Take-home naloxone to prevent fatalities from opiate-overdose: Protocol for Scotland’s public health policy evaluation, and a new measure to assess impact

Figures & data

Box 1. Scotland’s public health policy on THN.

Policy break-through: Neither of Scotland’s two previous THN pilot studies - based on Glasgow’s Drug Problem Centre during March 2007 to March 2008 (Shaw & Egan, 2008), and in Lanark (McAuley et al., 2010) – had included prescribing prior to prison-release. From August 2009, harm-reduction nurse-specialist Lisa Ross had overlapped community-based with prison-release prescribing of naloxone in Inverness, the constituency of Fergus Ewing, Scotland’s Minister for Safety and Communities (Gould, 2011).

Impressed by Inverness’s achievement in issuing 125 THN-kits in six months (and 19 “reported uses” including one fatality and one self-administration) when Highland region, as a whole, had an estimated 16 ORDs annually, Ewing (2010) decided to make THN available throughout Scotland to those at risk of opiate-overdose.

The N-ALIVE team was alerted by the Scottish Prison Service (SPS) to a likely change in Scotland’s policy on THN. We wrote to Scottish ministers in March 2010 to urge that prisons be in the vanguard of any national THN policy; and to underline that, just as we could not have expected Scottish prisons to implement the N-ALIVE Trial’s randomised intervention without being resourced to do so, resourcing (to half the level envisaged for the pilot N-ALIVE Trial) would still be required for Scottish prisons properly to inform prisoners on how to administer naloxone and for its prescription to those with a history of heroin-injection, who are about one third of Scottish inmates (Taylor et al., 2013).

From 2011, Scotland’s prisons were resourced to prescribe naloxone-on-release for 5 000 eligible releases per annum. In addition, 6 000 prescriptions of THN by drug treatment agencies and doctors in the outside community were envisaged – in principle, sufficient to reach more than a third of all Scotland’s current injectors (King et al., 2013) and at least 20 times more prescriptions than Scotland’s annual number of ORDs which would have guaranteed a very high level of potential distribution.

Table 1. Drugs-related deaths in Scotland, 2000–2009.

					Males: by age-group at death
Period	Count	Both genders	Females	Males	15–24	25–34	35–44	45+ years
All drugs-related deaths (DRDs)
2006–09	Totals	1994	394	1600	261	575	513	251
2000–05		2000	368	1632	381	659	433	159
2006–09	Per annum	499	99	400	65	144	128	63
2000–05		333	61	272	64	110	72	27
Opiate–related drug deaths (ORDs). Here defined as the presence of heroin/morphine and/or methadone
2006–09	Totals	1571	280	1291	211	490	418	172
2000–05		1554	240	1314	304	556	354	100
2006–09	Per annum	393	70	323	53	123	105	43
2000–05		259	40	219	51	93	59	17

Table 2. Power to differentiate THN-related-reduction in the percentage of opiate-related deaths (ORDs) with prison-release as 4-week antecedent when the pre-THN percentage was assumed to be 16.7% (or 200/1200) but was actually 10%.

	After-THN percentage of ORDs in 2011–2013 with prison-release as 4-week antecedent
Pre-THN percentage: 16.7% of ORDs with prison-release as 4-week antecedent	20% Reduction from Pre-THN to 13.3%	25% Reduction from Pre-THN to 12.5%	30% Reduction from Pre-THN to 11.7%
Such as 200/1200 in 3-years: 2007–09	Power based on  900 ORDs in 2011–13: 59%	Power based on  900 ORDs in 2011–13: 78%	Power based on  900 ORDs in 2011–13: 91%
	Power based on 1200 ORDs in 2011–13: 65%	Power based on 1200 ORDs in 2011–13: 85%	Power based on 1200 ORDs in 2011–13: 94%
	After-THN percentage of ORDS in 2011–2013 or in 2011–2015 with prison-release as 4-week antecedent
Pre-THN percentage: 10% of ORDs with  prison-release as 4-week antecedent	20% Reduction from Pre-THN to 8%	25% Reduction from Pre-THN to 7.5%	30% Reduction from Pre-THN to 7%
Such as 120/1200 in 3-years: 2007–09	Power based on 1200 ORDs in 2011–13: 40%	Power based on 1200 ORDs in 2011–13: 58%	Power based on 1200 ORDs in 2011–13: 75%
	Power based on 2000 ORDs in 2011–15: 47%	Power based on 2000 ORDs in 2011–15: 66%	Power based on 2000 ORDs in 2011–15: 82%
Such as 200/2000 in 5-years: 2006–10	Power based on 2000 ORDs in 2011–15: 67%	Power based on 2000 ORDs in 2011–15: 80%	Power based on 2000 ORDs in 2011–15: 93%

Effectiveness requires: some-one else being present at opiate overdose (80%), naloxone being also present (75% in the first 4 weeks, reduced thereafter), and that the person present has the presence of mind to locate and administer naloxone intramuscularly (50%). Plausible THN-impact on opiate-overdose fatalities is thus 30% initially (i.e. 80% * 75% * 50%).

Table A1. Summary of key event-rates: THN studies in UK and USA.

Study	Trainees’ take-home naloxone rate	Trainees’ follow-up rate at 3 or 6 months (m)	Witnessed overdose rate per 100 person-months (pms)	Experienced overdose rate per 100 person-months (pms)	Reported outcome of witnessed overdose-events
Strang et al., 2008a	160/176	186/239	3.4 {16 in 186*2.5 m = 465 pms}	0.43 {2 in 186*2.5 m = 465 pms}	1/16 died. {Two uses by staff}
Gaston et al., 2009		[49/70 but 46/70 were analysed who had 0, 3, 6 m follow-ups]	5.8 [16 in 46* 6 m = 276 pms]	0.36 [1 in 46 * 6 m = 276 pms]	1/16 died or 1/7. {already dead; but outcome not known for nine. No trainee used Naloxone at witnessed overdose.}
National Treatment Agency, 2011	417 Naloxone kits supplied to trained carers in 16 pilots costing £98,280 during July 2009 to Feb. 2010 {per kit supplied: £236}.				0/20 died. 18 Naloxone-uses before August 2011, one to prescribee, all survived as did two non-N resuscitations.
HMP Eastwood Park	447 trainees in 1st 6 m, of whom 96 released with Naloxone.				3 “reported” uses of Naloxone.
McAuley et al., 2010	19/23 clients were issued with Naloxone (18 “buddies” also trained)	[17/19 at 6 m]	2.9 [3 in 17*6 m = 102 pms]		1/3 died; two “saves” via naloxone administrations
Inverness, via Lisa Ross	(120 + 5)/(120 + 40) = 125/160 (Community + prison)				1/19 died in 19 reported uses of naloxone: Aug. 2009 to Jan. 2010 (1st 6 m), one self-use.
Glasgow Naloxone Programme, March 2007 to March 2008 as reported by Shaw and Egan, 2008.	207/221	40/176 user-trainees re-interviewed at 3 months (at least …) and 15/31 family-members: p26	1.6 {2 Naloxone-used overdoses witnessed in ≥120 pms: 40*>3 m}:p32	0.83 {1 in at least 40* 3 ms ≥ 120 pms}	1/11 overdose victims died. {naloxone used for 10, two by staff; re-supply obtained by 2/8 users who had administered naloxone}; 1/11 recent prison-release: p37–39.
Welsh evaluation: cases, Bennett and Holloway, 2011	Over 600 trained during 1-year pilot	644 kits given out by Feb 2011; 48 used.			1/22 died when N-used, or 1/28 replenishments (6 = status NK)
Welsh evaluation: controls, see Bennett & Holloway,2011	34 users in control areas, of whom 4 reported no events		11.8 [24 overdose events in 34* 6 m = 204 pms]	4.9 [10 overdose events in 34* 6 m = 204 pms]	1/34 died, see Pages 117–120. Or 1/24 witnessed events
UK summary			5.2 [61 in at least 1167 ms]	1.3 [14 in at least 1065 ms]	7/137 = 5.1% died {1 in 20} or 4/59 = 6.8% died {1 in 15}
Enteen et al., 2010	Between September 2003 and December 2009, 1,942 unduplicated users trained, all prescribed naloxone		399 overdose-events were reported-back by 215 trainees (11%) who had sought refills. Overdoses-events were reason for 399/1020 (40%) refill requests. >0.6 {399+ overdose events in approx. 1,942 * 3 yrs * 12 = 69,912 pms}.		6/363 naloxone-treated overdose victims died; outcome not known for 36 naloxone-administered overdose victims.
Wagner et al., 2010	93 IDU-trainees; 69 agreed to 3 m follow-up, but 3 not trained.	47/66 IDU-trainees followed-up at 3 months.	24.8 {35 overdoses responded to by 22/47 responder-trainees in 3*47 = 141 pms}. Also note 74.7 {148 overdoses witnessed by 32/66 trainees in 3 m prior to training = 198 pms}	12.1{24 overdoses reported by 10/66 trainees in 3 m prior to training, i.e. in 3 * 66 = 198 pms}	4/30 died {but outcome unknown for 5 overdoses; naloxone administered at 28/35 witnessed overdoses}.
Tobin et al., 2009		[85/250 participants assessed at 6 m]	>9.4 [48/85 witnessed at least 1 overdose in 85 * 6 m = 510 pms]	Not stated	0/22 naloxone-used overdose victims died.
Seal et al., 2005		24/24 IDU-trainees had monthly re-interviews for 6 ms	13.9 [20 witnessed in 24 * 6 m = 144 pms]		0/20 died. Naloxone was administered at 15/20.
Galea et al., 2006		22/25 trainees followed-up at 3 ms	39.4 {11/22 witness 26 overdoses in 22 * 3 m = 66 pms}		1/17 died in specified/most recent overdoses with known outcome, naloxone was used for 10/17.
USA summary			15.0 [129 in 861 pms]	No data prospectively	5/94 = 5.3% died {1 in 19}

Table A2. Opiate-related drug deaths (here defined by mention of heroin/morphine or methadone or buprenorphine) by year of death: for Scotland, Wales and England.

Year of Death	Scotland: population of 5.3 millions*	Wales: population of 3.1 millions*	England: population of 53.5 millions*	Great Britain
2006	328	62	978	1368
2007	370	76	1126	1572
2008	445	92	1041	1578
2009	432	109	1115	1656
4-year MEAN	394	85	1065	1544
Take-Home Naloxone (THN) was introduced in half of Wales in 2010.
THN became public policy in Scotland from January 2011 & in Wales from mid 2011.
Crop failure in Afghanistan contributed to UK’s decrease in opiate-related deaths in 2010.
2010	395	69 THN @ 50%	882	1346
2011	430	74	917	1421
2012	399	>65	>809	>1273
2013	383	** Due to late registration of coroner-referred deaths in England and Wales, ORDs in 2012 in England and Wales (and hence in Great Britain) are, as yet, under-counts by about 5%.

*See http://www.ons.gov.uk/ons/rel/pop-estimate/population-estimates-for-uk–england-and-wales–scotland-and-northern-ireland/mid-2011-and-mid-2012/stb—mid-2011—mid-2012-uk-population-estimates.html

Link to latest data for 2011 and 2012, which were provided in early September 2014 at our request: www.ons.gov.uk/ons/about-ons/business-transparency/freedom-of-information/what-can-i-request/published-ad-hoc-data/health/september-2014/index.html

**See https://www.rss.org.uk/site/cms/newsarticle.asp?chapter=15&nid=79

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