|2005D-0340||Guidance for Industry on Acne Vulgaris: Developing Drugs for Treatment|
|FDA Comment Number :||EC4|
|Submitter :||Dr. Todd Plott||Date & Time:||12/21/2005 11:12:16|
|Organization :||Medicis Pharmaceutical|
|Category :||Private Industry|
| The following comments are being submitted electronically in four parts. The section below is part 3 of 4.
8. The IGA scale is insensitive to detecting differences between two products that may act on the same lesion type.
The development of combination acne products requires the comparison of the combination against each of its components. Comparisons of the combination (containing ingredients improving inflammatory and non-inflammatory lesions) to the product containing only the anti-inflammatory lesion component should show the superiority of the combination in improving non-inflammatory lesions. However, the IGA is not adequately sensitive to detect clinically meaningful changes in non-inflammatory lesions, and therefore the IGA will consistently fail to support the efficacy of the combination product when efficacy exists. Because the IGA is heavily weighted in favor of inflammatory lesions the above comparison will both show similar IGA improvements even though the single component provides little or no improvement in non-inflammatory lesions.
9. Use of the IGA scale imposes an unreasonably high degree of certainty upon success since the scale is in addition to lesion counting.
Since lesion counting is still used, and one must meet statistically significant success on both lesion counts and the IGA, the Division is increasing the difficulty of identifying success above the statutory and regulatory level of two adequate and well-controlled trials. There should be a corresponding upward modification of the p value to account for requiring the product to meet two independent tests of success. If the two scales are dependent upon each other, of course, a new scale is not required.
10. Inter- and intra-observer validation has not been performed.
There is no evidence that the scale CAN be validated to inter-observer or intra-observer accuracy. These forms of validation have never been done in the retrospective analyses of Wilkins and Alosh. Before implementation, identification as to whether any version (including scales with photographs) of the IGA scale can be implemented alike by different observers. Since the scale also requires future assessments, we need to know if the same patient with the same features would be graded the same by the same observer at two different time points. This may be difficult to ascertain unless good photographic standards can be developed. Again, both validations should be performed on some permutation of the IGA scale prospectively BEFORE a requirement is imposed to demonstrate that at least one permutation of the scale may be possible.
11. There is no perceived need for a new scale.
The draft guidance does not identify any scientific or medical rationale for supplementation or replacement of the lesion counting scale.
12. The Draft Guidance is not specific as to whether the IGA scale is a visual only scale.
Physical palpation and physical examination of the patient is needed to identify lesion types and lesion number. Completing the IGA without
| palpation assures inaccurate use of the IGA grade descriptions. The IGA requires identification of lesion types and number. In addition, photographic scales do not permit the standardization of lesion identification and counting because palpation is not possible.