Table 1.

Primary, secondary and other objectives and measures in the main trial

Objectives	Outcome measures	Timepoint(s) of evaluation of this outcome measure
Co-primary objectives
To compare the effect of introducing the behavioural intervention on 30-day mortality post-admission as an acute/general medical inpatient (non-inferiority)	Death, ascertained from hospital records which are routinely updated from national death reporting	30 calendar days after admission to acute/general medicine
To compare the effect of introducing the behavioural intervention on antibiotic exposure per acute/general medical admission (superiority)	Defined daily doses (DDDs) of antibiotics per acute/general medical admission, ascertained from electronic hospital prescribing records	Over each acute/general medical admission, including antibiotics prescribed at discharge
Secondary objectives
To compare the effect of introducing the behavioural intervention on antibiotic exposure using different metrics	DDD per occupied bed-day, days on antibiotics per admission and bed-day (length of therapy (LOT)),a antibiotic days per admission and bed-day (days of therapy, DOTa), carbapenem DDD, DOTa and LOTa (per admission and per bed-day), broad-spectrum DDD, DOTa and LOTa (per admission and per bed-day), IV and oral DDD, DOTa and LOTa (per admission and per bed-day), WHO-defined ’Access’, ’Watch’ and ’Reserve’ DDD, DOTa and LOTa (per admission and per bed-day), ’Access’ as a percentage of all antibiotic use	Over each acute/general medical admission, including antibiotics prescribed at discharge
To compare the effect of introducing the behavioural intervention on adverse outcomes	ICU admission during the current admission, total length of stay (hours), antibiotic restart after discontinuation,a emergency re-admission in the 30 days after discharge, C. difficile diarrhoea, mortality over the longer term	ICU admission over the current admission; for emergency re-admission, up to 30 days post-discharge; for C. difficile diarrhoea, up to 90 days post-admission; for mortality up to 90 days post-admission
To evaluate the impact of the intervention on the faecal flora	Proportion of discarded faecal samples from medical inpatients from which extended spectrum beta-lactamase (ESBL)-carrying Enterobacteriaceae can be isolated	Repeated cross-sectional surveys over time
Tertiary objectives
To evaluate the cost-effectiveness of the behavioural intervention	Resource utilisation and costs	Over the current admission and up to 30 days post-discharge
To quantify uptake and acceptability of the online training component of the behavioural intervention (process outcome)	Proportion of locally identified and pre-specified essential individuals who drive prescribing decisions for acute/general medical inpatients at the organisation who complete the online training (recorded electronically by individuals entering their name and work (NHS) email on the last page) or on an attendance list if the local organisation has opted to do face-to-face training sessions	Within 3 months of invitation to complete training
To quantify uptake of the ARK ‘review and revise’ procedure within the behavioural intervention (process outcome)	Proportion of regularly audited antibiotics prescriptions which document the ARK classification criteria Proportion of regularly audited antibiotics prescriptions which are stopped at ‘review and revise’	Over 12 weeks following implementation date

^aIn organisations with individual electronic prescribing (rather than bulk) antibiotic data

Note: WHO definitions of ’Access’, ’Watch’ and ’Reserve’ antibiotics will be used, following the 2017 Essential Medicines List, using the PHE interpretation. Broad-spectrum is defined as co-amoxiclav; piperacillin/tazobactam; second (e.g. cefuroxime), third (e.g. ceftriaxone ceftazidime) or fourth (e.g. cefepime) generation cephalosporins or cephalosporin-beta-lactamase inhibitor combinations (e.g. ceftazidime-avibactam, ceftolozane-tazobactam); carbapenems; quinolones; azithromycin; tigecycline; aztreonam; and telithromycin. Cefaclor is not included as a second generation cephalosporin because it is administered orally and is not well absorbed