Clinically relevant difference CRD

We see that in contrast to the type-1 error, the type-11 error is defined as occurring when accepting the null hypothesis if it is false. The power of a test is defined to be the probability of detecting a true difference and is equal to 1 — probability (type-11 error). The type-11 error and power depend upon the type-1 error, the sample size, the clinically relevant difference (CRD) that we are interested in detecting and the expected variability. Where do these values come from ... 

In this example of a group difference of 3 mmHg, development would probably not continue. However, at what point would a decision to continue likely be made This leads to another question What is the smallest effect size that is clinically meaningful, or clinically relevant This effect size can be called the clinically relevant difference (CRD). Its determination is a clinical one, not a statistical one. This determination may well be strongly influenced by existing empirical evidence (for example, actuarial statistics), but, unlike statistical significance, its determination is not simply formulaic. 

The clinically relevant difference (CRD) that the test is required to detect. This is the treatment effect size, i.e., the difference between the mean drug treatment group response and the mean placebo treatment group response, that the sponsor deems clinically relevant. 

PpLACEBO value that is considered the minimally clinically relevant difference (CRD). 

We commonly refer to the level of effect to be detected as the cliniMlly relevant difference (crd) what level of effect is an important effect from a clinical standpoint. Note also that crd stands for commercially relevant difference it could well be that the decision is based on commercial interests. Finally crd stands for cynically relevant difference It does happen from time to time that a statistician is asked to do a sample size calculation, oh and by the way, we want 200 patients The issue here of course is budget and the question really is what level of effect are we able to detect with a sample size of 200 ... 

For continuous data, the sample size is inversely proportional to the square of the clinically relevant difference. So if the crd is reduced by a factor of two then the sample size is increased by a factor of four, if the crd is increased by a factor of two then the sample size is reduced by a factor of four. In our earlier example the sample size requirement to detect a difference of 8 mmHg was 33... 

The clinically/commercially relevant difference (crd). If the expected difference is larger than this then it could be worth considering powering for the expected effect, the sample size will be lower. 

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