Experimental Pediatric Medicine: Allergic Children in Clinical Trials
Typical allergic reactions cause some discomfort, but are otherwise normally mild. In severe cases, however, children can die of anaphylaxis (a serious allergic reaction that can cause breathing to stop) when exposed to small amounts of allergens. These allergic reactions can be particularly severe when related to food, forcing the parents of affected children to constantly monitor their children’s surroundings. Should the child come in contact with the allergen, the only known treatment is an injection of adrenaline through a device called an EpiPen, but even this only reduces the severity of the symptoms. (Thernstrom, 2013) An ideal treatment would prevent the symptoms from occurring altogether, rather than stop the symptoms from getting any worse.
Clinical trials, standardized methods of developing experimental treatments, are being conducted to develop a potential cure for allergies. Oral immunotherapy (treatment of allergies through decreasing amounts of allergen consumption) has emerged as a relatively new treatment, but parents and scientists may be reluctant to include children in these trials because of the dangers of the practice. This creates a lack of interest and leads to insufficient funding from the government. (Thernstrom, 2013) These factors impede the development of new treatments, leaving children vulnerable to life-threatening conditions. Although clinical trials carry risks, the practice of including allergic children in experimental medicine is ultimately beneficial for both the patient and the scientific community.
Introduction to Clinical Trials
Jonathan Wu
1559 words

Clinical trials are studies conducted on human test subjects to determine the effectiveness of new medical treatments. They are designed to minimize the amount of risk to their participants while providing needed information on the effectiveness of the procedure. The
United States Congress coined the term “substantial evidence” in 1962 to mean “evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified….”(as cited in Meinert, 1986) Without “substantial evidence” of the effectiveness of a treatment, the United States’ FDA (Food and Drug Administration) is unable to approve medicine for widespread use. In this age of evidence-based medicine and healthcare, clinical trials are necessary for medicine to advance.
When children are involved, moral and legal issues often arise, producing the need for more strict regulations. Participants of clinical trials are normally protected by informed consent, a condition that requires researchers by law to provide potential and enrolled participants with information about their clinical study. This information includes, but usually consists of more than, the risks, potential benefits, and alternatives to said study. (“Clinical Trials”, n.d.) Even though they may be presented with this information, “children are not fully capable of informed consent and cannot adequately weigh the risks or benefits [of experimental procedures]”
(PCRM). Thus, the decision to enroll children in clinical trials lies in the decisions of the child’s guardian. Although parents are able to weigh the risks against the benefits of the trial, they are ultimately making the decision on practices that could potentially affect the rest of their children’s lives. Children still have a say in the matter though, as “parental consent will probably be invalid if it is given against the child’s interests.” (Costello, 2007) Current regulations on clinical trials are very strict in order to protect participants, especially in the case of children.

This ensures that they will receive the greatest benefit out of experimental treatments while minimizing the risks they must take.
Why Child Participants are Necessary
Allergic children must be included in clinical trials, as it would be incredibly difficult to develop effective treatments without trial participants. Child medicine comes with its own complications because some conditions—such as prematurity and many of its sequelae—occur only in children.
Similarly, certain genetic conditions such as phenylketonuria (PKU) will, if untreated, lead to severe disability or death in childhood. The diagnosis, prevention, and treatment of these conditions cannot be adequately investigated without studying children. Other conditions such as influenza and certain cancers and forms of arthritis occur in both adults and children, but their pathophysiology, severity, course, and response to treatment may differ for infants, children, and adolescents. Treatments that are safe and effective for adults may be dangerous or ineffective for children. (Field, 2004)
Statistics on severe allergic reactions only support many of the reasons why children must be included in clinical trials. These allergies often lead to a carefully monitored dietary regimen in childhood that, if not followed, can cause death due to anaphylactic shock. (Thernstrom, 2013)
The majority of children outgrow their allergies with age, so securing ordinary adult participants would become difficult. Even if enough adults volunteer, effective treatment for allergic adults may not have the same effect on children. (Field, 2004) As food allergies among children are increasing in prevalence (Thernstrom, 2013), the need for an effective treatment increases.

Children volunteering to test potential treatments benefit not only themselves, but provide valuable information used to treat future generations.
The Treatment
Oral immunotherapy, a type of desensitization treatment, emerged as a method of treating allergens in the 1980s. The treatment is performed by feeding allergic children small amounts of allergen in a closely monitored environment, starting at the smallest possible dose that can trigger an allergic reaction. The amount ingested can be carefully controlled by processing the protein from the food that the child is allergic to. This level of control allows the child to build up a resistance while keeping the adverse effects to a minimum. Over time, the child is able to take larger and larger doses of the allergen until their reaction to a relatively large dose no longer becomes life threatening. Desensitization is treated as a different clinical trial for each specific allergen because of greatly varying factors from allergen to allergen, including the severity of the reaction and the effectiveness of the treatment. Due to the rarity and risks of their situation, children who are allergic to multiple foods can find it very difficult to obtain treatment, or even participate in clinical trials. With greater interest and increased funding, more clinical trials could be made available. (Thernstrom, 2013)
Oral immunotherapy is still an experimental practice, as reactions to the treatment can vary. In a recent clinical trial, child participants underwent desensitization to peanuts over a period of six months (Anagnostou et al, 2014). Although 24 of the 39 participants reached the desired outcome (desensitization to peanut allergies), the procedure was ineffective on the remaining 15, resulting in a mere 62% success rate. Adverse effects included widespread (31 of
39 participants) vomiting and nausea. This may seem discouraging, but the study reported an

overall improvement in the quality of life (a score on the standard of living, calculated by a formula to assess the effectiveness of the treatment) of the participants, who were able to ingest peanut products with only mild discomfort. The side effects were also relatively mild for potentially fatal allergic reactions. (Anagnostou et al, 2014) Further trials should be carried out in order to refine the process, phasing out the unwanted side effects while increasing the success rate.
Desensitization has made a large amount of progress in a relatively short amount of time, but is still a treatment of great controversy. In the early 1990s, immunotherapy was performed with subcutaneous treatment (under the skin). This was mostly discontinued by the United
Kingdom’s Committee on the Safety of Medicines when several deaths occurred from the treatment of hay fever. The treatment became more controlled, reserved only for extreme cases of hay fever. Oral immunotherapy has since emerged as an entirely different practice for treating food allergies with roughly the same underlying process.
Despite promising results, there is little knowledge about how long the effects last, leading some clinicians to question whether the short-term benefits are worth the child’s discomfort and risk of death. Safety is also a concern, due to the severity of anaphylactic shock.
(Sheik et al, 2010) Because of this, clinical trials on children are not met without resistance.
Some clinicians oppose the practice, stating “reports that a few clinicians in the United States have taken this leap [of oral immunotherapy for peanut allergies] are thus very worrying.” (Sheik et al, 2010) However, the clinicians practicing the treatment in the United States are following strict guidelines to ensure the safety of their patients, and oral immunotherapy as an effective treatment can be best refined through additional clinical trials.

What Should be Done
Life-threatening allergies create large amounts of unnecessary stress for children and their parents. Oral immunotherapy shows promise, but in order to develop and refine this treatment, more clinical trials must be run. Without child participants, the safety and effectiveness of treatments are unable to be properly evaluated. Participants often benefit from these trials, as they are receiving treatment while none would otherwise be available. Parents and doctors should make more of an effort to include allergic children in clinical trials in order to benefit both the children suffering today and the future population. Although immunotherapy may seem dangerous, desensitization to a life-threatening allergen increases the quality of life for children overall.
An increase of interest in clinical trials for oral immunotherapy is necessary for this field of study to receive the funding it deserves. Clinicians are often forced to fund their own research or turn to private parties for finances due to a lack of interest from the government. Hopefully these clinical trials will acquire more government funding as the number of allergic children continues to rise.

Sources
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potentially important advance, but long term effectiveness and safety need to established.
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