An investigative site is chosen to recruit patients into an approved trial.
After patients give their consent, the investigative centers (sites) enroll them into trials.
The sites conduct assessments, evaluations, and laboratory analyses according to the study protocol.
Data are recorded in source documents and transcribed later by a coordinator into the study-specific case report form (CRF).
A monitor compares each data point in the CRF with the source record.
The monitor then ships a paper copy of the CRF to a central data management center (per FDA regulations, the site maintains the original source documents and a copy of the CRF).
For accuracy, data-entry technicians double-enter each data point into a clinical database.
A computerized review of the database then generates queries about data inconsistencies, missing information, and incomplete entries. The monitor resolves the queries with the site.
Data-entry technicians double-enter the resolutions.
Another computerized review occurs, and the review–query–resolution loop continues until the data are “clean”.
Finally, the database is transferred to the clinical statistician for analysis.
Clinical research is regulated by the Food and Drug Administration, an agency of the United States Federal Government. A part of that agency, called the Center for Drug Evaluation and Research, is directly responsible for clinical trial regulation. It set a protocal for using computer systems in clinical trials and posted a draft of the document online in 2004. The purpose is to get feedback from the community, much like Requests For Comments for IEEE protocols. The document posted in 2004 contains a section on Data Entry. This section defines a protocol for Access Controls, Audit Trails, Security Measures and Timestamping.
Paper is an important tool in clinical trials because it allows for recording complex information on a cheap and portable medium. The problem with paper is that it is diffucult to use and perform computation on paper-based data. Since clinical trials are so data-intensive, computerizing their data is an obvious goal.
Clinical trials are largely data-driven, so a client-server architecture is sufficient for entering the data. Many systems use Personal Data Assistants for data entry,while others use more powerful portable computers. Oracle has developed a system for clinical trials that uses such an architecture, but requires a client machine powerful enough to run desktop-like software:
Desktop-like software does not require a desk anymore. Machines like the TabletPC put powerful machinery in a portable, key-less "electronic notebook." See this review by Aventis (published by Microsoft):
Problems
There are two problems with using portable devices for clinical study data entry. First, according to Modern Drug Discovery Magazine, scientists are actually more likely to make errors when entering data into a portable computer than when writing on paper. This problem must be addressed with immediate data review, but the timeframes for patients and other aspects of clinical trials make this difficult. Some software is somewhat intelligent and attempts to recognize potentially erred data entry and alert the scientist in real time. Of course, there is a tradeoff between efficiency/convenience and error-alerts, and if a system like this has more than just a few flaws, it could cause more data entry problems than it solves.
The second problem stems for an FDA requirement. The FDA mandates that, in clinical trials, all original data entered for a study must be available forever. When the initial data is entered on a battery-powered device with limited storage space, such a policy becomes a problem. Fortunately, the FDA allows the data to be downloaded directly to a harddrive for storage of the "original" data.
Examples
Portable data entry is becoming the quintessential method for data entry in clinical trials. It provides cheaper, faster, more consistant data entry. See the following examples of portable data entry systems:
