Review and Adjust Monitored Data on the Monitoring Tab

On the Monitoring tab you can specify information about the global and by location monitoring assumptions in a plan.

Your edit mode determines the fields shown on the Monitoring tab. For more information about any field, click the field name to display online help.

• Specify the Monitoring Methods
  Specify whether monitoring will be performed on-site, remotely, centrally, or by a combination of these methods and whether to specify monitoring assumptions globally or by location.
• Accept or Modify the On-site Monitoring Schedule
  The default on-site monitoring schedule uses a frequency-based model to calculate the total number of on-site visits. The frequency impacts the length or duration of the visits.
• Review the Remote Monitoring Schedule
  If you chose Remote from the Monitoring Methods section of the Monitoring tab, the default schedule uses a frequency-based model to calculate the total number of remote visits.
• Review the Remote Monitoring Schedule for Centralized Monitoring
  If you chose Centralized from the Monitoring Methods section of the Monitoring tab, then corresponding default labor will be included in the budget.
• Define the Monitoring Approach
  In the Monitoring Approach section of the Monitoring tab, enter detailed assumptions about who will perform monitoring and how they will work.
• Specify Total CRF Pages Expected
  In the Monitored Data section of the Monitoring tab, enter the total number of CRF pages to be generated and monitored.
• Review and Adjust Medical Monitoring Assumptions
  In the Medical Monitoring section of the Monitoring tab, review and adjust the time for a medical monitor to serve as the team medical lead and provide support to the CRA monitoring staff and investigators for issues beyond safety reporting.
• Review and Adjust Separate Drug Accountability Visits
  Will there be additional drug accountability visits? Separate drug accountability generally applies to oncology and some vaccine studies and is done by someone other than the CRA that monitors the site.

Specify the Monitoring Methods

Specify whether monitoring will be performed on-site, remotely, centrally, or by a combination of these methods and whether to specify monitoring assumptions globally or by location.

Your edit mode determines which fields are displayed and available to override to enter a different value than the default value provided.

1. On the Monitoring tab, in the Monitoring Methods section, specify the types of monitoring to be performed.
   • On-site—On-site monitoring is linked to Source Data Verification (SDV) where the monitor (CRA) reviews the Case Report Form (CRF) data against the clinical source data (EMR/EHR data, lab data, imaging data, etc.) to verify accuracy and completeness in accordance with ICH GCP regulatory guidelines. Calculation of the on-site monitoring effort is based on the number of CRF pages planned per subject multiplied by the monitoring minutes per CRF page (driven by the therapeutic area and indication of a study) to determine the total effort to monitor/SDV the CRF data.

     In addition to the monitoring effort required for SDV, the effort for the visit preparation, travel time, on-site time not related to SDV (defined below), report/follow-up, is calculated by the frequency defined from the First Subject First Screening Visit to the Last Subject Last Follow-Up Visit (FSFV-LSLV).

     If you already know the total on-site monitoring visits and you don’t want ClearTrial to calculate that for you, you can override the system-calculated value to use downstream and ignore the default or ClearTrial-defined on-site monitoring schedule.

   • Remote—Remote visits may be added on top of any on-site SDV monitoring strategy, but aren't linked to SDV. Remote monitoring supplements the on-site activities done by the monitor (CRA) and is calculated based on the assumption values you defined for the frequency or average hours per remote visit.

     If you already know the total remote monitoring visits and you don’t want ClearTrial to calculate that for you, you can override the system-calculated value to use downstream and ignore the default or ClearTrial-defined remote monitoring schedule.

   • Centralized—Centralized monitoring is conducted centrally and performed by a centralized team by default, as opposed to a field-based monitoring team (CRAs). Incorporating centralized monitoring as part of a risk-based monitoring approach helps reduce risk and ensure quality by allowing potential anomalies or risks to be detected more quickly.

     Centralized monitoring looks across all subject data across all sites and identifies any outliers to determine if there is an anomaly. When an anomaly is detected, a query may be issued, closer examination of data at a site may be completed, an extra visit may be added, or some other Risk-based Monitoring (RBM) mitigation action may be performed.

     Activities include identifying Key Risk Indicators (KRIs) upfront at the beginning of a study and setting risk thresholds. During the study, activities include conducting and reviewing monthly KRI data dashboards and performing analyses across all subjects and sites to identify anomalies for action remediation.

     Sites with multiple issues detected through centralized monitoring can provide an early signal of a need for an on-site visit and corrective actions to minimize the likelihood of similar issues occurring during the remainder of the trial.

   You can select all three options.

2. In the Manage monitoring schedule values field, specify whether to manage monitoring schedules globally or per location.
   • If you manage monitoring schedules globally, ClearTrial applies all of the assumptions you enter in the On-Site Monitoring Schedule section or Remote Monitoring Schedule section to all the plan locations in the study.
   • If you manage monitoring schedules per location, you can modify schedules for each location within the study. On the Edit Per Location Monitoring Schedule screen you can select each location and edit that location's monitoring methods, define the schedules by frequency, or override the total number of visits to be leveraged downstream.
3. Continue by reviewing and fine-tuning the on-site and remote monitoring schedules as necessary.

Accept or Modify the On-site Monitoring Schedule

The default on-site monitoring schedule uses a frequency-based model to calculate the total number of on-site visits. The frequency impacts the length or duration of the visits.

If you chose on-site from the Monitoring Methods section of the Monitoring tab, you can specify details about the on-site monitoring schedule.

1. In the On-Site Monitoring Schedule section of the Monitoring tab, in the Monitor every field, specify how frequently a monitor (CRA) will visit the sites in the study during each period of the monitoring schedule across screening, treatment, and follow-up sements (between FSFV and LSLV).
2. Choose the frequency:
   • If visits will continue at the specified frequency throughout the study enrollment, treatment, and follow-up segments (FSFV to LSLV or Last Subject Last Follow-up Visit, select until LSLV.

     When there are no treatment arms with a follow-up treatment defined, then LSLV = LSLT. When there is a follow-up period defined for one or more treatment arms, then LSLV = LSLFU (Last Subject Last Follow Up visit/data collection event).

   • If the monitoring frequency will change during the treatment or follow-up period, select the until week radio button and define a new frequency for the next or remaining intervals.
   • If you want to use a variable monitoring frequency; for example, visiting every four weeks in the beginning of the study, every two weeks in the middle of the study, and every six weeks at the end of the study:
     1. In the Monitor every field, enter the frequency for the first period.
     2. Select the until week radio button and enter the week at which this frequency ends and a new monitoring frequency begins. This is the week number corresponding to the start of the next monitoring period and must be greater than or equal to the value for the monitoring frequency for the prior period.
     3. Now, specify what happens in the next monitoring period. Enter a value for the Monitor every field and choose until LSLV or until week.
     4. Repeat as necessary to define each change in frequency over the course of the monitoring schedule.

        ClearTrial calculates the total number of visits to be made, derived from the remote monitoring frequency and the subject enrollment rate, and displays it in the Total Remote Visits field.

     5. If you know the total on-site visits and you can’t achieve it by adjusting the frequency of visits per interval, you can override the system-calculated value. The overridden value will be used downstream instead of the ClearTrial default or the user-defined on-site monitoring schedule values.
3. Override the total number of monitoring visits in the Total on-site visits field, if necessary (for example, if the value in the RFP is different from the generated value).
   • ClearTrial derives the default value shown from the total number of sites, monitoring frequency, and subject enrollment rate, treatment, and follow-up periods (FSFV to LSLV). You can increase this number to add more monitoring visits. You can also lower the total number of monitoring visits.
   • If you are working with new sites that have limited research experience or where you know that there is a need to accelerate monitoring for some reason, add monitoring visits. For example, if ClearTrial calculates 1068 visits and there are 89 sites in the study of which 35 are inexperienced, you might add one additional monitoring visit for these 35 sites. The new number of monitoring visits is 1103.
   • Oracle recommends that the total number of visits entered be as close to the value calculated by ClearTrial as possible. That is, try to adjust the monitoring frequencies to arrive at the desired value and, only if you cannot achieve the desired number, enter a new value to override the calculated value.
4. From the Monitoring Travel Strategy drop-down list, specify the monitoring visit strategy to use for most of the monitoring trips.
   • Spoke monitoring— The monitors return to their homes or offices between each visit.
   • Loop monitoring— Monitors travel to site 1, then to site 2, then to site 3, and so on, before returning to their homes or offices.

     For studies that have slower enrollment, with slower data being generated and slower distribution, such as Oncology studies, Oracle recommends using the Spoke travel strategy because there will be less frequent visits but of longer duration.

     For studies with shorter enrollment periods and more even distribution and generation of CRF data across sites, use the Loop visit strategy to leverage more frequent visits of shorter durations. A local CRA can monitor multiple sites in one trip before returning home. ClearTrial defaults to Loop visits because they are more cost efficient.

   • Use the Monitoring Schedule chart or the Monitoring sections of the Assumptions report to verify the schedule.
   • Note that ClearTrial always assumes Spoke travel for closeout visits.
5. Set up the monitoring approach or click Next to open the Provider tab.

Review the Remote Monitoring Schedule

If you chose Remote from the Monitoring Methods section of the Monitoring tab, the default schedule uses a frequency-based model to calculate the total number of remote visits.

Note:

When you select Centralized monitoring, corresponding labor activities are included by default in the budget.

1. In the Remote Monitoring Schedule section of the Monitoring tab, in the Monitor every field, specify how frequently a monitor will contact the sites during each period of the monitoring schedule.
2. If the remote monitoring will continue at the specified frequency throughout the study enrollment, treatment and follow-up periods (FSFV to LSLV), select until LSLV.
   • If the monitoring frequency will change during the treatment or follow-up period, the select the until week radio button and define a new frequency for the next (or remaining) period.
   • If there are no treatment arms with a follow-up treatment defined, then LSLV = LSLT. When there is a follow-up period defined for one or more treatment arms, then LSLV = LSLFU (Last Subject Last Follow Up visit or data collection event).
3. If you want to use a variable monitoring frequency; for example, contacting every four weeks in the beginning of the study, every two weeks in the middle of the study, and every six weeks at the end of the study:
   1. In the Monitor every field, select until week and enter the week at which this frequency ends and a new monitoring frequency begins.
   2. Now, specify what happens in the next monitoring period. Enter a value for the Monitor every field and choose until LSLV or until week.
   3. Repeat as necessary to define each change in frequency over the course of the monitoring schedule.

      ClearTrial calculates the total number of contacts to be made, derived from the remote monitoring frequency and the subject enrollment rate, and displays it in the Total Remote Visits field.

   4. If you know the total remote visits and you can’t achieve it by adjusting the frequency of visits per interval, you can override the system-calculated value. The overridden value will be used downstream and instead of the ClearTrial default or the user-defined remote monitoring schedule values.
4. In the Average hours per remote visit field, specify the average number of hours required to perform a remote monitoring visit, including preparation and follow-up activities.
5. Set up the monitoring approach or click Next to open the Provider tab.

Review the Remote Monitoring Schedule for Centralized Monitoring

If you chose Centralized from the Monitoring Methods section of the Monitoring tab, then corresponding default labor will be included in the budget.

Note:

If you also chose Remote from the Monitoring Methods section of the Monitoring tab, the default schedule uses a frequency-based model to calculate the total number of remote visits.

1. In the Remote Monitoring Schedule section of the Monitoring tab, in the Monitor every field, specify how frequently a monitor will contact the sites during each period of the monitoring schedule.
2. If the remote monitoring will continue at the specified frequency throughout the study enrollment, treatment and follow-up periods (FSFV to LSLV), select until LSLV.
   • If the monitoring frequency will change during the treatment or follow-up period, the select the until week radio button and define a new frequency for the next (or remaining) period.
   • If there are no treatment arms with a follow-up treatment defined, then LSLV = LSLT. When there is a follow-up period defined for one or more treatment arms, then LSLV = LSLFU (Last Subject Last Follow Up visit or data collection event).
3. If you want to use a variable monitoring frequency; for example, contacting every four weeks in the beginning of the study, every two weeks in the middle of the study, and every six weeks at the end of the study:
   1. In the Monitor every field, select until week and enter the week at which this frequency ends and a new monitoring frequency begins.
   2. Now, specify what happens in the next monitoring period. Enter a value for the Monitor every field and choose until LSLV or until week.
   3. Repeat as necessary to define each change in frequency over the course of the monitoring schedule.

      ClearTrial calculates the total number of contacts to be made, derived from the remote monitoring frequency and the subject enrollment rate, and displays it in the Total Remote Visits field.

   4. If you know the total remote visits and you can’t achieve it by adjusting the frequency of visits per interval, you can override the system-calculated value. The overridden value will be used downstream and instead of the ClearTrial default or the user-defined remote monitoring schedule values.
4. In the Average hours per Remote Visit field, specify the average number of hours required to perform a remote monitoring visit, including preparation and follow-up activities.
5. Set up the monitoring approach or click Next to open the Provider tab.

Define the Monitoring Approach

In the Monitoring Approach section of the Monitoring tab, enter detailed assumptions about who will perform monitoring and how they will work.

Note:

These monitoring assumptions are only available in Advanced or Expert Edit Mode.

1. On the Monitoring tab, in the Monitoring Approach section, enter the following details.
   • Percentage of time monitors spend in the field—Specify the percentage of time monitors spend in the field. It is assumed that the remainder of their time is spent on site-management activities. Adjusting the percentage modifies the default calculation for site management.
   • Percentage of monitoring done by CRAs (vs. senior CRAs)—Specify the percentage of monitoring and site management that will be done by staff CRAs versus senior CRAs. In more complex studies, you might prefer that a senior CRA perform a larger percentage of the monitoring. If this is the case, decrease this percentage to indicate that less of the monitoring will be done by CRAs. Enter 100% if all monitoring will be done by CRAs; enter 0% if all monitoring will be done by senior CRAs.
   • Percentage of monitoring done by Regional Monitors—Specify the percentage of monitoring that will be done by regional monitors. The remaining monitoring and site management-activities are split between CRAs and senior CRAs, according to the value indicated in the Percentage of monitoring done by CRAs (vs. senior CRAs) field. Even when 100% of monitoring is done by regional monitors, some site management activities are still performed by CRAs or SCRAs..

     Note:

     The values in this field is not related to travel time or distance. This value is used to split the effort of monitoring and site-management tasks across resources that have different billing rates.

     When 100% of monitoring is done by regional monitors, some site management activities will still be performed by CRAs or SCRAs.

     When using regional monitors, time allocated for travel will be assigned to clean, monitored CRF and site management tasks.

   • Average travel time (in hours) for site monitors—Specify the average number of hours a monitor requires to travel to sites. This value should represent the average travel time from site to site as well as from a monitor's home.
     • If you chose Loop visits for the monitoring travel strategy, this value is used to calculate the time from the monitor's home to the first site, then to the second site, and so on, until the monitor returns home.
     • If you chose Spoke visits for the monitoring travel strategy, this value is multiplied by 1.75 to calculate the travel time to and from the monitor’s home or office to the site. Note that close-out visits are assumed to always use the Spoke travel strategy, even if the interim monitoring visits are performed via Loop travel.
   • Percent of source documentation verification—Specify the percent of data to be source-verified while monitoring the data. ClearTrial assumes and defaults to 100% of all data points per CRF page per study to be source-verified. You can define or override the default value and other related monitoring assumptions as needed based on their risk-based monitoring strategy.
     ClearTrial assumes 100% SDV by default, calculated by multiplying the Total Number of CRF Pages by the Monitoring Minutes per Page (driven by a study’s Therapeutic Area and Indication) to determine the total amount of time related to on-site SDV. If you are performing targeted or reduced SDV, there are two factors you can leverage to model this.

     • Adjusting the Percent of source document verification or SDV% assumption value—For example, if only 70% of the data points per page of each CRF page will be reviewed, define 70% SDV, which will reduce the Monitoring Minutes per Page by 70%.

       Note:

       Reducing the SDV% does not drive or adjust the Total CRF pages monitored assumption value.
     • Adjusting the Total CRF pages monitored assumption value—For example, if only the significant data points per CRF page (efficacy and safety) will be reviewed, then define or leave 100% SDV and adjust the Total CRF Pages monitored (accounting for subject drops) assumption accordingly.
   • Time to review queries from previous visit (minutes)—ClearTrial calculates this value representing the number of minutes required to re-review queries and CRF data from a previous monitoring visit, based on the phase, therapeutic area, and indication selected for the study. You can override this value.
   • Other (Non-SDV) hours on-site per visit—Specify the number of hours expected during each visit to perform activities not directly related to source document verification. Example activities include reviewing logs (subject screening, subject visit, subject discontinuation and termination, drug accountability, and others), confirming site adequacy or site status, and verifying adequate study supplies exist. The default value for this field is based on Phase, Therapeutic Area, and Indication. You can override this value.
   • Manage location-specific values—Enter monitoring approach assumptions per location by clicking the Edit location-specific overrides link. On the Edit Per Location Monitoring Approach screen, enter the monitoring approach assumptions for each location, overriding global default values where necessary, then click Ok.
2. Enter the details for monitoring data through CRF pages in the Monitored Data section or click Next to enter assumptions on the Provider tab.

Specify Total CRF Pages Expected

In the Monitored Data section of the Monitoring tab, enter the total number of CRF pages to be generated and monitored.

Note:

These monitoring assumptions are only available in Advanced or Expert Edit Mode.

1. On the Monitoring tab, in the Monitored Data section, enter the following details.
   • Total CRF pages generated (without subject drops)—ClearTrial calculates this value as the total number of expected CRFs that will be generated assuming no subjects drop out of the study (ignoring subjects expected to drop via the subject drop rate per segment). It is a summation of all CRF pages completed for each subject visit across all subjects and sites, as defined on the Subject Treatment/Visit Schedule.
   • Total CRF pages monitored (accounting for subject drops)—This value represents or ClearTrial calculates this value as the expected CRFs that will be monitored, accounting for any subjects that drop out of the study during the screening, treatment, or follow-up segments. The default value is derived from the subject drop rate per segment, which is applied to each week of the study to calculate the subject retention rate.

     To determine the total number of CRFs including drops, ClearTrial assumes the following:

     • For the first two weeks of enrollment, ClearTrial assumes that no subjects drop. Therefore, retention for weeks 1 and 2 is 100% and ClearTrial assumes that all scheduled CRF pages are completed.
     • For each week after week 2 of enrollment; that is, the total enrollment period minus the first two weeks, the system starts correcting the total number of CRFs completed by the drop rate. The drop rate is assumed to be linear, and the weekly reduction rate is calculated as the overall drop rate divided by the number of weeks after week 2.
     • Finally, the system takes the number of CRFs that would have been generated each week if no subjects had dropped out of the study, and multiplies it by the retention rate percentages described above to calculate the CRFs including drop outs.

     You may increase or decrease this value. The percentage change of your adjustment is applied to the CRF pages generated during each week of treatment to produce the total number of CRF pages, including drops.

2. Specify medical monitoring assumptions or click Next to enter assumptions on the Provider tab.

Review and Adjust Medical Monitoring Assumptions

In the Medical Monitoring section of the Monitoring tab, review and adjust the time for a medical monitor to serve as the team medical lead and provide support to the CRA monitoring staff and investigators for issues beyond safety reporting.

Note:

These monitoring assumptions are only available in Advanced or Expert Edit Mode.

1. On the Monitoring tab, in the Medical Monitoring section, select the 24/7 coverage radio button to require 24/7 coverage by the medical monitor for the study. This means the medical monitor is on call to address any site- or subject-related questions including, but not limited to, subject inclusion/exclusion criteria in accordance with the protocol, protocol violations or deviations that may occur during the study, or any other general medical monitor-related questions.
2. In the Number of medical data listing reviews field, enter the number of reviews required for the particular study being planned.
3. Enter drug accountability options in the Separate Drug Accountability section or click Next to enter assumptions on the Provider tab.

Review and Adjust Separate Drug Accountability Visits

Will there be additional drug accountability visits? Separate drug accountability generally applies to oncology and some vaccine studies and is done by someone other than the CRA that monitors the site.

Separate drug accountability visits are required when the study drug or test article is visibly different or packaged differently than the placebo. If the unblinded monitor conducts their drug accountability review of the study drug or test article, it could cause unintentional unblinding of the study monitor. In this scenario, the drug accountability is done by someone other than the CRA that monitors the site to ensure that all involved in the study are completely blinded.

Note:

These monitoring assumptions are only available in Advanced or Expert Edit Mode.

1. On the Monitoring tab, in the Separate Drug Accountability section, specify the following details:
   • Will there be additional drug accountability visits?—Specify whether drug accountability visits are required.

     Separate drug accountability visits are required when the study drug or test article is visibly different or packaged differently than the placebo. If the unblinded monitor conducts their drug accountability review of the study drug or test article, it could cause unintentional unblinding of the study monitor. In this scenario, the drug accountability is done by someone other than the CRA that monitors the site to ensure that all involved in the study are completely blinded.

   • Additional drug accountability visits performed by—Specify who will perform additional drug accountability visits, if applicable.
   • Additional drug accountability visits per site—Specify the number of additional drug accountability visits that will be made per site.
2. Save any changes you have already made.
3. Click Next to enter assumptions on the Provider tab.