Etelcalcetide for Treating Secondary Hyperparathyroidism: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal
The manufacturer of the calcimimetic drug etelcalcetide was invited to make an evidence submission as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal (STA) programme. Within this submission, they reported evidence on the clinical and cost effectiveness of etelcalcetide for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on haemodialysis. The Southampton Health Technology Assessments Centre (SHTAC), part of the Wessex Institute at the University of Southampton, was the independent Evidence Review Group (ERG) commissioned to appraise the company’s submission. This article describes the ERG’s review and critique of the company’s submission and summarises the NICE Appraisal Committee’s subsequent guidance (issued in June 2017). The clinical-effectiveness evidence submitted by the company consisted of two double-blind, randomised controlled trials (RCTs) comparing etelcalcetide with placebo, one RCT comparing etelcalcetide with cinacalcet, two single-arm extension studies of the above trials, and one single-arm study evaluating the effect of switching from cinacalcet to etelcalcetide. No study specifically examined the population specified in the NICE appraisal scope: patients refractory to standard therapy with phosphate binders and vitamin D (PBVD). None of these trials were designed to collect long-term efficacy data for outcomes such as mortality, bone fractures, cardiovascular events, or parathyroidectomies. Instead, biomarker data from the trials were mapped to long-term outcomes by an assumed linear relationship between the trial outcome, reduction of parathyroid hormone (PTH) by > 30%, and the log-hazard ratios for the occurrence of clinical events derived from a large, long-term RCT of cinacalcet (the EVOLVE trial). After submission of a confidential Patient Access Scheme (PAS) discount reducing etelcalcetide drug costs, the incremental cost-effectiveness ratio (ICER) for etelcalcetide versus cinacalcet was £14,778 per quality-adjusted life-year (QALY) gained in the company’s base case. While this value is lower than the NICE threshold range of £20,000 and £30,000 per QALY gained, it was the opinion of the ERG that the ICER was highly uncertain due to efficacy data limitations for etelcalcetide, inadequate synthesis of clinical-effectiveness evidence, and strong assumptions connecting short-term biomarker data with long-term clinical outcomes. The ERG produced an alternative base case for etelcalcetide versus cinacalcet, with an ICER of £22,400 per QALY gained, also subject to uncertainty. The NICE Appraisal Committee recommended etelcalcetide as an option for the treatment of SHPT in adults with CKD only if treatment with a calcimimetic is indicated and cinacalcet is not suitable, subject to the company’s provision of the agreed PAS discount.
The authors are very grateful to the clinical experts who provided them with information during the appraisal and who commented on the draft ERG report. They would also like to thank Karen Welch, Information Scientist, SHTAC, for appraising the literature search strategies in the company’s submission, running updates of the company’s clinical-effectiveness searches and searching for ongoing studies; and Emma Loveman and Jill Colquitt, Senior Reviewers/Partners, Effective Evidence LLP, for providing feedback on the ERG report.
All authors have commented on the submitted manuscript and have given their approval for the full version to be published. MR and JL summarised and critiqued the economic analysis submitted by the company. JS, KP, and PH summarised and critiqued the clinical-effectiveness evidence submitted by the company. MR drafted this manuscript and responded to feedback from all other authors. All authors reviewed, critiqued, and approved the final version submitted for publication. This summary has not been externally reviewed by PharmacoEconomics.
Compliance with Ethical Standards
This project was funded by the National Institute for Health Research (NIHR) HTA Program (project number 16/10/01 STA) [see the NIHR Journals Library website for further information—https://www.journalslibrary.nihr.ac.uk/#/]. The views and opinions expressed herein are the authors and do not necessarily reflect those of the HTA Programme, NICE, NIHR, NHS, or the Department of Health. Any errors are the responsibility of the authors. This summary of the ERG report was compiled after NICE issued the Final Appraisal Determination.
Conflict of interest
Micah Rose, Jonathan Shepherd, Petra Harris, Karen Pickett and Joanne Lord declare no conflicts of interest.
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