OBJECTIVES:   To review the various options that the Centers for Medicare & Medicaid Services (CMS) has to review new drugs and biologics under its National Coverage Determination (NCD) process, and conduct such review in the wake of its recent NCD for sipuleucel-T.  This analysis seeks to better understand if CMS will employ NCD’s to centralize its control over drug coverage.   METHODS:   NCD’s have primarily been applied to drugs and devices that have had some associated issue that could result in product misuse.  Such misuse may lead to unwarranted use, use that increases costs without commensurate outcomes, us that may impact patient safety or use outside of indication that is not deemed reasonable and necessary.  Review of the most recent CMS NCD covering sipuleucel-T provides some indication as to how CMS may use its NCD authority to control product coverage.  RESULTS:   Analysis of past CMS NCD’s indicates that CMS has historically regulated devices under NCD at a greater rate than drugs or biologics when there has been a concern over unwarranted use that would increase product utilization and costs over existing products.  This has resulted in coverage and payment being either restricted or tied to other products.  In the case of sipuleucel-T, CMS subjected it to review under NCD due to the fact that it is a vaccine, its cost is high and the high potential for use outside of castration resistant prostate cancer as reported in the media.  The result of CMS’ review was an NCD that allowed for coverage of on label use of sipuleucel-T, but reserved off label coverage decisions to individual contractors.  CONCLUSION:  Using CMS’ sipuleucel-T NCD as a potential predictor of future NCD actions, CMS may continue to make overall coverage decisions regarding labeled indications, but defer off label coverage determinations to local contractors.