Karina Loyo, Ph.D., eclinical trials specialist and Jim Pedzinski, vice president, business development, Prelude Dynamics05.04.16
Cost savings, reduced time to market, compliance, and accountability are just some of the many reasons why medical device researchers are considering their electronic data collection (EDC) and clinical trial management system (CTMS) solutions. This is not an easy task. It requires a shift in paradigm and complete process overhaul. Where do you get started? Who do you engage in the process? How will it affect the organization as a whole? How will research and manufacturing be impacted? These are some of the many questions that should be asked and addressed. Careful thought and strategic planning will ensure a successful adoption of processes that leverage the benefits of EDC/CTMS.
Typically, as a study is being designed, the researcher considers the data that should be collected. Paper case report forms are created in order to capture that information. Sites are identified and the research is carried out. Once the data is collected, a database is designed; a double data entry process ensures accurate transcription of data. Historically, this has been a long and tedious process. The data is then cleaned through queries and review of source documents. Finally, the data is submitted for analysis.
When using an EDC, the database is designed up front and data is collected straight into the database making it the source document. One of the benefits of EDC is the ability to clean the data in real time. As data is entered, the EDC automatically fires edit checks upon submission, alerting of any missing data, data out of range, or data not meeting the required format. This allows the person collecting the data to immediately fix any mistakes and clean the data in real time. For example, if a critical answer was omitted, the investigator can quickly ask the patient or make the observation before the patient leaves. This all occurs before the monitor even reviews the forms and queries them. The monitor can then review the forms on a regular basis close to the time of submission. No longer is there a need to rely on “paper-based” medical records and scribbled notes or memory of an event that may have occurred six months earlier or longer; accuracy increases; data quality improves. Costs related to double data entry and data cleaning are reduced or eliminated altogether.
One of the keys to capitalizing on the power of EDC is careful planning and defining requirements for appropriate edit checks and constraints—defining the calculations and logic wherever possible to eliminate accidental entry of contradicting information, and capturing all the required data in the EDC as a source document. Since planning the EDC includes planning the database, which will ultimately contain the data and allow its analysis, it makes sense that the planning process includes the data manager and biostatistician from the onset.
As the first draft of the research protocol is developed, engage the data manager to review the case report forms and recommend how the information should be captured. In reviewing the forms, the data manager may have insight into the attributes of the fields, constraints that should be included in the EDC to check the data for accuracy as it is entered, and fields that should be used to populate other fields or whether there should be constraints to ensure certain fields match. For example, dates on all forms for the same visit should match, questions that should be hidden until specific responses are given so they are not answered when they should not be, and any hidden fields that should be included. Studies can often benefit from calculating derived information for a report (e.g., duration of surgery, calculated when start and end time are collected). All of these are critical to ensure accurate and clean data is collected. The biostatistician can help not only with the considerations above, but also provide valuable insight into any summaries, filters, or reports that should be generated to keep track of mid-study progress.
Some technology solutions are more flexible than others and have a varying degree of additional features or modules that can be integrated to help streamline other study conduct processes. For example, customizable automatic notifications can be valuable in reducing study risk and improving response time. Adding a notification for adverse events or serious adverse events sends an email alert to the project manager or monitor, who can quickly review the information entered and follow up if needed.
Using inventory management and automatic inventory reordering tools can be extremely helpful in managing multi-site device inventory remotely. When inventory falls to a preset minimum, the system can automatically place an order to bring the device inventory back to a preset maximum. The inventory order can be placed directly with the manufacturer without waiting for the engagement of a project manager, which expedites order fulfillment. This might also allow the device manufacturers to maintain less on-hand inventory, thus reducing costs, as they are receiving requests in real time and can plan additional production runs in a just-in-time fashion. This can eventually lead to implementation of continuous bioprocessing. This also has the added benefit that if any changes are required to a device or manufacturing process, there is less wasted material and on-hand inventory of which to dispose.
The invoice capacity of the system will change the existing invoicing process and produce cost savings in management time. The EDC/CTMS solution should allow a more detailed master fee schedule to be implemented that is tied directly to specific critical events that encourage investigation sites to collect better and more complete data. Previously, invoicing requires many hours of data entry and checking to ensure contracted requirements were met prior to making payment. With integrated invoicing, once the monitor has reviewed the form containing the event, the fee automatically posts to the invoice. This makes the invoice generated by the system accurate and reliable. No additional monitoring of the invoice is necessary, freeing up labor for other, more critical purposes. In some systems, it is even possible to generate invoices to pay the device manufacturer after the site receives the new devices that were automatically ordered by the system. Essentially, once the sites enter new inventory, the fee is automatically entered to a study level invoice that can be paid on a monthly basis with confidence that the product has been delivered.
Some systems can be used to both carry out the initial medical device research, as well as an ongoing medical device registry, following not only the patients who participated in the initial studies, but also all patients who have had a given medical device implanted. This reduces the cost of recreating forms, migrating data, and planning a second system to remain in compliance with regulations. Depending on the system, the registry must be planned during the initial set up or can be an added feature after device approval.
Appropriate planning and long-term vision for EDC/CTMS allows medical device companies to leverage the power of these systems in order to streamline workflows. Up front planning may engage more than just the researcher, data manager, and biostatistician. It is also a good idea to have the input of at least one project manager, monitor and, if possible, a site-based investigator. Each of these will enhance the process by sharing their views on workflow and design. While it might seem that this would increase the planning time and push out the data collection time, the time spent planning and considering the input will ultimately improve data collection quality and compliance as the work flows integrate into the daily work of the site-based investigators using new medical devices and the surgeons implanting them. Knowing the system will make it easier for the monitor to track all the nuances related to the protocol and ensuring patient safety is also a critical factor in EDC/CTMS success.
Ultimately, while initial planning time and cost increases with EDC/CTMS, time and cost overall is decreased because the quality of data is cleaner, monitoring is occurring simultaneous to data collection, there is no post-data collection data entry time, and the database is able to be locked within days or weeks instead of months. Since mid-study analysis and reports have been occurring on a regular basis, the biostatistician has already had the opportunity to script the final analysis so it too occurs quickly after the database lock. The result is faster time to market at a lower cost.
Karina Loyo, Ph.D., is an eclinical trials specialist and Jim Pedzinski is vice president of business development at Prelude Dynamics. Prelude Dynamics is a global provider of customized web-based Clinical Trial Management Systems and Services. The company offers unique, innovative research and clinical solutions to all areas of the pharmaceutical and medical device industry worldwide. Authors can be reached at kloyo@preludedynamics.com and jpedzinski@preludedynamics.com.
Typically, as a study is being designed, the researcher considers the data that should be collected. Paper case report forms are created in order to capture that information. Sites are identified and the research is carried out. Once the data is collected, a database is designed; a double data entry process ensures accurate transcription of data. Historically, this has been a long and tedious process. The data is then cleaned through queries and review of source documents. Finally, the data is submitted for analysis.
When using an EDC, the database is designed up front and data is collected straight into the database making it the source document. One of the benefits of EDC is the ability to clean the data in real time. As data is entered, the EDC automatically fires edit checks upon submission, alerting of any missing data, data out of range, or data not meeting the required format. This allows the person collecting the data to immediately fix any mistakes and clean the data in real time. For example, if a critical answer was omitted, the investigator can quickly ask the patient or make the observation before the patient leaves. This all occurs before the monitor even reviews the forms and queries them. The monitor can then review the forms on a regular basis close to the time of submission. No longer is there a need to rely on “paper-based” medical records and scribbled notes or memory of an event that may have occurred six months earlier or longer; accuracy increases; data quality improves. Costs related to double data entry and data cleaning are reduced or eliminated altogether.
One of the keys to capitalizing on the power of EDC is careful planning and defining requirements for appropriate edit checks and constraints—defining the calculations and logic wherever possible to eliminate accidental entry of contradicting information, and capturing all the required data in the EDC as a source document. Since planning the EDC includes planning the database, which will ultimately contain the data and allow its analysis, it makes sense that the planning process includes the data manager and biostatistician from the onset.
As the first draft of the research protocol is developed, engage the data manager to review the case report forms and recommend how the information should be captured. In reviewing the forms, the data manager may have insight into the attributes of the fields, constraints that should be included in the EDC to check the data for accuracy as it is entered, and fields that should be used to populate other fields or whether there should be constraints to ensure certain fields match. For example, dates on all forms for the same visit should match, questions that should be hidden until specific responses are given so they are not answered when they should not be, and any hidden fields that should be included. Studies can often benefit from calculating derived information for a report (e.g., duration of surgery, calculated when start and end time are collected). All of these are critical to ensure accurate and clean data is collected. The biostatistician can help not only with the considerations above, but also provide valuable insight into any summaries, filters, or reports that should be generated to keep track of mid-study progress.
Some technology solutions are more flexible than others and have a varying degree of additional features or modules that can be integrated to help streamline other study conduct processes. For example, customizable automatic notifications can be valuable in reducing study risk and improving response time. Adding a notification for adverse events or serious adverse events sends an email alert to the project manager or monitor, who can quickly review the information entered and follow up if needed.
Using inventory management and automatic inventory reordering tools can be extremely helpful in managing multi-site device inventory remotely. When inventory falls to a preset minimum, the system can automatically place an order to bring the device inventory back to a preset maximum. The inventory order can be placed directly with the manufacturer without waiting for the engagement of a project manager, which expedites order fulfillment. This might also allow the device manufacturers to maintain less on-hand inventory, thus reducing costs, as they are receiving requests in real time and can plan additional production runs in a just-in-time fashion. This can eventually lead to implementation of continuous bioprocessing. This also has the added benefit that if any changes are required to a device or manufacturing process, there is less wasted material and on-hand inventory of which to dispose.
The invoice capacity of the system will change the existing invoicing process and produce cost savings in management time. The EDC/CTMS solution should allow a more detailed master fee schedule to be implemented that is tied directly to specific critical events that encourage investigation sites to collect better and more complete data. Previously, invoicing requires many hours of data entry and checking to ensure contracted requirements were met prior to making payment. With integrated invoicing, once the monitor has reviewed the form containing the event, the fee automatically posts to the invoice. This makes the invoice generated by the system accurate and reliable. No additional monitoring of the invoice is necessary, freeing up labor for other, more critical purposes. In some systems, it is even possible to generate invoices to pay the device manufacturer after the site receives the new devices that were automatically ordered by the system. Essentially, once the sites enter new inventory, the fee is automatically entered to a study level invoice that can be paid on a monthly basis with confidence that the product has been delivered.
Some systems can be used to both carry out the initial medical device research, as well as an ongoing medical device registry, following not only the patients who participated in the initial studies, but also all patients who have had a given medical device implanted. This reduces the cost of recreating forms, migrating data, and planning a second system to remain in compliance with regulations. Depending on the system, the registry must be planned during the initial set up or can be an added feature after device approval.
Appropriate planning and long-term vision for EDC/CTMS allows medical device companies to leverage the power of these systems in order to streamline workflows. Up front planning may engage more than just the researcher, data manager, and biostatistician. It is also a good idea to have the input of at least one project manager, monitor and, if possible, a site-based investigator. Each of these will enhance the process by sharing their views on workflow and design. While it might seem that this would increase the planning time and push out the data collection time, the time spent planning and considering the input will ultimately improve data collection quality and compliance as the work flows integrate into the daily work of the site-based investigators using new medical devices and the surgeons implanting them. Knowing the system will make it easier for the monitor to track all the nuances related to the protocol and ensuring patient safety is also a critical factor in EDC/CTMS success.
Ultimately, while initial planning time and cost increases with EDC/CTMS, time and cost overall is decreased because the quality of data is cleaner, monitoring is occurring simultaneous to data collection, there is no post-data collection data entry time, and the database is able to be locked within days or weeks instead of months. Since mid-study analysis and reports have been occurring on a regular basis, the biostatistician has already had the opportunity to script the final analysis so it too occurs quickly after the database lock. The result is faster time to market at a lower cost.
Karina Loyo, Ph.D., is an eclinical trials specialist and Jim Pedzinski is vice president of business development at Prelude Dynamics. Prelude Dynamics is a global provider of customized web-based Clinical Trial Management Systems and Services. The company offers unique, innovative research and clinical solutions to all areas of the pharmaceutical and medical device industry worldwide. Authors can be reached at kloyo@preludedynamics.com and jpedzinski@preludedynamics.com.