Age-related macular degeneration (AMD) is the leading cause of legal blindness in Americans over the age of 65. The cause of AMD it is thought to be related to multiple factors, and there is no cure for the disease. There are two basic types of AMD: dry and wet. Dry AMD is the most common type, accounting for 90% of all cases. Wet AMD accounts for 10% of cases and poses a higher risk of severe vision loss. There is no definitive treatment for dry AMD. For patients with wet AMD, several treatments are available.

Alan M. Garber, MD, PhD, Chairperson
Alex Krist, MD, Vice-Chairperson
Steve Phurrough, MD, MPA, Coverage and Analysis Group
Michelle Atkinson, Executive Secretary

Medicare Coverage Advisory Committee – Evaluative Questions – 11/29/05

Outcome Evaluation in the Treatment of Age-related Macular Degeneration (AMD)

1. At present, usual and approved care for AMD commonly includes laser photocoagulation, intravitreal injection, and vitamins.
      a) How confident are you that there is sufficient evidence to assess the health benefit of these modalities compared to watchful waiting only?
      b) How confident are you that there are modalities other than laser photocoagulation, intravitreal injection, and vitamins that provide a health benefit when compared to watchful waiting only?

2. a) How confident are you that each of the following measures is valid either in determining a final AMD health outcome or as an intermediate endpoint, - whose measurement would represent an unambiguous measure of visual aspects of patient well-being?

1. Visual Acuity
2. VFQ 25
3. Extent of CNV
4. Amsler Grid
5. Drusen extent/progression
6. Geographic Atrophy
7. Glare Recovery
8. Contrast Sensitivity
9. Fluorescein Angiography
10. Visual Fields
11. Ocular Coherence Tomography

      b) Are there other currently available outcome/intermediate measures that should be considered?

      c) As new technologies arise will new outcome/intermediate measures be needed to demonstrate benefit in the treatment of AMD?

      d) What are the appropriate chronological criteria for “short-term” and “long-term” outcomes for AMD treatments?

3. Based on evidence reviewed, how confident are you that the treatments discussed in Question 1 will positively affect the outcomes listed in Question 2?

4. a) Based on evidence reviewed, how confident are you that the approved treatment modalities reviewed in Question 1, used singly or in combination, produce clinically significant net health benefits in the treatment of AMD?

      b) Based on evidence reviewed, how confident are you that the other treatment modalities as discussed in Question 1, used singly or in combination, produce clinically significant net health benefits in the treatment of AMD?

5. What are the knowledge gaps in current evidence pertaining to the usual care of AMD?

6. What trial designs will support the development of sufficient evidence to determine the appropriate treatment of AMD?

7. Based on the scientific evidence presented, how likely is it that utilizing valid treatment outcomes in studying patients with AMD will result in conclusions that can be generalized to the Medicare population?

AMD – Age-related Macular Degeneration – both “wet” (neovascularization) and “dry” types.
Validity - CMS uses “validity” here as defined by Meinert, “Validity, in the context of a treatment difference, refers to the extent to which that difference can be reasonably attributed to a treatment assignment.” (Meinert CL. Clinical Trials, Overview. In: Redmond CK, Colton T, eds. Biostatistics in clinical trials. Wiley and Sons, 2001. pp. 37-51). This encompasses all issues of methodologic framework, study design, observed results, biological rationale, etc.
Net health benefit - Balance between risks and benefits including complications of surgery
Visual acuity – LogMAR

1. Charles Semba, MD; Genentech, Inc.

2. Robert Vitti, MD; Novartis Ophthalmics

3. Tony Adamis, MD; Eyetech, Inc

4. Peter Kaiser, MD; QLT

5. Jonathan Javitt, MD, MPH; Potomac Institute for Policy Studies and Wilmer Ophthalmological Institute, JHU

6. Carmen Puliafito; Bascom Palmer Eye Institute, University of Miami Miller  School of Medicine

7. Timothy Stoutt, MD, PhD; Prevent Blindness America

8. T. Mark Johnson, MD; National Retina Institute

9. Bert Glaser, MD; National Retina Institute

10. Jason Slakter, MD; Vitreous-Retina-Macula Consultants of NY