Appendix 18Summary of protocol changes

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.