Study design
This study is a clinical multicentre observational study of participants in HAT with a duration of three years and planned assessments at baseline, 4, 52, 104 and 156 weeks. All patients interested in receiving IN DAM in HAT were eligible for participation. Consenting participants switched to IN DAM from PO, IM, or IV DAM (treatment as usual) or initiated IN DAM in addition to DAM in other routes of administration. The HAT setting was not altered. Adjustments of DAM dose and route of administration remained an individual decision of patients and prescriber and was independent from study procedures. All patients were followed up regardless of further changes in route of administration of DAM.
Nasal DAM prescription
Initial conversion to nasal doses was calculated using factors of 1.3 for IV DAM and 0.75 for PO DAM derived from available pharmacokinetic data [13, 15, 16, 20], clinical expertise (JS, MV) and currently used factors for conversion of PO and IV DAM in Swiss HAT. Standardised DAM doses for reporting in this paper corresponded to oral morphine equivalent doses and were calculated using a factor of 1 for PO DAM, 2.0 for IV and IM DAM and 1.3 for IN DAM. Sterile DAM solution (100 mg/ml) was used in syringes with screw-on atomisers (Fig. 1). Atomisers were personalised, disinfected following each administration and replaced every seven days.
Recruitment
Recruitment started in December 2020 and is ongoing. Participants included in this study were recruited from ten Swiss HAT centres (Baar, Basel, Bern, Lausanne, Olten, Reinach, Schaffhausen, Solothurn, Winterthur, Zurich) during routine clinical practice by qualified staff. Inclusions took place after the shared decision to start IN DAM was made by participants and providers, fully independent from study procedures. Informed consent was obtained after participants had been explained the study procedures and had been given the opportunity to ask questions and consider the study. Participants received compensation for time and inconvenience (CHF 40.-) for each of the assessments completed (baseline and week 4 follow-up). Compensation was paid in cash at the end of each assessment, corresponding to a total amount of CHF 80.-. The Federal Office of Public Health provided an exceptional authorisation for off-label IN use of DAM for the time of study conduction. Since study initiation, no applications for IN DAM use outside of the study were made, meaning that all patients receiving IN DAM in Switzerland after December 2020 were successfully recruited for participation.
Inclusion and exclusion criteria
Inclusion criteria comprised ability to give informed consent, participate in HAT, and wish to receive IN DAM. Entry criteria for HAT in Switzerland include being at least 18 years old, a history of severe opioid dependence of more than two years, having failed at least two conventional treatments for opioid dependence and having documented social or health problems related to opioid dependence. Patients with severe cognitive impairment (e.g. dementia), precluding the completion of the self-report forms/questionnaires, as well as those with insufficient language proficiency were excluded. We excluded four participants from the analyses, because they were already in IN DAM treatment before the study began.
Assessments
Sociodemographic and medical characteristics were retrieved through electronic medical records (EMRs), interviews, and patient self-report. The last four weeks of DAM prescriptions by route of administration, and both scheduled and realised dispensings were assessed at baseline and four-week follow-up using EMRs.
At baseline, each patient provided the reasons for the switch from their previous route of administration to IN DAM. A series of predefined reasons were available, but participants were also able to expand in their own words. Participants were able to provide as many reasons as they deemed accurate.
Treatment retention for IN DAM was assessed by comparing DAM prescription at baseline to the follow-up assessment at 4-weeks using EMRs. Patients were also asked what their future intentions were regarding the route of administration of their DAM prescriptions.
Given the IN administration, patients’ perceived physical problems relating to their nose and nasal cavity were assessed at baseline and at the four-week follow-up in yes/no form (nasal congestion, runny nose, burning or itching nose, nose pain, epistaxis, and reduced or altered sense of smell).
All assessments were conducted by clinicians working at the respective treatment centre. While filling in self-report forms, participants could ask clarifying questions at any time.
Statistics
Descriptive statistics were used for sociodemographic characteristics, medical history, reasons for IN DAM, prescription and dispensing history, four-week retention, and nose-related problems. No inferential statistics were conducted. Statistical analyses were conducted with SPSS version 28 (IBM Corp., Armonk, NY, USA).