Statistical issues in clinical trials that involve the double-blind, placebo-controlled food challenge
Department of Health Evaluation Sciences, Penn State College of Medicine, Hershey, PA 17033-0855, USA. Journal of Allergy and Clinical Immunology
(Impact Factor: 11.48).
04/2005; 115(3):592-7. DOI: 10.1016/j.jaci.2005.01.008
The double-blind, placebo-controlled food challenge is a rigorous tool that has become popular for evaluating adverse reactions to foods. The standard use of the double-blind, placebo-controlled food challenge has been to document food allergies for individual patients, but it recently has been gaining acceptance as a procedure for investigating the effectiveness of therapies to prevent/minimize food-induced anaphylaxis. The purpose of this study was to describe the statistical design and analysis issues for clinical trials that use the double-blind, placebo-controlled food challenge in measuring sensitivity to food allergens. Nonparametric tests for within-group and between-group comparisons are described, as well as a discrete-time survival analysis. The statistical methods are applied to simulated data from a clinical trial that compares control therapy and experimental therapy groups. The results indicate that the experimental therapy is significantly better than control in improving the tolerance to peanut flour in patients with peanut allergy. Although simple nonparametric tests for within-group and between-group comparisons are easy to apply, a discrete-time survival analysis provides the best approach because of its flexibility in accounting for important independent variables (regressors) and longitudinal data. Statistical software packages can be adapted to perform such analyses.
Available from: osufacts.okstate.edu
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ABSTRACT: Adverse reactions to foods, aside from those considered toxic, are caused by a particular individual intolerance towards commonly tolerated foods. Intolerance derived from an immunological mechanism is referred to as Food Allergy, the non-immunological form is called Food Intolerance. IgE-mediated food allergy is the most common and dangerous type of adverse food reaction. It is initiated by an impairment of normal Oral Tolerance to food in predisposed individuals (atopic). Food allergy produces respiratory, gastrointestinal, cutaneous and cardiovascular symptoms but often generalized, life-threatening symptoms manifest at a rapid rate-anaphylactic shock. Diagnosis is made using medical history and cutaneous and serological tests but to obtain final confirmation a Double Blind Controlled Food Challenge must be performed. Food intolerances are principally caused by enzymatic defects in the digestive system, as is the case with lactose intolerance, but may also result from pharmacological effects of vasoactive amines present in foods (e.g. Histamine). Prevention and treatment are based on the avoidance of the culprit food.
Baillière' s Best Practice and Research in Clinical Gastroenterology 02/2006; 20(3):467-83. DOI:10.1016/j.bpg.2005.11.010 · 3.48 Impact Factor
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ABSTRACT: Intramuscular adrenaline is the treatment of choice for food-related anaphylactic reactions. Although auto-injectable adrenaline devices are routinely prescribed for patients at risk of serious reactions, previous studies have shown that only one-third to one and a half of patients or their carers are able to properly use these devices. The aim of this study was to determine which factors are most strongly associated with the effective use of these devices. A 122 children with food allergies who had previously been prescribed EpiPens and were attending a single specialist pediatric allergy center in the UK. were studied prospectively. A 69% of parents were unable to use the EpiPen, did not have it available, or did not know when it should be administered. A prior practical demonstration was associated with a 4-5 fold greater chance that parents would be able to use the device (p < 0.005). Prior consultation with an allergy specialist rather than a general physician, and parents who independently sought additional information from the national self-help allergy organization were also four to six times more likely to be competent with these devices (p < 0.005). The study clearly shows that for EpiPens to be used safely and effectively it is essential to educate the carer at the time the device is prescribed.
Pediatric Allergy and Immunology 05/2006; 17(3):227-9. DOI:10.1111/j.1399-3038.2006.00392.x · 3.40 Impact Factor
Available from: pediatrics.aappublications.org
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ABSTRACT: Food allergy is a common pediatric problem, affecting as many as 6% of young children, yet it is unclear whether pediatricians are well prepared to manage food-induced anaphylaxis.
The purpose of this work was to assess pediatricians' knowledge of diagnosis and management of children with food-induced anaphylaxis.
A survey designed to assess food allergy diagnosis and management was mailed to a US national random sample of 1130 pediatricians. Survey questions were based on a clinical scenario involving a child having an anaphylactic reaction after ingesting peanut. Primary outcome measures included correct responses to the 11 questions about anaphylaxis.
A total of 468 pediatricians (41%) responded to the survey. The majority of the respondents were women (58%), spent > 50% of their time in a clinical setting (78%), and reported providing care for food allergy patients (86%). Overall, 70% of the pediatricians agreed that the clinical scenario was consistent with anaphylaxis, and 72% chose to administer epinephrine. However, only 56% of respondents agreed with both the diagnosis of anaphylaxis and treating with epinephrine. Most pediatricians (70%) did not recognize that a 30-minute observation period after anaphylaxis was too short. Pediatricians who reported providing care for food allergy patients were more likely to agree with the diagnosis of anaphylaxis (73% vs 59%), with treating the reaction with epinephrine (73% vs 64%), and with prescribing self-injectable epinephrine (83% vs 66%) than pediatricians who did not care for food allergy patients. The more certain that pediatricians were that the child was having an anaphylactic reaction, the more likely they were to agree with treating the reaction with epinephrine. In general, recent continuing medical education was not predictive of improved knowledge.
Although the majority of pediatricians seem to have some knowledge of food-induced anaphylaxis, a substantial proportion has knowledge deficits that may hinder their ability to provide optimal care to children with food-induced anaphylaxis. Pediatricians who provide health care for patients with food allergy may be better equipped to manage food-induced anaphylaxis than those who do not. Because continuing medical education was not a significant predictor of increased knowledge, ensuring that pediatric residents develop experience managing patients with food allergies may be a better strategy to educate primary care pediatricians about food allergy.
PEDIATRICS 09/2006; 118(3):e554-60. DOI:10.1542/peds.2005-2906 · 5.47 Impact Factor
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