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A study sponsor should create a Data Management Plan for the study protocol. This plan should be shared with each of the study sites. The management plan is created to ensure that data is collected and managed properly and in compliance with current applicable regulations and guidelines. Each site can modify the data management plan to include site specifics, such as individuals responsible for collecting data, oversight, equipment used, and policies for access.

The FDA provides guidance documents and regulations (21 CFR 11) related to managing data collected in clinical trials. Guidance includes the capture, review, and retention of electronic source data in FDA-regulated clinical investigations. The guidance is the FDAs effort to ensure the reliability, quality, integrity, and traceability of data from electronic source to electronic regulatory submission. (FDA, 2013).

In Guidance for Industry Electronic Source Data in Clinical Investigations (2013) the FDA provides the following definitions related to data management:

· An “electronic record as any combination of text, graphics, data, audio, pictorial, or other information represented in digital form that is created, modified, maintained, archived, retrieved, or distributed by a computer system.”

· “An eCRF is an example of an electronic record. The eCRF is an auditable electronic record of information that generally is reported to the sponsor on each trial subject, according to a clinical investigation protocol. The eCRF enables clinical investigation data to be systematically captured, reviewed, managed, stored, analyzed, and reported.”

· “Source data includes all information in original records and certified copies of original records of clinical findings, observations, or other activities in a clinical investigation used for reconstructing and evaluating the investigation.”

A Data Management Plan should include the following:

· Data Elements - smallest unit of observation collected on a clinical trial subject. Examples of data elements are weight, height, race, pain severity, etc.

· Data Originators - each data element is associated with an originator, which is the source of that data. Originators might include the study coordinator, the investigator, medical devices such as EKG, consultants, etc.

· eCRFs - the electronic record where data elements are captured.

· Source Documents - the original source of the data element, which can be paper-based or electronic. The source data might be manually entered into the eCRF (for example a radiology report) or electronically transmitted by a medical device (blood pressure monitor).

· Transfer of Source Data Elements into EDC

Paper - manually transferred into the eCRF. The person transcribing the data from the paper source is considered the data originator.

Electronic Transmission - automatic transmission from the device into the eCRF.

· Access - limited access to data by appropriate study staff is important. Access should only be granted to the investigator, study coordinator, data entry staff (if applicable), and data manager (if applicable). Data management must comply with security and privacy measures covered in 21 CFR 11 and HIPAA. The data management plan should include a list of individuals with access to the eCRFs. Individuals with access should have completed appropriate training. Individuals with access should have their own identification codes and passwords. Site policy should include specific instructions to not share access codes and passwords and the consequences of doing so.

· Data Element Identifiers - this is the information that identifies the data originator. These identifiers include:date and time of data entry, originator identification, the subject tied to the data, any changes made and who made the change, when and the reason for change.

· Modifications and Corrections – all data must provide a complete audit trail that allows the reconstruction of the data from initial entry. Only the investigator or qualified clinical study staff should perform modifications to the data.

· Data Review

· Investigator - the investigator is responsible for the conduct of the study and should review and electronically sign-off on eCRFs.

· Monitor - the sponsor is responsible for verifying the data collected in the study is accurate and complete. A clinical research associate (CRA), representative from the sponsor must monitor the study data on a regular basis.

· DSMB - depending on the risk involved in a study, an independent data safety monitoring board (DSMB) may be assigned to review study events to determine that the risk to the subjects is not too great. This board will look for trends in adverse and serious adverse events and provide recommendations on study safety.

· Retention of Records - the investigator is responsible for ensuring that study records are accurate and complete, storing, and maintaining the study records for the required time.

References:

Food and Drug Administration (FDA). (2013) Guidance for Industry Electronic

Source Data in Clinical Investigations

FDA. Code of Federal Regulations, Title 21 part 11: Electronic Records; Electronic Signatures.

Code of Federal Regulations, Title 21 § 50.3: Definitions.

Code of Federal Regulations, Title 21 part 312: Investigational New Drug

Application.

Code of Federal Regulations, Title 21 part 812: Investigational Device Exemptions.

Code of Federal Regulations, Title 45 part 170: Health Information Technology Standards, Implementation Specifications, and Certification Criteria and Certification Programs for Health Information Technology.