Clinical Protocols case report forms

Case report forms (CRFs) are used throughout clinical trials to record data collected during a trial. They record all of the information specified in the protocol for each subject (all data recorded on the CRF must be verifiable from original source documentation). While the traditional paper CRF format is still used, electronic data collection is becoming more common. Voorhees and Scheipeter (2005) discussed CRF development in detail, highlighting some of the fundamental aspects of their purpose, design, and nature ... 

FOR PHASE 2 OR 3 INVESTIGATIONS. AN OUTLINE OF THE STUDY PROTOCOL INCLUDING AN APPROXIMATION OF THE NUMBER OF SUBJECTS TO BE TREATED WITH THE DRUG AND THE NUMBER TO BE EMPLOYED AS CONTROLS. IF ANY THE CLINICAL USES TO BE INVESTIGATED CHARACTERISTICS OF SUBJECTS BY AGE, SEX, AND CONDITION THE KIND OF CLINICAL OBSERVATIONS AND LABORATORY TESTS TO BE CONDUCTED THE ESTIMATED DURATION OF THE STUDY AND COPIES OR A DESCRIPTION OF CASE REPORT FORMS TO BE USED. 

The case report form is the vital record of a clinical trial. It is necessary to design the CRF to collect all the data required by the protocol. Carefully designed CRFs are essential for the following reasons ... 

Setting up clinical studies is a lengthy process, as there are many documents to prepare [e.g. protocols and case report forms (CRFs)], study facilities to be assessed (e.g. study sites, CROs, clinical laboratories, phase I units), regulatory review to be considered and negotiations and agreements with study sites (e.g. contracts, finances, confidentiality, indemnity, insurance) to be undertaken. In addition, as will be dealt with in subsequent sections, ethical aspects of the study must be considered (e.g. ethics committee and IRB review and informed consent requirements), and study medications/devices must be organized. 

To develop a data management plan pertinent to the project, a checklist of the project material is necessary to enhance the planning. The items to be collected include the protocol, annotated case report forms (CRFs), literature, log-in and tracking forms, file structures, coding rules, CRF review conventions, query handling procedure, required edit checklist, central laboratory address/file format, laboratory normal ranges, clinically... 

Scientists help design major portions of study protocols and clinical case report forms (CRFs). The study protocol is the overall plan that the study follows, and it must contain certain types of information, including the following 1) background data on the targeted disease 2) the empirical and structural formula of the drug being... 

Because the chief investigator had to play a leading role in the clinical trial, the person appointed by the sponsor was usually a physician or professor who was an authority on the subject of the clinical trial. In practice, however, such people were generally too busy to perform the duties mentioned here, and the sponsor wrote a draft protocol and a draft of the explanatory note used when obtaining informed consent from subjects. In addition, the sponsor s monitor conveyed data and information to the physician in charge, as well as collecting and checking the case report forms (CRFs). 

Whilst the conditions under which large simple trials can provide efficacy data are fairly well worked out, it is important to consider whether (or which) tolerability issues can be precisely addressed in this way. If a tolerability factor (adverse event) relates to the efficacy variable of interest (e.g. a fatal adverse event in a patient survival study), then a simple case report form may provide relevant information. However, if the adverse event type is rare or unanticipated (e.g. the test drug causes unanticipated, significant anemia in 0.1% of patients, and the protocol and case report form do not collect hemoglobin values before and after treatment), then it is very likely that the adverse event will be missed. Large simple studies can thus create undue confidence in product tolerability ( thousands of patients were exposed to the agent during clinical trials ). 

The clinical protocol needs only be an open-label, tolerability study in patients for whom inclusion and exclusion criteria are kept broad and to a bare minimum for safety. These abbreviated INDs are of orthodox composition (2ICFR para 312.23), but have the advantage that the complexities of the Treatment IND can be avoided. Furthermore, even with a rudimentary case report form, the pharmaceutical company can gather tolerability information by this means, even for products approved for other purposes, because the exemptions... 

Regulatory authorities play an important and active role to ensure regulatory compliance in the conduct of a clinical trial. Agencies such as the FDA inspect clinical studies. An inspection of a trial may reveal that the protocol is not being followed strictly, the Investigator may not be involved with the project as much as is expected, there may be a lack of patient care, changes to the protocol may not have been relayed to the IRB, and so on. In such cases, corrective actions have to be implemented immediately and the FDA must be satished before the trial can continue. Deficiencies found are reported on Form 583. 

Visit dates. All visit dates should be recorded in the medical file. Interim visit dates recorded in the medical file, but not in the CRF, should be noted by the monitor in case they signify occurrence of AEs or protocol violations. The final visit date should be so indicated, for example study finished or withdrew from study AEs. All AEs noted in the medical file during the time period specified by the protocol must be recorded in the CRF. The monitor must also carefully check other documents (e.g. diary cards, quality of life forms) for sources of information about AEs. Occurrence of out-of-range laboratory values, which are considered to be clinically significant by the investigator, must be reported and assessed as AEs... 

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