ImmunoCAP® ISAC and Microtest for multiplex allergen testing in people with difficult to manageallergic disease: a systematic review and cost analysis

Population

Adults and children with difficult to manage allergic disease who are being assessed in secondary or tertiary care settings. Owing to the paucity of available data, studies conducted in populations not specified as polysensitised or having difficult to manage allergic disease were also included. All presentations of allergic disease (respiratory, skin, gastrointestinal, anaphylaxis) were eligible for inclusion. Difficult to mange disease was defined as people who are allergic to two or more allergens and/or have allergies to unknown sources.

Intervention/index test

Multiplex allergen testing:

• ImmunoCAP ISAC 112 and previous generations of ImmunoCAP ISAC (Thermo Fisher Scientific/Phadia AB)

• Microtest (Microtest Matrices).

Comparator

The comparator for this assessment was current standard care, which included allergy-focused clinical history, alternative tests of IgE antibody status (single IgE antibody testing), tests of clinical reactivity (such as skin prick testing or allergen challenge testing) or a combination of these approaches.

Outcomes

• Clinical outcomes (e.g. allergy symptoms, incidence of acute exacerbations, mortality, AEs of testing and treatment, health-care presentations or admissions, HRQoL, patient anxiety/preferences).

• Change to management, that is, change to treatment or treatment plan (e.g. restriction diets, immunotherapies, use of other medications such as corticosteroids, number of allergen challenge tests required).

• Additional diagnostic information – accuracy (sensitivity and specificity) for the prediction of clinical reactivity, as defined by SPTs, allergen challenge tests or response to immunotherapy, plus numbers of participants for whom multiplex allergen testing provided additional information (e.g. allergens component-specific information, cross-reactivities, information on multiple sensitisation), diagnostic yield (number of participants with a definitive diagnosis).

Study design

There were no restrictions on study design. Randomised controlled trials (RCTs), controlled clinical trials, other comparative studies (e.g. ‘before-and-after’ studies) and diagnostic test accuracy studies were eligible for inclusion. Observational study designs were eligible for inclusion only if they reported measures of additional diagnostic information provided by multiplex allergen testing; studies that assessed only concordance between multiplex allergen testing and single IgE antibody testing or other tests were not included.

Protocol change The protocol stated that diagnostic accuracy studies would be included only if they reported both the accuracy (sensitivity and specificity) of multiplex allergen testing for the prediction of clinical reactivity, as defined by SPTs, allergen challenge tests or response to immunotherapy, and the numbers and details of participants for whom multiplex allergen testing provided additional information. No studies of this type were identified. The inclusion criteria were expanded to allow studies that reported direct comparisons of diagnostic accuracy between single IgE testing and multiplex allergen testing, using SPTs or allergen challenge tests as the reference standard. These studies do not address the primary aim of the project, ‘to assess the clinical effectiveness and cost-effectiveness of adding multiplex allergen testing to the investigation of people with difficult to manage allergic disease in secondary or tertiary care settings’, because they provide no information on any additional benefit conferred by the use of multiplex testing. Studies of this type were included with the aim of providing some indication of the performance of multiplex allergen testing, compared with current single IgE antibody testing practice, for predicting clinical response. Data of this type may inform the question of whether or not multiplex testing might, in some circumstances, replace single IgE testing as well as helping to guide possible future research recommendations.

Studies of changes to management, treatment or diagnosis

Seven studies investigated changes to treatment or management outcomes. 32–34,36–40 One very small cohort study,36 with nine participants, assessed the relationship between change in IgE levels (measured by ImmunoCAP single IgE and an unspecified version of ImmunoCAP ISAC before and after a 3-year course of SIT) and the clinicians’ evaluation of the benefit of SIT. The methodological quality of this study36 was assessed using the CASP cohort tool. The remaining studies used a ‘diagnostic before-and-after’ type study design, which compared clinicians’ views and decisions on management, treatment or diagnosis in a single group of patients, before and after access to the results of multiplex allergen testing. The methodological quality of these studies was assessed using a tool designed specifically for this review, which was based on the structure of QUADAS-2. Risk of bias and concerns regarding applicability are summarised in Tables 2 and 3 and Figure 2; full assessments for each study are provided in Appendix 4.

FIGURE 2.

Risk of bias across included ‘diagnostic before-and-after’ studies (change to management or treatment).

The ‘diagnostic before-and-after studies’ were generally poorly reported, resulting in a high number of ‘unclear’ ratings, with all studies rated as ‘unclear’ risk of bias on at least one domain; four of the studies were published as conference abstracts only. 33,34,36,37,40 Two studies33,38 were rated as ‘high’ risk of bias. One study33 was rated as ‘high’ risk of bias for patient selection; participants were selected from a database of children who were receiving special diets in school catering, and reasons for exclusion included ‘no longer allergic’ (according to self-report or nurse interview) and unwillingness to participate because of, for example, fear of needles, lack of trust in tests and multiple previous testing. The second study38 was rated as ‘high’ risk of bias for flow and timing because the standard care comparator differed between participants; all participants received SPT, and single IgE testing was used ‘as required.’ Although this is likely to be representative of standard practice, it remains a potential source of bias when estimating test performance.

Although this review included patients with any allergy, the primary objective was to assess the clinical effectiveness of multiplex allergen testing in people with complex or difficult to manage allergies, in UK health-care settings. Studies that did not specify that they included participants with difficult to manage allergic disease, or describe inclusion criteria which could be considered consistent with this classification (e.g. polysensitised patients), were therefore rated as having ‘high’ concerns regarding applicability. Studies that were conducted in non-UK settings and which assessed allergens considered unlikely to be relevant to UK populations (e.g. aeroallergens associated with Mediterranean countries) were also rated as having ‘high’ concerns regarding applicability. Two studies39,40 were rated as having ‘low’ concerns regarding participant applicability, and in two studies33,37 insufficient reporting details prevented a judgement and therefore they were rated ‘unclear’. The remaining two studies32,38 were rated as having ‘high’ concerns regarding participant applicability: for both this was because the patients were not from the UK and in one study38 patients did not have difficult to manage disease.

The small observational study36 that was assessed using the CASP cohort tool for risk of bias was reported only as conference abstract; therefore, risk of bias was largely unclear owing to lack of study details.

Studies of diagnostic accuracy

Eight studies41–47,49 compared the diagnostic accuracy of ImmunoCAP ISAC to that of alternative investigations (single IgE testing or SPT) to predict clinical reactivity as defined by SPT or OFC testing (the reference standard). The methodological quality of these studies was assessed using the QUADAS-2 tool (summarised in Table 4 and Figure 3). The full QUADAS-2 assessments for each study are provided in Appendix 4.

FIGURE 3.

Risk of bias across included diagnostic studies (accuracy).

The comparative accuracy studies were generally poorly reported; seven42–47,49 of the eight studies were rated as ‘unclear’ risk of bias on at least one QUADAS-2 domain. One study47 was reported only as a conference abstract.

Seven studies41–46,49 were rated as ‘high’ risk of bias on at least one domain. The main potential sources of bias were in relation to participant selection and application of the index test. Five studies41,43–46 were rated as ‘high’ risk of bias for participant selection because they used a diagnostic case–control design, a design likely to produce inflated estimates of test performance, or applied inappropriate exclusion criteria (patients with eczema,44 high levels of single IgE45 or complex allergy43). Five studies41,43–46 were rated as ‘high’ risk of bias for the index test. In all cases this was because diagnostic thresholds were not prespecified, but were optimised using ROC analyses in the same population that was used to assess test performance, an approach that is likely to result in inflated estimates of test performance. Two of these studies41,42 were also rated as ‘high’ risk of bias for flow and timing, because not all the participants were included in the analysis41 or because not all participants received the same reference standard. 42

As was the case for studies of change to management, treatment or diagnosis, studies that did not specify that they included participants with difficult to manage allergic disease or describe inclusion criteria that could be considered consistent with this classification (e.g. polysensitised patients) were therefore rated as having ‘high’ concerns regarding applicability, and studies that were conducted in non-UK settings and which assessed allergens considered unlikely to be relevant to UK populations (e.g. aeroallergens associated with Mediterranean countries) were also rated as having ‘high’ concerns regarding applicability. All eight comparative accuracy studies41–47,49 were rated as having ‘high’ concerns regarding participant applicability because they did not include people with difficult to manage allergic disease, and three of these studies41,43,45 also focused on allergens that were considered unlikely to be fully applicable to the UK.

Study details

Six studies32,33,37–40 assessed the effects of adding multiplex allergen testing to the standard diagnostic work-up (SPT/single IgE) on the management, treatment or diagnosis of patients. One study assessed ImmunoCAP ISAC 112,33 three studies assessed ImmunoCAP ISAC 103,37–39 one study assessed ImmunoCAP ISAC 9632 and the remaining study used an unspecified version of ImmunoCAP ISAC. 40 All six studies32,33,37–40 used a ‘diagnostic before-and-after’ type study design to assess the effects of adding ImmunoCAP ISAC results to the information available to clinicians on their judgements regarding the management, treatment or diagnosis of a given group of patients.

Change to management or treatment

Two studies investigated the use of ImmunoCAP ISAC to guide decisions on the discontinuation of restrictive diets in children with food allergies. 33,40 Both studies were reported as conference abstracts only and hence provided only limited study details and results. Hermansson et al. 33 used a database to identify 199 school children in Härkätie, Finland, receiving special diets in school catering; (confidential information has been removed) (e-mail from Johannes Savolainen, University of Turku, Finland, to Shona Lang, 23 June 2015, personal communication). (Confidential information has been removed) (Johannes Savolainen, personal communication). The Hermansson study33 did not report any information on clinical outcomes following changes to dietary management. Noimark and Harnik40 investigated 12 children selected from patients attending an East London allergy clinic (no details of the selection criteria were reported). Participants were investigated using SPT and/or single IgE, and an unspecified version of ImmunoCAP ISAC. The authors reported that ISAC enabled potential food reintroductions (peanut n = 4, soy n = 2, wheat n = 4), additional to that indicated by single IgE alone; the numbers of potential reintroductions based on standard diagnostic work-up (SPT and/or single IgE) were not reported. No details were reported of which single IgE/SPTs were conducted or which ISAC components were assessed. Noimark and Harnik40 did not report the number of food reintroductions that occurred following testing or clinical outcomes of any changes to dietary management.

Two studies37,38 assessed the views of clinicians on whether or not ImmunoCAP ISAC testing provided information useful in the management of patients. Luengo et al. 37 performed ImmunoCAP ISAC 103 testing in 55 well-characterised, polysensitised patients (as assessed by SPTs and single IgE tests) with various allergies; no details were reported of which ISAC components were assessed or how these were interpreted. Participating clinicians judged that ImmunoCAP ISAC 103 provided new information useful in the management of the patient in 50 (91%) cases. 37 The added value was in the ability of ImmunoCAP ISAC to differentiate between protein homologues and hence to aid in the discrimination of allergens that were cross-immunoreactive rather than those that were responsible for sensitisation. In 34 (62%) cases the clinicians considered that it would have been useful to perform ImmunoCAP ISAC 103 testing before SPT, as several protein homologues can be investigated at once using ImmunoCAP ISAC. 37 Passalacqua et al. 38 investigated 318 consecutive polysensitised (at least two positive SPTs) patients with respiratory allergy in six allergy units in Italy. Participants were initially investigated using clinical history, SPT and single IgE testing (including mites, grass, olive, Parietaria, birch, cypress, ragweed, mugwort, cat and dog dander, Alternaria and Aspergillus) and were assessed using ImmunoCAP ISAC 103 (no details reported of components assessed or interpretation, but cross-immunoreactive allergens were considered); treating clinicians were required to review their diagnosis/treatment based on the ImmunoCAP ISAC 103 results and provide a judgement of the value of any additional information provided. 38 New information was classified as ‘remarkable’ if it could not be obtained using standard diagnostic work-up and could impact upon accuracy of diagnosis or SIT prescription; new information related to patient management was classified as ‘remarkable’ in 299 (95%) cases and ‘to some extent’ (not defined) in 232 (73%) cases. 38

Two studies32,38 investigated the effect on SIT prescriptions of adding ImmunoCAP ISAC testing to the standard diagnostic work-up of people with respiratory allergy. Passalacqua et al. 38 (described above) reported that a SIT prescription was made for 85 new patients, following testing with ImmunoCAP ISAC 103, who would not have received SIT based on standard diagnostic work-up (SPT/single IgE) alone. In addition, the existing SIT prescription was changed in a further three patients, following ImmunoCAP ISAC 103 testing. 38 Sastre et al. 32 investigated 141 people with respiratory allergy (with or without concomitant food allergy) in one allergy outpatient clinic in Spain. SIT indications were initially assessed based on clinical history and SPT (Olea e, Platanus a, Cupressus a, grass mix, Cynodon d, Phragmites c, Artemisia v, Salsola k and Plantago I), blind to the results of ImmunoCAP 96 testing (Ole e1, Cup s1, Cry j1, Pla a1, Pla a2, Phl p1, Phl p5, Phl p4, Phl p6, rPhl p11, Phl p12, Cyn d1, Sal k1, Aln g1, Bet v1, Cor a1.0101, Amb a1, Art v1, Art v3 and Par j2). 32 Clinicians then reassessed SIT indications based on all diagnostic information, including ImmunoCAP ISAC 96 results. 32 Disagreements on the SIT prescription based on standard diagnostic work-up and that based on all information, including ImmunoCAP ISAC, occurred for 79 (54%) study participants; details are reported in Table 5. 32 Neither study reported details of which SIT prescriptions were actually used, or any subsequent clinical outcomes.

Change to diagnostic classification

Two studies investigated the effect on diagnostic classification of adding ImmunoCAP ISAC 103 testing to the standard diagnostic work-up of people with allergic disease. 38,39 Heaps et al. 39 investigated 110 patients, from five UK specialist allergy centres, who had a diagnosis of idiopathic anaphylaxis [based on clinical assessment, SPT, single IgE testing and mast cell tryptase (MCT)]. Study participants were reassessed using ImmunoCAP ISAC 103 and clinicians were asked to score the additional information provided. Information provided by ImmunoCAP ISAC 103 was given the highest score (new heat- and digestion-stable sensitisations found, which were thought to have a strong association with anaphylaxis) for 22 (20%) of participants; however, large numbers of sensitisations that were not thought to be associated with anaphylaxis were also identified (see Table 6 for full details). 39 In addition, for a further 35 (32%) of participants the information provided by ImmunoCAP ISAC was deemed to have identified only additional sensitisations which were not thought to be associated with anaphylaxis. 39 Passalacqua et al. 38 (described above; see Change to management or treatment) reported clinicians’ ratings of the value of additional diagnostic information provided by ImmunoCAP ISAC 103 (see Table 6). In addition, this study38 reported detailed information on changes to diagnostic category using five classifications (see Table 6); the addition of ImmunoCAP ISAC 103 testing resulted in increases in the numbers of people classified as ‘poly sensitised with suspected cross-reactivity’ and the number of people diagnosed with both inhalant and food allergies, as well as facilitating a diagnosis for eight previously unclassifiable patients. 38 Full details are provided in Table 6.

Other

We identified one additional study36 that assessed the relationship between change in IgE levels measured by ImmunoCAP single IgE and change in IgE levels measured by an unspecified version of ImmunoCAP ISAC before and after a 3-year course of SIT, and the clinicians’ evaluation of the benefit of SIT. This study36 included only nine participants who received a total of 31 courses of SIT (no details of diagnosis were reported). The median specific IgE levels, measured by ISAC, decreased from 5.6 ISU/ml at the beginning of SIT to 0.01 ISU/ml at the end of SIT, and this change correlated with clinical benefit of SIT (evaluated by clinicians) (Spearman’s r = 0.46; p = 0.02). 36 Conversely, allergen-specific single IgE measurements did not show a decrease from the beginning to the end of SIT. 36

Summary

The results of studies in this section provide some indication that the addition of ImmunoCAP ISAC to standard diagnostic work-up can change clinicians’ views on the diagnosis, management and treatment of patients. There was some indication that the use of ImmunoCAP ISAC testing may guide decisions on the discontinuation of restrictive diets, the content of SIT prescriptions, and whether or not patients should receive SIT. However, importantly, none of the studies that we identified reported any information on clinical outcomes subsequent to changes in treatment or management based on ImmunoCAP ISAC. Three studies report the usefulness of ImmunoCAP ISAC for discriminating allergens that are structurally similar and are recognised by the same IgE antibody (cross-immunoreactive); this discrimination appears to be particularly useful for identifying the cause of food allergies. The UK-based study on the use of ImmunoCAP ISAC to investigate idiopathic anaphylaxis indicated that the addition of ImmunoCAP ISAC to standard diagnostic work-up may identify a potentially causative agent in previously undiagnosed patients. However, it should be noted that the addition of ImmunoCAP ISAC also resulted in the identification of large numbers of sensitisations that were not considered to be associated with the anaphylaxis, that is, large numbers of clinically false-positive test results or sensitisations associated with other allergic conditions such as rhinitis.

Study details

Six studies41,42,44,46,47,49 were identified which compared the accuracy of ImmunoCAP ISAC to existing diagnostic tests (SPT or single IgE tests) in people with food allergies; two studies43,45 were identified of people with allergies to aeroallergens. None of the studies looked at ISAC 112, two investigated ISAC 103,42,43 one investigated ISAC 89,44 two investigated ISAC 50/5145,49 and three investigated unknown ISAC versions. 41,46,47 The results of the comparative diagnostic accuracy studies are summarised in Table 7.

Diagnosis of food allergy

De Swert et al. 41 investigated soy flour allergy. The diagnostic accuracy of an unknown ISAC version to measure the soy flour component rGly m4 was compared with the single IgE test for the same component and to a SPT for soy flour. Cut-off values were reported separately for each test and OFC testing was used as the reference standard. ISAC had the highest sensitivity, 86% (95% CI 42% to 100%), but the lowest specificity, 80% (95% CI 28% to 100%). The single IgE test and SPT had similar sensitivity (75%) and specificity (100%).

Alessandri et al. 42 investigated allergy to boiled or raw egg. The diagnostic accuracy of ISAC 103, when used to measure three individual egg components (Gal d1 or Gal d2 or Gal d3), was compared with the accuracy of single IgE tests (egg yolk or egg white) and compared with the accuracy of SPTs (egg white extract or raw egg white or boiled egg white or egg yolk extract or raw egg yolk or boiled egg yolk). Cut-off values were reported separately for each test and OFC testing was used as the reference standard. SPT had the highest sensitivity for prediction of allergic response to raw egg white, 88% (95% CI 71.8% to 96.6%), whereas Gal d3 measured using ISAC 103 had the highest specificity, 100% (95% CI 90% to 100%). Results for raw egg were similar to those for boiled egg. In general, single IgE performed similarly to SPT (both measured whole extracts), whereas ISAC 103 gave much more variable results for the three different components measured. No measure of the overall diagnostic performance of ISAC 103 (all components combined) was reported.

Two studies44,49 investigated allergy to cow’s milk and hen’s egg. D’Urbano et al. 44 compared the accuracy of ISAC 89, used to measure two individual components (Gal d1 or Bos d8), to the accuracy of single IgE tests (egg white or cow’s milk). Cut-off values were reported separately for each test and OFC testing was used as the reference standard. Specificity was consistent (96%) for both ISAC 89 components and for cow’s milk and egg white single IgE. Sensitivity values were higher for ISAC 89 components (78% for Bos d8 and 73% for Gal d1) than for the corresponding whole-allergen single IgE tests (41% for cow’s milk and 27% for egg white). When whole-allergen single IgE tests and ISAC 89 were used in series (i.e. ISAC 89 results were considered only in single IgE-negative participants), the combined sensitivity was greater than that for single IgE alone (84% compared with 41% for cow’s milk allergy, and 73% compared with 27% for hen’s egg allergy); specificity was 92% in both cases. Ott et al. 49 compared the accuracy of ISAC 51, used to measure eight individual components (α-casein, β-casein, κ-casein, Bos d4, Bos d5, Gal d1, Gal d2, Gal d4), with the accuracy of single IgE tests (hen’s egg or cow’s milk extract) and to the accuracy of SPTs (native hen’s egg or native cow’s milk). Cut-off values were reported separately for each test and OFC testing was used as the reference standard. The results were very variable between tests. SPT had the highest sensitivity for cow’s milk allergy, 93.6% (95% CI 78.5% to 99%). The ISAC 51 components all had low sensitivity for cow’s milk allergy (ranging from 23.9% to 50% for the five components assessed). Conversely, all five ISAC 51 components had high specificity for cow’s milk allergy (ranging from 88.4% to 97.7%), whereas SPT had low specificity, 48.2% (95% CI 28.7% to 68%). Single IgE testing had the highest sensitivity for hen’s egg allergy, 71.1% (95% CI 55.7% to 83.6%). All three ISAC 51 components had low sensitivity (ranging from 17.8% to 57.8%) and high specificity for hen’s egg allergy; the individual specificities of the ISAC 51 components were 100% for Gal d4, 86.7% for Gal d1 and 80% for Gal d2. Single IgE testing and skin prick testing had comparable specificity (86.7% and 100%, respectively). No measure of the overall diagnostic performance of ISAC 51 (all relevant components combined) was reported for either cow’s milk or hen’s egg allergy.

Sokolova et al. 46 investigated milk allergy. The diagnostic accuracy of an unknown ISAC version, used to measure nine individual components (Bos d 4, Bos d 6, Bos d 7, Bos d 8, casein α-S1, casein β and casein κ, Bos d lactoferrin, Bos d 5.0101), was compared with the accuracy of single IgE tests for four allergens (whole milk, α-lactoalbumin, ββ-lactoglobulin and casein). For both methods, a positive result was defined as positive for at least one component or whole allergen; the cut-off values used to define positivity for individual components and allergens were not reported. OFC testing was used as the reference standard. Both combined ISAC testing and combined single IgE testing had 100% sensitivity; however, ISAC testing had much higher specificity, 91.7% (95% CI 73% to 99%), than the single IgE testing, 37.5% (95% CI 18.8% to 59.4%).

Albarini et al. 47 investigated hazelnut allergy. The diagnostic accuracy of an unknown ISAC version, used to measure four individual components (Cor.a.1.1010, Cor.a.1.0401, Cor.a.8, Cor.a.9), was compared to the accuracy of single IgE tests (hazelnut) and to SPT. Cut-off values were not reported for the ISAC test. OFC testing was used as the reference standard. Both the SPT and the single IgE test had 100% sensitivity, whereas the ISAC components generally had low sensitivity (ranging from 6.3% to 56.3%). However, the ISAC components had higher specificity (ranging from 73.7% to 100%) than either single IgE (21.1%) or skin prick testing (52.6%).

Diagnosis of aeroallergy

Wöhrl 200645 investigated five different aeroallergens (HDM, cat dander, birch pollen, grass pollen and mugwort pollen). The diagnostic accuracy of ISAC 50, used to measure the presence of one or more aeroallergens (up to five), was compared with the accuracy of single IgE tests of whole allergens. Where multiple ISAC components were assessed, a positive result was defined as positive for at least one component. The cut-off points for each test were not reported. Skin prick testing was used as the reference standard. The specificity of ISAC 50 was high for all aeroallergens investigated, regardless of whether a single component or multiple components were assessed (range 89.9–98.1%), and, with the exception of mugwort pollen, was comparable to the specificity estimate for the corresponding whole allergen single IgE test for all aeroallergens investigated (see Table 7). The sensitivity of ISAC 50 was lower than that of single IgE tests for HDM, cat and mugwort pollen. The sensitivities and specificities of the individual components ISAC 50 components were not reported.

Cabrera-Freitag et al. 43 investigated two different pollens (grass pollen or Phleum pratense and cypress pollen or C. arizonica). Two cut-off points (manufacturers’ recommended and ROC optimised) were reported per test and SPT was used as the reference standard. The diagnostic accuracy of ISAC 103, when used to measure the eight components for grass pollen (rPhl p1, rPhl p2, nPhl p4, rPhl p5, rPhl p6, rPhl p7, rPhl p11, rPhl p12), was compared with the accuracy of a single IgE test to measure P. pratense; a positive result was defined as positive for at least one component. The sensitivity and specificity for ISAC 103 and single IgE were similar, irrespective of the cut-off point used. Sensitivity and specificity estimates for individual grass pollen ISAC 103 components were not reported. In addition, the accuracy of ISAC 103 was used to measure the presence of a one component for cypress pollen (nCup a1) in comparison with the accuracy of single IgE tests to measure C. arizonica. The sensitivity estimates for the two tests were equal at both cut-off points (91.7%); however, specificity was higher for ISAC 103 at both cut-off points (91.3% and 95.6%) than for the single IgE test (range 80.4–89.1%).

Summary

The diagnostic performance of ImmunoCAP ISAC in comparison with other tests (single IgE and SPT) varied considerably between studies, according to the allergens investigated and the way in which ISAC testing was applied. In general, individual ISAC components tended to have high specificity, but low sensitivity, relative to whole-allergen single IgE tests or SPT for the prediction of allergic response. The relatively low sensitivities of individual ISAC components are likely to be indicative of the proportions of patients in whom each component is associated with the observed allergic response. Conversely, a high specificity is indicative of a strong association between ISAC positivity for the individual component and an allergic response to whole allergen. However, when ISAC was used to measure the same component as single IgE testing or to measure multiple components (homologous proteins), with a positive test defined as any component positive, it appeared that equivalent sensitivities could be achieved without corresponding loss of specificity. The ability of ImmunoCAP ISAC to discriminate between allergens that are structurally similar and are recognised by the same IgE antibody (cross-immunoreactive) may represent clinically useful additional information (see Effects on management, treatment and diagnostic classification of adding multiplex allergen testing to the diagnostic work-up of people with difficult to manage allergic disease, above). Therefore, if the focused use of groups of ISAC components can achieve equivalent sensitivity and specificity to that of single IgE testing, ISAC testing may be preferred.

The results of the only study to investigate serial testing suggested that use of ImmunoCAP ISAC after single IgE testing only in participants who were negative on single IgE could increase sensitivity relative to single IgE alone without any loss in specificity. None of the comparative diagnostic accuracy studies included in this review was conducted in people with difficult to manage allergic disease, and all studies investigated the diagnostic performance of a limited range of ISAC components of a specified allergen. These studies are therefore unable to provide any information on the specificity of the whole ISAC panel when used to investigate people with difficult to manage allergic disease, that is, the extent to which the multiplex allergen testing may produce ‘false-positive’ results by detecting sensitisations that are not clinically relevant. This indicates the importance of using confirmatory tests after the array and that the current array cannot wholly replace OFC or SPT as a diagnostic procedure.

Hermansson 2014

Hermansson et al. 33,34 considered the cost-effectiveness of ImmunoCAP ISAC in addition to a standard diagnostic work-up compared with standard diagnostic work-up without ImmunoCAP ISAC for Finnish school children with a restricted diet as a result of suspected food allergy (community setting). The analysis was informed by 24 children from a larger database (including a total of 2317 school children). The results indicated an unnecessary restricted diet for 63% of the children, resulting in a cost per avoided unnecessary diet of €480 for ImmunoCAP ISAC.

Hermansson 2013 and Hermansson 2012

Another study by Hermansson et al. 54–56 examined the cost-effectiveness of ImmunoCAP ISAC compared with double-blind placebo-controlled food challenge (DBPCFC) and skin prick testing for children with suspected peanut allergy. For this purpose, a Markov model was constructed with a 5-year time horizon. Health states included non-allergic and allergic, and mild and severe allergic reactions were modelled as events. The costs were considered for Sweden, the USA and China. The results indicated that ImmunoCAP ISAC is least expensive, whereas SPT is most expensive, in all three countries. Moreover, ImmunoCAP ISAC was also found to be most effective, leading to 3.97 quality-adjusted life-years (QALYs), whereas the DBPCFC strategy is least effective (2.54 QALYs). Consequently, ImmunoCAP ISAC dominated both the SPT and DBPCFC strategies.

Glaumann 2013

Glaumann et al. 57 examined the cost-effectiveness of ImmunoCAP ISAC compared with DBPCFC, open OFC and SPT for children with suspected peanut allergy in Sweden. A Markov model with a 5-year time horizon was constructed for this purpose. Health states included non-allergic and allergic, and mild and severe allergic reactions were modelled as events. The results indicated that ImmunoCAP ISAC is least expensive, whereas SPT is most expensive. Furthermore, ImmunoCAP ISAC was also found to be most effective, leading to 4.34 QALYs, whereas the OFC strategy was considered least effective (2.23 QALYs). Consequently, ImmunoCAP ISAC dominated all three alternative strategies.

Mascialino 2013 and Hermansson 2012

Mascialino et al. 58,59 and Hermansson et al. 60 examined the cost-effectiveness of ImmunoCAP ISAC with SPT compared with SPT only for Spanish patients sensitised to pollen in a complex pollen area. The analysis was based on a Markov model with a 9-year time horizon and the assumption that patients on specific immunotherapy (SIT) continue this treatment for 3 years and remain healthy for the subsequent 6 years or discontinue SIT and move to symptom management treatment until year 9. The analysis was informed by a data set of 141 patients with allergic rhinoconjunctivitis and/or asthma sensitised to pollen. 32 The results indicated that the addition of ImmunoCAP ISAC to SPT reduces SIT prescriptions and hence results in cost savings compared with SPT only (€2538 vs. €2608). ImmunoCAP ISAC with SPT was also found to be more effective (7.03 QALYs) than SPT only (6.88 QALYs); hence ImmunoCAP ISAC with SPT dominated SPT only.

Decision tree

To inform the decision tree for the diagnostic pathway the following parameters are required:

• proportion of patients who receive a particular test (i.e. SPT, single IgE test, multiplex allergen test and/or OFC test) as well as the number of SPTs and/or single IgE tests per patient

• accuracy of the diagnostic pathways (i.e. proportion of true positives, false positives, false negatives and true negatives as a result of the combined diagnostic performance of SPT, single IgE and/or multiplex testing)

• the treatment decision.

The proportions of patients receiving a particular test and the number of tests per patient are unclear for both the standard diagnostic pathway and the diagnostic pathway including multiplex allergen testing. To alleviate this issue, a survey was sent to clinicians to inform these parameters (see Appendix 6 for the survey). However, no valid responses were received for multiplex allergen testing; the only respondent who indicated having any experience with ImmunoCAP ISAC responded that the number of OFC tests used was too few to comment on. Hence it was not possible to use the survey results in the cost analyses. Moreover, as described in the systematic review (see Effects on management, treatment and diagnostic classification of adding multiplex allergen testing to the diagnostic work-up of people with difficult to manage allergic disease, above), full information on the accuracy of the diagnostic pathways is not available. Finally, information on how treatment decisions relate to the diagnostic pathways is not available. Although two studies examined changes in SIT prescriptions32,38 following the addition of multiplex allergen testing results to standard diagnostic work-up, the results of these studies were not consistent: one study38 described an increase in SIT prescriptions following multiplex allergen testing, whereas the other study32 described a decrease in SIT prescriptions following multiplex allergen testing (see Table 5 for more details).

State-transition model

To inform the long-term state-transition model, the following parameters would be required (all conditional on the test result):

• probability of allergic reactions (might be multiple allergic reactions and population specific)

• probability of remission, and

• probability of dying.

No long-term consequences for multiplex allergen testing were identified in the systematic review (see Chapter 3, Overview of included studies).

Health-state utilities

The evidence on utility values for allergic conditions in the UK population was limited. For food allergies, no utility values were found. For seasonal allergic rhinoconjunctivitis, EuroQol VAS scores from Pitt et al. 68 or EQ-5D scores from a European study63–65 could be taken. Stephens et al. 75 used standard gamble to obtain utility values for atopic eczema in UK children. Only in the study by Stephens et al. 75 were utilities reported per degree of severity of the allergic conditions (see Tables 10 and 11). Utility values for complications of allergies, such as anaphylactic shock, could not be found in the literature, apart from the assumption made by Armstrong et al. 79 that the impact of anaphylactic shock on QoL was equal to zero utility for a duration of 9 days at maximum.

Resource use and costs

To estimate the costs of the individual tests, a detailed cost calculation (see Appendix 7) was performed considering test costs, capital costs (if applicable), service and maintenance costs and personnel costs for performing and interpreting the tests. The results of the detailed test cost calculation are presented in Table 12. For ImmunoCAP ISAC and Microtest testing, the minimum and maximum prices were calculated and subsequently averaged. For ImmunoCAP ISAC testing, the main differences between the minimum and maximum prices can be attributed to the difference in time (between 5 and 60 minutes) that was needed to interpret the test results. This also holds true for Microtest testing, although the range was smaller (between 5 and 10 minutes). Additionally, for Microtest testing it is assumed that the test sample would be sent to the Microtest DX laboratory, where the test would be performed (companies preferred and most conservative scenario), whereas for ImmunoCAP ISAC testing it is assumed that the test would be performed at the service provider laboratory. Hence, for ImmunoCAP ISAC testing capital costs are included while for Microtest testing it is assumed that these costs would be included in the test costs (see Appendix 7). Capital costs are annuitised using a cost discount rate of 3.5%.

Additional costs that would be considered in a long-term cost (-effectiveness) analysis may include the costs of SIT, health-state costs for being at risk of allergic reaction, and health-state costs for having experienced an allergic reaction. These costs are likely to be very specific for the population to be considered. Moreover, different types of SIT might be provided within a specific population (see, for example, the study by Sastre et al. 32). Hence the specific type(s) of SIT prescribed and the SIT duration would be required to calculate these costs (see, for example, the study by Meadows et al. 80 for a calculation of the immunotherapy costs for rhinitis).

Searched: 16 April 2015

1. allergy rapid test/ (334)

2. (ImmunoCAP or Immuno-CAP or Thermo Scientific).af. (2136)

3. ISAC.ti,ab,ot. (497)

4. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (49)

5. (compon$ adj3 resolv$ adj3 diagnos$).af. (545)

6. (multi adj3 compon$ adj3 assay$).af. (14)

7. 23$ allerg$.ti,ab,ot,hw. (52)

8. 26$ allerg$.ti,ab,ot,hw. (52)

9. 103$ allerg$.ti,ab,ot,hw. (35)

10. 112$ allerg$.ti,ab,ot,hw. (21)

11. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (807)

12. or/1-11 (3743)

13. exp microarray analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (138,557)

14. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (5972)

15. or/13-14 (144,221)

16. exp hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (572,729)

17. 15 and 16 (2744)

18. 12 or 17 (6131)

19. limit 18 to yr=“2005-Current” (5244)

Searched: 16 April 2015

1. (ImmunoCAP or Immuno-CAP or Thermo Scientific).af. (465)

2. ISAC.ti,ab,ot. (116)

3. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (9)

4. (compon$ adj3 resolv$ adj3 diagnos$).af. (223)

5. (multi adj3 compon$ adj3 assay$).af. (11)

6. 23$ allerg$.ti,ab,ot,hw. (33)

7. 26$ allerg$.ti,ab,ot,hw. (34)

8. 103$ allerg$.ti,ab,ot,hw. (9)

9. 112$ allerg$.ti,ab,ot,hw. (5)

10. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (520)

11. or/1-10 (1327)

12. exp Microarray Analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (103,970)

13. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (3489)

14. or/12-13 (107,253)

15. exp Hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (373,147)

16. 14 and 15 (1420)

17. 11 or 16 (2648)

18. limit 17 to yr=“2005-Current” (1955)

Searched: 16 April 2015

1. (ImmunoCAP or Immuno-CAP or Thermo Scientific).af. (97)

2. ISAC.ti,ab,ot. (37)

3. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (4)

4. (compon$ adj3 resolv$ adj3 diagnos$).af. (31)

5. (multi adj3 compon$ adj3 assay$).af. (0)

6. 23$ allerg$.ti,ab,ot,hw. (2)

7. 26$ allerg$.ti,ab,ot,hw. (2)

8. 103$ allerg$.ti,ab,ot,hw. (2)

9. 112$ allerg$.ti,ab,ot,hw. (1)

10. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (22)

11. or/1-10 (173)

12. exp Microarray Analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (7177)

13. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (423)

14. or/12-13 (7590)

15. exp Hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (11,416)

16. 14 and 15 (80)

17. 11 or 16 (237)

Searched: 22 April 2015

#6 Search (#4 and #5) (375)

#5 Search ((pubstatusaheadofprint OR publisher[sb] OR pubmednotmedline[sb])) (1,919,020)

#4 Search (#1 or #2 or #3) (2631)

#3 Search ((Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”)) (528)

#2 Search ISAC (373)

#1 Search (ImmunoCAP or Immuno-CAP or Thermo Scientific) (1776)

Searched: 16 April 2015

#1 (ImmunoCAP or Immuno-CAP or Thermo Scientific) (48)

#2 ISAC (20)

#3 (Immuno* near/3 solid* adj3 phase* near/3 allerg* near/3 chip*) (0)

#4 (compon* near/3 resolv* near/3 diagnos*) (5)

#5 (multi near/3 compon* near/3 assay*) (0)

#6 23* near/1 allerg* (46)

#7 26* near/1 allerg* (7)

#8 103* near/1 allerg* (2)

#9 112* near/1 allerg* (1)

#10 (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”) (56)

#11 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 (175)

#12 MeSH descriptor: [Microarray Analysis] explode all trees (275)

#13 (microarray* or micro array* or nanoarray*) (575)

#14 (multiplex near/3 (test* or assay*)) (65)

#15 #12 or #13 or #14 (747)

#16 MeSH descriptor: [Hypersensitivity] explode all trees (15,709)

#17 (allerg* or anaphyla* or hypersensiti* or hyper-sensiti* or poly-sensiti* or polysensiti* or paucisensiti*) (25,363)

#18 #16 or #17 (32,535)

#19 #15 and #18 (39)

#20 #11 or #19 (210)

#21 #20 Publication Year from 2005 to 2015 (147)

• CDSR search retrieved 41 records

• DARE search retrieved 0 records*

• Central search retrieved 104 records

• HTA search retrieved 0 records.

*Please note: Records ceased to be added to the DARE resource on 31 March 2015; this search was for archival material only.

Searched: 23 April 2015

Indexes=SCI-EXPANDED, CPCI-S Timespan=2005–2015

#13 (2626) #12 OR #7

#12 (1312) #11 AND #10

#11 (108,808) TS=(allerg* or anaphyla* or hypersensiti* or hyper-sensiti* or poly-sensiti* or polysensiti* or paucisensiti*)

#10 (105,467) #9 OR #8

#9 (5844) TS=(multiplex NEAR/3 (test* or assay*))

#8 (100,025) TS=(microarray* or micro array* or nanoarray*)

#7 (1450) #6 OR #5 OR #4 OR #3 OR #2 OR #1

#6 (149) TS=(Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”)

#5 (11) TS=(multi NEAR/3 compon* NEAR/3 assay*)

#4 (368) TS=(compon* NEAR/3 resolv* NEAR/3 diagnos*)

#3 (16) TS=(Immuno* NEAR/3 solid* NEAR/3 phase* NEAR/3 allerg* NEAR/3 chip*)

#2 (454) TS=(ISAC)

#1 (581) TS=(ImmunoCAP or Immuno-CAP or “Thermo Scientific”)

Searched: 23 April 2015

Indexes=BIOSIS Previews Timespan=2005–2015

#7 (1282) #6 OR #5 OR #4 OR #3 OR #2 OR #1

#6 (81) TS=(Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”)

#5 (9) TS=(multi NEAR/3 compon* NEAR/3 assay*)

#4 (202) TS=(compon* NEAR/3 resolv* NEAR/3 diagnos*)

#3 (22) TS=(Immuno* NEAR/3 solid* NEAR/3 phase* NEAR/3 allerg* NEAR/3 chip*)

#2 (230) TS=(ISAC)

#1 (914) TS=(ImmunoCAP or Immuno-CAP or “Thermo Scientific”)

Searched: 22 April 2015

Searched: 23 April 2015

Browsed with the following terms.

Searched: 23 April 2015

Searched Medical Devices.

Searched: 22 April 2015

Searched: 22 April 2015

Advanced search option – search terms box.

Searched: 22 April 2015

Advanced search – Text Search.

Searched: 22 April 2015

Advanced search option.

Searched: 19 May 2015

Searched for last 5 years.

Used “search within this issue” option and exported results for articles only:

2015: www.jacionline.org/issue/S0091-6749%2814%29X0003-5

2014: www.jacionline.org/issue/S0091-6749%2813%29X0015-6

2013: www.jacionline.org/issue/S0091-6749%2813%29X0013-2

2012: www.jacionline.org/issue/S0091-6749%2812%29X0002-2

2011: www.jacionline.org/issue/S0091-6749%2811%29X0002-7

Searched: 19 May 2015

2015: www.professionalabstracts.com/eaaci2015/programme-eaaci2015.pdf

2014: www.sessionplan.com/eaaci2014/

2013: http://onlinelibrary.wiley.com/doi/10.1111/all.2013.68.issue-s97/issuetoc

2012: http://onlinelibrary.wiley.com/doi/10.1111/all.2012.67.issue-s96/issuetoc

2011: http://onlinelibrary.wiley.com/doi/10.1111/all.2011.66.issue-s94/issuetoc

Searched: 19 May 2015

2015: NA – conference had not yet taken place at time of searching

2014: http://onlinelibrary.wiley.com/doi/10.1111/cea.12456/epdf

2013: http://onlinelibrary.wiley.com/doi/10.1111/cea.12197/epdf

2012: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2222.2012.012033.x/epdf

2011: http://onlinelibrary.wiley.com/wol1/doi/10.1111/j.1365-2222.2011.03897.x/abstract

Please note: Unable to access 2011 online without payment.

Searched: 19 May 2015

Searched for last 5 years.

Used ‘Control F’ to search within saved PDFs.

2015: NA – conference not yet taken place at time of search

2014: www.ctajournal.com/supplements/5/S3

2013: www.ctajournal.com/supplements/3/S3

2012: NA – No record on website of having run in that year

2011: www.ctajournal.com/supplements/1/S1

Searched: 20 May 2015

Searched for last 5 years.

Used ‘Control F’ to search within saved PDFs.

2015: Sixth conference had not yet taken place at time of search

2014: NA

2013: www.ctajournal.com/supplements/4/S2/all (5th conference)

2012: NA

2011: NA (Fourth conference 2010)

Searched: 26 May 2015

Searched for last 5 years.

2015: http://onlinedigitalpublishing.com/publication/?m=20143&l=1

2014: http://onlinedigitalpublishing.com/publication/?i=199001

2013: http://onlinedigitalpublishing.com/publication/?i=146375

2012: https://s3.amazonaws.com/aad-meetings/AM12_Program.pdf

2011: www.nxtbook.com/nxtbooks/aad/annualmeeting2011/#/0

Searched: 26 May 2015

Searched for last 5 years.

Used “Search within this issue”.

2015: Conference had not yet taken place at time of search

2014: http://onlinelibrary.wiley.com/doi/10.1111/bjd.2014.171.issue-s1/issuetoc

2013: http://onlinelibrary.wiley.com/doi/10.1111/bjd.2013.169.issue-s1/issuetoc

2012: http://onlinelibrary.wiley.com/doi/10.1111/bjd.2012.167.issue-s1/issuetoc

2011: http://onlinelibrary.wiley.com/doi/10.1111/bjd.2011.165.issue-s1/issuetoc

Searched: 21 May 2015

1. allergy rapid test/ (381)

2. (ImmunoCAP or Immuno-CAP or Thermo Scientific or phadia).af. (2718)

3. ISAC.ti,ab,ot. (517)

4. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (50)

5. (compon$ adj3 resolv$ adj3 diagnos$).af. (567)

6. (multi adj3 compon$ adj3 assay$).af. (14)

7. 23$ allerg$.ti,ab,ot,hw. (52)

8. 26$ allerg$.ti,ab,ot,hw. (53)

9. 103$ allerg$.ti,ab,ot,hw. (35)

10. 112$ allerg$.ti,ab,ot,hw. (22)

11. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (810)

12. or/1-11 (4290)

13. exp microarray analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (140,563)

14. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (6050)

15. or/13-14 (146,303)

16. exp hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (578,447)

17. 15 and 16 (2794)

18. 12 or 17 (6704)

19. health-economics/ (34,457)

20. exp economic-evaluation/ (226,212)

21. exp health-care-cost/ (217,693)

22. exp pharmacoeconomics/ (173,447)

23. or/19-22 (506,020)

24. (econom$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (670,947)

25. (expenditure$ not energy).ti,ab. (26,222)

26. (value adj2 money).ti,ab. (1530)

27. budget$.ti,ab. (26,297)

28. or/24-27 (696,870)

29. 23 or 28 (978,855)

30. letter.pt. (887,374)

31. editorial.pt. (477,247)

32. note.pt. (599,443)

33. or/30-32 (1964064)

34. 29 not 33 (886,862)

35. (metabolic adj cost).ti,ab. (989)

36. ((energy or oxygen) adj cost).ti,ab. (3348)

37. ((energy or oxygen) adj expenditure).ti,ab. (22,162)

38. or/35-37 (25,637)

39. 34 not 38 (881,415)

40. 18 and 39 (197)

Economics terms based on Costs filter

Centre for Reviews and Dissemination. Search strategies: NHS EED EMBASE using OvidSP (economics filter) (internet). York: CRD; 2014 (accessed 2 June 2014).

Available from www.crd.york.ac.uk/crdweb/searchstrategies.asp#nhseedembase

Searched: 21 May 2015

1. (ImmunoCAP or Immuno-CAP or Thermo Scientific).af. (471)

2. ISAC.ti,ab,ot. (116)

3. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (9)

4. (compon$ adj3 resolv$ adj3 diagnos$).af. (225)

5. (multi adj3 compon$ adj3 assay$).af. (11)

6. 23$ allerg$.ti,ab,ot,hw. (33)

7. 26$ allerg$.ti,ab,ot,hw. (34)

8. 103$ allerg$.ti,ab,ot,hw. (9)

9. 112$ allerg$.ti,ab,ot,hw. (5)

10. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (520)

11. or/1-10 (1335)

12. exp Microarray Analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (105,216)

13. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (3540)

14. or/12-13 (108,548)

15. exp Hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (375,235)

16. 14 and 15 (1439)

17. 11 or 16 (2675)

18. economics/ (26,620)

19. exp “costs and cost analysis”/ (187,805)

20. economics, dental/ (1859)

21. exp “economics, hospital”/ (20,266)

22. economics, medical/ (8615)

23. economics, nursing/ (3914)

24. economics, pharmaceutical/ (2572)

25. (economic$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (445,087)

26. (expenditure$ not energy).ti,ab. (18,132)

27. (value adj1 money).ti,ab. (24)

28. budget$.ti,ab. (17,825)

29. or/18-28 (571,847)

30. ((energy or oxygen) adj cost).ti,ab. (2735)

31. (metabolic adj cost).ti,ab. (818)

32. ((energy or oxygen) adj expenditure).ti,ab. (16,789)

33. or/30-32 (19,615)

34. 29 not 33 (567,494)

35. letter.pt. (847,644)

36. editorial.pt. (356,900)

37. historical article.pt. (316,205)

38. or/35-37 (1,505,328)

39. 34 not 38 (538,417)

40. 17 and 39 (67)

Costs filter

Centre for Reviews and Dissemination. NHS EED Economics Filter: MEDLINE (via Ovid) monthly search (internet). York: CRD; 2010 (cited 28 September 2010).

Available from: www.york.ac.uk/inst/crd/intertasc/nhs_eed_strategies.html

Searched: 21 May 2015

1. (ImmunoCAP or Immuno-CAP or Thermo Scientific).af. (95)

2. ISAC.ti,ab,ot. (39)

3. (Immuno$ adj3 solid$ adj3 phase$ adj3 allerg$ adj3 chip$).af. (4)

4. (compon$ adj3 resolv$ adj3 diagnos$).af. (33)

5. (multi adj3 compon$ adj3 assay$).af. (0)

6. 23$ allerg$.ti,ab,ot,hw. (2)

7. 26$ allerg$.ti,ab,ot,hw. (2)

8. 103$ allerg$.ti,ab,ot,hw. (2)

9. 112$ allerg$.ti,ab,ot,hw. (1)

10. (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”).af. (24)

11. or/1-10 (176)

12. exp Microarray Analysis/ or (microarray$ or micro array$ or nanoarray$).ti,ab,ot,hw. (7501)

13. (multiplex adj3 (test$ or assay$)).ti,ab,ot,hw. (453)

14. or/12-13 (7944)

15. exp Hypersensitivity/ or (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (11,612)

16. 14 and 15 (89)

17. 11 or 16 (248)

18. economics/ (0)

19. exp “costs and cost analysis”/ (128)

20. economics, dental/ (0)

21. exp “economics, hospital”/ (8)

22. economics, medical/ (1)

23. economics, nursing/ (1)

24. economics, pharmaceutical/ (0)

25. (economic$ or cost or costs or costly or costing or price or prices or pricing or pharmacoeconomic$).ti,ab. (60,839)

26. (expenditure$ not energy).ti,ab. (1828)

27. (value adj1 money).ti,ab. (3)

28. budget$.ti,ab. (2518)

29. or/18-28 (63,427)

30. ((energy or oxygen) adj cost).ti,ab. (312)

31. (metabolic adj cost).ti,ab. (101)

32. ((energy or oxygen) adj expenditure).ti,ab. (1452)

33. or/30-32 (1820)

34. 29 not 33 (62,936)

35. letter.pt. (32,097)

36. editorial.pt. (21,356)

37. historical article.pt. (131)

38. or/35-37 (53,569)

39. 34 not 38 (62,298)

40. 17 and 39 (8)

Costs filter

Centre for Reviews and Dissemination. NHS EED Economics Filter: MEDLINE (via Ovid) monthly search (internet). York: CRD; 2010 (cited 28 September 2010).

Available from www.york.ac.uk/inst/crd/intertasc/nhs_eed_strategies.html

Searched: 21 May 2015

#1 (ImmunoCAP or Immuno-CAP or Thermo Scientific) (48)

#2 ISAC (20)

#3 (Immuno* near/3 solid* adj3 phase* near/3 allerg* near/3 chip*) (0)

#4 (compon* near/3 resolv* near/3 diagnos*) (5)

#5 (multi near/3 compon* near/3 assay*) (0)

#6 23* near/1 allerg* (46)

#7 26* near/1 allerg* (7)

#8 103* near/1 allerg* (2)

#9 112* near/1 allerg* (1)

#10 (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”) (56)

#11 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 (175)

#12 MeSH descriptor: [Microarray Analysis] explode all trees 280)

#13 (microarray* or micro array* or nanoarray*) (586)

#14 (multiplex near/3 (test* or assay*)) (66)

#15 #12 or #13 or #14 (761)

#16 MeSH descriptor: [Hypersensitivity] explode all trees (15,764)

#17 (allerg* or anaphyla* or hypersensiti* or hyper-sensiti* or poly-sensiti* or polysensiti* or paucisensiti*) (25,504)

#18 #16 or #17 (32,705)

#19 #15 and #18 (39)

#20 #11 or #19 (210)

NHS EED search retrieved 1 record.

*Please note: records ceased to be added to the NHS EED resource on 31 March 2015; this search was for archival material only.

Searched: 21 May 2015

S13 S7 OR S12 (18)

S12 S10 AND S11 (0)

S11 TX(allerg* or anaphyla* or hypersensiti* or hyper-sensiti* or poly-sensiti* or polysensiti* or paucisensiti*) (49)

S10 S8 OR S9 (103)

S9 TX(multiplex N3 (test* or assay*)) (1)

S8 TX(microarray* or micro array* or nanoarray*) (102)

S7 S1 OR S2 OR S3 OR S4 OR S5 OR S6 (18)

S6 TX (Allerwatch or ComforTen or “MultiTest” or “true test” or “Microtest DX” or “Micro Test DX”) (13)

S5 TX (multi N3 compon* N3 assay*) (0)

S4 TX (compon* N3 resolv* N3 diagnos*) (0)

S3 TX (Immuno* N3 solid* N3 phase* N3 allerg* N3 chip*) (0)

S2 TX (ISAC) (5)

S1 TX (ImmunoCAP or Immuno-CAP or “Thermo Scientific”) (0)

Searched: 26 May 2015

IDEAS search interface

#1 (ImmunoCAP | Immuno-CAP | “Thermo Scientific”) (Results 1)

#2 (Allerwatch | ComforTen | “MultiTest” | “true test” | “Microtest DX” | “Micro Test DX”) (Results 17)

RePEc search retrieved 18 records.

Searched: 30 June 2015

1. (food$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (27,518)

2. ((Cereal$ or wheat or rye or barley or oat or oats or rice or maize or spelt or buckwheat or soybean or millet or sorghum or corn or Kamut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2562)

3. ((Gluten or (glutenin adj3 gliadin) or prolamins) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1408)

4. ((Dairy or milk or yog?urt$ or cream or butter$ or cheese$ or ice cream$ or kefir) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (6786)

5. ((Casein or whey or lactose) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (4128)

6. (Egg$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2858)

7. ((Peanut$ or arachid or Arachis hypog?ea or groundnut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (3239)

8. ((ground or earth or monkey) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1)

9. (arachis oil adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

10. ((Nut or nuts or hazelnut$ or cashew$ or walnut$ or pecan$ or almond$ or Macadamia$ or pistachio$ or chestnut$ or coconut$ or Candlenut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1338)

11. ((Brazil or pine or hickory or betel) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (91)

12. ((Crustacea$ or Mollusc$ or mollusk$ or shellfish or seafood or sea food or Lobster or crab$ or shrimp$ or prawn$ or squid$ or oyster$ or crayfish or cuttlefish or abalone or limpet$ or mussel$ or scallop$ or clam or clams or whelk$ or scampi or octopus or langoustine$ or cockle$ or winkles or krill) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1046)

13. ((Fish or finfish or sole or mackerel$ or hake or whiting or dab or plaice or Anchov$ or Catfish or Eel$ or Haddock or Halibut or Sardine$ or Scad or Snapper or Tilapia or Trout or shark or swordfish or cod or tuna or herring$ or flounder or mullet or salmon or kipper$ or caviar or seer or mackerel or tilefish or Pollock or whitebait or flatfish or john dory or carp) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1799)

14. (Fish adj3 roe adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (7)

15. ((Surimi or sashimi or sushi or cerviche or gravlax) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2)

16. ((Snail$ or frog$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (221)

17. ((Sulfites or sulphites) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (55)

18. (((sulphiting adj2 agents) or (sulphur adj2 dioxide)) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (13)

19. ((Lentil$ or chickpea$ or pea or peas or garbanzo or bengal gram or chana or channa or leblebi) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (132)

20. ((poppy or sunflower or cotton or flax) adj3 seed$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (59)

21. ((fruit or fruits or vegetable$ or legume$ or kiwi or melon or banana$ or Carrot$ or apple$ or tomato$ or Apricot$ or pepper$ or Cabbage$ or Celery or Celeriac or Cherry or cherries or Courgette$ or zucchini or Aubergine$ or Dates or Fig or figs or plum or plums or garlic$ or grape$ or Lettuce$ or Lychee$ or Mango$ or Peach$ or Pear or pears or Pineapple$ or Pomegranate or Potato$ or Pumpkin$ or Strawberry or strawberries or Turnip$ or Avocado$ or Persimmon) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2435)

22. ((Acerola or Aniseed or Camomile or Castor bean$ or Cocoa or linseed or Lupin$ or Lupine or Sesame or soy$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1227)

23. ((Condiment$ or spice$ or Mustard$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$, or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (230)

24. or/1-23 (42,706)

25. exp food allergy/ (24,867)

26. exp food allergen/ (4698)

27. or/25-26 (26,399)

28. 24 or 27 (42,706)

29. exp Food/ (721,540)

30. food additive/ (8744)

31. crab meat/ or crab/ or crayfish/ or lobster/ or shrimp/ or mollusc/ or fish/ or fish meat/ (111,052)

32. or/29-31 (822,648)

33. exp allergen/ (54,384)

34. exp hypersensitivity/ (498,826)

35. anaphylaxis/ (34,246)

36. anaphylactic shock/ (4751)

37. (allerg$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (479,818)

38. or/33-37 (649,918)

39. 32 and 38 (35,162)

40. 28 or 39 (58,974)

41. pollen allergy/ or hay fever/ (14,584)

42. ((Pollen or seasonal) adj3 (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (13,145)

43. (hayfever or hay fever or pollinosis or pollinoses).ti,ab,ot,hw. (11,916)

44. or/41-43 (21,333)

45. rhinitis/ or rhiniti$.ti,ab,ot,hw. (47,359)

46. (season$ or spring or summer or pollen$ or grass$ or birch or ragweed or tree$ or weed$ or mugwort or willow or alder).ti,ab,ot,hw. (397,576)

47. 45 and 46 (9392)

48. 44 or 47 (24,956)

49. 40 or 48 (79,964)

50. quality adjusted life year/ or quality of life index/ (16,036)

51. Short Form 12/ or Short Form 20/ or Short Form 36/ or Short Form 8/ (16,212)

52. “International Classification of Functioning, Disability and Health”/ or “ferrans and powers quality of life index”/ or “gastrointestinal quality of life index”/ (1859)

53. (sf36 or sf 36 or sf-36 or short form 36 or shortform 36 or sf thirtysix or sf thirty six or shortform thirtysix or shortform thirty six or short form thirty six or short form thirtysix or short form thirty six).ti,ab,ot. (26,380)

54. (sf6 or sf 6 or sf-6 or short form 6 or shortform 6 or sf six or sfsix or shortform six or short form six).ti,ab,ot. (1612)

55. (sf12 or sf 12 or sf-12 or short form 12 or shortform 12 or sf twelve or sftwelve or shortform twelve or short form twelve).ti,ab,ot. (5102)

56. (sf6D or sf 6D or sf-6D or short form 6D or shortform 6D or sf six D or sfsixD or shortform six D or short form six D).ti,ab,ot. (855)

57. (sf20 or sf 20 or sf-20 or short form 20 or shortform 20 or sf twenty or sftwenty or shortform twenty or short form twenty).ti,ab,ot. (352)

58. (sf8 or sf 8 or sf-8 or short form 8 or shortform 8 or sf eight or sfeight or shortform eight or short form eight).ti,ab,ot. (492)

59. “health related quality of life”.ti,ab,ot. (34,378)

60. (Quality adjusted life or Quality-adjusted-life).ti,ab,ot. (10,293)

61. “assessment of quality of life”.ti,ab,ot. (1910)

62. (euroqol or euro qol or eq5d or eq 5d).ti,ab,ot. (8735)

63. (hql or hrql or hqol or h qol or hrqol or hr qol).ti,ab,ot. (17,838)

64. (hye or hyes).ti,ab,ot. (98)

65. health$ year$ equivalent$.ti,ab,ot. (39)

66. (hui or hui1 or hui2 or hui3 or hui4 or hui-4 or hui-1 or hui-2 or hui-3).ti,ab,ot. (2295)

67. (quality time or qwb or “quality of well being” or “quality of wellbeing” or “index of wellbeing” or index of well being).ti,ab,ot,hw. (837)

68. (Disability adjusted life or Disability-adjusted life or health adjusted life or health-adjusted life or “years of healthy life” or healthy years equivalent or “years of potential life lost” or “years of health life lost”).ti,ab,ot. (2463)

69. (QALY$ or DALY$ or HALY$ or YHL or HYES or YPLL or YHLL or qald$ or qale$ or qtime$ or AQoL$).ti,ab,ot. (13,192)

70. (timetradeoff or time tradeoff or time trade-off or time trade off or TTO or Standard gamble$ or “willingness to pay”).ti,ab,ot. (6245)

71. 15d.ti,ab,ot. (1802)

72. (HSUV$ or health state$ value$ or health state$ preference$ or HSPV$).ti,ab,ot. (340)

73. (utilit$ adj3 (“quality of life” or valu$ or scor$ or measur$ or health or life or estimat$ or elicit$ or disease$)).ti,ab,ot. (11,429)

74. (utilities or disutili$).ti,ab,ot. (7194)

75. or/50-74 (108,471)

76. letter.pt. (896,144)

77. editorial.pt. (482,372)

78. note.pt. (606,238)

79. or/76-78 (1,984,754)

80. 75 not 79 (105,171)

81. 49 and 80 (433)

Health-related quality of life free-text terms based on:

• Figure 4 Common free-text terms for electronic database searching for HSUVs in Papaioannou D, Brazier JE, Paisley S. NICE DSU Technical Support Document 9: the identification, review and synthesis of health-state utility values from the literature (internet), 2011 (accessed 18 August 2011). Available from: www.nicedsu.org.uk.

Searched: 30 June 2015

1. (food$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (16,959)

2. ((Cereal$ or wheat or rye or barley or oat or oats or rice or maize or spelt or buckwheat or soybean or millet or sorghum or corn or Kamut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1605)

3. ((Gluten or (glutenin adj3 gliadin) or prolamins) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (876)

4. ((Dairy or milk or yog?urt$ or cream or butter$ or cheese$ or ice cream$ or kefir) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (3865)

5. ((Casein or whey or lactose) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (3292)

6. (Egg$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1416)

7. ((Peanut$ or arachid or Arachis hypog?ea or groundnut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1419)

8. ((ground or earth or monkey) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

9. (arachis oil adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

10. ((Nut or nuts or hazelnut$ or cashew$ or walnut$ or pecan$ or almond$ or Macadamia$ or pistachio$ or chestnut$ or coconut$ or Candlenut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (643)

11. ((Brazil or pine or hickory or betel) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (63)

12. ((Crustacea$ or Mollusc$ or mollusk$ or shellfish or seafood or sea food or Lobster or crab$ or shrimp$ or prawn$ or squid$ or oyster$ or crayfish or cuttlefish or abalone or limpet$ or mussel$ or scallop$ or clam or clams or whelk$ or scampi or octopus or langoustine$ or cockle$ or winkles or krill) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (636)

13. ((Fish or finfish or sole or mackerel$ or hake or whiting or dab or plaice or Anchov$ or Catfish or Eel$ or Haddock or Halibut or Sardine$ or Scad or Snapper or Tilapia or Trout or shark or swordfish or cod or tuna or herring$ or flounder or mullet or salmon or kipper$ or caviar or seer or mackerel or tilefish or Pollock or whitebait or flatfish or john dory or carp) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1154)

14. (Fish adj3 roe adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2)

15. ((Surimi or sashimi or sushi or cerviche or gravlax) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (2)

16. ((Snail$ or frog$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (173)

17. ((Sulfites or sulphites) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (36)

18. (((sulphiting adj2 agents) or (sulphur adj2 dioxide)) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (3)

19. ((Lentil$ or chickpea$ or pea or peas or garbanzo or bengal gram or chana or channa or leblebi) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (84)

20. ((poppy or sunflower or cotton or flax) adj3 seed$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (27)

21. ((fruit or fruits or vegetable$ or legume$ or kiwi or melon or banana$ or Carrot$ or apple$ or tomato$ or Apricot$ or pepper$ or Cabbage$ or Celery or Celeriac or Cherry or cherries or Courgette$ or zucchini or Aubergine$ or Dates or Fig or figs or plum or plums or garlic$ or grape$ or Lettuce$ or Lychee$ or Mango$ or Peach$ or Pear or pears or Pineapple$ or Pomegranate or Potato$ or Pumpkin$ or Strawberry or strawberries or Turnip$ or Avocado$ or Persimmon) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1449)

22. ((Acerola or Aniseed or Camomile or Castor bean$ or Cocoa or linseed or Lupin$ or Lupine or Sesame or soy$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (743)

23. ((Condiment$ or spice$ or Mustard$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$, or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (166)

24. or/1-23 (27,183)

25. exp Food Hypersensitivity/ (15,608)

26. exp Food/ (1,100,276)

27. exp Food Additives/ (239,057)

28. or/26-27 (1,101,303)

29. allergens/ or exp Hypersensitivity/ (288,187)

30. (allerg$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (324,188)

31. or/29-30 (442,055)

32. 28 and 31 (28,934)

33. 24 or 25 or 32 (45,050)

34. Rhinitis, Allergic, Seasonal/ (12,580)

35. ((Pollen or seasonal) adj3 (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (15,942)

36. (hayfever or hay fever or pollinosis or pollinoses).ti,ab,ot,hw. (3989)

37. (rhiniti$ adj3 (season$ or spring or summer or pollen$ or grass$ or birch or ragweed or tree$ or weed$ or mugwort or willow or alder)).ti,ab,ot,hw. (12,979)

38. or/34-37 (17,192)

39. 33 or 38 (60,503)

40. quality-adjusted life years/ or quality of life/ (133,433)

41. (sf36 or sf 36 or sf-36 or short form 36 or shortform 36 or sf thirtysix or sf thirty six or shortform thirtysix or shortform thirty six or short form thirty six or short form thirtysix or short form thirty six).ti,ab,ot. (16,140)

42. (sf6 or sf 6 or sf-6 or short form 6 or shortform 6 or sf six or sfsix or shortform six or short form six).ti,ab,ot. (1038)

43. (sf12 or sf 12 or sf-12 or short form 12 or shortform 12 or sf twelve or sftwelve or shortform twelve or short form twelve).ti,ab,ot. (2869)

44. (sf6D or sf 6D or sf-6D or short form 6D or shortform 6D or sf six D or sfsixD or shortform six D or short form six D).ti,ab,ot. (460)

45. (sf20 or sf 20 or sf-20 or short form 20 or shortform 20 or sf twenty or sftwenty or shortform twenty or short form twenty).ti,ab,ot. (336)

46. (sf8 or sf 8 or sf-8 or short form 8 or shortform 8 or sf eight or sfeight or shortform eight or short form eight).ti,ab,ot. (265)

47. “health related quality of life”.ti,ab,ot. (22,368)

48. (Quality adjusted life or Quality-adjusted-life).ti,ab,ot. (6465)

49. “assessment of quality of life”.ti,ab,ot. (1174)

50. (euroqol or euro qol or eq5d or eq 5d).ti,ab,ot. (4266)

51. (hql or hrql or hqol or h qol or hrqol or hr qol).ti,ab,ot. (10,537)

52. (hye or hyes).ti,ab,ot. (54)

53. health$ year$ equivalent$.ti,ab,ot. (38)

54. (hui or hui1 or hui2 or hui3 or hui4 or hui-4 or hui-1 or hui-2 or hui-3).ti,ab,ot. (901)

55. (quality time or qwb or quality of well being or “quality of wellbeing” or “index of wellbeing” or “index of well being”).ti,ab,ot,hw. (617)

56. (Disability adjusted life or Disability-adjusted life or health adjusted life or health-adjusted life or “years of healthy life” or healthy years equivalent or “years of potential life lost” or “years of health life lost”).ti,ab,ot. (1788)

57. (QALY$ or DALY$ or HALY$ or YHL or HYES or YPLL or YHLL or qald$ or qale$ or qtime$ or AQoL$).ti,ab,ot. (7212)

58. (timetradeoff or time tradeoff or time trade-off or time trade off or TTO or Standard gamble$ or “willingness to pay”).ti,ab,ot. (3886)

59. 15d.ti,ab,ot. (1173)

60. (HSUV$ or health state$ value$ or health state$ preference$ or HSPV$).ti,ab,ot. (238)

61. (utilit$ adj3 (“quality of life” or valu$ or scor$ or measur$ or health or life or estimat$ or elicit$ or disease$)).ti,ab,ot. (6934)

62. (utilities or disutili$).ti,ab,ot. (4124)

63. or/40-62 (158,071)

64. letter.pt. (854,881)

65. editorial.pt. (359,484)

66. historical article.pt. (317,628)

67. or/64-66 (1,516,490)

68. 63 not 67 (150,867)

69. 39 and 68 (739)

Health-related quality of life free-text terms based on:

• Figure 4 Common free-text terms for electronic database searching for HSUVs in Papaioannou D, Brazier JE, Paisley S. NICE DSU Technical Support Document 9: the identification, review and synthesis of health state utility values from the literature (internet), 2011 (accessed 18 August 2011). Available from: www.nicedsu.org.uk.

Searched: 30 June 2015

1. (food$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1007)

2. ((Cereal$ or wheat or rye or barley or oat or oats or rice or maize or spelt or buckwheat or soybean or millet or sorghum or corn or Kamut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (204)

3. ((Gluten or (glutenin adj3 gliadin) or prolamins) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (115)

4. ((Dairy or milk or yog?urt$ or cream or butter$ or cheese$ or ice cream$ or kefir) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (229)

5. ((Casein or whey or lactose) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (76)

6. (Egg$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (126)

7. ((Peanut$ or arachid or Arachis hypog?ea or groundnut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (155)

8. ((ground or earth or monkey) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

9. (arachis oil adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

10. ((Nut or nuts or hazelnut$ or cashew$ or walnut$ or pecan$ or almond$ or Macadamia$ or pistachio$ or chestnut$ or coconut$ or Candlenut) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (51)

11. ((Brazil or pine or hickory or betel) adj3 nut$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (5)

12. ((Crustacea$ or Mollusc$ or mollusk$ or shellfish or seafood or sea food or Lobster or crab$ or shrimp$ or prawn$ or squid$ or oyster$ or crayfish or cuttlefish or abalone or limpet$ or mussel$ or scallop$ or clam or clams or whelk$ or scampi or octopus or langoustine$ or cockle$ or winkles or krill) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (44)

13. ((Fish or finfish or sole or mackerel$ or hake or whiting or dab or plaice or Anchov$ or Catfish or Eel$ or Haddock or Halibut or Sardine$ or Scad or Snapper or Tilapia or Trout or shark or swordfish or cod or tuna or herring$ or flounder or mullet or salmon or kipper$ or caviar or seer or mackerel or tilefish or Pollock or whitebait or flatfish or john dory or carp) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (83)

14. (Fish adj3 roe adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1)

15. ((Surimi or sashimi or sushi or cerviche or gravlax) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1)

16. ((Snail$ or frog$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (4)

17. ((Sulfites or sulphites) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (0)

18. (((sulphiting adj2 agents) or (sulphur adj2 dioxide)) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (1)

19. ((Lentil$ or chickpea$ or pea or peas or garbanzo or bengal gram or chana or channa or leblebi) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (9)

20. ((poppy or sunflower or cotton or flax) adj3 seed$ adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (3)

21. ((fruit or fruits or vegetable$ or legume$ or kiwi or melon or banana$ or Carrot$ or apple$ or tomato$ or Apricot$ or pepper$ or Cabbage$ or Celery or Celeriac or Cherry or cherries or Courgette$ or zucchini or Aubergine$ or Dates or Fig or figs or plum or plums or garlic$ or grape$ or Lettuce$ or Lychee$ or Mango$ or Peach$ or Pear or pears or Pineapple$ or Pomegranate or Potato$ or Pumpkin$ or Strawberry or strawberries or Turnip$ or Avocado$ or Persimmon) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (130)

22. ((Acerola or Aniseed or Camomile or Castor bean$ or Cocoa or linseed or Lupin$ or Lupine or Sesame or soy$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (65)

23. ((Condiment$ or spice$ or Mustard$) adj4 (allerg$ or sensitivit$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$, or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (8)

24. or/1-23 (1826)

25. exp Food Hypersensitivity/ (16)

26. exp Food/ (1220)

27. exp Food Additives/ (177)

28. or/26-27 (1220)

29. allergens/ or exp Hypersensitivity/ (201)

30. (allerg$ or hypersensitiv$ or hyper-sensiti$ or intolerance$ or adverse reaction$ or anaphyla$ or pseudoanaphyla$ or poly-sensiti$ or polysensiti$ or paucisensiti$).ti,ab,ot,hw. (15,177)

31. or/29-30 (15,275)

32. 28 and 31 (28)

33. 24 or 25 or 32 (1845)

34. Rhinitis, Allergic, Seasonal/ (1)

35. ((Pollen or seasonal) adj3 (allerg$ or anaphyla$ or hypersensiti$ or hyper-sensiti$ or poly-sensiti$ or polysensiti$ or paucisensiti$)).ti,ab,ot,hw. (324)

36. (hayfever or hay fever or pollinosis or pollinoses).ti,ab,ot,hw. (194)

37. (rhiniti$ adj3 (season$ or spring or summer or pollen$ or grass$ or birch or ragweed or tree$ or weed$ or mugwort or willow or alder)).ti,ab,ot,hw. (97)

38. or/34-37 (502)

39. 33 or 38 (2301)

40. quality-adjusted life years/ or quality of life/ (282)

41. (sf36 or sf 36 or sf-36 or short form 36 or shortform 36 or sf thirtysix or sf thirty six or shortform thirtysix or shortform thirty six or short form thirty six or short form thirtysix or short form thirty six).ti,ab,ot. (1709)

42. (sf6 or sf 6 or sf-6 or short form 6 or shortform 6 or sf six or sfsix or shortform six or short form six).ti,ab,ot. (448)

43. (sf12 or sf 12 or sf-12 or short form 12 or shortform 12 or sf twelve or sftwelve or shortform twelve or short form twelve).ti,ab,ot. (418)

44. (sf6D or sf 6D or sf-6D or short form 6D or shortform 6D or sf six D or sfsixD or shortform six D or short form six D).ti,ab,ot. (50)

45. (sf20 or sf 20 or sf-20 or short form 20 or shortform 20 or sf twenty or sftwenty or shortform twenty or short form twenty).ti,ab,ot. (14)

46. (sf8 or sf 8 or sf-8 or short form 8 or shortform 8 or sf eight or sfeight or shortform eight or short form eight).ti,ab,ot. (39)

47. “health related quality of life”.ti,ab,ot. (3142)

48. (Quality adjusted life or Quality-adjusted-life).ti,ab,ot. (927)

49. “assessment of quality of life”.ti,ab,ot. (121)

50. (euroqol or euro qol or eq5d or eq 5d).ti,ab,ot. (723)

51. (hql or hrql or hqol or h qol or hrqol or hr qol).ti,ab,ot. (1442)

52. (hye or hyes).ti,ab,ot. (2)

53. health$ year$ equivalent$.ti,ab,ot. (1)

54. (hui or hui1 or hui2 or hui3 or hui4 or hui-4 or hui-1 or hui-2 or hui-3).ti,ab,ot. (109)

55. (quality time or qwb or quality of well being or “quality of wellbeing” or “index of wellbeing” or “index of well being”).ti,ab,ot,hw. (48)

56. (Disability adjusted life or Disability-adjusted life or health adjusted life or health-adjusted life or “years of healthy life” or healthy years equivalent or “years of potential life lost” or “years of health life lost”).ti,ab,ot. (331)

57. (QALY$ or DALY$ or HALY$ or YHL or HYES or YPLL or YHLL or qald$ or qale$ or qtime$ or AQoL$).ti,ab,ot. (1076)

58. (timetradeoff or time tradeoff or time trade-off or time trade off or TTO or Standard gamble$ or “willingness to pay”).ti,ab,ot. (541)

59. 15d.ti,ab,ot. (116)

60. (HSUV$ or health state$ value$ or health state$ preference$ or HSPV$).ti,ab,ot. (21)

61. (utilit$ adj3 (“quality of life” or valu$ or scor$ or measur$ or health or life or estimat$ or elicit$ or disease$)).ti,ab,ot. (832)

62. (utilities or disutili$).ti,ab,ot. (552)

63. or/40-62 (8337)

64. letter.pt. (30,812)

65. editorial.pt. (22,136)

66. historical article.pt. (227)

67. or/64-66 (53,144)

68. 63 not 67 (8298)

69. 39 and 68 (20)

Health-related quality of life free-text terms based on:

• Figure 4 Common free-text terms for electronic database searching for HSUVs in Papaioannou D, Brazier JE, Paisley S. NICE DSU Technical Support Document 9: the identification, review and synthesis of health state utility values from the literature (internet), 2011 (accessed 18 August 2011). Available from: www.nicedsu.org.uk.

Searched: 1 July 2015

#1 food* near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (1044)

#2 (Cereal* or wheat or rye or barley or oat or oats or rice or maize or spelt or buckwheat or soybean or millet or sorghum or corn or Kamut) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (103)

#3 (Gluten or glutenin or prolamins) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (24)

#4 (Dairy or milk or yog*urt* or cream or butter* or cheese* or ice cream* or kefir) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (532)

#5 (Casein or whey or lactose) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (278)

#6 Egg* near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (266)

#7 (Peanut* or arachid or “Arachis hypog*ea” or groundnut) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (150)

#8 “arachis oil” near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (1)

#9 (Nut or nuts or hazelnut* or cashew* or walnut* or pecan* or almond* or Macadamia* or pistachio* or chestnut* or coconut* or Candlenut) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (55)

#10 (Crustacea* or Mollusc* or mollusk* or shellfish or seafood or “sea food” or Lobster or crab* or shrimp* or prawn* or squid* or oyster* or crayfish or cuttlefish or abalone or limpet* or mussel* or scallop* or clam or clams or whelk* or scampi or octopus or langoustine* or cockle* or winkles or krill) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (22)

#11 (Fish or finfish or sole or mackerel* or hake or whiting or dab or plaice or Anchov* or Catfish or Eel* or Haddock or Halibut or Sardine* or Scad or Snapper or Tilapia or Trout or shark or swordfish or cod or tuna or herring* or flounder or mullet or salmon or kipper* or caviar or seer or mackerel or tilefish or Pollock or whitebait or flatfish or “john dory” or carp) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (89)

#12 roe near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (1)

#13 (Surimi or sashimi or sushi or cerviche or gravlax) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (0)

#14 (Snail* or frog*) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (0)

#15 (Sulfites or sulphites) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (6)

#16 (sulphating or sulphur) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (5)

#17 (Lentil* or chickpea* or pea or peas or garbanzo or “bengal gram” or chana or channa or leblebi) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (8)

#18 (poppy or sunflower or cotton or flax) near/3 seed* near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (0)

#19 (fruit or fruits or vegetable* or legume* or kiwi or melon or banana* or Carrot* or apple* or tomato* or Apricot* or pepper* or Cabbage* or Celery or Celeriac or Cherry or cherries or Courgette* or zucchini or Aubergine* or Dates or Fig or figs or plum or plums or garlic* or grape* or Lettuce* or Lychee* or Mango* or Peach* or Pear or pears or Pineapple* or Pomegranate or Potato* or Pumpkin* or Strawberry or strawberries or Turnip* or Avocado* or Persimmon) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (101)

#20 (Acerola or Aniseed or Camomile or “Castor bean*” or Cocoa or linseed or Lupin* or Lupine or Sesame or soy*) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti*) (83)

#21 (Condiment* or spice* or Mustard*) near/4 (allerg* or sensitivit* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla*, or “poly-sensiti*” or polysensiti* or paucisensiti*) (8)

#22 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 (2007)

#23 MeSH descriptor: [Food Hypersensitivity] explode all trees (618)

#24 MeSH descriptor: [Food] explode all trees (22,580)

#25 MeSH descriptor: [Food Additives] explode all trees (545)

#26 #24 or #25 (22,598)

#27 MeSH descriptor: [Allergens] explode all trees (1554)

#28 MeSH descriptor: [Hypersensitivity] explode all trees (15,778)

#29 allerg* or hypersensitiv* or “hyper-sensiti*” or intolerance* or “adverse reaction*” or anaphyla* or pseudoanaphyla* or “poly-sensiti*” or polysensiti* or paucisensiti* (36,164)

#30 #27 or #28 or #29 (43,237)

#31 #26 and #30 (1384)

#32 #22 or #23 or #31 (2743)

#33 MeSH descriptor: [Rhinitis, Allergic, Seasonal] explode all trees 1611)

#34 (Pollen or seasonal) near/3 (allerg* or anaphyla* or hypersensiti* or “hyper-sensiti*” or “poly-sensiti*” or polysensiti* or paucisensiti*) (3657)

#35 hayfever or “hay fever” or pollinosis or pollinoses (951)

#36 rhiniti* near/3 (season* or spring or summer or pollen* or grass* or birch or ragweed or tree* or weed* or mugwort or willow or alder) (2962)

#37 #33 or #34 or #35 or #36 (4095)

#38 #32 or #37 (6656)

#39 MeSH descriptor: [Quality-Adjusted Life Years] this term only (3930)

#40 MeSH descriptor: [Quality of Life] this term only (15,292)

#41 sf36 or sf 36 or “sf-36” or “short form 36” or “shortform 36” or “sf thirtysix” or “sf thirty six” or “shortform thirtysix” or “shortform thirty six” or “short form thirty six” or “short form thirtysix” or “short form thirty six” (6646)

#42 sf6 or “sf 6” or sf-6 or “short form 6” or “shortform 6” or “sf six” or sfsix or “shortform six” or “short form six” (137)

#43 sf12 or “sf 12” or “sf-12” or “short form 12” or “shortform 12” or “sf twelve” or sftwelve or “shortform twelve” or “short form twelve” (975)

#44 sf6D or “sf 6D” or “sf-6D” or “short form 6D” or “shortform 6D” or “sf six D” or sfsixD or “shortform six D” or “short form six D” (186)

#45 sf20 or “sf 20” or “sf-20” or “short form 20” or “shortform 20” or “sf twenty” or sftwenty or “shortform twenty” or “short form twenty” (74)

#46 sf8 or “sf 8” or “sf-8” or “short form 8” or “shortform 8” or “sf eight” or sfeight or “shortform eight” or “short form eight” (58)

#47 “health related quality of life” (6922)

#48 “Quality adjusted life” or “Quality-adjusted-life” (6557)

#49 “assessment of quality of life” (318)

#50 euroqol or “euro qol” or eq5d or “eq 5d” (2744)

#51 hql or hrql or hqol or “h qol” or hrqol or “hr qol” (2599)

#52 hye or hyes (53)

#53 “health* year* equivalent*” (5)

#54 hui or hui1 or hui2 or hui3 or hui4 or “hui-4” or “hui-1” or “hui-2” or “hui-3” (1262)

#55 “quality time” or qwb or “quality of well being” or “quality of wellbeing” or “index of wellbeing” or “index of well being” (231)

#56 “Disability adjusted life” or “Disability-adjusted life” or “health adjusted life” or “health-adjusted life” or “years of healthy life” or “healthy years equivalent” or “years of potential life lost” or “years of health life lost” (350)

#57 QALY* or DALY* or HALY* or YHL or HYES or YPLL or YHLL or qald* or qale* or qtime* or AQoL* (5218)

#58 timetradeoff or “time tradeoff” or “time trade-off” or “time trade off” or TTO or “Standard gamble*” or “willingness to pay” (1916)

#59 15d (107)

#60 HSUV* or “health state* value*” or “health state* preference*” or HSPV* (83)

#61 utilit* near/3 (“quality of life” or valu* or scor* or measur* or health or life or estimat* or elicit* or disease*) (4632)

#62 utilities or disutili* (1656)

#63 #39 or #40 or #41 or #42 or #43 or #44 or #45 or #46 or #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58 or #59 or #60 or #61 or #62 (33,724)

#64 #38 and #63 (393)

NHS EED search retrieved 34 records.*

*Please note: Records ceased to be added to the NHS EED resource on 31 March 2015, this search was for archival material only.

Searched: 1 July 2015

Basic search for ‘articles’.

Searched: 1 July 2015

Basic search