FUTURE RESEARCH IN SUBSTANCE MISUSE FUTURE RESEARCH IN SUBSTANCE MISUSE AN OVERVIEVW PERSPECTIVEAN OVERVIEVW PERSPECTIVE

Michael FarrellMichael Farrell

PHRN ManchesterPHRN Manchester

2020thth October 2006 October 2006

Political and moral values of the social system

Research Evidence

SERVICE Provider AND USER VIEW

A model for evidence-based clinical decisions(from Haynes et al, 1996)

AIDS cases by transmission group* and year of diagnosis (1987-2003) adjusted for reporting delays, European Union, data reported by 31 December 2003

0

2000

4000

6000

8000

10000

1987 1989 1991 1993 1995 1997 1999 2001 2003Year of diagnosis

HBM IDU HC Transmission group not reported

NOTE Excluding France, Netherlands (data not available for the w hole period) and Cyprus (no data available) source EuroHIV

Injecting

HIV infections newly diagnosed in injecting drug users in selected EU countries, Russia and Ukraine, by year of report, cases per million population

(EUROHIV)

0

100

200

300

400

500

600

700

800

900

1000

1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Ca

ses

pe

r m

illio

n p

op

ula

tion

Estonia Latvia Lithuania

Portugal Russia Ukraine

Note: no data available from tw o EU countries w ith highest AIDS incidence among IDUs (Spain, Italy)

HIV prevalence among IDUs in HIV prevalence among IDUs in the EUthe EU

EMCDDA 2004Notes: Colour indicates midpointsLocal data shown in ()

HIV in IDUs in EuropeHIV in IDUs in Europe Marked difference between countries and within some Marked difference between countries and within some

countriescountries– High prevalence countries (old MS) Italy, Spain, Portugal, High prevalence countries (old MS) Italy, Spain, Portugal,

followed by Francefollowed by France– Some high prevalence estimates from new MS (Latvia, Some high prevalence estimates from new MS (Latvia,

Estonia), and worries about others (Poland) Estonia), and worries about others (Poland) – Low prevalence countries in both old and new MS including Low prevalence countries in both old and new MS including

countries with high prevalence IDUcountries with high prevalence IDU– Cautious assessment is the long term trend appears to be Cautious assessment is the long term trend appears to be

stable or downwards stable or downwards Some small increases in recent data in some countries or in specific Some small increases in recent data in some countries or in specific

subpopulationssubpopulations Data quality problems so analysis must be made with caution Data quality problems so analysis must be made with caution

A note on HCV prevalence in A note on HCV prevalence in IDUsIDUs

Prevalence estimates higher and more Prevalence estimates higher and more convergent than for HIVconvergent than for HIV

Clear need to finding effective prevention Clear need to finding effective prevention strategiesstrategies

Routine disease surveillance sources of Routine disease surveillance sources of limited valuelimited value

Drug injecting principle route of transmission Drug injecting principle route of transmission for HCV in Europefor HCV in Europe

50

100

150

200

250

300

Inde

x %

(19

85=

100%

)

INDEX 100,0 104,5 118,7 136,9 153,7 181,0 216,4 223,5 201,8 212,2 225,4 252,4 230,1 235,6 241,1 255,4 240,1 205,8 194,9

1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003*

Long term trend in acute drug-related Long term trend in acute drug-related deaths (1985-2003)deaths (1985-2003)

EU 15, 1985 to 2003 index year 1985=100

Introduction of MMT & NSP, Introduction of MMT & NSP, 1967 to 20011967 to 2001

(EU, Norway and Bulgaria)(EU, Norway and Bulgaria)

ES

DK, NL, SE

MT, UK

NO

IE, PL

AT, ITCZ

DELU, PT

SK FR

SI

LV, LT,FI

ELBG

HU

BE, EE

SE

NL, UKDK

DE

FIIT

ESPT

MTAT

LUSI

EL, IE,CZ

PL

FR, LT, HU, BU

LVBE

NOEE

0

5

10

15

20

25

30

1967 1969 1971 1973 1975 1977 1979 1981 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001

Cu

mu

lati

ve n

um

ber

of

cou

ntr

ies

Year first publicly funded NSP Methadone treatment first available

Estimated number of drug users in Estimated number of drug users in substitution treatment in 29 European substitution treatment in 29 European

countries (2003) per 100.000 population countries (2003) per 100.000 population aged 15-64aged 15-64

0

50

100

150

200

250

300

350

400

450

LU UK ES IE MT FR PT IT SI DK EU

+ 4

DE NL NO SE EL BE CZ LT FI HU BG LV PL RO

10-year trend in the number of substitution treatment clients in Europe (EU-15)

73,400

207,000

265,000

351,000

537,000

0

100,000

200,000

300,000

400,000

500,000

600,000

1993 1995 1997 2000 2003

Proportion of substitution Proportion of substitution drugs used in medically drugs used in medically

assisted treatment in Europe, assisted treatment in Europe, 20032003

Methadone79%

Other1%

Buprenorphine20%

Prevalence of HIV in Injecting Prevalence of HIV in Injecting Drug Users some country Drug Users some country

estimatesestimates European Union, Northern Europe low prevalence, Southern European Union, Northern Europe low prevalence, Southern European countries higher prevalence but decliningEuropean countries higher prevalence but declining

Central and Eastern European countries upward trend, Central and Eastern European countries upward trend, especially Ukraine, Russia, especially Ukraine, Russia,

USA and Canada generally stable low levels, outbreak USA and Canada generally stable low levels, outbreak Vancouver British Columbia related to cocaine injectingVancouver British Columbia related to cocaine injecting

Australia less than 2%Australia less than 2% India Manipur Estimated at 50% plusIndia Manipur Estimated at 50% plus China Yunnan Province 10% to 70% in three yearsChina Yunnan Province 10% to 70% in three years Rapid increase in 31 provinces in China Rapid increase in 31 provinces in China Myanmar 56% IDUs HIV positive in one studyMyanmar 56% IDUs HIV positive in one study Vietnam 63% IDUs Vietnam 63% IDUs

HIV prevalence in injecting drug HIV prevalence in injecting drug usersusers

0

10

20

30

40

50

60

70

80

90

1983 1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999

Year

HIV

pre

vale

nce

, %

Edinburgh

Bangkok

Myanmar

Manipur &Yunnan

Ho Chi Minh City

Odessa

Jakarta

Lithuania

HIV infection rates in and out of HIV infection rates in and out of substitution treatment substitution treatment (Metzger et al. (Metzger et al.

1993)1993)

2127

35 3636

39 39 42 48 49 51

13 15 16 17 17 18 18 19 19 20 21

baseline6 m

ths

12 mths

18 mths

24 mths

30 mths

36 mths

42 mths

48 mths

60 mths

72 mths

Out %

In %

Drug Overdose and MortalityDrug Overdose and Mortality

Mean of 5+ non fatal overdoses in heroin Mean of 5+ non fatal overdoses in heroin using cohortsusing cohorts

Mortality 1 to 2% Mortality 1 to 2% In methadone treatment down to 0.2%In methadone treatment down to 0.2% Recent Hser 33 year longitudinal study Recent Hser 33 year longitudinal study

reports over 50% mortality in cohortreports over 50% mortality in cohort Suicide completion rates high and significant Suicide completion rates high and significant

contributor to overall suicidecontributor to overall suicide

Excess mortality ratio for different time periods post-release by cause of death (Singleton, Farrell, Marsden et al 2003)

05

1015202530354045

Time since release (w eeks)

Exce

ss m

orta

lity ra

tio

Drug-related deaths Not drug-related

The odds of a drug-related death in The odds of a drug-related death in the first week of release the first week of release

among womenamong women

over over 1010 times greater than that observed at one year (OR 10.6; 95%CI 4.8-22.0) times greater than that observed at one year (OR 10.6; 95%CI 4.8-22.0)

70 70 times higher than age matched general population times higher than age matched general population

among menamong men

around around 88 times greater than at one year (OR 8.3: 95%CI 5.0-13.3). times greater than at one year (OR 8.3: 95%CI 5.0-13.3).

3030 times higher than age matched general population times higher than age matched general population

(Singleton, Farrell et al 2003)(Singleton, Farrell et al 2003)

IN SUMMARY A 8-10 FOLD INCREASED RISK OF IN SUMMARY A 8-10 FOLD INCREASED RISK OF MORTALITY IN THE EARLY RELEASE PERIODMORTALITY IN THE EARLY RELEASE PERIOD

Substitution in prisonsSubstitution in prisons

Estimated that over 30 million imprisoned annuallyEstimated that over 30 million imprisoned annually Major risk for blood borne virus spreadMajor risk for blood borne virus spread In most countries where measured between one third and In most countries where measured between one third and

half have drug dependencehalf have drug dependence RCT of methadone in prison (Dolan et al) demonstrates RCT of methadone in prison (Dolan et al) demonstrates

role in reduction of blood borne virus, and general role in reduction of blood borne virus, and general improvement, and post release reduction in mortality for improvement, and post release reduction in mortality for those who continuethose who continue

Rapid expansion in Europe in substitution in prisonsRapid expansion in Europe in substitution in prisons Huge challenge for Asia pacific region where insitutional Huge challenge for Asia pacific region where insitutional

incarceration standard response to opioid dependenceincarceration standard response to opioid dependence Consistently 90% relapse to heroin use, no studies on Consistently 90% relapse to heroin use, no studies on

mortalitymortality

Drug Substitution TreatmentDrug Substitution Treatment Strong evidence for the benefits of oral methadone Strong evidence for the benefits of oral methadone

treatment RCTs +++ REASONABLE EFFECT SIZEtreatment RCTs +++ REASONABLE EFFECT SIZE REDUCES DRUG CRIME .70REDUCES DRUG CRIME .70     REDUCES OPIATE CONSUMPTION .35REDUCES OPIATE CONSUMPTION .35 REDUCES INJECTING & RISK TAKING 0.22REDUCES INJECTING & RISK TAKING 0.22 Now good evidence for buprenorphine and LAAM Now good evidence for buprenorphine and LAAM

RCTs ++ (LAAM CURRENTLY UNDER REVIEW)RCTs ++ (LAAM CURRENTLY UNDER REVIEW) Use of injectable diamorphine and other drugs Use of injectable diamorphine and other drugs

building evidence base for comparative effectiveness, building evidence base for comparative effectiveness, more dicussion on comparative cost effectiveness.more dicussion on comparative cost effectiveness.

Gunne & Gronbladh (1981) RCT:Gunne & Gronbladh (1981) RCT:Methadone versus no methadoneMethadone versus no methadone

34 subjects using heroin by injection34 subjects using heroin by injection

17 experimental (methadone)17 experimental (methadone)

17 controls (no methadone)17 controls (no methadone)

Controls not allowed to enter MMT for 2 yearsControls not allowed to enter MMT for 2 years

Followed up at 2 years and again at 4 yearsFollowed up at 2 years and again at 4 years

Gunne & Gronbladh (1981): BaselineGunne & Gronbladh (1981): BaselineExperimental Group Experimental Group

(methadone)(methadone)Control group Control group

(no methadone)(no methadone)

UU UU UU UU UU UU UU UU

UU UU UU UU UU UU UU UU

UU UU UU UU UU UU UU UU

UU UU UU UU UU UU UU UU

UU UU

U U – ongoing daily heroin – ongoing daily heroin UUsese

Gunne & Gronbladh (1981): 2 yearsGunne & Gronbladh (1981): 2 years

Experimental group Experimental group (methadone)(methadone)

Control group Control group

(no methadone)(no methadone)

AA AA AA AA UU UU UU AA

AA AA AA AA UU UU UU UU

AA AA AA AA UU UU UU UU

UU UU UU UU UU UU UU DD

UU DD

AA – – AAbstinent bstinent

UU – on-going daily – on-going daily UUsese

DD – – DDeceasedeceased

Gunne & Gronbladh (1981): 4 yearsGunne & Gronbladh (1981): 4 years

Experimental Group Experimental Group (methadone)(methadone)

Control group Control group

(methadone)(methadone)

Control group Control group

(no methadone)(no methadone)

AA AA AA AA UU UU UU AA

AA AA AA AA AA AA UU UU

AA AA AA AA AA AA UU DD

UU UU UU AA AA AA DD DD

UU DD

AA – – AAbstinent bstinent

UU – on-going daily – on-going daily UUsese

DD – – DDeceasedeceased

A 33 year follow-up of narcotic A 33 year follow-up of narcotic addictsaddicts

(Hser et al., 2001)(Hser et al., 2001)

0

20

40

60

80

100

56 60 64 68 72 76 80 84 88 92 96

Unknown Dead Incarcerated Daily use MMT Occasional use Abstinence

22% 2% 6% 7% 4%

48%

12%

N 581 439 354 242Age 24.5 (3.9) 36.8 (5.4) 47.6 (5.1) 57.4 (4.0)

A 33 year follow-up of narcotic A 33 year follow-up of narcotic addictsaddicts

(Hser et al., 2001)(Hser et al., 2001)

0

20

40

60

80

100

56 60 64 68 72 76 80 84 88 92 96

Unknown Dead Incarcerated Daily use MMT Occasional use Abstinence

22% 2% 6% 7% 4%

48%

12%

N 581 439 354 242Age 24.5 (3.9) 36.8 (5.4) 47.6 (5.1) 57.4 (4.0)

COMPOSITE SLIDECOMPOSITE SLIDE3-Year Reincarceration Rates3-Year Reincarceration Rates

0

20

40

60

80

100

Per

cent

No Tx Prison Tx Prison+Parole

DE TX CA

** * *

Methadone maintenance for Methadone maintenance for prisonersprisoners

LocationLocation No. MMTNo. MMT Prison Prison PopulationPopulation

Rate % Rate %

NSWNSW 10001000 81508150 12.2612.26

AustriaAustria 345345 69156915 4.94.9

DenmarkDenmark 290290 31503150 9.29.2

FranceFrance (Bup 879) 157(Bup 879) 157 5071450714 0.30.3

GermanyGermany 800800 7870778707 1.01.0

SpainSpain 1800018000 5065650656 35.535.5

New YorkNew York 400400 6706567065 0.50.5

SwitzerlandSwitzerland 180180 49854985 3.63.6

Source: NSW DCS Inmate Census, UK Home Office, World Prison Population List 4th Ed, US Department of Justice

NSW prison methadone programNSW prison methadone program1986 1986 as a pilot pre release program by Department of as a pilot pre release program by Department of

Corrective Services (DCS)Corrective Services (DCS)

CriteriaCriteria

3-6 months prior to release3-6 months prior to release

Past or present history of opiate dependencePast or present history of opiate dependence

History of returning to injecting and crime on History of returning to injecting and crime on

previous releasesprevious releases

3 designated community clinics3 designated community clinics

1990 1990 those entering custody on MMT were continuedthose entering custody on MMT were continued

Since 1990 Since 1990 12% NSW MMT received in custody12% NSW MMT received in custody

NDARC Methadone StudyNDARC Methadone Study

NSW prison methadone NSW prison methadone

maintenancemaintenance– Randomised control trail of 384 IDUs in Randomised control trail of 384 IDUs in

1997 and re-interviewed in 19981997 and re-interviewed in 1998

– Heroin use was significantly less for those Heroin use was significantly less for those

receiving methadone, as measured by hair receiving methadone, as measured by hair

analysis.analysis.

Source: Dolan & Wodak

RCT ResultsRCT Results

MMTMMT ControlControl

HCV incidence %HCV incidence % 24.324.3 31.731.7

Heroin (hair) %Heroin (hair) % 2727 4242

Heroin (SR) %Heroin (SR) % 3333 7878

No cases of HIVNo cases of HIV

NDARC Methadone StudyNDARC Methadone Study

Follow up after release from gaol study Follow up after release from gaol study

of above 384 IDUs examining rate of:of above 384 IDUs examining rate of:

– Incarceration Incarceration

– Mortality Mortality

– Hepatitis CHepatitis C

0.95

0.96

0.97

0.98

0.99

1

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54

MMT

Non MMT

Mortality rates Mortality rates (Intent)(Intent)

HCV incidence HCV incidence (Intent)(Intent)

MMT MMT (N=52)(N=52) CONTROL CONTROL (N=56)(N=56)

CasesCases 1414 2323

Rate Rate per 100 person per 100 person yearsyears

18.318.3 36.536.5

95% CI95% CI 10 - 3110 - 31 23 - 5523 - 55

Previous rate at 5 months was 24 CI: 7-62 vs 31 CI: 9-81Previous rate at 5 months was 24 CI: 7-62 vs 31 CI: 9-81

Source: Dolan, K

Re- incarceration up to May Re- incarceration up to May 20022002

ContinuousContinuous n=45n=45

Non- Non- ContinuousContinuous

n= 216n= 216

pp

Mean total Mean total weeks in prison weeks in prison (sd)(sd)

41 41 67 67 .007.007

Source: Dolan, K

Re- incarceration

Days of follow up

160012008004000

Cu

m S

urv

iva

l

1.0

.8

.6

.4

.2

0.0

Treatment exposure

continuous

non continuous

Source: Dolan, K

Need for upscaling of treatmentNeed for upscaling of treatment

Urgent need in many regions for concerted Urgent need in many regions for concerted effort to expand treatmenteffort to expand treatment

Discussions and research required on the Discussions and research required on the challenge of upscalingchallenge of upscaling

IDTS a major development within English IDTS a major development within English PrisonsPrisons

Major expansion in substitution treatment Major expansion in substitution treatment and psychosocial treatmentand psychosocial treatment

NEED TO EVALUATE IDTSNEED TO EVALUATE IDTS Implementation assessmentImplementation assessment Cost EffectivenessCost Effectiveness Environmental ImpactEnvironmental Impact Individual OutcomeIndividual Outcome Impact on RecidivismImpact on Recidivism Impact on Post Release MortalityImpact on Post Release Mortality

Research FrameworkResearch Framework

Need pragmatic studies in prison context Need pragmatic studies in prison context More longitudinal studiesMore longitudinal studies A 10 year mortality outcome study from the A 10 year mortality outcome study from the

National Psychiatric Morbidity SurveyNational Psychiatric Morbidity Survey Consider a longitudinal Study of Young Offenders Consider a longitudinal Study of Young Offenders

and exploration of trajectory of drug histories and exploration of trajectory of drug histories within the criminal justice systemwithin the criminal justice system

Prisons ideal enviroments for exploration of issues Prisons ideal enviroments for exploration of issues of psychiatric comorbidity and substance useof psychiatric comorbidity and substance use

Studies linked to community studiesStudies linked to community studies Linking treatment in prison up to the Linking treatment in prison up to the

National Drug Treatment Monitoring SystemNational Drug Treatment Monitoring System Currently Outcomes Monitoring Project Currently Outcomes Monitoring Project

Underway, Important to have Prison Underway, Important to have Prison Treatment Linked into this.Treatment Linked into this.

Infectious Diseases remain a big threat Infectious Diseases remain a big threat especially BBVsespecially BBVs

ConclusionsConclusions

The huge challenge in all settings is to The huge challenge in all settings is to develop a comprehensive range of develop a comprehensive range of interventions that are humanitarian, effective interventions that are humanitarian, effective and impactful for the all those who require and impactful for the all those who require interventionsinterventions

To ensure that ethical and humane To ensure that ethical and humane treatment is delivered as effectively as treatment is delivered as effectively as possible in all settings possible in all settings