RSABE templates for Phoenix 1.4

I realized that I didn’t make these templates available to the forum members even if the information was sent to attendees of the original webinar on RSABE templates.

If you are interested, we have updated the RSABE (reference-scaled average bioequivalence) templates to work with Phoenix 1.4 (Phoenix WinNonlin 6.4). These templates follow the FDA and EMA guidances included as part of the documents within the project. Please read the instructions (documents/instructions) before using these templates. Be advised that these templates were developed as part of an AAPS poster and have been tested by the authors but have not followed a Pharsight development process.

Phoenix 1.4 RSABE Templates

Thanks,

Ana

This webinar was recorded a while ago but bumping it up as a few people had asked me about it recently;

Also the AAPS poster from 2013 is linked in here;

"http://info.certara.com/roundtable/support-drug-approvals-phoenix-winnonlin-rsabe

Simon

EDIT - https://www.youtube.com/watch?v=s6G-16jYffA

added Youtube video link; https://www.youtube.com/watch?v=s6G-16jYffA

Note of caution: The video was recorded with Phoenix 1.3 and the steps in Phoenix 1.4 are highly simplified.

Tomorrow, (25th Sept 2018) there is a free Webinar using the latest version of Phoenix: Learn how reference-scaled average bioequivalence (RSABE) templates can save time and increase users’ productivity. Register here: http://bit.ly/2nSFjsl

Simon.

The focus of the session was RSABE for NTID (narrow therapeutic index drugs).

So sad that I’ve missed the webinar. Is there anyway for me to watch it without an business email?

I have one additional question: could I use phoenix FDA RSABE template for 3-period full-replicate design (TRT/RTR)?

Thanks in advance

Gigi

Hi Gigi,

You can register for free (and with a non-business email) at Certara University where you can download all the available templates by following the link below. For highly variable drugs, FDA RSABE for 3-period full-replicate design is included. However, the narrow therapeutic drug templates are only for 4-period full design.

https://www.certarauniversity.com/lms/index.php?r=course/details&id=318

Hope this helps,

Ana

[quote=“Ana Henry, username:ana.henry”]

Hi Gigi,

You can register for free (and with a non-business email) at Certara University where you can download all the available templates by following the link below. For highly variable drugs, FDA RSABE for 3-period full-replicate design is included. However, the narrow therapeutic drug templates are only for 4-period full design.

https://www.certarauniversity.com/lms/index.php?r=course/details&id=318

Hope this helps,

Ana

[/quote]Dear Ana,
I read this statement from the instruction document provided in FDA RSABE template:
“For Full replicate designs the only design accepted is a 4-period with sequences TRTR and RTRT where R=reference and T=Test. No other designs are accepted”.
So I want to reconfirm it again. Does FDA accepted a RTR/TRT design? Please help me on this!
Thanks so much,
Gigi

I’m sorry I’m not able to confirm what the FDA will accept for NTI; did you see this 2011 presentation;

https://www.fda.gov/downloads/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/abbreviatednewdrugapplicationandagenerics/ucm292676.pdf

or this 2012 paper?

https://link.springer.com/article/10.1208%2Fs12248-012-9406-x

I did find there are some substance specific guidances e.g. digoxin revised Aug 2017, that used a 4-way, fully replicated cross over

https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm085610.pdf

So I would be inclined to lean that way but I’m not a statistician so I can’t confirm their rationale. Perhaps you would be best contacting them directly yourself for your compound if you can’t find a specific guidance. Or you could see if anyone on the BEBAC forum has asked a similar question; e.g. http://forum.bebac.at/forum_entry.php?id=16315.

Simon.

Maybe my question wasn’t clear enough.

I’ve tried to use the template for a TRT/RTR dataset and it did not work, there was an error (no degree of freedom).

So I read the instruction document, “the user can analyze full-replicate (4-period) and partial-replicate (3-period) designs”.

Can I analyze full-replicate (3-period-RTR/TRT) design with RSABE template according to FDA guidance, and how to do it.

Thanks,

Gigi

Hi Gigi,

Where did you read this? Section 5.e. states: “NTID’s can only be analyzed with a full replicate design (4-period TRTR | RTRT). The template is set up to only work with this type of study design.”

Can I analyze full-replicate (3-period-RTR/TRT) design with RSABE template according to FDA guidance, and how to do it.

With some ambition, yes. Personally I think that 3-period full replicate designs (TRT | RTR or TRR | RTT) should do the job as well. Now for the (big!) but: The FDA’s guidance specifically recommends a four-period full replicate design. I would not deviate from this recommendation without a controlled correspondence. Otherwise, you risk an RtR. I can imagine that the FDA will not accept such a design because s ²wT and s ²wR are estimated in different subjects. No problems with scaling and the CI but the comparison of variances is tricky.

This free online course at our training site may be interesting;

https://www.certarauniversity.com/store/637337-106-fl-free-phoenix-templates-for-bioequivalence-regulatory-guidances

there is a lot of other material there.