Trial Outcomes & Findings for AESOPS Trial 2 (AESOPS-2): Availability of Opioid Harm (NCT NCT04758637)
NCT ID: NCT04758637
Last Updated: 2025-10-07
Results Overview
The primary outcome is the change in daily average number of 5 morphine milligram equivalent (MME) pill counts ordered by clinicians during the last week of baseline (week 26) and the last week of the intervention period (week 53) letter intervention.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
61 participants
Primary outcome timeframe
13 months (6 months pre-intervention, 30-day washout period, 6 months post-intervention)
Results posted on
2025-10-07
Participant Flow
Prescriber did or did not receive the letter based on the randomization assignment (intervention or control) of the overdose victim. Clinician prescribing data was collected during the study timeframe.
Patients who experienced an opioid overdose were randomized to either the letter intervention (fatal or non fatal overdose) or control; however, patients were not considered enrolled in the study. We analyze how the prescribing behavior of clinicians who had prescribed opioids to these patients changed pre-to-post intervention.
Participant milestones
| Measure |
Nonfatal Control Group
Physicians in the nonfatal control group will receive no notification of their patient's nonfatal overdose.
|
Non Fatal Overdose Notification Group
Non Fatal Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
Fatal Overdose Notification: We will identify overdoses from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
19
|
20
|
11
|
11
|
|
Overall Study
Patient Overdose Victims
|
16
|
14
|
10
|
10
|
|
Overall Study
COMPLETED
|
19
|
19
|
11
|
11
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
Nonfatal Control Group
Physicians in the nonfatal control group will receive no notification of their patient's nonfatal overdose.
|
Non Fatal Overdose Notification Group
Non Fatal Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
Fatal Overdose Notification: We will identify overdoses from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
|---|---|---|---|---|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Age data not collected.
Baseline characteristics by cohort
| Measure |
Non Fatal Control Group
n=19 Participants
Physicians in the non fatal control group will receive no notification of their patient's nonfatal overdose.
|
Non Fatal Overdose Notification Group
n=20 Participants
Non Fatal Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased or surviving patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
n=11 Participants
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
n=11 Participants
Fatal Overdose Notification: We will identify overdoses from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased or surviving patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Age
|
0 Participants
Age data not collected.
|
0 Participants
Age data not collected.
|
0 Participants
Age data not collected.
|
0 Participants
Age data not collected.
|
0 Participants
Age data not collected.
|
|
Sex/Gender, Customized
Female
|
9 Participants
n=19 Participants
|
11 Participants
n=20 Participants
|
5 Participants
n=11 Participants
|
2 Participants
n=11 Participants
|
27 Participants
n=61 Participants
|
|
Sex/Gender, Customized
Male
|
8 Participants
n=19 Participants
|
9 Participants
n=20 Participants
|
6 Participants
n=11 Participants
|
9 Participants
n=11 Participants
|
32 Participants
n=61 Participants
|
|
Sex/Gender, Customized
Missing
|
2 Participants
n=19 Participants
|
0 Participants
n=20 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=11 Participants
|
2 Participants
n=61 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Region of Enrollment
United States
|
19 Participants
n=19 Participants
|
20 Participants
n=20 Participants
|
11 Participants
n=11 Participants
|
11 Participants
n=11 Participants
|
61 Participants
n=61 Participants
|
PRIMARY outcome
Timeframe: 13 months (6 months pre-intervention, 30-day washout period, 6 months post-intervention)Population: Participating clinicians from Northwestern Medicine and AltaMed who prescribed an opioid during the study period
The primary outcome is the change in daily average number of 5 morphine milligram equivalent (MME) pill counts ordered by clinicians during the last week of baseline (week 26) and the last week of the intervention period (week 53) letter intervention.
Outcome measures
| Measure |
Non Fatal Control Group
n=19 Participants
Physicians in the non fatal control group will receive no notification of their patient's nonfatal overdose.
|
Non Fatal Overdose Notification Group
n=19 Participants
Non Fatal Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
n=11 Participants
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
n=11 Participants
Fatal Overdose Notification: We will identify overdoses from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
|---|---|---|---|---|
|
Change in Daily Average Number of 5 MME Pill Counts
|
-3.73 Difference in estimated mean pill counts
Interval -6.0 to -0.79
|
3.89 Difference in estimated mean pill counts
Interval 1.61 to 7.58
|
9.8 Difference in estimated mean pill counts
Interval 3.86 to 18.9
|
-4.85 Difference in estimated mean pill counts
Interval -6.24 to -3.11
|
SECONDARY outcome
Timeframe: 13 months (6 months pre-intervention, 30-day washout period, 6 months post-intervention)The change in the clinician-level, pre-to-post mean proportion of high dose (=\> 50 MME) patient visits by study arm. The numerator is whether a patient visit was =\> 50 MME, and the denominator is the number of opioids. We quantified this measure using logistic regression. Higher dose prescriptions are not recommended and are associated with the potential for greater patient harm.
Outcome measures
| Measure |
Non Fatal Control Group
n=19 Participants
Physicians in the non fatal control group will receive no notification of their patient's nonfatal overdose.
|
Non Fatal Overdose Notification Group
n=19 Participants
Non Fatal Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
n=11 Participants
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
n=11 Participants
Fatal Overdose Notification: We will identify overdoses from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
|---|---|---|---|---|
|
Change in Clinician-level, Pre-to-post Mean Proportion of High Dose (=> 50 MME) Patient Visits
|
0.004 proportion of high dose patient visits
Interval -0.012 to 0.045
|
0.014 proportion of high dose patient visits
Interval -0.001 to 0.098
|
0.01 proportion of high dose patient visits
Interval -0.06 to 0.15
|
-0.09 proportion of high dose patient visits
Interval -0.12 to 0.07
|
Adverse Events
Non Fatal Control Group
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Non Fatal Overdose Notification Group
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Fatal Control Group
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Fatal Overdose Notification Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Non Fatal Control Group
n=861 participants at risk
Physicians in the non fatal control group will receive no notification of their patient's non fatal overdose.
|
Non Fatal Overdose Notification Group
n=973 participants at risk
The overdose notifications will alert prescribers to the patient's opioid-related non fatal overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses.
Overdose Notification: We will identify overdoses from insurance claims data linked to emergency departments. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a non-fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the surviving patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
Fatal Control Group
n=524 participants at risk
Physicians in the fatal control group will receive no notification of their patient's fatal overdose.
|
Fatal Overdose Notification Group
n=801 participants at risk
The fatal overdose notifications will alert prescribers to the patient's fatal opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses.
Overdose Notification: We will identify overdose deaths from state vital records. We will use electronic health record data to identify prescriptions of scheduled drug to patients who experienced a fatal overdose within the health system. If randomized to the overdose notification group, physicians who prescribed the controlled substances to the deceased patient in the year prior to their overdose will be informed of the overdose via letter. The letters will alert prescribers to the patient's opioid-related overdose, recommend the use of the state-level PDMP, and list evidence-based interventions to lower opioid-related overdoses. The letters will increase the salience and availability of opioid-related harms, which may cause clinicians to be more wary of a future overdose when prescribing opioids, benzodiazepines, muscle relaxants, or sedative-hypnotics.
|
|---|---|---|---|---|
|
Nervous system disorders
Emergency Department or Hospitalization for Opioid Withdrawal
|
0.12%
1/861 • Number of events 1 • 6 months
Adverse event collection is based on the patients of randomized clinicians, not the clinicians themselves. Deaths and adverse events were not collected for clinicians.
|
0.10%
1/973 • Number of events 1 • 6 months
Adverse event collection is based on the patients of randomized clinicians, not the clinicians themselves. Deaths and adverse events were not collected for clinicians.
|
0.19%
1/524 • Number of events 1 • 6 months
Adverse event collection is based on the patients of randomized clinicians, not the clinicians themselves. Deaths and adverse events were not collected for clinicians.
|
0.00%
0/801 • 6 months
Adverse event collection is based on the patients of randomized clinicians, not the clinicians themselves. Deaths and adverse events were not collected for clinicians.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place