Objectives

1. Treatment demand and drug related deaths: results and hints from the VEdeTTE studyPatrizia SchifanoEMCDDA - 2006 Annual expert meetingLisbon

2. Objectives The VEdeTTE Study has been designed to evaluate the effectviness of treatments offered in public treatment centers in preventing overdose mortality among heroin users in Italy

3. Objectives and…. to evaluate retantion in treatment according to type of treatment and…. to describe treatment offer • tipology • lenght • therapeutic aim and differences among services

4. Design: National Multicenter Longitudinal Prospective Study: • Target population: heroin users seeking for treatment, >18 yrs old • 115 (out of 554) PTCs (NHS) • Enrollment and follow-up: October 1998 - March 2000 • Vital status ascertainment: March 2001 • Study population: 10454 subjects

5. The cohort • 86% males • 12% new clients • Average age: 31 yrs • 80% intravenous users • 41% had previous overdose episodes • 8.2% HIV positive (33.6 MV)

6. The Treatments methadone maintenance methadone detoxification Pharmacological therapies naltrexone detoxification with syntomatic not-substitutive syntomatic residential community semi-residential community emergency center Therapeutic community psychoterapy support counselling orientation and work fellowship Psychosocial therapies

7. The Treatments • Total time in treatment: 10,208 p-yrs (78%) • Total time out of treatment: 2,914 p-yrs (22%) • Median lenght of follow-up: 547 days (99%) • Average number of treatments per person: 3.1

8. The Treatments N trt N subjects Average n per person Median lenght (days) Methadone Maintenance 11311 6837 1.7 120.0 10684 4764 Detoxification Methadone 28.0 2.3 Other Pharmacological 1876 1274 1.5 32.0 1563 1.2 192.5 1830 Therapeutic Community 3582 30.0 5931 1.7 Psychosocial Therapies

9. The sequence of treatments: starting with MMT …………….  MMT 6,3 MD 74,7 concluded (33.2%) TC 1,7 Other 12,2 No treatment 5,1 MMT 40,6 MD 12,9 drop-out (20.4%) TC 0,9 Other 25,8 No treatment 19,8 2nd treatment % MMT N=4412

10. MMT 34,5 MD 34,6 TC 1,7 Other 26,6 No treatment 5,6 MMT 23,1 MD 47,0 TC 1,1 Other 21,5 No treatment 7,3 The sequence of treatments: starting with MD.…………….  2nd treatment % concluded (66.7%) MD N=1718 drop-out (20.4%)

11. Methadone Manteinance • Dose • Average: 40.9 mg/day • Median: 39.7 mg/day 19% of subjects >60mg/day

12. Mortality analysis • Study population: 10258 • Observed deaths: 189 • 36.8% overdose • 20.0% AIDS • 15.8% violent causes

13. Mortality analysis Rate /1000 p-y 95% CI Males 12.7 4.9 – 20.5 Females 8.4 4.7 – 12.2 Total 12.0 5.4 – 18.6

14. Mortality analysis SMR 95% CI in treatment 3.9 5.7 – 7.8 16.7-27.4 out of treatment 22.8 9.9 8.6 – 11.4 total

15. Mortality and treatment • Study period: 18 months • Deaths: 100 (53% of the total) • Overdose deaths:41(59% of the total)

16. Mortality by overdose and treatment Hazard Ratio of overdose mortality for heroin users in treatment, VEdeTTE study Number of Rate deaths Person - years Crude RR Adjusted RR* 95% IC 1000 p - y (41) 31 2913.79 10.64 1.00 1.00 Out of treatment 10 1020 7.72 0.98 0.09 0.09 0.04 0.19 In treatment In treatment 0.04 0.24 Methadone maintenance 7 5751.28 1.22 0.11 0.10 Therapeutic Community 0 1188.94 - - - - - 1495.72 0.01 0.50 Methadone detoxification 1 0.67 0.06 0.07 Other pharmacological 1 422.59 2. 37 0.22 0.37 0.05 2.76 Psychosocial 1 1349.23 0.74 0.07 0.07 0.01 0.55 * Adjusted for age, gender, psychiatric co - morbidity, HIV status, previous non fatal overdose, route of administration, length of use

17. Mortality by overdose and treatment Hazard Ratio of overdose mortality for heroin users out of treatment by treatment and by time since last treatment , VEdeTTE study Number of deaths Rate 1000 Crude Adjusted Person - years 95% IC (41) p - y RR RR* In treatment 10 10207.72 0.98 1 - - Out treat ment 31 2913.79 10.64 10.86 11.11 5.29 23.35 Out of treatment 9 997.68 8.26 3.27 20.88 Methadone maintenance 9.02 9.21 Therapeutic Community 5 231.74 21.58 22.02 23.00 7.63 69.31 7 814.06 9.35 3.46 25. 26 Methadone detoxification 8.60 8.78 Other pharmacological 7 612.20 11.43 11.67 12.09 4.48 32.60 Psychosocial 3 250.46 11.98 12.23 22.31 5.88 84.58 Time since last treatment (days) <=30 13 561.44 23.15 23.64 26.57 11.56 61.10 >30 18 2352.36 7.65 7.81 7.29 3.28 16.22 * Adjusted for age, gender, psychiatric co - morbidity, HIV status, previous non fatal overdose, route of administration, length of use

18. Is no treatment better than a short-period treatment? out of treatment out of treatment 1 month A 7.7 x 1000 7.7 x 1000 in treatment out of treatment B 2.67 x 1000 19.26 x 1000

19. Is no treatment better than a short-period treatment? Excess of mortality attributable to being in a short-term treatment in a 2-month period 5.52 deaths x 10000 episodes

20. Summary of results • High heterogeneity in treatment offer • Apparent PTC’s preference towards abstinence oriented therapies (70% of patients at their first visit) • Methadone Maintenance offered on avearage at lower doses than those known to be effective (40 mg/day) • a range of specialist drug treatments are protective, substantially reducing the risk of drug related overdose during treatment • the risk of death is substantially higher in the month after treatment discharge or drop out; • leading to an excess of 6 deaths per 10,000 treatment episodes lasting less than one month

21. What to change if designing a new Vedette study • Necessisity to simplify information collected on treatment • Is there a better way to collect information on treatment? • 18 months of follow-up. Is it a too short period? 100 deaths after 18 months, 189 after 30 months. • Do we have to plan longer studies to evaluate treatments correctly? • Tretaments already ongoing at the start of the study are difficult to be analyzed. Who to enroll? How many?

22. Strenght points of the Vedette study • Valuable information about effectiveness of treatments for drug-dependance on more than one outcome • An insight of treatment demand and offer • Mortality follow-up. Easy to be updated • It provides the unique possibility of studying the occurance of outcomes in the “real world” where: • Patients are not randomized • Treatments are not optimal • Resources are limited

23. Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE

24. Results from A STYSTEMATIC REVIEW OF the OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID DEPENDENCE

25. What do you need to implement a study similar to Vedette? 1 Ministry 2 coordination centres 10 researchers 13 regions 119 treatment services + di 1000 health operators + di 15000 clients and A strong collaboration among the coordination centres and the services It contributed to spread the aweraness of the importance of evidence based practice, and of quantitative evaluation of treatments

26. CONCLUSION The Vedette study is still ongoing: • Imputing missing treatment to use all the deaths registered at the last vital status ascertainment • Continuing the analysis of the effect of short-period treatments • Updating the follow-up of mortality • Designing a nested case-control study to better understand the determinants of overdose mortality • Ongoing follow-up on treatments on a sub-cohort (one region) • . . . . . . . . . . . . . . . . . . . . . . .

27. CONCLUSION • Do you think it would be • valuable • feasible • to replicate the Vedette study in other European countries?