Best Practices for Remote Clinical Monitoring 

What does it mean to conduct effective remote clinical monitoring? It’s critical to be using an EDC in order to accomplish this, but what else is necessary? Keeping the primary goals of the monitor in mind, we will outline several techniques for streamlining this process.   

What are the primary goals of the study monitor? First, and most critical, is to ensure the safety of all study participants – including clinical personnel. Second, is ensuring data quality and integrity.  

Let’s discuss the EDC features that can help in each of these areas. 

Ensuring Safety 

Monitors are relied upon to use their knowledge and expertise to recognize potential safety risks, and to report them when discovered.  The EDC can’t replace monitors, but it can assist them greatly in their daily workflow. 

Use of Notifications. The EDC can be configured to automatically notify monitors when certain events occur. Examples of this include the entry of adverse events, the reporting of out-of–range lab results and new subject enrollment. When automatic notifications are used, monitors are informed in real time and the need to continually review eCRFs for potential issues is eliminated – saving valuable time. Think about the potential risk factors for a study and consider how notifications can be configured to assist the monitor.  

Use of Reports and Graphs. Some EDCs support flexible, configurable reporting tools that facilitate the aggregation of data for review. Graphs can be used to more intuitively spot outliers and aid in understanding trends. If such tools are not available, consider asking your EDC provider for custom summary reports that can be used to review study endpoints, exam results and adverse events in a comprehensive way. 

Use of Study Dashboards. Dashboards that aggregate reports from multiple sources can provide a convenient starting point for a monitor’s daily workflow. Monitors can log in to the EDC and navigate to a central page to review notifications, study metrics and risk-aware reports. 

By proactively thinking about the types of information monitors need, each study can be configured to provide tools such as these before the first subject is enrolled. With the VISION™ EDC system, mid-study updates can easily be made to support data monitoring needs that weren’t anticipated at study build time. 

Ensuring Data Quality and Integrity 

Sophisticated EDC systems support automated data cleaning in a variety of ways, which naturally improves data quality. Monitors and data managers can contribute their expertise at study build time to make sure that this automation is included as comprehensively as possible.  

Use of “Completeness” Checks. Completeness checks answer the question “is all required data on the eCRF?”. This is especially important when some data can be entered conditionally (e.g., only if another data entry element has a certain value). A related question is “why wasn’t this form been filled out?”. It’s a good practice to implement a “Not Done” checkbox on forms such as Adverse Events and Necropsy that are (hopefully) not often used. This practice lets monitors know in a proactive way that the form is intentionally blank, which effectively reduces the amount of questions from the monitor. 

Use of “Correctness” Checks. Correctness checks help answer the question “is the data correct and in the right format?”. While study protocols usually provide information about the resolution (e.g., number of decimal places) of data to be collected, they don’t always specify things such as the expected range for data points. Enlisting the support of data managers at study build time will help ensure these checks are in place and are as complete as possible. 

Use of Visual Error Indicators. When visual error clues are present and easily viewable, monitors don’t have to spend time manually reviewing each form for errors. They can focus their efforts on strategic reviews instead. Such indicators also provide immediate feedback when data is entered, which prompts clinical personnel to correct entries in real time. 

Use of Document Uploads. When it is necessary to transcribe data from paper forms, it’s good practice to provide an upload mechanism for those forms so the transcription can be reviewed more easily. This mechanism, along with Source Data Verification (SDV) functionality, is also useful in converting a paper study to EDC. VISION’s SDV functionality allows the monitor to sign off on each data entry field individually or at the form level. 

Use of Integrated Query Functionality. Having the ability to enter queries directly into the EDC system, and to easily see whether queries have been resolved, is an enormous aid to monitors. It eliminates the need for them to revisit queries that have been resolved and move on to more important work. 

Qualify the EDC Vendor’s Infrastructure. We’ve defined mechanisms for ensuring the completeness and correctness of data, but how secure is it? EDC vendors should be asked about their backup strategy.  How often is data backed up? How much data could I potentially lose? How long does it take to restore data? How long is data retained? These are some good questions to ask your EDC provider before your study commences.  Prelude recommends (and performs) hourly backups. Questions about barriers to system access are also important. Ask your vendor what their average up-time is. If clinical personnel can’t enter data in real time, data integrity could be impacted. 

Monitor Workflow – Continuous Monitoring 

 Here are some recommendations for conducting remote clinical monitoring using VISION™. 

  • Identify a monitoring schedule and stick to it. For slow-enrolling studies, this might be once or twice a week. Larger, more active, studies may require full time monitoring efforts. 
  • Create focused reports that highlight potential risk areas and promote identification of outliers or undesired patterns. Configure the Dashboard to include these reports and share them with other clinical personnel to promote awareness. 
  • Consult the Dashboard to make sure notifications have been handled and to get an idea of emerging trends that require analysis. 
  • Review forms that have been submitted by clinical personnel and use the Query function to call attention to questionable data. 
  • Review recent lab results for out-of-range results and determine if those relate to Adverse Events. 
  • Review fields with changes to see if there are any patterns and clarify their use with clinical personnel. 

It’s important to perform these activities continuously. Contemporaneous identification of issues is critical when safety is concerned and helps clinical personnel recall specifics they are likely to forget after time passes. Also, when monitoring is done continuously, study close-out activities can be completed much earlier since most of the work has already been done! 

Conclusion 

Monitors who understand the capabilities of their EDC provider and the automation that has been included in their study have an advantage. They can rely on the EDC system to handle the “grunt work” and concentrate instead on critical outcomes and analyses that can’t be automated.  

Inventory Management & Automatic Reordering

 

Challenge

 

It is challenging for working clinics to ensure sufficient inventory of treatment and control medications or supplies are available throughout a clinical study. Prelude Dynamics was challenged to identify an inventory management system that was smart enough to know when medications and supplies were used at the patient level, keep track of current inventory, and reorder supplies as they became low. One challenge to accomplish this is the varied sizes of clinics and expected enrollment for each site, which required something more sophisticated than a one-size-fits-all solution. Rather, inventory thresholds would have to be able to be customized per site, and at least some portions of the inventory management system needed to be blinded from other site personnel.

 

Proposal

 

Prelude Dynamics proposed the client use VISION™, an electronic data capture system, which already has an Inventory Management Module to manage inventory. As the Treatment Dispenser recorded when a patient had received medication or supplies and the amount dispensed, the inventory module would update the inventory on-hand. Prelude proposed to add to VISION™ a feature that would trigger an automatic order when supplies reached a certain threshold, which could be set separately for each site. In addition to VISION™ automatically placing an order, the Treatment Dispenser, study Project Manager and Monitor would be automatically notified via email that the order had been placed.

 

Background

 

It is often difficult for busy clinics participating in clinical research studies often to manage the inventory required to be available for the study. Successful inventory management requires a designated person to keep track of how much is on-hand and order additional inventory as necessary. This person usually has other day-to-day responsibilities that make keeping up with this task difficult. If the designated person were to forget or put off the task the enrollment and treatment of subjects could be jeopardized because medication or supplies are not available. Automating this process would greatly reduce the effort involved in participating in the study and would ensure a better outcome.

 

Solution

 

Prelude staff trained the study staff to utilize VISION™’s existing Inventory Management Module to keep track of inventory as it is dispensed to the patient and logged in the dosing eCRF. The solution included setting the module up to handle the following scenarios:

 

  • Allow study management to initial inventory sent and site shipping information.
  • Allow initial inventory and future inventory received to be logged and tracked.
  • Aggregate the dispensing information into a summary table.
  • Reconcile the on-hand inventory in real-time.
  • Allow minimum and maximum inventory threshold levels to be set at the site level.
  • Automatically order additional medication and/or supplies when the inventory meets or falls below the minimum threshold, for the difference between the actual amount on-hand and the maximum inventory threshold.
  • Notify the study management personnel at site treatment dispenser that an order has been placed.
  • Manage final reconciliation at the end of the study, allowing the site to enter return shipment information for remaining inventory and study management to reconcile the shipment when received.
  • Provide tracking method for deviations or comments/notes to file when medication is not returned by subject or when medication is missing or lost.
  • Provide ability to track if empty bottles are collected and shipped back or disposed of as required by the sponsor and protocol.
  • Allow site personnel access to certain information, such as inventory received, but not any information that might disclose the treatment group provided to each subject in order to protect study masking during the study, but allow access to all the information upon study completion.

 

Results & Benefits

 

As a result of using VISION™, the burden on site personnel to keep track of inventory has been greatly reduced. The sites report that they appreciate the automatic reordering and email notifications of placed orders, adding that it is “such as stress relief to have VISION™ order for them.”

 

The study Project Manager was able to enter initial inventory ordered and shipped to the site, along with site shipping information, simplifying tracking all inventory information in a central location. She received email notification when the Treatment Dispenser entered the initial receipt of the inventory into the system, confirming its arrival. She was very pleased with the entire module, noting that, “It is wonderful to know that I can relax about whether the sites are keeping up with the inventory and reordering meds and supplies when they are getting low because it happens automatically. There are so many other things I have to keep track of. It is helpful not to have to be burdened by the inventory management.”

 

The Treatment Dispenser finds it useful view a single table for a full history dispensed medication and/or supplies. He appreciates instant viewing of aggregate dispensed and automatic reconciliation of inventory, and is able to add notes directly on the dispensing form if there is a discrepancy in the amount of medication returned or if there are missing medications or supplies. All these notes are aggregated automatically in a note to file with details about the form and field, who entered the note and when it was entered. This makes it much easier than having to enter all these details manually. He indicated that he was extremely satisfied with the inventory management. He said that keeping up with the inventory and reordering was so much less burdensome and stressful that it had been previously. In fact, the Treatment Dispense indicated he wished all studies used VISION™’s Inventory Management module and thinks everyone should consider using VISION™ for future studies. He said it was intuitive, easy to use, and followed the work flow well. Other treatment dispensers at other sites had similar positive experiences.

 

Throughout the study, sufficient inventory levels were maintained to be able to enroll all patients eligible for the study who were willing to participate. This gave all study personnel more confidence in their ability to successfully enroll a new subject every time.

 

VISION™ Clinical Trial Optimization Platform (CTOP) Instrumental in Conducting Head Injury Research in a Multi-Hospital Study.

AUSTIN, TX – April 26, 2017 – VISION™ Clinical Trial Optimization Platform (CTOP) instrumental in conducting head injury research in a multi-hospital study.

This study enabled BrainScope® Company Inc. to receive FDA clearance for the AHEAD® 300. The study’s principal investigator was Daniel Hanley Jr., M.D., the Legum Professor of Neurological Medicine and director of the Brain Injury Outcomes Program at Johns Hopkins University School of Medicine.

The AHEAD technology is a hand-held EEG device that is now commercially available for use at point of care to determine if a person with a head injury is likely to have a brain bleed requiring further evaluation and treatment. This new technology will assist in finding patients the right care pathway, ultimately reducing the time and cost of care.

Prelude Dynamics provided BrainScope with a fully customized solution that allowed patient histories, head injury related information, symptoms and assessments to be directly entered in VISION™. Based on certain criteria, VISION™ also ran a series of complex calculations to determine traumatic brain injury scoring. BrainScope took advantage of VISION’s™ document management tool to store critical study documents that needed to be shared across study personnel and researchers.

Doug Oberly, Vice President, Customer Care at BrainScope, commented, “We have used other EDC systems in the past and BrainScope Clinical Affairs staff and our clinical site partners have been very pleased with the VISION™ system. We found VISION™ to be more than capable to suit all our study needs and have chosen to use VISION™ for three other clinical studies.”

Emissary used VISION’s™ integrated monitoring tools to ensure the validity of data. These tools included a dashboard, automatic and custom queries attached to each field, query summaries and charts, and ad- hoc reports.

Steven Mayo, Pharm.D., CEO of Emissary International, commented, “Prelude Dynamic’s VISION™ was instrumental in allowing us to remotely monitor the study. We collected CT and AHEAD-300 data files directly in VISION™, which greatly simplified our ability to process this data and close the database quickly after the last enrollment. I can’t imagine doing this study without VISION™.”

Emissary International served as the contract research organization (CRO) providing data management, monitoring, training and project management in conjunction with the Brain Injury Outcomes coordinating center at Johns Hopkins University. Emissary is an award-winning CRO that has been accelerating clinical trials since 1995 and has worked collaboratively with Johns Hopkins University since 2006.

Alicia Browner, Ph.D., CTO of Prelude Dynamics said, “We are excited that BrainScope’s AHEAD technology will help people with head injuries get the treatment they need faster by identifying potential bleeds sooner. We are glad to be a part of enabling critical clinical research with our Clinical Trial Optimization Platform, bringing such devices and pharmaceuticals to market quicker.”

About Emissary

Emissary International LLC is a contract clinical research organization (CRO) providing services to biopharmaceutical, medical device and academic organizations engaged in the conduct of clinical trials. Since 1995, Emissary has been leading medically-intensive research studies across a broad range of therapeutic areas, helping clients bring dozens of new medical products to market quickly and efficiently.

Emissary is recognized as one of the more innovative CROs in the industry, having received awards for being one of the first companies to develop an international network of monitors and trialists, pioneering one of the first commercial electronic data capture (EDC) systems, developing the TeamTrials® clinical project management system, and more recently for its involvement in the NIH’s Trial Innovation Network along with a number of large academic medical institutions, a major 7-year effort to streamline the conduct of multicenter clinical trials.

About Prelude Dynamics

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.

Prelude Dynamics has earned the reputation for helping accelerate and advance product approvals for our customers worldwide, including global pharmaceutical companies, biotechnology, diagnostic, and device companies, along with leading academic medical centers, such as The Johns Hopkins University Medical Center, and contract research organizations.

The company’s flagship product, VISION™ often referred to as the industry’s first “Clinical Trials Optimization Platform” (CTOP), offers a validated, secure, and configurable platform, compliant with FDA/CVM 21 CFR Part 11 Guidance and EMEA regulations.

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

Customization Enrollment Graphs And Tables

 

Challenge

 

Clients challenged Prelude Dynamics to develop customizable enrollment graphs and tables in order to quickly reflect current enrollment rates and/or adjusted projected enrollment at any point, per site or across the whole study.  In evaluating this challenge, Prelude anticipated the need for a highly customizable function for creating the enrollment graph to accommodate a variety of different studies and sponsors. Additionally, field names may vary from study to study and different studies have different criteria for actual enrollment. For example, some studies may determine enrollment by if a treatment group has been assigned while others may use screening results as enrollment criteria, and still others may not consider a subject fully enrolled until the first dose is administered.

 

Proposal

 

Prelude Dynamics proposed to add an enrollment graph module to VISION™, an electronic data capture system built explicitly to support clinical research.  In particular, Prelude proposed development of an administrative panel where enrollment graphing information could be set up. A separate form would be employed for graphical display of the specified information. Prelude Project Managers would determine initial settings with the study project manager. Then study project managers would be trained on how to change the criteria if necessary.

 

Background

 

Successful tracking of enrollment for a clinical study is imperative in order to maintain study schedule and budget. When multiple sites are involved, this can be complex, particularly because some studies have sites location across the globe. A single location within the EDC where enrollment could be monitored would be very helpful in tracking study progress.

 

Solution

 

Prelude developed an enrollment graph and table settings panel and a corresponding results display section. The enrollment settings allow the selection of the form and field to be used as an indication of successful enrollment. The expected and projected total and monthly enrollment can be put into the settings and changed at any time. The project manager can choose to view graphs, tables or both for each site, all sites or a combination.

 

Results & Benefits

 

The Prelude project manager worked with the study project manager to input initial enrollment settings. As data was collected, the enrollment graph and tables were used to quickly view the progress of the study. The project managers using this feature found it helpful to be able to track the study progress, and reported that the location of enrollment information in a single location better facilitated planning subject recruitment activities and working with the clinics experiencing difficulty meeting monthly enrollment goals.

 

The study project manager was able to modify projected enrollment settings mid-study to address realistic enrollment. The project managers were quickly able to identify which sites were successful at enrollment and which were struggling, which contributed to beneficial strategic planning sessions to improve enrollment at low-enrollment sites. Project managers used this information to communicate with the sponsor to decide if successful enrollment sites could enroll additional subjects to mitigate the reduced enrollment at other sites. This allowed them to stay on track and meet the study enrollment projections.

 

About Prelude Dynamics & VISION™

 

Prelude Dynamics is a global provider of customized web-based software systems for data collection, analysis and management of clinical trials, studies and registries. We streamline eClinical operations through our unique and innovative VISION software system, which allows us to rapidly configure data collection solutions for pharmaceutical, CRO, medical device, animal health, and university organizations.

Handling a Surgical Study with Repeated Observation Times

 

Challenge

 

While collecting repeated observations of animals using a standardize scale is not in itself a challenge, allowing access to only one scale at a time during the appropriate time frame to the correct individual is a challenge. For this particular study, up to three individuals could conduct the observations around the clock at specific intervals over a minimum of a 72-hour time-frame and were restricted to conducting observations at specific times. The scale needed on-demand functionality as well in case additional observation times were necessary. The clock for the observation period started running off the surgical start time, which also had to be incorporated into the solution. Additionally, if the score was above a certain threshold, the researcher had to be alerted that an alternate procedure (medication or treatment protocol) had to be followed and/or the animal had to be removed from the study.

 

Proposal

 

Prelude Dynamics proposed utilization of VISION™, an electronic data collection system, to allow researchers to capture information in real-time, provide the standardized scales in a just-in-time manner, follow the natural work flow of the study process, and ease the data collection process. In order to restrict the scales to the appropriate individuals, form level permissions would be assigned to specific roles. VISION™ would be programmed to use custom calculations to automatically start the clock from the surgical start time entered and provide the correct dosing amount of any medications administered.

 

Background

 

It is a common study objective to understand how animals respond to a certain surgical procedure, anesthesia, or post-surgery medications. Researchers examine an animal’s response at specific time intervals over a period of time to reach this understanding. When this time period extends over multiple days, it is necessary to utilize multiple observers to complete standardized scales.

 

When the data is collected on paper, it is difficult to blind current observers from information completed on forms by a previous observer. Access to previously entered information can bias the current observer, regardless of whether he or she collected the prior observation or it was collected by someone else. Reducing bias is important to obtaining reliable information.

 

Solution

 

Prelude staff trained the study staff to utilize VISION™ to show and provide access to only one scale at a time, restricting access to the individual with the appropriate permission at the designated time. VISION™ was programmed to start running the time clock off the entered surgical start time. Permissions were assigned to roles that corresponded with access to particular scale forms as indicated in the study protocol. Some scales could only be filled out by a certain role while others had multiple roles that could fill them out. Once a scale was filled in, reviewed and approval given, that scale became inaccessible or hidden and the next scale became accessible. Based on the initial entered surgical start time, each scale displayed the expected date and time that scale needed to be filled in.

 

As a standard, VISION collects full audit trail information on each data point entered into the system, including who entered the information and a date and time stamp. It also allows data entry fields to be augmented with comments or notes, which is an important feature if additional information needs to be added that might otherwise be limited to a selection of choices.

 

VISION™ also contains pre-existing summaries which assist in monitoring the data being collected at the patient level, at each site or for the study as a whole. Using VISION™’s search and filter capacity allows these summaries to display data of only the cases fitting the search criteria. Additionally, VISION™ provides users with certain permissions the ability to create ad-hoc reports which they can use for monitoring additional criteria or in order to answer important research questions. The data within the system is available for export 24/7/365 with the appropriate user permission. Export features the ability to export in multiple formats including SAS-ready format.

 

Results & Benefits

 

Real-time data is being entered into VISION™, and standardized scales are being filled in and signed off on, the completed form is no longer accessible to the individuals completing forms.  Using VISION™ eliminates observer bias since current observers cannot view or compare findings entered by a prior observer. There are certain roles designated by the Sponsor to maintain read-only access to view all the scales at any time.

 

Scale scores are immediately calculated and feedback automatically provided if scores indicate necessity for removal from the study or other treatment. This identifies potential problems quickly and reduces the risk to the participating animal.

 

VISION™ also identifies these animals quickly so they can be taken out of the study and prevent further costs associated with tracking an ineligible subject. Additionally, when an animal is removed from the study, the VISION™ Randomization module, which is behind the scenes, will reassign the withdrawn animal’s treatment to a new case to ensure that sufficient cases are enrolled for each treatment group.

 

The need for data collection on paper CRF has been eliminated. Researchers spend less time entering data after the fact because they are able to enter information directly into the system in real-time. There is also a cost savings and error reduction by eliminating data entry at a later date.

 

Data is accessible in real time for query, review, analysis and export. Users report the streamlining of the process has helped reduce errors and improved efficiency