Consent (Updated 2-8-22)
Screening and Inclusion/Exclusion
Q: Who is the IRB of record? What about other pertinent IRB information?
A: See below
- Name of the IRB of record: Advarra
- Name of the contact person at the IRB of record: Sarah Weir
- IRB of record project number: Pro00024234
- IRB of record FWA number: FWA00023875
- IRB of record registration number: IRB00000971.
Q: What is required to submit in WebDCU for the central IRB?
A: Sites must complete 3 tables in WebDCU. Start with the Site Overview table. Go to [SIREN] Icon in WebDCU – click on [Central IRB] – click on [Site Overview] to complete the table.
Next, complete the Site Regulatory Inspection History table as needed; go to the [SIREN] icon in WebDCU – click on [Central IRB] – click on [Site Regulatory Inspection History]. You must complete a new record for each regulatory inspection for the Investigator or your research location(s) that have occurred in the last 5 years. If there are no inspections, you will need to attest that the site nor the investigator has had any reportable audits in the past 5 years.
Lastly, complete the Initial Site Submission table; go to the [HOBIT] icon in WebDCU – click on [Central IRB] – click on [Initial Site Submission] to complete.
Q: How do I respond to a participant who says they want to withdraw from the study? (Updated 2-8-22)
A: The goals in responding to this kind of inquiry are to make sure participants know and understand their options, that we respect the choice of the participant, and that we preserve the integrity of data collection as much as possible.
- Do not pressure the participant (or LAR) to remain in the study. A research participant always has the right to withdraw from the study at any time and for any reason.
- Often your site PI will be in the best position to discuss options, as well as the importance of participation. Ask if the participant (or LAR) would like to talk with the PI.
- Inform the PI as soon as is practical either way.
- Try to clarify what they want to stop. Often requests to withdraw from the study are just requests to withdraw from certain elements of the intervention, or to skip a blood draw or other assessment or visit. Participants may opt out of most elements without withdrawing from the study.
- Ask specifically if they would like to completely withdraw from the study or are reticent about a particular part of the study (the outcome evaluation, monthly phone calls, for example).
- Study personnel should be aware that we can usually forgo the more burdensome portions of the study.
- If they are amenable to a short phone call in 6 months to see how they are doing, let them know that you can speak with the LAR, a friend or relative, or them. The study’s primary goal is to obtain the GOSE at the 6-month post-injury point.
- Ask “even If you want to stop everything else, may we look at your medical record while you are in the hospital?” Even if they only agree to continued chart review, this should not be considered a withdrawal of consent for participation.
- If they want no further contact, honor their wishes and thank them. Document withdrawal of consent on the end-of-study case report form.
Q: Do subjects need to be consented when they regain the capacity to consent?
A: No. Enrollment will be based on obtaining consent from a legally authorized representative. Subjects will not need to be consented when they gain the capacity to consent. However, subjects may withdraw from the study at any time.
Q: The timestamp on the e-consent does not reflect my time zone. What should I do?
A: A generic note to file is now available that reflects clarification on the time zone reflected on the e-consent PDF and the solution moving forwarded.
Q: What happens to the equipment that has been installed by Bill Gossett at the monoplace sites after the trial is over? Do the sites keep this?
A: The equipment remains the property of the Federal Government throughout the trial. After the trial ownership will normally be turned over to the hospital.
Q: Where do I find my site’s FWA number?
A: You will need to pull your site’s FWA number from the OHRP website: https://ohrp.cit.nih.gov/search/fwasearch.aspx?styp=bsc.
Q: Who can administer the GOSE exam?
A: We are looking for a neuropsychologist, physician or nurse. This person must be blinded to study treatment.
Q: What should I do if a subject in randomized with the intent to get the initial treatment within the prescribed time windo, but is unable to? (NEW 9-24-19)
A: Once a subject is randomized, they are in the trial whether they receive the treatment or not. This event should be reported in WebDCU as a protocol deviation, however, the subject is still eligible to receive subsequent HBO treatments if feasible. Treatment should be initiated as soon as feasible.
Q: Can you transport a patient with elevated ICP to the HBO chamber for HBO treatment
A: Subject with persistently elevated ICP despite treatment should not be transported to the HBO chamber. Myringotomy prior to HBO treatments can help with preventing ICP elevation during HBO treatment. While in the HBO chamber, elevated ICP can be treated as per standard of care (see clinical standardization guidelines).
Q: If a subject has a seizure can they still receive HBO treatment?
A: Severe TBI patients are at risk for developing seizures and need prophylaxis with anticonvulsants for 7 days per standard care. All subjects should receive anticonvulsant prophylaxis. Subjects may receive HBO treatments so long as they are not actively seizing. If a subject develops a seizure during HBO treatment, the treatment should be aborted. However, the subject may continue to receive the next scheduled HBO treatment if their seizure is under control. If they seize again during HBO treatment, the treatment should be aborted and future treatments cancelled.
Q: Since HBO treatments are for 5 days, should intracranial monitors (ICP and PbtO2 monitors - if present) be left in place for the entire 5 days?
A: No. Intracranial monitors should only be left in place for as long as it is clinically necessary.
Q: What should I do with remaining treatments if subject starts following commands?
A: If subject starts following commands, treatment should be stopped. However, prior to stopping treatment, please call the PI hotline (833-HOBIT-PI (833-462-4874)) to discuss the case.
Q1: Who does the study say needs to be present with the subject during TRANSPORT to and from the HBO chamber? Q2: Who does the study say needs to be present with the subject during HBO TREATMENT?
A (to Q1 and Q2): During the transport of the HOBIT subject to and from a monoplace or multiplace HBO chamber, there should be at least one clinician trained in ventilatory management and one critical care nurse present and available to address subject’s clinical needs. During the HBO treatment in a monoplace chamber, the HBO nurse and a clinician trained in ventilatory management should be physically present with the subject. For subjects treated in multiplace chambers, a clinician trained in ventilatory management should be physically present with the subject. Institutional policies should also be adhered to
Q: Does an ABG need to be done after the patient is placed on the hyperbaric ventilator?
A: Yes. Ventilation should be adjusted to ensure that the CO2 is documented as within normal limits before HBO treatment.
Q: Is hand bagging with a resuscitation bag allowed during descent and ascent for subjects being treated in a multiplace hyperbaric chamber?
A: It is allowed but there should be some means of monitoring the tidal volume and respiratory rate during these extended times off of the ventilator. For the 2.5 ATA HOBIT profile compressing at 2 feet per minute, this amounts to 50 minutes of hand bagging time
Q: Why is it necessary to have the subject ventilated with their baseline FiO2 up to the time they start the hyperbaric treatment?
A: The HOBIT protocol is set up to evaluate which of the HOBIT treatment arms is effective. This is based on a determined dose of oxygen which has been calculated based on the treatment time of 100% oxygen in the chamber and also the normobaric 100% oxygen time after the hyperbaric treatment. If the subject is placed on 100% oxygen prior to their hyperbaric treatment it will cause uncertainty in the trial results. Also, oxygen toxicity units (OTU’s) were calculated based on 100% oxygen treatment times and depth of treatment in the chamber. Adding more 100% oxygen prior to the hyperbaric treatment will add to their OTU’s and put the subject at risk for pulmonary oxygen toxicity.
Q: Should the ETT cuff be changed back to air after the hyperbaric treatment?
A: No, the ETT cuff should remain filled with NS for the duration of the HOBIT trial hyperbaric treatments. Changing the cuff from air to NS and then back from NS to air after each hyperbaric treatment (10 times in 5 days) can easily damage the cuff and or pilot balloon. It also increases the chance for subglottic oral secretions to be aspirated into the subject’s lungs and set them up for a ventilator associated pneumonia.
Q: Its day 5. Patient has missed HBO treatments on days 2-4. Is it okay to treat subject on day 5 after missing days 2-4?
A: Yes
Q: If the ICP is elevated during a dive, what should I do?
A: Treat ICP as per the clinical standardization guidelines. However, if ICP cannot be controlled, abort the HBO treatment. Subjects will remain eligible for subsequent HBO treatments so long as their ICP is within normal limits.
Q: Do you have any tips for identifying potential HOBIT subjects who are at high risk for pulmonary dysfunction, before they are randomized?
A: Yes. Patients with a high FiO2 requirement (>40%); or an aspiration event; or acute lung injury (contusion, pneumothorax) are all at risk for pulmonary dysfunction. Prior to randomization, these patients need a thorough pulmonary evaluation and optimization of their pulmonary status. A PF ratio should be calculated. If the PF ratio is close to 200 and you have compelling reasons for enrolling the patient, please call the HOBIT PI line to discuss it. However, patients with PF ratio<200 should not be enrolled.
Q: A subject has intractable ICP prior to HBO treatment. Can they still receive HBO treatment?
A: Ideally, the ICP should be stablilized prior to transporting the subject for HBO treatment. Treat the ICP according to the clinical standardization guidelines for at least one hour prior to deeming it intractable. In addition, ICP should not be evaluated in isolation. It should be evaluated in the context of the subject's clinical condition, while also considering the MAP and CPP. Since every subject is unique, if you have questions regarding whether a subject is stable enough for HBO treatment, please call the HOBIT PI line.
Q: If a subject has multiple SAEs that are related, should they be reported individually or as one SAE?
A: Ideally, if the SAEs are related, they should be reported as one. For example, if a subject has fever, hypoxia and infiltrates on chest x-ray and is suspected to have pneumonia, all these SAEs can be reported as pneumonia. You can report the fever, hypoxia and infiltrates on chest x-ray in the pneumonia SAE. Similarly, if a patient has an elevated ICP and a decreased MAP all due to cerebral edema, you can report cerebral edema and mention elevated ICP and decreased MAP in the cerebral edema SAE.
Q: If neurosurgery performs a decompressive craniotomy and they don’t feel that ICP monitoring is indicated and do not want to place an ICP monitor, can the patient be enrolled?
A: On a case-by-case basis, the HOBIT leadership may allow the enrollment of potential subjects who do not have an ICP monitor placed post decompressive craniotomy, because the treating neurosurgeons do not think it is clinically indicated. If you have such a potential subject, call the HOBIT PI hotline to discuss it further. (833-462-4874)
Q: Should sites bill for HBO treatments done as part of the study?
A: Since HBO treatments will be performed for research reasons, sites should not bill insurance companies for them. The study will make payments of $1000 per dive. However, enrolling sites can bill for non-HBO treatments provided as part of standard TBI clinical management. HBO treatment can be documented in the electronic medical record.
Q: Is the SIREN e.consent platform part 11 compliant?
A: Yes. SIREN uses the University of Michigan implementation of the REDCap platform to obtain electronic consent and (in some SIREN studies) participant contact information in a process that is 21 CFR Part 11 compliant. Part 11 compliance requires information technology that is capable of supporting compliant processes, and specific operating procedures that use the IT appropriately. Documentation from the University of Michigan Health Information Technology and Services (HITS) of the physical and network information technology security that supports Part 11 compliance in this implementation is available here. Documentation that the SIREN processes are Part 11 compliant is found in the SIREN Network e.consent SOP.
Q: If a subject has both Pulmonary Dysfunction (defined as PaO2/FiO2 ≤ 200 or requiring PEEP > 10cm of water to maintain a PaO2/FiO2 ratio of > 200) and pneumonia (or ARDS), should these events be reported as separate SAEs? (NEW 2-21-20)
A: No, combining groups of events reflecting the same underlying pathophysiology is important. For instance, report the diagnosis such pneumonia or ARDS as the SAE not the symptoms or signs such as pulmonary dysfunction, cough, chest pain, fever, and/or infiltrates on chest x-ray separately. However, if the pulmonary dysfunction occurs with no other concurrent related diagnosis, it should be reported as a separate SAE. There is a new pneumonia SAE template located in the HOBIT Safety Monitoring Plan in the MOP.
Q: When should critical hypotension or critical decrease in cerebral perfusion pressure (CPP) be recorded as an serious adverse event (SAE)?
A: If the mean arterial pressure (MAP) is <70 mmHg on at least two consecutive measurements that are performed at least 30 minutes apart. During the first 5 days of treatment, all episodes of critical hypotension should be recorded as one SAE. The start time is the time of the first occurrence of critical hypotension and the end time is when the critical hypotension finally resolved. Similarly, critical decrease in CPP is defined as CPP<60 mmHg on at least two consecutive measurements that are performed at least 30 minutes apart. During the first 5 treatment days, all episodes of critical decrease in CPP should be recorded as one SAE. The start time is the time of the first occurrence of critical decrease in CPP and the end time is when the critical decrease in CPP finally resolved.
Q: If an AEs occurs after Day 6 but before hospital discharge, what day would this fall under?
A: Enter this AE under Day 6. It will be analyzed based on date of onset.
Q: Should death be considered an SAE?
A: No. Death is considered an outcome. The event causing death should be reported as the SAE. For instance, if fulminant sepsis causes the death, sepsis should be considered the SAE. If the subject dies after being withdrawn from life support and placed on comfort care secondary to their neurological injury, that should be reported in one of 2 ways. 1) If they were deteriorating neurologically, the SAE should be reported as “neurological deterioration.” In the vast majority of cases, the death should be reported this way. 2) In the unusual circumstance that the subject remained neurologically stable or improved, the SAE may be reported as “withdrawn from life support.” The GCS at the time of enrollment and the one closest to withdrawal from life support should be included in the SAE narrative.
Screening and Inclusion/Exclusion
Q: How do you identify subjects with a Marshall Head CT score >1?
A: Any subject with evidence of traumatic intracranial abnormality on head CT can be classified as having a Marshall Head CT score>1.
Q: Do all HOBIT subjects need to have a Marshall Head CT score>1?
A: No. Subjects with a GCS of 3-6 who do not have an alcohol level > 200 mg.dl do not need to have evidence of traumatic intracranial abnormality prior to enrollment, however, there should be good clinical reason to suspect that their low GCS is due to brain trauma. Subjects with GCS of 7 and 8, and any subject with blood alcohol level greater than 200 mg/dL should have a Marshall Head CT score>1.
Q: When should GCS be obtained?
A: When subject has been resuscitated and is medically stable. Subjects should be off sedatives and paralytics prior to obtaining GCS.
Q: Which GCS should be used to determine eligibility for HOBIT?
A: The GCS used to determine eligibility is not necessarily the initial GCS or the lowest GCS but the most RELIABLE GCS. The GCS exam should be performed after resuscitation, off sedatives and paralytics and closest to the time of enrollment. This is because patients frequently improve or deteriorate neurologically during the first hours following injury. Alcohol and recreational drugs may suppress neurological function, resulting in a low GCS which may improve quickly. Therefore it is particularly important especially in patients with an initial GCS of 7 and 8 to obtain a repeat GCS close to enrollment. Do not hesitate to call the PI hotline if you have questions regarding eligibility.
Q: If a potential subject is intubated, which GCS should be used to determine eligibility for HOBIT?
A: Since the verbal component of GCS cannot be calculated reliably in intubated patients, you should use the motor score component of the GCS. Potential subjects are eligible for HOBIT if the most reliable motor score (obtained after patient has been stabilized and is off sedatives and paralytics) is 5 or less.
Q: If a potential subject presents with a GCS of 3 - 8, but the GCS improves to > 8 prior to randomization, should that potential subject be included in the screening log? (NEW 9-24-19)
A: Yes. The screening log should include all patients 16 - 65 years of age who presented to the enrolling institution within 18 hours of blunt head trauma, had a GCS of 3 - 8, and were hospitalized but not randomized. When completing the screening log, select “Improved GCS” as the reason for screen failure.
Q: If a subject has a pneumothorax from the presenting trauma, should they be excluded from HOBIT?
A: No. So long as they have a chest tube in place, they can still be enrolled in HOBIT and receive HBO treatments. However, potential subjects with PaO2/FiO2 (PF) ratio<200 despite PEEP of 10 cm of H2O should be excluded from HOBIT.
Q: Should patients with spinal fractures be excluded from HOBIT?
A: Not necessarily. Only those with spinal cord injury and resultant neurologic deficits should be excluded from the study. Subjects without spinal cord injuries who have unstable spine fractures that are securely immobilized (surgical fixation, TLSO, HALO) can be treated with HBO.
Q: We have a potential subject with spinal fracture and possible cord contusion. Subject is neurologically intact. Should they be enrolled?
A: If the fracture is stabilized they can be enrolled. If they are going to need surgical intervention for the fracture, they should not be enrolled.
Q: Can we film the simulation in segments?
A: Yes, sites can divide the simulation video into segments. It does not necessarily have to be done all at once. Sites could do the HBO separate from the ICU, and so forth.
Q: Who should be involved in the simulation?
A: We recommend that the following study personnel should be present for the simulation: the study PI, a study coordinator, ICU physician responsible for caring for TBI patient, a HBO tech, an HBO physician investigator, a respiratory therapist (if that is different from the HBO tech), and an ICU nurse.
Q: How should we film the simulation?
A: We recommend using a smart phone or video camera.
Q: Are there plans for site monitoring?
A: Yes. Onsite monitoring will occur after the enrollment of the first subject at each site. In addition, there will be central data monitoring. There may be additional site monitoring as needed.
Q: How do I add a NEW team member to the database?
A: All study team members will need to be added to the HOBIT database and then added eDOA.
- Click on [Study Team Member Request] under the [User Management] tab
- On the right hand top corner of screen, click on [Add New]
- This opens a new Study Team Member Request record – complete fields 1 through 8 and Save record.
Q: How do I set up a team member’s user permissions to access WebDCU (eg. Study Coordinator)?
A: To request user permissions in WebDCU, please go to HOBIT >> [User Management] >> [User Permission Request]. In that table you’ll see a list of all your site personnel. Click on the blue number next to the name of the person you wish to request permissions for, then click “Edit Record.” You can then add rows to request their permissions. Please note that “WebDCU User” is required for all users. Once permissions have been requested and the DOA log submitted and approved, SDMC will approve the permissions and they will receive an email with account login and password.
NOTE: Study team members will need to have an account set up using the [Study Team Member Request] table before user permissions can be requested.
Q: How do I modify a team member’s role and/or responsibilities?
A: First, add an end date for the team member’s whose role and/or responsibilities are being modified; then, add a new entry for the same team member with updated details for role/responsibilities and submit the eDOA for CCC review and approval. Discuss with site manager if the 1572 (and/or IRB Application) needs to be updated as well.
Q: I have a new team member on my study team. What are the steps to upload regulatory document for this new team member?
A: Follow the steps below:
- Add the new team member to the Database using the Study Team Member Request entry (See FAQs on adding a new study team member to database)
- Then add the team member to the eDOA log with start date, study role, and responsibilities.
- Submit eDOA log for CCC review and approval.
- After eDOA is approved by CCC, upload regulatory documents for new team member.
- Discuss with site manager and update 1572 if needed; upload updated 1572.
NOTE: It is the site’s responsibility to ensure that all new team members are added to the IRB application and approval is obtained before the study team member performs study related tasks.
Q: How can I submit site (or people) regulatory documents?
A: Follow the steps below.
- From the main menu page, click on [Regulatory Document] and then [Site (or People) Reg Doc Submission] table.
- To upload a new document, click on the Green Arrow for the document that you want to upload
- If there are any existing documents available for selection, they will be listed.
- If there are no existing document available, or none that you would like to select, click on the ‘upload new file’ link, browse for the document, and then click upload.
- Enter the required information, and then click ‘Save Record.’
Tip: User Management Site Reg Doc Status table: This will display a table view of the documents required at your site as well as the submission status of each document.
Q: I have a 1572 completed for my site. Do I need a Delegation of Authority (DOA) log as well? What is eDoA?
A: All sites need a DOA log and completed 1572. For HOBIT, in WebDCU, the DOA is entered electronically and is called eDOA. Upload the completed and signed 1572 for your site as “FDA Form 1572 – Statement of Investigator.”
Q: Where can I find the electronic Delegation of Authority (eDOA) log and how do I complete the entry?
A:
- Login into WebDCU-HOBIT,
- Click on the [User Management] tab
- Click on [DOA submission]
- Click on the blue # (number) link to the left to edit the eDOA
- Lastly, click [Edit Record] on the top right hand corner of the page.
- Add the team members to the eDOA list (They need be added to the study team member request table first, see Q on “How to add NEW team member to the database?”)
- Add responsibilities for each team member.
- Click [Submit] for the entry to be sent to the site manager for review and approval.
Q: How do I remove a team member's permissions from WebDCU?
A: A team member’s user account access is NOT updated once an end date is added to the eDOA log. User permissions also need to be updated.
Remove all user groups in the [user permission request] table for the departed team member. Please refer to the steps below.
- Click on the [User Management] tab, and then [User Permission Request] .
- On the list record page, click on the blue number link to the left of the study team member name you are looking for.
- Click on [Edit Record] in the top right hand corner of the screen. Remove all user group permissions in Question 5. When done, click [Save Record].
- SDMC Data manager will review and approve the request.
Q: How can a team member stop receiving WebDCU’s automated regulatory document emails?
A: Follow the steps below.
- Contact the coordinator in charge of adding people/submitting reg docs (usually the primary study coordinator) and request that your permissions be updated.
- Coordinator in charge, click on [user permission request] tab.
- Click edit record, and remove the user group [Submit Regulatory Document].
- Data manager at SDMC will approve the entry.
Q: What is the address of Advarra’s IRB to include in section 5 of the 1572?
A: Advarra
6940 Columbia Gateway Drive
Suite 110
Columbia, MD 21046
Q: Who should be listed on the 1572?
A: All study team members performing the following responsibilities MUST be on the 1572: overall responsibility for the trial, informed consent, AE/SAE reporting. All investigators should be listed as well.
Q: How should screened patient be entered into the WebDCU Screening Log during the COVID19 enrollment hold? (New 3-25-20)
A: Sites should continue to screen as they normally would and indicate the reason(s) why the subject was not eligible. If the subject is otherwise eligible for the trial, then the site will select “other reason” and enter “COVID19 hold”.