How to Design an Auditor Friendly Clinical Study

Knock, Knock! The BIMO (or FDA QSR) auditor is at the door. It’s time to race around, retrieve documents from file cabinets, and make them easily digestible.

Or is it? If your study is designed with audits in mind, you can relax instead of panicking. But how? One of our industry leading clients shared some of their ideas with us recently. We were excited to hear that Prelude’s eClinical platform, VISION, provides tools and capabilities that help our user community smoothly navigate common audit challenges. Let’s explore several of these.

Personnel Training – Auditors are always asking “how do we know your clinicians have been trained and have the right credentials?”. Why not keep training records and credential certificates in the study database? User forms can be configured to upload and store copies of paper documents – making them accessible directly from the EDC. These forms can be reviewed and finalized by study Monitors as part of their normal activities.

Informed Consent – You know auditors will want to verify that trial participants have been informed about the purpose and risk of the clinical trial and have consented to participate in it. eConsent is becoming more and more popular in the age of COVID-19. Implement eConsent with electronic signatures as part of your study. This helps eliminate problems with missing or incomplete information and ensures your consent documentation will pass inspection.

Summaries – When the auditor asks for a list of Adverse Events, Deviations, or Notes to File – you don’t have to navigate through all subjects and sites to find them. Instead, implement summary forms in your study that capture all occurrences directly from the study database. Now there is only one place to look.

Dosing Records – Too often, subjects or their owners are given paper dosing forms that then must be transcribed into the EDC database. Why not implement these forms directly in the EDC and either allow subject log in or provide subjects with access to an ePRO app. Either of these mechanisms will allow the entry of dosing information directly into the EDC – and best of all, the data is fully attributable.

Owner/Dose Administer Training – One question that comes up frequently is whether dose administrators have been given the proper training – and if you can show evidence of this. Remember, if it’s not documented, it didn’t occur. Record evidence of dose administrator training directly in the study database for easy reference. Also, allow for training of multiple dose administrators to handle the case where a substitute (e.g., another family member or boarding facility staff) will be required to administer the dose.

The VISION data capture platform supports Subject/Owner log in, ePRO, eConsent, custom summaries, and an HTML archive capability. These tools combined can have you and your clinical team confident and ready for when that inevitable knock on the door comes.

Introducing the VISION SOP Manager

Why use two different systems to manage clinical data and SOPs?

Organizations who use VISION™ will be interested to know that Prelude Dynamics offers an out-of-the-box SOP Management tool.  This flexible tool is implemented using VISION and supports all the familiar tools and features our user community is familiar with. The SOP Manager fosters compliance by providing notifications in advance of required SOP review dates and is 21 CFR Part 11 Compliant.

The concept of Sites and Subjects is overloaded in the VISION SOP Manager. Sites are SOP Sections and Subjects are SOPs. Two key areas of functionality are supported: SOP Management and SOP Training Records.

SOP Management

SOPs are authored using any standard text editor (i.e., Microsoft Word) that supports change tracking, and a description of revisions is contained within each document. The following process is used to revise an SOP.

  1. With change tracking turned on, a subject matter expert authors/edits the content to comply with current best practices.
  2. The edited source document along with a PDF is uploaded to the SOP’s form.
  3. A different subject matter expert performs a content review of the SOP and electronically signs off on the SOP’s form.
  4. A QA staff member performs a QC review of the SOP and electronically signs off on the SOP’s form.
  5. Once the reviews are done, the SOP is finalized.
The SOP List page contains columns that show the effective date, last review date and next required review date for each SOP. These columns can be used to sort the list page and quickly see which SOPs are due for review in the near future. This helps the quality department stay on top of SOP update deadlines.
There is also a feature that allows users to view all the SOPs that were effective on a certain date. This is especially useful when regulators are interested in knowing the state of the organization’s SOPs when a particular clinical trial was conducted. We use the VISION SOP Manager internally and have noted that auditors find it easy to navigate.

As a bonus, we have an “SOP Management” SOP that we can provide as a template. This template can be used as a baseline and adapted to suit your organization’s process.

SOP Training Records

An important aspect of any organization’s Quality System Management Plan is to record and track staff SOP training. This is done in the context of study users, who each have a demographics form and an annual training form group. This form group contains on-demand forms that can be created for each training session. These on-demand forms are automatically populated with the list of SOPs and are used to record when training on each SOP was completed.

The system supports multiple types of training including “self study”, “group training”, “annual training” and “new employee training”. It also supports an annual training summary for each staff member that facilitates compliance assessment.

Customization Options

While the SOP Management tool can be used “out-of-the-box”, it is natural for organizations to request customizations. Because the tool is implemented in VISION, these can be accommodated in a fast, cost-effective manner. Some popular customization options include:

  • Setting up user roles to match your organization structure.
  • Review cycle requirements (e.g., Annual, Biennial, etc.). Internally, we use Biennial – but this can easily be modified.
  • Custom summaries.

Conclusion

The VISION SOP Management tool is an intuitive and flexible system that is already familiar to VISION users – reducing the training requirements associated with migrating to a new SOP Management tool. It allows organizations to migrate completely away from binders of paper documents and seamlessly integrates staff training – helping to assure compliance.

Schedule a Demo

What is the Purpose of User Acceptance Testing?

The importance of testing all aspects and features of a study before Go-Live cannot be over-emphasized. That being said, testing can be a very messy process. If not undertaken with a great deal of planning and documentation, the whole process of testing a study can be rendered not only ineffective but counterproductive. In comes User Acceptance Testing (UAT) to the rescue!

First, you might ask, what is UAT and how is it different from other forms of testing? Think of UAT as a dress rehearsal before a play. The actors all know their lines, the lighting director knows all their queues, and the sets have all been built and tested for safety. But you need to see it all together before you fill the seats with spectators. What if those perfectly built sets don’t line up with the spotlights or what if the bulky costumes get in the way of the actors’ performances? All the parts are there and accounted for, but the picture as a whole has yet to be validated.

 

 

The study-build process is similar. After each form has been tested separately, and all of the summaries and reports have been set up to your satisfaction, there is still the issue of unforeseen scenarios. You won’t be able to find or fix all the potential conflicts until you test the entire study as one. Set up a new site, enroll several patients, take each one through the entire screening/dosing/withdrawal/etc., process. Then do it again with another patient and another, until you have ironed out as many eventualities as possible. Even then, there may still be unforeseen problematic scenarios, but the purpose of UAT is to mitigate the number of issues that might come up during the Live study as thoroughly as possible. UAT is also a good way to provide you and your team with a finalized, succinct idea of what, exactly, you are signing off on before your sites begin entering patients. Once you complete your final run-through of the study, you can rest assured that you have done everything you can to make your study run smoothly.

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!

Prelude Returns to Speak & Exhibit at 2019 SQA Annual Conference

Prelude Dynamics is thrilled to be returning as the premiere EDC exhibitor at this year’s 2019 Annual Society of Quality Assurance Conference in Atlanta. We are excited to exhibit and engage with SQA members on the increasing demands of electronic data capture in conducting human and animal clinical trials.

Make sure to drop by our booth #’s: 319 & 320 on 4/30-5/01, Tuesday through Wednesday, to get a first-hand sneak-peek of our most exciting software upgrade yet, VISION 10.0™! We will have Prelude members on-hand to give demos and answer any questions you may have.

We are also pleased to announce three of our executive members, Dr. Alicia Browner, Ph.D. (CTO); Richard Tieken (President); and Dr. Karina Loyo, Ph.D. (Director of Clinical Research Services), will be featured on panels and roundtable discussions over the course of the conference.

They will be speaking on the following topics:

  • Audit Trails: “Over the River and Through the Woods: Following the Audit Trail” with Alicia Browner
  • EDC Challenges and Opportunities: Challenges and Opportunities Using Electronic Data Capture Systems in Animal Health Studies” with Richard Tieken
  • Best Practices to Build a Study: “The Secrets of a Good Study Build: What You Wish You Knew” roundtable discussion with Karina Loyo
  • IT Compliance: 90-minute Session “Open Microphone with CVIC” with Richard Tieken

[Note: Make sure to check the SQA program schedule for their exact speaking sessions and times]

As the only attending EDC provider at SQA, we are honored to be given the opportunity to contribute to meaningful conversations on compliance and data quality as more clinical trials are integrating with EDC platforms. So, make sure to visit us at our booth, or attend one of our speaking sessions during the conference and see the #1 EDC platform for human and animal health in action!

We hope to see you in Atlanta!!

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.