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FDA releases draft guidance on dry eye therapies

Posted 18 December 2020 | By Kari Oakes 

FDA releases draft guidance on dry eye therapies

A new draft guidance from the US Food and Drug Administration (FDA) addresses considerations for developing drugs to treat dry eye. The guidance encompasses development of both pharmaceutical and biological products to address the common eye condition.
The best trial design, said FDA, is a per-patient randomized, double-masked trial that looks for superiority of an investigational product over the control, which could be the vehicle. Either a traditional environmental exposure trial or a trial design that uses an environmentally controlled chamber could be acceptable; trials where the investigational drug is add-on therapy to standard of care are also acceptable, according to the guidance.
Efficacy should be assessed either in natural exposure trials that last at least 2 weeks, or in single-day controlled environment trials. Safety trials should last at least 6 weeks.
Generally, two multicenter independent trials should be conducted; sponsors should demonstrate a statistically significant difference in at least one “objective prespecified sign of dry eye” as well as at least one “subjective prespecified symptom of dry eye.”  Alternatively, sponsors can demonstrate a statistically significant difference between the number of participants in each group that demonstrate complete resolution of corneal staining, or the number of participants who show a specified improvement in Schirmer’s tear test scores.
When comparative clinical trials are conducted, the sponsor’s product should have both statistical and clinical superiority over the vehicle or alternative regimen. “Water is known to be an effective component of topically applied treatments for dry eyes,” noted FDA, so the investigational drug’s vehicle should generally be the control agent.
Since trials of dry eye therapies, even those known to be effective, may not always show efficacy, “FDA does not recommend equivalence or noninferiority trials,” in general.
In terms of the trial population, individuals with both objective signs and subjective dry eye symptoms should be included. In addition to ensuring demographic diversity across age, gender and racial/ethnic categories, investigators should make sure to include individuals from different eye color groups.
The draft guidance recommends that individuals with dry eye symptoms that are the result of scarring conditions such as burns or irradiation, or of conjunctival goblet cell destruction be studied separately from routine dry eye, since these patients “represent a specific, severely affected patient population.” Additionally, patients with evidence of high levels of lid margin inflammation or blepharitis should not be included in a trial designed to study “routine dry eye conditions.”  
The guidance provides recommended objective signs and subjective symptoms to include in clinical trial endpoints, provides recommendations for clinical evaluation and outlines how trials should be structured to capture efficacy both for signs and symptoms.
Safety considerations highlighted in the draft guidance include the recommendation to enroll at least 400 patients, so less frequent adverse events are more likely to be captured. At the point when a marketing application is filed, sponsors should have at least 300 patients who have completed the minimum 6-week followup period.
The draft guidance is open for public consultation for a 90-day period.


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