Documentation (Updated 6-20-19)
Protocol/Protocol Adherence (Updated 6-25-19)
Q: What are the documentation requirements for capture of Tier therapies during the monitoring period?
A: It is the study personnel’s responsibility to examine all options used for documentation to ensure that any intervention used to address low brain oxygen or raised ICP was performed and documented into the Moberg CNS monitor. As a study coordinator, if it is apparent that an intervention was performed but not documented in the Moberg CNS system, it will need to be added at a later time. Study coordinators should assess for this during their daily check on a BOOST3 patient during the monitoring period. Upon initial use, it will be important for the study coordinators to be present at the bedside to make sure that the nurses are comfortable with the options presented for data capture for BOOST3. Three documentation options are listed below:
Medical Record: From a patient care/clinical perspective, clinical nurses should be documenting (any) interventions done for patient care in the medical record; for example, a change in PEEP should be documented along with the rationale.
Moberg CNS Monitor: The Moberg CNS monitor will be used for BOOST 3 subjects for data capture. An alarm will be programmed into the monitor to alert the nurse when a sustained (> 5 minutes) ICP or PbtO2 abnormality is detected; at minimum, the nurse should acknowledge the alarm using the touch screen function on the CNS monitor. Once the alert is acknowledged, the Moberg monitor will display a menu of Tier 1 interventions to address the abnormality. This should trigger the need to perform a Tier 1 intervention—the nurse will need to select the intervention chosen to address the abnormality and perform the intervention, and then document the time that the intervention was performed using the touch screen function on the Moberg, as these interventions will be programmed into the CarePath software.
Nursing Documentation Tool (OPTIONAL): An optional paper Nursing Documentation Tool was developed for nurses who prefer to document Tier Interventions on paper vs interacting with the CNS monitor software (they will still have to acknowledge/silence the alarm), OR if there is a technical issue with the CNS monitor. This tool lists all of the tier interventions for each Scenario. In the event of an abnormality, depending on the scenario, the nurse can simply write their initials in the appropriate column that corresponds with the tier intervention performed, and document the date and time using the far left column. The study team should provide a new set of papers either each shift, or day the subject is being monitored. If a nurse chooses to document using the Moberg, they are NOT required to double document on the Nursing Documentation Tool.
NOTE: The Moberg has a feature in which the nurse can review events/interventions that were documented throughout their shift. If the nurse had a busy shift, they can simply use the review events feature to quickly chart in the medical record the interventions that were performed for their patient that will also include the correct time the intervention was performed. They can also do this with the Nursing Documentation tool, if used in place of Moberg, especially if the paper tool is available in the room so that they can quickly chart interventions.
Q: When does a scenario begin? (NEW 6-20-19)
A: A Scenario begins at the time an abnormality is noted on the Moberg CNS monitor or on the ICP and/or PbtO2 monitor. The Moberg alarm will sound when there is an abnormality. It is generally accepted that an abnormality sustained for 5 minutes is a true abnormality that requires a response by the medical care provider. However, it is not necessary to wait 5 minutes from the time the abnormality began in order to respond if the provider believes the abnormality is valid. The medical care provider may use his or her best judgment as to whether or not to wait 5 minutes from the beginning of the abnormality to respond. The protocol requires treatment initiation within 15 minutes from the very beginning of the abnormality.
Q: How do we record 2 abnormalities that occur within one hour?
A: If an abnormal ICP or PbtO2 is corrected and then becomes abnormal again within one hour, treat as one episode. May select treatments from Tier 1, 2, 3.
Example: ICP was reduced after initiating treatment from Tier 1 in 10min, but back up within the hour. These two Scenarios (2 abnormalities) occurred within one hour and should be considered one Scenario.
Q: What is required for a NEW Scenario to begin?
A: If you have already been working in a Scenario (B, C, or D) to correct an abnormality (or abnormalities) and the treatments successfully corrected the abnormalities for minimum of one hour that Scenario is ended. Remember that the abnormal ICP and PbtO2 that began the Scenario must be within NORMAL limits for AT LEAST ONE HOUR. Then if another abnormality occurs, begin a NEW SCENARIO.
Q: What are common mistakes regarding the FiO2 challenge?
A: Not doing one or doing it too late (> 2 hours after placement).
Remember to record the following:
- The FiO2 before beginning the challenge
- The time at the beginning of the challenge
- The FiO2 number at the end of the challenge
- The time at the end of the challenge
- Whether it was successful (rose at least 5 mm Hg within 20 min. maximum).
Q: How long will placement of the ICP and PbtO2 probes take? Where will this procedure be performed?
A: The procedure takes approximately 20-30 minutes. This procedure is performed most commonly in the intensive care unit. In some occasions it is performed in the operating room if the patient requires a surgical procedure. In rare cases, in some institutions, the probes are placed in the emergency department.
Q: Will this be an inpatient or outpatient procedure?
A: This is an inpatient treatment protocol with all procedures being done in the hospital setting.
Q: Will there be anesthesia required for placement of intracranial monitors?
A: Yes. In the intensive care unit or emergency department, the probes are placed under local anesthesia with moderate or unconscious sedation protocols. If the probes are being placed in the operating room, there is no need for additional sedation or anesthesia as they are typically being placed under for other surgical procedures that are determined to be necessary by the treating neurosurgeon.
Q: Why are children included in BOOST-3?
A: Children aged 14 years and older will be enrolled in the study. We plan to exclude children younger than age 14 years for several reasons. First, the outcome measures proposed are not fully validated in young children. Second, pre-pubertal children have a distinct cerebrovascular physiology, and in particular are at greater risk of hyperemia and malignant intracranial hypertension. This may place them at greater risk of PbtO2 directed therapies and may confound the interpretation of our results.
Q: Is it required that the treatment team always adhere to the protocol?
A: Yes, adherence to the protocol is required. There is substantial room within each Scenario and within each Tier for neurointensivists, neurosurgeons, and other treatment team members at each site to choose the particular intervention to implement, which should be informed by the detailed knowledge of the pathophysiology active in a particular patient at a particular time. The treatment team may choose not to do interventions responding to an abnormal PbtO2 or ICP for medical/safety reasons. However, for Tiers 1 and 2, the available treatment options are broad enough that it would be highly unusual that all of the treatment options would be contraindicated in a given patient. Tier 3 treatments are optional in all cases and are included in the CRFs so we can record therapies that could be instituted. If site investigators chose not to implement any Tier 1 or Tier 2 therapies, the rationale for that decision needs to be clearly documented in the medical chart and recorded by the research team to avoid protocol violations.
Q: Is it ok to disable the alarm on the ICP/PbtO2 monitors? (NEW 6-25-19)
A: Only the PbtO2 alarm in the blinded group should be disabled. Do not disable the alarms in the unblinded (PbtO2 and ICP treatment) group. If the alarms are disabled, abnormalities will be missed in the open treatment group.
Q: Is it ok to alter the ICP and/or PbtO2 thresholds on the external monitors in order to minimize the number of times the alarms are sounding? (NEW 6-25-19)
A: No. Coordinators need to check the monitors every morning in order to ensure that the treatment staff is not altering the threshold numbers of the ICP/PbtO2 monitors. The PbtO2 monitor alarm MUST be silenced prior to the cover being placed if the participant is in the blinded group so that the treatment team will not be made aware of PbtO2 abnormalities.
Q: Who are the personnel at the SIREN CCC and who should we communicate with for various trial related questions?
A: The easiest way to reach out to the SIREN CCC is to use the BOOSTfirstname.lastname@example.org. This will ensure that your message gets to the appropriate team member who can provide a prompt response.
Q: How can we confirm prospective trial sites, affiliated SIREN Hubs and critical study team member contact information with the SIREN CCC?
A: This is a great question, as we want to be sure that we have the contact information to reach all critical study team members at all prospective BOOST 3 sites. If there have been any changes to your site's Hub affiliation, BOOST 3 PI, or BOOST 3 Primary Study Coordinator since you completed the initial survey, please let us know. We are happy to work with you to confirm this information.
Q: What if a treatment that is listed in the Tiers is already being done prior to the beginning of an abnormality that signals the beginning of a Scenario? (An episode is sometimes referred to as a Scenario. It is the period of beginning of an abnormality and the treatment period).
A: Only treatments initiated AFTER an abnormality has begun which begins an episode or Scenario should be entered on the case report form (CRF) as treatments included in the study protocol. The CRF will document the time of the new episode, and any new treatment initiated. If the treatment was already being actively used before the episode started, it should NOT be entered on the CRF as a new treatment. Treatments already being actively used when an episode occurs should be noted in the medical record, but NOT listed as a new treatment initiated in response to the abnormality for the study. Select another treatment (not already in place) from Tier 1 to address the new episode or select from Tier 2 if Tier 1 treatments are already actively being used and the treatment team chooses not to do another treatment from Tier 1. Note this information and rationale.
- If the head of bed is already elevated when the ICP increases to begin a new episode, the raising head of bed is not a new treatment unless the head of the bed is raised further.
- If any intervention is initiated for an episode of elevated ICP and the ICP responded, then that episode has resolved in response to the treatment(s) given. This is documented in the CRF. If a few hours later, there is another episode of elevated ICP, the team can choose to give any Tier 1 treatment again, including the agent given for the earlier episode, if it is thought to be clinically indicated. This is considered a new intervention for a new Scenario or episode.
- If you are doing a treatment that says “ensure temperature” or “maintain a temp”, you must note WHICH treatment was INITIATED in order to “ensure” or “maintain
Q: How will sites be rolling out and how many sites will participate in the study?
A: While taking all sites into consideration, we will be prioritizing sites based on experience with placement and management of PbtO2 monitors. We will be contacting the highest priority sites no later than September 10. BOOST will only include sites that use PbtO2 monitors. For sites who do not currently have or use PbtO2 monitors but intend to, you will need to demonstrate experience in using brain tissue oxygen monitors for patient care in TBI patients. Our expectation is that sites should have successfully placed and used PbtO2 monitors at least 3 times in the past 6 months to be considered as a BOOST site. After your site has placed at least 3 PbtO2 monitors, the site PI should contact Dr. Shutter (email@example.com) to confirm this information. We encourage all sites to begin preparations now, and will move forward with sites as they complete this process and are ready to get started. We budgeted for 45 actively enrolling sites in BOOST3.
Q: Does my site have to use the Central/Single IRB?
A: Yes. BOOST-3 is an NIH-funded study awarded after Jan. 25, 2018. The NIH requires mandatory use of a single IRB for all SIREN trials (NIH Policy).
Q: What is the Central IRB #?
Q: What will be involved in the process of ceding to the central IRB (Advarra)?
A: Consistent with NIH guidelines, BOOST 3 will be using a central IRB. The answer to this question and others about cIRB can be found on the following SIREN page: Resources and Steps for Relying on the SIREN ER-CIRB
Q: My site IRB uses Smart IRB for reliance agreements. How does that work?
A: Please contact your IRB for assistance with this. You can also reference instructions from Advarra: Using Smart IRB
Q: What is expected of each site for the EFIC process for this trial?
A: Sites with experience conducting EFIC activities can expect to propose community consultation and public disclosure (CC/PD) activities similar to the efforts undertaken in previous trials. However, the cIRB may yet request the overall trial EFIC plan to have some additional or different requirements. An EFIC plan for sites to use to build out your local CC/PD plan will be made available as soon as it has been cIRB approved. Centrally, the CCC will create CC/PD related resources and templates for local use, e.g, videos, brochures, ads, flyers, slide sets, self-administered survey instruments, etc. CC and PD results and event data will be collected centrally in WebDCU™ for generating reports for the cIRB. There will be startup funds allocated to perform the required EFIC activities. If you have additional questions please contact Deneil Harney firstname.lastname@example.org 734-232-2132
Q: How will BOOST 3 data be managed?
A: The BOOST 3 database is currently being built in the WebDCU™ clinical trial management system. WebDCU is housed at the Data Coordination Center (DCC) at the Medical University of South Carolina (MUSC). All trial data will be maintained in this secured system, including CRFs, regulatory requirements, and EFIC CC and PD activities. The central IRB application process will also take place in this system. Training and instructional materials will be provided to facilitate use of each component of the database.
Q: How will local site training take place?
A: Sites will be responsible for training their local study teams and clinical staff initially and throughout the course of the trial. The SIREN CCC will provide training materials, available online for easy access (protocol training, in-service slides, etc.), as well as study materials to be distributed locally (e.g. pocket cards, trial posters, etc.). As sites develop their own materials, we encourage sharing across the network and can post these materials in the BOOST 3 Toolbox.
Q: What trial equipment will be provided to sites?
A: The SIREN CCC will be lending Moberg CNS monitors (CNS-310) to all enrolling sites. So long as sites continue to enroll, the devices will remain on site. Should sites discontinue enrollment, the devices will be returned to the SIREN CCC. Pbt02 monitors will NOT be provided by the SIREN CCC. For enrolling sites, startup payments will include some funds to partially offset the cost of site’s PbtO2 ownership, and may be applied to equipment necessary to connect the PbtO2 device (Integra Licox or Raumedic Neurovent) to the Moberg monitor. The cost of probes is built into per subject payments.
Q: What do you do if it appears that the PbtO2 monitor is not functioning properly?
A: If there is evidence that a probe is not working and a first and second FiO2 challenge have failed, follow the next steps as outlined in the MOP (CT and replacement of probe if indicated but only in the unblinded group). In the blinded group, there is no remedy. However, you must do an FiO2 challenge daily until the 5th day after placement or the probes are removed.
Open PbtO2 treatment arm: If, after replacement of the probe, the new probe still fails the FiO2 challenge, the team may then choose to ignore the PbtO2 numbers. The protocol does not require replacing the probe a second time. If FiO2 challenges in subsequent days show that the probe starts working (i.e., the FiO2 challenge is successful), interventions for low PbtO2 can be re-started.
In all cases, the primary analysis will be performed using intention to treat principles.
Q: What is the per subject reimbursement?
A: The per subject reimbursement has not yet been finalized. However, it is expected to be approximately $12,500, which is inclusive of indirects. Per subject reimbursement will be milestone driven.
Q: Are we billing insurance for the procedure?
A: Yes. Placement of probes are considered routine care of TBI patients at all study sites.
Q: Are we billing insurance for the device?
A: The ICP probe is standard of care and the cost of the probe should be billed to the 3rd party payors. The PbtO2 probe is the target of the study, and the cost of the probe is included in the per-patient capitated cost. There is no charge for the use of the Moberg CNS monitor.
Q: Will the sponsor pay for the device or procedure if insurance denies?
A: No. As placement of the probes is part of routine care, the cost for the procedure to place the probes and the ICP probe itself should be billed to insurance. The cost of the PbtO2 probe is covered by the sponsor. There is no cost associated with the monitoring device. As a reminder: Please discuss your local practices for intracranial monitoring with the treating neurointensivist or neurosurgeon at your site.
Q: Will there be an initial BOOST 3 Investigator Meeting?
A: Yes. We anticipate that this will take place in the first quarter of 2019. Meeting details and location will be distributed as soon as we have further information.
Q. What is the management strategy for the BOOST-3 trial?
A. BOOST-3 is a trial assessing a management strategy of patient care; it is NOT a study assessing an experimental drug, device or procedure. The procedures being done for this trial, including placement of intracranial monitoring probes, is part of the routine care for patients admitted to the hospital (i.e. inpatients) with severe TBI.
Q. Do you have the IDE #?
A. No, there is an IDE waiver from the FDA since PbtO2 devices are FDA-cleared for this indication.
Q. Where can I get more information on Integra/Raumedic products or their IFUs?