Identifying key priorities for research to protect the consumer with food hypersensitivity: A UK Food Standards Agency Priority Setting Exercise

Abstract Introduction Food hypersensitivity (FHS), including food allergy, coeliac disease and food intolerance, is a major public health issue. The Food Standards Agency (FSA), an independent UK Government department working to protect public health and consumers’ wider interests in food, sought to identify research priorities in the area of FHS. Methods A priority setting exercise was undertaken, using a methodology adapted from the James Lind Alliance—the first such exercise with respect to food hypersensitivity. A UK‐wide public consultation was held to identify unanswered research questions. After excluding diagnostics, desensitization treatment and other questions which were out of scope for FSA or where FSA was already commissioning research, 15 indicative questions were identified and prioritized by a range of stakeholders, representing food businesses, patient groups, health care and academia, local authorities and the FSA. Results 295 responses were received during the public consultation, which were categorized into 70 sub‐questions and used to define 15 key evidence uncertainties (‘indicative questions’) for prioritization. Using the JLA prioritization framework, this resulted in 10 priority uncertainties in evidence, from which 16 research questions were developed. These could be summarized under the following 5 themes: communication of allergens both within the food supply chain and then to the end consumer (ensuring trust in allergen communication); the impact of socio‐economic factors on consumers with FHS; drivers of severe reactions; mechanism(s) underlying loss of tolerance in FHS; and the risks posed by novel allergens/processing. Discussion In this first research prioritization exercise for food allergy and FHS, key priorities identified to protect the food‐allergic public were strategies to help allergic consumers to make confident food choices, prevention of FHS and increasing understanding of socio‐economic impacts. Diagnosis and treatment of FHS was not considered in this prioritization.

The provision of safe food to consumers with FHS is a major priority for the FSA, an independent Government department working to protect public health and consumers' wider interests in food.
The FSA has been a significant funder of FHS-related research in the UK. 4 The FSA's Board requested its Science Council, a group of independent scientific advisers, to undertake a review of its research programme on FHS in 2019 and help inform its future direction in terms of commissioning research.
Research priorities are often developed without wide and coordinated stakeholder contributions. 5 To address this concern, the James Lind Alliance (JLA) has developed a methodology for Priority Setting Partnerships (PSPs), which brings together patients, carers and clinicians to identify and prioritize the evidence uncertainties in any given topic area. 6 The aim of a PSP is to help ensure that those The aim of the PSE was to identify and prioritize the current knowledge gaps in providing safe food to individuals with FHS in the UK from key stakeholder perspectives, including (but not limited to) consumers (both allergic and non-allergic), healthcare professionals, regulators, industry and wider stakeholders. The scope of the PSE included the following: enabling safe food choices for consumers with FHS; practises to handle and produce food safely for those with FHS; and behaviours surrounding food safety with specific reference to FHS. Although the scope of the PSE did not include underlying health delivery (including access to diagnosis and treatment of FHS) as these are not within the FSA's remit, information regarding these issues were collected and reported here, although not included in the prioritization exercise. In reporting this exercise, we have referred to the REPRISE Reporting guideline for priority setting of health research. 9 2 | ME THODS There were 5 stages to the PSE, outlined as follows and in Figure 1: • Initiation and identification of potential stakeholders: a Steering Group made up of members of the FSA Science Council and Secretariat was established to write a protocol, 10 oversee the PSE activity and identify potential stakeholders. The protocol was aligned with JLA methodology as per the JLA Guidebook 6 and finalized in December 2019.
• Identifying knowledge gaps: A UK-wide, online consultation of public stakeholders was undertaken to identify 'unanswered questions' and knowledge gaps (referred to as 'evidence uncertainties') relating to the provision of safe food to consumers with FHS.
• Analysis and formulation of research questions: refinement of responses generated in (ii) to formulate summary questions. This work was contracted to Ipsos MORI and overseen by the PSE Steering Group.
• Prioritization workshop, where the summary questions identified in (iii) were prioritized through consensus, with the input F I G U R E 1 Outline of methodology from representatives of the various stakeholder groups, held in September 2020.
• Development of research questions based on the identified priorities, to help the FSA understand the existing evidence base and thus the need for future research.

| Identification of knowledge gaps and public consultation
Five themes were identified by the Steering Group to provide structure to the PSE: • Eating out: the consumption of food prepared and served away from home, especially at a restaurant, café or take away establishment.
• Buying prepacked food that is food that has been prepared in advance of sale, for example ready meals and packaged sandwiches.
• Handling and Understanding Food-helping consumers to make informed choices about buying safe food, which involves the following: food preparation, labelling, food/ingredient supply, preventing cross-contamination, effective cleaning, testing and monitoring to ensure food safety.
• How we interact with food, including changes in how and where consumers obtain food today, for example new foods and novel allergens, food banks, food business practices, new, reusable and biodegradable packaging and online purchasing through the Internet.

| RE SULTS
The public consultation received 295 responses by the time the survey closed (a month earlier than anticipated, due to COVID- 19) on 26 March 2020, representing a broad group of stakeholders ( Figure 3), 96% of whom were based in the UK. Responses were categorized according to 'tags' (Table 1) which were then used to identify more specific sub-questions. In total, 17 broad themes were generated, with 70 sub-questions within these themes (see Supporting information: Table S1; further details appear in the Ipsos MORI report available online 11 ). Very broadly the questions and issues identified by different stakeholders were similar, although specific types of respondents had slightly greater interest in certain issues.
• Healthcare professionals-allergen contamination (eg due to the use of shared production lines); communication of (potential) allergen presence to consumers, including through labelling and precautionary allergen ('may contain') labels; knowledge and understanding of FHS; and science underlying the development or loss of tolerance resulting in FHS. The Steering Group then reviewed these sub-questions, and after excluding out-of-scope questions or those areas in which FSA is currently commissioning research (Table 2), 15 indicative questions were developed (see supporting information, Table S2) and taken forwards for prioritization at the PSE workshop in September 2020 (virtual meeting, postponed from early 2020 due to COVID). Using the JLA prioritization framework, this resulted in 10 priority indicative uncertainties, from which 16 research questions were developed (Table 3).

| DISCUSS ION
The JLA methodology was originally developed to bring patients and clinicians together in a non-hierarchical manner to identify and address the most important uncertainties with respect to the effects of care and treatments. 12 It has since been used to prioritize questions for research in over 100 clinical areas internationally. We report the outputs from a prioritization exercise using this methodology to highlight priority unanswered questions in terms of providing safe food to consumers with FHS. This is the first research prioritization exercise ever conducted for food allergy and FHS. A major strength is the very significant and comprehensive input from patients/ consumers achieved as a result of the initial public consultation.
Although the focus was on UK consumers, it is likely that many (if not all) of the identified indicative uncertainties would apply elsewhere. Healthcare delivery, including therapeutics, are outside the FSA's remit and were therefore considered out of scope. However, the public consultation demonstrated that these remain priorities for consumers with FHS, and we therefore list these unanswered questions in Table 2. A need to improve diagnostics (accuracy, accessibility) and develop new therapeutics for FHS (including, but not limited to allergen desensitization and interventions targeting the microbiome) are highlighted. Given that respondents were encouraged not to consider issues relating to healthcare provision when completing the public consultation, the list of out-of-scope priorities should not be considered exhaustive, and a future PSP focussed on food allergy management and treatment is justified. We attempted as broad a public consultation as possible, using specific targeting of community charities and religious organizations to capture the inclusion of consumers who might otherwise be excluded, for example children/young people and minority groups. Despite this, it is possible that some groups may have been under-represented. In this respect, it will be interesting to compare the outputs of the ongoing concern to consumers, FBOs and regulators alike. 16  Are staff in food establishments trained in how to use adrenaline autoinjector devices?
Is there a link between childhood eczema and food allergy?
Are food allergies in adults treated with the same seriousness as those in children?
Thresholds for clinical reactivity, that is how much allergen is needed to trigger reactions Is there a link between food poisoning and the development of FHS?
What is the defined safe level of lead in game birds?

Indicative uncertainty Suggested research question(s) Notes
Risks posed to people with FHS by new/novel foods and/or processes In consumers with FHS, what measures are needed to monitor for reactions due to: • new uses of known allergens? • novel proteins which might induce sensitization and thus clinical reactivity?What protocols should the FSA use when assessing the risk to consumers with FHS posed by novel foods/processes/packaging? What data exist as to the likelihood of allergenic proteins in biobased food contact materials migrating into foods?
For example, the use of pea protein in protein concentrates, which is often declared only as 'vegetable protein' in ingredients listing. For example, wheat-based starch in packaging, latex-based binders in packaging and sustainable cutlery.
Improving traceability of allergens in the food supply chain How should information be communicated (through the food supply chain) to consumers with FHS, to: • improve consumer confidence in terms of possible allergen content? • reduce the incidence of unintended allergen exposure?
The sensitivity and reliability of analytical tests was also discussed, but development of these and the responsibility to ensure such tools are used appropriately was felt to be outside the FSA's research remit.
Risks posed due to shared production of foods, and how can these be mitigated What are the health risks to consumers with FHS due to allergen cross-contamination during food production? How effective are different control options (such as cleaning protocols) in reducing these health risks?
For example, the use of shared ovens (eg gluten-free foods cooked in the same oven as gluten-containing foods) Communicating risk, so that consumers with FHS can be confident that the food they are provided is safe What are the most effective ways for FBOs to communicate a level of competence (with respect to allergen risk management) to consumers?
What forms of allergen labelling are effective in order for consumers to make informed decisions as to whether a food is 'safe' for purchase/consumption? ing should be targeted, from the perspectives of the various stakeholders who will be the beneficiaries and end users of FHS research.
The hope is that this will better provide for the significant proportion of the population with FHS and reduce the day-to-day impact of a diagnosis of FHS on patients.