sury
☆    

India,
2019-04-03 12:28

Posting: # 20117
Views: 631
 

 Sample Size Based on Pharmacodynamic endpoints [Power / Sample Size]

Hii All,

Hope all are doing well....

Recently i have received to provide the sample size based on the Pharmacodynamic endpoints.

As we use the ISCV for the estimation of sample size in general Bioequivalence studies.

Can anyone have any idea how can we provide sample size for the PD endpopints


Responses are highly appreciated.:-)

Thanks all


Edit: Category changed; see also this post #1[Helmut]
ElMaestro
★★★

Denmark,
2019-04-03 13:22

@ sury
Posting: # 20118
Views: 580
 

 Sample Size Based on Pharmacodynamic endpoints

Hi sury,

» Can anyone have any idea how can we provide sample size for the PD endpopints

The overarching principle is the same:
You need to guesstimate the resemblance along with the variability of the quantity on which equivalence is determined. The first one is entirely formulation dependent, the latter is biological in nature.
In consequence you first decide on the design and the stats model, and then you work out the sample size from that model.

You will need to be very, very specific in order for anyone here to help you with the actual sample size. Very often you will not find info in the public domain that can be used to calculate sample size (like variability for certain nasal and inhalation drug PD endpoints). In those cases where you can't look up variability in literature/FOI act access/journals/etc you will not get a qualified sample size without at least a pilot study.
Note also that for FDA some PD endpoints are complex in that superiority to placebo is required along with proof of equivalence for T vs R. This is not always entirely straightforward.

I could be wrong, but...
Best regards,
ElMaestro
nobody
nothing

2019-04-03 13:36

@ ElMaestro
Posting: # 20119
Views: 575
 

 Sample Size Based on Pharmacodynamic endpoints

» This is not always entirely straightforward.

I like this kind of understatement. In fact you are in full-blow development mode for sumfink like that.

Kindest regards, nobody
sury
☆    

India,
2019-04-05 06:36

@ ElMaestro
Posting: # 20122
Views: 478
 

 Sample Size Based on Pharmacodynamic endpoints

Thanks for your reply.....but i have few more doubts on this

Can we use the pharmacokinetic parameter ISCV for the sample size estimation for the clinical endpoint bioequivalence study?
is it will be in accordance with the regulatory requirement?


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 #5[Helmut]
ElMaestro
★★★

Denmark,
2019-04-05 08:22

@ sury
Posting: # 20123
Views: 470
 

 Sample Size Based on Pharmacodynamic endpoints

Hi sury,

» Can we use the pharmacokinetic parameter ISCV for the sample size estimation for the clinical endpoint bioequivalence study?

That is a catastrophic approach. It will most likely lead to way too low power because PD endpoints are often (I am not saying always) somewhat more variable both between and within subjects.


» is it will be in accordance with the regulatory requirement?

There is no specific requirement telling you what to do. But if you do something along the lines of thinking PK and PD have the same variability, an asssumption which to the best of my knowledge does not have any theoretical or practical backing, then you may be headed directly for a futile trial; you will be exposing volunteers to IMP without any truly justified anticipated benefit and that would be a strong ethical concern.

The fact that it is also a royal waste of money is of course only secondary.

I could be wrong, but...
Best regards,
ElMaestro
nobody
nothing

2019-04-05 08:37

@ ElMaestro
Posting: # 20124
Views: 470
 

 Sample Size Based on Pharmacodynamic endpoints

» The fact that it is also a royal waste of money is of course only secondary.

Full-blown development mode. Accept it. Tell the sponsor you can't do the trial, if you are not qualified for PD-endpoint testing.

Kindest regards, nobody
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