4x4-fasting-fed study [Design Issues]
Dear all,
we plan to perform a pilot study as 4-period BE study fed/fasting conditions.
Some issues were discusssed in:
http://forum.bebac.at/mix_entry.php?id=3820#p3820
Approach 1:
Williams Design as 4x4, 4 Sequences
- Rfe Rfa Tfa Tfe
- Tfa Rfe Tfe Rfa
- Tfe Tfa Rfa Rfe
- Rfa Tfe Tfe Tfa
T vs. R (BE): Statistical Data evaluation (ANOVA + CI) will be done separately for each conditions without the data of the other condition.
fed vs. fast (Food effect): Statistical Data evaluation (ANOVA + CI) will be done separately for each formulation withour the data of the other formulation.
pros:
- balanced design
cons:
- statistical data evaluation using only 50 % of the whole data, the influence (effects, ...) of the other 50 % of the data is lost.
Approach 2:
2x2-Design for feating conditions in Periode 1 and 2, 2x2-Design for fed conditions in Periode 1 and 2 leads to 2 sequences
- Rfa Tfa Rfe Tfe
- Tfa Rfa Tfe Rfe
T vs. R (BE): Statistical Data evaluation (ANOVA + CI) will be performed as 2x2x2-Design for each condition.
fed vs. fast: Statistical Data evaluation (ANOVA + CI) will be done separately for each formulation without the data of the other formulation.
fed vs. fast (Food effect): Statistical Data evaluation (ANOVA + CI) will be done separately for each condition withour the data of the other condition without the factor period in the ANOVA.
pros:
- 2x2-Design for each condition
cons:
- period effect could not be captured in food effect analysis
Because the pivotal studies will be perfomed in two seperate 2x2-crossover studies, one under fasting and one under fed conditions, Approach 2 would be the best for our purpose.
In the current EMA-Guideline is stated, it is acceptable to conduct either two seperate 2x2-crossover studies or a four way crosssover study. My question is, which approach is the best for a 4x4-Pivotal study in your oppinion?
Thank you in advance for your answers.
Best regards.
beman
we plan to perform a pilot study as 4-period BE study fed/fasting conditions.
Some issues were discusssed in:
http://forum.bebac.at/mix_entry.php?id=3820#p3820
Approach 1:
Williams Design as 4x4, 4 Sequences
- Rfe Rfa Tfa Tfe
- Tfa Rfe Tfe Rfa
- Tfe Tfa Rfa Rfe
- Rfa Tfe Tfe Tfa
T vs. R (BE): Statistical Data evaluation (ANOVA + CI) will be done separately for each conditions without the data of the other condition.
fed vs. fast (Food effect): Statistical Data evaluation (ANOVA + CI) will be done separately for each formulation withour the data of the other formulation.
pros:
- balanced design
cons:
- statistical data evaluation using only 50 % of the whole data, the influence (effects, ...) of the other 50 % of the data is lost.
Approach 2:
2x2-Design for feating conditions in Periode 1 and 2, 2x2-Design for fed conditions in Periode 1 and 2 leads to 2 sequences
- Rfa Tfa Rfe Tfe
- Tfa Rfa Tfe Rfe
T vs. R (BE): Statistical Data evaluation (ANOVA + CI) will be performed as 2x2x2-Design for each condition.
fed vs. fast: Statistical Data evaluation (ANOVA + CI) will be done separately for each formulation without the data of the other formulation.
fed vs. fast (Food effect): Statistical Data evaluation (ANOVA + CI) will be done separately for each condition withour the data of the other condition without the factor period in the ANOVA.
pros:
- 2x2-Design for each condition
cons:
- period effect could not be captured in food effect analysis
Because the pivotal studies will be perfomed in two seperate 2x2-crossover studies, one under fasting and one under fed conditions, Approach 2 would be the best for our purpose.
In the current EMA-Guideline is stated, it is acceptable to conduct either two seperate 2x2-crossover studies or a four way crosssover study. My question is, which approach is the best for a 4x4-Pivotal study in your oppinion?
Thank you in advance for your answers.
Best regards.
beman
Complete thread:
- 4x4-fasting-fed studybeman 2014-04-04 13:48 [Design Issues]
- 4x4-fasting-fed study Helmut 2014-04-04 14:00
- Two stage design in a 4 way crossover fasting-fed BE study Tina 2014-05-16 10:35
- TSD: 2 cross-overs Helmut 2014-05-16 12:03
- Two stage design in a 4 way crossover fasting-fed BE study Tina 2014-05-16 10:35
- 4x4-fasting-fed study Dr_Dan 2014-04-04 19:44
- 4x4-fasting-fed study Tina 2014-05-16 12:31
- 4x4-fasting-fed study Helmut 2014-04-04 14:00