ImmunoCAP® ISAC and Microtest for multiplex allergen testing in people with difficult to manage allergic disease: a systematic review and cost analysis. A combination of innovative biochip technology with cutting edge research in molecular allergology has resulted in ImmunoCAP® ISAC – the most advanced in. The immuno-solid phase allergen chip (ISAC) test (Thermo Fisher ImmunoCAP ISAC) is a microarray assay system designed to assay specific.
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Health Technology Assessment, No. A systematic review was conducted to summarise the evidence on the clinical effectiveness and cost-effectiveness of ImmunoCAP ISAC and Microtest for multiplex allergen testing in people with allergic disease. Development of search strategies followed the recommendations of the CRD guidance for undertaking reviews in health care. Candidate search terms were identified from target references, browsing database thesauri e.
These scoping searches were used to generate test sets of target references, which informed text mining analysis of high-frequency subject indexing terms using EndNote X7 reference management software Thomson Reuters, CA, USA. Strategy development involved an iterative approach testing candidate text and indexing terms across a sample of bibliographic databases, aiming to reach a satisfactory balance of sensitivity and specificity.
Search strategies were developed specifically for each database. The following key conference proceedings, were identified in consultation with clinical experts, and were screened for the last 5 years where available:. No restrictions on language or publication status were applied. Searches took into account generic and other product names for the intervention. See Appendix 1 for all search strategies. References in retrieved articles were checked for additional studies.
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. The comparator for this assessment was current standard care, which included allergy-focused clinical history, alternative tests of IgE antibody status single IgE antibody testingtests of clinical reactivity such as skin prick testing or allergen challenge testing or a combination of these approaches. There were no restrictions on study design.
Randomised controlled trials RCTscontrolled clinical trials, other comparative studies e. 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.
No studies of this type were identified. The inclusion criteria were expanded to osac studies that reported direct comparisons of diagnostic accuracy between single IgE testing and multiplex allergen testing, using SPTs or allergen challenge tests immunoczp the reference standard.
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.
Two reviewers MW and SL independently screened the titles and abstracts of all reports identified by searches and any discrepancies were discussed and resolved by consensus. Full copies of all studies deemed potentially relevant were obtained and the same two reviewers independently assessed these for inclusion; any disagreements were resolved by consensus.
Details of studies excluded at the full paper screening stage are presented in Appendix 3. The principal investigators of completed trials identified through searches of clinical trials registries that appeared to meet our inclusion criteria but for which no publication could be identified were contacted and asked to provide publication details or unpublished data.
Data were extracted on the following: SPT, OFC, single IgE ; details of the reference standard test diagnostic accuracy studies only ; outcome measures included change to treatment or treatment plan, e. Data were extracted by one reviewer, using a piloted, standard data extraction form, and checked by a second MW and SL ; any disagreements were resolved by consensus. Full data extraction tables are provided in Appendix 2. This tool has been designed to focus on elements of study design that we considered relevant to this specific study type, and is based upon the structure of the QUADAS-2 im,unocap.
The results of the quality assessment have been used for descriptive purposes to provide an evaluation of the overall isaac of the included studies and to provide a transparent method of recommendation for design of any future studies.
Quality immunocxp was undertaken by one reviewer and checked by a second reviewer MW and SL and any disagreements were resolved by consensus. The applicability of studies to current UK practice was also considered and a narrative description of potential applicability issues is provided.
The results of the risk-of-bias assessments are summarised and presented in tables and graphs in the results of the systematic review see Study quality and are presented in full, by study, in Appendix 4. However, because iisac review identified a small number of studies with between-study variations in participant characteristics allergy historymultiplex allergen testing methods, allergens tested for, standard care comparators, and outcomes assessed, we did not consider meta-analyses to be appropriate and have provided a structured narrative synthesis.
The results of studies included in this review are summarised by outcome type clinical, change to management and diagnostic accuracy and are further stratified by allergen type food and aeroallergens.
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The results of individual studies are summarised in text and tables. The results of studies providing comparative accuracy data are also illustrated in receiver operating characteristic ROC space immunocsp.
The searches of bibliographic databases and conference abstracts identified references. After initial screening of titles and abstracts, were considered to be potentially relevant and ordered for full paper screening; of these, 20 were included in the review 30 — 49 and one 50 could not be obtained.
All potentially relevant studies cited in documents supplied by the test manufacturers had already been identified by bibliographic database searches.
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Additional data, relating to the study by Hermansson et al. Figure 1 shows the flow of studies through the review process, and Appendix 3 provides details, with reasons for exclusions, of all publications excluded at the full paper screening stage.
Based on the searches and inclusion screening described above see Search strategy and Inclusion and exclusion criteriaabove20 publications, 30 — 49 of 15 studies, were included in the review; the results section of this report cites studies using the primary isacc and, where this isc different, the publication in which the referenced data were reported.
Two of the included studies 3940 were conducted in the UK and, where reported, the remaining studies were conducted in other European countries; one study 47 did not report location. Of the 15 included studies, four were funded by, 3846 or received reagents and isaf 39 or testing services 45 from, the manufacturer. Five studies were publicly funded 3242 — 4449 and six studies 333637404147 did not report funding sources. Full details of funding are reported in the baseline study details tables see Appendix 2Tables A—C.
We did not identify any studies of Microtest which met the inclusion criteria for this review. We did not identify any studies that reported clinical outcomes i. None of the five studies 3233373840 reported the inclusion of patients with difficult to manage allergic disease; one study 40 reported inclusion criteria which may have been consistent with this classification moderate to severe eczema and multiple food allergies ; however, this study 40 was reported only as a conference abstract and immunlcap provided very limited details of participants.
One study 40 was conducted in the UK, two studies 3237 were conducted in Spain, and one study was conducted in each of Finland 33 and Italy. None of these studies reported test accuracy data.
One study 39 was conducted in the UK, one study 38 was conducted in Italy and one study 36 did not report location. None of the eight studies 41 — 4749 reported the inclusion of patients with difficult to diagnose and manage allergic disease, or described inclusion criteria that could be considered consistent with this jmmunocap e.
None of the studies was conducted in the UK, seven studies 41 — 4649 were European and one study 47 issac unreported. Full details of the characteristics of study participants, study inclusion and exclusion criteria, and intervention and comparator or reference standard are reported in the data extraction tables presented in Appendix 2 see Tables A—E.
One hundred and forty-eight full-text articles were retrieved: In all but two cases, 5152 these studies reported no relevant outcomes. Further details of the excluded full papers and the reasons for exclusion can be found in Appendix 4. One study 50 could not be obtained.
Seven studies investigated changes to treatment or management outcomes. The methodological quality of this study 36 was assessed using the CASP cohort tool. The methodological quality of these studies was assessed using a tool jmmunocap specifically for this review, which was based on the structure of QUADAS 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.
Risk of bias for included diagnostic studies change to management or treatment: 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 iszc with difficult to manage allergic disease, or describe inclusion criteria which could be considered consistent with this classification e. Studies that were conducted in non-UK settings and which assessed allergens considered unlikely to be relevant to UK populations e. The small observational study 36 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.
Immunpcap of bias across included diagnostic studies accuracy. One study 47 was reported only as a conference abstract. The main potential sources of bias were in relation to participant selection and application of 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.
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.
Confidential information has been removed Johannes Savolainen, personal communication.
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The Hermansson study 33 did not report any information on clinical outcomes following changes to dietary management. Noimark and Harnik 40 investigated 12 children selected from patients attending an East London allergy clinic no details of the selection criteria were reported. Noimark and Harnik 40 did not report the number of food reintroductions that occurred following testing or isca outcomes of any changes to dietary management. Two studies 3738 assessed the views of clinicians on whether or not Iac ISAC testing provided information useful in the management of patients.
Two studies investigated the effect on diagnostic classification of adding ImmunoCAP ISAC testing to the standard diagnostic work-up of people with allergic disease. This study 36 included only nine participants who received a total of 31 courses of SIT no details of diagnosis were reported.
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.
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. Six studies 414244464749 were identified which compared the accuracy of ImmunoCAP ISAC to existing diagnostic tests SPT or single IgE tests in people with food allergies; two studies 4345 were identified of people with allergies to aeroallergens.
De Swert et al. Cut-off values were reported separately for each test and OFC testing was used as the reference standard. The diagnostic accuracy of ISACisa used to measure three individual egg components Gal d1 or Gal d2 or Gal d3was 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 ijmunocap boiled egg yolk.
Results for raw egg were similar to those for boiled egg. In general, single IgE performed similarly to SPT both measured whole extractswhereas ISAC gave much more variable results for the three different components measured. No measure of the overall diagnostic performance of ISAC all components combined was reported. The results were very variable between tests.
All three ISAC 51 components had low sensitivity ranging from Single Isav testing and skin prick testing had comparable specificity For both methods, a positive result was defined as positive lsac 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.