Clinical Protocols objective

In drug development, time is of the essence. Clinical protocols should be concise, straightforward, and logical. The demands upon the investigators, their staffs, and the patients must be reasonable. The FDA s guidelines for drug development by disease must be considered in order to expedite the final NDA review and approval. The objective to remember throughout protocol development, and execution and presentation of the acquired data, is to demonstrate efficacy and safety to fulfill FDA s requirements for NDA approval. 

The clinical protocol describes the objectives, design, methodology, statistical considerations and organization of the trial. The sponsor is usually responsible for developing the protocol in industry-sponsored clinical trials. However, internal and external content experts (e.g. specialists, key opinion leaders) are frequently consulted. Protocols must be written ensuring medical soundness and clinical practicality. 

All clinical protocols and supporting documents are reviewed and approved internally by a group of senior Clinical Research Development managers. This group assesses the overall study design and ability of the study to meet its objectives, as well as the quantity and quality of the data. In addition, the group reviews the procedures for the safety and welfare of the subjects to ensure compliance to good clinical practices and ethical principles. 

Integration of biomarkers into clinical protocols requires incorporation of biomarker analysis into one of the study objectives. For novel biomarkers this is typically achieved by including an exploratory objective that examines the feasibility of measuring the biomarkers in the study population. Within the protocol a summary of preclinical or translational evidence for the biomarkers should be provided. When available, biomarker qualifications or letters of support from regulatory authorities should be referenced. A schedule of events describing when samples for biomarker analysis should be collected in context with all other clinical visits and tests should be included. When special collection, processing, or storage considerations are required, a separate... 

Clinical trials are costly to conduct, and results are often critical to the commercial viability of a phytochemical product. Seemingly minor decisions, such as which measurement tool to use or a single entry criterion, can produce thousands of dollars in additional costs. Likewise, a great deal of time, effort and money can be saved by having experts review the study protocol to provide feedback regarding ways to improve efficiency, reduce subject burden and insure that the objectives are being met in the most scientifically sound and cost-effective manner possible. In particular, I recommend that an expert statistician is consulted regarding sample size and power and that the assumptions used in these calculations are reviewed carefully with one or more clinicians. It is not uncommon to see two studies with very similar objectives, which vary by two-fold in the number of subjects under study. Often this can be explained by differences in the assumptions employed in the sample size calculations. 

The requirements of GCP, as described in the ICH guidelines, are presented in Chapter 7 and will not be discussed further here. However, it is emphasised that the standards required of large clinical trials in patients apply equally to small clinical pharmacological studies in healthy subjects. Studies should be conducted in accordance with SOPs. Many SOPs will resemble those pertaining to later phase clinical trials, but some will be specific to healthy volunteer studies. Details of procedures not covered by SOPs should be specified in the protocol. Studies must be monitored by the sponsor or a representative the monitor should not be one of the investigators so that monitoring visits and assessments can maintain objectivity. 

This document describes the objectives, design, methodology, statistical considerations and organisation of a trial. Other information should be present, such as the background and rationale, for the clinical trial. It is a document key to any clinical trial. There should be a logical approach to preparing a protocol (see Box 7.2). 

Table 2.8. Typical issues addressed when designing a clinical trial protocol. The trial objectives should clearly define what questions the trial should answer. The study design section should contain comprehensive information detailing trial size, criteria used to choose the study population, and enrolment procedures. Description of intervention section should give the background to the intervention itself, its therapeutic rationale and how it is to be administered. Measurement of response should detail the data to be collected, how it will be collected and analysed. The organization and administration section should give full details of all the investigators, where the trial is being run, and its project management details...

Although the primary goal of the analysis of a clinical trial should be to answer the questions posed by its main objectives, new questions based on the observed data may well emerge during the unblinded analysis. Additional and perhaps complex statistical analysis may be the consequence. This additional work should be strictly distinguished in the report from work which was planned in the protocol. ... 

IRBs approve the clinical trial protocols, which describe the type of people who may participate in the clinical trial, the schedule of tests and procedures, the medications and dosages to be studied, the length of the study, the study s objectives, and other details. IRBs make sure the study is acceptable, that participants have given consent and are fully informed of their risks, and that researchers take appropriate steps to protect patients from harm. 

A sample-size estimation must be based on a specific objective in a clinical trial s study protocol. By the time sample-size estimation becomes particularly meaningful, i.e., in later-stage clinical trials designed to demonstrate efficacy, it is a very good idea to have a single objective (the primary objective) and a single... 

Together, these specialists can provide both the criteria for all aspects of the study and the rationale used to develop them. Once the specific objectives of the protocol have been established, it is customary for a protocol introduction to summarize these objectives, give a brief overview of the information found in the Investigator s Brochure (referencing the Brochure), and state the purpose of conducting the study. The rationale for the criteria to be used for patient selection, exclusion, and randomization (if any) and the clinical variables to be monitored during the trial should also be stated. 

An interested investigator should read the entire protocol to understand the objective ) of the study. However, sometimes certain sections of the protocol are of more interest than others to different participants conducting the clinical trial. A protocol may, for example, contain separate sections devoted to the interests of the project coordinator, a nurse, a psychologist, a cardiologist, and others. When one or more individuals have to refer quickly to a section of the protocol... 

The objective is the essence of a protocol. It should state explicitly the purpose of the clinical research project. One short statement should describe the type of... 

Many approaches and different styles are useful in the development and preparation of a sound clinical research study protocol. The foregoing guidelines can be modified to suit the applicant s needs and objectives. No matter which path is mapped out, it is imperative that investigators abide by the final protocol. Strict adherence to a well-designed protocol will result in research projects that reflect the stated objectives in the required amount of time leading to successful and definitive conclusions. 

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