2  Ethics and study administration

2.1 Independent ethics committee

The protocol, the informed consent form and all subject-facing material were reviewed and approved by the independent ethics committee or institutional review board responsible for each participating site before any subject was enrolled. Substantial amendments were submitted for approval before implementation.

2.2 Ethical conduct of the study

The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, the ICH guideline for Good Clinical Practice, and applicable local regulatory requirements.

2.3 Subject information and consent

Written informed consent was obtained from every subject, or from a legally acceptable representative where the subject was unable to provide consent, before any study-specific procedure was performed.

2.4 Study administrative structure

Study conduct was overseen by the sponsor’s clinical development team, with data management, statistical programming and medical writing performed by the sponsor. Statistical analyses reported here were produced with the open-source R packages listed in Appendix B.