Peanut Threshold Study

[rebekahc]

I fully understand that numbers are not indicative of severity of reaction nor sensitivity of the individual and simply suggest the likelihood of a reaction.  I post about it often. 

My point is, however, that you would presumably have people who are not allergic (5% or more of those qualified by test results alone) participating in the study.  Therefore their threshold would be extremely high (nonexistent) which would influence the result of the average threshold dose needed to illicit a reaction thus helping to prove the bias of the researchers (PA isn't as big a deal as people make it out to be).

[maeve]

I see your point. 

Looking at the entrance criteria for the study vs. that for the peanut immunotherapy challenge, and they're not dissimilar. In fact, this study sets PPV value much lower than the immunotherapy study and doesn't exclude participants with asthma.

http://clinicaltrials.gov/show/NCT01274429

I agree that confirmation bias is a concern with this study.  A greater concern for me is that the purpose of this study is not to determine a method for testing individual reaction thresholds/sensitivity to devise a protocol to test for this clinically but rather that this is intended to be used in commerical food production and it ignores a pretty basic fact: food production is not like pharmaceutical production in that the finished product will have the exact amount of active (or in this case allergenic) ingredient. The amount of peanut will vary within a batch and from one production run to another. And yet the study's authors envision this as a means to remove warning labeling.

[twinturbo]

^

Going upthread a bit to individuals getting IOFC for low dose challenges. See, that's the difference between recruiting for research (you have a threshold theory you want to test out) and recommending a course for a specific patient as a doctor because the reward outweighs the risks. Patient benefit vs. researcher's benefit. Do no further harm, informed participants who have the ability to opt out, protection of minors, et cetera. Remember the supposed opt out here was hey you fill out this quality of life form you big fraidy cat.

[booandbrimom]

I'm sure this study is like most studies now: you probably have to have a reaction with objective symptoms to qualify. Most don't accept just test results.

[CMdeux]

I thought so, too-- so I looked at both eligibility criteria as well as exclusion criteria.

There are some funky things about BOTH of those criteria, I thought-- and they seem to most likely wind up skewing the distribution away from the low end, sensitivity-wise.

a) inclusion of those who have never had clinically significant reaction Hx.

b) EX-clusion of anyone with asthma (or maybe it was just certain categories. Anyway).

c) EX-clusion of anyone on maintenance antihistamines.

[CMdeux]

PPV doesn't correllate to the sensitivity of the individual.  You could have someone who while just barely above the PPV threshold reacts to minute amounts of an allergen and also have the converse where someone has high RAST levels but is only ingestive reactive.  For example, McC's son's RAST levels are significantly lower than my DD's and have been for quite a while; however, he's had more reactions and airborne reactions. Whereas my DD has not.  I don't think I'm being any more careful in controlling DD's environment than McC. In fact, I might be a little more loose.  Our kiddos just have different reaction thresholds that in no way correllate to their test results.

So even in a group pulled from 95% PPV, you will have people with varying thresholds.

Great point-- which is why most studies won't accept anyone that doesn't have reaction history as part of the "allergic" cohort.

It's a confounding factor otherwise.

[booandbrimom]

The criteria look exactly the same as the criteria for the study we did. FEV1 <80% just means asthma must be well-controlled. They're not saying you can't be on antihistamines - just that you have to be willing and able to discontinue them before challenges.

They had two kids in my son's study who discovered they didn't HAVE a peanut allergy during the first challenge. The doctors and nurses were so happy about those - I'm sure they love including kids who have no real history. The proof is (literally) in the pudding, so I don't know why it matters if they include kids who have never had a reaction. They can't count them in the study results if they don't have an initial reaction. I'm sure they're doing everything they can to dig up participants. 

[candyguru]

I react to airborne peanut so I would never participate in any ingestion study... not even 1.5 mg.   And I would never let me daughters participate either (we've been to the emergency room too many times)

[DrummersMom]

My son is participating in this study. We have agreed to participate based upon some things that were brought up in this thread - IgE >100 but no known ingestion; has had possible contact or airborne reactions but weren't able to determine if it was from dairy, eggs or peanuts as.

Study consists of the challenge and component blood testing, as well as surveys filled out by myself and DS. Doc doesn't think component testing will tell us much as DS does not have environmental allergies. I feel it would mean a lot to us if he tests low/negative to the proteins that are indicators that anaphylaxis is likely to occur upon ingestion. If that is the case, we will likely ask for an actual peanut challenge. He has challenged dairy with known past anaphylaxis and IgE of >100, so we might be the exception to the rule of not wanting to participate a study on thresholds when one has experienced prior anaphylaxis.

Any specific questions you'd like me to ask?

[CMdeux]

Doc doesn't think component testing will tell us much as DS does not have environmental allergies.

I'm not sure that I understand the reasoning here-- is this because some components are more associated with OAS and pollen-cross-sensitization than others?

I'm with you-- given the possibility that reaction history is NOT to peanut at all, I'd think that component testing and a possible challenge are a great idea and possibly a good source of information for you.


I'm also a little confused-- without INGESTION history supporting diagnosis of peanut allergy, is it fair to call your child "allergic" for the purposes of the study?

It seems like that could result in inclusion of any number of patients who are not actually peanut allergic.  What am I missing? 

[DrummersMom]

Inclusion criteria
Each patient must meet all of the following criteria to be enrolled in this study.
• Age between 1 to 18 years old and
• Demonstrate evidence of peanut allergy as defined by either
(a) History of unequivocal exposure (including accidental) and typical acute
allergic reaction within the preceding 2 years and positive peanut SPT/sIgE, or
(b) Positive oral food challenge with peanut performed within 2 years - either
open oral food challenge or DBPCFC (Double-blind, placebo-controlled food challenges)
(c) Peanut never ingested, but sensitisation to peanut above the 95% positive predictive value (PPV) for clinical allergy, i.e. peanut serum IgE ≥ to 15 kU/L (by CAP FEIA) and/or peanut SPT wheal size ≥ to 8 mm within 2 months of the single dose challenge.


DS meets the criteria based upon (c) above.

He had reactions via breastmilk. He has also had contact reactions of which we were not able to determine origin. Daycare provider served and herself ate dairy, eggs and peanuts while caring for DS when the reactions occured. This happened on a few occasions after which we pulled him from daycare.

Your point about whether or not it is fair to include him as peanut allergic in this study goes along with what has been mentioned in this whole thread. That's why I asked "any questions to ask."

[DrummersMom]

Doc doesn't think component testing will tell us much as DS does not have environmental allergies.

I'm not sure that I understand the reasoning here-- is this because some components are more associated with OAS and pollen-cross-sensitization than others?

Yes some components are associated with cross-sensitivity,  to birch tree pollen, I believe. Given my son has no environmental allergies he should test negative to those components.

[CMdeux]

Well, selfishly (since I know you) I'm hoping that your son's RAST is the result of some quirky thing, and that he passes his challenge.   

If that happens, though-- will he still be counted "allergic" for the purposes of the study?

What exactly constitutes a "pass" or a "fail" in the challenge itself?

I'm wondering what they consider to be a normal tolerance.

[twinturbo]

Speaking for myself my questions would actually not be for the test subjects but the researchers. My only concern for test subjects directly would be limited to making sure all human subjects received all due ethical consideration owed to each and every one. And that is the responsibility of the IRB, not me.

Now the ultimate plan on the data use and strategy behind the criteria, especially if there will be some suggestion to correlation through population. Previous stated issues on primitive math modeling in another thread. Depends on what is going to be done with it, their conclusions.

[LinksEtc]

I could be totally wrong here, but I am curious if the results will influence VITAL (the authors seem to have a lot of Australian connections).

http://www.allergenbureau.net/vital/vital

The VSEP is a collaboration between the Allergen Bureau, Food Allergy Research & Resource Program (FARRP) of the University of Nebraska & the Netherlands Organisation for Applied Scientific Research (TNO).

The study could impact advisory labeling.

The thing about FARRP is I keep seeing them push for less labeling.

For example:

sesame seed study.

Survey on Thresholds from FARE (page 4)

http://allergy.hyperboards.com/action/view_topic/topic_id/17461

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New exemptions from Food Allergen Labeling

http://www.regulations.gov/contentStreamer?objectId=090000648121e481&disposition=attachment&contentType=pdf
page 130 & 154