An EDC improves efficiency and reliability while conducting clinical research. Here are some ways it does that:
1. Efficient Communication
The efficiency of communication between team members is what determines the success or failure of a clinical trial. If a team does not have a streamlined process for disseminating information throughout the life of a project that deals with the staggering amount of data typically generated by a drug trial, everything else can fall apart. An Electronic Data Capture (EDC) system provides a platform for making sure information gets to the proper people in a timely manner in a way that paper will never be able to match.
With an EDC, there is a much lower risk of communications being lost or seen by the wrong people. Updates can be shared instantly to ensure that everyone who needs to know will have the pertinent information at their fingertips with no waiting. The only thing you will have to wait for is federal approval (sorry, can’t help you there).
2. Instant Documentation
Every time a user changes a field or makes an entry into the EDC system, the time, date, and user information is captured and recorded instantaneously. Indeed, as soon as a user logs onto the study, the EDC system records how much time they spent on each form even if they simply left their browser open while they played Solitaire in another window (disclaimer: we do not, as yet, have a way to track for you who on your team is playing games and who is actually working).
The EDC system can also record signatures on forms along with accurate date/time stamps. Say an investigator forgot to sign off on a form, and it goes unnoticed until the end of the trial. With paper, the monitor would have to track down who the investigator at that site was and mail them the form to sign. Then the offending investigator would have to mail the signed form back to the Monitor. If the investigator forgot to sign the form initially, who is to say they won’t also forget to send the signed form back? This process is time-consuming and susceptible to errors. With electronic data-capture, signatures are a given and no one has to wait by the mailbox for clerical corrections.
3. Intuitive Summaries
Most clinical trial personnel would agree the most time-consuming aspect of a drug trial is the extrapolation of useful information from the massive amounts of data generated throughout any given study. Where paper fails, an EDC system thrives. The EDC platform is designed specifically to make combing through data as efficient as possible (we won’t go so far as to say it’s enjoyable, but efficient, definitely). An EDC accomplishes this by providing user-friendly summaries directly within the system, which saves time and energy by doing all the work of combing through patient data for you.
Summaries can be set up to meet almost any parameters you can think of, and they can be set up in a matter of seconds. You can compare infinite pieces of data (provided you have infinite pieces of data) to help you come up with the most accurate results possible for your study without wasting man-hours (or woman-hours). Most importantly, EDC summaries can be saved, altered, and shared as fast as thought, so you can keep up with the continuously evolving business of producing safe drugs for people and animals.
4. Real-time monitoring
Monitors can review data entered into an EDC System as soon as the person entering the data hits ‘Save’. There are even features which allow monitors to view data-entry live from a remote location to ensure that patients are kept safe during difficult or potentially dangerous procedures. An EDC system keeps a study moving forward by removing lag-time between clinical observations of patients and safety monitoring of documentation.
5. Error Minimization
The biggest shortcoming with recording data on paper might be the amount of errors that go undetected. When using an EDC system, where every field utilizes automatic constraints and calculations, often in tandem, errors are not only much easier to detect but they are also much easier to prevent.
Constraints can be placed on fields to restrict an impossible value from ever being entered in the first place. If there are unforeseen types of errors that the constraints do not account for, then the monitors can easily attach a query directly onto the field in question. Then the system can be updated to catch any future errors of the same kind. More levels of validation lead to less mistakes.
6. Customizable Forms
Every clinical trial is unique, and, therefore, every clinical trial has unique requirements when it comes to forms and fields. An EDC system, being highly customizable, offers the ability to only show the fields necessary to be filled out for each patient and visit. This saves time for the investigators when recording their observations. They do not need to waste time filling out an entire stock form as they would on paper.
Forms in an EDC system can be set up so that the next field or form becomes visible or remains suppressed depending on the answer to a previous field or form. In this way, the system guides the data entry personnel through the appropriate process and prevents a lot of headaches. Plus, not having papers means no paperwork!
Currently FDA official submissions must be in XML or PDF format, with the preference being the submission of at least the XML format. The rationale for these is the need to have a document that will be readable and accessible in perpetuity. This is definitely an important consideration. However, these formats contain limitations when it comes to the review, oversight and approval process as clinical reviewers are more effective “seeing” a case as a set of forms the way the Investigator filled out those forms, while analysis staff are more effective with the XML raw information. How do you handle ancillary data, such as images and graphical information that were part of the process which cannot be imbedded in XML?
Below we will present a case for allowing HTML archives to be added as a part of or one of the allowable formats for FDA submission, fundamentally to support clinical case review. The raw XML would continue to be favored format for data analysis.
HTML, Hyper Text Markup Language, is the foundation of all computer languages used to create web-based interfaces. HTML is a specialized form of XML that when combined with images and style sheets (CSS) make a web page appear as it does. The Internet has been growing exponentially since its inception transforming business and everyday life; the Internet is here to stay and so is HTML. “Billions and billions” of HTML web pages exist in the world today. HTML can be compared to the alphabet. Like the alphabet, it provides us with basic element in which we can combine in order to communicate via web pages. HTML does for computer language what the alphabet does for our language. It is safe to say HTML will stand the test of time.
One might assume that HTML requires a web server to operate, but in fact, an HTML page is just a document that resides on a computer hard drive on a server, and can also be saved locally. All browsers support “Save As” and can save a web page for later viewing when the computer is disconnected from the Internet. All that’s needed is any brand of web-browser. As such, these HTML/XML pages are safe, secure, and as perpetual as any computer file on the hard drive.
Now that we have established that HTML is a viable solution in perpetuity, let’s examine the differences between XML, PDF and HTML archives. The main differences are listed in the table below.
| ||XML Archive||PDF Archive||HTML Archive
|Accessing software||XML can be imported into many database software programs as well as some spreadsheet programs. It is truly non-proprietary, and readable by humans with just a text viewer.||PDFs can be read using a number of portable file document readers. The PDF format has been made public, but is proprietary and licensed by Adobe.||HTML is truly non-proprietary, and can be read like XML, but looks best when combined with CSS in any browser.
|Availability of software to access archive type||Most of these have to be purchased.||Some of the readers are available free, but the population in general does not all have them.||All computer users have access to free browsers.
|Navigation||XML is typically hierarchical which reduces duplication compared to repeating table rows. Navigation is by drilling into the hierarchy much like opening folders with subfolders.||Data is presented in lengthy documents that are difficult to navigate, but that display the forms upon which data was entered. Limited capabilities to search and find information.||Displays the data in the forms that they were entered in providing the viewer an experience similar to what was used when the data was input. The viewer is able to navigate through pages using the same process the data collector did.
|Handling of uploaded documents||Not contained within the XML file.||Usually available as separate PDFs in a separate folder with no link back to the patient or form.||Documents are accessible through clicking the embedded hyperlink. Documents are in their original format or PDF.
|Visibility of queries, field notations, and changes to data ||Prelude’s XML has queries, comments, and changes co-located with the field variable to which they apply. No separate files. However, XML while a simple structure and open format, is verbose and reviewers are challenged to view a “case” as an entity.||The PDF as a screen image will show what was on the screen, but may also be a separate page or even a separate document. This can make searching and finding difficult.||HTML Archives are saved web pages, and when done properly, allow users to click the hyperlinks to view and navigate the specific query, field notation or change to data related to a given field at the point of viewing the field.
|Overall functionality for analysis (e.g. SAS)||XML provides data that can be freely processed by many non-proprietary systems to support a data analysis.||Does not allow data processing.||Does not allow data processing.
|Overall functionality for case review||Most FDA personnel who review and provide study oversight are not data managers or statisticians; they are monitoring personnel who are more familiar with a paper-based analog (CRFs) process where they can look at the forms and see the data being collected in context as the Investigator staff viewed the case. XML does not provide a format that is easy for them to use.||It is difficult to navigate through long PDFs of patient case report forms and to navigate between patients is nearly impossible or requires opening multiple individual patient PDFs.||Provides excellent functionality allowing navigation from patient to patient and form to form in the same fashion that a person entering data would have done so. It makes the process of reviewing and providing oversight much faster because they do not have to organize the data and can focus on reviewing the data to ensure the safety and efficacy of drugs.
In conclusion, while the XML archive is a natural non-proprietary requirement for data submission because it does allow quick processing of the data in order to analyze the safety and efficacy of a drug, providing HTML data in addition is superior to PDF files in that it facilitates the case review within the same context in which the data was originally collected by Investigators. HTML will increase FDA reviewer’s confidence in the quality of the data and its outcomes.
Prelude Dynamics has initiated conversations with FDA CVM to discuss allowing HTML archives to be submitted. Among the discussion is also the possibility that Sponsors could chose to allow CVM to have access to the server in read-only mode where they could interact with the study data and even run reports, statistics and graphs within the system before final submission occurs in order to guide sponsors on any additional requirements or concerns they might have in order to help expedite the final review process, reduce the need for clarifications, and be quicker to market.
Jim Pedzinski – VP of Business Development
jpedzinski[at]preludedynamics.com – 512-476-5100 ext. 210