Table 3:

Evidence to decision for desidustat as an alternative to ESA for anemia in NDD-CKD patients

Benefits and harms	Small net benefit or little difference between alternatives
Desidustat decreased adverse events up to 26 weeks in ESA-naïve patients by 24/1000 as compared to darbepoetin alpha. Almost 100% of GDG members (not including patients) find such a cut-off acceptable for using HIF-PHIs. However, evidence on this was uncertain. Compared to ESAs, Desidustat had little or no difference on hemoglobin levels from baseline up to 24 weeks. However, evidence on this was uncertain. All GDG find such a scenario acceptable to switch to HIF-PHIs. Compared to ESA, the desidustat group had little or no difference on QoL measured by SF-36 score at 24 weeks in ESA-naïve patients, but evidence on this was uncertain. About 59% GDG members (not including patients) are comfortable using HIF-PHIs over ESAs in a scenario where there is evidence of no difference in QoL. Similarly, desidustat had no difference on all-cause mortality up to 26 weeks as compared to darbepoetin alpha. However, evidence on this was uncertain. About 74% GDG members (not including patients) find such a cut-off acceptable for using HIF-PHIs. There were too few ESA-naïve patients who experienced the need for ESA up to 24 weeks, to determine whether desidustat (any dose) made a difference when compared with darbepoetin alpha. Evidence on this was uncertain. There was no data available in the included studies that examined fatigue, incidence of MACE and MACE plus, progression to end-stage kidney disease (defined by stage 5 CKD), need for oral or intravenous iron supplementation or patients requiring blood transfusion. Overall, the panel judged that there were comparable anticipated effects and trivial harms for using desidustat (over ESAs), noting there was very low certainty on the evidence base. There is concern regarding the lack of robust evidence on cardiovascular safety in NDD-CKD patients with anemia.
Certainty of the evidence	Low [Table 2]
Values and preferences	No substantial variability expected
Empirical examinations of patients’ values and preferences from South Asia are not available. This section is based on unstructured interactions with individual patients and caregivers and discussions with panel members. The consensus statement places a relatively high value on the belief that patients, clinicians, and caregivers prefer oral drugs over subcutaneous injections for those who are NDD and may not have access to refrigeration facilities. However, the GDG also inferred that some healthcare workers and patients might be reluctant to use desidustat due to the low certainty of evidence and lack of evidence on cardiovascular risk.
Resources	No important issues with the recommended alternative
Desidustat is administered orally and does not require cold chain maintenance, thereby minimizing the resources required as compared to ESAs which require refrigeration prior to administration. This is especially relevant to rural areas where these resources are scarce.
Equity	No important issues with the recommended alternative
Desidustat does not need refrigeration (cold chain) as compared to ESAs. It is thus more useful in remote areas with irregular supply of electricity and in equity groups who might not have refrigeration in their homes. Furthermore, as ESAs require injection, a certain level of training will be needed to learn how to self-administer the treatment.
Acceptability	No important issues with the recommended alternative
Desidustat has a preferable route of administration for patients; patients either must self-administer ESA injections or make a hospital visit for the injection. However, ESAs have weekly/fortnightly dose requirements, whereas desidustat should be taken daily or on alternate days. Both these factors can impact compliance and treatment adherence. ESAs may also be easier to supervise than desidustat due to the differences in dose frequency requirements. Overall, for NDD patients, the oral nature of desidustat was thought to be more acceptable by the GDG.
Feasibility	No important issues with the recommended alternative
Desidustat can be orally administered and does not require cold chain, unlike ESAs, which is relatively easy to administer and store. In addition, desidustat may increase accessibility, particularly for non-dialysis patients, as it does not require hospital visit or self-injection. As desidustat is approved in India, the treatment seems to be feasible at the current time.

ESA: Eythropoiesis-stimulating agents, NDD: Nondialysis dependent, CKD: Chronic kidney disease, MACE: Major adverse cardiovascular events, QoL: Quality of life, GDG: Guideline development group, HIF PHI: Hypoxia-inducible factor prolyl hydroxylase inhibitor