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Dear Helmut!
Since I'm only a bloody raw recruit in statistics and since I haven't done serious meta-analysis up to now I can't answer these questions really professional.
But what I have read scarcely about that topic there is actually no such thing in meta-analysis like alpha-adjustment or alpha-spending.
How should it be? Meta analysis was invented for pooling studies (mostly from literature) which generally are not under control of the meta-analyst and had generally already been evaluated with some alpha. Therefore there is little or no room for alpha-spending at all. Thats why meta-analyses are not generally accepted as confirmatory proof.
But there are regulatory concerns, f.i. in CPMP/EWP/2330/99 "Points to consider with 1. meta-analysis 2. one pivotal study". On page 2 is stated:
"When a meta-analysis is included in an application it should be performed in accordance with a protocol specifying
...
-Statistical methods (including methods for investigation of heterogeneity). In case where the meta-analysis provides the pivotal evidence for an indication, a p-value more extreme then the conventional significance level of 0.05 would generally required, and narrow confidence intervals for the treatment effect would be expected. The required degree of significance will be judged on a case by case basis considering factors such as amount of supportive data, plausibility of hypothesis tested and whether the analysis is pre-specified or not."
Emphasis by me.
BTW: I would incorporate a treatment by study interaction in the model as test of heterogeneity.
BTW2: What big differences did you expect with such a very low intra-subject variability?
BTW3: See Chow/Liu "Design and Analysis ...", Chapter 16 "Meta-analysis for bioequivalence review" to be more confused
.
❝ Is it really that easy?
❝ ... Why all the fuzz with sequential designs, alpha-adjustements and the like - if I can simply throw all data into the big pot, stir it up, and voilá...
❝
❝ Again: Is it really that easy?
❝ Both studies were already evaluated, the alpha is 'consumed' - any professional statisticians out there?
Since I'm only a bloody raw recruit in statistics and since I haven't done serious meta-analysis up to now I can't answer these questions really professional.
But what I have read scarcely about that topic there is actually no such thing in meta-analysis like alpha-adjustment or alpha-spending.
How should it be? Meta analysis was invented for pooling studies (mostly from literature) which generally are not under control of the meta-analyst and had generally already been evaluated with some alpha. Therefore there is little or no room for alpha-spending at all. Thats why meta-analyses are not generally accepted as confirmatory proof.
But there are regulatory concerns, f.i. in CPMP/EWP/2330/99 "Points to consider with 1. meta-analysis 2. one pivotal study". On page 2 is stated:
"When a meta-analysis is included in an application it should be performed in accordance with a protocol specifying
...
-Statistical methods (including methods for investigation of heterogeneity). In case where the meta-analysis provides the pivotal evidence for an indication, a p-value more extreme then the conventional significance level of 0.05 would generally required, and narrow confidence intervals for the treatment effect would be expected. The required degree of significance will be judged on a case by case basis considering factors such as amount of supportive data, plausibility of hypothesis tested and whether the analysis is pre-specified or not."
Emphasis by me.
BTW: I would incorporate a treatment by study interaction in the model as test of heterogeneity.
BTW2: What big differences did you expect with such a very low intra-subject variability?
BTW3: See Chow/Liu "Design and Analysis ...", Chapter 16 "Meta-analysis for bioequivalence review" to be more confused
.—
Regards,
Detlew
Regards,
Detlew
Complete thread:
- Meta-analysis earlybird 2010-04-09 07:54
![[Mix]](https://static.bebac.at/img/mix.png "open in Mix view")
- Meta-analysis in SAS d_labes 2010-04-09 08:35
- Meta-analysis vs. naïve pooling Helmut 2010-04-09 20:33
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-09 22:02
- Meta-analysis vs. naïve pooling Helmut 2010-04-09 22:11
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-09 22:20
- Meta-analysis vs. naïve pooling Helmut 2010-04-10 00:49
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-10 08:13
- Yes, but... Helmut 2010-04-10 14:46
- Yes, but... ElMaestro 2010-04-11 11:44
- Yes, but... Helmut 2010-04-11 14:27
- Yes, but... ElMaestro 2010-04-11 11:44
- Yes, but... Helmut 2010-04-10 14:46
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-10 08:13
- Meta-analysis vs. naïve pooling Helmut 2010-04-10 00:49
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-09 22:20
- Meta-analysis vs. naïve pooling Helmut 2010-04-09 22:11
- Meta-analysis alphad_labes 2010-04-12 13:32
- Meta-analysis alpha Helmut 2010-04-12 14:25
- 2-Study Meta-analysis d_labes 2010-04-12 15:03
- 2-Study Meta-analysis Helmut 2010-04-12 15:18
- Anatomical miracle d_labes 2010-04-12 15:33
- Anatomical miracle Helmut 2010-04-12 15:40
- Anatomical miracle d_labes 2010-04-12 15:33
- 2-Study Meta-analysis Helmut 2010-04-12 15:18
- 2-Study Meta-analysis d_labes 2010-04-12 15:03
- Meta-analysis alpha Helmut 2010-04-12 14:25
- Meta-analysis vs. naïve pooling ElMaestro 2010-04-09 22:02
- Meta-analysis vs. naïve pooling Helmut 2010-04-09 20:33
- Meta-analysis in SAS d_labes 2010-04-09 08:35
Ing. Helmut Schütz