Discussion
The EAACI Food Allergy Guidelines need to be updated, in particular the
section on diagnostic tests for food allergy. The systematic review of
the literature on diagnostic tests that informed the current EAACI Food
Allergy Guidelines was conducted prior to 2014, thus a new systematic
review is needed, especially since emerging tests such as CRD, MAT and
BAT were not included in the previous review. We report herein the
protocol for a systematic review of the literature, as registered at
PROSPERO (CRD42021259186), and provide a description of the rationale
and methods chosen for the review.
OFC is the reference-standard diagnostic test for food allergies;
however, there are considerable risks involved. OFC involve ingesting
the suspected allergen, which is associated with a risk of allergic
reaction and may result in a life-threatening event. As a result, OFC
must be conducted in a controlled environment with intensive care
facilities in easy reach, and not all clinical settings can offer this
service. Additionally, this risk of reaction may lead to significant
anxiety in patients and their families, therefore a reliable and
cost-effective alternative to OFC is needed. Since the previous
guideline was published, newer tests such as CRD have entered mainstream
use in Europe and other regions. Also, studies assessing the efficacy of
novel diagnostic tests such as BAT and MAT have been published. All of
these new tests must be reviewed to assess whether they are acceptable
diagnostic tools for use in routine clinical practice. For more
established allergy tests, such as SPT and sIgE, new studies have been
performed since the previous review which may require updating of the
previous recommendation. We aim to evaluate the diagnostic test accuracy
of any index test, from SPT, sIgE to extracts, sIgE to individual
allergens, sIgE to allergen peptides, BAT and MAT. Thus, we do not
include search terms for the index test. We apply a specific filter for
diagnostic test accuracy studies, though, which implicitly captures
studies on diagnostics and/or tests. We only include search terms for
“challenge” as part of the common terminology for the comparator, i.e.
oral food challenge, to have a sensitive search regarding the comparator
test.
The population of interest will include all ages and diverse clinical
settings and geographical locations. We deliberately do not include
search terms to specify the target population and studies that do not
have evidence from all populations will be included in the review and
judged for risk of bias. We expect to encounter very few if any
diagnostic test accuracy studies conducted in animals; however, we will
refrain from specifying search terms that will exclude animal studies
because of the risk of falsely excluding studies on animal allergen
sources. Certain food allergies are more prevalent in different areas.
As such, we will include studies focussing on any food, to be inclusive
to all populations, although we anticipate that there will be more
studies on milk, egg and peanut allergies.
Although the gold standard is DBPCFC, we will also include studies where
open oral food challenges are performed and allow for the inclusion of
studies where a small proportion of patients were diagnosed without an
oral food challenge due to previous severe or anaphylactic reactions.
Studies focusing only on IgE sensitisation will be excluded, as some
patients who experience sensitisation to foods are not necessarily
allergic. It is important to note that the comparator reference standard
test is oral food challenge and as such, the systematic review will
inform on the diagnostic accuracy of potential alternative tests.
However, the systematic review will not clarify which of these tests is
best used in subjects in whom the oral food challenge is
contraindicated.
As outcomes we are assessing sensitivity and specificity as measures of
diagnostic test accuracy. The positive and negative predictive value of
the test, which depends on the prevalence of the given food allergy in
the population, is not within the scope of this systematic review. The
details collected as part of the quality assessment and risk of bias
will allow us to select high-quality studies at low risk of bias. The
planned sensitivity analyses on these features may help to identify
factors that influence the performance of the test and the modulation of
the identified diagnostic cut-offs. If sufficient high quality studies
are identified, the planned meta-analyses will provide evidence which
may help to reduce the number of patients that have to undergo an OFC
procedure.