INSTITUT FUR SUCHTFORSCHUNG [seal] INSTITUT FOR SOZIAL- UND
IN VERBINDUNG MIT DER UNIVERSITAT ---- PRAVENTIVMIEDIZIN DER
PROGRAMME FOR A MEDICAL PRESCRIPTION
FINAL REPORT OF THE RESEARCH REPRESENTATIVES
Ambros Uchtenhagen, Felix Gutzwiller and Anja Dobler-Mikola (Eds.)
SUMMARY OF THE SYNTHESIS REPORT
Summary of the synthesis report
The Medical Prescription of Narcotics Programme (PROVE) was designed
according to scientific tenets and criteria. A detailed research protocol
was drawn up to govern the three year collection of data for analysis. It
also describes the methods and times of the data collection as well as the
rules governing data transfer and data protection. Data collection began on
1 January 1994 and ended on 31 December 1996.
The objectives of the study concern the effects of the prescribed
narcotics: the effects on the health, social integration and dependent
behaviour of the research participants; the suitability of this treatment
for heroin dependents whose previous therapy had been unsuccessful; and
the effectiveness of this treatment compared with that of other therapies
The general conditions for the conduct of the programme are described in
the programme's research plan of 1 November 1993, based on the Swiss
government decree of 21 October 1992. They set out the admission
criteria for patients, the modalities of treatment and safety regulations.
The admission criteria stipulated a minimum age of 20 years, a history of
heroin dependency of at least 2 years, and participation in other
treatments had to have failed on several occasions. An indication of the
adverse affects of drug use on health and/or social relations also had to
be present. The injections of prescribed narcotics had to be given under
supervision and injectable narcotics could not be taken home. The
treatment had to involve the provision of psychosocial care as well as the
prescription of narcotics.
In accordance with the government decree, the narcotics to be tested in
the programme were morphine, methadone and heroin for intravenous and
oral use. In addition, use of the cigarette form of heroin was examined,
and a pilot study was conducted based on the use of cocaine cigarettes.
The research issues which were to be analysed, therefore, span a wide
range of topics relating to the pharmacology and toxicology of the
prescribed substances; the participants' state of health lifestyle and
dependent behaviour; the practicability of the study and its economic
Research plan and organisation
A research plan governing the distribution of the different narcotics
amongst the patients was drawn up to deal with these issues. Two double
blind studies (the prescribed substance is not known to either the patient
or the therapist), three randomised studies (treatment is allocated by
randomisation) and eleven studies with individual indications (treatment
is allocated after discussion with the patient) were set up. The feasibility
of each was tested on three occasions in a methadone outpatient clinic
and once in a penal institution. One treatment centre was allocated the
prescription of intravenous and oral methadone only. On the basis of
initial treatment findings, the original plan for the distribution of
treatment places was modified; this, however, did not necessitate any
amendments to the research protocol itself. A second series of additional
treatment centres was approved in order to increase the scope of the
A total of 18 treatment centres were approved; one was in a penal
institution, the others were all outpatient clinics. They were located in
Basel, Berne, Biel, Fribourg, Geneva, Horgen, Lucerne, Olten, St Gallen,
Solothurn, Thun, Wetzikon, Winterthur, Zug and Zurich. One application was
withdrawn, one refused, and one approved treatment centre was not, in the
event, set up.
In view of the large number of treatment centres involved and the range of
research issues to be addressed, a clear organisation of the research,
including uniform rules about powers and responsibilities as well as the
flow of data, was needed. A particularly rigorous audit of the programme's
research procedures was also required. An independent research team
were mandated the tasks of devising the research protocol, data
collection procedure and analysis, and the write-up of reports. Even before
the start of the study, the programme's research protocol and research
plan had been submitted to the supraregional Ethics Committee of the
Swiss Academy of Medical Sciences for approval. Similarly each individual
treatment centre had obtained the prior approval for its project from a
regional or local ethics committee. The Federal Data Protection Officer
checked that the relevant provisions were observed. In addition, a national
specialist group was established to oversee and
assess the activities of the research team. An additional specialist group
(the Safety Assurance Group) was responsible for checking and analysing
in detail any side-effects of the prescribed substances.
At the request of the INCB (International Narcotics Control Board), an
international specialist group was appointed by the World Health
Organisation to appraise the overall research programme and results.
Overview of research studies and data sources
This summary report incorporates the results of a series of studies
The main study was primarily focused on the participants and their
characteristics on admission, during and on leaving treatment or on
switching to another treatment programme. The information was derived
from periodic interviews with the patients, conducted by specially trained
interviewers. It also includes the daily treatment data on all prescribed
narcotics (recorded electronically at the treatment centres). In addition,
the main study examines the organisation of the treatment centres,
narcotics dispensation, the professional background of the staff and the
problems which arose during treatment. This information was obtained
from periodic interviews with project managers.
Special medical studies examined trials carried out according to
methodological designs (double-blind and randomised studies); side
effects of the prescribed substances; pregnancies which occurred during
treatment; deaths, the pharmacological properties of the heroin injected
and the trial of non-injectable heroin products. The data were collected
and analysed according to the terms outlined in the relevant research
Special social science studies considered the changes in criminal
behaviour, the incidence of offences and of convictions. For this,
information from police records and the central criminal register were
extracted and compared with information obtained from the patient.
Another special study examined the prison-based heroin-by-prescription
Special economic studies were commissioned to determine, firstly, the
costs arising from treatment and, secondly, the economic benefit of
treatment. Additional data were collected for these studies.
Comparison of treatment results are based on systematically recorded
reference data from abstinence-based in-patient treatment institutions in
Switzerland and from methadone substitution treatments in the canton of
Zurich. This has enabled a comparative analysis of the findings after at
least one year's treatment. The randomised study in Geneva provides the
additional data needed to compare the participants' treatment results
with those from other treatment programmes. In addition, a comparative
study is being carried out for patients who have recently entered selected
methadone maintenance clinics.
The analysis of the overall programme is based on the data of the 1,146
patients admitted to the programme who effectively started treatment.
For such cases where all admission data were recorded (n=1,035), 2
cohorts were formed (A admitted before the extension and 8 admitted
after the extension of the study) in order to determine any differences
between the two. By the end of 1996, 350 patients had dropped out of the
study. Electronically recorded data on 403,402 treatment days were
included in the analysis. The in-treatment study was based on the changes
observed during 6, 12 and 18 months of treatment. The permanence of such
changes, however, can only be ascertained after a longer period of time.
For the special studies, the analysis was based on data drawn from
various samples, the size of which varied according to the characteristics
of the study (e.g. according to the observation period and the prescribed
substance). The smallest-sized samples were the pharmacological pilot
studies (in accordance with their governing guidelines).
The summary of results below refers to the substance-related, patient
related and projectrelated research issues.
Recruitment of patients, retention rate (the duration of continuing
participation) and compliance (adherence to the treatment instructions)
were better with the prescription of injectable heroin than with that of
injectable morphine and methadone.
- Of the injectable narcotics used, morphine and methadone
proved to be of limited use; heroin was also more suitable in
therapeutic terms because of its fewer side-effects.
- There are as yet no apparent absolute contra-indications to the
prescription of heroin; particular caution is necessary in cases of
Heroin cigarettes are relatively ineffective (up to 90% of the
is destroyed) and may be replaced by other non-injectable forms (for
example, slow-release tablets).
This summarises the extent to which the designated target group of heroin
dependents could effectively be reached, what changes occurred in their
state of health during treatment, how illicit drug use and social
integration among patients in the programme developed, and what changes
were observed in criminal behaviour.
- The programme was able, to a greater extent than other
treatments, to reach its designated target group: those with chronic
heroin dependency, a history of failed attempts with other forms of
treatment and marked deficiencies in terms of health and social
- Those patients admitted to the project who had previously
been following methadone substitution treatment had continued to
use illicit heroin to a large extent during their methadone treatment.
Development of the state of health
- The improvements in physical health which occurred during
treatment with heroin also proved to be stable over the course of
one and a half years and in some cases continued to increase (in
physical terms, this relates especially to general and nutritional
status and injection-related skin diseases).
- In the psychiatric area, depressive states in particular
continued to regress, as well as anxiety states and delusional
- Pre-existing HIV infections were referred for suitable medical
treatment in the majority of cases; the same applied to other
clinically apparent infectious diseases.
- Three new HIV infections, 4 hepatitis B infections and 5
hepatitis C infections occurred during the study (in a total of 11
people). This was very probably related to cocaine injected outside
- The pregnancies and births which occurred during treatment
were adequately supervised and progressed normally (with the
exception of one spontaneous miscarriage during heroin withdrawal);
there were no indications of developmental defects in the neonates.
- Illicit heroin and cocaine use rapidly and markedly regressed,
whereas benzodiazepine use decreased only slowly and alcohol and
cannabis consumption hardly declined at all.
- In a minority of patients, the continued regular use of cocaine
(5%) and benzodiazepines (9%) even after 18 months of treatment
constituted a difficult therapeutic problem to manage.
- The participants' housing situation rapidly improved and
stabilised (in particular, there were no longer any homeless).
- Fitness for work improved considerably; those with permanent
employment more than doubled (from 14% to 32%), and the number of
unemployed fell by more than a half (from 44% to 20%); the
remainder lived on benefits or irregular employment or were
engaged in housework.
- Debts during the treatment period were constantly and
- A third of patients who, on admission, were dependent on
welfare required no further support; on the other hand, others turned
to welfare support (as a result of the loss of illicit income).
- Contact with drug dependents and the drug scene declined
massively, but was not adequately replaced by new social contacts
during the observation period.
- Income from illegal and semi-legal activities decreased
dramatically: 10% as opposed to 69% originally.
- Both the number of offenders and the number of criminal
offences decreased by about 60% during the first six months of
treatment (according to information obtained directly from the
patients' and from police records).
- Court convictions also decreased significantly (according to
the central criminal register).
In some cases, the improvement in the participants' health and social
situation referred to above occurred soon after the beginning of
treatment, but in others, not until after several months of treatment. The
extent to which early discontinuation of treatment can be avoided
therefore plays a major role. The retention rate in the study, 89% over a
period of 6 months and 69% over a period of 18 months, proved to be above
average compared with other treatment programmes for heroin
An analysis of the drop outs shows:
- More than half of the drop outs switched to another treatment.
- By the end of 1996, a total of 83 people had decided to give up heroin
and switch to abstinence therapy. The probability of this switch to
abstinence therapy grows as the duration of individual treatment
- The longer a patient remains in treatment, the more the rate of drop
outs and exclusions from treatment decreases.
- Severe physical illness, particularly in conjunction with Aids,
is over-represented among drop outs as it leads to hospitalisation.
- Improvements in the social situation which occurred in the
course of treatment persisted for at least six months, whether or
not follow-up treatment was administered.
- The use of illicit drugs increased somewhat after withdrawal
but remained clearly below the initial level; the same applied to
contacts with the drug scene and illicit income.
- Of the 1, 146 patients in the study, 36 had died by the end of
- 17 deaths are attributable to Aids and other infectious
diseases., other causes of death include overdosage of non
prescribed narcotics, suicide and accidents. In the study itself there
were no fatal overdoses.
- Despite a high toll on health, the annual mortality rate of 1% in
the total cohort remains at the lower limit of what is known from
other studies on treated heroin dependents (0.7 to 2.6% per year).
The mortality of untreated patients is markedly higher.
As far as the organisation and operation of the treatment centres is
concerned, the following remarks may be made:
Initially, the main problems lay in recruiting patients in some cases as
well as in financing and in organisational problems in many.
- The treatment centres in the second series, having benefited
from the experience of the first series, had considerably fewer
- No disturbance of note was caused to the local neighbourhoods,
or if so only temporarily.
- Security problems (storage and control of narcotics,
safeguarding against forced entries, etc.) were resolved
- There remained a residual risk of overdosage among patients
who were heavily consuming other drugs at the same time: the
precautions which were taken helped prevent the occurrence of any
Heroin prescription in methadone outpatient clinics
In the eventuality of the possible continuation of heroin-assisted
treatment, we examined to what extent this form of treatment Could be
given in the same institution providing methadone substitution treatment,.
The findings from three treatment centres showed that the accompanying
problems could be overcome and that prescription-based heroin treatment
is completely feasible in the context of polyvalent outpatient clinics.
Heroin prescription in prison
The pilot study of heroin prescription in a prison environment showed that
this procedure required changes (in its operation and in the attitude of
staff), but that the positive findings increasingly took precedence.
Furthermore, it was noted that good collaboration with outpatient
treatment centres could be readily established for the follow-up
treatment of discharged inmates.
Costs and benefits
A detailed examination of the costs arising in the outpatient treatment
centres showed average total costs per patient day of Fr. 51.---, compared
with revenue of on average Fr. 35.--- per patient day (revenue includes
contributions to costs by patients, and contributions from health
insurance funds and the public purse).
- The resultant deficits as a rule were borne by the public purse
and exceptionally by private sponsors.
- The study of the overall economic evaluation of the programme
in terms of a cost-benefit analysis according to detailed bases for
assessment shows an overall economic benefit per patient day of Fr.
96.--- (the greater part relates to savings in criminal
investigations and prison terms, followed by improvements in the
state of health). After deduction of the costs mentioned, this yields
a net economic benefit of Fr. 45.--- per patient day.
On the basis of these results, the report comes to the following
conclusions and recommendations:
- Heroin-assisted treatment is useful for the designated target
group and can be carried out with sufficient safety.
- As a result of above average retention rates, significant
improvements can be obtained in terms of health and lifestyle and
these persist even after the end of treatment of special interest is
the striking decline of criminal activities.
- Such improvements are of great public interest too (prevention
of dangerous infections diseases, struggle against drug-related
- In view of the considerably impaired state of health of
patients on admission to the programme, the mortality rate of 1%
per year is relatively low.
- The economic benefit of heroin-assisted treatment is
considerable, particularly due to the reduction in the costs of
criminal procedures and imprisonment and in terms of disease
- These improvements were achieved subject to the prescription
of heroin as part of a comprehensive programme of patient education
- The same can be said with regard to the general conditions
governing the organisation and operation of the programme, the
safety of participants and others can only be guaranteed by
establishing appropriate supervisory measures
The continuation of heroin-assisted treatment can be recommended for
the indications described in this research and as long as the general
organisational and operational conditions set out in the research protocol
If the programme is continued. the unresolved questions and problems
mentioned in the report should be further examined and elucidated through
scientific research. The treatment itself should be appropriately
monitored. documented and evaluated.
It is apparent from these conclusions that a continuation of heroin
assisted treatment can be recommended for the group targeted by this
programme. provided that it is administered in suitably equipped and
supervised outpatient clinics which meet the general conditions and
criteria as described above.