Introduction
Methods and materials
Systematic review
Identified economic evaluations and model designs
References | Country setting | Chronic pain type | Therapies considered | Time horizon | Cycle length | Dose titration included | Treatment lines | Model type | Costs | Assumption of efficacy (analgesic effect) |
---|---|---|---|---|---|---|---|---|---|---|
Coluzzi and Ruggeri [18] | Italy | Non-malignant | Oxycodone/naloxone; tapentadol; oxycodone | 1 year | 15 weeks | No | 1 line | Markov | Direct | Equivalent efficacy |
Dunlop et al. [17] | UK | Non-malignant | Oxycodone/naloxone; oxycodone | 43 weeks | 1 week | No | 1 line | Markov | Direct | Equivalent efficacy |
Frei et al. [7] | Denmark | Non-malignant | Fentanyl; morphine | 1 year | 30 days | No | 2 lines | Markov | Direct | Equivalent efficacy |
Hass et al. [15] | Germany | Non-specific | Buprenorphine; fentanyl; oxycodone; morphine | 6 years | 1 year | No | 1 line | Markov | Direct | Equivalent efficacy |
UK | Non-malignant | Tapentadol; oxycodone | 1 year | 4 weeks | Yes | 3 lines | Markov | Direct | Equivalent efficacy | |
USA | Non-specific | Fentanyl; morphine; oxycodone | 1 year | NA | Yes | 2 lines | Decision tree | Direct | Equivalent efficacy | |
NICE [10] | UK | Malignant | Morphine; oxycodone; fentanyl; buprenorphine | 1 year | 1 week | No | 2 lines | Markov | Direct | Equivalent efficacy |
Neil et al. [5] | USA | Non-malignant | Tapentadol; oxycodone | 1 year | NA | Yes | 2 lines | Discrete event simulation | Direct | Equivalent efficacy |
Key design themes
Reference model
Model transparency and coding
Model structure
Time horizon
Titration and stabilisation
Withdrawal
Treatment lines/subsequent treatment
Model inputs
Treatment comparison/analysis perspective
Adverse event and withdrawal rates
Parameter description | Estimate | Source |
---|---|---|
Cycle probability tolerable AE, morphine | 0.436 | Calculated from [12]a
|
Cycle probability withdraw because of AE, morphine | 0.056 | Calculated from [12]b
|
Cycle probability withdraw because of other reason, morphine | 0.013 | Calculated from [12]b
|
Cycle probability tolerable AE, oxycodone | 0.464 | Calculated from [13]c
|
Cycle probability withdraw because of AE, oxycodone | 0.033 | Calculated from [13]d
|
Cycle probability withdraw because of other reason, oxycodone | 0.002 | Calculated from [13]d
|
Cycle probability tolerable AE, novel therapy | 0.324 | Assumption: proportional reduction of 0.3 relative to oxycodone |
Cycle probability withdraw because of AE, novel therapy | 0.023 | Assumption: proportional reduction of 0.3 relative to oxycodone |
Cycle probability withdraw because of other reason, novel therapy | 0.002 | Assumption: proportional reduction of 0.3 relative to oxycodone |
Cycle probability discontinue after failed 1st-line treatment | 0.050 | Assumption |
Resource use and cost estimates
Parameter description | Estimate | Source |
---|---|---|
Treatment cost per cycle, morphine | £2.63 | |
Co-medication cost per cycle, morphine | £2.26 | |
Treatment cost per cycle, oxycodone | £9.20 | |
Co-medication cost per cycle, oxycodone | £0.04 | |
Treatment cost per cycle, novel therapy | £55.21 | Assumption: 6 times oxycodone treatment cost |
Co-medication cost per cycle, novel therapy | £0.03 | Assumption: proportional reduction of 0.3 relative to oxycodone |
Adverse event cost per cycle | £6.99 | |
Cost associated with withdrawal | £106.91 | |
Treatment discontinuation cost per cycle | £18.50 | Assumption: Half discontinued patients visit GP weekly; Curtis et al. [21] |
Utility estimates
Parameter description | Estimate | Source |
---|---|---|
Utility, on treatment, no AEs | 0.695 | Ikenberg et al. [13] |
Utility, on treatment, tolerable AEs | 0.583 | Ikenberg et al. [13] |
Utility, withdrawn from treatment due to AEs | 0.503 | Ikenberg et al. [13] |
Utility, withdrawn from treatment due to other reasons | 0.405 | Ikenberg et al. [13] |
Utility multiplier, failed 1st-line treatment | 0.900 | Assumption |
Utility multiplier, failed 2nd-line treatment | 0.800 | Assumption |
Scenario and sensitivity analyses
Scenario analyses
Reference | Description |
---|---|
Scenario 1: “Base case” | The model time horizon is 1 year and two lines of treatment are considered |
Morphine is compared to the novel therapy as a first-line treatment | |
The cost and HRQL implications of drug titration and stabilisation are not modelled | |
After withdrawal from 1st-line therapy, patients on either model arm either discontinue treatment or switch to oxycodone treatment | |
After withdrawal from 2nd-line therapy, all patients are assumed to discontinue treatment | |
Scenario 2: “3rd-line treatment with morphine” | Explores the consequences of different assumptions about subsequent treatment lines for model results, as scenario 1 with the exception that: Following withdrawal from 2nd-line treatment, 90 % of patients move to a subsequent 3rd-line treatment. The cycle costs attributed to the “Subsequent treatment” health state are set to morphine treatment; the utility tariff attributed to this health state is the average of the four utility estimates in Table 4, multiplied by 0.8 to represent an assumed reduction in patient HRQL (having experienced two failed treatment lines) |
Scenario 3: “Morphine as 2nd-line treatment on novel therapy arm” | Explores the consequences of different assumptions about treatment pathways following 1st-line treatment across both model arms, as scenario 1 with the exception that: Novel Therapy patients are assumed to switch to morphine as opposed to oxycodone as a 2nd-line therapy |
Scenario 4: “Titration and stabilisation” | Explores the consequences of different assumptions about titration and stabilisation, as Scenario 1 with the exception that: For the first 4 weeks of 1st-line treatment, drug doses and AE probabilities are adjusted in line with clinical data from previous studies (Ikenberg et al. [13] reported doses of around two-thirds of the maintenance dose and withdrawal rates over twice as high as those observed during maintenance therapy, during the first 4 weeks of treatment in their study). Withdrawal rates are doubled and treatment costs multiplied by 0.65 in the first four model cycles |
Scenario 5: “Improvement in analgesic effect” | Explores the consequences of different assumptions about achieving pain control superiority, as scenario 1 with the exception that: Utility values for patients receiving 1st-line novel therapy are increased by 5 % to reflect improved levels of pain control when on treatment and responding. Future generations of pharmacological therapies for chronic pain may offer analgesic improvement which directly affects patient HRQL outcomes |
Scenario 6: “2-year time horizon” | Explores the consequences of different assumptions about the time horizon, as Scenario 1 with the exception that: The time horizon is set to 2 years rather than 1 year. Extrapolation of data over time has been routinely practiced in the majority of models but involves implicit assumptions. The consequences of choice of time horizon has not always been robustly tested in previous models, and results from scenario 6 will explore the consequence of simple extrapolation of assumptions over time for model outcomes |
Sensitivity analyses
Results
Scenario analyses
Outcome | Morphine | Novel therapy | Incremental, novel therapy versus morphine |
---|---|---|---|
Scenario 1: “Base case” | |||
Costs | 845.3130 | 2126.7532 | £1281.44 |
QALYs | 0.505 | 0.572 | 0.067 |
ICER | £19,126.66 | ||
Scenario 2: “3rd-line treatment considered” | |||
Costs | £652.18 | £2022.08 | £1369.90 |
QALYs | 0.536 | 0.589 | 0.053 |
ICER | £25,899.20 | ||
Scenario 3: “Morphine as 2nd-line treatment on novel therapy arm” | |||
Costs | £845.31 | £2125.49 | £1280.18 |
QALYs | 0.505 | 0.554 | 0.048 |
ICER | £26,550.64 | ||
Scenario 4: “Titration and stabilisation” | |||
Costs | £874.29 | £1867.79 | £993.50 |
QALYs | 0.490 | 0.561 | 0.070 |
ICER | £14,170.81 | ||
Scenario 5: “Improvement in analgesic effect” | |||
Costs | £845.31 | £2126.75 | £1281.44 |
QALYs | 0.505 | 0.591 | 0.085 |
ICER | £15,000.22 | ||
Scenario 6: “2-year time horizon” | |||
Costs | £1787.01 | £3390.83 | £1603.82 |
QALYs | 0.864 | 0.996 | 0.132 |
ICER | £12,182.50 | ||
Scenario 7: “No assumed HRQL decrement over successive treatment lines” | |||
Costs | £845.31 | £2126.75 | £1281.44 |
QALYs | 0.557 | 0.603 | 0.046 |
ICER | £27,970.41 |