The estimation of the threshold dose for allergic reaction to peanut in peanut allergic subjects has potential value for public health measures. The use of statistical dose-distribution modelling based upon the results of low-dose clinical challenges of peanut-allergic individuals has been viewed as a strong approach to estimation of the population threshold for peanut [13, 14].
However, the clinical determination of individual thresholds is based upon graded incrementally increasing challenge doses administered at convenient time intervals, sometimes as short as 15–20 minutes between doses. The individual threshold doses are frequently reported as cumulative doses because it is impossible to claim that each dose is fully assimilated before administration of the next dose .
Allen et al. (2013) used this approach to estimate a population threshold for the peanut-allergic population based upon challenges of 750 individuals. The ED05 from the log normal dose-distribution was 6 mg of whole peanut or 1.5 mg of peanut protein. Since cumulative doses were used in the evaluation of individual challenges and subsequent statistical dose-distribution modelling, it is important to validate the peanut ED05 using a single-dose approach. Peanut is the best-studied food allergen in terms of low dose OFC to date. This novel PATS approach could be adapted for other major food allergens, if this proposed clinical study supports the statistically determined ED05 based upon population dose-distribution modelling .
The plan to approach all peanut allergic subjects in 3 distinct geographical regions the varied or permissive entry criteria and the analysis of the non-participants will address the most common criticism of OFC studies: how representative of the general peanut allergic population are the subjects who volunteered? Peanut allergic subjects who have food challenges are highly selected and they may not represent the whole spectrum of reactivity to peanut in peanut allergic subjects .
The strict requirement for only objective signs being used to determine a case is important, because subjective reactions are known to resolve during a routine OFC that is continued until objective signs are recorded [10, 17].
Peanut allergic patients are usually advised to avoid foods that are labelled as “may contain” peanut. A recent study by Madsen et al. (2012) has showed that it is understood and accepted by clinicians, patients and food producers that zero risk is not a realistic or attainable option . However clinical risk communications that are not specific may increase anxiety and risk taking behaviours without increasing awareness, confidence or safety .
Currently there is no standard approach being used by all manufacturers in relation to precautionary labelling. This may be due, in part, to the lack of agreement among the scientific community regarding clinically safe threshold levels. If this current study validates the ED05 this will aid the scientific and medical communities and also the manufacturing industry in the use of quantitative precautionary labelling, backed with sound scientific evidence for the establishment of safe threshold levels for 95% of the peanut allergic community.
The PATS study offers a new clinical paradigm and methodology with regards to assessing clinical risk; this current study may potentially define the 5% of patients who are most highly sensitive. Validated questionnaires assessing FAQL have shown patients gain nearly as much from a “failed” OFC as they do from a “passed” OFC, probably due to decreased uncertainty about the next and future reactions  and we hypothesise that individual families may also show such an improvement after a PATS single dose challenge. This tangible impact could promote adoption of PATS single dose peanut challenges in units not currently performing diagnostic OFC. If this proposed clinical study supports the statistically determined ED05 based upon population dose-distribution modelling of peanut, it may show promise for clinical validation of other allergenic food sources where sufficient threshold data is available to model the population dose-distribution. Eventually a single-dose diagnostic OFC using other food allergens may be adopted as well.
Clinicians may be able to use PATS single dose OFCs as they are easier to perform than routine diagnostic OFC or DBPCFC and they could contribute to the complex analysis of risk that clinicians currently make in a heuristic fashion that varies between practitioners. Currently clinicians make value judgements about whether they believe a child to be exquisitely sensitive to a food or not and therefore what to advise with regards to avoiding trace amounts of allergen in food (i.e. foods with precautionary labelling).
The single dose protocol does not replace current clinical food challenges which are for the diagnosis of food allergy but would provide extra clinical information of patients’ level of risk and could help inform consumer choices and physician advice to patients regarding precautionary labelling [20, 21]. This project may offer a practical way to discern whether allergic patients can safely ingest foods with labels such as “may contain traces”, although this outcome would require collaboration with the food industry and more uniform adoption of criteria for use of precautionary labels as proposed in the Australian VITAL strategy.