Indirect adjusted comparisons in BE [General Sta­tis­tics]

posted by Helmut Homepage – Vienna, Austria, 2019-07-21 15:20  – Posting: # 20417
Views: 1,063

Dear all (and esp. Shuanghe),

I don’t want to hi-jack ElMaestro’s thread about spreadsheets any longer.

Shuanghe and I had an OT-discussion about indirect adjusted comparisons in BE starting here.

I must confess that I don’t get what Luther Gwaza et al.1,2 means by his “pragmatic method”:

This method does not require the assumption of homogeneity of variances (\(SE_d=SE_{A}^{2}+SE_{B}^{2}\)), since it is un­likely verifiable, between studies with small sample sizes that follow Student’s t-test distribution (t0.9,d.f.), whose degrees of freedom are approximated for simplicity as if the variances were homogeneous (n1+n2–2).


Sounds great but how does he pool variances here? If they are weighted by the studies’ sample sizes – which IMHO, is the correct method – we end up in the homoscedastic method, where (in his notation):$$SD_{pooled}^{2}=\frac{(n_1-1)SD_{1}^{2}+(n_2-1)SD_{2}^{2}}{n_1+n_2-2}$$ BTW, is this a typo in the quote? A pooled variance as the sum? I suspect that he simply used the arithmetic mean which would not be correct even for equal samples & variances.
@Shuanghe: How did you do it?


  1. Gwaza L, Gordon J, Welink J, Potthast H, Hansson H, Stahl M, García-Arieta A. Statistical approaches to indirectly compare bioequivalence between generics: a comparison of methodologies employing artemether / lume­fantrine 20/120 mg tablets as prequalified by WHO. Eur J Clin Pharmacol. 2012;68(12):1611–8. doi:10.1007/s00228-012-1396-1.
  2. Gwaza L. Adjusted Indirect Treatment Comparisons of Bioequivalence Studies. PhD Thesis: Utrecht. 2016. [image] free resource.

Cheers,
Helmut Schütz
[image]

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

Complete thread:

Activity
 Admin contact
20,138 posts in 4,246 threads, 1,387 registered users;
online 10 (0 registered, 10 guests [including 3 identified bots]).
Forum time (Europe/Vienna): 15:34 CET

The fundamental cause of trouble in the world today is
that the stupid are cocksure
while the intelligent are full of doubt.    Bertrand Russell

The Bioequivalence and Bioavailability Forum is hosted by
BEBAC Ing. Helmut Schütz
HTML5