Drug-Related Deaths (DRDs)
soon after release: I
Effectiveness on Trial: II
Naloxone (heroin antidote) on
release to reduce overdose deaths
(sheila.bird@mrc-bsu.cam.ac.uk)
HMP
Edinburgh
John Pearce, former governor of
Edinburgh Prison, 1990
Dr. A. Graham
Bird, clinical
immunologist.
1991 WASH
Willing [ethical]
Anonymous
[no deductive disclosure]
Saliva & linked self-Q
[high volunteer rate]
HIV surveillance
Linked to self-Q on
[frank answers]
risks
1. Seaman, Brettle & Gore:
BMJ (1998)
Overdose deaths in 2 weeks after
HIV injectors’ releases from HMP
Edinburgh [1983-94]
8
times higher than for comparable
other fortnights at liberty (p < 0.01)
7 drug-related deaths, 6 from overdose.
2. Male index releases from Scottish
prisons in July to Dec. 1996-99
[Bird & Hutchinson: Addiction 2003]
Eligibility set by [B+H]
Applied by Scottish Prison Service
[SPS]
male
born in 1960+ & aged 15-35 years on release
served 14+ days in prison
1st release in July-December
calendar years: 1996 to 1999
Design assumptions
1. ~ 20,000 eligible releases
2. At least 40% adult & 20% young offender
male index releases = injectors (IDUs)
3. Drugs-Related Deaths (DRDs): mainly IDUs
4. In 1990s: one DRD per 3000 recently
released IDU-days (not 1 per 1000, as Seaman)
5. Relative Risk: 1st fortnight DRDs = 4
Drugs-related deaths in fortnight
after prison: 19 486 male ex-prisoners, aged
15-35 years, released after 14+days’ incarceration
DEATHS
Drugsrelated
Other
causes
1st 2
weeks
subsequent RELATIVE
5 fortnights
34
23
RISK(95% CI)
7 (3 to 16)
(11 in 2nd
fortnight +12 in
next 8 wks)
3
18
0.8 (0.2 to 2.4)
1 in 200 adult injectors dead
within 2 weeks after prison
Judges
aware?
Internationally, 6 major studies
Merrall et
al., 2010
Addiction
Studies
UK (E&W +
DRDs; pys at risk
DRD rate per 1 000 pys
1st
fortnight
2nd
fortnight
next 8
weeks
92; 2 588 20; 2 547
Scotland)
36
8
Australia 187; 7 759 64; 7 416
(NSW &
24
9
Western)
42; 10 795
4
144; 27 334
5
USA
10;
(Washington
State &
New Mexico
prisons)
27; 1 466
18
8; 462
17
5; 1 426
4
3; 462
6
5 409
2
10; 1 845
5
1st fortnight
Relative
Risk
(95% CI)
7.5
(5.7 to 9.9)
4.0
(3.4 to 4.8)
8.4
(5.0 to 14.2)
3.1
(1.3 to
7.1)
Why prisoners + outside implications?
Need +
Research Efficiency
i) concentration of adult
heroin injectors (~ 40%)
ii) at very high risk
iii) well-defined period
soon after release
iv) Third to half injectors
in prison in past year
v) proof-of-principle for
other settings
1 in 8 Scottish DRDs
occurs in 4 weeks after
release!
Prison-based interventions
a) Information
leaflet: how to
avoid overdose
risk after release
b) Naloxone on
release:
heroin antidote
UK’s Advisory Council on the Misuse of
Drugs: already on the case in 2000 . . .
2005
Naloxone was added
to UK’s exempt list
of
Prescription Only
Medicines
for administration by
anyone
in an emergency to
save life
N-ALIVE: randomise 56,000 eligible
prisoners in 50 UK prisons in 5 years
“Good luck, Prof Bird . . . “
Three musketeers (2008): John Strang, Max Parmar &
Sheila Bird
Design assumptions: N-ALIVE
Eligibility: 18-44 years, history of heroin injection,
7+ days’ incarceration.
1. At 80% of overdoses, some-one else is present
2. 75% chance ex-prisoner carries Naloxone in 1st 4 weeks postrelease; 50% chance in next 8 weeks
3. 50% chance that Naloxone is administered by present other.
 Effectiveness in 1st 4 weeks = 30%
Effectiveness in weeks 5 to 12 = 20%
4.
21st C: One overdose death in 1st 4 weeks per 200
ever-IDUs randomised to control group.
5. Contamination . . .
Prison-based, with-consent* RCT
for 56,000 pre-release adult IDUs
Expected
drugs deaths
Controls
[28,000 IDUs]
Naloxone
[28,000 IDUs]
1st 4 weeks
after
release
Next 8
weeks
after release
140
35
98
28
UK-affordable cost of Naloxone
If CE threshold is
£20K ($40K) per
life year gained, &
Naloxone prevents
42 drug deaths in
1st+2nd fortnight per
28,000 IDU releases 
Per injector-inmate,
UK’s NHS can afford
to pay:
{42 * £20K }/28,000
= £30
for pre-release
Naloxone
N-ALIVE designed to fit with UK
prison routines . . .
Induction: drug awareness + N-ALIVE DVD
1-1 consent: each randomized prisoner
has an assigned N-ALIVE pack.
Assigned N-ALIVE packs held in Pharmacy or
Prisoner’s valuables.
Prisoner escort  release from court . . .
Date of release is critical.
*N-ALIVE DVD copy for prisoner’s family
** Re-randomization of recidivists . . . ?
N-ALIVE cleaves to prison routines
Prisoner-induction includes drugs awareness
session: N-ALIVE DVD added.
(educates peers/family re N-ALIVE & Naloxone)
N-ALIVE addiction workers: informed
consent, randomisation, liaison with
pharmacy & Clinical Trials Unit re release
dates.
(half-time is research activity)
N-ALIVE pack handled by pharmacy &
escort staff as a medicine that accompanies
prisoner to court, on transfers.
(issued only on release)
Informed consent by prisoners
• Treatments = Naloxone or control pack at release
[information leaflet & prepaid reply card]
• Confidential database linkage to deaths register
[and NFO A&E admissions in N-ALIVE PILOT RCT]
• Random assignment ~ blinded until release
• Follow-up of recidivists via brief self-Q (unique #)
• Single phone contact in 1st or 2nd fortnight after
release (for HALF only of randomised participants
& in PILOT RCT only . . . Because phone-contact
contaminates N-ALIVE intervention)
N-ALIVE Recidivist self-Q
RCT flag against prisoner number so that
on re-incarceration [applies to 60% of IDUs]
IDU attends prison health to answer
no-names, selotape-seal, self-Q re
overdose(s) witnessed [fatal/non],
overdose(s) experienced [alone/accompanied] &
naloxone [use/disposal/acquisition/where kept] &
heroin use.
Pilot N-ALIVE . . . & kicking via
Medical Research Council’s Clinical Trials
Unit: welcomes international collaborations
Scottish Prison Service
(Karen Norrie, Andrew Fraser; Ruth Parker, Stephen Heller-Murphy;
governors, security & HC)
Health Department/Prison Service in E&W
(Dave Marteau, Martin Lee)
Prisoners in both services