Drug-Related Deaths (DRDs) soon after release: I Effectiveness on Trial: II Naloxone (heroin antidote) on release to reduce overdose deaths ([email protected])

Drug-Related Deaths (DRDs) soon after release: I

Effectiveness on Trial: II Naloxone (heroin antidote) on

release to reduce overdose deaths

([email protected])

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 risks [frank answers]

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.

1. Seaman, Brettle & Gore: BMJ (1998)

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]

maleborn in 1960+ & aged 15-35 years on release

served 14+ days in prison1st release in July-Decembercalendar 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 1st 2 weeks

subsequent 5 fortnights

RELATIVERISK(95% CI)

Drugs-related

34 23(11 in 2nd fortnight +12 in next 8 wks)

7 (3 to 16)

Other causes

3 18 0.8 (0.2 to 2.4)

1 in 200 adult injectors dead within 2 weeks after prison

Judgesaware?

Internationally, 6 major studies

Merrall et al., 2010 Addiction Studies

DRDs; pys at risk

DRD rate per 1 000 pys

1st fortnight Relative

Risk(95% CI)1st

fortnight2nd

fortnightnext 8 weeks

UK (E&W +

Scotland)

92; 2 588

36

20; 2 547

8

42; 10 795

4

7.5(5.7 to 9.9)

Australia(NSW & Western)

187; 7 759

24

64; 7 416

9

144; 27 334

5

4.0(3.4 to 4.8)

USA (Washington State & New Mexico prisons)

27; 1 466

18

8; 462

17

5; 1 426

4

3; 462

6

10; 5 409

2

10; 1 845

5

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 riskiii) well-defined period

soon after releaseiv) Third to half injectors

in prison in past yearv) 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

Medicinesfor 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 post-release; 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

1st 4 weeks after release

Next 8 weeks

after release

Controls

[28,000 IDUs]140 35

Naloxone

[28,000 IDUs] 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