Protocol is a pivotal document for conducting a clinical trial. All the different steps that would be implemented and executed in a clinical trial have to be clearly documented in protocol. Generally the sponsor of a clinical trial would draft the protocol. Once a protocol is drafted initially it undergoes different corrections and modifications before deciding the final version. But drafting and finalizing a clinical study protocol is not sufficient to start a clinical trial.
Before starting a clinical trial the protocol along with other important documents like Informed consent form (ICF), case report form (CRF) has to be sent to the regulatory authorities for approval. The regulatory authorities in different countries would check the proposed protocol thoroughly with special emphasis on the safety, well being of the subjects. If the design of the study in the protocol and well as the methodologies that is depicted in protocol, reflects that trail subjects safety is maintained, then the protocol gets approved. Designing a scientifically strong protocol is one of the most important steps in any clinical trial. Thus ICH-GCP guidelines as well as CDSCO-GCP (Central Drug Standard Control Organization-Good Clinical Practices) have provided basic designing guidelines of a scientifically sound protocol. Within ICH-GCP section no 6, protocol and protocol amendments has been drafted/depicted.
According to ICH-GCP guidelines a protocol must have sixteen different sections.
(1). General Information: This section should contain (1.1) Protocol title, protocol identifying number, and date, any amendment(s) should also have the amendment number(s) and date(s). (1.2) Name and address of the sponsor and monitor (if other than the sponsor).(1.3) Name and title of the person(s) authorized to sign the protocol and the protocol amendment(s) for the sponsor. (1.4) Name, title, address, and telephone number(s) of the sponsor's medical expert (or dentist when appropriate) for the trial.(1.5)Name and title of the investigator(s) who is/(are) responsible for conducting the trial, the address and telephone number(s) of the trial site(s). (1.6) Name, title, address, and telephone number(s) of the qualified physician, who are responsible for all trial-site related medical decisions. (1.7) Name(s) and address(es) of the clinical laboratory(ies) and other medical and/or technical department(s) and/or institutions involved in the trial.
(2). Background Information: In this section, name and description of the investigational product(s), a summary of findings from non-clinical studies that potentially have clinical significance and from clinical trials that are relevant to the trial has to be mentioned. Summary of the known potential risks and benefits, if any, to human subjects should be described. Description and justification for the route of administration, dosage, dosage regimen, and treatment period(s) of a drug or medicinal product has to be mentioned. A statement that the trial will be conductedin compliance with the protocol and in compliance to GCP andapplicable regulatory requirement has to be stated. Description of the population to be studied and references to literature and data relevant to the trial has to be described.
(3). Trial Objectives and Purpose: detailed description of the objectives and the purpose of the trial have to be drafted in this section.Thesections would vary from one study to another.
(4). Trial Design: In this trial section primary and the secondary endpoints, description of the type/design of trial to be conducted (e.g. double-blind, placebo-controlled, parallel design) and a schematic diagram of trial design, procedures and stages have to be described. Any measure (if any) has been taken to minimize/avoid bias, includingrandomization and blinding has to be mentioned. Description of the trial treatment(s) and the dosage, the dosage regimen of the investigational product(s), dosage form, packaging, and labeling of the investigational product(s) have to be included. The expected duration of study, description of the sequence and duration of all trial periods, including follow-up (if any) should be mentioned.
(5). Selection and Withdrawal of Subjects: In this sectionsubject’s inclusion and exclusion criteria, subject withdrawal criteria has to be mentioned. Within subject withdrawal criteria, when and how to withdraw subjects from the trial/ investigational product treatment should be mentioned. The type and timing of the data to be collected for withdrawn subjects should be clarified. If required how the subjects has to be replaced, follow-up for subjects withdrawn from investigational productshould be mentioned.
(6). Treatment of Subjects : The name of the treatment/(s) to be administered, the dose(s), the schedule of dose (s), the route of administration, duration of the treatment period follow-up period(s) for subjects for each investigational product treatment or treatment group (arm) has to be mentioned clearly. Concomitant medication/medication(s) permitted including rescue medication and those that are not permitted before and/or during the trial should be mentioned. Monitoring the subject compliance procedure has to be mentioned.
(7). Assessment of Efficacy: For every study efficacy parameter differ, thus study specific efficacy parameters and methods, timings for assessing, recording, and analyzing of those parameters has to be mentioned.
(8). Assessment of Safety: Detailed description of safety parameters, the methods, timing for assessing, recording, and analyzing safety parameters has to be mentioned. Within this section, procedures for eliciting reports of and for recording and reporting adverse event and intercurrent sickness, after any adverse event the type and duration of the follow-up treatment of subjects should be mentioned.
(9). Statistics: Statistical methods to be employed, including timing of any planned interim analysis, number of subjects planned to be enrolled etc has to be mentioned in this section. In multicentric trials, the numbers of enrolled subjects from each trial site should be specified. Legitimate reasons for sample size selection, level of significance, criteria for the termination of trial, missing, unused, and spurious data accounting procedure has to be mentioned.
(10). Direct Access to Source Data/Documents: The sponsor should ensure that it is specified in the protocol or other written agreement that the investigator(s)/institution(s) will permit trial-related monitoring, audits, IRB/IEC review, and regulatory inspection(s), providing direct access to source data/documents.
(11). Quality Control and Quality Assurance: The steps that should be followed for Quality Control (QC) and Quality Assurance (QA) has to be mention clearly.
(12). Ethics: During the clinical trial what ethical guidelines would be followed has to be mentioned here.
(13). Data Handling and Recordkeeping: This section has to clearly mention the ways of managing all the data collected during a clinical trial as well as on the ways of storing/record keeping of the collected data.
(14). Financing and Insurance: For a clinical trial all the financing/sponsored details and the insurance that has been taken for the subject’s safety should be mentioned in this section.
(15). Publication Policy: After the clinical trial is over what would be the publication plan and policies for the outcome of the clinical study results has to mentioned in this section. This part is also drafted to avoid further complications.
(16). Supplements: Any supplements/additional documentations as required for this studyshould me mention in this section.
Finally designing a scientifically strong protocol is the major step for a clinical trial to be performed successfully and that the generated results can be relied upon to obtain a conclusion. However just designing the methods, rules, study designs are not sufficient, when the clinical trial is being conducted, compliance to the approved protocol, following the stated procedures exactly as planned in a protocol and maintaining the ethical guidelines is absolutely compulsory. (Reference – ICH-GCP guidelines, www.ich.org, www.ichgcp.net).
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