The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia.

BACKGROUND: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results. METHODS: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg-1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals. RESULTS: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm. CONCLUSION: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. CLINICAL TRIAL REGISTRATION: ISRCTN registry: ISRCTN18296119.

Personalised versus standard text message prompts for increasing trial participant response to telephone follow-up: an embedded randomised controlled retention trial.

BACKGROUND: Improving retention within randomised controlled trials is important. The effectiveness of different strategies can be assessed using a Study Within A Trial (SWAT). Previous research has shown personalised text message reminders improve clinic attendance rates; however, the results are mixed on improving postal questionnaire return. This SWAT aims to assess whether personalised text message reminders improve completion rates for scheduled telephone follow-ups. METHODS: This SWAT is a two-arm, multi-centre randomised controlled trial with equal allocation. The host trial was the Melatonin for Anxiety prior to General anaesthesia In Children trial (ISRCTN 18296119), where the child's caregiver was to answer a scheduled telephone follow-up 14 days post-surgery; participants for the SWAT were therefore the caregiver. Text messages were sent 24-48 h before the scheduled call and the personalised version contained the first name of the caregiver which was omitted in the non-personalised version. The primary outcome was questionnaire completion rate, defined as the proportion of caregivers successfully contacted, and completed any of the questionnaires, over the telephone within the follow-up window (day 14 + 7 days). RESULTS: The SWAT included 100 of the 110 (91%) participants randomised into the host trial. Randomisation within the SWAT was equal between non-personalised (n = 50) and personalised (n = 50) interventions. The overall questionnaire response rate was 73% with a difference between the two interventions of 68% in the non-personalised text message arm and 78% in the personalised text message arm. The adjusted absolute risk difference was 7.1% (95% confidence interval = -10.2%, 24.4%). There was no difference in either the time to response or the number of contact attempts between the two interventions. CONCLUSIONS: There is some evidence that personalised text messages could be effective at increasing response rates when data is collected via telephone and in a population of caregivers for paediatric trial participants. However, similar SWATs have shown mixed results. Given the low-cost and low risks associated with personalising text message reminders, this SWAT could be implemented easily in other RCTs scheduling telephone follow-up appointments. TRIAL REGISTRATION: ISRCTN 18296119 , SWAT 35 (MRC Northern Ireland Network for Trials Methodology Network).

Patient advocate involvement in the design and conduct of breast cancer clinical trials requiring the collection of multiple biopsies.

PLAIN ENGLISH SUMMARY: Breast cancer is a diverse and varied disease. Recent research has shown that the collection of multiple biopsies before surgery can help researchers determine how the cancer is responding to treatment and can predict for long-term outcomes. However biopsies can be uncomfortable, and sometimes clinicians and research teams in hospitals may be reluctant to offer clinical trials requiring several biopsies to patients who have been recently diagnosed with breast cancer. The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) oversees a large number of breast cancer clinical trials where multiple biopsies are required. ICR-CTSU recognises that patient advocates (patients who have previously had, or cared for someone with, cancer) are key members of the trial design group and should be involved in the clinical trial throughout its lifespan. Patient advocates can provide reassurance regarding the acceptability of trial designs involving multiple biopsies from a patient perspective. This paper summarises patient advocate involvement in ICR-CTSU breast cancer trials activity and how this has benefited our research. ABSTRACT: The importance of collecting tissue samples in breast cancer has become increasingly recognised, as the diversity of the disease has become better known. It has been documented in recent research that tumours may change in response to treatment prior to surgery (the neoadjuvant treatment setting). The collection of sequential biopsies over time can identify changes within tumours and potentially predict how the tumour may respond to certain treatments. However, the acceptability of multiple biopsies amongst patients, clinicians and other research staff in hospitals is variable and recruitment into clinical trials requiring multiple biopsies may be challenging.The Institute of Cancer Research Clinical Trials and Statistics Unit (ICR-CTSU) is responsible for a portfolio of breast cancer trials where multiple biopsies are key to the trial design. Patient advocate involvement has been essential in helping us to design and deliver complex and innovative cancer trials which require multiple invasive tissue biopsies, often without any direct benefit to the trial participants. The views expressed by patient advocates involved in ICR-CTSU trials supports the published evidence that patients are willing to donate additional tissue for research and that clinicians' concerns about approaching patients for trials involving multiple biopsies are often unfounded.Patient advocate involvement in ICR-CTSU trials activity takes various forms, from membership on protocol development groups and trial management groups, attendance at focus groups and forums, and presentations at trial development and launch meetings. This involvement has provided reassurance to research teams within the NHS and research ethics committees of the importance and acceptability of our trials from a patient perspective. Patient advocate involvement throughout the lifetime of our trials ensures that the patient remains central to our research considerations.