Transcript Presentazione di PowerPoint

Treatment demand and drug
related deaths:
results and hints from the
VEdeTTE study
Patrizia Schifano
EMCDDA - 2006 Annual expert meeting
Lisbon
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
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
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
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)
The Treatments
methadone maintenance
methadone detoxification
Pharmacological
therapies
naltrexone
detoxification with syntomatic
not-substitutive syntomatic
Therapeutic
community
residential community
semi-residential community
emergency center
Psychosocial
therapies
psychoterapy
support
counselling
orientation and work fellowship
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
The Treatments
N
trt
N
subjects
Average n
per person
Median
lenght
(days)
Methadone Maintenance
11311
6837
1.7
120.0
Detoxification Methadone
10684
4764
2.3
28.0
Other Pharmacological
1876
1274
1.5
32.0
Therapeutic Community
1830
1563
1.2
192.5
Psychosocial Therapies
5931
3582
1.7
30.0
The sequence of treatments:
starting with MMT …………….
2nd treatment %
concluded
(33.2%)
MMT
6,3
MD
74,7
TC
1,7
Other
No treatment
MMT
12,2
5,1
N=4412
MMT
40,6
MD
12,9
drop-out
(20.4%) TC
Other
0,9
25,8
No treatment 19,8
The sequence of treatments:
starting with MD.…………….
2nd treatment %
MMT
34,5
MD
34,6
(66.7%) TC
1,7
concluded
Other
No treatment
MD
26,6
5,6
N=1718
drop-out
(20.4%)
MMT
23,1
MD
47,0
TC
1,1
Other
No treatment
21,5
7,3
Methadone Manteinance
Dose
Average: 40.9 mg/day
Median: 39.7 mg/day
19% of subjects >60mg/day
Mortality analysis
 Study population: 10258
 Observed deaths: 189
• 36.8% overdose
• 20.0% AIDS
• 15.8% violent causes
Mortality analysis
Rate /1000 p-y
Males
95% CI
12.7
4.9 – 20.5
Females
8.4
4.7 – 12.2
Total
12.0
5.4 – 18.6
Mortality analysis
SMR
in treatment
95% CI
3.9
5.7 – 7.8
out of treatment 22.8
16.7-27.4
9.9
8.6 – 11.4
total
Mortality and treatment
 Study period: 18 months
 Deaths: 100 (53% of the total)
 Overdose deaths: 41 (59% of the total)
Mortality by overdose and treatment
Hazard Ratio of overdose mortality for heroin users in treatment, VEdeTTE study
Out of treatment
In treatment
In treatment
Methadone maintenance
Therapeutic Community
Methadone detoxification
Other pharmacological
Psychosocial
Number of
deaths
(41)
31
10
7
0
1
1
1
Person-years
Rate
1000 p-y Crude RR Adjusted RR*
95% IC
2913.79
10207.72
10.64
0.98
1.00
0.09
1.00
0.09
0.04 0.19
5751.28
1188.94
1495.72
422.59
1349.23
1.22
0.67
2.37
0.74
0.11
0.06
0.22
0.07
0.10
0.07
0.37
0.07
0.04
0.01
0.05
0.01
0.24
0.50
2.76
0.55
* Adjusted for age, gender, psychiatric co-morbidity, HIV status, previous non fatal overdose, route of administration,
length of use
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
In treatment
Out treat ment
Out of treatment
Methadone maintenance
Therapeutic Community
Methadone detoxification
Other pharmacological
Psychosocial
Number of deaths
Rate 1000 Crude
Person-years
(41)
p-y
RR
10
10207.72
0.98
1
31
2913.79
10.64
10.86
9
997.68
5
7
7
3
Time since last treatment (days)
<=30
13
>30
18
Adjusted
95% IC
RR*
11.11 5.29 23.35
9.21
22.02
8.78
11.67
12.23
8.26
3.27 20.88
231.74
814.06
612.20
250.46
9.02
21.58
8.60
11.43
11.98
23.00
9.35
12.09
22.31
7.63
3.46
4.48
5.88
561.44
2352.36
23.15
7.65
23.64
7.81
26.57
7.29
11.56 61.10
3.28 16.22
* Adjusted for age, gender, psychiatric co-morbidity, HIV status, previous non fatal overdose, route of
administration, length of use
69.31
25.26
32.60
84.58
Is no treatment better than a shortperiod treatment?
1 month
out of treatment
out of treatment
A
7.7 x 1000
7.7 x 1000
in treatment
out of treatment
2.67 x 1000
19.26 x 1000
B
Is no treatment better than a shortperiod treatment?
Excess of mortality attributable to
being in a short-term treatment in a
2-month period
5.52 deaths x 10000 episodes
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
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?
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
Results from A STYSTEMATIC REVIEW OF the
OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID
DEPENDENCE
Review:
Outcome:
Comparison:
Observational studies on treatment for opioid dependence and mortality
any cause mortality
in methadone maintenance vs out of methadone maintenance
Study
or sub-category
Davoli, Italy 1998-2001
Caplehorn, Australia 1970-1991
Fugelstad, Sweden 1986-1993
Appel, USA 1966-1976
Brugal, Spain 1992-1999
in MMT
n/N
27/5751
11/1975
7/177
93/6118
119/5400
19421
Total (95% CI)
Total events: 257 (in MMT), 1063 (out MMT)
Test for heterogeneity: Chi² = 7.98, df = 4 (P = 0.09), I² = 49.9%
Test for overall effect: Z = 7.44 (P < 0.00001)
out MMT
n/N
RR (random)
95% CI
Weight
%
24/998
36/2279
33/330
83/2358
887/17649
15.04
11.17
8.60
28.72
36.46
23614
100.00
0.001 0.01
0.1
Favours treatment
1
10
100
Favours control
1000
RR
0.20
0.35
0.40
0.43
0.44
[0.1
[0.1
[0.1
[0.3
[0.3
0.37 [0.2
Results from A STYSTEMATIC REVIEW OF the
OBSERVATIONAL STUDIES ON TREATMENT OF OPIOID
DEPENDENCE
Outcome:
Comparison
Study
or sub-category
Overdose mortality
in methadone maintenance vs out of methadone maintenance
in MMT
n/N
Davoli, Italy 1998-2001
Appel, USA1966-1976
Brugal, Spain1992-1999
Van Ameijdem, The Netherlands 1989-1995
Buster, The Netherlands. 1986-1998
out MMT
RR (random)
95% CI
n/N
7/5751
2/6118
11/5400
8/1500
42/18747
Weight
%
9/998
36/2358
338/17649
7/466
26/10983
19.78
17.62
21.30
19.67
21.63
Total (95% CI)
Total events: 70 (in MMT), 416 (out MMT)
Test for heterogeneity: Chi² = 53.93, df = 4 (P < 0.00001), I² = 92.6%
Test for overall effect: Z = 2.66 (P = 0.008)
0.001 0.01
0.1
Favours treatment
1
10
100
Favours control
1000
R
0.13
0.02
0.11
0.36
0.95
[0
[0
[0
[0
[0
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
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 shortperiod 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)
. . . . . . . . . . . . . . . . . . . . . . .
CONCLUSION
Do you think it would be
valuable
feasible
to replicate the Vedette study in other
European countries?