Trial Outcomes & Findings for Deep Brain Stimulation for the Treatment of Traumatic Brain Injury (NCT NCT02881151)
NCT ID: NCT02881151
Last Updated: 2022-12-23
Results Overview
The Trail Making Test is a measure of attention, speed and mental flexibility. It also tests spatial organization, visual pursuits, recall, and recognition. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility. Both sections are timed and the score represents the amount of time required to complete the task. Lower scores (shorter times) correspond to a better outcome.
COMPLETED
NA
6 participants
Pre-surgery baseline to treatment phase end (up to 197 days)
2022-12-23
Participant Flow
Participant milestones
| Measure |
Treatment
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Hospital Admission and Surgery (3 Days)
STARTED
|
6
|
|
Hospital Admission and Surgery (3 Days)
COMPLETED
|
6
|
|
Hospital Admission and Surgery (3 Days)
NOT COMPLETED
|
0
|
|
Post-surgical Washout (65 to 93 Days)
STARTED
|
6
|
|
Post-surgical Washout (65 to 93 Days)
COMPLETED
|
5
|
|
Post-surgical Washout (65 to 93 Days)
NOT COMPLETED
|
1
|
|
DBS Titration-Optimization (14 Days)
STARTED
|
5
|
|
DBS Titration-Optimization (14 Days)
COMPLETED
|
5
|
|
DBS Titration-Optimization (14 Days)
NOT COMPLETED
|
0
|
|
Unblinded Treatment Phase (90 Days)
STARTED
|
5
|
|
Unblinded Treatment Phase (90 Days)
COMPLETED
|
5
|
|
Unblinded Treatment Phase (90 Days)
NOT COMPLETED
|
0
|
|
Withdrawal Phase (21 Days)
STARTED
|
3
|
|
Withdrawal Phase (21 Days)
COMPLETED
|
3
|
|
Withdrawal Phase (21 Days)
NOT COMPLETED
|
0
|
|
Continuation Phase (6 Months)
STARTED
|
5
|
|
Continuation Phase (6 Months)
COMPLETED
|
5
|
|
Continuation Phase (6 Months)
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Treatment
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Post-surgical Washout (65 to 93 Days)
Device explantation
|
1
|
Baseline Characteristics
Deep Brain Stimulation for the Treatment of Traumatic Brain Injury
Baseline characteristics by cohort
| Measure |
Treatment
n=6 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Age, Continuous
|
34 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
|
Years since injury
|
6.5 years
n=5 Participants
|
|
Years of education
|
14 years
n=5 Participants
|
|
Trail-making test, part B
|
116.9 seconds
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Trail Making Test is a measure of attention, speed and mental flexibility. It also tests spatial organization, visual pursuits, recall, and recognition. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility. Both sections are timed and the score represents the amount of time required to complete the task. Lower scores (shorter times) correspond to a better outcome.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Trail Making Test Part B Time to Completion
|
-25.6 percent change in time
Interval -42.26 to -23.94
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Trail Making Test is a measure of attention, speed and mental flexibility. It also tests spatial organization, visual pursuits, recall, and recognition. Part A requires the individual to draw lines to connect 25 encircled numbers distributed on a page. Part A tests visual scanning, numeric sequencing, and visuomotor speed. Part B is similar except the person must alternate between numbers and letters and is believed to be more difficult and takes longer to complete. Part B tests cognitive demands including visual motor and visual spatial abilities and mental flexibility. Both sections are timed and the score represents the amount of time required to complete the task. Lower scores (shorter times) correspond to a better outcome.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Trail Making Test Part A Time to Completion
|
-27.4 percent change in time
Interval -33.06 to -25.34
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The TBI-QOL was developed as a comprehensive patient-reported outcomes (PRO) measurement system specifically for individuals with TBI. It consists of 20 independent calibrated item banks and 2 uncalibrated scales that measure physical, emotional, cognitive, and social aspects of health-related quality of life. We will administer the short form (6-10 questions each) of the TBI-QOL Fatigue, Attention/Concentration, and Executive Function subscales. Executive Function score range: 10-50, higher scores correspond to better executive function.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Traumatic Brain Injury Quality of Life - Executive Function Short Form (TBI-QOL) Scale Score
|
28.0 percent change in score
Interval 19.44 to 53.57
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The TBI-QOL was developed as a comprehensive patient-reported outcomes (PRO) measurement system specifically for individuals with TBI. It consists of 20 independent calibrated item banks and 2 uncalibrated scales that measure physical, emotional, cognitive, and social aspects of health-related quality of life. We will administer the short form (6-10 questions each) of the TBI-QOL Fatigue, Attention/Concentration, and Executive Function subscales. Attention/Concentration score range: 6-30, higher scores correspond to better attention and concentration.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change Traumatic Brain Injury Quality of Life - Attention/Concentration Short Form Scale Score
|
66.7 percent change in score
Interval 57.85 to 92.86
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The TBI-QOL was developed as a comprehensive patient-reported outcomes (PRO) measurement system specifically for individuals with TBI. It consists of 20 independent calibrated item banks and 2 uncalibrated scales that measure physical, emotional, cognitive, and social aspects of health-related quality of life. We will administer the short form (6-10 questions each) of the TBI-QOL Fatigue, Attention/Concentration, and Executive Function subscales. Fatigue score range: 10-50, lower scores correspond to less fatigue.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Traumatic Brain Injury Quality of Life - Fatigue Short Form Scale Score
|
2.9 percent change in score
Interval -20.0 to 5.0
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Rivermead PCS Questionnaire (RPQ) was originally developed as a measure of severity of symptoms following mild TBI. It consists of 16 post-concussion symptoms including headaches, dizziness, nausea/vomiting, noise sensitivity, sleep disturbance, fatigue, irritability, feeling depressed/tearful, feeling frustrated/ impatient, forgetfulness, poor concentration, taking longer to think, blurred vision, light sensitivity, double vision and restlessness. In the original version of the RPQ, participants are asked to rate the degree (on a scale of 0 to 4) to which a particular symptom has been absent or a mild, moderate or severe problem over the previous 24 hours compared with premorbid levels. Score range: 0-64, lower scores correspond to fewer symptoms
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Rivermead Post-Concussion Symptom Questionnaire Scale Score
|
-36.6 percent change in score
Interval -62.16 to -6.25
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Ruff 2 \& 7 Test was developed to measure two aspects of visual attention: sustained attention (ability to maintain consistent performance level over time) and selective attention (ability to select relevant stimuli while ignoring distractors). The test consists of a series of 20 trials of a visual search and cancellation task. The respondent detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test. Speed scores reflect the total number of correctly identified targets (hits). Score range: 0 to 300, with higher numbers representing more correctly identified targets within the allotted time (5 minutes)
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Ruff 2 and 7 Automatic Detection Speed Score
|
21.1 percent change in score
Interval 3.87 to 23.17
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Ruff 2 \& 7 Test was developed to measure two aspects of visual attention: sustained attention (ability to maintain consistent performance level over time) and selective attention (ability to select relevant stimuli while ignoring distractors). The test consists of a series of 20 trials of a visual search and cancellation task. The respondent detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test. Accuracy scores evaluate the number of targets identified in relation to the number of possible targets (n=300), expressed as a percentage. Higher scores represent higher accuracy of target identification.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Ruff 2 and 7 Automatic Detection Accuracy Score
|
5.2 percent change in score
Interval 1.83 to 7.94
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase, and who had calculable scores
The Ruff 2 \& 7 Test was developed to measure two aspects of visual attention: sustained attention (ability to maintain consistent performance level over time) and selective attention (ability to select relevant stimuli while ignoring distractors). The test consists of a series of 20 trials of a visual search and cancellation task. The respondent detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test. Speed scores reflect the total number of correctly identified targets (hits). Score range: 0 to 300, with higher numbers representing more correctly identified targets within the allotted time (5 minutes)
Outcome measures
| Measure |
Treatment
n=4 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Ruff 2 and 7 Controlled Search Speed Score
|
17.3 percent change in score
Interval 14.47 to 25.39
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase, and who had calculable scores
The Ruff 2 \& 7 Test was developed to measure two aspects of visual attention: sustained attention (ability to maintain consistent performance level over time) and selective attention (ability to select relevant stimuli while ignoring distractors). The test consists of a series of 20 trials of a visual search and cancellation task. The respondent detects and marks through all occurrences of the two target digits: "2" and "7." In the 10 Automatic Detection trials, the target digits are embedded among alphabetical letters that serve as distractors. In the 10 Controlled Search trials, the target digits are embedded among other numbers that serve as distractors. Correct hits and errors are counted for each trial and serve as the basis for scoring the test. Accuracy scores evaluate the number of targets identified in relation to the number of possible targets (n=300), expressed as a percentage. Higher scores represent higher accuracy of target identification.
Outcome measures
| Measure |
Treatment
n=4 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Ruff 2 and 7 Controlled Search Accuracy Score
|
2.7 percent change in score
Interval 1.29 to 5.03
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Participant Health Questionnaire 9 is a standardized assessment instrument designed to screen, diagnose, monitor, and measure the severity of depression. Score range: 0 to 27, lower scores correspond to better health outcomes.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Percent Change in Patient Health Questionnaire - 9 Scale Score.
|
-41.7 percent change in score
Interval -80.0 to -30.77
|
SECONDARY outcome
Timeframe: Pre-surgery baseline to treatment phase end (up to 197 days)Population: Subjects who completed all study assessments through the open label treatment phase
The Glasgow Outcome Scale Extended (GOS-E) is a measure of disability and handicap intended for use following head injury. The GOS-E subdivides the upper three categories of the original Glasgow Outcome Scale (GOS), severe disability, moderate disability and good recovery, into an eight-category scale: 1 = dead, 2 = vegetative state, 3 = lower severe disability, 4 = upper severe disability, 5 = lower moderate disability, 6 = upper moderate disability, 7 = lower good recovery, and 8 = upper good recovery to provide more detailed assessment of the functional effects of the injury. A structured interview has been developed to standardize assignment of an outcome category (Wilson et al. 1998). Increase of 1 point on this scale represents a meaningful change in health outcome.
Outcome measures
| Measure |
Treatment
n=5 Participants
Subjects were treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that was be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Number of Participants With ≥1 Point Increase in Glasgow Outcome Scale - Extended Scale Score
|
2 Participants
|
Adverse Events
Treatment
Serious adverse events
| Measure |
Treatment
n=6 participants at risk
Subjects will be treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that will be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Infections and infestations
Infection of DBS device
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Nervous system disorders
Syncope
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
Other adverse events
| Measure |
Treatment
n=6 participants at risk
Subjects will be treated with deep brain stimulation throughout the study, with the exception of a brief, 21 day blinded withdrawal phase that will be undertaken to assess for any possible therapeutic effect.
Deep brain stimulation: Delivery of continuous, low-voltage electrical pulses to deep portions of the brain via an implantable pacemaker-like device.
|
|---|---|
|
Nervous system disorders
Fatigue
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Nervous system disorders
Headache
|
33.3%
2/6 • Number of events 2 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Surgical and medical procedures
Wound site bleeding
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Product Issues
Unintended stimulator deactivation
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Nervous system disorders
Gait disturbance
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Musculoskeletal and connective tissue disorders
Lower extremity pain
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Nervous system disorders
Tinnitus
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Nervous system disorders
Cognitive difficulty
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
|
Infections and infestations
COVID-19
|
16.7%
1/6 • Number of events 1 • 1 year (treatment phase plus continuation phase)
Adverse events are presented in a single group because the study was designed to assess any adverse events during the study as a whole, not whether adverse events were associated with any particular study phase.
|
Additional Information
Dr. Jaimie Henderson
Stanford University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place