Clinical Protocols elements

The requirements for a clinical protocol are described in detail in Chap. 8 of this book however, a brief overview of the protocol content is provided here. A protocol is required to contain the following, with the specific elements and detail of the protocol reflecting the above distinctions depending on the phase of study ... 

The quality of a clinical protocol can be assessed by how well the elements of the protocol are... 

All clinical protocols and supporting documents are reviewed and approved internally by a group of senior clinical research 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 GCP and ethical principles. The quality of a clinical protocol can be assessed by how well the elements of the protocol are prepared. The elements of clinical protocols are described in Table 3.1. 

Table 22.1. The ultrasound meal accommodation test (UMAX) was developed at Haukeland University Hospital on the basis of close interaction between scientific and clinical work in patients with dyspepsia. Before entering the protocol, the patients have been carefully studied with history, physical examination, blood tests, testing for H. pylori and upper endoscopy. In some cases, additional examinations are performed to rule out organic causes of their symptoms. The protocol presented here is the mainstream clinical protocol. In scientific studies, other elements are often added. A 500-ml liquid meal of commercial meat soup (Toro clear meat soup, Rieber Son A/S, Bergen, Norway) containing 1.8 g protein, 0.9 g bovine fat, and 1.1 g carbohydrate (20kcal) is ingested over a period of 4 min. The soup is preheated and then cooled to 37°C to improve imaging quality by reducing the amount of air bubbles. Psychometric evaluation is also performed...

The application for a clinical trial authorisation (CTA) for the first administration of a NME to man comprises the same elements as all other CTAs but, of course, there will be no clinical data. The regulatory authority known as the competent authority (CA) of the EU member state requires receipt of confirmation of the EU clinical trials database (EUDRACT) number, a covering letter, a completed application form, the protocol with all current amendments, the IB and a full Investigational Medicinal Product Dossier (IMPD) (see below). If the study is to be conducted in more than one member state, a list of CAs should be included. If the opinion of the lEC is available, it should be provided. 

The key elements of an inspection are to ensure that the facility is capable of fulfilling the application commitments to manufacture, process, control, package, and label a drug product following GMP the adequacy and accuracy of analytical methods submitted, to ensure that these methods are proper for the testing proposed correlation between the manufacturing process for clinical trial material, bioavailability study material, and stability studies and submitted process that the scientific data support full-scale production procedures and controls that only factual data have been submitted and that the protocols are in place to validate the manufacturing process. 

Mass cytometry uses stable isotopes as lanthanide series because of the huge number of elements of this family and their similar chemical structure, allowing their incorporation into the same tag (45,46). They also exhibit very low background due to their intrinsic low natural abundance (45-47). These rare earth elements are relatively biocompatible and easily conjugated to biomolecules by broad availability and simple protocols. Finally, they proffer high sensitivity for traces of molecules in biological samples, being attractive markers for their use in the clinical routine (47). 

The controlled clinical trial (CCT) is the scientific tool for demonstrating causality. Two essential elements characterize the CCT (a) it contains a control group and an experimental group (b) with the exception of treatment, all other conditions and procedures to which the subjects are exposed during the trial are constant. These two characteristics of the CCT enable the researcher to establish a causal relationship between treatment and the outcome of the trial. The tool for standardizing the trial is the study protocol, the document defining the subjects eligible for inclusion in the study, the study procedures and schedules. 

The answers to such questions will clarify safety pharmacology study requirements, key protocol design elements, and the necessary timing of such trials relative to the clinical research program. 

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