Table 21:

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

Benefits and harms	Small net benefit or little difference between alternatives
Desidustat improved QoL assessed by SF-36 up to 24 weeks. But evidence on this was uncertain. All GDG members (not including patients) are comfortable using HIF-PHIs over ESAs in a scenario where there is evidence of improved QoL for HIF-PHI. Desidustat reduced all-cause mortality up to 26 weeks by 16/1000. However, evidence on this was uncertain. About 64% of GDG members (not including patients) find such a cut-off acceptable for using HIF-PHIs. Desidustat had little or no difference for hemoglobin levels from baseline up to 16–24 weeks. However, evidence on this was uncertain. All GDG members (not including patients) find such a scenario acceptable to switch to HIF-PHIs. In the group that received desidustat, there were 15/1000 more treatment emergent adverse events up to 26 weeks compared to ESAs. Evidence on this was uncertain. About 97% of GDG members (not including patients) would find such a scenario unacceptable. There is no evidence on fatigue, incidences of MACE and MACE plus, patient requiring blood transfusion, need for iron supplements (oral/IV), and need for ESA from the trials. All these outcomes were thought to be critical for decision-making. Overall, the panel judged that the anticipated benefits and harms of desidustat over HIF-PHIs were small, but there was very low certainty in the evidence. There is some concern regarding the lack of robust evidence on cardiovascular safety in DD-CKD patients with anemia.
Certainty of the evidence	Very low [Table 20]
Values and preferences	Substantial variability is expected or uncertain
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. Subcutaneous ESA administration is challenging due to its invasive nature; its use has a learning curve and there are logistic issues (refrigeration). Use of HIF-PHIs might have concerns around pill burden and adherence in some patients. However, some patients might prefer injections because of the need to limit fluid intake
Resources	No important issues with the recommended alternative
There was no empirical assessment of costs for resources. The direct price of sesidustat (which is available in India) for a month is substantially lower than that of the ESAs. Additionally, desidustat does not need refrigeration and can be administered orally (compared to subcutaneously when given at home or intravenously during hemodialysis). Overall, it is likely to have resource savings. The assessment is based on opinions of GDG members collected through a survey.
Equity	No important issues with the recommended alternative
Desidustat does not need refrigeration and can be administered orally (unlike ESA). DD patients of CKD undergoing hemodialysis however can be administered ESA during hospital visits, irrespective of health literacy status or affordability. For those undergoing peritoneal dialysis, oral drugs will probably increase equity more.
Acceptability	Important issues or potential issues not investigated
There are no qualitative studies on preference of South Asian patients with DD-CKD with respect to the acceptability of HIF-PHIs. Patients with hemodialysis might get ESAs intravenously, thus not requiring additional pricks through subcutaneous routes. However, there are concerns around polypharmacy on the use of HIF-PHIs.
Feasibility	No important issues with the recommended alternative
There are no formal studies on facilitators and barriers to the use of HIF-PHIs in South Asia. The panel adjudged that desidustat, which is licensed for use in India, because of its oral route of administration, is a feasible intervention.

DD: Dialysis-Dependent, CKD: Chronic kidney disease, ESA: Eythropoiesis-stimulating agents, MACE: Major adverse cardiovascular events, SF 36: Short Form 36 Health Survey, QoL: Quality of life, HIF PHI: Hypoxia-inducible factor prolyl hydroxylase inhibitor, GDG: Guideline development group