Helmut ★★★ Vienna, Austria, 2021-04-08 19:09 (1085 d 20:50 ago) Posting: # 22305 Views: 24,991 |
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Dear all, we are collecting data for a publication about the annoying ‘Group-by-Treatment interaction’ (for some thoughts see this article). Below what we have so far in a meta-analysis of multi-group studies: To make a long story short: As expected, significant Group-by-Treatment interactions were detected at approximately the level of the test (0.05) and below the upper 95% significance limit of the binomial test. Hence, based on our observations in well-controlled studies likely they are mere ‘statistical artifacts’, i.e., false positives. The Kolmogorov–Smirnov tests were not significant, accepting the expected standard uniform distribution of \(\small{p(G\times T)}\). At a recent BE workshop1 I had a conversation with a prominent member of the FDA. She told that the agency tests the Group-by-Treatment interaction at the 0.05 level, thus reducing the false positive rate observed at the previously used 0.1 level. But then she also said »We often see not only p-values just below 0.05, but also some with 0.001…« It’s a common fallacy to regard the p-value as the probability that the null hypothesis is true (or the alternative hypothesis is false).2 The outcome of a level \(\small{\alpha}\)-test is dichotomous: Hypotheses are considered true or false, not something that can be represented with a probability.Any type of comparative BA study (BE, food-effect, DDI, dose-proportionality) is welcome. Of course, data will be treated strictly confidential and not published . The preferred data format is CSV (though xls(x), ODS, SAS XPT or Phoenix project files would serve as well). Columns (any order is fine):
No cherry-picking, otherwise we will fall into the trap of selection bias and the outcome will be useless. Hence, if you decide to provide data, please do so irrespective of whether you ‘detected’ a significant Group-by-Treatment interaction or not. We are primarily working on 2×2×2 crossover designs. However, if you have data of replicate designs, fine as well. In Higher-Order crossover designs indicate which of the treatments is the test and the reference. If possible, give the analyte. Once we have enough data sets, we will perform sub-group analyses. So far we have only data of one multi-site study. If you could share some data, great. THX in advance!
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
Helmut ★★★ Vienna, Austria, 2023-02-23 11:46 (400 d 03:13 ago) @ Helmut Posting: # 23775 Views: 8,512 |
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Dear all, I’m also collecting data to assess a ‘Sex-by-Formulation interaction’ because in Section 2.1.1 of ICH M13A we find: Subjects should be at least 18 years of age and preferably have a Body Mass Index between 18.5 and 30.0 kg/m2. If a drug product is intended for use in both sexes, it is recommended the study include male and female subjects. […] Subjects should preferably be non-nicotine users. Obviously there are no concerns about extrapolating results to patients < 18 years, to obese patients (in the US a whopping 42% of the adult population), or to 23% of adults smoking tobacco. However, this sentence is similar to what the FDA recently recommended but is not stated in any other of the global guidelines. Where does this come from and why? Science or rather (gender)politics?1,2 We have only few anecdotal reports and small meta studies with contradicting results. Nevertheless, authors of the largest one concluded:3 There is no evidence to require studies in both sex groups, combined or separately. In the past – at least in Europe – the majority of studies were performed in males only. We know that pharmacovigilance is not very sensitive. However, in 23.8 million drug switches in The Netherlands only 1,348 ADRs were reported (i.e., in 0.006% of switches)…4Recently I gave presentations on the topic.5,6 In the meantime I have more data (228 mixed-sex datasets, 190 passing BE for AUC; 3,970 males, 3,302 females):
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |