Patient-oriented allergy

This month we launch a new call for submissions related to ‘patient-oriented allergy’. These will form part of a special collection, guest edited by Dr Daniel Munblit, who has a special interest in core outcome set development. Some readers may be unfamiliar with the concepts of core outcome sets or patient-oriented allergy. These terms were born out of a recognition that biomedical research has historically been driven by academic or commercial interests that often neglect the priorities of patients. This may seem counter-intuitive, but there is plenty of evidence that patient priorities are overlooked at multiple levels. Even the charities which represent patient interests to organizations such as NICE often find their agenda being influenced by other actors, such as commercial sponsors.¹

Patient-oriented allergy starts with the prioritization of research—what are the most important questions and which projects should be funded? The inclusion of patient voices in these decisions is supported by the work of charities such as the James Lind Alliance, who have developed a methodology for prioritizing research questions in specific disease areas using a partnership approach between patients, clinicians and researchers. In this journal, we recently published the first priority-setting work in food allergy undertaken using James Lind Alliance methodology.² Such exercises often reveal overlooked areas of research, which are important to patients and their carers.

A second focus of patient-oriented allergy is the design of research studies, specifically the outcomes measured in clinical trials. Some outcomes are easier to measure than others, and some are easier to change than others—but the concept of core outcomes is that what is measured as an endpoint in a clinical trial should be something, which is important to people affected by the relevant health condition. In clinical trials of food allergy immunotherapy, for example, we see frequent measurement of thresholds of reactivity and serological markers, which quite reliably change with the intervention but are not a direct measure of patient benefit. There is much less consistent reporting of measures that matter to people with food allergy, such as safety data, quality of life measures and outcomes of accidental exposures in the community—and when measured, the findings related to these outcomes are often less favourable.³ The Core Outcome Measures in Food Allergy (COMFA) consortium chaired by Dr Munblit is a partnership between people with lived experience of food allergy, health professionals and researchers which anyone interested in food allergy can join https://comfa.eu/. COMFA aims to develop a set of core outcomes that should be measured in all food allergy treatment trials, in order to ensure that patient-important outcomes are captured and to make study reports more consistent. There are many other areas of allergy care and research where a patient-oriented perspective can illuminate our field, and we welcome submissions relevant to patient-oriented allergy to Clinical and Experimental Allergy in the coming months.

One specific area where the patient perspective is critical is the development of clinical practice guidelines. This is because guidelines directly influence clinical practitioners and can also be used by commissioners and providers of healthcare, advocacy groups and lawyers as a benchmark for current or acceptable practice. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) group, based at McMaster University in Canada, have established evidence-based methodology, which is the gold standard for guiding clinical practice guideline development. However, many aspects of guideline development remain a matter of judgement, even when the GRADE framework is used—from prioritizing and framing the key questions posed by the guideline to interpreting the evidence and making practice recommendations. It is, therefore, a source of some concern, that few clinical practice guidelines involve patient and public contributors, and many guidelines appear to have significant conflicts of interest, which could serve to undermine patient priorities. Financial conflicts of interest in guideline panel members are almost universal and may introduce unconscious bias into decision-making; such conflicts are also seen in the professional bodies or charities contributing to guideline development. One widely used allergy guideline was found to label 74% of infants with symptoms of milk allergy, in a cohort where less than 1% of infants developed milk allergy—an imbalance which can only benefit those who sell tests or treatments for milk allergy.⁴ It is surprisingly common to still see allergy guidelines not fully state their funding arrangements, or accepting funding from industries that may profit from the recommendations—this includes pharmaceutical company support of asthma, rhinitis and eczema guidelines and formula milk industry support of milk allergy guidelines such as the World Allergy Organization Diagnosis and Rationale for Action against Cow's Milk allergy (DRACMA).⁵

The first step in managing conflicts of interest in guideline development is complete transparency. Our parent society, the British Society for Allergy and Clinical Immunology (BSACI), has a dedicated website where all funding received in the previous calendar year is documented https://www.bsaci.org/about-bsaci/partnership-working/, and BSACI guidelines contain full conflict of interest statements, as do all Clinical and Experimental Allergy publications. This level of transparency is a minimum standard, but the ideal scenario is that clinical practice guidelines should be developed independently of those who might profit financially from the recommendations, and with patient priorities at the core of the guideline development process. This is something for all speciality organizations to strive towards in the future. BSACI guidelines are typically widely disseminated and used beyond the United Kingdom, and often provide pragmatic solutions to evidence-poor areas. In this issue, Dr Isabel Skypala and team present a thorough and practical BSACI guideline for oral allergy syndrome, which is relevant not just to the United Kingdom but to Northern Europe and indeed other temperate areas of the world where silver birch trees are commonly found.⁶ Key recommendations are that for people with seasonal hay fever and typical mild symptoms of oral allergy syndrome with raw foods, no further testing is needed; and the team make specific recommendations for how investigations should be undertaken when they are needed (Figure 1).

Over the past 30 years, publications from high-income countries have repeatedly documented increasing numbers of people labelled as having suffered, or being at risk of, anaphylaxis. This has been noted in rates of hospital admission coded as anaphylaxis, in numbers of people reporting an IgE-mediated allergy and in prescription data for adrenaline autoinjectors.⁷ However, other data have suggested these trends may be mainly related to behavioural change rather than an increase in underlying disease—for example, fatal anaphylaxis rates appear to be stable in these countries, and objective markers of allergy to common anaphylaxis triggers such as peanut, egg or milk also appear to be stable.⁸ In this issue of the journal, Tanno et al report the first comprehensive national dataset for a low- or middle-income country and show a different pattern of anaphylaxis to previous, largely high-income country studies.⁹ In a study covering 9 years of national data in Brazil, a total of over 2 billion person years, they found, like other studies, that hospital anaphylaxis admissions steadily increased—at approximately 2%–3% higher each year over the study period. However, unlike previous studies, they also found an increase in fatal anaphylaxis during the study period. While this increase may have been artefactual—for example, due to improved awareness and ascertainment of anaphylaxis as a cause of death during the past decade—it is the first signal that there may be a real increase in anaphylaxis and its underlying causes in low- or middle-income countries (Figure 2).