Introduction: The VEdeTTE study

VEdeTTE is the Italian acronym for “Evaluation of Effectiveness of Treatments for Heroin Dependence”. The VEdeTTE study is the first multi-centre observational outcome study of treatments for heroin addicts conducted in Italy. The study aims to measure the effectiveness of the treatments provided by drug abuse treatment centres run by the National Health Service (NHS).


Ethical aspects

Patients were formally asked to participate in the study after being informed of its objectives, the methods to be used and data management procedures. The study protocol and research instruments were also available for compliant patients. Subjects who enrolled could decide to leave the study at any time, in which case, their data would be erased. Patients were also asked whether they were willing to be contacted afterwards.

To ensure confidentiality, information was gathered anonymously. A unique identification code was assigned to each subject. On all study instruments the subject was identified through that code only. The code - name combination was recorded on a specific form, which was kept under lock and key at the drug abuse treatment centre. An ethical committee periodically verified compliance with a list of rules that had been adopted.

The study consisted of several stages:

• VEdeTTE 1 pilot study
• VEdeTTE 1
• VEdeTTE 1bis
• VEdeTTE 2 pilot study
• VEdeTTE 2

The VEdeTTE 1 pilot study

Objectives

To test:

1. the feasibility of the study, in terms of operators’ and patients’ availability to participate in the study, and the acceptability of the Intake Questionnaire;

2. the efficiency of different models for recruiting patients already being treated at the beginning of the study (prevalent subjects);

3. the validity of study instruments, particularly: Consent Form, Intake Questionnaire, Treatment Registration Form.

Study population

One drug abuse treatment centre from each region involved in the pilot study (Friuli Venezia Giulia, Piedmont, Emilia Romagna, Tuscany, Apulia, Sicily, Liguria, Autonomous Province of Trento, Marche, Lazio, Campania, Calabria, Sardinia) participated in the study, with the exception of Piedmont, Lazio and Emilia Romagna, where two centres participated. In each drug abuse treatment centre a population of one hundred patients was considered in the study (90 prevalent subjects and 10 incident subjects, i.e. 10 subjects unknown to the centre at the beginning of the study), excluding Emilia Romagna, where each of the two centres contributed with 50 subjects.

A total of 1110 patients (978 prevalent and 132 incident) were contacted; 970 (87.4%) of them agreed to participate (871 prevalent and 99 incident).

Time period

Patients were enrolled over two months, between December 1997 and January 1998. During that period all the study instruments were written out by drug abuse treatment centre staff. In February and March 1998 two trained students collected data from clinical records about treatments given during the study period to patients enrolled in the study. This second data collection took place under different conditions and using a different form in order to evaluate the Treatment Registration Form (see above).

Study instruments

A number of forms were created for this study.

Three different forms were used to evaluate the feasibility of the study, in terms of operators’ and patients’ availability to participate, and the acceptability of the Intake Questionnaire. The first form was designed to quantify the level of cooperation offered by the various people working at drug abuse treatment centres.

The second form aimed to assess the acceptability of the questionnaire among operators and patients as well as the adequacy of the questions in relation to the information to be collected.

The purpose of the third form was to rate patients’ availability to participate in the study. The following information was collected: number of patients to whom participation was proposed; number of patients who agreed to participate; comprehensibility of the objectives of the study as set out in the consent form and acceptability of the consent form itself.

Two models of the consent form were tested. Only one model included a request asking whether the patient would agree to be contacted for another interview within two years. The purpose was to find out whether such a possibility could increase the refusal rate.

Due to the difficulty of enrolling the numerous prevalent patients eligible for the study in a short time and in order to avoid arbitrary selections, three different models of enrollment were tested.

According to the dilution model, the enrolment (consisting of signing the consent form and answering the Intake Questionnaire) of all prevalent eligible subjects should be possible at any time during the first year of the study, and thus diluted, but with information about treatments being collected right from the start of the study. The random model provides for the enrolment, within six months from the starting date, of only one third of all prevalent patients, based on a random selection. The restriction model restricts enrolment, during the first six months of the study, to prevalent patients whose current treatment was prescribed within 6 months before the starting date of the study.

The reproducibility and quality of the Intake Questionnaire were evaluated by assessing test-retest reliability (which consisted of interviewing each patient twice in a few days, once by a physician and the second time by a psychologist) and inter-rater reliability (patients were interviewed once only, but their answers were recorded separately in the questionnaire by both a physician and a psychologist).

A validation form was created to verify the accuracy and completeness of the Treatment Registration Form. Two trained students used this form to record data collected from clinical records about therapies administered during the study period to enrolled patients. These data were compared with those (relating to the same period and the same cohort) recorded in the Treatment Registration Form by staff at the drug abuse treatment centres involved.

The protocol and instruments of the VEdeTTE 1 study were modified according to the results of the pilot study.

The VEdeTTE 1 study

Objectives

To evaluate the effectiveness of treatment programmes provided by drug abuse treatment centres run by the National Health Service (NHS), in terms of mortality prevention and retention in treatment.

Drug abuse treatment centres that participated in the study

A non-random sample of 115 (21%) treatment centres, out of 554 operating in Italy at that time, participated in the study. They represented thirteen out of the twenty-one Italian regions and autonomous provinces.

Study population

The study population included Italian heroin addicts, aged 18 years or over, who received treatment at the participating centres during the study period.

At the time of enrolment the subjects were defined, according to the treatment status, as:
- Incident: subjects entering the specific treatment centre for the first time
- Re-entry: subjects not receiving treatment at the beginning of the study but who had been treated by the centre in the past and started a new course of treatment during the study period
- Prevalent: subjects receiving treatment when the study started.
All participants provided their written consent to participate in the study.

Time period

Between September 1998 and March 2001 each participating centre enrolled subjects over an 18-month period.

Study instruments

Data were collected using three research instruments: the Intake Questionnaire, the Treatment Registration Form and the Centre Information Form.

The Intake Questionnaire consisted of a structured interview administered at the time of enrolment. The objective of the Intake Questionnaire was to gather information on factors that could act as potential confounders in estimating the association between treatment and outcomes. Items investigated were: socio-demographic characteristics (civil status, educational level, accommodation, job); legal problems; drug addiction history and drug use (frequency, dose, route of administration) in the last 30 days and, for prevalent cases only, during the month before the start of therapy; overdoses; previous attempts to give up drug consumption; risky behaviour; HIV, HBV, HCV and other pathologies as per clinical records and as reported by the patient. Some information about socio-demographic characteristics and heroin use was also collected for non-enrolled patients.

The Treatment Registration Form aimed to gather details about each treatment: type, start and end date, doses and compliance. Staff at the centres were asked to record each episode of the following treatments: methadone maintenance; detoxification with tapering doses of methadone; detoxification with non-opiate drugs (in and outpatient based); maintenance with naltrexone; therapy with psychotropic drugs; psychotherapy; counselling; job guidance; social advice; and residential and semi-residential treatment (semi-residential patients do not spend the night at the facility).

The Centre Information Form was used to gather information about the NHS centre’s characteristics, such as the professional background of staff, diagnostic instruments utilised, the clinic’s policy and strategy.

Vital status ascertainment

31 March 2001 was the chosen date for the first follow-up. A second follow-up was carried out with reference to 30 June 2006. Vital status was assessed, first at each treatment centre and, for those not receiving treatment at the time of ascertainment, through the patients’ Municipal Registry Offices. The cause of death was retrieved from the municipality in which the death occurred and coded according to the International Classification of Diseases (IX revision).

Results

From September 1998 through to March 2001, 15,779 heroin addicts were contacted by agency staff and requested to give their consent to be included in the cohort. At the end of the enrolment period, 3,876 refused to participate in the study (24.6%) and 11,903 people were recruited (75.4%).

For more results see the following articles published in English:

Davoli M, Bargagli AM, Perucci CA, Schifano P, Belleudi V, Hickman M, Salamina G, Diecidue R, Vigna-Taglianti F, Faggiano F, for the VEdeTTE Study Group. Risk of fatal overdose during and after specialist drug treatment: the VEdeTTE Study, a national multisite prospective cohort study. Addiction 2007 Dec;102(12):1954-9.

Bargagli AM, Faggiano F, Amato L, Salamina G, Davoli M, Mathis F, Cuomo L, Schifano P, Burroni P, Perucci CA; VEdeTTE Study Group. VEdeTTE, a longitudinal study on effectiveness of treatments for heroin addiction in Italy: study protocol and characteristics of study population. Subst Use Misuse. 2006;41(14):1861-79.

Schifano P, Bargagli AM, Belleudi V, Amato L, Davoli M, Diecidue R, Versino E, Vigna-Taglianti F, Faggiano F, Perucci CA. Methadone treatment in clinical practice in Italy: need for improvement. Eur Addict Res. 2006;12(3):121-7.

Bargagli AM, Schifano P, Davoli M, Faggiano F, Perucci CA; VEdeTTE Study Group. Determinants of methadone treatment assignment among heroin addicts on first admission to public treatment centres in Italy. Drug Alcohol Depend. 2005 Aug 1;79(2):191-9. Epub 2005 Feb 25.

Italian publications are available and may be downloaded from the “Pubblicazioni” page

Slides in English (see the “Presentazioni” page for more slides in Italian)

EMCDDA Annual Expert meeting “Drug-related deaths and mortality among drug users”, Lisbon, 29-30 November 2007 “The VEdeTTE national Italian cohort study: Evaluation of effectiveness of treatments for heroin addiction in retaining patients and reducing mortality” 
Dimension 472 KB – PDF File

15th Annual EUPHA Meeting, Helsinki, 11-13 October 2007. "Gender differences in heroin addiction: results from the VEdeTTE cohort" 
Dimension 165 KB – PDF File

"Effectiveness of treatment for heroin addiction in retaining patients and reducing mortality: results from the VEdeTTE Cohort Study" 
Dimension 320 KB – PDF File

EUPHA meeting - Rome - 20-22 November 2003 (provisional data, not to be cited). "VedeTTe - Effectiveness of treatments for heroin addiction. A cohort study in Italy"        Dimension 191 KB – PDF File



The VEdeTTE 1bis study


This was a two-year extension of the VEdeTTE 1 study.

Objectives

-    To enlarge the VEdeTTE cohort through the enrolment of heroin or cocaine addicted subjects entering the NHS treatment centre for the first time (incident patients)
-    To continue the collection of data about treatments for all patients enrolled in the VEdeTTE cohort.

A parallel study of infectious diseases involved the subjects enrolled in the VEdeTTE 1bis study. The objectives of this parallel study were: to evaluate the frequency of testing for infectious diseases among this type of patients; to calculate the incidence of HIV, HBV, HCV, TBC and sexually transmitted diseases; to evaluate possible determinants for access to services for the treatment of infectious diseases; to promote half-yearly screening procedures for two years for the cited diseases among new patients of drug abuse treatment centres; to make estimates and analyse scenarios.


Study population

All heroin or cocaine addicted subjects who started treatment at the centre for the first time during this phase were to be asked to participate in the study. Meanwhile, staff at the centres had to continue recording treatments for patients already enrolled in VEdeTTE 1, leaving no gaps between the start of VEdeTTE 1 and the end of the VEdeTTE 1bis study.

The centres could choose between two procedures for recording treatments for patients already enrolled in VEdeTTE 1:

1)   to continue recording treatments for all the patients already enrolled in VEdeTTE       (VEdeTTE 1 "heavy" = maintenance of the whole cohort)

2)   to continue recording treatments only for incident patients already enrolled in VEdeTTE 1 (VEdeTTE 1 "light" = maintenance of a cohort of incident patients).


Time period

In the regions involved in this phase (Piedmont, Liguria, Lombardy, Autonomous Province of Trento, Emilia, Tuscany, Marche, Lazio, Campania, Apulia, Calabria and Sicily), the two-year study took place in different periods between June 2002 and December 2005.


Study instruments

The VEdeTTE 1 study instruments were used, with changes limited to just a few points, in order to comply with new enrolment criteria and suggestions put forward by staff. In particular, a few treatments were added to the Treatment Registration Form: Naloxone (single administration) and buprenorphine (maintenance treatment, detoxification with tapering doses, single administration).

Results

Analysis in progress.


The VEdeTTE 2 pilot study

Objectives

The specific objectives of the pilot study were:

   - to assess the feasibility of the VEdeTTE2 study with regard to the effectiveness of contact procedures and patients’ acceptance rate;
   - to compare the contact rate of external interviewers and NHS drug abuse treatment    centre personnel;
   - to test the acceptability of study instruments (questionnaire, biological sample, monitoring form), among both patients and interviewers; - to evaluate the reliability of self-reported drug use, by comparison with hair test results.

Study population and time period

The pilot study was carried out in the Piedmont region between April and June 2001, involving 10 NHS drug abuse treatment centres. Out of 1,062 patients enrolled in the first six months of the VEdeTTE 1 study, 60 were selected for the pilot study: all new patients and a random sample of re-entry and prevalent patients.

Methods

Detailed procedures were devised to minimize attrition and achieve a good contact rate. If still attending, patients were contacted at the drug abuse treatment centre. If that failed, they were sought at their domicile. Subsequently, research was made in collaboration with relatives, friends and with the General Registry Office. Staff at the treatment centre were required to collaborate with the interviewer in the contact process.

To help patients feel free to answer honestly, they were assigned to interviewers they had never met before, and could choose to be interviewed outside the NHS treatment centre.

To assess the difference in contact rates, about half of the sample were assigned to three external interviewers (29 patients) and three NHS treatment centre personnel (31 patients).

Participating patients were required to provide a sample of nape, axillary or pubic hair. Hair analysis was performed to ascertain the reliability of self-reported drug use in the last month.

Patients were paid, both for the interview (15.49 euros) and for the hair sample collected (36.15 euros).

Interviewers were paid 129 euros for each interview and 15.49 euros for each refusal or loss at follow up.

For more details see Vigna-Taglianti F, Mathis F, Diecidue R, Burroni P, Iannaccone A, Lampis F, Zuccaro P, Pacifici R, Versino E, Davoli M, Faggiano F. A follow-up study of heroin addicts (VEdeTTE2): study design and protocol. Substance Abuse Treatment Prevention Policy. 2007 Mar 15;2(1):9.

Study instruments

The questionnaire consisted of eleven sections. Most of the questions were identical to those in the VEdeTTE 1 Intake Questionnaire, in order to compare any changes that had occurred in the meanwhile. The items investigated were: socio-demographic characteristics (civil status, educational level, accommodation, job); HIV, HBV and HCV and other pathologies as recorded in the case history and as reported by the patient; changes in civil status, educational level and life events since the VEdeTTE1 interview (e.g. marriage, divorce, births); illegal activity; drug use since the VEdeTTE1 interview (frequency, dose, route of administration) and in the last 30 days; overdose; use of legal drugs without a medical prescription; risky behaviour; friendships, financial help, hobbies. Some socio-demographic data were also obtained from clinical records for those subjects who refused to be interviewed or could not be traced. The questionnaire was administered by the interviewer.

The study process was monitored using the Monitoring form made out by the interviewers.

Results

See published article:

Vigna-Taglianti F, Mathis F, Diecidue R, Burroni P, Iannaccone A, Lampis F, Zuccaro P, Pacifici R, Versino E, Davoli M, Faggiano F. A follow-up study of heroin addicts (VEdeTTE2): study design and protocol. Substance Abuse Treatment Prevention Policy. 2007 Mar 15;2(1):9.

For more results see the Italian slides on the “Presentazioni” page.


The VEdeTTE 2 study

Objectives

To evaluate the effectiveness of treatments with regard to:
- long-term legal and illegal drug use;
- overdose;
- family and social re-integration;
- HIV, HBV and HCV morbidity.

Drug abuse treatment centres that participated in the study

All the regions which had participated in the VEdeTTE 1 study and had valid data in the study database were invited to take part in the VEdeTTE 2 study. Piedmont, Tuscany, Campania, Apulia, Calabria and Sicily participated with a total of 41 drug abuse treatment centres.








Study population

The study population of the VEdeTTE2 study consisted of a sample of patients enrolled in the VEdeTTE1 cohort between September 1998 and March 2001: all new patients and a random sample of re-entry and prevalent patients.


Time period

The study took place between February 2003 and December 2006. According to the protocol, the study had to last at least six months. The National Coordinating Centre monitored the enrolment process and decided whether the study should continue over the first six months in order to avoid recruiting only subjects who were still attending the NHS drug abuse treatment centres (patients easier to be contacted).

Methods

Active follow-up of a sample of the VEdeTTE 1 cohort, at least two years after their enrolment in the cohort. The selected subjects had to be traced if still resident in Italy. They also had to be contacted if they were in prison or in a residential therapeutic community.

Data were collected through interview (for all outcomes), by checking clinical records (to verify HIV, HBV and HCV morbidity as well as to record therapeutic treatments), and through collection of a biological sample consisting of nape, axillary or pubic hair (to verify heroin and cocaine use in the last two months, as declared in the interview). As regards the biological sample, morphine and 6-monoacetylmorphine were examined as markers of heroin use; cocaine and its metabolite benzoylecgonine were the markers of cocaine use. The test results were qualitative (positive/negative), with a quantitative measure (ng/mg of hair) for specimens that screened positive or uncertain.

Detailed procedures were devised to minimize attrition and achieve a good contact rate, in an attempt to cover all the possible situations the interviewers could face. If still attending, patients were contacted at the drug abuse treatment centre. If that failed, they were sought at their domicile. Subsequently, research was made in collaboration with relatives, friends and with the General Registry Office. As a last resort, a letter had to be sent three times to the subject’s domicile. Staff at the treatment centre were required to collaborate with the interviewer in the contact process.

To encourage interviewers to obtain the consent of as many patients as possible and to avoid the temptation of only contacting those patients still attending the treatment centres (who were easier to contact), the interviewers received 90 euros for every completed interview, with an extra 100 euros for each additional interview after interviewing 50% of their assigned patients; and 5 euros for each refusal or drop-out.

Since in the pilot study treatment centre personnel had a lower contact rate than external interviewers, in each region treatment centre personnel could represent no more than half of the interviewers, and they were assigned fewer patients (20-25 patients) compared to external interviewers (30-35 patients). To overcome the difficulties in contacting patients in prison, an official statement of collaboration obtained by the Ministry of Justice was cited when contacting prisons.

To help patients feel free to answer honestly, they were assigned to interviewers they had never met before, and could choose to be interviewed outside the NHS treatment centre. To encourage subjects to participate, they were paid 15 euros for the interview and 37 euros for the biological sample.


Study instruments

The questionnaire consisted of eleven sections. Most of the questions were identical to those in the VEdeTTE 1 Intake Questionnaire, in order to compare changes that had occurred in the meanwhile. The items investigated were: socio-demographic characteristics (civil status, educational level, accommodation, job); HIV, HBV and HCV and other pathologies as recorded in the case history and as reported by the patient; changes in civil status, educational level and life events since the VEdeTTE1 interview (e.g. marriage, divorce, births); illegal activity; drug use since the VEdeTTE1 interview (frequency, dose, route of administration) and in the last 60 days; overdose; use of legal drugs without a medical prescription; risky behaviour; friendships, financial help, hobbies. Some socio-demographic data were also obtained from clinical records for those subjects who refused to be interviewed or could not be traced. The questionnaire was administered by the interviewer. A twelfth section was included on a separate sheet, as it was to be filled in by the patient and sealed in a pre-stamped envelope which was sent by regular mail to the National Coordinating Centre. This procedure was adopted for this section as it investigated criminal activity and prostitution. It was hoped that this modality would encourage patients to answer honestly, without fear of legal consequences.

The VEdeTTE 1bis Treatment Registration Form study was used to collect information on treatments from clinical records in order to complete the collection of data covering the entire period between the first treatment received during the VEdeTTE1 study and the VedeTTe 2 interview.

The study process was monitored through two monitoring forms made out by the interviewers. The aim of these forms was to give the coordinators the possibility of monitoring the progress of the study and to provide the interviewers with a diary of what they had already done and what they still had to do.

Results

Analysis in progress.

See published article: Vigna-Taglianti F, Mathis F, Diecidue R, Burroni P, Iannaccone A, Lampis F, Zuccaro P, Pacifici R, Versino E, Davoli M, Faggiano F. A follow-up study of heroin addicts (VEdeTTE2): study design and protocol. Substance Abuse Treatment Prevention Policy. 2007 Mar 15;2(1):9.

For more results see the Italian slides on the “Presentazioni” page.


Contacts

Piedmont Centre for Drug Addiction Epidemiology:

Osservatorio Epidemiologico delle Dipendenze della Regione Piemonte (OED) – ASL 5
Via Sabaudia, 164
10095 Grugliasco (TO) - Italy
Tel. +39 011 40188307
Fax +39 011 40188301
e-mail :studio.vedette@oed.piemonte.it

Working group:
G. Luca Cuomo, Roberto Diecidue, Stefania Difonzo, Fabrizio Faggiano, Federica Mathis, Federica Vigna-Taglianti

Department of Epidemiology, ASL Rome E:

Dipartimento di Epidemiologia ASL RME
Via di Santa Costanza, 53 - Italy
Tel. +39 06 83060440
Fax +39 06 83060463
e-mail:pirasgiovanna@asplazio.it

Working group:
Laura Amato, Anna Maria Bargagli, Valeria Belleudi, Marina Davoli, Giovanna Piras, Patrizia Schifano, Carlo A. Perucci

Department of Clinical and Experimental Medicine, Avogadro University, Novara

Dipartimento di Scienze Mediche - Università del Piemonte Orientale "A. Avogadro"

Via Solaroli 28100 Novara - Italy
Tel: +39 0321 660661
Fax +39 0321 620421
Referece: Prof. Fabrizio Faggiano
e-mail:fabrizio.faggiano@med.unipmn.it

Ministry of Health:

Ministero della Salute – Dipartimento della prevenzione - Dipartimento della Prevenzione e della Comunicazione -
Direzione Generale Prevenzione Sanitaria - Ufficio VII
Viale della Civiltà Romana, 7
00144 Roma - Italy