Machine-Learning Prediction and Reducing Overdoses With EHR Nudges (mPROVEN)

June 16, 2026 updated by: Walid Gellad, University of Pittsburgh

The goal of this cluster randomized clinical trial is to test a clinician-targeted behavioral nudge intervention in the Electronic Health Record (EHR) for patients who are identified by a machine-learning based risk prediction model as having an elevated risk for an opioid overdose.

The clinical trial will evaluate the effectiveness of providing a flag in the EHR to identify individuals at elevated risk with and without behavioral nudges/best practice alerts (BPAs) as compared to usual care by primary care clinicians.

The primary goals of the study are to improve opioid prescribing safety and reduce overdose risk.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In response to the opioid overdose crisis, health systems have instituted multiple interventions to reduce patient risk, including decreasing unsafe opioid prescribing among high-risk patients and dispensing naloxone. However, these interventions face two key challenges. First, there are limited and poorly performing tools to identify who is truly at risk of overdose, leading to burdensome interventions targeting an overly broad population or missing key high-risk individuals. Second, even with more accurate identification of high-risk patients, highly effective strategies to change clinician behavior remain limited. Common cognitive biases may underlie clinicians' lack of response to risk factors for overdose.

This project aims to address both of these limitations by combining more accurate risk prediction tools to identify those at elevated risk of opioid overdose with novel "nudge" interventions based on principles of behavioral economics that have been shown to address cognitive biases and change prescribing behavior. The primary hypothesis is that high-risk patients in primary care practices randomized to the elevated-risk flag + nudge intervention will have safer prescribing compared to usual care.

Study Type

Interventional

Enrollment (Estimated)

1350

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Lead Research Program Coordinator, CP3
  • Phone Number: (412) 692-4889
  • Email: cp3@pitt.edu

Study Locations

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Recruiting
        • University of Pittsburgh
        • Principal Investigator:
          • Walid F Gellad, MD, MPH

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Received an opioid prescription within the past year
  • Age 18 years or older at the time of the opioid prescription
  • At least one visit to an internal medicine or family care practice within the past year

Exclusion Criteria:

  • Diagnosis of malignant cancer within the past year
  • Enrollment in hospice care

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Health Services Research
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Usual Care
Patients in the practices randomized to the Usual Care arm will receive standard care practice without change.
Behavioral: Usual Care
Patients in the practices randomized to the Usual Care arm will receive standard care practice without change.
Experimental: EHR-Embedded Elevated-Risk Flag
An elevated-risk flag will be embedded in the EHR and prominently displayed in the chart during encounters for patients identified as having elevated-risk for opioid overdose.
Behavioral: EHR-Embedded Elevated-Risk Flag
Clinicians seeing patients at elevated predicted risk will see a flag on the EHR 'storyboard' during in person or telephone encounters indicating the patient is at elevated predicted risk of opioid overdose. The clinician will have the option of including this information into their decision-making process when providing care. There will be no best practice alerts/behavioral nudges in this arm.
Experimental: EHR-Embedded Elevated-Risk Flag with Behavioral Nudges
An elevated-risk flag will be embedded in the EHR and prominently displayed in the chart during encounters for patients identified as having elevated-risk for opioid overdose. This flag will be combined with a set of best practice alerts/behavioral nudges that will trigger when certain conditions are met during encounters with elevated-risk patients.
Behavioral: EHR-Embedded Elevated-Risk Flag with Behavioral Nudges

Clinicians seeing patients at elevated predicted risk for opioid overdose will see a flag on the EHR storyboard indicating that the patient is at elevated predicted risk.

Clinicians will also receive up to 4 best practice alerts/behavioral nudges during an in-person or telephone primary care encounter with elevated risk patients when certain requirements are met: 1) if the patient does not have an active naloxone prescription on their medication list, the clinicians will receive an active choice alert during any medication ordering to encourage naloxone prescription; 2) if the patient's opioid dosage is >50 MME, OR they are ordered a new opioid prescription, OR they have an overlapping opioid and benzodiazepine prescription order, the clinicians will receive an accountable justification alert when the relevant order is entered.

Other Names:
  • EHR-Embedded Elevated-Risk Flag with Best Practice Alerts (BPAs)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prescribing Practices Composite Score
Time Frame: Assessed at 4 months following study enrollment (i.e., at 4 months after the first encounter in the study period. An encounter refers to the 1st primary care visit for a patient enrolled in the study.)

This outcome measures a composite of three prescribing practices associated with a reduced risk of opioid overdose. Each of the three is assigned a value of one point, with the composite score ranging from 0 to 3:

  1. Naloxone prescription: Evidence of a prescription for naloxone.
  2. Opioid dosage < 50 morphine milligram equivalents (MME) per day: No prescriptions exceeding 50 MME/day during the measurement period.
  3. No opioid and benzodiazepine overlap: No concurrent prescriptions for opioids and benzodiazepines.

The composite score will be treated as a 3-point ordinal measure reflecting adherence to these prescribing practices.
Assessed at 4 months following study enrollment (i.e., at 4 months after the first encounter in the study period. An encounter refers to the 1st primary care visit for a patient enrolled in the study.)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prescribing Practices Composite Score--6 Month Measure
Time Frame: Assessed at 6 months following study enrollment (i.e., at 6 months after the first encounter in the study period. An encounter refers to the 1st primary care visit for a patient enrolled in the study.)
This outcome measures a composite of three prescribing practices associated with a reduced risk of opioid overdose. Each of the three is assigned a value of one point, with the composite score ranging from 0 to 3: 1. Naloxone prescription: Evidence of a prescription for naloxone. 2. Opioid dosage < 50 morphine milligram equivalents (MME) per day: No prescriptions exceeding 50 MME/day during the measurement period. 3. No opioid and benzodiazepine overlap: No concurrent prescriptions for opioids and benzodiazepines. The composite score will be treated as a 3-point ordinal measure reflecting adherence to these prescribing practices.
Assessed at 6 months following study enrollment (i.e., at 6 months after the first encounter in the study period. An encounter refers to the 1st primary care visit for a patient enrolled in the study.)
Active Naloxone Prescription
Time Frame: Assessed at 4 & 6 months after study enrollment by reviewing data from 12 months preceding index date (i.e., at 4 & 6 months after enrollment). An active naloxone prescription is recorded if one exists at any point during the year before the index date.
The presence of an active naloxone prescription, determined by evidence of a naloxone order, a naloxone fill, or both.
Assessed at 4 & 6 months after study enrollment by reviewing data from 12 months preceding index date (i.e., at 4 & 6 months after enrollment). An active naloxone prescription is recorded if one exists at any point during the year before the index date.
Average Daily Opioid Dosage > 50 MME
Time Frame: Assessed at 4 and 6 months after study enrollment, based on the average daily MME calculated over the 7 days preceding the index date (i.e., 4 and 6 months after enrollment).
The average daily opioid dosage, calculated in morphine milligram equivalents (MME), is evaluated using prescription fills data as the primary source. If fills data are unavailable, prescription orders data will be used. This measure reflects whether the average daily MME exceeds 50 during the specified time period.
Assessed at 4 and 6 months after study enrollment, based on the average daily MME calculated over the 7 days preceding the index date (i.e., 4 and 6 months after enrollment).
Overlapping Opioid Benzodiazepine Prescriptions
Time Frame: Assessed at 4 and 6 months after study enrollment, based on overlap occurring on the index date (i.e., 4 and 6 months after enrollment) or within the 28 days preceding the index date.

This outcome evaluates overlapping opioid and benzodiazepine use, determined by the following criteria:

(A) Active overlap on the index date: Both an opioid and a benzodiazepine prescription fill are active on the index date.

(B) Historical overlap: At least one opioid and one benzodiazepine prescription order within the past 28 days.

Overlap is defined as meeting any of the above.
Assessed at 4 and 6 months after study enrollment, based on overlap occurring on the index date (i.e., 4 and 6 months after enrollment) or within the 28 days preceding the index date.
Overlapping Opioid Benzodiazepine Prescriptions Where Average Daily Opioid MME > 50
Time Frame: Assessed at 4 and 6 months after study enrollment, based on overlap occurring on the index date (i.e., 4 and 6 months after enrollment) or within the 28 days preceding the index date.
This outcome evaluates the presence of overlapping opioid and benzodiazepine use where opioid MME is > 50, defined as above.
Assessed at 4 and 6 months after study enrollment, based on overlap occurring on the index date (i.e., 4 and 6 months after enrollment) or within the 28 days preceding the index date.
Emergency Department or Inpatient Visits
Time Frame: Assessed at 4 and 6 months after study enrollment, based on visits occurring within the 30 days prior to the index date (i.e., 4 and 6 months after enrollment).
This outcome measures the occurrence of any emergency department (ED) or inpatient visit during the specified time period.
Assessed at 4 and 6 months after study enrollment, based on visits occurring within the 30 days prior to the index date (i.e., 4 and 6 months after enrollment).
Emergency Department or Inpatient Visits for Overdose
Time Frame: Assessed at 4 and 6 months after study enrollment, based on visits occurring within the 30 days prior to the index date (i.e., 4 and 6 months after enrollment).
This outcome measures the occurrence of any emergency department (ED) or inpatient visit specifically attributed to an overdose during the specified time period.
Assessed at 4 and 6 months after study enrollment, based on visits occurring within the 30 days prior to the index date (i.e., 4 and 6 months after enrollment).

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pittsburgh

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: Walid F Gellad, MD, MPH, University of Pittsburgh Center for Pharmaceutical Policy and Prescribing

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 10, 2025

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

February 1, 2027

Study Registration Dates

First Submitted

January 31, 2025

First Submitted That Met QC Criteria

January 31, 2025

First Posted (Actual)

February 3, 2025

Study Record Updates

Last Update Posted (Actual)

June 17, 2026

Last Update Submitted That Met QC Criteria

June 16, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY22040068
  • R01DA044985-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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