Protocol Development

The first step in the set up of a clinical trial is the development of a Clinical Study Protocol (CSP). A carefully designed and well written CSP will ensure quick regulatory approval, efficient study team FTE allocations and budgeting and finally a successful execution of the trial.
To achieve the best possible results, one must first set the scientific objectives of the study and the corresponding endpoints. It is very good practice to produce a preliminary document with a short background and rationale for the study, the objectives and endpoints as well the characteristics of the population to be studied. This study concept will form the basis of the development of the protocol.
After finalizing the study concept between the different stake holders, the development of the CSP can take place. The main sections to include in a CSP are the following:

1. Synopsis

A condensed version of the Protocol mainly containing a very brief introduction, the objectives/endpoints, key inclusion criteria, a short overview of study treatment (if applicable) as well as the study duration.

3. Study Design

The study design section should include the objectives/endpoints as well as describe the type of study (e.g. Phase 3, open label, randomized). A clear outline of the objectives and corresponding endpoints is crucial in order to illustrate the backbone of the trial. It is under these objectives and endpoints that the rest of the protocol sections will fall.

5. Study Treatment

Another crucial section is study treatment where the details of how to administer each regimen are fully explained. Also, the criteria under which each of the regimens might be interrupted/withdrawn are also included here. ATTENTION: One MUST be very careful in the exact language used in order to make it clear what is mandatory and what is only suggested.

7. Safety

The safety section for obvious reasons is of major importance in clinical trials. Here one must include definitions for all safety events (Adverse Events, Serious Adverse Events, Adverse Events of Special Interest) as well as their classification in terms of severity. In case there are study specific requirements for safety reporting, these must be clearly stated in this section to ensure compliance. Pregnancy and Product Quality Complaint reporting should also be included here.

2. Introduction

Introduction is one of the sections that often gets overlooked yet is crucial in the completeness and integrity of the CSP. Here one should introduce the disease area that is under study and the available data so far. A clear build up to the rationale of the study is important in order to guide the reader (who might not necessarily possess the same technical expertise) through the protocol. A risk benefit assessment is also crucial.

4. Patient Population

A careful and very clear outline of the eligibility criteria is needed in this section. ATTENTION: the majority of the issues/questions that arise throughout the life cycle of a study are related to the inclusion/exclusion criteria. As such they MUST be written as clear as possible in order to avoid potential misunderstandings leading to considerable mistakes in patient inclusion.

6. Study Procedures

Another section which attracts a lot of attention during the clinical trial is study procedures. Here one must be especially careful in creating an easy to follow yet detailed schedule of assessments. This is a table which outlines all the procedures to be performed during the study and the relevant timepoints. As this table will be ‘religiously’ followed and consulted by CRAs, regulatory personnel and of course hospital staff, investing time in making sure that it contains all the procedures and iseasy to follow will yield a definitereturn on investment. The rest of the section shall expand on each of the procedures outlined in the schedule of assessments and clearly explain the relevant details.

8. Statistical methods

In such a section, the statistical design of the study shall be introduced with a  breakdown of the sample size estimation and the various analysis sets. The analysis of each of the study endpoints will be depicted as well with emphasis put on the primary endpoint. Fine details such as sub group analyses are best to be included in the Statistical Analysis Plan (SAP) instead.

1. Synopsis

A condensed version of the Protocol mainly containing a very brief introduction, the objectives/endpoints, key inclusion criteria, a short overview of study treatment (if applicable) as well as the study duration.

2. Introduction

Introduction is one of the sections that often gets overlooked yet is crucial in the completeness and integrity of the CSP. Here one should introduce the disease area that is under study and the available data so far. A clear build up to the rationale of the study is important in order to guide the reader (who might not necessarily possess the same technical expertise) through the protocol. A risk benefit assessment is also crucial.

3. Study Design

The study design section should include the objectives/endpoints as well as describe the type of study (e.g. Phase 3, open label, randomized). A clear outline of the objectives and corresponding endpoints is crucial in order to illustrate the backbone of the trial. It is under these objectives and endpoints that the rest of the protocol sections will fall.

4. Patient Population

A careful and very clear outline of the eligibility criteria is needed in this section. ATTENTION: the majority of the issues/questions that arise throughout the life cycle of a study are related to the inclusion/exclusion criteria. As such they MUST be written as clear as possible in order to avoid potential misunderstandings leading to considerable mistakes in patient inclusion.

5. Study Treatment

Another crucial section is study treatment where the details of how to administer each regimen are fully explained. Also, the criteria under which each of the regimens might be interrupted/withdrawn are also included here. ATTENTION: One MUST be very careful in the exact language used in order to make it clear what is mandatory and what is only suggested.

6. Study Procedures

Another section which attracts a lot of attention during the clinical trial is study procedures. Here one must be especially careful in creating an easy to follow yet detailed schedule of assessments. This is a table which outlines all the procedures to be performed during the study and the relevant timepoints. As this table will be ‘religiously’ followed and consulted by CRAs, regulatory personnel and of course hospital staff, investing time in making sure that it contains all the procedures and iseasy to follow will yield a definitereturn on investment. The rest of the section shall expand on each of the procedures outlined in the schedule of assessments and clearly explain the relevant details.

7. Safety

The safety section for obvious reasons is of major importance in clinical trials. Here one must include definitions for all safety events (Adverse Events, Serious Adverse Events, Adverse Events of Special Interest) as well as their classification in terms of severity. In case there are study specific requirements for safety reporting, these must be clearly stated in this section to ensure compliance. Pregnancy and Product Quality Complaint reporting should also be included here.

8. Statistical methods

In such a section, the statistical design of the study shall be introduced with a  breakdown of the sample size estimation and the various analysis sets. The analysis of each of the study endpoints will be depicted as well with emphasis put on the primary endpoint. Fine details such as sub group analyses are best to be included in the Statistical Analysis Plan (SAP) instead.

Other Sections

Apart from the core sections outlined above there are of course other sections that can be included in a CSP including but not limited to: data collection and record keeping, publication policy, ethical aspects of the trial and quality assurance processes.

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