Table 2. Protocol amendments since trial registration.

Amendment Number	Protocol Section	Original protocol	Amended details	Date of Amendment REC/HRA approval	Rationale for amendment
AM02 NSA02	iFraP intervention training Patient identification Nested studies	Omission of iFraP clinical champion role Patient variables described as ‘sex’ and ‘age’ [Interviews with primary care clinicians could be completed in-person or remotely (by telephone or Microsoft Teams)]	Additional detail about Clinical Champion role included Minor changes to variable names: ‘sex at birth’ and ‘age at invite’, update Trial Manager and timeline [Primary care clinician interview method to remove face-to-face option]	Dec 2022	To describe FLS Clinical Champion role and clarify patient variables [The HRA queried the number of GP sites involved in the study – this was not possible to predict given that the location/site of each primary care participant would not be known in-advance. Given the geographical spread of potential primary care practitioners, interviews were likely to be remote.]
AM04 NSA04	Medical record review [Nested studies]	Discontinuation of osteoporosis medicines in medical record review determined by last date of prescription ≥ 6 weeks prior to MRR = yes [A member of the FLS clinical team to upload consultation recording to Keele CTU] [Informed consent for face-to-face interviews to be gained in-person prior to interview]	Additional method of identifying discontinuation in medical records: recorded discontinuation in the patient medical record = yes [An NHS site staff member to upload consultation recordings to Keele CTU] [Informed consent for face-to-face interviews can be obtained in-person or remotely prior to interview]	April 2023	A review of medical records revealed that discontinuation can be explicitly recorded (in addition to only inferring from date prescription filled) [Greater flexibility required so that NHS research teams can support the uploading of consultation recordings, where needed.] [iFraP-i clinicians can consent to interview and consultation recording in one process. Remote consent to additional data collection enables consultation recordings to begin even if the interview has yet to be scheduled.]
AM07 NSA 07	Patient identification	If a patient provides consent to be contacted, Keele CTU send a study recruitment pack containing the consent form and baseline questionnaire, using their preferred method. If the patient does not return the consent form and/or baseline questionnaire within an agreed time window an FLS appointment will be booked, as per normal NHS care.	A courtesy phone call to be made with patients who consent to be contacted but who do not return the consent form and baseline questionnaire within a defined time window. If the patient cannot be contacted by telephone, they will be sent a reminder postcard.	August 2023	When reviewing recruitment rates, there was evidence that a portion of patients were consenting to contact but not returning the consent form and/or baseline questionnaire. This additional telephone call and/or postcard aimed to improve consent rates.
AM08 NSA 08	Patient identification Follow up assessments	Patient identification: At a mid-point in patient recruitment, the Data Monitoring Committee (DMC) will examine the characteristics of the patients recruited to the trial to determine if the sample is representative of the general population. Dependant on results, NHS sites will be asked to adapt their approach to focus recruitment to underserved groups. Follow up assessments: Non-responders to the 2-week and/or 3 month questionnaires will receive their first reminder after approximately 10 days, as per their contact preference.	Patient identification: Flexibility to consider alternative approaches to recruit underserved groups. Follow up assessments: Non- responders to 2-week and/or 3 month questionnaires, whose preference is for online follow ups, will be sent an additional postal reminder if the follow up questionnaire is not returned.	November 2023	The sample at interim review was 100% self- reported White British. In efforts to address this lack of diversity, an additional FLS site joined the trial (from 3 sites to 4 sites). The FLS was chosen because it served a larger proportion of underserved groups, comparatively to other enrolled FLSs. Wording was changed to allow alternative approaches other than asking NHS sites to adapt their approach to focus recruitment to underserved groups, because it was identified that this may be difficult if ethnicity was not recorded well in medical records. Recruitment and follow up rates were identified as lower than expected. Additional postal reminders for those completing online also aimed to improve follow up rates.
AM09 SA09	Sample size	The original target sample size was 328 patients to achieve 200 patients completing the primary outcome at 2 weeks. Patients will be recruited during an 8-month recruitment period. End of study date = September 2024	The amended target sample size is 380 to achieve 200 patients completing the primary outcome at 2 weeks. Patients will be recruited during an 11-month recruitment period. End of study date = May 2025.	February 2024	The original sample target assumed that approximately 32% of patients would not receive a medicine recommendation (hence for whom the primary outcome is not relevant) and for 10% loss to follow-up in the primary outcome at 2-weeks. Resulting in 200 patients completing the primary outcome. When reviewing recruitment and follow up rates with the DMC and TSC, it was identified that 27% of patients did not receive a medicine recommendation, 20% loss to follow-up in the primary outcome at 2-weeks and for 10% loss due to ‘Do Not Attends’ (DNAs). A target sample of 380 was required to meet 200 responses in the primary outcome.

Amendments related to the process evaluation are provided in italics and square brackets.

Amendments 1, 3, 5 and 6 are not included here as they did not have implications for the trial protocol