Close
Window
MEDICAL CO-PRESCRIPTION OF HEROIN
TWO RANDOMIZED
CONTROLLED TRIALS
CENTRAL COMMITTEE ON THE TREATMENT OF HEROIN ADDICTS
This report was prepared by:
Wim van den Brink
Vincent M. Hendriks
Peter Blanken
Ineke A. Huijsman
Jan M. van Ree
© 2002 by Central Committee on the Treatment of Heroin Addicts (CCBH)
Stratenum (fifth floor)
Universiteitsweg 100
3584 CG Utrecht
The Netherlands
ISBN 90-806932-2-7
NUGI 746
All rights reserved. Any part of this report may be reproduced, provided that the reproduction serves a non-commercial purpose, and the source of the report is cited.
Contents:
Letter of submission
Note to the reader
Chapter 1 Background, rationale and objectives of
the study
1.1 Introduction
1.2 Good medical practice
1.3 Illicit heroin use in the Netherlands
1.4 Methadone treatment in the Netherlands
1.5 Prescription of opiates other than oral methadone
in the Netherlands
1.6 Effectiveness of medically prescribed heroin
1.7 Rationale for the study
1.8 Objectives of the study
PART II STUDY DESIGN AND METHODS
Chapter 2 Methods
2.1 Study population
2.1.1 Target population
2.1.2 Selection criteria
2.1.3 Recruitment and selection procedure
2.2 Study design
2.2.1 Randomized controlled trial
2.2.2 Separate trials for injectable and inhalable
heroin
2.2.3 Blinding
2.2.4 Randomization
2.3 Multicenter study
2.4 Stages of the study
2.5 Ethics, informed consent, and remuneration
2.6 Non-adherence to the protocol
2.7 Organization and responsibilities
2.8 Medication and treatment in the study
2.8.1 Objective of the treatment
2.8.2 Prescribed medications
2.8.3 Study supplies and drug accountability
2.8.4 Termination of the co-prescription of heroin
2.8.5 Concurrent treatments
2.8.6 Treatment units and dispensing procedures
2.9 Assessments
2.9.1 Instruments and outcome measures
2.9.2 Timing of the assessments
2.9.3 Primary outcome measure
2.10 Documentation of safety and public order
aspects
2.10.1 Adverse events, and serious/unexpected
adverse events
2.10.2 Public order and controllability
2.11 Data quality assurance
Chapter 3 Data analysis
3.1 Calculation of sample size
3.2 Statistical analysis of the primary study question
3.2.1 Null hypothesis
3.2.2 Primary assessment-points
3.2.3 Study population in the primary analysis
3.2.4 Missing endpoint-assessments
3.2.5 Robustness of the findings
3.2.6 Exploratory analyses of the validity of the
findings
3.2.7 Analysis model and statistical program
3.2.8 Verification of self-report data
3.3 Statistical analyses of the secondary study questions
3.4 Supplementary analyses
PART IIIA STUDY FINDINGS INJECTABLE HEROIN TRIAL
Chapter 5A Selection and disposition of patients
5A.1 Selection procedure
5A.2 Treatment participation and treatment completion
5A.3 Adherence at two-monthly assessments
Chapter 6A Characteristics of the study population
at baseline
6A.1 Intention-to-treat population
6A.1.1 Baseline characteristics
6A.1.2 Inclusion profiles
6A.1.3 Comparability of the treatment groups
6A.1.4 Baseline characteristics across the six
study sites
6A.1.5 Comparison of the study populations in
the injectable and inhalable heroin trials
6A.2 Treatment completers
Chapter 7A Effectiveness of co-prescribed injectable
heroin versus methadone alone treatment
7A.1 Treatment response after 12 months
7A.1.1 Treatment response after 12 months in
the intention-to-treat population
7A.1.2 Treatment response after 12 months among
the treatment completers
7A.2 Treatment response after six months
7A.3 Exploratory analyses of effectiveness
7A.3.1 Improvement and deterioration as components
of treatment outcome
7A.3.2 Response at subsequent assessments
7A.3.3 Relative contribution of the outcome domains
to response
7A.3.4 Sustained response
7A.3.5 Patients no longer meeting inclusion thresholds
of the trial
7A.4 Consequences of discontinuing the co-prescribed
heroin treatment
Chapter 8A Safety of co-prescribed injectable
heroin treatment
8A.1 Focus of the evaluation
8A.2 Serious adverse events in the experimental
treatment phase of the trial
8A.3 Drug overdoses, psychoses and seizures during
the experimental phase
8A.4 SAEs, drug overdoses, psychoses and seizures
following the
discontinuation of co-prescribed heroin treatment
PART IIIB STUDY FINDINGS INHALABLE HEROIN TRIAL
Chapter 5B Selection and disposition of patients
5B.1 Selection procedure
5B.2 Treatment participation and treatment completion
5B.3 Adherence at two-monthly assessments
Chapter 6B Characteristics of the study population
at baseline
6B.1 Intention-to-treat population
6B.1.1 Baseline characteristics
6B.1.2 Inclusion profiles
6B.1.3 Comparability of the treatment groups
6B.1.4 Baseline characteristics across the six
study sites
6B.1.5 Comparison of the study populations in
the injectable and inhalable heroin trials
6B.2 Treatment completers
Chapter 7B Effectiveness of co-prescribed inhalable
heroin versus methadone alone treatment
7B.1 Treatment response after 12 months
7B.1.1 Treatment response after 12 months in
the intention-to-treat population
7B.1.2 Treatment response after 12 months among
the treatment completers
7B.2 Treatment response after six months
7B.3 Exploratory analyses of effectiveness
7B.3.1 Improvement and deterioration as components
of treatment outcome
7B.3.2 Response at subsequent assessments
7B.3.3 Relative contribution of the outcome domains
to response
7B.3.4 Sustained response
7B.3.5 Patients no longer meeting inclusion thresholds
of the trial
7B.3.6 Underreporting of illegal drug use and
treatment effect
7B.4 Consequences of discontinuing the co-prescribed
heroin treatment
Chapter 8B Safety of co-prescribed inhalable heroin
treatment
8B.1 Focus of the evaluation
8B.2 Serious adverse events in the experimental
treatment phase of the trial
8B.3 Drug overdoses, psychoses and seizures during
the experimental phase
8B.4 SAEs, drug overdoses, psychoses and seizures
following the discontinuation of co-prescribed heroin treatment
PART IV FEASIBILITY OF HEROIN ON MEDICAL PRESCRIPTION
Chapter 9 Public order and controllability
9.1 Focus of the evaluation
9.2 Events not attributed to individual patients
9.3 Events in the trial on injectable heroin
9.4 Events in the trial on inhalable heroin
Chapter 11 The costs of medical co-prescription of heroin
PART V CONCLUSIONS AND RECOMMENDATIONS