Posterior Capsule Opacity Rate Superiority Claims for IOL Studies

**Questions for Panel Members**

[Clinical Endpoints]{.underline}\--Sugar:

-   Since not all measurable PCOs are associated with clinically
    significant affects on a subject's visual function, do you believe
    that demonstration of decline in [measures of visual
    function]{.underline} (eg. BCVA, glare testing, contrast
    sensitivity, etc.) should be a required endpoint for a PCO study? If
    so, what degree of [visual impact]{.underline} (eg. \>2 lines
    decline) do you recommend? If not, what quantitative measurement of
    PCO grade do you recommend as an appropriate endpoint ?

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-   Is a claim of [delay in onset]{.underline} of visually significant
    PCO within the duration of the study clinically relevant? If so,
    what period of time do you consider a clinically significant delay?

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-   What minimum [difference in PCO rate]{.underline} between 2 IOLs do
    you consider clinically significant, for which a claim of
    superiority should be considered? For your consideration, a [sample
    size]{.underline} analysis table has been provided below for various
    deltas. Do you suggest a minimum number of subjects allowable for
    such a study?

  ---------------- ---------------- ------------------ ------------------
  desired Delta    anticipated PCO  anticipated PCO    sample size per
  (difference      rate trial IOL   rate control IOL   group
  between trial                                        
  and control)                                         

  10%              5%               15%                138

  10%              10%              20%                157

  10%              20%              30%                231

  15%              10%              25%                50

  15%              20%              35%                88
  ---------------- ---------------- ------------------ ------------------

[Study Controls]{.underline}\--Weiss:

-   What factors should be considered in choosing an appropriate
    [control IOL]{.underline}? Is there a "gold-standard" control lens
    or PCO rate that could be designated by FDA in order to permit
    inter-study comparisons of PCO incidence?

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-   What factors are important to be [matched]{.underline} in the trial
    and control populations (eg. age)?

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-   With regard to the HCFA NT IOL designation, what additional
    considerations must be factored into the choice of a [control
    IOL]{.underline} for the sponsor to demonstrate superiority over all
    IOLs (or over a "class" of IOLs)? Do you believe it is feasible to
    allow claims of superiority over all IOLs with respect to PCO rate?

[Methodology]{.underline}\--Bullimore:

-   Regarding current [methods of PCO analysis]{.underline}, do you
    consider particular methods acceptable for PCO IOL studies? Are
    there particular criteria that you consider critical (eg. region of
    posterior capsule evaluated, level of reproducibility, etc.)? Do you
    consider any of the current methods not valid? Do you think that
    subjective clinical grading systems should be permitted (eg.
    comparison to standard reference photos)?

[Clinical Protocol]{.underline}\--Ferris:

-   Based on review of current literature, the following [exclusion
    criteria]{.underline} are proposed for PCO studies: subjects with
    pseudoexfoliation syndrome, uveitis, non-age-related cataracts,
    previous intraocular surgery or laser treatment, diabetes, glaucoma,
    current use of systemic steroids or topical ocular medications,
    previous use of cytotoxic drugs or total body irradiation, and
    previous ocular trauma, and intraoperative exclusions for tear in
    the capsulorexis, zonular dehiscence, posterior capsule rupture,
    vitreous loss, and other unexpected surgical complications which
    could reasonably be assumed to affect PCO development. Do you
    suggest any deletions or additions to this list?

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-   Regarding [time points for PCO assessment]{.underline}, FDA guidance
    for IOL studies suggests scheduled follow-up at day 1, week 1, month
    1, month 4-6, and years 1, 2, and 3. What time points do you suggest
    for PCO assessment? Do you suggest follow-up beyond 1 year? If so,
    at what intervals and for what duration?

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-   What factors are critical to be [standardized within a PCO
    study]{.underline}? Across all studies? (eg. surgical techniques
    such as incision size, capsulorhexis size, post-op medications, and
    capsule polishing, as well as measurement techniques, etc.).

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-   If a sponsor wishes to claim reduction in [Nd:YAG capsulotomy rate,
    what standardized clinical criteria]{.underline} would you suggest
    for performance of capsulotomy after objective documentation of PCO
    (ie. specified number of lines decrease and/or minimum threshold
    level of BCVA, contrast sensitivity, glare effect, subjective
    complaints, PCO grade level, or any combination of these)? Do you
    feel that all PCO studies should evaluate both outcomes (Nd:YAG
    capsulotomy rate and PCO incidence)?

[Summary Question]{.underline}\--All:

-   Having reviewed the PCO study discussion paper, are there any areas
    for which you have [additional suggestions]{.underline}?