## Sample size calculation (Pilot study result vs literature) [Power / Sample Size]

Hi,

We have a product, conducted pilot study, 2x2x2 , 18 subjects.

Geometric Lease square Mean Cmax (ng/mL) T = 15032.282
Geometric Lease square Mean Cmax (ng/mL) R = 15227.106
T/R ratio % = 98.70
90% CI = 84.41 – 115.46
ISCV (%) = 26.4
Power(%) = 76.6%

However, based on published literature (Public assessment report, PAR) for the same product. 3 way crossover, reference replicate with 41 subjects completed, the results shows below:-

Geometric Lease square Mean Cmax (ng/mL) T = 16530.654
Geometric Lease square Mean Cmax (ng/mL) R = 15064.108
T/R ratio % = 109.7
90% CI = 96.25-125.11%
ISCV (%) = 42.6%
Power(%) = NA

Based on the CRO in house data for their past experience, Range of Intra-Subject Variability of Reference Formulation (CVWR): 26.8% – 50.3% (Pass studies)

Question:
1. Usually ISCV result of the 3 way crossover or 4 way crossover, replicate study published in the PAR is CVwR or CVw?

2. Which ISCV should i consider to use for sample size calculation as our own pilot study shows promising result, however, published literature and CRO past experience shows the other way. CRO advised us to go for 4 way crossover, replicate design, with ratio 90-111%, ISCV = 35-40%

3. What would be the recommended ISCV and study design for product like this? I have to balance between passing the study and the company's budget.

Hope the expert here can give me some recommendation. Appreciated. TQ   Ing. Helmut Schütz 