Treatments for Anemia in Chronic Kidney Disease: Effectiveness and Value
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Treatments for Anemia in Chronic Kidney Disease: Effectiveness and Value Supplemental Materials November 30, 2020 Prepared for ©Institute for Clinical and Economic Review, 2020 Table of Contents A. Background: Supplemental Information ........................................................................................... 1 A1. Definitions .................................................................................................................................... 1 A2. Potential Cost-Saving Measures .................................................................................................. 1 B. Patient Perspectives: Supplemental Information .............................................................................. 3 B1. Methods ....................................................................................................................................... 3 C. Clinical Guidelines .............................................................................................................................. 4 D. Comparative Clinical Effectiveness: Supplemental Information ....................................................... 5 D1. Detailed Methods ........................................................................................................................ 5 D2. Supplemental Results ................................................................................................................ 13 D3. Evidence Tables ......................................................................................................................... 48 D4. Heterogeneity and Subgroups ................................................................................................. 114 D5. Ongoing Studies ....................................................................................................................... 116 D6. Previous Systematic Reviews and Technology Assessments .................................................. 121 E. Long-Term Cost-Effectiveness: Supplemental Information ........................................................... 124 E1. Detailed Methods..................................................................................................................... 124 E2. Model Inputs and Assumptions ............................................................................................... 126 E3. Results ...................................................................................................................................... 136 E4. Sensitivity Analyses .................................................................................................................. 136 E5. Scenario Analyses ..................................................................................................................... 140 E6. Heterogeneity and Subgroups ................................................................................................. 142 E7. Model Validation ...................................................................................................................... 142 F. Potential Other Benefits and Contextual Considerations .............................................................. 144 G. Potential Budget Impact: Supplemental Information ................................................................... 146 Methods ......................................................................................................................................... 146 References ......................................................................................................................................... 147 Evidence Table References ................................................................................................................ 154 ©Institute for Clinical and Economic Review, 2020 A. Background: Supplemental Information A1. Definitions Anemia is defined as “a condition in which the number of red blood cells or their oxygen-carrying capacity is insufficient to meet physiological needs.”1 In anemia, insufficient numbers of circulating red blood cells or inadequate quantities of iron or functional hemoglobin (Hb) are available to transport and release oxygen to tissues. The World Health Organization (WHO) and the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines define anemia as a Hb level of <12 g/dL in females and <13 g/dL in adult males. However, this definition does not provide goals of treatment for different patients’ groups.2,3 Chronic kidney disease (CKD) is a condition characterized by a gradual loss of kidney function over time. The definition and classification of CKD guidelines were established and endorsed by the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (KDOQI) and the international KDIGO guideline group.4-7 CKD is defined by the presence of kidney damage or decreased kidney function for three or more months.8 Decreased kidney function refers to a decreased in glomerular filtration rate (GFR), which is usually estimated (eGFR) using serum creatinine and one of several available equations.9-11 Patients who are diagnosed with CKD can be categorized into different stages according to the cause, their GFR (six G-stages; G-I: ≥90 ml/min per 1.73 m2, G-II: 60-89, G-IIIa: 45-59, G-IIIb: 30-44, G-IV: 15-29, G-V: <15 ml/min per 1.73 m2), and the amount of albumin or protein in the urine (three A-stages; A-1: <30, A-2: 30-299, and A-3: ≤300 mg/g). Additionally, patients with CKD can advance from being dialysis independent (DI-CKD) to renal failure (also known as end-stage kidney disease [ESKD]), which is defined as severely reduced kidney function or treatment with dialysis (dialysis dependent [DD-CKD]) or transplantation. Risk factors for CKD include genetic or sociodemographic predisposition, or the presence of diseases that can initiate and propagate kidney disease. A2. Potential Cost-Saving Measures ICER includes in its reports information on wasteful or lower-value services in the same clinical area that could be reduced or eliminated to create headroom in health care budgets for higher-value innovative services (for more information, see https://icer-review.org/final-vaf-2017-2019/). These services are ones that would not be directly affected by roxadustat (e.g., reduction in blood transfusion), as these services will be captured in the economic model. Rather, we are seeking services used in the current management of CKD beyond the potential offsets that arise from a new intervention. During stakeholder engagement and public comment periods, ICER encouraged all stakeholders to suggest services (including treatments and mechanisms of care) currently used for ©Institute for Clinical and Economic Review, 2020 Page 1 Supplemental Materials – Treatments for Anemia in CKD Return to Table of Contents patients with CKD that could be reduced, eliminated, or made more efficient. No suggestions were received. ©Institute for Clinical and Economic Review, 2020 Page 2 Supplemental Materials – Treatments for Anemia in CKD Return to Table of Contents B. Patient Perspectives: Supplemental Information B1. Methods ICER engaged with patients with CKD (DI-CKD, DD-CKD, and post-transplant), caregivers, representatives from professional and advocacy organizations, and clinical experts to understand the specific challenges associated with ongoing management of anemia in CKD from the patient perspective. ICER engaged with these groups using different platforms including webinars, one-on- one meetings, group meetings, and written communication. ©Institute for Clinical and Economic Review, 2020 Page 3 Supplemental Materials – Treatments for Anemia in CKD Return to Table of Contents C. Clinical Guidelines Multiple organizations have issued guidelines about management of anemia in CKD. However, most of these guidelines are out of date and do not include roxadustat or any other HIF-PH inhibitors as potential treatment options. Kidney Disease: Improving Global Outcomes In 2012, KDIGO issued an anemia guideline, providing recommendations on treatment including the use of iron agents and ESAs.12 Since then, KDIGO convened a Controversy Conference in December 2019 and had been planning a second one in 2020. These conferences aim to review the latest evidence and assess change implications for the 2012 KDIGO anemia guideline. Given that studies of the effects of HIF-PH inhibitors were still in progress, the first conference was focused on iron and target iron therapeutic agents. The second conference will be focused on ESAs and HIF-PH inhibitors; however, the conference has been postponed indefinitely due to the COVID-19 pandemic. National Institute for Health and Care Excellence (NICE) In 2015, NICE published their guidelines about anemia management in CKD, which did not include guidance about HIF-PH inhibitors.13 Since then, NICE has conducted an update of the evidence in 2017 and concluded that there was no new evidence to issue recommendations about HIF-PH inhibitors as larger trials were underway. NICE was planning a scoping workshop in preparation for conducting an appraisal about roxadustat in March 2020, which was cancelled due to updates about the timing of the regulatory review. ©Institute for Clinical and Economic Review, 2020 Page 4 Supplemental Materials – Treatments for Anemia in CKD Return to Table of Contents D. Comparative Clinical Effectiveness: Supplemental Information D1. Detailed Methods Population, Intervention, Comparators, Outcomes, Timing, and Settings Framework (PICOTS)