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Dear Dr_Dan!
This is an interesting question but IMHO this is a non-inferiority hypothesis, i.e. the sponsor would like to show that the occurrence of AEs with the test treatment is non-inferior to the reference treatment. However, I think a consensus on a-priori definition of relevance threshold is difficult or hopeless. According to my opinion it’s very similar to statistical problems occurring in non-clinical toxicological studies. Hothorn (2010) suggests estimation of confidence intervals and their post-hoc interpretation in terms of tolerable thresholds when no a-priori definition of relevance thresholds is available.
What do you think by providing a confidence interval plot? The y-axis depicts the different type of AEs (e.g. according to MedDRA classification) and the x-axis shows the difference in proportion between test and reference and the corresponding confidence interval. A similar plot - for statistical analysis of organ weights - can be found in Hothorn (2010, slide 30) for illustration of this idea.
Please let me know what you think about this approach!
Best regards
Martin
Hothorn LA (2010). Statistical analysis of short-term studies in regulatory toxicology using R. Webinar organized by the American Statistician Association, Biopharmaceutical Section on Thursday, May 20.
http://www.biopharmnet.com/doc/doc03002-07.html or http://www.biopharmnet.com/doc/2010_05_20_webinar.pdf
PS.: when you would like to use the McNemar test you can calculate the odds ratio and the corresponding confidence interval instead of differences in proportions using the R function
This is an interesting question but IMHO this is a non-inferiority hypothesis, i.e. the sponsor would like to show that the occurrence of AEs with the test treatment is non-inferior to the reference treatment. However, I think a consensus on a-priori definition of relevance threshold is difficult or hopeless. According to my opinion it’s very similar to statistical problems occurring in non-clinical toxicological studies. Hothorn (2010) suggests estimation of confidence intervals and their post-hoc interpretation in terms of tolerable thresholds when no a-priori definition of relevance thresholds is available.
What do you think by providing a confidence interval plot? The y-axis depicts the different type of AEs (e.g. according to MedDRA classification) and the x-axis shows the difference in proportion between test and reference and the corresponding confidence interval. A similar plot - for statistical analysis of organ weights - can be found in Hothorn (2010, slide 30) for illustration of this idea.
Please let me know what you think about this approach!
Best regards
Martin
Hothorn LA (2010). Statistical analysis of short-term studies in regulatory toxicology using R. Webinar organized by the American Statistician Association, Biopharmaceutical Section on Thursday, May 20.
http://www.biopharmnet.com/doc/doc03002-07.html or http://www.biopharmnet.com/doc/2010_05_20_webinar.pdf
PS.: when you would like to use the McNemar test you can calculate the odds ratio and the corresponding confidence interval instead of differences in proportions using the R function
mcnemar.exact of R package exact2x2.Complete thread:
- Adverse events Dr_Dan 2011-09-01 11:27
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Significant differences in AEs Helmut 2011-09-01 12:18
- Significant differences in AEs Dr_Dan 2011-09-01 15:44
- Significant differences in AEs ElMaestro 2011-09-01 13:40
- Adverse events ElMaestro 2011-09-01 18:12
- Adverse eventsmartin 2011-09-02 11:02
- Significant differences in AEs Helmut 2011-09-01 12:18
Ing. Helmut Schütz