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Anand Gopal, Joshua Wallach, Saloni Shah, Carl Regillo, Joseph Ross; Characteristics of Clinical Studies Evaluating Off-Label Indications for Novel FDA-Approved Therapeutics in Ophthalmology. Invest. Ophthalmol. Vis. Sci. 2020;61(7):3070.
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Little is understood about how novel therapeutics garner evidence for off-label (i.e., non-FDA approved) use in ophthalmology. While the US Food and Drug Administration (FDA) prohibits off-label promotion, industry may sponsor and distribute peer-reviewed studies supporting off-label indications, regardless of the studies’ rigor. We characterized and compared clinical studies of FDA-approved and off-label indications for novel therapeutics in ophthalmology and assessed differences between industry and non-industry funded studies of off-label use.
We performed a retrospective analysis of prospective clinical studies, registered on ClinicalTrials.gov or PubMed-indexed through December 2018, of novel therapeutics approved by FDA for an ophthalmologic indication between 2008 and 2012. We characterized the proportion of studies evaluating original FDA-approved indications, supplemental FDA-approved indications, and off-label indications, stratified by therapeutic and study characteristics. We used Chi-squared testing to assess differences with a corrected Type I error of 0.006.
There were 7 novel therapeutics approved by FDA for an ophthamologic indication between 2008 and 2012; we identified 469 unique prospective clinical studies of these therapies. Over half (256; 54.6%) assessed the original FDA-approved indication, while 24.3% (114) assessed off-label indications. 67.0% (314) were for a single therapeutic (aflibercept) (Figure). Median number of off-label indications studied was 4 (IQR, 0-12; range 0-27). Median number of studies evaluting an off-label indication was 1 (IQR, 1-2; range 1-19). Compared to FDA-approved indication studies, off-label indication studies were smaller (p<0.0001) and less frequently used an active comparator (44.4% vs 68.1%; p=0.002). Industry-funded off-label studies did not differ statistically from non-industry funded off-label studies, but tended to be larger and more rigorously designed (Table).
For most therapies, few studies of any indication are conducted after FDA approval. Most off-label indications are infrequently studied. Understanding the rigor of these studies is important when considering adopting approved therapies for new uses.
This is a 2020 ARVO Annual Meeting abstract.
Clinical studies across time, by therapeutic and study indication.
Comparison of industry vs. non-industry funded studies of off-label indications, by study characteristics.
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