2 Research recommendations

The Guideline Development Group has made the following recommendations for research, based on its review of evidence, to improve NICE guidance and patient care in the future. The Guideline Development Group's full set of research recommendations is detailed in the full guideline.

2.1 Designing systems for documenting drug allergy

Which documentation strategies would be most clinically and cost effective to minimise the number of people who are re‑exposed to drugs to which they have a suspected or confirmed allergy, looking in particular at:

  • electronic health records that include features specifically designed to record and alert clinicians to drug allergy information, compared with systems without such features and

  • different formats for patient‑held, structured drug allergy documentation?

Why this is important

Evidence from patient safety incident reports to the National Reporting and Learning System and from published research shows that a large number of NHS patients with known drug allergies are being re‑exposed to these drugs in error each year. Over the past few decades, many people have been inaccurately diagnosed and recorded as either having or not having a drug allergy. While re‑exposure to a drug has not caused harm in the majority of people, a minority of these incidents have caused harm or death.

The systematic review undertaken for this guideline identified a wide range of documentation strategies, including patient‑held records; information worn by patients; hospital‑based notices worn by patients (such as coloured arm bands); automated messages (for example, screensavers); mandatory reporting of drug allergy status in paper or electronic medication records; mandatory documentation of details related to adverse drug reactions; design of drug charts; use of Summary Care Records; and computerised physician or prescriber order entry (CPOE) systems.

Most of the studies included in the systematic review were from the USA and their focus was largely on adverse drug events or medication prescribing errors, and not specifically on drug allergy. In addition, few studies assessed the effectiveness of patient‑held documentation strategies. The quality of the evidence from studies was generally very low. Research is therefore needed to determine which strategy or combination of strategies is most effective in reducing harm by minimising accidental re‑exposure to a known drug allergen.

2.2 Communicating information about drug allergy

In people with suspected or confirmed drug allergies, are patient‑focused information strategies more effective than standard NHS practice in increasing people's likelihood of disclosing their drug allergy (or their suspected drug allergy) and therefore reducing the risk of being re‑exposed to the affected drug?

Why this is important

Administering drugs to which patients have a reported allergy can be fatal, but inadvertent prescription or administration of such drugs is common. Data from the UK General Practice Research Database indicate that the incidence of contraindicated antibiotics being re‑prescribed to patients with suspected penicillin allergy is as high as 48.5%, suggesting that even electronic systems with reminders do not eliminate the risk of inappropriate prescribing. Also, few allergy documentation systems communicate across healthcare organisations, so this information may be lost when patients move to new areas.

Patients and their families and carers have been identified as a resource to prevent inappropriate prescribing. This is in line with the concept of 'patient responsibility' described in the NHS Constitution (2010). Patients and their families and carers are encouraged to be involved in decisions about their care and this includes decisions about drug choice. However, in current practice information is usually not provided unless drug allergy is confirmed by specialists. Suitable information provision is important to encourage people to volunteer their allergy status (be it suspected or confirmed) and make sure that this is appropriately documented by healthcare professionals.

The British Society for Allergy and Clinical Immunology (BSACI) recommends giving patients written details about their allergy, including information on drugs they should avoid. However, it is unclear what factors influence patients to disclose their allergy status to healthcare professionals and what would empower them to do so, to improve safety.

Research is therefore needed to determine which information strategy would be most effective (and preferred by patients) to:

  • increase patients' knowledge about their allergy and ability to remember this information

  • increase patient empowerment and confidence to discuss their drug allergy with healthcare professionals

  • minimise harm from inadvertent re‑exposure to a suspected drug allergen.

2.3 Using selective cyclooxygenase 2 inhibitors in people with previous severe allergic reactions to non‑selective non‑steroidal anti‑inflammatory drugs

Should all patients who have experienced a severe allergic reaction to a non‑selective non‑steroidal anti‑inflammatory drug (NSAID) be assessed by specialist drug allergy services or should they be advised to take a selective cyclooxygenase 2 (COX 2) inhibitor without further investigations if clinically appropriate?

Why this is important

There are about 5.4 million people with asthma in the UK, 1–5% of whom are unable to take non‑selective NSAIDs without developing a severe and sometimes life‑threatening asthma attack. In addition, 0.1–1% of the general population report allergic reactions to NSAIDs with symptoms ranging from urticaria and angioedema to anaphylaxis. NSAIDs are extremely widely used, available over the counter and present within many compound preparations (for example, cold and flu remedies). People who are allergic to NSAIDs are therefore at risk of inadvertent exposure and this presents a significant public health issue.

Commonly encountered NSAIDs such as aspirin, ibuprofen, diclofenac and naproxen are non‑selective COX‑2 inhibitors that block the enzymatic effects of both cyclooxygenase 1 (COX‑1) and COX‑2. More recently introduced NSAIDs include a group which are selective inhibitors of the COX‑2 isoform alone. Studies have shown that the allergic response to NSAIDs is mediated through inhibition of COX‑1 and therefore the majority of people with a history of allergic reactions to non‑selective NSAIDs are able to tolerate selective COX‑2 inhibitors. However, the same studies have also reported that a small proportion of these people also react adversely to selective COX‑2 inhibitors. This group has not been properly characterised and therefore it is not possible to predict who should be offered a selective COX‑2 inhibitor without undertaking specialist drug allergy investigations. This clinical guideline recommends that people who have had a mild reaction to a non‑selective NSAID could be offered a selective COX‑2 inhibitor but that all those who have had a severe reaction, such as anaphylaxis, severe angioedema or an asthmatic reaction, should not be offered a selective COX‑2 inhibitor in a non‑specialist setting.

Well‑designed, appropriately powered, controlled studies characterising people with a history of severe reactions to non‑selective NSAIDs may enable them to have treatment with an anti‑inflammatory without specialist drug allergy investigation.

2.4 Oral antibiotic challenge for diagnosing antibiotic allergy in children

In children who have a suspected allergy to an antibiotic, is it clinically and cost effective to proceed directly (without prior skin or intradermal tests) to a diagnostic oral antibiotic challenge rather than referring them to specialist drug allergy services?

Why this is important

Antibiotics are an important class of drug and one of the most common groups of drugs prescribed to children. Many childhood illnesses are associated with skin rashes, and it can be clinically difficult in the acute setting to be certain if an atypical rash is caused by the underlying illness, the antibiotic, or both. Adverse drug reactions to antibiotics are common and frequently result in a child being diagnosed with 'drug allergy', a diagnosis which generally remains for life.

Current clinical experience suggests that most patients in a community setting who are believed to be allergic to an oral antibiotic (approximately 3% for children, 10–20% for adults) will be challenge 'negative' – that is, they are able to tolerate the oral antibiotic on the day of the challenge and on subsequent days. While patients who are correctly diagnosed with an allergy are kept safe through avoidance, there are health and cost implications for patients who are incorrectly diagnosed with an antibiotic allergy.

The evidence review for this clinical guideline found no evidence to support the reliability of allergy testing (skin, intradermal or IgE determination) for the diagnosis of antibiotic allergy in children. In addition, these tests are painful and restricted to only a few specialist centres in the UK. The result is that only a small fraction of children in the UK with a diagnosis of antibiotic allergy ever undergo investigations to confirm or exclude this diagnostic 'label'. It would therefore be beneficial to prospectively investigate the use of the oral supervised challenge in a safe clinical setting without prior allergy testing. This novel diagnostic approach could be compared with an intervention of 'antibiotic avoidance'.

If the oral antibiotic challenge is found to be safe, acceptable and cost effective, it could be rolled out across all centres that offer paediatric allergy services. This would substantially reduce the number of children who receive a lifelong label of antibiotic allergy.

  • National Institute for Health and Care Excellence (NICE)