1. 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)

2. HMP Edinburgh

3. John Pearce, former governor of Edinburgh Prison, 1990 Dr. A. Graham Bird, clinical immunologist.

4. 1991 WASH W illing [ethical] A nonymous [no deductive disclosure] S aliva & linked self-Q [high volunteer rate] H IV surveillance Linked to self-Q on risks [frank answers]

6. 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)

7. 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

8. 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: 1 st fortnight DRDs = 4

9. Drugs-related deaths in fortnight after prison: 19 486 male ex-prisoners, aged 15-35 years, released after 14+days’ incarceration DEATHS1 st 2 weeks subsequent 5 fortnights RELATIVE RISK (95% CI) Drugs- related 3423 (11 in 2 nd fortnight +12 in next 8 wks) 7 (3 to 16) Other causes 3180.8 (0.2 to 2.4)

10. 1 in 200 adult injectors dead within 2 weeks after prison Judges aware?

11. Internationally, 6 major studies Merrall et al., 2010 Addiction Studies DRDs; pys at risk DRD rate per 1 000 pys 1 st fortnight Relative Risk (95% CI) 1 st fortnight 2 nd fortnight next 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)

12. 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!

13. Prison-based interventions a)Information leaflet: how to avoid overdose risk after release b) Naloxone on release: heroin antidote

14. 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

15. 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

16. 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 1 st 4 weeks post-release; 50% chance in next 8 weeks 3. 50% chance that Naloxone is administered by present other.  Effectiveness in 1 st 4 weeks = 30% Effectiveness in weeks 5 to 12 = 20% 4.21 st C: One overdose death in 1 st 4 weeks per 200 ever-IDUs randomised to control group. 5. Contamination...

17. Prison-based, with-consent* RCT for 56,000 pre-release adult IDUs Expected drugs deaths 1 st 4 weeks after release Next 8 weeks after release Controls [28,000 IDUs] 140 35 Naloxone [28,000 IDUs] 98 28

18. UK-affordable cost of Naloxone If CE threshold is £20K ($40K) per life year gained, & Naloxone prevents 42 drug deaths in 1 st +2 nd 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

19. 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... ?

20. 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)

21. 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 1 st or 2 nd fortnight after release (for HALF only of randomised participants & in PILOT RCT only... Because phone-contact contaminates N-ALIVE intervention)

22. 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.

24. 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