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Invited Commentary
Allergy
July 15, 2020

Clinician Adoption of US Peanut Introduction Guidelines—A Case for Conditional Recommendations and Contextual Considerations to Empower Shared Decision-Making

Author Affiliations
  • 1Dartmouth-Hitchcock Medical Center, Section of Allergy and Clinical Immunology, Lebanon, New Hampshire
  • 2Department of Pediatrics, Medicine, and Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire
  • 3Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
  • 4Department of Pediatrics, Section of Allergy/Immunology, Children’s Hospital Colorado, University of Colorado School of Medicine, Aurora
JAMA Netw Open. 2020;3(7):e2011535. doi:10.1001/jamanetworkopen.2020.11535

Although screening before peanut introduction in infants is not an international standard of care, Gupta and colleagues1 provide valuable insights into clinician adoption of the 2017 Addendum Guidelines for the Prevention of Peanut Allergy in the United States. More than 1700 pediatricians who completed the survey by Gupta and colleagues1 described their full (29% of respondents) or partial (64% of respondents) adoption of these guidelines. The authors concluded that more work is needed to increase guideline implementation; however, the broader question is whether screening infants with severe eczema and/or egg allergy should be viewed as a physician-directed requirement (and a quality metric) or as a contextual family preference–sensitive discussion. Within a shared decision-making framework, perhaps universal adherence to the 2017 guidelines is neither appropriate nor desired.

The 2015 Learning Early About Peanut Allergy (LEAP) trial provided high-certainty evidence that a previous recommendation to delay peanut introduction was ill-informed and harmful. In the LEAP trial, introduction of peanut to infants (between 4 and 11 months of age) with severe eczema and/or egg allergy was associated with an 81% reduction in peanut allergy prevalence at 5 years of age.2 Based on these results, the 2017 guidelines aimed to encourage peanut introduction during infancy with a risk-stratified approach that incorporated peanut screening before introduction.3 However, the LEAP trial did not specifically examine whether screening to presumptively diagnose peanut allergy without introduction was effective; the LEAP trial only showed that early introduction worked within a screened clinical trial population.2 This distinction is critical because peanut allergy screening, like any screening test, is imperfect. For example, at an 8-mm cutoff, the sensitivity of peanut skin prick testing has been reported to be 0.54 (95% CI, 0.46-0.62), with a specificity of 0.98 (95% CI, 0.95-0.99) and a positive result likelihood ratio of 22.3 (95% CI, 10.5-46.8).4 Although these testing characteristics are good, they may have a role in the overdiagnosis of at least 5% of a screened population. Infants with an overdiagnosis are the most vulnerable because they are excluded from a critical window of opportunity for appropriate peanut introduction to establish peanut tolerance. Thus, screening may save some infants with a true peanut allergy from an index reaction, but the screening recommendation is associated with a preventable life-long peanut allergy in a small but statistically significant percentage of an at-risk group.4

The 2017 guidelines screening recommendation becomes more harmful if only partially adopted. As demonstrated in the study by Gupta and colleagues,1 partial implementation was the most commonly reported scenario. When screening is performed without recommended confirmatory testing (ie, supervised oral challenge), overdiagnosis is associated with a failure in early peanut introduction on a much larger scale, which translates into missed opportunities for preventing peanut allergy. In the LEAP trial per-protocol analysis of infants with positive skin testing results, 34% of infants who avoided peanut developed a peanut allergy, compared with 0% of those who received a peanut introduction during infancy.2 In the real world, barriers to oral food challenges may prevent peanut introduction in those infants with positive peanut testing results because of resource limitations and caregiver or clinician hesitancy.

In addition, substantial harm is associated with screening creep to lower-risk populations, given that many infants who do not meet the 2017 guidelines’ high-risk criteria of severe eczema and/or egg allergy are tested for peanut allergy before consumption. This screening creep is understandable because the distinction between severe and moderate eczema is unclear and variably interpreted.3 In a recent study of 84 infants screened for peanut allergy at a single tertiary allergy center, less than half of infants screened actually met the criteria outlined in the 2017 guidelines, and most infants with positive test results were presumptively labeled peanut allergic and not offered a supervised challenge.5

The health and economic consequences of infant peanut screening are substantial,6 with estimates suggesting that the downstream costs of annual screening could reach $654 115 322 from a US societal perspective and result in 3208 additional peanut allergy diagnoses.6 When considering missed opportunities to prevent peanut allergy, the rate of severe allergic reactions was not considerably different between the screened and unscreened populations.6 A screening approach to peanut introduction is not cost-effective and appears to have low acceptance among clinicians and caregivers.1,5,6 As suggested by the low rate (29%) of full adoption by pediatricians in the study by Gupta and colleagues,1 screening would also be viewed as less feasible.

In the context of these considerations, it is time to reflect on how the 2017 guidelines should be incorporated into practice. Although the guidelines used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) terminology to describe evidence certainty, this method was narrowly applied to the evidence for early peanut introduction but not to the evidence for early peanut screening.3 Although the evidence for early peanut introduction is of high certainty, the evidence supporting screening is not.1,3,6 Briefly, GRADE is a guideline-development framework that results in either a strong or a conditional recommendation for or against any given strategy.7 A strong recommendation would be appropriate for most patients, would be advisable for most practitioners to follow, and could be adopted as a quality metric.7 In contrast, a conditional recommendation indicates that shared decision-making is appropriate on the basis of individual patient values and preferences.7

Because GRADE explicitly and transparently separates certainty of evidence from the strength of recommendations, it is a useful lens through which to view the 2017 guidelines.3,7 In translating evidence to recommendations, GRADE considers key features, including whether the problem is a priority, the balance of harms and benefits, values, resources required, cost-effectiveness, equity, acceptability, and feasibility.7 Because the certainty of evidence for screening is very low and many of the domains within an evidence-to-recommendations matrix would not favor a screening approach over an approach allowing careful, gradual peanut introduction at home, early peanut introduction would receive a strong recommendation within GRADE, but screening would not.1,3,6,7 In a formal GRADE parameter, the issues of timing vs method of introduction would be addressed as separate questions.

The clinician may wonder whether simply feeding peanut to infants without screening (and medicalization) is safe. Although medical complexity has surrounded peanut introduction in the US, this is not the case elsewhere in the world; the US is the only country to recommend universal peanut screening for high-risk infants.6 In Australia, New Zealand, the United Kingdom, and Canada, early peanut introduction at home in infants is encouraged without screening, and infants who display a reaction are evaluated per standard practice.6 No fatality has been reported in the literature from an infant eating peanut for the first time. This risk is low (the risk of fatal anaphylaxis in an unselected population is approximately 1 in 10 million) and is likely outweighed by the risk of a fatal automobile accident from repeated travel to a pediatric or an allergy clinic for a screening and an oral food challenge.6 Therefore, families and clinicians should be given options, and the method of early introduction should be made a preference-sensitive care choice.

As clinicians, we must help families find the balance between the risks and benefits of peanut introduction during infancy. In some circumstances, family preferences may lean toward screening, presumptive peanut allergy diagnosis, or a supervised oral food challenge. However, our recommendations must be contextual and tailored to each patient and family so that we can provide the right care at the right time every time.

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Article Information

Published: July 15, 2020. doi:10.1001/jamanetworkopen.2020.11535

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Shaker M et al. JAMA Network Open.

Corresponding Author: Marcus Shaker, MD, MSc, Dartmouth-Hitchcock Medical Center, Section of Allergy and Clinical Immunology, One Medical Center Drive, Lebanon, NH 03756 (marcus.s.shaker@hitchcock.org).

Conflict of Interest Disclosures: Dr Abrams reported serving on the Healthcare Advisory Board of Food Allergy Canada during the conduct of the study. Dr Greenhawt reported receiving grants from the Agency for Healthcare Quality and Research as well as personal fees from Intrommune, Aimmune, DBV Technologies, Thermo Fisher, Nutricia, Kaleo, Sanofi/Genzyme, Nestle, Genentech, AllerGenis, Aquestive, Allergy Therapeutics, Prota, Monsanto, Merck, GlaxoSmithKline, Aravax, and American College of Allergy Asthma and Immunology outside the submitted work. No other disclosures were reported.

References
1.
Gupta  RS, Bilaver  LA, Johnson  JL,  et al.  Assessment of pediatrician awareness and implementation of the Addendum Guidelines for the Prevention of Peanut Allergy in the United States.   JAMA Netw Open. 2020;3(7): e2010511. doi:10.1001/jamanetworkopen.2020.10511Google Scholar
2.
Du Toit  G, Roberts  G, Sayre  PH,  et al; LEAP Study Team.  Randomized trial of peanut consumption in infants at risk for peanut allergy.   N Engl J Med. 2015;372(9):803-813. doi:10.1056/NEJMoa1414850 PubMedGoogle ScholarCrossref
3.
Togias  A, Cooper  SF, Acebal  ML,  et al.  Addendum guidelines for the prevention of peanut allergy in the United States: report of the National Institute of Allergy and Infectious Diseases-sponsored expert panel.   J Allergy Clin Immunol. 2017;139(1):29-44. doi:10.1016/j.jaci.2016.10.010 PubMedGoogle ScholarCrossref
4.
Peters  RL, Allen  KJ, Dharmage  SC,  et al; HealthNuts Study.  Skin prick test responses and allergen-specific IgE levels as predictors of peanut, egg, and sesame allergy in infants.   J Allergy Clin Immunol. 2013;132(4):874-880. doi:10.1016/j.jaci.2013.05.038 PubMedGoogle ScholarCrossref
5.
Volertas  S, Coury  M, Sanders  G, McMorris  M, Gupta  M.  Real-life infant peanut allergy testing in the post-NIAID peanut guideline world.   J Allergy Clin Immunol Pract. 2020;8(3):1091-1093.e2. doi:10.1016/j.jaip.2019.12.008PubMedGoogle ScholarCrossref
6.
Shaker  M, Stukus  D, Chan  ES, Fleischer  DM, Spergel  JM, Greenhawt  M.  “To screen or not to screen”: comparing the health and economic benefits of early peanut introduction strategies in five countries.   Allergy. 2018;73(8):1707-1714. doi:10.1111/all.13446 PubMedGoogle ScholarCrossref
7.
Shaker  MS, Oppenheimer  J, Wallace  DV,  et al; Joint Task Force for Allergy Practice Parameters; Contributors.  Making the GRADE in anaphylaxis management: toward recommendations integrating values, preferences, context, and shared decision making.   Ann Allergy Asthma Immunol. 2020;124(6):526-535.e2. doi:10.1016/j.anai.2020.03.009 PubMedGoogle ScholarCrossref
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