short generalization of a known method for sample size determination in the case of more than two parallel groups. The term 'set of allocation ratios' corresponding to the allocation ratio from the two-group design is defined. A formula using these ratios to determine the non-centrality parameter of the F distribution is deduced. It is shown that in case of more than two groups, equal group numbers does not constitute an optimal design. Two worked examples are presented.
