Six Ways an Electronic Data Capture System Saves Time

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!

Best Practices for Conducting Clinical Trial EDC User Acceptance Testing

User Acceptance Testing (UAT) is a critical component of clinical trial development using Electronic Data Capture (EDC). It’s the responsibility of the Sponsor/CRO to perform UAT prior to using the EDC to collect data in accordance with a protocol.

Early and thorough UAT can result in studies that are easy to use and monitor, and have short submission preparation timelines. We’ve found this to be especially true when our best practices for conducting UAT are followed. Our VISION EDC provides tools and features that facilitate UAT every step of the way, making it a faster and more effective process. Prelude Dynamics’ seven best practices are described in more detail below. Perhaps you have some of your own you can share with us!

  1. Thoroughly test every e-CRF
  2. Verify masking and role-dependent access
  3. Involve a site
  4. Test the electronic lab interface
  5. Consider risk factors
  6. Involve the statistician early
  7. Conduct Pre-UAT

Thoroughly test every e-CRF

This may seem obvious, but it’s surprising how often this is not done. Sometimes test personnel become complacent when most e-CRFs work as expected, and abandon test efforts early. But then during study conduct it turns out that the Investigator Signoff form – which is the typically the last subject form to be filled out – isn’t working correctly.

It’s especially important to verify that the Inclusion/Exclusion e-CRF is working correctly. Imagine the consequences to the clinical trial if subjects that should be excluded are not. Similarly, dosing calculations should be rigorously vetted.

This is a good time to check the upper and lower limits on data entry fields and to make sure all calculations are operating as intended. VISION’s embedded Field Specification displays this information for every form in the study, which facilitates this process.

Verify Masking and Role-dependent Access

There’s almost nothing worse than unmasking a study, so don’t risk it! Identify every e-CRF where the treatment group (or other masked field) is present and verify that masked roles cannot see the value in either the e-CRF or the audit trail. VISION’s Field Specification is also useful for performing this task.

Inversely, imagine that the treatment dispenser has no access to the Dosing form. Avoiding mid-study changes to permissions reduces the probability of non-contemporaneous entry of critical study data. VISION’s Study Requirements Document (SRD) Configuration can be used to verify that permissions to view, edit, review and finalize each study form have been configured correctly.

Involve a Site

Sites are ultimately one of the most critical components of any successful clinical trial. If e-CRF layouts are clumsy or non-intuitive, sites will have trouble completing them correctly. When this is the case, site enrollment may suffer due to user frustration with the EDC.

Involving one or more trusted sites early in the UAT process can provide early insight into usability issues and allow them to be corrected before the study goes live. VISION’s Feedback function can be useful in capturing site input on usability issues. Happy sites require less monitor intervention and produce cleaner data.

Test the Electronic Lab Interface

Studies that benefit from the use of electronic lab interfaces, such as those supported by IDEXX and Marshfield, enjoy more accurate and timely lab results data in their study. It’s important to coordinate with lab company personnel to assure that data required by their LIMS is included in electronic lab requests, and in the e-CRFs if necessary. It’s typical to configure study-specific parameters used for tracking and billing in the EDC, and to test the interface in a training study (or training site) prior to going live. VISION supports fully validated electronic interfaces for both IDEXX and Marshfield Labs.

Consider Risk Factors

Every study has risks, but for every risk there is a way for the EDC to assist in detecting when a risk is becoming a reality. Many EDCs support ad-hoc query functions that generate reports based on user-entered criteria.  These can be configured to generate reports pertaining to potential risks such as a high number of reactions at a drug injection site, or abnormally high blood glucose level after dosing.

Losing subjects due to lack of adequate follow up poses both a financial and a schedule risk. Tools such as the VISION Event Calendar provide ways to quickly and easily detect missed visits before a protocol deviation occurs. EDC statistics functions can also be used to view data in graphical format, which is more intuitive than rows of numbers and can be used to identify outliers.

Custom reports can be developed in the EDC that are tailored to look for specific potentially risky outcomes. These can be developed at study build time, or added later when unanticipated risks begin to arise during study conduct.

Involve the Statistician Early

Configuring the study database so that the data is organized in a way that makes it easy for the statistician to prepare the data for submission is something that is sometimes overlooked when studies are being developed. This can result in both time delays in submission and difficulty with data analysis.

We recommend entering test data into either a training study or training site, and exporting the data for analysis as part of UAT. This approach allows the statistician to take an early look at the exported data, and test it with their statistical analysis software. If changes are needed to the database to facilitate analysis, these can be made and testing prior to going live.

Conduct Pre-UAT

Pre-UAT? It’s not unusual to identify multiple study changes while testing, especially when unfamiliar with the power and flexibility of EDC. Conducting a Pre-UAT ahead of the UAT schedule can help identify and address most of these changes ahead of time. When this is done, UAT consists of verifying that all requested changes have been implemented, tested and work together in an intuitive way.

Starting study test early is generally recommended to avoid cramming test efforts into the last week prior to going live. When testing is deferred, sites have a more difficult time entering data and study conduct is more difficult and lengthy than it needs to be.

Conclusion

In our experience, following these best practices for performing UAT results in less risky, higher quality studies with excellent usability and data integrity. EDCs such as VISION provide many validated, integrated tools that facilitate both UAT and study conduct. Prelude Dynamics provides training in the use of these tools prior to the conduct of Pre-UAT and/or UAT. We are increasing receiving requests to deliver the data from training studies/sites as part of study closeout. This data serves to demonstrate that UAT has been conducted.

If you’d like more information about any of the tools and features discussed in this article, or would like to schedule a demo, please contact us.

The Future of Visual Study Archives

Your EDC study has come to a close. All data has been finalized and the database has been locked, and now –it’s time to generate your study archive. How do you make sense of all that data visually? The last thing you or your data reviewers want to do is struggle to make sense of overwhelming data delivered in an endless and flat-lined, row-by-row spreadsheet.

In Today’s results-driven landscape, data aesthetics can often play a back-seat role. Large XML files storing computer-strung data points are comprehensive but not entirely human intuitive. Data reviewers can easily overlook relevant data while struggling to understand the visual context in which that data was entered. Flat XML files provide the full data in a raw form, but the visual picture of the study’s conductive methods is incomplete without…. well, visuals of the CRFs. What are the current solutions around this data presentation problem?

In recent years, visual PDF copies of case report forms have been the answer, but with PDFs there is still the problem of how to manage and bookmark every single screen of the study that was once viewed online, in a web-based EDC system. The PDFs are stagnant screenshots and require scrolling through a library of them, in a tiresome fashion. The ability to scroll through and navigate among every single PDF, paralleling the method in which the data was entered is just not feasible.

Prelude Dynamics has a better solution: an offline HTML archive. Dynamic and intuitive in structure it is easy to generate, access, and use. an HTML archive means no longer becoming entangled in a web of spreadsheet columns, unmanageable libraries of PDFs, and no more costly server fees to perpetually host the study for intermittent visual access. The HTML archive displays the entire study and its layout for you with a visual presentation of all data and function captured in one place.

The beauty of an offline HTML archive lies in its dynamic use and its cost reduction; all the appropriate links, highlights and audit trail per form are preserved and navigable exactly as they were presented within the EDC upon collection, but without the cost and security concerns of keeping a server running indefinitely. An offline HTML archive captures all the same data and their hierarchies in a read-only format just as it appeared within the EDC. This makes it infinitely easier for the auditor or data reviewer to navigate and visually scrutinize data results in question. Who entered what where and why are frequent data review questions easily answered with a visual archive.

With Prelude Dynamics’ VISION™ solutions, clients can receive the offline HTML archive in addition to a fully provided XML database (a SAS-approved import format and a native format.) The HTML archive really shines in providing a visual glimpse of studies past in read-only fashion, without altering the data format and results which were initially entered. HTML pages remain locked so they are not editable or alterable when viewing through any browser.

As clients grow the scope of their studies to get the most out of EDC, Prelude Dynamics provides greater solutions for data organization and presentation, in line with the expanding data submission requirements from regulatory agencies world-wide. Regulatory groups are putting increasing emphasis on the review process, and we believe that an offline HTML archive solution will surpass the PDF standard in greater visual accuracy, navigation, and preservation of data.

The future of visual study archives is offline HTML, an emerging standard that makes archives, data review and submission simpler and more fluid for all stakeholders and sponsors, and effectively expedites and refines the review of clinically studied products and their efficacy. HTML archive is an archive solution worth the investment.

Tailored Exports: SAS xport format available with VISION

While XML exports and archives are the preferred format for FDA/CVM submission, the older SAS xport (XPT) format is still allowed by and is being used by some companies for their data submission. VISION™ has always provided XML format and and now it’s possible for you to generate XPT files, on-demand, of any and all your data.

The three acceptable file formats for FDA/CVM submission are XML, XPT and PDF. The choice of which format is largely in the hands of the sponsor uploading the data via e-Submitter. A PDF option is currently available as part of the final archive but Prelude’s VISION™ platform provides Clients with the ability to export both XML and XPT files directly from within the system. Log in, select your data set, and click to download.

XPT has been around for a long time and as such is used in a legacy fashion by those that have been working in the industry for decades. XPT has some limitations, as its variable names are constrained to a maximum of 8 characters; labels, to 40 characters and maximum variable value is 200 characters. The 8 character variable names must be unique and usually require a dictionary (README) that explains what each of the cryptic 8 character names really mean. Despite these limitations, XPT offers the advantage that SAS will read it into row/column tables very quickly compared to SAS’s ability to read XML format.

XML format, which is the VISION™ platform’s raw source data format, is more robust than XPT. It allows data to be stored hierarchically with multiple levels. This provides many advantages in non-proprietary readability without XPT limitations. The FDA has recognized this and for more than a decade has provided guidance on the move to XML in conjunction with standards such as C-DISC and SEND.

In conclusion, even as the XPT format fades away to be replaced by the more robust XML format, Prelude has added the XPT file format to be exported and downloaded with the same ease as XML files. This provides the legacy transformation of XML to XPT at the push of a button and provides Clients with more choices and compatibility and flexibility for older software tools.

A Case for HTML Archives for FDA Submission

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 ArchivePDF ArchiveHTML Archive
Accessing softwareXML 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.
Security and Virus vulnerabilityNo vulnerability.No current vulnerability but PDF enhancements may someday add scripting.HTML can have embedded JavaScript that a scanner would need to remove. These same malware detection components are included in all modern browsers.
Availability of software to access archive typeMost 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.
NavigationXML 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 documentsNot 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 reviewMost 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.

Contact

Jim Pedzinski – VP of Business Development
jpedzinski[at]preludedynamics.com – 512-476-5100 ext. 210

Tips from CVM to Streamline Submissions

WASHINGTON, D.C. – April 20, 2017 – Tips from CVM to Streamline Submissions

At the recent SQA Conference, we had an opportunity to meet with numerous representatives of the FDA Center for Veterinary Medicine (CVM). We spoke at length about protocols for data submissions and their review process. Several sessions included significant sections on EDC and submissions.

Highlights from Conversations and Presentations

CVM is pro-technology, seeing the benefits for everyone involved. Their requests for more information come from a genuine interest in learning more. They want to engage in dialogue with sponsors to understand and clarify, not prevent the adoption of new systems.

They are realistic and know there is no such thing as a “perfect study”. Many of the issues raised by reviewers which result in “refusal to review” or “rejection because of incomplete tech sections” could be eliminated if they avoided many of these very common problems:

  • Lack of clarity on how data was initially collected. It is difficult to determine if copies of raw data were submitted and where to find that data in the submission.
  • Submissions are often made without a full copy of study database as electronic files (XPT or non-propietary XML).
  • Files received were not in English.
  • Inconsistencies in data when compared to audit trail or PDF copies.
  • Data variable formats changing (e.g. date format) when moving from XML to XPT.
  • Large files which are difficult to open and review.
  • Inadequate documentation of files and incomplete “readme” files.
  • Variable description is not clear, missing units or coding description.
  • Variable names don’t correspond well to the questions or field labels.
  • Insufficient description of data flow from collection through analysis and how it relates to electronic data files.

How to improve your back-end data submissions after trial is complete

  • Data recording must be credible, corroborated and consistent.
  • XML files are preferred, but should be submitted with a “readme” file describing the XML structure and the relationship to the forms the site filled out.
  • Avoid large data arrays presented in huge spread sheets. A hierarchy that consolidates patient information by nesting related data simplifies the audit process.
  • Provide the audit trail close to the actual variable.
  • Provide a summary in the final report to match raw data.
  • Document and explain deviations.
  • Fully describe procedures with data flow so the reviewer can reconstruct the study conduct.
  • Provide data as close to “raw” as possible. (Reviewers will check the study report against the raw).
  • While ordinary PDFs are acceptable, they are awkward and there is NO requirement for all cases to be in PDF. However, an annotated Case Report Form (CRF) in PDF format that shows mapping of variables to pages for a single blank case is very helpful.

HTML on the Horizon?

One of the more interesting conversations we had focused on the acceptability of HTML for submissions. While CVM’s eSubmitter does not currently support HTML we were encouraged that many CVM members, including Debi Garvin, Director at CVM, are interested in seeing such a system developed.

We are planning follow up conversations with members of CVM to present a case for HTML to be added to the legal formats for submission.

If you would like to know more about our conversations or the presentations at the SQA conference, please give us a call.

Prelude Dynamics is a global provider of innovative software for conducting both human and veterinary clinical trials. Prelude’s VISION™ software system, the only Clinical Trial Optimization Platform (CTOP) available in the industry, takes EDC to the next level by supporting a continuum of study development options that fully integrate into your workflow through do-it-yourself and full-service custom study builds.

Contact

Jim Pedzinski – VP of Business Development
jpedzinski[at]preludedynamics.com – 512-476-5100 ext. 210