Protocol Summary
The clinical trial protocol titled “The Use of Sleephormone1in Children with Neuro-Developmental Disorders and Impaired Sleep: a Randomized, Double-Blind, Placebo-Controlled Parallel Study” is structured according to the norms of clinical research. The protocol covers the research on the efficiency of Sleephormone1 versus placebo for solving insomnia issues and reducing the latency sleep time in patients 5 to 15 years old suffering from neuro-developmental and sleep disorders. The sampling technique used for the protocol requires the parents’ consent and absence of any medical factors not allowing the clinical trial and treatment procedures.
Data are collected through the five major survey questionnaires including the Children’s Sleep Habits Questionnaire (CSHQ), PedsQL™ Family Impact Module, Epworth Sleepiness Scale, Aberrant Behaviour Checklist, and Composite Sleep Disturbance Index. The results will be analyzed through the comparison of the subjective and objective data retrieved through the use of sleep diaries and actigraphy before and after the clinical trial.
Dictionary and Coding Management
The dictionary and coding management procedures are of vital importance for clinical trials, especially when the matter concerns that drug trials, testing procedures of the non-licensed medications, and the drugs whose potential positive or negative influence are studied not enough or completely unknown (Rondel, Varley, and Webb, 2000, p. 97). Thus, for the properly structured management of data in the above stipulated clinical trial protocol, the names of the medications used in the trial and for treating the potential adverse effects of the tried drugs will be listed in the research facility register (DeRenzo and Moss, 2005, p. 198).
For this purpose, the auto-coding services will be implemented as they allow saving time and effort in the process of compiling the company’s dictionary of terms and codes used with medications and drugs used or tested (Rondel, Varley, and Webb, 2000, p. 98).
Definitions and Acronyms
For the better management of the data that are planned to be retrieved from the clinical trial procedures, the following list of the definitions and acronyms used in the trial process is given (DeRenzo and Moss, 2005, p. 201). This list includes the acronyms used to refer to the medical substances, drugs, and other medications, as well as to various testing methods, questionnaires used in the clinical trial process, etc.:
- ABAS – Adaptive Behaviour Assessment System
- ABC – Aberrant Behaviour Checklist;
- AE – Adverse Event, i. e. any untoward medical occurrence in a subject to whom a medicinal product has been administered, including occurrences which are not necessarily caused by or related to that product;
- ASD – autistic spectrum disorder;
- CRF – Case Report Form;
- MHRA – Medicines and Healthcare products Regulatory Agency;
- OSAS – Obstructive Sleep Apnoea Syndrome;
- RCT – randomized controlled trials;
- SAE – Serious Adverse Event, i. e. any adverse event or reaction that results in death or is life-threatening;
- Sleephormone1 – medication that allegedly eases the sleep disorders and reduces the sleep latency in children with developmental and sleep disorders; it is the subject of the planned clinical trial;
- TESS – Treatment-Emergent Signs and Symptoms.
Personnel/Role Identification/Training
The personnel involved in the clinical trial can be divided into three major groups. The first group consists of the local pediatricians who are familiar with the health records of their patients and can recommend potential clinical trial participants. The second group of personnel involved includes the research clinicians, and the third group consists of the research and study nurses. The role identification among the three personnel groups is determined by the planned clinical trial schedule discussed further (DeRenzo and Moss, 2005, p. 202).
Thus, the local pediatricians will be charged with the task of selecting and recommending the potential trial participants based on their health records and data on developmental or sleep disorders of theirs. The role of the clinicians in this trial is reduced to the preliminary examination and enrollment of the trial participants, and the concluding clinical examination of these people taken up during the completion stage of the trial.
The research clinicians will review the trial results, analyze the participants’ diaries and questionnaire results, and make respective conclusions about the effectiveness of Sleephormone1 versus placebo for sleep disorder treatment and sleep latency time reduction. Finally, the research and study nurses will be responsible for gathering the specific data from every single trial participant. The nurses will also be charged with the synthesis of the data collected and presenting them for the consideration of the research clinicians.
Timelines
The timelines will also be rather important for the success of the clinical trial. Thus, the whole trial procedure will take 12 weeks that will be divided between the processes of sampling and preliminary examination of the potential trial participants, the enrollment of the samples people, the clinical and outpatient observation and examination of the trial participants, and analyzing the retrieved results (Gallin and Ognibene, 2007, p. 198). Also, the trial will need 4 additional weeks for participants’ screening and home visiting. The timeline for the clinical trial will look as follows:
Table 1: Clinical Trial Timeline.
Case Report Forms
The case report forms for reporting the clinical trial findings will be executed in double copies combining the printed and the electronic variants. The five major case report forms that the clinical trial will resort to include Children’s Sleep Habits Questionnaire (CSHQ), PedsQL™ Family Impact Module, Epworth Sleepiness Scale, Aberrant Behaviour Checklist, and Composite Sleep Disturbance Index (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, pp. 111 – 112).
The case report forms will include all detailed information on the clinical trial progress in every single participant of this research. Each of the case report forms will contain information on a particular aspect of the sleep disorder and its influence upon the family development, the progress of the clinical trial, the changes in the rates of daylight sleepiness and weariness, the rates of waking during a night’s sleep, and of course the possible adverse effects of the drug tried during this clinical research, i. e. Sleephormone1. Clinical research nurses will be charged with the task of preparing the case report forms, filling them with the respective data, and presenting them for the research clinicians’ consideration (Rondel, Varley, and Webb, 2000, p. 101).
Database Design, Creation, and Maintenance
Naturally, the data retrieved during the clinical trial research of Sleephormone1 need to be placed into a single and secure database where they can be stored, retrieved for analysis, or reassessment. The design of such a database should include all the data obtained by the stages of the clinical trial (Rondel, Varley, and Webb, 2000, p. 100). Therefore, the database design for the Sleephormone1 clinical trial should include sections containing data on participants’ screening and sampling, the preliminary examination of the participants, and their inclusion and exclusion criteria.
As well, the database should contain the sections to store the data obtained from every questionnaire survey carried out during the trial, and these data should be separated by every particular participant (DeRenzo and Moss, 2005, p. 204). The creation of the database will be carried out simultaneously with the obtaining of the data, so every database section will be compiled successively (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 113).
The database maintenance will be limited to two major activities. First, the protection of the data contained in this database will be ensured by the specially appointed research nurse that will be responsible for supervising the database and creating the spare copies of data that can be used in case if the original database is damaged. Second, the security and privacy of the data regarding every clinical trial participant will be ensured by the privacy policy statement and the legal responsibility of the institution carrying out the trial of Sleephormone1 (Gallin and Ognibene, 2007, p. 199).
Database Archive
As every clinical trial research should follow the specific scheme of collecting, processing, analyzing, maintaining, transmitting, or archiving the data obtained in its progress, the current clinical trial of Sleephormone1 will place its archiving stage between the data collection and data analysis stages. This will allow achieving two major research goals, i. e. obtaining the specific clinical trial data on the efficiency of Sleephormone1 in comparison to placebo and the opportunity for the secure analysis of these data, provided that they are grouped and archived in the clinical trial database (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 128).
Archiving a trial database involves also the use of the special database maintenance software, whose choice should be based on the best relation of quality and security guarantees available in the market (Gallin and Ognibene, 2007, p. 202). Thus, under the conditions of the proper handling, the database archive might be one of the powerful tools of the clinical trial results analysis alongside statistical analysis, the examination of adverse effects, and the analysis of the effect of the concomitant medications upon the performance of the tried medication (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 129).
Database Roles and Privileges, Security, Data Entry and Processing
The great role in creating, handling, and processing the clinical trial databases is attributed to the trial sponsors, i. e. companies that produce the medication or drug that is to be tried and further licensed (or eliminated from the production list of this company if the trial data are negative) (Rondel, Varley, and Webb, 2000, p. 102). One of the major tasks of the trial sponsors and researchers is to ensure the security of data during the procedures of collection, processing, archiving, and long-term storing.
The point here is that the data of the Sleephormone1 clinical trial, as well as the data of numerous other trials, are intended to be stored in the Electronic Data Capture System (EDC), which is an online database environment subjected to the vulnerability and privacy infringement threats (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 118). To protect the trial databases from these threats, the EDC used should be supplied with the standard operating procedures that have the introduction of the role-based design for the database as one of their major conditions (DeRenzo and Moss, 2005, p. 204). The use of this database design involves passwords and other means of authentication of any person accessing the system, like samples of handwriting, etc.
Data Validation and Quality Assurance/Control Processes
Further on, the sponsor of any clinical trial is responsible for the guarantee of the quality of trial data and findings. In this respect, the concepts of data validation, quality assurance, and control are of special importance (Gallin and Ognibene, 2007, p. 219). Defined as “several steps needed to turn the original or “raw” item or items into a finished item, that is to turn the CRF data into a clean database“(Rondel, Varley, and Webb, 2000, p. 110), the data validity should be considered by the trial researchers, trial sponsors, and the clinical data management (CDM) department of the company initiating the Sleephormone1 clinical trial.
The investigators will assure the data validity through strict control over the CFRs being numbered and perfectly compiled. Needless to say, the timely data added to the trial database will also be needed in this respect (Gallin and Ognibene, 2007, p. 220). The investigators will also provide the trial sponsor with the guarantee that the data they report to the sponsors are identical with the ones they retrieve directly from the research participants during their screening, questionnaire surveys processes, or physical examination procedures (DeRenzo and Moss, 2005, p. 207).
The sponsors should at the same time serve as the trial monitors that would control and check the data validity and correct any possible intentional or unintentional mistake occurring. In respect to the CDM role in the data validation, the importance of the data coordinating centers becomes paramount, as only the proper work of the latter assures the clear and precise data being obtained by the sponsors of the trial and by the public (Gallin and Ognibene, 2007, p. 199).
SAE Data Reconciliation
Ethical considerations are also of primary importance to the clinical trial procedure (DeRenzo and Moss, 2005, p. 201). The reporting and reconciliation of the adverse events (AE), and especially serious adverse events (SAE), is one of the major conditions under which a clinical trial can be carried out and is considered to be properly structured (DeRenzo and Moss, 2005, p. 204). As far as every single clinical trial has its terms and limits or SAE reporting and reconciliation established by the trial sponsors, the current trial will have to report the SAE happenings within a day after their occurrence.
This will allow avoiding any speculations about the trial being biased or fabricated in any way. As well, the timely SAE reporting will provide for the positive image of the trial and its sponsors and initiators (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 194).
Reconciliation of SAE involves more effort from the side of investigators and trial sponsors. First, this practice demands the establishment of terms according to which SAE cases should be reconciled (Rondel, Varley, and Webb, 2000, p. 100). The timeline and terms of reconciliation should also be supported by the people that are charged with the task of SAE reporting and reconciliation (DeRenzo and Moss, 2005, p. 205). In the current clinical trial of Sleephormone1, this task will be the exclusive responsibility of the safety group, the special detachment of the investigation team that will deal with identifying, reporting, and reconciling SAE cases that might occur in the progress of the Sleephormone1 clinical trial.
External Data Transfers
The procedure of external data transfers will be carried out concerning the internationally accepted rules of the clinical trials. The external data transfers will involve the use of the Clinical Data Management System (CDMS), further used as the destination of the externally collected information (Emanuel, Grady, Crouch, Lie, Miller, and Wendler, 2009, p. 119). On the whole, during the current clinical trial of Sleephormone1, the data collected through the study of external sources, or external data regarding the Sleephormone1 versus placebo efficiency in the given context, will be placed in the common database where all other trial data will be stored. This will allow a comprehensive approach to the topic and the focused reporting of the trial results (Rondel, Varley, and Webb, 2000, p. 100).
Audit Plans
The financial side of the clinical trial process has no less important than the scholarly side (Rondel, Varley, and Webb, 2000, p. 105). The so-called audit plans are essential to saving the resources directed by the trial sponsors to the investigators of the efficiency of Sleephormone1 in the struggle with sleep disorders. As well, the use of the audit trail is necessary for the proper structure and supervision of the clinical trial, as the audit trail makes the task of checking and monitoring the clinical trial site and procedures easier for the sponsors or the monitoring organizations hired by the latter (Pocock, 1984, pp. 98 – 99).
Reports and Communications
Finally, reports of the trial findings and the professional skills required for communicating those findings to the trial participants are also obligatory conditions for successful clinical research. In the current trial, the reports will be prepared in two forms, electronic and printed, to allow the wider audience to get acquainted with the trial results. As well, such a method of results reporting will add to the positive image of the trial sponsor (Rondel, Varley, and Webb, 2000, p. 109).
Communications with the trial participants will be at a high level of proficiency as the personnel involved in the trial will be specially trained to meet the sponsor’s requirements regarding communications. Finally, positive communication with the trial participants will facilitate the progress of the clinical research and provide for the participants’ inclination to cooperate and report specific data.
Reference List
DeRenzo E. and Moss, J. (2005) Writing Clinical Research Protocols: Ethical Considerations. Academic Press.
Emanuel, E., Grady, C., Crouch, R., Lie, R., Miller, F., and Wendler, D. (2008) The Oxford Textbook of Clinical Research Ethics. Oxford University Press, USA.
Gallin, J. and Ognibene, F. (Eds.) (2007) Principles and Practice of Clinical Research, Second Edition. Academic Press.
Pocock, S. (1984) Clinical Trials: A Practical Approach. Wiley.
Rondel, R., Varley, S., and Webb, C. (2000) Clinical data management. John Wiley and Sons.