Bioequivalence and Bioavailability Forum

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

posted by Alyssa – Malaysia, 2020-05-04 06:35 (1625 d 00:47 ago) – Posting: # 21389
Views: 11,304

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

Complete thread:

• Sample size calculation (Pilot study result vs literature)Alyssa 2020-05-04 04:35 [Power / Sample Size] 
  • Sample size calculation (Pilot study result vs literature) Dr_Dan 2020-05-04 08:46
    • Sample size calculation (Pilot study result vs literature) Alyssa 2020-05-04 09:26
  • Estimation of CVw and/or CVwR Helmut 2020-05-04 12:07
    • Estimation of CVw and/or CVwR ElMaestro 2020-05-04 12:14
      • Mea culpa! Helmut 2020-05-04 12:40
        • It must be Myco ElMaestro 2020-05-04 13:46
          • It is, it is! Helmut 2020-05-04 14:07
            • It is.... Alyssa 2020-05-05 05:00
              • Tutorial Helmut 2020-05-05 12:45
                • Tutorial Alyssa 2020-05-08 06:48
                  • library d_labes 2020-05-08 11:16
                  • Tutorial (from the start) Helmut 2020-05-08 13:08
                    • Tutorial (from the start) Alyssa 2020-05-12 04:05
                      • Tracking down error Helmut 2020-05-12 11:49
                        • Tracking down error: stringsAsFactors d_labes 2020-05-13 11:34
                          • R <4.0.0 Helmut 2020-05-13 12:07
                            • R <4.0.0 ElMaestro 2020-05-13 14:18
                              • R <4.0.0? Helmut 2020-05-13 14:21
                            • PowerTOST’s functions with as.character(design) d_labes 2020-05-13 18:50
                              • PowerTOST’s functions with as.character(design) Helmut 2020-05-13 18:55
                        • Tracking down error Alyssa 2020-05-15 05:08
                          • All’s well that ends well. Helmut 2020-05-15 10:52