Cost-effectiveness of distributing naloxone to heroin users for lay overdose reversal in Russian cities

Figures & data

Figure 1. Model of naloxone distribution to heroin. EMS = emergency medical services. OD = overdose. Markov model with annual cycles and unlisted background mortality. Outcome of overdose events determined by decision analytic tree on right of figure. *Receive naloxone is adjusted in sensitivity analyses by the social network modifier.

Table 1. Naloxone distribution model parameters.

Parameter	Base–case (Range)	References
Proportions
Join probability that naloxone is used^a	0.153 (0.004–0.668)	Calculated
Proportion of heroin users prescribed naloxone	0.20 (0.05–0.50)	19
Proportion of witnesses with naloxone who use it	0.8 (0.5–0.9)	69
Proportion of overdoses witnessed	0.9 (0.32–0.99)	23,44,70,71
Social network modifier^b	1.0 (0.5–1.5)	Assumption
Proportion call EMS		2,72
First-time overdose	0.2 (0.1–0.3)
Subsequent overdoses	0.15 (0.075–0.225)
Proportion call EMS after naloxone		45,72
First-time overdose	0.2 (0.1–0.3)
Subsequent overdoses	0.15 (0.075–0.225)
Proportion survive overdose
Unwitnessed	0.900 (0.800–0.940)	1,8,23,24
Witnessed	0.930 (0.900–0.960)	1,8,23,24
Reduction in survival for second overdose	0.015	Calibrated
Reduction in survival for subsequent overdoses	0.03	Calibrated
Relative increase in survival with EMS	1.0 (0.9–1.158)	23,24,73
Relative increase in survival with naloxone administration	1.089 (1.02–1.158)	11,12,41,69,74,75
Annual transitions
Heroin use to non-overdose death (in excess of background mortality)	0.0750 (0.0025–0.0125)	8
Heroin use to overdose		2,17,23,38,40,41
First overdose	0.16 (0.09–0.27)
Second overdose	0.22 (0.05–0.30)
Subsequent overdoses	0.34 (0.27–0.60)
Annual relative reduction in risk of first overdose^c	0.93305 (0.9–1.0)	40,76
Heroin use to discontinuation of heroin use	0.05646 (0.01–0.1)	21,22
Discontinuation of heroin use to heroin use	0.35 (0.056–0.4)	32,33,35
Annual relative reduction in risk of relapse^c	0.93305 (0.9–1.0)	36
Overdose to discontinuation of heroin use	0.05646 (0.01–0.1)	21,22
Costs
Naloxone kit (2 doses + distribution costs)	$8 ($4–$25)	Warsaw Pharmaceutical, Annual Reports
EMS and hospital care	$235 ($161–$282)	50,51
Reduced cost after lay naloxone (less transport)	$0 (0–$152)	Assumption
Annual heroin user cost to society^d	$832 ($584–$1080)	57,58,60,61
Utilities
Heroin user	0.65 (0.52–0.78)	52–54,77
Relative increase in utility for heroin user in recovery	1.08 (1.00–1.16)	53,78

EMS, emergency medical services.

^aSummary value based on indented parameters listed below.

^bParameter used in sensitivity analyses to estimate possible effects of social network characteristics on the probability of naloxone being present at an overdose.

^cParameter is exponentiated to the years elapsed and multiplied by its reference parameter to reduce likelihood of the event over time.

^dSet at $0 for baseline analysis and used for secondary analysis.

Table 2. Key epidemiologic parameters for model calibration.

Parameter	Literature estimate (source)	Model forecast
Annual rate of overdose	9–53%2	17.7%
Proportion ever experiencing an overdose	75%22	77.0%
Proportion of overdoses resulting in death	9.3%23	9.3%
Likelihood of survival witnessed	90.7%23	90.9%
Likelihood of survival with emergency medical services	90%22	90.9%
Likelihood of survival with naloxone	96–100%10,11,40,67,71–73	98.0%
Likelihood of distributed naloxone being used to reverse an overdose	9–40%10,14,62	15.3%
Annual rate of overdose death	2.3%22,77	1.7%
Median age of overdose death	35 years23,24	36 years
Median duration of heroin use	Unknown in Russia; 10–11 years in the US25,61	31 years
Annual rate of death from all causes	1.5–2.5%8,78–82	2.7% (0.4--2.0% over initial 40 cycles of model)

Figure 2. Reduction in overdose death rate from naloxone distribution for lay overdose reversal. Deterministic results represented by solid lines and 2.5% and 97.5% limits of the probabilistic analysis are represented by the dashed lines. Absolute rates were adjusted by the number of active heroin users to represent the effect in a community of users.

Table 3. Sensitivity analyses.

	% OD deaths averted (5 y/lifetime)*	Number needed to treat*	Increased QALYs of naloxone	Increased costs of naloxone	ICER of naloxone
Base case (deterministic)	13.4%/7.6%	54	0.152	$11	$71
Base case (probabilistic)	11.3%/7.2%	89	0.137	$13	$94
Sensitivity analyses (deterministic)
Mean age of targeted heroin users
SA1: 28 years	11.4%/7.7%	67	0.126	$10	$76
SA2: 38 years	10.7%/8.0%	71	0.095	$8	$87
Intervention characteristics
SA3: Distribution of naloxone to 5% of heroin users	3.3%/1.8%	55	0.038	$3	$72
SA4: Distribution of naloxone to 50% of heroin users	33.6%/20.0%	52	0.392	$28	$71
SA5: Tripled cost of naloxone distribution	13.4%/7.6%	54	0.152	$30	$199
SA6: Efficacy of naloxone reduced to a 2% relative survival benefit	3.5%/1.9%	216	0.039	$10	$256
SA7: EMS activation after naloxone halved	13.4%/7.6%	54	0.152	$6	$38
Heroin use characteristics
SA8: Risk of first overdose halved	13.4%/7.7%	104	0.097	$11	$109
SA9: Risk of first overdose doubled	13.3%/7.4%	33	0.204	$11	$54
SA10: Rate of discontinuing heroin use halved	13.4%/6.9%	55	0.162	$12	$74
SA11: Rate of discontinuing heroin use after overdose doubled	13.4%/7.9%	55	0.148	$10	$70
SA12: Likelihood overdose is witnessed halved	5.7%/3.1%	96	0.072	$9	$12
SA13: Likelihood naloxone recipient carries naloxone at a witnessed overdose halved	6.7%/3.7%	89	0.075	$9	$122
SA14: Likelihood naloxone recipient carries naloxone at a witnessed overdose increased 50%	20.1%/11.6%	43	0.230	$13	$54
SA15: No improved quality-of-life for abstinence	13.4%/7.6%	54	0.149	$11	$73
SA16: 20% reduction in baseline quality-of-life for heroin user	13.4%/7.6%	54	0.122	$11	$89
Worst-case scenario
SA17 (SA5 + SA6 + SA12 + SA14): Naloxone expensive, marginally efficacious and rarely carried; overdoses rarely witnessed	0.7%/0.4%	677	0.009	$24	$2605
Best-case scenarios
SA18: Upper limit joint probability naloxone used	73.5%/48.9%	36	0.892	$44	$49
SA19: Lower limit OD risk in setting of naloxone	48.8%/40.4%	11	0.490	−$36	Dominant
Structural sensitivity analysis
SA20: SA4 + naloxone cost increases 50% per absolute 10% increase in coverage	33.6%/20.0%	52	0.392	$65	$166

OD, overdose; QALYs, quality-adjusted life years; ICER, incremental cost-effectiveness ratio; SA, sensitivity analysis; EMS, emergency medical services.

*Number of kits needed to prevent one death.

Figure 3. Cost-effectiveness acceptability curve of naloxone distribution. y-axis represents the probability that naloxone distribution is preferred at willingness to pay defined on x-axis.

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