2-stage design with interim sample size estimation [Two-Stage / GS Designs]
Dear all,
I have been questioned about the following design:
The sponsor/experimenter has no sufficient information about CV and point estimate ('true' value) to be able to make an "educated" guess of the sample size for a BE study. Some distinct shift in the point estimator is expected.
To save resources (its a fixed combination drug with 3 constituents, analytical expensive) he is not willing to do a pilot study and based on this a pivotal with BE decision not using the data from the pilot.
Thus the design shall be a 2-stage design. A first group of subjects (conception is 8-12) shall be dosed, analyzed and statistical evaluated. Based on the data (CV and point estimate) a final sample size shall be derived which will be utilized for the second stage.
There is the idea of a formal extreme small alpha to spend after the first stage =0.001 (to conform EMA guideline). This will ensure with great probability that the second stage will be reached. Practical no stopping will occur by that.
The only stopping rule is a maximum sample size constraint Nmax the sponsor is willing to fund. If the estimated sample size after stage 1 is greater the second stage will not performed.
Any body out there who knows how to handle such a design?
Is there something to do to protect the overall alpha (lower nominal alpha at second stage)?
Is the sample size estimation done as usually?
Any input will be highly appreciated.
I have been questioned about the following design:
The sponsor/experimenter has no sufficient information about CV and point estimate ('true' value) to be able to make an "educated" guess of the sample size for a BE study. Some distinct shift in the point estimator is expected.
To save resources (its a fixed combination drug with 3 constituents, analytical expensive) he is not willing to do a pilot study and based on this a pivotal with BE decision not using the data from the pilot.
Thus the design shall be a 2-stage design. A first group of subjects (conception is 8-12) shall be dosed, analyzed and statistical evaluated. Based on the data (CV and point estimate) a final sample size shall be derived which will be utilized for the second stage.
There is the idea of a formal extreme small alpha to spend after the first stage =0.001 (to conform EMA guideline). This will ensure with great probability that the second stage will be reached. Practical no stopping will occur by that.
The only stopping rule is a maximum sample size constraint Nmax the sponsor is willing to fund. If the estimated sample size after stage 1 is greater the second stage will not performed.
Any body out there who knows how to handle such a design?
Is there something to do to protect the overall alpha (lower nominal alpha at second stage)?
Is the sample size estimation done as usually?
Any input will be highly appreciated.
—
Regards,
Detlew
Regards,
Detlew
Complete thread:
- 2-stage design with interim sample size estimationd_labes 2010-10-05 15:09
- 2-stage design with interim sample size estimation Jack 2010-10-25 18:20
- Null = bioINequivalence Helmut 2010-10-25 19:16
- 2-stage design with interim sample size estimation d_labes 2010-10-26 13:28
- 2-stage design with interim sample size estimation Jack 2010-10-26 18:26
- Blind or not, Indecisions or Decisions d_labes 2010-10-27 16:01
- Blind or not, Indecisions or Decisions Jack 2010-10-27 18:14
- Blind ? Ohlbe 2010-10-27 23:37
- Blind ? Jack 2010-10-28 10:24
- Blind 2Stage Astea 2019-05-30 10:37
- Blind 2Stage Helmut 2019-05-30 12:56
- Blind 2Stage and an elephant Astea 2019-05-31 14:36
- Which elephant? Helmut 2019-06-02 20:14
- Blind interim in parallel design? Astea 2019-06-03 01:47
- Blind men d_labes 2019-06-05 12:23
- The Blind Leading the Blind Astea 2019-06-06 00:55
- Blind men d_labes 2019-06-05 12:23
- Blind interim in parallel design? Astea 2019-06-03 01:47
- Which elephant? Helmut 2019-06-02 20:14
- Blind 2Stage and an elephant Astea 2019-05-31 14:36
- Blind 2Stage Helmut 2019-05-30 12:56
- Blind 2Stage Astea 2019-05-30 10:37
- Blind ? Jack 2010-10-28 10:24
- Blind ? Ohlbe 2010-10-27 23:37
- Blind or not, Indecisions or Decisions Jack 2010-10-27 18:14
- Blind or not, Indecisions or Decisions d_labes 2010-10-27 16:01
- 2-stage design with interim sample size estimation Jack 2010-10-26 18:26
- 2-stage design with interim sample size estimation Jack 2010-10-25 18:20