Table 11.
Probabilistic sensitivity analysis: input parameters and distributions
| Input parameters | Distribution | PSA parameters | Comments | ||||
|---|---|---|---|---|---|---|---|
| Mortality data | Median | ET | µ | σ | |||
| SMR (median): stable: male | Log-normal | 3.02 | 0.15 | 1.1 | 0.1 | Hypothesis: SD = 10 % × mean | |
| SMR (median): stable: female | Log-normal | 2.37 | 0.12 | 0.9 | 0.1 | Hypothesis: SD = 10 % ×mean | |
| SMR median: relapse | Log-normal | 6.20 | 0.32 | 1.8 | 0.1 | Hypothesis: SD = 10 % ×mean | |
| Treatment sequences | |||||||
| First line: % of pts initiating AP1 at the hospital | Min | Max | a | b | |||
| PLAI | Uniform | 80 % | 100 % | 0.8 | 1.0 | ||
| RLAI | Uniform | 80 % | 100 % | 0.8 | 1.0 | ||
| ALAI | Uniform | 80 % | 100 % | 0.8 | 1.0 | ||
| OLAI | Uniform | 80 % | 100 % | 0.8 | 1.0 | ||
| HLAI | Uniform | 80 % | 100 % | 0.8 | 1.0 | ||
| OO | Uniform | 00 % | 20 % | 0.0 | 0.2 | ||
| Second line | Mean | Var | αj | β = 1 | |||
| After PLAI | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| After RLAI | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| After ALAI | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| After OLAI | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| After HLAI | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| After OO | |||||||
| PLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| RLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| ALAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| OLAI | Dirichlet | 25 % | 0.25 % | 25.0 | 1.0 | Hypothesis: Var = mean/100 | |
| Probabilities of interruption | |||||||
| Probabilities of interruption and being stable at 3 months | Events | Pop. | α | β | |||
| PLAI: initiation | Beta | 88 | 607 | 88 | 519 | ||
| PLAI: prevention | Beta | 28 | 206 | 28 | 178 | ||
| Events | Pop. | α | β | ||||
| RLAI: initiation | Beta | 89 | 613 | 89 | 524 | ||
| RLAI: prevention | Beta | 28 | 206 | 89 | 178 | ||
| Mean | Variance | α | β | ||||
| ALAI: initiation | Beta | 0.1767 | 0.0004 | 70.11 | 326.67 | ||
| Events | Pop. | α | β | ||||
| ALAI: prevention | Beta | 28 | 206 | 28 | 178 | ||
| Mean | Variance | α | β | ||||
| OLAI: initiation | Beta | 0.1412 | 0.0002 | 96.24 | 585.15 | ||
| Events | Pop. | α | β | ||||
| OLAI: prevention | Beta | 28 | 206 | 28 | 178 | ||
| Mean | Variance | α | β | ||||
| HLAI: initiation | Beta | 0.2203 | 0.0004 | 98.79 | 349.57 | ||
| Events | Pop. | α | β | ||||
| HLAI: prevention | Beta | 28 | 206 | 28 | 178 | ||
| Mean | Variance | α | β | ||||
| OO: initiation | Beta | 0.1412 | 0.0002 | 96.24 | 585.15 | ||
| Events | Pop. | α | β | ||||
| OO: prevention | Beta | 28 | 206 | 28 | 178 | ||
| Transition probabilities of stable pts | Mean | Variance | αj | β = 1 | |||
| 1. Probability of being stable without treatment | Dirichlet | 0.2307 | 0.0023 | 23.07 | 1 | Hypothesis: Var = mean/100 | |
| 2. Probability of initiating the same antipsychotic than the previous treatment line | Dirichlet | 0.2307 | 0.0023 | 23.07 | 1 | Hypothesis: Var = mean/100 | |
| 3. Probability of initiating a new antipsychotic | Dirichlet | 0.2307 | 0.0023 | 23.07 | 1 | Hypothesis: Var = mean/100 | |
| Mean | Variance | α | β | ||||
| 4. Median time before relapse | Gamma | 172 | 25.5 | 45.5 | 3.8 | ||
| Probabilities of relapse | |||||||
| Probabilities of relapse at 3 months | Events | Pop. | α | β | |||
| PLAI: initiation | Beta | 40 | 607 | 40 | 567 | ||
| Moy/an | Var/an | α | β | ||||
| PLAI: prevention | Beta | 0.2915 | 0.0163 | 3.4092 | 8.2855 | ||
| Mean | Pop. | α | β | ||||
| RLAI: initiation | Beta | 43 | 613 | 43 | 570 | ||
| Mean/year | Var/an | α | β | ||||
| RLAI: prevention | Beta | 0.2915 | 0.0163 | 3.4092 | 8.2855 | ||
| Mean | Variance | α | β | ||||
| ALAI: initiation | Beta | 0.0820 | 0.0001 | 62.336 | 698.06 | ||
| Mean/year | Var/an | α | β | ||||
| ALAI: prevention | Beta | 0.2915 | 0.0163 | 3.4092 | 8.2855 | ||
| Mean | Variance | α | β | ||||
| OLAI: initiation | Beta | 0.0640 | 0.000 | 87.937 | 1285.1 | ||
| Mean/year | Var/an | α | β | ||||
| OLAI: prevention | Beta | 0.2915 | 0.0163 | 3.4092 | 8.2855 | ||
| Mean | Variance | α | β | ||||
| HLAI: initiation | Beta | 0.1052 | 0.0001 | 85.501 | 727.18 | ||
| Mean RR | Var RR | α | β | ||||
| HLAI: prevention | Beta | 0.5300 | 0.0115 | 10.971 | 9.7287 | ||
| Mean | Variance | α | β | ||||
| OO: initiation | Beta | 0.0640 | 0.000 | 87.937 | 1285.1 | ||
| Mean RR | Var RR | α | β | ||||
| OO: prevention | Beta | 0.6000 | 0.0183 | 7.2774 | 4.8516 | ||
| Proportions of pts in relapse leaving the hospital | Mean | Variance | αj | β = 1 | |||
| Within the 3 months | Dirichlet | 0.8493 | 0.0009 | 84.9315 | 1 | ||
| Between 3 and 6 months | Dirichlet | 0.1027 | 0.0006 | 10.274 | 1 | ||
| Between 6 and 9 months | Dirichlet | 0.0205 | 0.0001 | 2.0548 | 1 | ||
| Between 9 and 12 months | Dirichlet | 0.0068 | 0.000 | 0.6849 | 1 | ||
| After 12 months | Dirichlet | 0.0205 | 0.0001 | 2.0548 | 1 | ||
| Proportion of relapse requiring a hospitalisation | Mean | Variance | α | β | |||
| % hospitalised patients | Beta | 0.6700 | 0.0012 | 126.10 | 62.110 | Hypothesis: SD = 10 %*Mean | |
| Proportion of pts treated by the same antipsychotic than the previous line after a relapse | Mean | Variance | α | β | |||
| % of patients initiating the same antipsychotic | Beta | 0.1500 | 0.0001 | 326.39 | 1849.5 | Hypothesis: SD = 10 %*Mean | |
| Probabilities of switch (due to lack of tolerance) | |||||||
| Probabilities of switch at 3 months | Events | Pop. | α | β | |||
| PLAI: initiation | Beta | 20 | 607 | 20 | 587 | ||
| PLAI: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Events | Pop. | α | β | ||||
| RLAI: initiation | Beta | 10 | 613 | 10 | 603 | ||
| RLAI: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Mean | Variance | α | β | ||||
| ALAI: initiation | Beta | 0.0413 | 0.000 | 59.435 | 1378.1 | ||
| Events | Pop. | α | β | ||||
| ALAI: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Mean | Variance | α | Β | ||||
| OLAI: initiation | Beta | 0.0320 | 0.0000 | 84.855 | 2567.5 | ||
| Events | Pop. | α | β | ||||
| OLAI: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Mean | Variance | α | β | ||||
| HLAI: initiation | Beta | 0.0537 | 0.000 | 80.547 | 1418.4 | ||
| Events | Pop. | α | β | ||||
| HLAI: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Mean | Variance | α | β | ||||
| OO: initiation | Beta | 0.0320 | 0.0000 | 84.855 | 2567.5 | ||
| Events | Pop. | α | β | ||||
| OO: prevention | Beta | 3 | 206 | 3 | 203 | ||
| Adverse events | |||||||
| Extrapyramidal syndrome (3-monthly probabilities) | |||||||
| Initiation and prevention phases | Events | Pop. | α | β | |||
| PLAI | Beta | 55 | 1000 | 55 | 945 | ||
| RLAI | Beta | 55 | 1000 | 55 | 945 | ||
| Mean | Variance | α | β | ||||
| ALAI | Beta | 0.0353 | 0.0001 | 8.6805 | 237.14 | ||
| OLAI | Beta | 0.0321 | 0.0001 | 17.849 | 538.03 | ||
| HLAI | Beta | 0.1328 | 0.0007 | 20.496 | 133.82 | ||
| OO | Beta | 0.0321 | 0.0001 | 17.849 | 538.03 | ||
| Clozapine | Beta | 0.0098 | 0.000 | 4.1602 | 420.47 | ||
| Tardive dyskinesia (3-monthly probabilities) | |||||||
| Initiation phase | Events | Pop. | α | β | |||
| PLAI | Beta | 1 | 606 | 1 | 605 | ||
| RLAI | Beta | 1 | 608 | 1 | 607 | ||
| ALAI | Beta | 1 | 606 | 1 | 605 | ||
| OLAI | Beta | 0 | 234 | 0 | 234 | ||
| HLAI | Beta | 5 | 219 | 5 | 214 | ||
| OO | Beta | 0 | 234 | 0 | 234 | ||
| Clozapine | Beta | 0 | 234 | 0 | 234 | ||
| Prevention phase | Min | Max | α | β | |||
| PLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| RLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| ALAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| OLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| HLAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| OO | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| Clozapine | Uniform | 0.0000 | 0.0001 | 0.0000 | 0.0001 | ||
| Diabetes (3-monthly probabilities) | |||||||
| Prevention phase | Min | Max | α | β | |||
| PLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | Hypothesis: ranges of the SmPC used for all treatments with an uniform distribution | |
| RLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| ALAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.100 | ||
| OLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| HLAI | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| OO | Uniform | 0.0010 | 0.0100 | 0.0010 | 0.0100 | ||
| Clozapine | Uniform | 0.0001 | 0.0010 | 0.0001 | 0.0010 | ||
| Weight gained (3-monthly probabilities) | |||||||
| Initiation phase | Events | Pop. | α | β | |||
| PLAI | Beta | 55 | 1000 | 55 | 945 | ||
| RLAI | Beta | 55 | 1000 | 55 | 945 | ||
| ALAI | Beta | 55 | 1000 | 55 | 945 | ||
| Mean | Variance | α | β | ||||
| OLAI | Beta | 0.4680 | 0.0006 | 203.905 | 231.79 | ||
| Events | Pop. | α | β | ||||
| HLAI | Beta | 55 | 1000 | 55 | 945 | ||
| Mean | Variance | α | β | ||||
| OO | Beta | 0.4680 | 0.0006 | 203.905 | 231.79 | ||
| Events | Pop. | α | β | ||||
| Clozapine | Beta | 55 | 1000 | 55 | 945 | ||
| Prevention phase | Min | Max | α | β | |||
| PLAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| RLAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| ALAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| OLAI | Uniform | 0.1000 | 1.0000 | 0.1000 | 1.0000 | ||
| HLAI | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| OO | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| Clozapine | Uniform | 0.0100 | 0.1000 | 0.0100 | 0.1000 | ||
| Costs and resources | |||||||
| Initiation of a new treatment in case of interruption or switch (relapse excluded) | |||||||
| PLAI, RLAI, ALAI, OLAI, HLAI, OO | Mean | Variance | α | β | |||
| Outpatient care | Beta | 0.9000 | 0.0021 | 37.5160 | 4.1684 | ||
| Clozapine | Mean | Variance | α | β | |||
| Outpatient care | Beta | 0.1000 | 0.000 | 645.644 | 3110.80 | ||
| Number of hospitalised weeks required after the stabilisation phase for the initiation of each antipsychotic | Min | Max | α | β | |||
| PLAI | Triangular | −1 | 1 | 0 | 2 | ||
| RLAI | Triangular | −1 | 1 | 1 | 3 | ||
| ALAI | Triangular | −1 | 1 | 1 | 3 | ||
| OLAI | Triangular | −1 | 1 | 1 | 3 | ||
| HLAI | Triangular | −1 | 1 | 0 | 2 | ||
| OO | Triangular | −1 | 1 | 0 | 1 | ||
| Clozapine | Triangular | −1 | 1 | 0 | 1 | ||
| Hospitalisation cost (1 day) | Min (− %) | Max (+ %) | α | β | |||
| Initiation phase | Triangular | −1 | 1 | 218 | 655 | ||
| Relapse | Triangular | −1 | 1 | 218 | 655 | ||
| Mean duration of stabilisation (days) at the hospital | Mean | σ | α | β | |||
| Within 3 months | Trunc.normal | 30 | 33 | 0 | 90 | Hypothesis: | |
| Between 3 and 6 months | Trunc.normal | 135 | 33 | 90 | 180 | ||
| Between 6 and 9 months | Trunc.normal | 225 | 33 | 180 | 270 | ||
| Between 9 and 12 months | Trunc.normal | 315 | 33 | 270 | 360 | ||
| After 12 months | Trunc.normal | 715 | 240 | 360 | 1800 | ||
| Maintenance costs: outpatient care | Min (− %) | Max (+ %) | α | β | |||
| Annual cost | Triangular | −1 | 1 | 531 | 1592 | ||
| Additional psychiatrist visits | Min | Max | α | β | |||
| Initiation phase | Triangular | −1 | 1 | 5 | 7 | ||
| Relapse | Triangular | −1 | 1 | 5 | 7 | ||
| Resources and costs associated with adverse events | |||||||
| Extrapyramidal syndrome | Min | Max | α | β | |||
| GP | Triangular | −1 | 1 | 0 | 2 | ||
| Psychiatrist | Triangular | −1 | 1 | 0 | 2 | ||
| Tardive dyskinesia | Min | Max | a | B | |||
| GP | Triangular | −1 | 1 | 0 | 2 | ||
| Psychiatrist | Triangular | −1 | 1 | 0 | 2 | ||
| Neurologist | Triangular | −1 | 1 | 0 | 2 | ||
| Diabetes | Min (− %) | Max (+ %) | α | β | |||
| Global cost (3 months) | Triangular | −1 | 1 | 659 | 1977 | ||
| Weight gained | Min | Max | α | β | |||
| GP | Triangular | −1 | 1 | 0 | 2 | ||
| Psychiatrist | Triangular | −1 | 1 | 0 | 2 | ||
| Nutritionist | Triangular | −1 | 1 | 0 | 2 | ||
| Endocrinologist | Triangular | −1 | 1 | 0 | 2 | ||
| Blood glucose analysis | Triangular | −1 | 1 | 0 | 2 | ||
| Lipid abnormality investigations | Triangular | −1 | 1 | 0 | 2 | ||
| Utility data | |||||||
| Utility data by health states | Mean | SD | µ | σ | |||
| Stable (without adverse events) | Log-normal | 0.23 | 0.01 | −1.57 | 0.45 | Hypothesis: SD = 10 % × mean | |
| Relapse (without hospitalisation) | Log-normal | 0.19 | 0.01 | −1.78 | 0.49 | Hypothesis: SD = 10 % × mean | |
| Relapse (requiring hospitalisation) | Log-normal | 0.15 | 0.01 | −2.04 | 0.54 | Hypothesis: SD = 10 % × mean | |
| Utility decrement by adverse events | Mean | SD | µ | σ | |||
| Extrapyramidal syndrome | Log-normal | 0.0493 | 0.0025 | −3.3663 | 0.8432 | Hypothesis: SD = 10 % × mean | |
| Tardive dyskinesia | Log-normal | 0.0493 | 0.0025 | −3.3663 | 0.8432 | Hypothesis: SD = 10 % × mean | |
| Diabetes | Log-normal | 0.0375 | 0.0019 | −3.7129 | 0.9268 | Hypothesis: SD = 10 % × mean | |
| Weight gained | Log-normal | 0.0235 | 0.0012 | −4.3278 | 1.0743 | Hypothesis: SD = 10 % × mean | |
ALAI aripiprazole long-acting injectable, AP antipsychotic first-line, HLAI haloperidol long-acting injectable, Max maximum, Min minimum, OLAI olanzapine long-acting injectable, OO oral olanzapine, PLAI paliperidone long-acting injectable, Pop population, PSA probabilistic sensitivity analysis, pts patients, RLAI risperidone long-acting injectable, SD standard deviation, SMR standardised mortality rate, Var variance