Substantial Clinical Improvement: Optimizing CMS Guidelines for New Products

Despite the growing incidence and prevalence of kidney disease on a worldwide basis, there have been fewer nephrology-themed randomized controlled trials than in any other internal medicine subspecialty, less funding from public and private sources, and fewer innovative devices or medications developed than for all other diseases combined.1,2,3 In response to increasing demand to address this inequity, the Centers for Medicare and Medicaid Services (CMS) established the end stage renal disease (ESRD) Prospective Payment System (PPS) Transitional Add-on Payment Adjustment for New and Innovative Equipment and Supplies (TPNIES). Its purpose is to facilitate beneficiary access to certain qualifying new and innovative renal dialysis equipment and supplies, by providing an add-on payment adjustment to support ESRD facilities in the uptake of new and innovative equipment and supplies under the ESRD PPS.

The TPNIES program began in 2020, and in its inaugural year had two applicants: a dialyzer that was touted to improve several aspects of the life of someone receiving dialysis, and a home dialysis machine cartridge that was to encourage greater use of home hemodialysis. Neither of these were successful in their TPNIES quest. 

In the case of the dialyzer, CMS opined that the studies and data presented (by the applicant) either were low powered, did not provide statistical significance in their results, and/or did not include a control population. In addition, they cautioned that the studies provided signaled that albumin might be filtered by the product, resulting in low levels of albumin for some individuals receiving dialysis.4 In the case of the home dialysis machine cartridge, CMS clarified that capital-related assets were not covered in the first version of TPNIES and that the stand-alone cartridge (without the home dialysis machine) could not be evaluated on its own. In the Final Rule, published in the Federal Register on November 9, 2020, CMS modified the original criteria to expand the dates a device would be eligible and included capital-related home dialysis machines when used in a home for a single person.

What are the criteria and how does CMS make a decision? Although the details are lengthy and complex, the main determinant is evidence that the renal dialysis device shows substantial clinical improvement for Medicare beneficiaries in at least one of the following ways: 

  • It must offer a new treatment option for people who are unresponsive to or ineligible for current treatments. 
  • It must offer the ability to diagnose a medical condition earlier in the disease course or one that is currently undetectable. 
  • It must significantly improve clinical outcomes relative to services or technologies previously available.
  • The totality of information must otherwise demonstrate substantial improvement relative to renal dialysis services previously available. 

How does one determine what constitutes significant improvement of clinical outcomes? The relative and absolute risks of mortality in dialysis have fallen in the past several decades in the U.S.5 Despite this, mortality remains very high. Does prolonging life on dialysis constitute substantial clinical improvement? Individuals report fatigue, insomnia, cramps, depression, anxiety, and frustration as their major concerns, so wouldn’t alleviating symptoms or improving quality of life be as or even more important? 

Although CMS has created a framework for defining substantial clinical benefit, is the framework optimal and how should substantial clinical benefit be defined? Advances that significantly impact quality-of-life should be of the highest priority. Imagine a therapy that eliminated the need for phosphate binders, stopped cramping completely, prevented any post-therapy fatigue, or reduced the number of days dialysis was needed (yet provided comparable or even better clearances and ultrafiltration). Think of the factors that contribute to the morbidity on dialysis: cardiovascular complications, infections, bleeding, and cognitive changes. Let’s really spur thought, investigation, and the creation of changes that would provide new meaning to “substantial.”

New products ideally should have rigorous, well-designed, large randomized controlled trials to clearly demonstrate substantial clinical improvement, including careful study design and endpoints. Support of investigator-initiated research studies needs to be promoted to address potential data gaps. There should be attempts to generate health economic data from these trials and studies to demonstrate product value. Finally, publications and meta-analysis supporting the new device will be critical in helping establish a network of advocates including key opinion leaders, individuals receiving dialysis, and healthcare organizations. 

With this approach, great advances may be realized to better all aspects of life for those who suffer with the spectrum of kidney ailments.

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Senior Vice President and Chief Medical Officer, Renal Therapies Group, Fresenius Medical Care North America Chief Medical Officer, Frenova Renal Research


  1. Strippoli GF, Craig JC, Schena FP. The number, quality, and coverage of randomized controlled trials in nephrology. J Am Soc Nephrol 2004 Feb;15(2):411-19. doi: 10.1097/01.asn.0000100125.21491.46.
  2. Deo A, Schmid CH, Earley A, et al. Loss to analysis in randomized controlled trials in CKD. Am J Kidney Dis 2011 Sept;58(3):349-55. doi: 10.1053/j.ajkd.2011.04.023.
  3. Palmer SC, Sciancalepore M, Strippoli GF. Trial quality in nephrology: how are we measuring up? Am J Kidney Dis 2011 Sep;58(3):335-7. doi: 10.1053/j.ajkd.2011.06.006.
  4. Centers for Medicare and Medicaid Services. Medicare program: End-Stage Renal Disease Prospective Payment System, payment for renal dialysis services furnished to individuals with acute kidney injury, and End-Stage Renal Disease Quality Incentive Program. Fact sheet, Nov. 2, 2020. https://www.cms.gov/newsroom/fact-sheets/medicare-program-end-stage-renal-disease-prospective-payment-system-payment-renal-dialysis-services.
  5. Wetmore JB, Gilbertson DT, Liu J, Collins AJ. Improving outcome in patients receiving dialysis: the PEER Kidney Care Initiative. Clin J Am Soc Nephrol 2016 Jul 7;11(7):1297-1304. doi: 10.2215/CJN.12981215.