The study was conducted under the provisions of the Declaration of Helsinki, as amended in Hong Kong (1989). The study protocols, patient information form, and informed consent form and procedure were approved by the Central Committee on Medical Ethics of the Netherlands, prior to the start of the study. The study was conducted according to the specifications of the Dutch law and the ICH/EU guidelines for Good Clinical Practice (ICH, 1996). In addition, the central laboratory involved in the study was a CKCL-certified laboratory. The liability for study medication induced injury or damage was arranged in accordance with the Dutch law.

All study data were treated confidentially and processed anonymously. The data could only be made available to the treatment staff, police or the justice system after written consent of the patient. Conversely, the research-assistants could only obtain information about the patient from the treatment staff, police or the justice system after written consent of the patient. If utilized, these data were only used for the purpose of this study, and were treated confidentially. Each subject received a unique identification number, which did not contain initials and/or date of birth. These identification numbers were linked with the name and address of the subject on only one location, and were kept in a safe which could only be accessed by authorization from the study co-ordinator. In the Case Report Forms (CRFs) and other study documents, the subjects could only be identified by their unique identification number. Documents not for submission to the study co-ordinator (e.g. the patient's completed consent forms) were retained at each local treatment site in strict confidence. The CRFs and the subjects' medical records pertinent to the study were regularly reviewed by the independent monitoring organization. In addition, they could also be subjected to review by the study auditor(s), the medical ethics committee, and by representatives of the Inspectorate of Health Care. Any review was conducted with strict adherence to professional standards of confidentiality.

All potential candidates for the study received - in lay terms - extensive written and oral information about the objectives of the study, the study procedures, and the potential benefits, discomforts, and risks related to the study, prior to the start of the qualification period, and again prior to the start of the baseline assessment. The subjects were explicitly informed that they could refuse to participate in the study, or withdraw from the study at any time, without consequences for further care and treatment. At the start of the qualification period, all potential candidates provided provisional written informed consent. Prior to the baseline assessment, all participants signed and dated the final informed consent form.

In addition to urinalyses (which took place monthly), the participants in the study were assessed every two months by means of questionnaires and interviews. For their co-operation with the assessments, each patient received a financial compensation of Dfl. 50,- (EURO 23,-) per assessment (i.e. once every two months), but only during the periods that he/she received methadone alone in the study. This remuneration is comparable to the usual compensations given, and provides an incentive for continued participation, while being insufficient to substantially contribute to maintaining the addiction. Although the patients were not paid for the assessments during the periods that they received co-prescribed heroin, the remuneration of less than one Dutch guilder a day was expected to be too low to jeopardize the contrast between the experimental group and control group in the study. The participants were not required to pay for the prescribed heroin. From a medical-ethical perspective, it is not correct to let a patient pay for a yet unproven medication.