Understanding the Paradox of the More Clinically Meaningful Acne Global Severity Scale and the More Precise Acne Lesion Counts

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• Understanding the Paradox of the More Clinically
  Meaningful Acne Global Severity Scale and the
  More Precise Acne Lesion Counts
• Jonathan Wilkin, M.D.

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Methodology

• A model is the simplest system that has the
• relevant properties.

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Purpose of the Study

• To characterize the relationship between the
• Actual Number of acne lesions and the
• Perceived Severity of acne lesions.

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Materials Methods

• 33 research subjects evaluated kodachromes of 2
  models for acne severity
• 2 models with up to 200 acne lesions created by
  a professional theatrical cosmetic artist
• Acne severity scored on a 10cm linear horizontal
  visual analogue scale
• VAS scoring by digimatic calipers

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Conclusion

• The psychometric model provides a curvilinear
  relationship between
• the more clinically meaningful acne global
  severity scale and
• the more precise acne lesion counts.

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• Historical Approach to Evidence for
  Effectiveness for Acne Drug Products for Mild to
  Moderate Acne
• Jonathan Wilkin, M.D.

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Success Criteria

• Lesion Counts - total plus either inflammatory or
  noninflammatory
• AND
• Investigators Global Assessment (dichotomized
  into success and non-success)

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Why Two Primary Endpoints

• Lesion Counts - more accurate, precise,
• objective, informs lesion type most responsive
• Investigators Global - imprecise, subjective,
• more clinically relevant

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Variations Among NDAs

• Different baseline lesion counts
• Different lesion count analyses
• absolute change
• percent change
• (variety of) transformed values
• Different Investigators Global Scales

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Questions

• 1. Should the current success criteria using
  the co-primary endpoints be retained?
• 2. How should lesion counts be analyzed?
• 3. What investigators global severity scale
  should be used? At what level should it be
  dichotomized into success and non- success?

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Acne vs. Lesion Type as Indication

• Sponsors seek the indication of mild to moderate
  acne vulgaris as monotherapy.
• Inflammatory lesions only as indication when
  difficult to demonstrate success in total lesion
  count change and investigators global evaluation.

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Questions

• 4. Should acne lesion types (inflammatory or
  noninflammatory) be medically acceptable
  indications?
• 5. Should lesion counts be assessed at multiple
  time-points late in the study and averaged to
  increase power?

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Questions (contd)

• 6. How should the efficacy outcomes of clinical
  trials be portrayed in labeling to be maximally
  useful to clinicians and patients? What graphics
  and tables should be provided?

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Goal

• A guidance document that describes how the
  evidence for effectiveness of drug products for
  mild to moderate acne vulgaris may be obtained
  and analyzed.