Table A35:
Other Parameter-Specific Sensitivity Analyses: Remission, Relapse, Disutilities, and Costs
| Sensitivity Analysis: Parameter Uncertainty | Reference Case Analysis | Sensitivity Analysis | ||||
|---|---|---|---|---|---|---|
| Remission After Baseline | ||||||
| Parameter | Mean (95% CI/SE) a | Distribution a,b | Source | Mean (95% CI or SE) a | Distribution a,b | Source |
| Risk Ratio for Remission Based on MA | ||||||
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal | Greden et al, 201957 (GeneSight) | 1.50 (1.14; 1.96) | Lognormal | Clinical review, meta-analysis (two GeneSight RCTs57,65) |
| % Change in Risk of Remission (± 25%; ± 50% on Reference Case Log Odds Ratio Distribution), With or Without Assumption on the RR of Relapse: 8 Pas | ||||||
| Risk ratio for remission (intervention vs. TAU) Relative risk, relapse (intervention vs. TAU) |
1.47 (1.12; 1.94) 0.39 (0.04) |
Lognormal (mean: 0.385; SE: 0.140) Lognormal (mean: –0.942; SE: 0.0512) |
Greden et al, 201957 (GeneSight) Tanner et al, 202078 |
1.64 (1.18; 2.26) 0.39 (0.04) |
Lognormal (mean: 0.385 + 0.25 × 0.385; SE: 0.14 + 0.14 × 0.25) Lognormal |
PA1: +25% on the log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 — |
| Risk ratio for remission (intervention vs. TAU) Relative risk, relapse (intervention vs. TAU) |
1.47 (1.12; 1.94) 0.39 (0.04) |
Lognormal (mean: 0.385; SE: 0.140) Lognormal (mean: –0.942; SE: 0.0512) |
Greden et al, 201957 (GeneSight) Tanner et al, 202078 |
1.64 (1.18; 2.26) 1 |
Lognormal (mean: 0.385 + 0.25 × 0.385; SE: 0.14 + 0.14 × 0.25) NA |
PA2: +25% on log odds ratio, RR of relapse = 1 — |
| Risk ratio for remission (intervention vs. TAU) Relative risk, relapse (intervention vs. TAU) |
1.47 (1.12; 1.94) 0.39 (0.04) |
Lognormal (mean: 0.385; SE: 0.140) Lognormal (mean: –0.942; SE: 0.0512) |
Greden et al, 201957 (GeneSight) Tanner et al, 202078 |
1.34 (1.10; 1.63) 0.39 (0.04) |
Lognormal (mean: 0.385 – 0.25 × 0.385; SE: 0.14 – 0.14 × 0.25) Lognormal |
PA3: –25% on log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 — |
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | 1.34 (1.10; 1.63) | Lognormal (mean: 0.385 – 0.25 × 0.385; SE: 0.14 – 0.14 × 0.25) | PA4: –25% on log OR of remission, RR of relapse = 1 |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 1 | NA | — |
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | 1.81 (1.22; 2.66) | Lognormal (mean: 0.385 + 0.50 × 0.385; SE: 0.14 + 0.14 × 0.50) | PA5: +50% on the log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 0.39 (0.04) | Lognormal | — |
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | 1.81 (1.22; 2.66) | Lognormal (mean: 0.385 + 0.50 × 0.385; SE: 0.14 + 0.14 × 0.50) | PA6: +50% on the log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 1 | NA | — |
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | 1.21 (1.07; 1.39) | Lognormal (mean: 0.385 – 0.50 × 0.385; SE: 0.14 – 0.14 × 0.50) | PA7: –50% on log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 0.39 (0.04) | Lognormal | — |
| Risk ratio for remission (intervention vs. TAU) | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | 1.21 (1.07; 1.39) | Lognormal (mean: 0.385 – 0.50 × 0.385; SE: 0.14 – 0.14 × 0.50) | PA8: –50% on log OR of remission, RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 1 | NA | — |
| Threshold Analysis | ||||||
| Risk ratio for remission | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | Threshold analysis | NA | DA1: Threshold analysis on risk ratio for remission, assuming RR of relapse unchanged (RR = 0.39 [SE: 0.04])78 |
| Relative risk, relapse | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 0.39 (0.04) | NA | — |
| Risk ratio for remission | 1.47 (1.12; 1.94) | Lognormal (mean: 0.385; SE: 0.140) | Greden et al, 201957 (GeneSight) | Threshold analysis | NA | DA2: Threshold analysis on risk ratio for remission, assuming RR of relapse = 1 |
| Relative risk, relapse | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 1 | NA | — |
| Relapse | ||||||
| Parameter | Mean (SE) a | Distribution a,b | Source | Mean (95% CI or SE) a | Distribution a,b | Source |
| Relative risk, relapse (intervention vs. TAU) | 0.39 (0.04) | Lognormal (mean: –0.942; SE: 0.0512) | Tanner et al, 202078 | 1 | NA | NA, assumption based on lack of comparative long-term clinical data |
| Medication-Related Disutility | ||||||
| Parameter | Mean (SE) a | Distribution a,b | Source | Mean (95% CI or SE) a | Distribution a,b | Source |
| Disutility associated with medication side effects | –0.055 (0.03) | Beta | Mrazek et al, 2013,109,110 Najafzadeh et al, 201781 |
–0.01 (0.03∗) | Beta | Revicki, 1998110 |
| Disutility associated with medication side effects | –0.055 (0.03) | Beta | Mrazek et al, 2013,109,110 Najafzadeh et al, 201781 |
–0.12 (0.03∗) | Beta | Revicki, 1998110 |
| Cost of Testing | ||||||
| Parameter | Mean (SE) a | Distribution a,b | Source | Mean (SE) a | Distribution a,b | Source |
| Cost of PGx: lower range | $2,500 (625)78 | Gamma | Tanner et al, 202078 | $450 (112.5) | Gamma | Assumption on range for this cost was based on Maruf et al, 2020,21 and Tanner et al78 |
| Cost of PGx: upper range | $2,500 (625)78 | Gamma | Tanner et al, 202078 | $3,750 (937.5) | Gamma | Assumption on range for this cost was based on Maruf et al, 2020,21 and Tanner et al78 |
| Cost of PGx: threshold analysis | $2,500 (625)78 | Gamma | Tanner et al, 202078 | NA | NA | Deterministic, one-way threshold analysis |
| No. of Required Visits With a Physician or a Health Care Provider During Testing | ||||||
| Parameter | Mean | Distribution a,b | Source | Mean | Distribution a,b | Source |
| Visits required during testing | 2 | NA | Expert consultation | 0, 1, and 3 | NA | Expert consultation, 3 visits were assumed to accommodate pharmacists as another provider in circle of care or a delay in receiving results of test |
| Costs of Prescription Drugs in Remission (2020 CAD) | ||||||
| Parameter | Mean (SE) a | Distribution a,b | Source | Mean (SE) a | Distribution a,b | Source |
| Medication costs, monthly (2020 CAD): first 6 mo/Rest of follow-up (see Table 6)c | $122.86 (0.58)/44.93 (0.29) | Gamma | Tanner et al, 201987; Tanner et al, 202078 | $122.86/mo | Gamma | Constant higher prescription drug costs over 1-year time horizon; source for cost inputs was Tanner et al, 201987 |
| Medication costs, monthly (2020 CAD): first 6 mo/Rest of follow-up (see Table 6)c | $122.86 (0.58)/$44.93 (0.29) | Gamma | Tanner et al, 201987; Tanner et al, 202078 | $44.93 (0.29) | Gamma | Constant lower prescription drug costs over 1-year time horizon; source for cost inputs was Tanner et al, 201987 |
| Costs Associated With Health Care Service Use and Hospitalization in Remission (2020 CAD) | ||||||
| Parameter | Mean (SE) a | Distribution a,b | Source | Mean (SE) a | Distribution a,b | Source |
| Health care service and hospitalization costs, monthly (see Table 6)c | $145.02 (0.92) | Gamma | Tanner et al, 201987; Tanner et al, 202078 | 0–6 mo: $613.17 (7.58) 7–12 mo: $145.02 (0.92) |
Gamma | Time-dependent decrease in health care spending (see Table 6); source for cost inputs was Tanner et al, 201987 |
| Health care service and hospitalization costs, monthly (see Table 6)c | $145.02 (0.92) | Gamma | Tanner et al, 201987; Tanner et al, 202078 | $290.04 (0.92) | Gamma | 2x higher spending in remission |
Abbreviations: CI, confidence interval; NA, not applicable; PGx, multi-gene pharmacogenomic-guided treatment that includes a decision support tool; SE, standard error; TAU, treatment as usual.
a
Standard errors were estimated whenever data were available; SEs associated with relative risk of relapse was assumed to be 10% of mean; SEs associated with price of tests were assumed to be 25% of the mean.
b
Beta distributions were assigned to probability estimates in probabilistic analysis where applicable. Standard error of the mean (SE) was estimated from 95% CIs or from original data. Two parameters of the beta distribution (α, β) were derived from mean and SE (stated for each model parameter). Formulas for these calculations, derived from the mean and SE, are: α = ([Mean2] × [1 – Mean])/([SE2] – Mean); β = ([{1 – Mean} × {1 – Mean}] × Mean)/([SE2] – 1). Lognormal distributions were assigned for risk ratio inputs (wherever possible), using two distribution parameters: μ (mean of logs) and σ (SE, standard deviation of logs). Distribution parameters' values were based on original data; further adjustments and transformations to model cycle of 1 month were performed. We assigned gamma distributions to cost input parameters. Two parameters of the gamma distribution (α, λ) are derived from the mean and SE. Formulas for these calculations are: α = (Mean2)/(SE2); λ = Mean/([Mean × SE] 2).
c
Cost estimates were adjusted per model cycle of 1 month; see Table 6 for more information.