During the course of the trial, three substantial amendments to the protocol were submitted to, and subsequently approved by, the Research Ethics Committee (REC).

Substantial amendment 1, dated 6 December 2010 and reviewed 20 December 2010 included:

• Change of investigator at Addenbrooke’s maxillofacial laboratory.
• Clarification of inclusion and exclusion criteria.
• Sections on degree of protrusion and randomisation added to the study plan.
• Clarification of timelines.
• Outcome measures updated.
• Strengths and limitations added as a response to peer-review comments.
• Clarification of adverse event reporting.
• Updating of patient information sheet and patient diaries.

Substantial amendment 2, dated 1 June 2012 and reviewed 26 June 2012 included:

• Increasing number of participants randomised from 90 to a maximum of 96.
• Longer-term follow-up at 1 year and 2 years post-trial completion.
• Extension of current trial end date.
• Minor changes throughout protocol for clarification purposes.

Substantial amendment 3, dated 19 September 2012 and reviewed 16 October 2012 included:

• Removal of a contact from the protocol.
• Change to FOSQ questionnaire.
• Change to sponsor contact.
• Change to follow-up questionnaire.

A fourth substantial amendment was approved by the REC, but the amendment applied to the follow-up questionnaire alone and not the protocol. Substantial amendment 4, dated 1 May 2013 and reviewed 27 May 2013 included:

• Adding an extra question to the follow-up up questionnaire.