This course is a basic introduction to the VISION Electronic Data Capture system used in Emissary's clinical trials. It is the prerequisite for advanced courses and specific case report form training on an Emissary clinical study. The course consists of a written discussion, a short video and an online quiz. Registered and logged-in students obtaining a passing score on the quiz will receive a certificate of course completion. For members of an Emissary study project team, this certificate should be saved and uploaded to the eTMF to serve as part of the regulatory documentation for the trial.
Time required: 30 minutes.
What is VISION Electronic Data Capture?
VISION is a Web-based Electronic Data Capture system for the collection of clinical data and the management of clinical trials. The core software was developed by Prelude Dynamics, a closely-affiliated partner to Emissary International. Each specific trial is implemented in the core VISION system using proprietary templates and data management standards in accordance with the needs of the particular clinical study. VISION is more than simply an online case report form (CRF). It is part of an elaborate clinical trial management platform (eClinical system) which allows Emissary to conduct completely paperless trials, with higher data quality, that are completed faster and at less cost. Emissary College, where you are now, is another such tool that empowers Emissary's clinical trials.
Prelude hosts and maintains the VISION system at a dedicated, state-of-the-art 15,000- square foot Tier-3 data center that is staffed 24/7/365 and certified under SAS-70 Type-2 and PCL-1 standards. This means the clinical data is maintained under the highest industry standards for data security, storage, backup and disaster recovery. The VISION website can be accessed from any modern browser such as Internet Explorer v7+, Firefox v2+, Chrome or Safari running on a desktop, laptop or tablet computer such as the Apple iPad. In a pinch, the browser in a cell phone can even be used to access the case report form.
- The SITE area stores information such as the site status and the date of initiation. This is also where a site stores their regulatory documents and enters reference ranges for their lab.
- INFO is the repository for the trial master file documents such as the protocol and investigator brochure, documents that are global across all sites. This is also where calendar-based notifications are managed.
- PATIENTS is home for the online case report form. Additionally, source documents are uploaded here for monitor verification.
- USERS is where the project manager assigns roles and access rights. There is also a user setting to tell VISION where you want to receive notifications.
- One of these selections is to have messages sent to the NOTIFICATION area, the last structural area on this list. This can be the repository for all immediate messages that are sent by the system, or alternatively you can have messages sent to your email as well.
- The LIST VIEW is home base. You can click items in this list to drill-down to the detail view.
- DETAIL VIEW is analogous to a 3-ring binder. Here you have tabs that encompass groups of pages similar to the traditional paper CRF binder.
At the top of the LIST VIEW is the SHOW SELECTOR, where you access various lists, each representing a structural area: Sites, Patients, Users, etc.
Most lists have a FORM STATES column, which we will review in a later discussion about workflow.
A set of buttons that change based on where you are in the system can be found in a FLOATING TOOLBAR that remains near the bottom of the window as you scroll down the page.
Finally, in the top-right corner of the detail view is the all-important RETURN-TO-LIST button. Click it to get back to the Detail View. As with most other secured websites, clicking the BACK BUTTON on your browser will break the connection with the server. User the navigation control in the interface instead to move between pages. Also, VISION will automatically save your work if you click on a different page/visit tab, but closing the browser or click a browser link for an another website could result in losing the current form's unsaved data. Be sure to SAVE your work before leaving the page suing the button in the floating toolbar.
As VISION runs in your browser, it uses the standard internet field controls (radios, checkboxes, text fields, and dropdowns) that you see on any web form, but some of these controls have unique enhancements.
For example, there is a popup calendar for entering dates, and also images with clickable sections.
Back in the days of paper case forms, coordinators were instructed to never leave any question/field blank. The reason for this is that paper forms were inherently insecure; there was nothing to prevent someone fraudulently putting data in that spot after the coordinator had signed the page. Conversely, EDC systems have secure access restrictions, electronic signatures and change-tracking ("audit trials") that eliminate such risk. As a result, with an EDC system, it's not necessary to put useless text into a blank field, albeit other less inexperienced CROs may still require such outmoded procedures. Instead, VISION handles blank fields without problem. If it's an important mandatory data point, the system will flag it. And, there will be NOT DONE/NOT APPLICABLE checkboxes and automated protocol deviation tracking for missed procedures/visits. The result is a cleaner, more analyzable database.
As it was with paper case forms, the pages in VISION need to be signed by the coordinator. You do this by entering your password in the floating footer, then clicking the SUBMIT-FOR-REVIEW button just to the left of the password box. This alerts the Clinical Research Associate (also called a CRA or monitor) that the form is ready for monitoring.
The monitor will review your entries, verify against source documentation, and then sign the form as well.
VISION can be set-up in different ways, but for the studies managed by Emissary, we generally create a special section at specific milestones in the study where the investigator can sign and release that section of the case form for regulatory reporting.
At the bottom of the accompanying graphic is an example taken from the FINAL STATUS form in one of Emissary's clinical trials. Here the PI signs a statement confirming review of the entire case report form. In our studies we want the investigator to sign only after all the data is complete, so there will be a Last Form Change calculation to ensure that the signature date occurs after all data have been monitored and any queries resolved.
These thermometer-like icons appear at the top of visit and page tabs and in the far-right column of most listings. The form state is also displayed in the signature block at the bottom of every case form page.
- The blank thermometer indicates a new form with no data having been entered yet.
- A ¼-blue thermometer indicates an in-work form...data is incomplete.
- A ¼-red thermometer indicates there are errors that need to be resolved before the form can be signed.
- A half-orange thermometer indicates that the form has been signed by the coordinator and is ready for monitoring.
- A ¾-yellow thermometer marks the completion of monitoring, and
- A solid green icon says the form is final. Thus, the goal is to advance all case forms to solid green.
Errors & Warnings - Constraints
Like every EDC system, VISION has a robust capability to flag all entries that fall outside of certain constraints, such as a valid range for a blood pressure reading, for example. These constraints on the allowed data entry are sometimes called automated edit checks.
These constraints can have two levels of severity.
- The most serious are RED ERRORS. These are entries that are absolutely wrong, such as a screening visit that predates the study initiation.
- YELLOW WARNINGS flag entries that are outside of expected limits. It may or may not be an error; it needs a second look.
Here's where using an experienced CRO like Emissary to develop the specifications for your EDC implementation is imperative. Designing a case form for EDC is far more complex than what was required in the days of the old 3-part carbonless paper forms. It takes someone who simultaneously can think like a programmer and a clinician at the same time. And it takes a team that has worked closely together for many years, as have Emissary and Prelude Dynamics.
Emissary was one of the first companies to implement EDC across all clinical trials, now almost 10 years ago. In fact, we invented one of the first commercial systems that is still being sold by one of the large publicly-traded EDC vendors. Prelude is an extremely customer-focused company and has one of the most flexible and extensible systems available today.
Let’s now review how VISION both implements the regulatory requirements for a robust audit trail and how VISION handles the workflow and communication tasks of a coordinator and monitor working in concert on a case report form.
A good CRF should have lots of instructions to walk a new coordinator thru the study. But after the first patient or so, these instructions can get cumbersome and take up lots of space. So, VISION has a toggle, represented by a little blue circle-I icon that can hide or show the instructions.
In the floating footer, there is a button that turns on the note icons next to every field. You can click on one of these to add a field-level comment, then turn it off to hide the musical icons again.
Regulatory agencies require an audit trail, so VISION uses little triangles or delta symbols to flag a field where the value has changed. At the bottom of the form, there is a button, not shown here, to show a summary of all the changes to the form.
Monitors can attach queries to any field, and they appear in VISION as red question marks next to the applicable field in the coordinator’s view.
Most of these icons change color and/or shape as they progress thru a workflow. For example, a new query is a red question mark. Once the coordinator has responded, it becomes a dark-blue exclamation point. After the CRA has verified the correction, it turns pale-green.
Having explained the basic structure, status symbols and field markers, we can now review the general workflow for collecting data in the VISION EDC system.
First, the coordinator will log-in with an assigned username + password, go to the SHOW:PATIENTS main listing and click ADD NEW PATIENT in the floating footer menu. The coordinator will then complete a form providing demographic information for the new patient. In most studies, this registration form is also used to document screen failures, eliminating the need for any paper-based patient tracking log.
Saving the registration form (after resolving any red errors) will create the remainder of the case report form and generate a patient screening number. Each newly-created blank page will start with the status of NEW and have a blank status thermometer.
Next, the coordinator will complete the various pages of this online case form, clicking SAVE in the footer of each page. The status thermometer will change to 1/4-blue.
Most fields will have programmatic verification checks that will automatically display yellow warnings or red errors upon clicking SAVE should the data not mean certain constraints; explanations for the highlighting will appear at the top of that section. Yellow warnings should be re-reviewed; red errors will need to be corrected before the page can be signed. In the interim, the page can still be saved (by clicking SAVE or moving to another page). Upon returning to the page later, clicking SHOW ERRORS in the footer will again display explanations for why the fields have been highlighted. In the interim, the status thermometer on the page and visit tabs will turn red to indicate there are unresolved red errors.
As each page is completed and any red errors have been resolved, the coordinator will enter his or her password in the floating footer and click SUBMIT FOR REVIEW to advance the page to the IN-REVIEW status. The status thermometer will change to 1/2-orange.
In our fully paperless studies using the Emissary Electronic Trial Master File (eTMF), the coordinator would also upload scanned images or PDFs of the patients medical records ("source documents"). Document uploads, which may include imaging files, source documents, etc., are usually collected on a page near the end of the case form which uses Emissary's eTMF system, or they may be incorporated directly into each page as a simple upload control.
The Clinical Research Associate (CRA or Monitor), upon receiving an email notification from VISION, would next sign-in to review the submission and verify the coordinator's entries against the uploaded source documents (or alternatively during a on-site monitoring visit). The Monitor can then create queries (red question marks) next to questionable data for the coordinator to resolve, or if the data was acceptable as is, electronically sign the page by entering a password and clicking SUBMIT AS REVIEWED in the footer toolbar to advance the page in the workflow. The status thermometer will change to 3/4ths-yellow. Alternatively, the monitor can advance the page to FINAL status (solid-green thermometer). A page that has been finalized is no longer editable by the site (but can be reverted back by the monitor later if necessary).
A page that has been signed by the coordinator as In-Review (1/2-orange) or which has been signed by the monitor as REVIEWED (3/4th's yellow) will automatically revert back to IN-WORK should the coordinator or investigator make any subsequent change to the page, say due to a late monitor query. After making such a change, the coordinator should therefore sign the page again to get it back into IN-REVIEW for re-monitoring and finalization by the Clinical Research Associate.
The next step will vary among different studies/sponsors, but generally the investigator will need to confirm his or her review of the patient case and to release the data for analysis. In Emissary's trials, the investigator's electronic signature is generally only collected after certain milestones (such as to confirm medical review of patient eligibility or after a Serious Adverse Event). As it can sometimes be difficult to know when all the data is ready for investigator review, we will generally advise the investigator to wait until specifically asked before completing this review and sign-off. Otherwise, the system which tracks all changes to the pages pertaining to that investigator sign-off, will invalidate the signature should there be a subsequent change. The investigator can always sign-off again, but to avoid wasted effort, it's best to wait until the coordinator and monitor have finished all their work.
- A new enrollment into the study
- A randomization event
- A serious adverse event
- A breaking of the blind
- A new document having been uploaded
- ...or the email that coordinators so love to get, a new query.
There is a setting in the SHOW:USERS area where the user can decide if notifications should be sent internally or externally as an email.
A unique feature of VISION is the ability to send messages on a future calendar date. For example, when a coordinator enters a visit date, VISION can set a trigger that will send a reminder in 30 days to the coordinator that the next visit is due.
This capability is also a key component of the Electronic Trial Master File, where triggers are set upon uploading a document. For example, when a coordinator uploads an IRB Approval Letter, VISION can send a reminder 30 days before the next IRB Review is due. Please see the eTMF course for details.
In the SHOW:USERS area in your user account document, there is a setting where you can select whether notices should remain in the notification area, or if you want them also sent via email.
Emails will have a link that, upon log-in, will take you directly to the corresponding form where the notification was triggered.
Roles control whether you can view, edit, query, sign or finalize a form.
Roles are also used to identify you as part of a group for the purposes of certain notifications. For example, serious adverse event notifications need to be sent to the Safety Coordinator and Medical Monitor. By employing roles, the specific assignment of staff to a role can change without having to change the configuration of the EDC. A new coordinator can step in and pick up where the prior coordinator left off.
Finally, roles can provide data for user selection lists. For example, in the CRF, there might be a question about who conducted a certain procedure; the list of names can be taken from a specific role, say investigators or coordinators. This functionality is used to link events in the case form with the Electronic Trial Master File, for example, when asking who conducted an assessment, to present a list of people who were qualified to do the assessment based on their training documentation.
Calculations in VISION have robust data validation so they can compensate for missing or invalid data used in the calculation. For example, VISION understands it cannot calculate the due date of the next visit if the patient has not yet been randomized.
For example, VISION will only present a pregnancy screening section if the patient is female.
A derivative of the show/hide functionality is what we call expandable sections. A toggle, in this case the +/- icon in the second column of the accompanying graphic, is used to collapse or expand a listing.
This design element is used extensively in the document manager of the electronic Trial Master File (eTMF), to show/hide prior revisions of a document.
VISION uses a repeating-row table design element to simplify the collection of such information. When you enter a row of data and save the form, a new blank row is automatically appended to the table. These blank rows are not exported or included in reports; they just make it easier to enter lists. Remember, you must first save the form before a new blank row will appear.
Generally, this is done by clicking a button in the floating footer, but it can also be triggered automatically. For example, entering an Adverse Event with the SAE Yes/No box set to YES, can automatically add an SAE form to the database (if that is how the study is designed).
VISION has the ability to pull data from anywhere in the system, whether it be a list of lab reference ranges stored in the site area or even a list of site personnel who have appropriately uploaded their training documentation in the Electronic Trial Master File area. This functionality is used in designs such as lab reports (to eliminate having to type reference ranges for your local lab). You may also notice non-editable fields elsewhere that pull-in information from other pages; these are there to help you remember important information without having to refer back to that page. An example is the Adverse Event form, where you may see a list of drugs that you stated on the concomitant medication page were used to treat this AE.
From the Main List, click SEARCH FOR PATIENTS, enter one or more selection criteria, then click APPLY to show a subset of the list matching those criteria.
It is an AND comparison, meaning a patient must meet ALL the criteria.
Patients in the list can be sorted by clicking the header buttons at the top of each column.
You can create as many SETS of selection criteria as you want, by clicking ADD SEARCH to create a new form.
To remove the search selection, click CLEAR in the footer.
A few of these summaries appear in virtually all studies, but most are custom-designed according to the needs of the study.
Remember, summaries generally apply only to those patients in the selection list, so run the SEARCH before running the SUMMARIES.
In situations where there is not a custom summary, you can use the REPORTS tool to generate a custom data listing. Let's say you want a list of blood pressures for just the female patients; you should use the Reports button.
Clicking REPORTS in the footer toolbar from the main list takes you to a form where you can enter a selection of fields. Afterward, VISION will immediately generate a report with those columns.
This is a basic document management system designed specifically for clinical trials. With this tool, you can completely eliminate the need to maintain site regulatory document files and the parallel sponsor shadow file.
Emissary developed the concepts and specifications for this. Our main goal was for it to be easy-to-use but nonetheless it still handles revision tracking, private documents and version status and comments.
As we discussed earlier, the eTMF is fully integrated with the notification system. That means, that whenever a document is uploaded, it can send messages to roles such as the coordinators or specific users. It also collects meta data, for example the date of an IRB approval, that be used to trigger ca alendar-based notification that documents require revision.