Written Consent to Use the Drug in Children: The Problem of Off-Label Drugs

Abstract

Cardiac arrhythmias in pediatric patients have different mechanisms and frequencies compared to adult patients. There are many physiological differences between children and adults that may affect the pharmacodynamic and pharmacokinetic of the antiarrhythmic drugs in pediatric population. Children, and specially breast feeding children, cannot be considered low weighted adults to select antiarrhythmic drug doses. Although radiofrequency ablation has experienced great technological advances, it is performed in selected pediatric patients. Therefore, the main therapeutic strategy is the use of antiarrhythmic drugs in children. The medical management of arrhythmias in pediatric patients is challenging and complex. There are few clinical guidelines. There is scarce and incomplete information about the efficacy and safety of antiarrhythmic drugs in pediatric population. Most of the doses and drug administration intervals are extrapolated from adult population and applied to children. Antiarrhythmic drug doses have been extensively studied in adult population. However, in pediatric population, there are very few clinical trials and the safety of these drugs is not well known. In general, dose regimens are based on small uncontrolled studies, extrapolation of drug doses from studies performed in the adult population or physician experience. As a consequence, there is a need for further studies to assess the most effective antiarrhythmic drug regimens in children reducing the risk of side effects. Evidence suggests that medical research in pediatric population is necessary and morally valuable. But investigators involved must take care of moral and ethical values, including the respect for the child-subject and his parents or legal representatives, and this respect compels them to consider the patient and family in the decision making process. The participation request and the informed consent must be obtained according to the competitions the patient exhibits, trying to anticipate information about benefits and possible damages derived from the investigation in an understandable language for him. In our opinion the pharmacologic clinical investigation of antiarrhythmic treatments in pediatrics is necessary. More clinical studies must be carried out under rigorous scientific rules that contemplate the particular ethical dilemmas this population faces.

Prediction of antiarrhythmic therapy effectiveness in children

“…Ряд исследователей сообщает о высокой эффективности лекарственной терапии у новорожденных и детей раннего возраста и рекомендуют схемы терапии, включающие комбинации двух и даже трех препаратов для пролонгированного лечения аритмий [21][22][23][24][25]. Однако большое количество публикаций свидетельствует об ограниченной эффективности и безопасности ААТ для контроля аритмий у детей [2][3][4][5][6]25].…”

“…По мнению Maid G, et al основные принципы ААТ у детей, дозировки и интервалы приема ААТ заимствованы из "взрослой" аритмологии без учета физиологических особенностей новорожденных и детей раннего возраста. Поэтому многие авторы призывают медицинское сообщество к организации многоцентровых рандомизированных плацебо-контролируемых клинических испытаний, в которых бы изучалась профилактическая эффективность данных препаратов, результаты которых могут отличаться от результатов ретроспективных исследований [6].…”

“…Данные о медикаментозной рефрактерности, имеющихся летальных исходах и жизнеугрожающих событиях в результате применения антиаритмической терапии (ААТ) у детей, заставляют с определенной осторожностью относиться к широко распространенному убеждению, что ААТ у новорожденных и детей раннего возраста эффективна и безопасна и может являться этапом терапии, предшествующим радикальному катетерному лечению аритмии при достижении рекомендуемого возраста [2][3][4]. Учитывая, что ААТ в настоящее время остается основной терапевтической стратегией в лечении аритмий у детей раннего возраста, необходима оптимизация лечебной тактики на основе оценки эффективности антиаритмических препаратов и определение предикторов медикаментозной резистентности аритмий [5][6][7].…”

Ethics in child and adolescent psychiatric care: An international perspective

“…Transparency and informing the patient remain essential requirements for several treatments in everyday practice (Bakker, Kolling, van den Berg, De Walle, & De Jong van den Berg, 2008;Maid, Guerchicoff, & Falconi 2008;Tan & Koelch, 2008;Volkers, Heerdink, & van Dijk, 2007;Waller, 2007). The vulnerability of the population must be kept in mind, but the danger of paternalism must also be considered since this would conflict with the right of the child to self-determination and inclusion.…”

IMI – Industry Guidelines and Ethical Considerations for Myopia Control Report

“…Unless treatments for MC are specifically approved for that purpose, their use is considered off-label and, therefore, adequate informed consent prior to their use should be obtained to minimize potential misinterpretations and/or legal claims. [58][59][60][61] For detailed information on the informed consent process, readers are referred to the US Office for Human Research Protection 62 and for more specific information on informed consent for MC to the accompanying IMI -Clinical Management Guidelines Report. 63 Informed consent is not simply a signature on an informed consent form but, rather, it is a process of communication between the HCP and the patient.…”