Cost-effectiveness model for a hypothetical monotherapy vs standard of care in adult patients with treatment-resistant depression

Figures & data

Figure 1 Decision tree component of the model.

Abbreviation: TRD, treatment-resistant depression.

Figure 2 Markov component of the model.

Note: For all health states, patients can also remain in their current health state (circular arrows for remaining in state are not illustrated).

Table 1 Summary of treatment-specific model inputs

Input type	Base	Low	High	DSA info: low and high source	PSA info: SE used; assumed distribution	Comment/ Source
Acute treatment efficacy simulation
Percentage change in total MADRS score from baseline to end of acute treatment
Hypothetical monotherapy
Mean	–46.8%	–37.4%	–56.1%	Percentage improvement over SSRI + AAP: 25% (0%–50%)	Simulated in base case; normal	Calculated per percentage improvement over SSRI + AAPa
SD	32.2%	NA	NA	Not varied	Not varied
SSRI + AAP
Mean	–37.4%	–29.9%	–44.9%	±20%	Simulated in base case; normal	16,18–20
SD	32.2%	NA	NA	Not varied	Not varied
Depression outcomes by threshold total MADRS scores
Partial remission (≤ MADRS score)	16	13	19	Expert opinion	Not varied	Expert opinion
Full remission (≤ MADRS score)	10	10	12	Clinical definition	Not varied	Clinical definition
Baseline total MADRS score
Modeb (Min – Max)	26 (24–29)	24 (22–27)	28 (26–31)	Expert opinion	Simulated in base case; triangular	Expert opinion
Acute treatment discontinuation
Hypothetical monotherapy	20.90%	18.81%	22.93%	RR over SSRI + AAP: 0.9 (0.8–1.0)	Calculated;c normal	Calculated per RR over SSRI + AAPd
SSRI + AAP	22.93%	17.98%	28.09%	OR 95% CI	Calculated;c beta	16,18–21
Treatment-related costs (2017 GBP)
Hypothetical monotherapy
Drug (per month)	£52.41	£34.94	£69.88	Percentage increase over SSRI + AAP: 50% (0%–100%)	Calculated;c Gamma	Calculated per percentage increase over SSRI + AAP
Treatment monitoring
During acute treatment (over 2 months)	Assumed same as SSRI + AAP
During maintenance treatment (over 10 months)	Assumed same as SSRI + AAP
SSRI + AAP
Drug (per month)	£34.94	£2.79	£82.43	Market shares variede	Calculated;c Gamma	16,25
Treatment monitoring
During acute treatment (over 2 months)	£62.58	£50.06	£75.09	±20%	Calculated;c Gamma	16,33–35
During maintenance treatment (over 10 months)	£28.47	£22.78	£34.16	±20%	Calculated;c Gamma	16,33–35

Notes:

a For the hypothetical monotherapy with efficacy advantage, the percentage change in total MADRS score from baseline to end of acute treatment was calculated per acute treatment efficacy percentage improvement over SSRI + AAP, which was set to 25% in the base case and varied 0% to 50% in DSA. For the hypothetical monotherapy without efficacy advantage, the percentage change in total MADRS score from baseline to end of acute treatment was assumed to be same as SSRI + AAP. The SD of the resulting percentage change in total MADRS score was assumed to be the same as SSRI + AAP.

b Baseline MADRS scores were simulated using a triangular distribution with the given mode, lower limit (min), and upper limit (max).

c SE calculated as ((base – low)+(high – base))/(2*1.96).

d For the hypothetical monotherapy with tolerability advantage, the acute treatment discontinuation rate was calculated per RR of discontinuation over SSRI + AAP, which was set to 0.9 in the base case and varied 0.8–1.0 in DSA. For the hypothetical monotherapy without tolerability advantage, the RR of discontinuation was assumed to be 1.0 (same rate of discontinuation as SSRI + AAP).

e The prices of individual SSRIs and AAPs were assumed fixed, while their assumed market shares were varied from higher to lower shares for cheaper (vs more expensive) drugs.

Abbreviations: AAP, atypical antipsychotics; DSA, deterministic sensitivity analysis; GBP, British pound; MADRS, Montgomery-Åsberg Depression Rating Scale; NA, not applicable; PSA, probabilistic sensitivity analysis; SE, standard error; SSRI, selective serotonin reuptake inhibitors.

Table 2 Summary of treatment-unspecific model inputs

Input type	Base	Low	High	DSA info: low and high source	PSA info: SE used; Assumed distribution	Comment/Source
Acute treatment: clinical improvement following discontinuation
Partial remission	2.67%	2.14%	3.21%	±20%	Calculated;a Beta	16
Full remission	0.85%	0.68%	1.02%	±20%	Calculated;a Beta	16
Maintenance treatment and follow-up: transition probabilities
Maintenance treatment discontinuation	21.92%	18.39%	25.51%	OR 95% CI	Calculated;a Beta	16,18–21
Partial remission to full remission
Continued	3.80%	3.04%	4.56%	±20%	Calculated;a Beta	Assumed to be the same^Citation22
Discontinued	3.80%	3.04%	4.56%	±20%	Calculated;a Beta
Full remission to relapse
Continued	8.90%	7.12%	10.68%	±20%	Calculated;a Beta	Assumed to be the same^Citation4
Discontinued	8.90%	7.12%	10.68%	±20%	Calculated;a Beta
Partial remission to relapse
Continued	21.20%	16.96%	25.44%	±20%	Calculated;a Beta	Assumed to be the same^Citation4
Discontinued	21.20%	16.96%	25.44%	±20%	Calculated;a Beta
In episode to partial remission (discontinued)	2.67%	2.14%	3.21%	±20%	Calculated;a Beta	16
In episode to full remission (discontinued)	0.85%	0.68%	1.02%	±20%	Calculated;a Beta	16
Patient care costs (2017 GBP)
During acute treatment (over 2 months)	£2,367	£1,894	£2,841	±20%	Calculated;a Gamma	16,34,36
During maintenance treatment (over 10 months)
Full remission	£980	£784	£1,176	±20%	Calculated;a Gamma	16,34,36
Full remission discontinued	£980	£784	£1,176	±20%	Calculated;a Gamma	16,34,36
Partial remission	£980	£784	£1,176	±20%	Calculated;a Gamma	16,34,36
Partial remission discontinued	£980	£784	£1,176	±20%	Calculated;a Gamma	16,34,36
In episode discontinued	£2,645	£2,116	£3,175	±20%	Calculated;a Gamma	16,34,36
Relapse discontinued	£2,645	£2,116	£3,175	±20%	Calculated;a Gamma	16,34,36
Health utilitiesb
Full remission	0.860	0.688	1.000	±20%	Calculated;a Beta	26
Partial remission	0.740	0.592	0.888	±20%
In episode/relapse	0.440	0.352	0.528	±20%

Notes:

a SE calculated as ((base – low)+(high – base))/(2*1.96).

b Health utilities high values are bounded in the [0,1] interval using the minimum function in Excel.

Abbreviations: DSA, deterministic sensitivity analysis; GBP, British pound; PSA, probabilistic sensitivity analysis; SE, standard error.

Table 3 Simulated acute treatment efficacy

Depression outcome probability (%)	Hypothetical monotherapy (%)	SSRI + AAP (%)	Difference (Hypothetical monotherapy – SSRI + AAP) (%)
Partial (without full) remission (10< MADRS ≤ 16)	27.5	25.6	2.0a
Full remission (MADRS ≤10)	31.8	22.3	9.5
Partial and full remissions total (MADRS ≤16)	59.3	47.8	11.5

Note:

a The difference is not 1.9% because of rounding issue.

Abbreviations: AAP, atypical antipsychotics; MADRS, Montgomery-Åsberg Depression Rating Scale; SSRI, selective serotonin reuptake inhibitors.

Table 4 Base case model results

Model result	Hypothetical monotherapy	SSRI + AAP	Difference (Hypothetical monotherapy – SSRI + AAP)
Costs (2017 GBP)
Acute treatment cost	£2,524	£2,492	£32
Maintenance treatment and follow-up	£2,440	£2,535	–£95
Total costs	£4,963	£5,027	–£63a
Effectiveness
QALYs	0.580	0.552	0.028
Cost per effectiveness
Costs per QALY	£8,559	£9,114	–£555
ICUR (cost per QALY)			Hypothetical monotherapy dominant
INMB @ WTP=£30,000 per QALY			£914
Optimal price for the hypothetical monotherapy @ WTP=£30,000 per QALY			£359

Note:

a The difference is not –£64 because of rounding issue.

Abbreviations: AAP, atypical antipsychotics; GBP, British pound; ICUR, incremental cost-utility ratio; INMB, incremental net monetary benefit; QALY, quality-adjusted life year; SSRI, selective serotonin reuptake inhibitors; WTP, willingness-to-pay.

Figure 3 Deterministic sensitivity analysis on INMB at WTP of £30,000 per QALY for the hypothetical monotherapy with both efficacy and tolerability advantages.

Abbreviations: AAP, atypical antipsychotics; INMB, incremental net monetary benefit; MADRS, Montgomery-Åsberg Depression Rating Scale; QALY, quality-adjusted life year; SSRI, selective serotonin reuptake inhibitors; WTP, willingness-to-pay.

Figure 4 Cost-effectiveness plane for the hypothetical monotherapy with both efficacy and tolerability advantages.

Abbreviation: QALY, quality-adjusted life year.

Figure 5 Cost-effectiveness acceptability curves for the hypothetical monotherapy with both efficacy and tolerability advantages.

Abbreviations: AAP, atypical antipsychotics; QALY, quality-adjusted life year; SSRI, selective serotonin reuptake inhibitors; WTP, willingness-to-pay.

Figure 6 Combinations of acute treatment discontinuation and efficacy percentage advantages over SSRI + AAP that result in dominance of the hypothetical monotherapy (lower costs and higher QALYs).

Note: Results were based on a 50% price premium of the hypothetical monotherapy over SSRI + AAP.
Abbreviations: AAP, atypical antipsychotics; QALYs, quality-adjusted life years; SSRI, selective serotonin reuptake inhibitors.

Table S1 Commonly prescribed drugs and the weighted monthly costs used in the model

Drug (total daily dose)	No. in pack	Cost/pack	Cost/day	Cost/montha	Weighted drug use (%)	Weighted cost/ month used in the model
SSRIs
Citalopram (40 mg)	28	£1.21	£0.04	£1.31	35	£0.46
Sertraline (150 mg)b	28	£3.58	£0.13	£3.89	30	£1.17
Fluoxetine (40 mg)c	30	£1.11	£0.07	£2.25	25	£0.56
Escitalopram (20 mg)	28	£1.66	£0.06	£1.80	10	£0.18
Total cost						£2.37
AAPs
Quetiapine (300 mg)	60	£4.41	£0.07	£2.24	30	£0.67
Olanzapine (7.5 mg)	56	£2.58	£0.05	£1.40	20	£0.28
Aripiprazole (7.5 mg)d	28	£96.04	£5.15	£156.49	20	£31.30
Risperidone (3 mg)	60	£2.10	£0.04	£1.06	30	£0.32
Total cost						£32.57

Notes: Price per month of SSRI + AAP in the model: £2.37+£32.57=£34.94.

a Calculations based on 1 month =365/12 =30.417 days.

b Assume taken as one 100 mg and one 50 mg tablet per day, costing £1.75 and £1.83 per 28-tab pack, respectively.

c Assume taken as two 20 mg capsules per day.

d Assume taken as one and a half 5 mg tablets per day.

Abbreviations: AAP, atypical antipsychotics; SSRI, selective serotonin reuptake inhibitors.

Table S2 ICUR of the hypothetical monotherapy for different combinations of acute treatment discontinuation and efficacy percentage advantages over SSRI + AAP

Acute treatment discontinuation percentage advantage over SSRI + AAP (%)	Acute treatment efficacy percentage advantage over SSRI + AAP (%)
	14	12	10	8	6	4	2	0
20	Dominant	Dominant	Dominant	£164	£974	£2,135	£4,128	£7,786
15	Dominant	Dominant	Dominant	£529	£1,508	£2,972	£5,672	£11,339
10	Dominant	Dominant	£57	£976	£2,187	£4,102	£7,990	£18,105
5	Dominant	Dominant	£420	£1,537	£3,079	£5,703	£11,850	£35,979
0	Dominant	£72	£866	£2,255	£4,296	£8,140	£19,523	£215,211

Note: Results were based on a 50% price premium of the hypothetical monotherapy over SSRI + AAP.

Abbreviations: AAP, atypical antipsychotics; ICUR, incremental cost-utility ratio; SSRI, selective serotonin reuptake inhibitors.

Table S3 Optimal monthly prices of the hypothetical monotherapy for different combinations of acute treatment discontinuation and efficacy percentage advantages over SSRI + AAP at WTP per QALY of £30,000

Acute treatment discontinuation percentage advantage over SSRI + AAP (%)	Acute treatment efficacy percentage advantage over SSRI + AAP (%)
	25	20	15	10	5	0
20	£381	£323	£262	£201	£141	£83
15	£370	£311	£251	£190	£130	£71
10	£359	£300	£239	£178	£118	£60
5	£347	£288	£227	£166	£106	£48
0	£335	£275	£215	£154	£93	£35

Abbreviations: AAP, atypical antipsychotics; QALY, quality-adjusted life years; SSRI, selective serotonin reuptake inhibitors; WTP, willingness-to-pay.

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