November 1, 2010 (Vol. 30, No. 19)

James Netterwald, Ph.D.

Electronic Data Capture Helps Researchers Take Control of Unwieldy Clinical Trial Information

Electronic data capture (EDC), simply put, is the process of using software to collect data during clinical trials. EDC technology is really a subset of eClinical technology, which includes clinical data management systems. It took a number of years before EDC became a staple in clinical trials, and although the technology has been embraced industry-wide, challenges still remain.

Clinical trial data is typically recorded initially on paper. Data is then transcribed at the clinical trial site into the EDC system. In its humble beginnings—in the late 1980s and early 1990s—EDC systems were stand-alone laptops where data from clinical trials would be keyed in a process known as remote data entry.

“Electronic data capture technology really did not take off until we got pretty thorough infrastructure improvements and Internet speeds. In the beginning, only big pharma companies were able to afford electronic data capture technology,” said Mark Paul, CEO at Statworks. Today, EDC technology is more affordable.

Paul was one of the presenters at “OpenClinica”, which was held recently in Bethesda, MD. At the meeting, he spoke about managing trial data. He also talked about FDA requirements, which include computer system validation, electronic signatures, monitoring, standard operating procedures, and training.

Prior to the establishment of EDC, the data-collection process for clinical trials was onerous. At a clinical trial site, the site coordinator would transcribe the source notes into a paper-based, controlled case report form document, which was then reviewed and retrieved by a clinical monitor and sent to a central place (e.g., firms like Statworks) that would enter it into a database.

One of the drawbacks of using paper is that it required a pretty extensive manual data-cleaning process. “We scrubbed data in detail, and the industry spent a huge amount of money cleaning its data. The process was time consuming, taking between six and eight weeks for a coordinator to receive feedback on data they had created,” Paul explained.

“This process existed for a long time and emerging technologies at the time such as the fax machine were used to try to speed up the process. With the advent of electronic data capture, instead of the site transcribing the data on a case report form source document, they would record it on a web-based application, which would immediately give them real-time feedback,” he added.

Most EDC systems offer a master subject matrix screen that provides a quick reference for all subjects, all visits, the color-coded status of each visit, and the icon key for each event status. This portrayal is a quick and powerful reference to the real-time overall study status.

The OpenClinica Platform

The use of EDC technology in clinical trials changed dramatically with the development of OpenClinica software, according to Akaza Research, which sponsored the “OpenClinica” meeting. “One of the key trends in electronic data capture is the move toward more flexible, more easily consumable software, and as far as we’re concerned, that means a move toward open source,” said Benjamin Baumann, co-founder and director of business development.

“The OpenClinica technology is developed and distributed under an open-source license, which means that the product is available to anyone who wants to use it.  Developers also have access to the underlying source code, which makes OpenClinica a very transparent technology.” With OpenClinica, site coordinators just need a browser with Internet access to enter their data.

“OpenClinica has been out there for at least five years, and we’ve been using it for the last four years. Over the last two years, OpenClinica has gotten a lot better and some of that improvement can be attributed to the nature of the open-source world,” Paul explained. “You have a lot of people using, suggesting, and/or modifying OpenClinica to fix various bugs in the software program.”

To collect data from Phase I and II trials, Social and Scientific Systems  relies on case report forms using OpenClinica as a data repository, according to Naji Younes, Ph.D., principal scientist.

Essentially, data entry clerks, located at various locations across the country, key in the data that is received electronically through OpenClinica. “Once the case report forms become available for data entry, they are scanned in a central scanning facility, quality controlled and verified, and then the image of that case report form appears at the keyers’ location.

 “What comes out of OpenClinica is data that has to be transformed into a format that can be read by statistical analysis software (SAS), the primary language that we use for data analysis.”

Modern EDC systems are typically web based, which is the feature that makes them readily available to clinical trial coordinators. “Web-based data-capture systems usually have a relational database at the back end. The fact that the captured data is stored in a relational database dictates how it is organized. At the other end, statisticians analyze data that is in SAS. The goals of SAS and the goals of a relational database are pretty different and the transformation requires some thought.” According to Dr. Younes, Social and Scientific Systems is working on merging those two different worlds.

Every clinical trial involves the collection of complex data with each trial containing different levels of complexity. “We do not have the luxury of being able to build from scratch custom pieces for every study. Every piece of software used in a pharma study has to be validated so it is to your advantage to build generic stuff that is clever enough to adapt itself to the idiosyncrasies of a trial. And that is just one of the issues when you are extracting data from OpenClinica,” Dr. Younes added.

Trends and Predictions

“In the past, there was a lot of work done with handheld diaries for patients. And for some studies, that still makes sense, but for others, leveraging existing electronic data capture tools can be a more cost-effective solution,” explained Susan Bornstein, executive vp of eClinical Solutions. The company has developed its own clinical data repository offering, which is designed to enable clinical trial sponsors to keep all data from a trial housed together utilizing the industry standard—Clinical Data Interchange Standards Consortium (CDISC) guidelines.

According to Bornstein, the repository “makes a difference because companies are moving out of the paper world into an electronic world where data is available in almost real time, allowing for proactive data management.”

eClinical Solutions partners with companies to help them standardize their data to meet CDISC guidelines and also comply with Title 21 CFR Part 11, which governs how electronic systems can be used in clinical trials.

In order to meet FDA guidelines for clinical trial data collection, web-based EDC technologies have to be transparent, not proprietary. “One of the key challenges that eClinical technologies should try to address is bringing greater transparency and efficiency across the clinical trial process, for example, by enhancing connectivity and removing silos among the various clinical constituencies,” noted Ashwin Mundra, director of strategic initiatives for Medidata Solutions.

According to Mundra, clinical constituencies include not just the clinical department but also finance, data management, trial management, and trial sites. “One of the main goals of pharma is to remove these silos to help enhance and streamline clinical processes and solve problems that are common to all these departments, not just data management.”

Baumann agreed that transparency in EDC systems is essential. “The way I see this technology moving in the next five years is toward a lighter-weight approach. I really think that open source is one of the primary drivers of the trend. What electronic data capture systems provide today is really centered on the quality of data, the speed at which data can be collected, and the transparency that the system provides the progress of the clinical trial.”

Previous articleBruker Daltonics Chosen to Build World’s First 21.0 Tesla FT-ICR Magnet
Next articleNovartis’ Afinitor Cleared by FDA for Treating SEGA Tumors in Tuberous Sclerosis