Case report forms tabulations

Adverse events should be tabulated for easy inspection but the case report form should be available and all laboratory data such as blood coimts, renal function and liver function tests should be inspected closely The absence of obvious adverse events does not mean that all is well, and careful scrutiny of data by an experienced physician can often spot problems before they become troublesome. Not infrequently one or more volunteers become imwell during the course of a study, usually due to intercurrent viral infections, and decisions about postponement of study days and subject withdrawal follow-up can be made during these meetings. Data that are missing because of non-attendance of volunteers, for whatever reason, may lead to a delay in the study, with postponement of dose escalation imtil they have caught up. 

Archival Copy. This is a complete copy of the entire submission and serves as a reference for information not included in specific review copies and also as a repository for case report tabulations and case report forms. This copy is maintained on file at FDA after the review of the submission is completed. In accordance with recent guidances, certain sections (Sections 11 and 12) of a marketing application archival copy maybe submitted in electronic format. 

Additional data. The applicant shall submit to FDA additional case report forms and tabulations needed to conduct a proper review of the application, as requested by the director of the FDA division responsible for reviewing the application. The applicant s failure to submit information requested by the FDA within 30 days after receipt... 

Applicants are invited to meet with the FDA before submitting an application to discuss the presentation and format of supporting information. If the applicant and the FDA agree, the applicant may submit tabulations of patient data and case report forms in a form other than hard copy, for example, on microfiche or computer tapes. 

In addition to Form FDA 356h, an NDA contains an index, a summary, five or six technical sections, tabulations of clinical data and case report forms, and patent information and various certifications. Safety update reports submitted after the initial filing are also considered part of an NDA. 

The index should be comprehensive, with the volume number and page number indicated for the sections of the summary, the individual technical reports, the tabulations of clinical data by study, the case report forms, and any other information or certifications. It is also advisable to have indices for each technical section and volume. 

This section should contain a complete alphabetical list of all the names and addresses of all known investigators that the applicant supplied with the drug substance or product. In addition, all dosage forms used by these investigators should be stated. This list should also include the kinds of studies carried out, study identifier, location of each report, case report tabulations, and case report forms. In addition, a list of all known INDs under which the drug was studied and any other NDAs submitted for the same drug substance should be included. 

Case report forms should be kept as simple as possible by use of checklists, fill-ins, or the recording of specific measurements. Detailed narratives should be used for an investigator s written summary of the study. Complicated CRFs make the preparation of good tabulations more difficult. Where abbreviations or little-used terms are used on tables or graphs, explanations or definitions should be provided for ease of review. 

During the FDA s most recent revision of its NDA regulations, the agency declared that an efficient agency review of individual patient data should be based primarily on well-organized, concise data tabulations. Reviews of the more detailed patient case report forms should be reserved for those instances where a more complete review is necessary. ... 

The agency advises sponsors to meet with FDA to discuss the extent to which tabulations of patient data in clinical studies, data elements within tables, and case report forms are needed. Such discussions can also cover alternative modes of data presentation and the need for special supporting information (for example, ECGs, x-rays, or pathology slides). 

In addition to the Section 5.3.7 of Module 5, Case Report Forms and Individual Patients Listing , the following tabulations and charts are required. 

This is a complete copy of an application submission and is intended to serve as a reference source for FDA reviewers to locate information not contained in the section of the review copy assigned to them. It serves as a reference source for other FDA officials, and as the repository of the copies of tabulations and clinical trial case report forms. 

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