**10. Randomization**

Single-arm trials with historical controls for comparison may be biased by differences in subject characteristics (age, sex, prior therapy, phase of disorder, and supplemental care). Still, when matched controls can be selected, unknown confounding factors may be haphazardly distributed between two groups.

Designing a two-arm trial with distributing the subjects between two groups using randomization can help to minimize potential bias caused by unknown confounding factors. However, a placebo-controlled trial may be ethically defensible when the use of placebo would not add any risk or serious harm to the subjects. Sometimes, crossover design is more ethical and adheres to the principle of good clinical practice. In crossover studies, the subjects are randomly allocated to the treatment or control groups, after the first phase ends, the subjects will change the groups. In this design, all subjects receive all treatments. Of course, the priority of treatments should not harm the subjects.

When an uneven distributed factor between groups recognized, then controlling by statistics method at the analyses level may be considered. One strategy is to stratify the variable and discuss the results at different levels of the variable. A better solution is stratification process at the time of randomization using the permuted blocked randomize allocation. In this method, randomization will be performed using different age and sex blocks. Hence, the subjects will distribute evenly between treatment arms.

In a randomized clinical trial to control for the placebo effect and minimize the study bias, the subjects and researchers should be blinded using placebo, coding, and allocation concealment. In the case of a blinded trial, the protocol must declare who and in what conditions is allowed to break the codes (for example, the supervisor and in emergencies). Breaking the codes must be justified and must be reported [21].

### **11. Reports**

Moving in accordance with protocol allows its accurate reporting, interpretation, monitoring, and verification of the trial. Furthermore, it assures the quality of every aspects of the trial. The data obtained from the trial must be handled, analyzed, synthesized, and reported in a sound approach. In addition, the sponsor or the research institute should be able to carry out on-site inspections of the validity of reported results. Hence, brilliant documentations and reporting are very important as well as the monitoring processes. For this purpose, the research institute should have easy access to all patient files and raw data during the trial [21].

• To verify supply, control, storage, and disposition of investigational product/s

*Turning back additional materials after the trial is finished is one of the inspector's duties.*

• To verify adherence to good clinical practice and standard operating procedures

• To monitor recruitment rate, safety evaluation, and compliant observations

• To check the accuracy and completeness of all trial data and case report forms

• To discuss study plan and problems with main investigator and staff

*trial. They may also verify that trial documents are complete and up-to-date [25].*

*Adherence to the approved protocol ensures that data are correctly gathered and reported. Any changes* 

Good Clinical Practice in Children and Adolescents http://dx.doi.org/10.5772/intechopen.70191 35

*Standard operating procedure (SOP) is a standard comprehensive framework for administration of* 

*Validity and quality of data gathered and safety of patients are monitored by the inspector during the* 

*Case report form is a paper-based or computer-based sheet that is used to record and gather the data on each trial subject during the trial, as defined by the protocol. The documentation should allow easy* 

*Monitors are trained in clinical trial and medical research and may collaborate to improve the quality of* 

During prestudy visit, the monitor ensures feasibility of trial in the center and interest of the investigator. Also he/she makes sure that the investigator understands the required "trial procedures" and sufficient site staff, proper facilities, location, equipment, laboratory, product

• Case report form and documentation of findings including adverse effects, standard oper-

• To verify adherence to the approved protocol/amendments

*to the protocol should be documented and reported.*

*access for verification, audit, and inspection.*

storage, and archive exist to support the study.

The inspector may discuss with investigator(s) about

*clinical trials.*

**13. Monitoring visits**

• The protocol in detail

ating procedures

• Assenting children (if present)

• Consent form

**13.1. Pretrial monitoring visit**

*trial.*
