Table 1.
Model input parameters, ranges of variation, and distribution type, in sensitivity analyses
| Parameter | Base-case analysis | DSA | PSA | Data source |
|---|---|---|---|---|
| Clinical efficacy | ||||
| Reduction of serum phosphorus level, PA21 | 1.93 mg/dL | 95 % CI 1.78–2.08 | Normal, mean 1.93, SD 2.08 | See Footnote 1 a |
| Reduction of serum phosphorus level, SC | 1.95 mg/dL | 95 % CI 1.73–2.17 | Normal, mean 1.95, SD 2.13 | See Footnote 1 a |
| Cohort characteristics | ||||
| Withdrawals due to TEAEs first 6 months, PA21 | 14.3 % | 95 % CI 13.1–18.6 | β, a = 89, b = 534 | See Footnote 1 |
| Withdrawals due to TEAEs first 6 months, SC | 6.6 % | 95 % CI 4.2–9.8 | β, a = 21, b = 290 | See Footnote 1 |
| Withdrawals due to TEAEs subsequently, PA21 | 5.4 % | 95 % CI 2.6–8.2 | β, a = 13, b = 228 | See Footnote 1 |
| Withdrawals due to TEAEs subsequently, SC | 2.3 % | 95 % CI 2.0–2.7 | β, a = 3, b = 108 | See Footnote 1 |
| Withdrawals due to sustained hyperphosphatemia (off-target), PA21 | 9.9 % | 95 % CI 7.8–12.3 | β, a = 66, b = 598 | See Footnote 1 |
| Withdrawals due to sustained hyperphosphatemia (off-target), SC | 6.3 % | 95 % CI 4.0–9.4 | β, a = 19, b = 289 | See Footnote 1 |
| Modality of dialysis treatment (HD) | 91.9 % | PE ± 15 % | β, a = 1041, b = 957 | [6] |
| Modality of dialysis treatment (PD) | 8.1 % | 1-value for dialysis (HD) | 1-distribution of dialysis (HD) | [6] |
| Survival | ||||
| RR of survival in ESRD patients (RR increase per mg/dL) | 1.35 | 95 % CI 1.16–1.57 | Log-normal, µ = 0.298, ơ = 0.072 | [8] |
| Survival of patients receiving dialysis | Weibull survival function: S(t) = exp{−λtγ}, λ = 0.15, γ = 0.94 | – | – | [14] |
| Survival of kidney transplant patients | Weibull survival function: S(t) = exp{−λtγ}, λ = 0.036, γ = 0.85 | – | – | [12] |
| AE occurrences | ||||
| Diarrhoea, PA21 | 20.1 % | 95 % CI 17.2–23.2 | Uniform, PE ± 50 % | [6] |
| Diarrhoea, SC | 7.5 % | 95 % CI 4.9–10.8 | Uniform, PE ± 50 % | [6] |
| Nausea, PA21 | 7.2 % | 95 % CI 5.4–9.4 | Uniform, PE ± 50 % | [6] |
| Nausea, SC | 11.2 % | 95 % CI 8.1–15.0 | Uniform, PE ± 50 % | [6] |
| Abdominal pain, PA21 | 5 % | 95 % CI 1.5–5.8 | Uniform, PE ± 50 % | [7] |
| Abdominal pain, SC | 4.9 % | 95 % CI 1.4–5.2 | Uniform, PE ± 50 % | [7] |
| Vomiting, PA21 | 4.4 % | 95 % CI 3.0–6.2 | Uniform, PE ± 50 % | [6] |
| Vomiting, SC | 5.5 % | 95 % CI 3.3–8.4 | Uniform, PE ± 50 % | [6] |
| Constipation, PA21 | 3.8 % | 95 % CI 2.5–5.5 | Uniform, PE ± 50 % | [6] |
| Constipation, SC | 7.2 % | 95 % CI 4.7–10.4 | Uniform, PE ± 50 % | [6] |
| Resource use | ||||
| Mean number of tablets/day, PA21 | 3.3 | PE ± 1.3 (SD) | γ, a = 2622, b = 813 | [7] |
| Maximum daily dose, PA21 | 6 | – | – | [6, 7] |
| Mean number of tablets/day, SC | 8.7 | PE ± 3.6 (SD) | γ, a = 2078, b = 239 | [7] |
| Maximum daily dose, SC | 18 | – | – | [6, 7] |
| GP appointments for AEs | 1 | – | – | [11] |
| Health-state utilities | ||||
| Utility of ESRD patients receiving dialysis | 0.565 | 95 % CI 0.514–0.616 | β, a = 205, b = 158 | [11, 15] |
| Utility of kidney transplantation | 0.809 | 95 % CI 0.71–0.91 | β, a = 38, b = 6 | [11, 15] |
| Event utilities (relative preserved utility associated with events)c | ||||
| Transplant | 87 % | PE ± 15 % | β, a = 38, b = 6 | [11] |
| Diarrhoea | 92 % | PE ± 15 % | β, a = 26, b = 2 | [11] |
| Nausea | 91 % | PE ± 15 % | β, a = 29, b = 3 | [11] |
| Abdominal pain | 73 % | PE ± 15 % | β, a = 57, b = 21 | [11] |
| Vomiting | 91 % | PE ± 15 % | β, a = 29, b = 3 | [11] |
| Constipation | 85 % | PE ± 15 % | β, a = 43, b = 8 | [11] |
| Duration of disutilityc | ||||
| Transplant | 1 month | PE ± 15 % | – | [11] |
| Drug-related AEs | 5 days | PE ± 15 % | γ, a = 10,000, b = 2000 | [11] |
| Costs | ||||
| Drug cost per tablet, PA21 (GBP)b | 1.99 | PE ± 15 % | Uniform, PE ± 15 % | [16] |
| Drug cost per tablet, SC (GBP)b | 0.93 | PE ± 15 % | Uniform, PE ± 15 % | [16] |
| AE cost (GBP) | 36 | PE ± 50 % | Uniform, PE ± 50 % | [17] |
| Parameter | Scenario analysis | DSA | PSA | Data source |
|---|---|---|---|---|
| Difference in survival (PA21 vs. SC) | 0.714 | 95 % CI 0.37–1.40 | See Footnote 1 | |
| Transplants in prevalent patients, yearly | 4.4 % | PE ± 15 % | β, a = 4600, b = 269 | [12] |
| RR of survival in ESRD patients (RR increase per mg/dL) | 1.18 | – | – | [8] |
| Costs | ||||
| Annual dialysis cost, HD (GBP) | 24,216 | PE ± 15 % | Uniform, PE ± 15 % | Weighted mean [12, 19] |
| Annual dialysis cost, PD (GBP) | 9115 | PE ± 15 % | Uniform, PE ± 15 % | Weighted mean [12, 19] |
| Initial kidney transplantation cost (GBP) | 15,855 | PE ± 15 % | Uniform, PE ± 15 % | [20] |
| Follow-up cost kidney transplantation per year, year 1 (GBP) | 19,044 | PE ± 15 % | Uniform, PE ± 15 % | [21] |
| Follow-up cost kidney transplantation per year, subsequent years (GBP) | 7877 | PE ± 15 % | Uniform, PE ± 15 % | [21] |
AE adverse event, CI confidence interval, DSA deterministic sensitivity analysis, ESRD end-stage renal disease, GBP Great Britain pound, GP general practitioner, HD haemodialysis, PA21 sucroferric oxyhydroxide, PD peritoneal dialysis, PE point estimate, PSA probabilistic sensitivity analysis, RR relative risk, SE standard error, SD standard deviation, SC sevelamer carbonate, TEAEs treatment-emergent adverse events
aFor the cost-effectiveness analysis, the results of the combined endpoint of the PA-CL-05A/B trials obtained in the full analysis set were used. In the studies by Floege et al. [6, 7], the mean reduction of serum phosphorus levels was presented only for completers of the study
bDrug strengths: 2.5 g of PA21 and 0.8 g of SC per tablet
cSE was unknown and assumed to be 0.05