Penicillin allergy assessment pathway to improve antibiotic use: the ALABAMA intervention development, RCT, process and cost-effectiveness evaluation

Background People with penicillin allergy labels receive more antibiotics, different antibiotics and have worse health outcomes when compared to people without a penicillin allergy label. Objective To determine if a pre-emptive penicillin allergy assessment pathway can remove incorrect penicillin allergy labels, improve antibiotic prescribing and health outcomes, and is cost-effective. Design A multi-work package programme to develop and evaluate a complex intervention (penicillin allergy assessment pathway), including rapid literature review (work package 1.1), behaviour change material development (work packages 1.2 and 1.3), medical record updating processes (work package 1.4), a pragmatic randomised controlled trial (work package 2.1) with nested pilot (work package 1.5), health economic evaluation (work package 2.2) and process evaluation (work package 2.3). Setting English general practices and hospital sites in West Yorkshire, South Yorkshire and Cornwall. Participants Trial participants were adult general practice patients with a record of penicillin allergy. Interview subjects were general practitioners and healthcare workers involved in penicillin allergy assessment, trial and non-trial participants with a penicillin allergy. Interventions Complex intervention involving: identification of appropriate participants, risk stratifying and testing for penicillin allergy, promoting behaviour change and updating medical records. Main outcome measures Penicillin prescribing, total antibiotic prescribing, treatment response failure, duration of symptoms, hospital admission/length of stay, mortality, meticillin-resistant Staphylococcus aureus status and Clostridioides difficile infection, penicillin allergy de-labelling’ rates. People’s views about penicillin allergy and testing. Results Work package 1.1: Our review showed that patients had some worries about penicillin allergy testing but could see advantages. Clinicians were uncertain about referral criteria. Clinicians were wary about prescribing and patients were wary about consuming penicillins after a negative test. Fear of subsequent reactions were drivers. This informed WP1.3 development of resources to aid penicillin allergy assessment. Work package 1.2: Our qualitative research showed that patients were unaware of the benefits of penicillin allergy testing. Experience of negative effects of penicillin allergy labels motivated patients to be tested. Clinicians were reluctant to de-label patients using clinical judgement alone. Clinicians and patients were generally supportive of penicillin allergy testing. This informed work package 1.3. Work package 1.3: Materials were developed to increase knowledge of penicillin allergy testing, support beliefs about the importance of testing, and to increase confidence in performing the behaviours safely by providing a supportive environment. Materials comprised information booklets for general practitioners and participants, electronic health record (SystmOne) pop-ups, post testing result cards, trial work instructions/training material, participant and clinician letters. Work package 1.4: General practitioners were happy to update medical records after a negative test result. ‘Marking in error’ was used to update SystmOne if a participant had a negative penicillin allergy test, which removed allergy alerts but maintained an audit trail. General practitioner trial training/procedures informed general practitioners how to update records. SystmOne functions developed to facilitate de-labelling. Work package 1.5: Target recruitment for the pilot target was achieved. Identification of suitable patients from SystmOne was successful. Willingness of general practitioners to refer patients and participants to undergo testing was demonstrated. A data-secure ‘ALABAMA unit’ was set up within SystmOne. Processes for referring and following-up participants via the ALABAMA unit were established. Low symptom diary completion rate indicated case note data would also be needed. Work package 1.6: During the nested pilot trial, multiple measures were developed, approved and implemented to maximise recruitment for the main trial; including additional testing sites were recruited in South Yorkshire and Cornwall. Work package 2.1: The randomised controlled trial found there was a statistically significant increase in the number of patients de-labelled and penicillin prescribing was statistically significantly increased (adjusted relative risk 5.26) and median total defined daily dose of antibiotics was reduced by 25% in the intervention group. There were no significant differences in other secondary outcomes. Work package 2.2: Within-trial assessment indicated the assessment pathway was likely to be cost-effective. The cost-effectiveness modelling suggested the net benefit of testing was high but uncertainties were high. The value of information studies indicated another trial including health outcomes was worthwhile. Work package 2.3: General practitioners were motivated to join the trial because of perceived benefit to patients. General practitioners were positive about the trial design/delivery and support from the trial team. Many participants sought clarity about penicillin allergy status. Participants reported feeling safe and well looked after during testing. Most participants accepted test results and were relieved to receive a negative test that enabled them to take penicillin. The process evaluation provided important information on how to improve future National Health Service implementation. Specifically, the need for a safe, accessible and reliable service where general practitioners need to be provided with step-by-step guidance how to identify patients with different risk of true penicillin allergy to facilitate onward referral/assessment. The resources developed within the programme could be used as part of wider implementation to encourage and support patients and healthcare workers to engage with and deliver penicillin allergy assessment. Limitations The coronavirus disease discovered in 2019 pandemic affected recruitment and reduced the sample size meaning the primary outcome had to be agreed and changed to an antibiotic prescribing outcome. The research was conducted using functionality developed in SystmOne; there needs to be consideration of how to maximise knowledge transfer this functionality to other electronic health record systems. Conclusion The pre-emptive penicillin allergy assessment pathway was safe, increased penicillin prescribing reduced overall antibiotic prescribing, produced sustained de-labelling and was cost-effective. The assessment pathway was well received by participants and general practitioners. We conclude that patients who are recent users of antibiotics and are lower risk for true penicillin allergy would likely benefit from penicillin allergy assessment. Future work A larger trial is needed to determine if penicillin allergy assessment can improve patient health outcomes. Implementation studies are needed to determine how best to safely embed penicillin allergy assessment into clinical practice and to widen access beyond the current referral guidelines. Trial registration This clinical trial is registered as Current Controlled Trials ISRCTN20579216 and ClinicalTrials.gov NCT04108637. Funding This award was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research Programme (NIHR award ref: RP-PG-1214-20007) and is published in full in Programme Grants for Applied Research ; Vol. 14, No. 11. See the NIHR Funding and Awards website for further award information.