Bioequivalence and Bioavailability Forum

Dear BE-proff,

❝ AFAIK, authorities want to see validated software while R-based scripts seem not to be validated...

❝ How to prove officials that PowerTOST is reliable soft?

I'm not a friend of software validation, whatever that is.

Ask the same question to statements like:
"I have calculated the sample size with SAS, PASS, nQuery, Brain-Pencil-Paper ... (or whatever soft-/wetware you prefer ). Is that SAS, PASS, nQuery, Brain-Pencil-Paper ... validated and reliable?"

See also this thread.

Then act. Others, more trained in this ugly field of software validation may give you more hints what to do in detail. In short:

• Write a validation plan
• Do what you have written in the validation plan
• Write a validation report

BTW: PowerTOST is not an R-based script. It is a package providing you the possibility (via functions) to estimate power / sample size with your R-based script.

Hi BE-proff,

❝ Do you make references to calculations done by PowerTOST in documents submitted to regulatory authorities (i.e. study protocols, clarifications, etc)?

Yes, I do.
In tricky cases (e.g., justification of an adjusted α in two-stage design) I give my script in an appendix to the protocol.

❝ How to prove officials that PowerTOST is reliable soft?

Hart is’ hart und weich is’ weich.
Aber allweil weich is’ auch hart.    Austrian proverb

My translation:

Hard is hard and soft is soft.
But always soft is hard as well.

Hi,

As far as I understand, regulatory authorities in Europe are not that troublesome with software as FDA. They don't even ask the sponsor to send the datasets of the study or the Logs of the statistical software execution. I believe that in some countries, you could state in the Protocol and in the SAP that you will used Winonlin and SAS in your analysis and use R in all of them and never have a problem in submission's nor in inspections. For instance, regulatory inspections in Portugal care only about GCP compliance in the clinical site. They don't even check in detail eDC software or data management & analysis process. Lack of qualified resources I think.
Nevertheless, my personal opinion is that you should always "validate" yourself the results of the software. For instance, when I use a new R package to implement a new statistical method I always validate the results with SAS, being the job for regulatory purposes or not. I also do that when I'm doing an analysis I'm not very comfortable with and I store both outputs (R and SAS) for my own protection in case of questions (the main trouble with R arises from the clients, much of them used to SAS and don't want to take the risk of using R just by "superstition").

Regards,
David

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Edit: Full quote removed. Please delete everything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

Hi BE-proff,

as far as I know PowerTOST and other packages will generally be accepted.
Power is usually the sponsor's problem: It is the chance of showing BE when a set of assumptions are met. It usually does not affect patient's risk and so isn't where you get the most deficiency letters. At the end of the day, your assumptions are guess and guesses tend to have a lot of uncertainty, so power is in that perspective not a question of having a boatload of decimals right. Besides there is no regulatory power minimum or maximum though 80% or thereabouts is quite common.
Regulatory questions -or inspection triggers- may arise from bad guesses; for example it may be somewhat unethical to assume a CV of 8% and a GMR of 100.00% for most drugs (you'd be including too few patients for a realistic chance of showing BE). Thus, what the industry generally needs is a healthy dose of common sense rather than validation of power-calculating software to the 17th decimal. It is difficult to validate someone's ability to guess well anyhow.