Trial Outcomes & Findings for Mental Stress Reduction in Defibrillator Patients (NCT NCT00624520)
NCT ID: NCT00624520
Last Updated: 2014-12-22
Results Overview
Maximum Mental Stress induced elevation in "Double Product" , (equal to Heart Rate , beats/minute, x Systolic Arterial Blood Pressure, mmHg), following serial heart rate and blood pressure measurements during mental stress task of mental arithmetic (serial subtraction). Heart rate and blood pressure responses were recorded at 2.5 minute intervals before , during, and after each test using a Philips automated blood pressure recording device. The math task was applied for 10 minutes, with 10 minutes recovery time. An average of 3 measurements was taken as baseline prior to stress tasks. Stress induced double product elevations were measured as the difference between baseline and maximal values in units of mmHg.beats/minute. Higher values represent a greater mental stress induced effect, and lower values, a lower effect.
TERMINATED
PHASE3
129 participants
Immediate to 6 months post intervention
2014-12-22
Participant Flow
Recruitment commenced October 2009, completed December 2011 Recruitment from Cardiology Clinics W S Middleton Veterans Hospital, Madison, and Zablocki VA Medical Center, Milwaukee
Some enrolled participants were excluded from the trial if determined to have severe mental illness after administration of an SCID-I questionnaire and/or interview by a clinical psychologist. Others were excluded as drop-outs due to travel issues, weather, family issues, and illness. 2 subjects died before group assignment.
Participant milestones
| Measure |
Cognitive Behavioral Stress Management
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Overall Study
STARTED
|
56
|
47
|
|
Overall Study
COMPLETED
|
44
|
39
|
|
Overall Study
NOT COMPLETED
|
12
|
8
|
Reasons for withdrawal
| Measure |
Cognitive Behavioral Stress Management
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
12
|
7
|
|
Overall Study
Death
|
0
|
1
|
Baseline Characteristics
Mental Stress Reduction in Defibrillator Patients
Baseline characteristics by cohort
| Measure |
Cognitive Behavioral Stress Management
n=56 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=47 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
Total
n=103 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65.7 Years
STANDARD_DEVIATION 9.0 • n=93 Participants
|
66.2 Years
STANDARD_DEVIATION 8.6 • n=4 Participants
|
65.7 Years
STANDARD_DEVIATION 8.9 • n=27 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
32 Participants
n=93 Participants
|
23 Participants
n=4 Participants
|
55 Participants
n=27 Participants
|
|
Age, Categorical
>=65 years
|
24 Participants
n=93 Participants
|
24 Participants
n=4 Participants
|
48 Participants
n=27 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
56 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
102 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
51 Participants
n=93 Participants
|
41 Participants
n=4 Participants
|
92 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
56 Participants
n=93 Participants
|
45 Participants
n=4 Participants
|
101 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
56 participants
n=93 Participants
|
47 participants
n=4 Participants
|
103 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Immediate to 6 months post interventionPopulation: Response to Mental Stress by Math Stress Task.
Maximum Mental Stress induced elevation in "Double Product" , (equal to Heart Rate , beats/minute, x Systolic Arterial Blood Pressure, mmHg), following serial heart rate and blood pressure measurements during mental stress task of mental arithmetic (serial subtraction). Heart rate and blood pressure responses were recorded at 2.5 minute intervals before , during, and after each test using a Philips automated blood pressure recording device. The math task was applied for 10 minutes, with 10 minutes recovery time. An average of 3 measurements was taken as baseline prior to stress tasks. Stress induced double product elevations were measured as the difference between baseline and maximal values in units of mmHg.beats/minute. Higher values represent a greater mental stress induced effect, and lower values, a lower effect.
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=43 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=38 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Mental Stress Induced Elevation in "Double Product" by Math Stress Task
6 months post
|
1693 mmHg x beats/min
Standard Error 343
|
1137 mmHg x beats/min
Standard Error 228
|
|
Mental Stress Induced Elevation in "Double Product" by Math Stress Task
3 months post
|
1399 mmHg x beats/min
Standard Error 201
|
1063 mmHg x beats/min
Standard Error 158
|
|
Mental Stress Induced Elevation in "Double Product" by Math Stress Task
Immediate post
|
1514 mmHg x beats/min
Standard Error 246
|
1538 mmHg x beats/min
Standard Error 224
|
PRIMARY outcome
Timeframe: 3 months post interventionPopulation: Response to mental stress by math task testing at 3 months post intervention, compared with pre-intervention. Within-group comparison is shown for matched pair data. The lower number of participants analyzed than at study entry is due to patient drop-outs during follow-up post-intervention.
Maximum Mental Stress induced elevation in "Double Product" , DP, (equal to Heart Rate , beats/minute, x Systolic Arterial Blood Pressure, mmHg), following serial heart rate and blood pressure measurements during mental stress tasks of mental arithmetic (serial subtraction). Heart rate and blood pressure responses were recorded at 2.5 minute intervals before , during, and after each test using a Philips automated blood pressure recording device. The math task was applied for 10 minutes, with 10 minutes recovery time. An average of 3 measurements was taken as baseline prior to stress tasks. Stress induced double product elevations were measured as the difference between baseline and maximal values in units of mmHg.beats/minute. Higher values represent a greater mental stress induced effect, and lower values, a lower effect.
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=36 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Mental Stress Induced Elevation in Double Product by Math Stress Task
Pre intervention
|
1915 mmHg x beats/minute
Standard Error 263
|
—
|
|
Mental Stress Induced Elevation in Double Product by Math Stress Task
3 months post intervention
|
1399 mmHg x beats/minute
Standard Error 201
|
—
|
PRIMARY outcome
Timeframe: Immediate to 6 months post interventionPopulation: Response to Mental Stress by Anger-Recall Stress Task
Maximum Mental Stress induced elevation in "Double Product" , (equal to Heart Rate , beats/minute, x Systolic Arterial Blood Pressure, mmHg), following serial heart rate and blood pressure measurements during mental stress of anger-recall task. Heart rate and blood pressure responses were recorded at 2.5 minute intervals before , during, and after each test using a Philips automated blood pressure recording device. The anger-recall test was applied for 25 minutes with 10 minutes monitoring post-test. An average of 3 measurements was taken as baseline prior to stress tasks. Stress induced double product elevations were measured as the difference between baseline and maximal values in units of mmHg.beats/minute. Higher values represent a greater mental stress induced effect, and lower values, a lower effect
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=44 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=39 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Mental Stress Induced Elevation in "Double Product" by Anger-recall Task
6 months post intervention
|
711 mmHg x beats/minute
Standard Error 232
|
631 mmHg x beats/minute
Standard Error 292
|
|
Mental Stress Induced Elevation in "Double Product" by Anger-recall Task
3 months post intervention
|
353 mmHg x beats/minute
Standard Error 167
|
548 mmHg x beats/minute
Standard Error 308
|
|
Mental Stress Induced Elevation in "Double Product" by Anger-recall Task
Immediate post intervention
|
406 mmHg x beats/minute
Standard Error 93
|
681 mmHg x beats/minute
Standard Error 244
|
SECONDARY outcome
Timeframe: Immediate post interventionPopulation: Serial psychometric scores up to 6 months post intervention Reduced numbers of participants analyzed reflect drop-outs or failure to fully complete questionnaires during follow-up, with inclusion only of participants having accurate and appropriate data.
Psychosocial score of negative mood derived from self-report questionnaires. Scale range was 15-45. Lower values represent better outcome, and higher values represent worse outcome..
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=39 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=36 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
State Anger
|
16 units on a scale
Standard Deviation 2
|
19 units on a scale
Standard Deviation 7
|
SECONDARY outcome
Timeframe: Immediate post interventionPopulation: Immediate post intervention Reduced numbers of participants analyzed reflect drop-outs or failure to fully complete questionnaires during follow-up, with inclusion only of participants having accurate and appropriate data.
Psychometric score by self-report questionnaire Scale range is 3-29. Lower values represent better outcome, and higher values represent worse outcome..
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=39 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=38 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Tension/Anxiety
|
8 units on a scale
Standard Deviation 4
|
12 units on a scale
Standard Deviation 7
|
SECONDARY outcome
Timeframe: Immediate post interventionPopulation: Immediate post intervention Reduced numbers of participants analyzed reflect drop-outs or failure to fully complete questionnaires during follow-up, with inclusion only of participants having accurate and appropriate data.
Psychometric score from self-report questionnaire Scale range is 2-27. Lower values represent better outcome, and higher values represent worse outcome..
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=39 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=38 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Perceived Stress
|
10 units on a scale
Standard Deviation 6
|
14 units on a scale
Standard Deviation 8
|
SECONDARY outcome
Timeframe: 3 months post interventionPopulation: 3 months post intervention Reduced numbers of participants analyzed reflect drop-outs or failure to fully complete questionnaires during follow-up,with inclusion only of participants having accurate and appropriate data.
Psychometric score from self-report questionnaire Scale range is 9 to 60. Lower values represent better outcome, and higher values represent worse outcome..
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=38 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=38 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Depression/Dejection
|
20 units on a scale
Standard Deviation 6
|
24 units on a scale
Standard Deviation 11
|
SECONDARY outcome
Timeframe: 6 months post interventionPopulation: 6 months post intervention, from ECG recordings during mental stress tasks Reduced numbers of participants analyzed reflect drop-outs or non-diagnostic recordings for HRV analyses during follow-up, with inclusion only of participants having accurate and appropriate data.
Heart Rate Variability measure of cardiac autonomic activity, believed to reflect a combination of cardiac sympathetic and parasympathetic activity. Data are derived from ambulatory ECG recordings during serial mental stress testing (math and anger-recall tasks) using a General Electric MARS Holter analysis system. Time series are created from beat-to-beat intervals, from which frequency domain measures are calculated. Low frequency heart rate variability correlates with cardiac sympathetic and parasympathetic activity. Increased sympathetic activity and/or decreased parasympathetic activity occur in this study population at high risk for cardiac arrhythmia. Normalized units are used, reflecting percentage of total frequency power.
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=17 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=23 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Low Frequency Heart Rate Variability
|
59 percentage of spectral power
Standard Deviation 19
|
70 percentage of spectral power
Standard Deviation 21
|
SECONDARY outcome
Timeframe: 6 months post interventionPopulation: Reduced participant numbers reflect drop-outs and exclusion of participants with non-diagnostic recordings for HRV analyses, with inclusion only of participants having accurate and appropriate data.
Heart Rate Variability measure of Cardiac Parasympathetic activity. Data are derived from ambulatory ECG recordings during serial mental stress testing (math and anger-recall tasks) using a General Electric MARS Holter analysis system. Time series are created from beat-to-beat intervals, from which frequency domain measures are calculated. Increased High Frequency heart rate variability correlates with increased cardiac parasympathetic activity. Normalized units are used, reflecting percentage of total frequency power.
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=17 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=23 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
High Frequency Heart Rate Variability
|
41 percentage of spectral power
Standard Deviation 19
|
26 percentage of spectral power
Standard Deviation 16
|
SECONDARY outcome
Timeframe: 6 months post interventionPopulation: Reduced numbers of participants analyzed reflect drop-outs or non-diagnostic recordings for heart rate variability analyses during follow-up, with inclusion only of participants having accurate and appropriate data. Data are shown for Ratios of Low and High Frequency power shown above.
Heart Rate Variability measure of cardiac autonomic activity Data are derived from ambulatory ECG recordings during serial mental stress testing (math and anger-recall tasks) using a General Electric MARS Holter analysis system. Time series are created from beat-to-beat intervals, from which frequency domain measures are calculated. Decreased Low/High Frequency ratio reflects Increased High Frequency heart rate variability which correlates with increased cardiac parasympathetic activity, which may be beneficial in this patient population. Normalized units are used, reflecting percentage of total frequency power.
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=17 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=23 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Low Frequency/High Frequency Ratio of Heart Rate Variability
|
1.99 Ratio
Standard Deviation 1.47
|
4.01 Ratio
Standard Deviation 3.26
|
SECONDARY outcome
Timeframe: 6 months post interventionPopulation: Cardioverter-defibrillator interrogation data between 3 and 6 months post intervention
Cardioverter-Defibrillator therapies for treatment of serious ventricular arrhythmia
Outcome measures
| Measure |
Cognitive Behavioral Stress Management
n=38 Participants
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=33 Participants
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Cardioverter-DefibrillatorTherapies
|
0 percentage of participants
|
6 percentage of participants
|
Adverse Events
Cognitive Behavioral Stress Management
Patient Education
Serious adverse events
| Measure |
Cognitive Behavioral Stress Management
n=56 participants at risk
10 week program of Cognitive Behavioral Stress Management (CBSM) group sessions
Cognitive Behavioral Stress Management (CBSM): 10 week program of weekly CBSM therapy group sessions
|
Patient Education
n=47 participants at risk
10 week program of once weekly Patient Education group sessions
Patient Education: 10 week program of "Patient Education" group sessions, involving presentations of educational materials relating to heart disease.
|
|---|---|---|
|
Cardiac disorders
Death
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Atrial flutter
|
3.6%
2/56 • Number of events 2 • 6 to 12 months, from enrollment to study completion
|
0.00%
0/47 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 2 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Heart Failure
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Dizziness
|
1.8%
1/56 • Number of events 2 • 6 to 12 months, from enrollment to study completion
|
4.3%
2/47 • Number of events 2 • 6 to 12 months, from enrollment to study completion
|
|
Cardiac disorders
Implantable Defibrillator malfunction
|
3.6%
2/56 • Number of events 3 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Gastrointestinal disorders
Diverticulitis
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Gastrointestinal disorders
Esophageal stricture
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
|
Vascular disorders
Carotid artery disease
|
1.8%
1/56 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
0.00%
0/47 • 6 to 12 months, from enrollment to study completion
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
3.6%
2/56 • Number of events 2 • 6 to 12 months, from enrollment to study completion
|
0.00%
0/47 • 6 to 12 months, from enrollment to study completion
|
|
Respiratory, thoracic and mediastinal disorders
Nasal polyps
|
1.8%
1/56 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
0.00%
0/47 • 6 to 12 months, from enrollment to study completion
|
|
Vascular disorders
Cerebrovascular Disease
|
0.00%
0/56 • 6 to 12 months, from enrollment to study completion
|
2.1%
1/47 • Number of events 1 • 6 to 12 months, from enrollment to study completion
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place