No relationship between inter- and intra-subject CV [Power / Sample Size]

posted by Helmut Homepage – Vienna, Austria, 2020-10-14 13:00 (1148 d 21:00 ago) – Posting: # 21998
Views: 2,195

Hi arl_stat,

❝ Mostly in public domain, the inter subject CV of drug is not mentioned.

You fell into trap of wrong terminology. Even if a study was performed in a parallel design, one gets the total (a.k.a. pooled) CV – not the inter-subject CV.$$CV_{\textrm{total}}=\sqrt{\exp\left(\log_{e}(CV_{\textrm{inter}}^{2}+1)+\log_{e}(CV_{\textrm{intra}}^{2}+1)\right)-1}\tag{1}$$
Simply: The total variance (which you observe in any design) is the sum of inter- and intra-subject variances.$$s_{\textrm{total}}^{2}=s_{\textrm{inter}}^{2}+s_{\textrm{intra}}^{2}\tag{2}$$ The inter-subject CV is only accessible in a crossover study (see this post).

❝ […] can we use this intra-subject CV to estimate sample size for parallel study design?


❝ Is there any formula to calculate inter-subject CV using 90% confidence interval ranges and number of subjects?

No, since you need the CVtotal calculated acc. to \((1)\) from a crossover – or directly observed in a parallel design – and there is no relationship between CVinter and CVintra. Hence, CVintra from a crossover alone does not help.
See also this post and followings.

❝ First can we calculate the sample size of 2 way crossover study design and then double the subjects and finalize the sample size for parallel study design?

No (see above). For ages rumors are swirling around a factor of two but that’s plain nonsense. Think about a drug with low CVintra and polymorphic metabolism. Then the factor can easily be >5 and by doubling the sample size of a crossover the parallel study will be grossly underpowered. BTW, in rare cases CVintra > CVinter.

Run a – not too small! – pilot study or a TSD.*

Dif-tor heh smusma 🖖🏼 Довге життя Україна! [image]
Helmut Schütz

The quality of responses received is directly proportional to the quality of the question asked. 🚮
Science Quotes

Complete thread:

UA Flag
 Admin contact
22,818 posts in 4,784 threads, 1,634 registered users;
36 visitors (1 registered, 35 guests [including 3 identified bots]).
Forum time: 09:01 CET (Europe/Vienna)

The greatest obstacle to discovery is not ignorance 
it is the illusion of knowledge.    Daniel J. Boorstin

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz