A review of evidence supporting NCCN category 2B off-label recommendations for determination of Medicare reimbursement eligibility.

6576 Background: Antineoplastic indications supported by a category 1 or 2A NCCN recommendation are reimbursed by insurance and Medicare, as are FDA-approved indications. While initial reimbursement requests for “off-label” NCCN category 2B indications may be denied, Medicare will reimburse off-label antineoplastic use supported by evidence from a peer-reviewed publication from one of 26 designated journals. Here, we evaluated the published clinical evidence supporting NCCN category 2B indications. Methods: Category 2B drug indications for the 10 most common solid tumor types were identified in the NCCN compendium (n=104). The results were then filtered to include drugs with only category 2B indications in a particular tumor type (n=14). Similarly, FDA-approved indications were excluded, resulting in a list of drugs with only a 2B indication that are not FDA approved in the specified cancer type (n=8). Published clinical studies supporting these category 2B indications were assessed for study type and journal name in PubMed, and journal names were cross-referenced with the CMS-supported list. Results: Among the 8 non-FDA-approved drug indications with only category 2B recommendations, 7 (87%) had at least one publication of a clinical trial in one of the 26 designated journals. The only 2B indication without supporting literature was single-agent gemcitabine hydrochloride in bladder cancer. For further details, see Table. Conclusions: These results suggest that clinicians should consider pursuing the appeals process and provide supporting evidence in cases of claim denial. While coverage is not guaranteed, the evidence supporting 2B indications frequently meets the criteria identified in the Medicare statute. Further studies will evaluate if these findings extrapolate to less common tumor types.[Table: see text]

ANALYTICAL METHOD DEVELOPMENT AND VALIDATION STUDIES OF GEMCITABINE NIOSOMES

Gemcitabine hydrochloride niosomes were developed in our laboratory in an effort to improve the efficacy of the drug via development of nanotechnology based delivery system. As a part of this exercise, an analytical method was developed and validated to evaluate the developed formulation for assay and release profile studies. A simple, precise, specific and rapid high performance liquid chromatographic method was developed for determination of gemcitabine hydrochloride in niosomes. The developed method exhibited good resolution, short run time and low cost of analysis. The chromatographic analysis was carried on a Waters® (C18, 250 mm x4.6 mm, 5µ) column using water: acetonitrile (95:5 v/v) as the mobile phase, flow rate of 1.2 ml/min and detection at 268 nm. The robustness of the method was evaluated using design of experiments. The validation studies of the developed method were conducted as per ICH guidelines Q2 (R1). The results indicated that the developed method as specific, accurate, precise, reliable, robust, reproducible, and suitable for the quantitative analysis of gemcitabine hydrochloride in the developed niosomes.