**Good Clinical Practice in Children and Adolescents**

**Good Clinical Practice in Children and Adolescents**

DOI: 10.5772/intechopen.70191

Mohammad Reza Mohammadi and Seyed-Ali Mostafavi Ali Mostafavi Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Mohammad Reza Mohammadi and Seyed-

http://dx.doi.org/10.5772/intechopen.70191

#### **Abstract**

[34] Stojkovic A, Simovic A, Bogdanovic Z, Bankovic D, Poskurica M. Optimal time period to achieve the effects on synbiotic‐controlled wheezing and respiratory infections in young children. Srpski Arhiv za Celokupno Lekarstvo. 2016;**144**(1‐2):38‐45. DOI: 10.2298/

[35] Million M, Lagier C‐J, Yahav D, Paul M. Gut bacterial microbiota and obesity. Clinical

[36] Henao‐Mejia J, Elinav E, Jin C, Hao L, Mehal ZW, Strowig T, et al. Inflammasome‐medi‐ ated dysbiosis regulates progression of NAFLD and obesity. Nature. 2012;**482**:179‐185.

[37] Litonjua AA, Sparrow D, Celedon JC, DeMolles D, Weiss ST. Association of body mass index with development of metacholine airway hyperresponsiveness in men: The nor‐

[38] Szefler JS. Advances in pediatric asthma in 2014: Moving toward a population health perspective. Journal of Allergy and Clinical Immunology. 2015;**135**:644‐652. DOI: http://

[39] Baffi WC, Winnica ED, Holguin F. Asthma and obesity: Mechanisms and clinical impli‐ cations. Asthma Research and Practice. 2015;**1**:1‐7. DOI: 10.1186/s40733‐015‐0001‐7 [40] Xystrakis E, Kusumakar S, Boswell S, et al. Reversing the defective induction of IL10 secreting regulatory T cell in glucocorticoid resistant asthma patients. Journal of Clinical

[41] Gupta A, Sjoukes A, Richards D, Banya W, Hawrylowicz C, Bush A, Saglani S. Relationship between serum vitamin D, disease severity, and airway remodeling in children with asthma. American Journal of Respiratory and Critical Care Medicine.

[42] Nanzer MA, Chambers SE, Ryanna K, Richards D, Black C, Timms MP, et al. Enhanced production of IL‐17A in patients with severe asthma inhibited by 1alfa,25‐dihydroxyvi‐ tamin D3 in a glucocorticoid‐independent fashion. Journal of Allergy and Clinical

[43] Moreira A, Bonini M, Garcia‐Larsen V, Bonini S, Del Giacco RS, AgacheI, Fonseca J, Papadopoulos GN, Carlsen HK, Delgado L, Haahtela T. Weight loss interven‐ tions in asthma: EAACI Evidence‐based clinical practice guideline (part I). Allergy.

[44] Kalliomäki M, Salminen S, Poussa T, Arvilommi H, Isolauri E. Probiotics and preven‐ tion of atopic disease: 4‐Year follow‐up of a randomised placebo‐controlled trial. Lancet.

[45] Macrolides. BNF for Children 2014. Vol. 15. London, UK: BMJ Group, Pharmaceutical

[46] Penicillins. BNF for Children 2014. Vol. 15. London, UK: BMJ Group, Pharmaceutical

mative aging study. Thorax. 2002;**57**(7):581‐585. DOI:10.1136/thorax.57.7.581

Microbiology and Infection. 2013;**19**:305‐313. DOI: 10.1111/1469‐0691.12172

SARH1602038S

28 Clinical Trials in Vulnerable Populations

DOI: 10.1038/nature10809

dx.doi.org/10.1016/j.jaci.2014.12.1921

Investigation. 2006;**116**(1):146‐155. DOI: 10.1172/JCI21759

2011;**184**:1342‐1349. DOI: 10.1164/rccm.201107‐1239OC

2013;**68**(4):425‐439. DOI: 10.1111/all.12106

2003;**361**(9372):1869‐1871. [PMID: 12788576]

Press. pp. 283‐286. Available from: www.bnf.org

Press. pp. 261‐269. Available from: www.bnf.org

Immunology. 2013;**132**:297‐304. DOI: 10.1016/j.jaci.2013.03.037

Good clinical practice (GCP) is a series of systematically developed ethical and quality standard of designing, registering, running, recording, and reporting of the clinical trials. Good clinical practice is very important regarding the trials usually performed on the vulnerable populations especially children and adolescents. The sensitivity of the issue is even higher in the children with psychiatric disorders. Usually, these children have little legal protection. Hence, the safety of interventions and the ethical considerations are among the most important issues in this field. The purpose of this chapter is to deal with above problems and globally applicable standards for the conduct of clinical trials on the under legal age subjects especially those with psychiatric disorders. Selection of trial subjects, ethical principles, regulatory requirements, protection of trial subjects, monitoring (compliance with the protocol), responsibilities of the investigator, and other requirements to perform a clinically and ethically sound clinical trial in children and adolescents will be discussed in this chapter.

**Keywords:** children and adolescents, ethics, good clinical practice, monitoring

#### **1. Introduction**

While new medical products (drugs and vaccines) are being developed and asking for registration, their efficacy and safety should be assessed in a well-designed clinical trial, ultimately on human beings [1]. This process is costly, and ethical considerations are controversial. The history of developing of good clinical practice (GCP) goes back to the end of World War 2 following the Nuremberg trials on war victims. In Nuremberg Nazi, physicians were accused for performing inhumane trials on human beings in the name of medical research. After the

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war, two American doctors who were present in Nuremberg invented a set of research ethics principles including 10 points which are in compliance to the human rights. These principles are known as Nuremberg Codes [2, 3].

needed to be developed for children and adolescents. Furthermore, some supplements are targeted for this group of population [8–10]. Hence, performing clinical trials on children and adolescents is a critical mission sometimes inevitable. Children are vulnerable population in medical research; hence, inclusion of children in clinical trials always is a matter of great concern for parents, researchers, and ethic committees. Children and adolescents who will attend in the clinical trials should be selected carefully by a qualified physician. The physician should be qualified by sufficient education, training, and experience and should be in charge for optimum health of the participants. All diagnosis should be supported by the latest clinical guidelines [11]. Furthermore, inclusion and exclusion criteria should be carefully set on the basis of study objectives and previous studies. The processes of medical care and every decisions made here should be based on evidence and guarantee the maximum safety of the patients in a way that the rights and well-being of the children would be protected. Blood sampling in children is not ethical if the benefits of the study do not exceed the harms for children. When a specific group of children directly benefit from blood sampling or blood sampling is necessary for diagnosis, the documents should be presented to the institutional ethics committee and benefits should be described to the parents or legal guardians. The subjects or his/her parent or legal guardian should be adequately informed about the processes of research, the rights and responsibilities. The aims and methods of the research should brightly be described to them. Furthermore, the subjects and their legal guardian must be aware of anticipated benefits and potential hazards of the intervention. Then, informed consent must be signed by the parents or legal guardian of the subjects below the legal age. Moreover, the subjects should ascent to participate. Then, after obtaining sufficient ethical approvals and consent forms, blood sampling could be gathered by a trained client under the guidance of existing guidelines [12, 13]. In clinical trials on pediatric psychiatry, a team-based approach involving the laboratory physician would help the quality assurance of examination, diagnosis, and reporting, as well

Good Clinical Practice in Children and Adolescents http://dx.doi.org/10.5772/intechopen.70191 31

In trials with the main objective of efficacy assessment, the safety assessment is usually the secondary objective. One of the responsibilities of the researcher is to carefully monitor the adverse effects and record immediately when a participant experiences any side effect [16]. Then, the investigator should report it in a suitable way. Furthermore, in respecting the privacy, the researchers should guarantee the confidentiality of records that could identify the subject. Another duty of the researcher is to provide best possible care available and follow until complete disappearance of adverse effect. Sometimes, it is necessary to stop the trial to protect one or more subjects. Sometimes, the subjects or the legal guardian themselves decide to stop medication. In pediatric psychiatry, loss to follow-ups happens due to adverse effects of the intervention, stigma, and lack of parent's knowledge about medicinal psychotherapy [17]. So, the researcher should conduct a thorough investigation and find the exact reason of each loss to follow-up and report it. Usually, identifying the barriers and reducing them would be helpful. Educating the parents and legal guardians to help reduce the stigma of referring to psychiatrist and fear of tacking psychiatry medications may support the children health [18].

as patient safety [14, 15].

**5. Safety reporting**

Later in 1964, the elected medical representatives came from all over the world, attended the 18th General Assembly of the World Medical Association in Helsinki. They decided to improve the points asserted in the Nuremberg Code and create a more formal statement of ethical principles. Its attitude was to provide detailed directions for medical science researchers to conduct the trials on human subjects with scientifically sound methods and in accordance with basic ethical principles. This statement is known as the "Declaration of Helsinki," and until now, several revisions have been released [4].

This history formed the basis for developing good clinical practice.
