Evaluation of statistical power function for various diclofenac bioequivalence trials with different subject numbers

Abstract

This study presents application of statistical power function for the t-test and ANOVA F-test on the evaluation of diclofenac bioequivalence in trials with the wide variations in sample sizes (N = 12, 18 and 24). The power function, together with appropriate equations tables and figures, is used to calculate the power of the ANOVA for crossover design, the number of subjects for a given value of power and the minimum detectable difference in treatment means for different pharmacokinetic parameters of the formulations. The power of the trial with a small, sample size (N = 12) to detect 20% differences between diclofenac formulations is shown to be more than 0.9 and almost the same as the power of the trial with a large sample size (N = 24). In all trials for all pharmacokinetic parameters the power to detect 20% difference is shown to be more than 0.8. For the power of 0.8, the needed subject number to detect 20% difference in treatment means is the same or smaller than used and the minimum detectable difference is smaller than 20% in all our trials. This investigation shows that bioequivalence studies with small number of subjects (N = 12) may be quite adequate for valid conclusions.

Assessing the risk of alcohol-induced dose dumping from sustained-release oral dosage forms: in vitro–in silico approach

“…On the other hand, the simulated profile for DS2 diverged from the mean in vivo profile obtained in the study of Rao et al (2001). The observed shift of C max to higher values has indeed been noticed in some clinical trials with diclofenac SR tablets, including the already mentioned study that involved DS2 tablets (Suleiman et al 1989;Popović et al 2009). But, the simulated profile for DS2 with relatively sharp decrease in drug plasma concentration (Figure 4) indicate that drug therapeutic effect might not last as long as expected for SR tablet formulation.…”

“…Although the selected in vitro data indicated notable differences in the rate of drug release from the two formulations, several arguments supported the assumption that this scenario might actually happen in vivo. Namely, the results from BE study with DS2 tablets (Popović et al 2009) indicated considerably higher C max and AUC in comparison to the average values observed for 100 mg DS SR tablets (Davies & Anderson 1997), and in addition several trials showed that pharmacokinetics of orally taken diclofenac are highly variable (Hooper et al 1996;Lötsch et al 2000;Garbacz et al 2008).…”

“…However, published data on drug plasma concentration profile following oral administration of DS2 tablets (Popović et al 2009) signify considerably higher C max (3.86 µg/ml) and AUC (11.60 µg h/ml) in comparison to majority of data obtained in other BA/BE studies for 100 mg SR DS tablets (average C max 1.04 µg/ml and AUC 3.60 µg h/ml for the data reported in (Davies & Anderson 1997)), supporting the assumption that DS2 might indeed exert relatively fast dissolution in vivo. Exposure of the two DS products to hydro-ethanolic media that emulate the 'worst case' scenario (correspond to scenario C1 in the case of IBU tablets) had opposite effects on drug release rates.…”

Bioequivalence trial of Diclofenac sodium tablets: Effects of Eudragit and tablet preparation, formulation characterization, release profiles, and bioavailability measurements

“…Determining a correlation between in vitro physical and release properties, and in vivo bioavailability profile of a drug has widely been presented in the bibliography studeis. 1,2 Assuming correlation, it is possible to use in vitro data to predict the behavior of the drug in the in vivo conditions. This is anticipated to significantly lower need for expensive bioequivalence evaluations in humans.…”