Real world safety of methoxyflurane analgesia in the emergency setting: a comparative hybrid prospective-retrospective post-authorisation safety study.

"Declarations Ethics approval and consent to participateThe studies were conducted in accordance with ethical principles of the Declaration of Helsinki, the European Directive 2001/83/EC and the guideline on good pharmacovigilance practices (GVP). The studies were also conducted in accordance with national and local laws of the countries where the study sites were located. According to local country-specific requirements, the protocol and associated documentation were submitted to all required relevant local approving bodies, which included Ethics committees and data protection bodies, as appropriate in each country. Written informed consent was obtained from all patients before enrolment. National ethics committee approval was obtained from the North of Scotland Research Ethics Committee (REC reference number: 16/NS/0057). To enable use of the retrospective data, the study was approved by the Medicines and Healthcare products Regulatory Agency’s Independent Scientific Advisory Committee (protocol number 19_195), and no separate ethical committee approval was required for use of this data. The protocol is available online. The manuscript has been written in accordance with STROBE [19], Good Pharmacoepidemiology Practice [20] and Good Publication Practice guidelines [21]. Consent for publicationNot applicable. Competing interestsMB, MO and SAY are employees of Medical Developments International Pty Limited which manufactures methoxyflurane (Penthrox®). NQ, IM, and AR work at OXON Epidemiology, which was funded by Medical Developments International Pty Limited to conduct all aspects of the study. The independent blinded adjudication committee members were paid for their review of cases by OXON Epidemiology. SP is a statistical consultant for OXON Epidemiology. The chief investigator and principal investigator´s sites were paid for inclusion and follow-up of patients via OXON Epidemiology. Rest all authors have no competing interest. Competing interests MB, MO and SAY are employees of Medical Developments International Pty Limited which manufactures methoxyflurane (Penthrox®). NQ, IM, and AR work at OXON Epidemiology, which was funded by Medical Developments International Pty Limited to conduct all aspects of the study. The independent blinded adjudication committee members were paid for their review of cases by OXON Epidemiology. SP is a statistical consultant for OXON Epidemiology. The chief investigator and principal investigator´s sites were paid for inclusion and follow-up of patients via OXON Epidemiology. Rest all authors have no competing interest."

"Funding The study was sponsored by Medical Developments International Pty Limited. The study sponsor was involved in the study design, data collection, and analysis. The authors had full access to all the data and this manuscript represents their interpretation of the data. Medical Developments International Pty Limited provided financial support for the preparation of the manuscript, including all article processing charges."

"Trial registration Study registered in the EU PAS Register (ENCEPP/SDPP/13040)."