Step 2: Conducting a Cancer Prevention Clinical Trial
Essential Documents
Federal regulations (Title 21 CFR Parts 54.4, Subpart D 56.115, Subpart B 312.30, 312.32, 312.33, 312.53, 312.62, 312.64) mandate that the investigator and sponsor of a clinical trial each maintain a complete set of regulatory documents pertaining both to specific participants and to general study records.
For more background information, refer to FDA's Good Clinical Practice: Consolidated Guideline, which was established under the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
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General Study Records
The general study records are commonly known as the regulatory documents or essential documents, and are usually kept in a Regulatory Binder (also known as Study Binder, Administrative Binder, Investigator Binder, Investigator Study File). It is the sponsor's responsibility to collect and file the regulatory documents with the Food and Drug Administration.
Once a site has submitted the regulatory documents to the sponsor they are typically reviewed by the monitor, known as the Clinical Research Associate (CRA), for compliance, completeness, and legibility at each monitoring visit.
IRB reviews, licenses, certifications, consent form documents, and any other regulatory document must be kept current for the duration of the clinical trial.
A typical regulatory binder contains:
- Protocol (all versions)
- Protocol amendments (all versions)
- Investigator brochure (all versions)
- Case Report Forms (a blank set of CRFs that can be duplicated)
- Form FDA 1572 (pdf, 265kb)
- Curriculum vitae or biosketch and documentation of professional licensure of all listed on FDA Form 1572
- Financial Disclosure Forms for all listed on FDA Form 1572
- IRB approval documentation
- Informed consent forms (all versions)
- Educational material
- Annual and periodic review reports
- Advertisements
- IRB correspondences
- Safety reports
- IRB roster and credentials of members
- Sponsor correspondences
- Written correspondences
- Telephone contacts
- Copies of faxes or e-mail correspondences
- Site signature log
- Patient screening/enrollment logs
- Clinical Laboratory Certifications (CAP, CLIA) and laboratory normal ranges
- Study drug documentation
- Drug shipment and receipt records/forms
- Drug accountability records
- Equipment and supplies (receipt, calibration logs)
- Monitoring log (includes documentation of sponsor's visits and reports)
- Study closeout information
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Participant Source Documentation
A source document is any document, form, or record where specific participants' data is first recorded. ICH guidelines define source documents as original documents, data and records.
FDA [21 CFR 312.62 (b)] requires that the investigator "...prepare and maintain accurate case histories designed to record all observations and other data pertinent to the investigation on each individual treated with the investigational drug or employed as a control in the investigation."
Among many other items, source documents include:
- Inpatient and outpatient medical records
- Progress notes
- Consults
- Nursing notes
- Pathology reports
- Radiology reports
- Medicine/radiation administration records
- Surgical reports
- Laboratory reports
- Admission forms
- Flow sheets that are signed and dated
- Protocol or study road maps
- Appointment books
- Participant diaries/calendars
Case Report Forms
FDA assesses study results through scientific evaluation of data contained in case report forms. While a critical part of the investigation records, they usually cannot serve as the complete investigation record.
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Record Retention
IRB records related to any federally supported clinical research must be retained for at least 3 years after study completion, according to Department of Health and Human Service Regulations (45 CFR 46.115; 21 CFR 56.115.)
Additional regulations (21CFR 312.57 and 21 CFR 312.62) require trial sponsors of FDA Investigational New Drug (IND) applications to retain records and reports for 2 years after a marketing application is approved. If the application is not approved, the sponsor retains records and reports until 2 years after shipment and delivery of the drug for investigational use is discontinued and the FDA notified. These regulations apply to investigational drug records, investigator financial interest records, and patient case histories.
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