Data management in clinical research

Clinical Data Management (CDM) is a critical phase in clinical research, which leads to generation of
high-quality, reliable, and statistically sound data from clinical trials. This helps to produce a drastic
reduction in time from drug development to marketing. Team members of CDM are actively involved in
all stages of clinical trial right from inception to completion. They should have adequate process
knowledge that helps maintain the quality standards of CDM processes. Various procedures in CDM
including Case Report Form (CRF) designing, CRF annotation, database designing, data-entry, data
validation, discrepancy management, medical coding, data extraction, and database locking are assessed
for quality at regular intervals during a trial.

The quality of data generated plays an important role in the outcome of the study. Often research
students ask the question, “what is Clinical Data Management (CDM) and what is its significance?”
Clinical data management is a relevant and important part of a clinical trial.

CDM is the process of collection, cleaning, and management of subject data in compliance with
regulatory standards. The primary objective of CDM processes is to provide high-quality data by keeping
the number of errors and missing data as low as possible and gather maximum data for analysis. Best
practices are adopted to ensure that data are complete, reliable, and processed correctly. This has been
facilitated by the use of software applications that maintain an audit trail and provide easy identification
and resolution of data discrepancies. Sophisticated innovations have enabled CDM to handle large trials
and ensure the data quality even in complex trials. High-quality data should be absolutely accurate and
suitable for statistical analysis. These should meet the protocol-specified parameters and comply with
the protocol requirements. This implies that in case of a deviation, not meeting the protocol-
specifications, we may think of excluding the patient from the final database. It should be borne in mind
that in some situations, regulatory authorities may be interested in looking at such data. Similarly,
missing data is also a matter of concern for clinical researchers. High-quality data should have minimal
or no misses

Many software tools are available for data management, and these are called Clinical Data Management
Systems (CDMS). In multicentric trials, a CDMS has become essential to handle the huge amount of data.
Most of the CDMS used in pharmaceutical companies are commercial, but a few open source tools are
available as well. Commonly used CDM tools are ORACLE CLINICAL, CLINTRIAL, MACRO, RAVE, and
eClinical Suite.

In regulatory submission studies, maintaining an audit trail of data management activities is of

paramount importance. These CDM tools ensure the audit trail and help in the management of
discrepancies. According to the roles and responsibilities (explained later), multiple user IDs can be
created with access limitation to data entry, medical coding, database designing, or quality check. This
ensures that each user can access only the respective functionalities allotted to that user ID and cannot
make any other change in the database. For responsibilities where changes are permitted to be made in
the data, the software will record the change made, the user ID that made the change and the time and
date of change, for audit purposes (audit trail). During a regulatory audit, the auditors can verify the
discrepancy management process; the changes made and can confirm that no unauthorized or false
changes were made. Since the pharmaceutical industry relies on the electronically captured data for the
evaluation of medicines, there is a need to follow good practices in CDM and maintain standards in
electronic data capture. These electronic records have to comply with a Code of Federal Regulations
(CFR), 21 CFR Part 11. This regulation is applicable to records in electronic format that are created,
modified, maintained, archived, retrieved, or transmitted. This demands the use of validated systems to
ensure accuracy, reliability, and consistency of data with the use of secure, computer-generated, time-
stamped audit trails to independently record the date and time of operator entries and actions that
create, modify, or delete electronic records. Adequate procedures and controls should be put in place to
ensure the integrity, authenticity, and confidentiality of data.

Database designing

Databases are the clinical software applications, which are built to facilitate the CDM tasks to carry out
multiple studies

Data collection

Data collection is done using the CRF that may exist in the form of a paper or an electronic version. The
traditional method is to employ paper CRFs to collect the data responses, which are translated to the
database by means of data entry done in-house.

CRF tracking

The entries made in the CRF will be monitored by the Clinical Research Associate (CRA) for completeness
and filled up CRFs are retrieved and handed over to the CDM team

Data entry

Data entry takes place according to the guidelines prepared along with the DMP. This is applicable only
in the case of paper CRF retrieved from the sites

Data validation

Data validation is the process of testing the validity of data in accordance with the protocol
specifications. Edit check programs are written to identify the discrepancies in the entered data, which
are embedded in the database, to ensure data validity

Discrepancy management

This is also called query resolution. Discrepancy management includes reviewing discrepancies,
investigating the reason, and resolving them with documentary proof or declaring them as irresolvable.
Discrepancy management helps in cleaning the data and gathers enough evidence for the deviations
observed in data.

Medical coding
Medical coding helps in identifying and properly classifying the medical terminologies associated with
the clinical trial. Medical coding helps in classifying reported medical terms on the CRF to standard
dictionary terms in order to achieve data consistency and avoid unnecessary duplication

Database locking

After a proper quality check and assurance, the final data validation is run. If there are no discrepancies,
the SAS datasets are finalized in consultation with the statistician. All data management activities should
have been completed prior to database lock.

Roles and Responsibilities in CDM

In a CDM team, different roles and responsibilities are attributed to the team members. The minimum
educational requirement for a team member in CDM should be graduation in life science and knowledge
of computer applications. Ideally, medical coders should be medical graduates. However, in the industry,
paramedical graduates are also recruited as medical coders. Some key roles are essential to all CDM
teams. The list of roles given below can be considered as minimum requirements for a CDM team:

Data Manager

Database Programmer/Designer

Medical Coder

Clinical Data Coordinator

Quality Control Associate

Data Entry Associate

CDM has evolved in response to the ever-increasing demand from pharmaceutical companies to fast-
track the drug development process and from the regulatory authorities to put the quality systems in
place to ensure generation of high-quality data for accurate drug evaluation. In spite of these, CDM is
evolving to become a standard-based clinical research entity, by striking a balance between the
expectations from and constraints in the existing systems, driven by technological developments and
business demands