Adverse Drug Event, Aging, Anticholinergic Adverse Reaction, Benzodiazepine Sedative Adverse Reaction
Conditions
Keywords
Benzodiazepine, Sedative hypnotic, Overprescribing, Anticholinergic
Brief summary
Prescribing of potentially unsafe medications for older adults is extremely common; benzodiazepines and sedative hypnotics are, for example, key drug classes frequently implicated in adverse health consequences for vulnerable older adults, such as confusion or sedation, leading to hospitalizations, falls, and fractures. Fortunately, most of these consequences are preventable. Physicians' lack of awareness of alternatives, ambiguous practice guidelines, and perceived pressure from patients or caregivers are among the reasons why these drugs are used more than might be optimal. Reducing inappropriate use of these drugs may be achieved through decision support tools for providers that are embedded in electronic health record (EHR) systems. While EHR strategies are widely used to support the informational needs of providers, these tools have demonstrated only modest effectiveness at improving prescribing. The effectiveness of these tools could be enhanced by leveraging principles of behavioral economics and related sciences.
Detailed description
This is a cluster randomized control trial (RCT) to evaluate whether newly designed EHR-based tools designed using behavioral principles reduce inappropriate prescribing and adverse outcomes among older adults. This study will be conducted in outpatient primary care practices at Mass General Brigham (MGB), specifically Massachusetts General Hospital. MGB has a fully functional EHR, EpicCare, that supports computerized ordering of medications. MGB is comprised of 150 outpatient practices with over 1,800 physicians. In this trial, approximately 190 primary care providers at MGH will be randomized to receive usual care or an active intervention. Providers randomized to one of the 2 selected treatment arms will receive an EHR tool to guide their care of eligible patients. They will be followed for 12 months. Providers randomized to usual care will receive no newly-designed EHR tool. Providers will receive these EHR tools for their patients who meet the following criteria: 1) older adults (aged 65 years or more), and 2) who have been prescribed at least 90 pills of benzodiazepine or sedative hypnotic or have been prescribed at least one active orders of at least 90 pills of two different anticholinergics in the last 180 days.
Interventions
Once the order entry or open encounter alert displays, the provider will have the option to schedule a follow-up message that will be sent 4 weeks after the alert is triggered
OTHERPre-commitment
A two-staged pre-commitment electronic health record alert will be used. In the 1st alert, the providers will be prompted to discuss risks of these high-risk medications and share a handout about the risks with their patients, at their own discretion. The second alert will be either an order entry or open encounter alert, depending on the arm the provider is assigned to.
OTHEREnhanced Alert
An enhanced alert (known as a Best Practice Advisory \[BPA\]) will appear on the provider's electronic health record screen and will contain several standard components such as information about why the medication is dangerous for their patient and an order set that will allow providers to order a gradual dose taper for their patient, order alternative medications, place a referral to a behavioral health specialist, provide instructions on how to make lifestyle modifications to improve patient symptoms, and add patient instructions for how to gradually taper off benzodiazepines and sedative hypnotics, as applicable.
Sponsors
Massachusetts General Hospital
National Institutes of Health (NIH)
National Institute on Aging (NIA)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary care provider at Mass General Brigham Providers will receive these EHR tools for their patients who meet the following criteria: 1. older adults (aged 65 years or more) 2. who have been prescribed at least 90 pills of benzodiazepine or sedative hypnotic in the last 180 days. Outcomes will be measured on the patient level.
Exclusion criteria
* N/A
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Inappropriate Prescribing | Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant | This outcome is measured as a composite of 1) discontinuation of study high-risk medications (i.e., active discontinuation or lack of an order during follow-up) or 2) ordering a dose taper (for benzodiazepine or sedative hypnotics) using EHR data by the primary care provider included in the study arm. If any of these actions occurred by the primary care provider, then the patient was considered to have had a change in prescribing (i.e., a reduction in inappropriate prescribing). This outcome was measured as a binary outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quantity of High-risk Medication Prescribed | Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant | This outcome is measured on the patient level as the number of pills of high-risk medications prescribed to patients by providers over the follow-up, measured within the EHR system. This outcome was measured as a continuous outcome. |
| Cumulative Lorazepam Milligram Equivalents Prescribed | Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant | This outcome is measured on the patient level as the number of lorazepam milligram equivalents of benzodiazepine and sedative hypnotic (Z-drug) prescribed to patients by providers over the follow-up, measured within the EHR system. This outcome was measured as a continuous outcome. |
Countries
United States
Participant flow
Recruitment details
Primary care providers were cluster-randomized to these arms based on data available from the electronic health record and were not recruited directly for the trial or evaluated for effectiveness outcomes. Patients were also not intervened upon nor directly enrolled into the study. As such, we received a waiver of informed consent for participation.
Pre-assignment details
Primary care providers were identified from electronic health record data and cluster randomized to a study arm. Patients who sought care from these primary care providers were identified based on electronic health record data for analyses and are classified as the participants. Providers were not assessed for effectiveness outcomes.
Participants by arm
| Arm | Count |
|---|---|
| No Alert (Usual Care) Providers randomized to usual care will receive no intervention. | 396 |
| Open Encounter + Pre-commitment There will be an enhanced EHR alert, known as a Best Practice Advisory \[BPA\], which will appear on each provider's EHR screen. We will also test a two-staged pre-commitment BPA in which the providers are prompted to discuss risks of the high-risk medications and share a handout about risks with their patients.
Pre-commitment: A two-staged pre-commitment electronic health record alert will be used. In the 1st alert, the providers will be prompted to discuss risks of these high-risk medications and share a handout about the risks with their patients, at their own discretion. The second alert will be either an order entry or open encounter alert, depending on the arm the provider is assigned to.
Enhanced Alert: An enhanced alert (known as a Best Practice Advisory \[BPA\]) will appear on the provider's electronic health record screen and will contain several standard components such as information about why the medication is dangerous for their patient and an order set that will allow providers to order a gradual dose taper for their patient, order alternative medications, place a referral to a behavioral health specialist, provide instructions on how to make lifestyle modifications to improve patient symptoms, and add patient instructions for how to gradually taper off benzodiazepines and sedative hypnotics, as applicable. | 394 |
| Open Encounter + Follow-up Booster There will be an enhanced EHR alert, known as a Best Practice Advisory \[BPA\], which will appear on each provider's EHR screen. We will add a boostering option in the enhanced BPA, which is a provider-directed option for a follow-up in-basket message sent 4 weeks after the BPA is triggered.
Follow-up booster Alert: Once the order entry or open encounter alert displays, the provider will have the option to schedule a follow-up message that will be sent 4 weeks after the alert is triggered
Enhanced Alert: An enhanced alert (known as a Best Practice Advisory \[BPA\]) will appear on the provider's electronic health record screen and will contain several standard components such as information about why the medication is dangerous for their patient and an order set that will allow providers to order a gradual dose taper for their patient, order alternative medications, place a referral to a behavioral health specialist, provide instructions on how to make lifestyle modifications to improve patient symptoms, and add patient instructions for how to gradually taper off benzodiazepines and sedative hypnotics, as applicable. | 356 |
| Total | 1,146 |
Baseline characteristics
| Characteristic | No Alert (Usual Care) | Open Encounter + Pre-commitment | Open Encounter + Follow-up Booster | Total |
|---|---|---|---|---|
| Age, Continuous | 73.5 years STANDARD_DEVIATION 6.4 | 73.7 years STANDARD_DEVIATION 6.5 | 73.6 years STANDARD_DEVIATION 6.5 | 73.6 years STANDARD_DEVIATION 6.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 21 Participants | 26 Participants | 33 Participants | 80 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 364 Participants | 348 Participants | 306 Participants | 1018 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 11 Participants | 20 Participants | 17 Participants | 48 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 12 Participants | 11 Participants | 13 Participants | 36 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 14 Participants | 10 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 12 Participants | 15 Participants | 25 Participants | 52 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 10 Participants | 6 Participants | 8 Participants | 24 Participants |
| Race (NIH/OMB) White | 350 Participants | 347 Participants | 298 Participants | 995 Participants |
| Sex: Female, Male Female | 275 Participants | 276 Participants | 248 Participants | 799 Participants |
| Sex: Female, Male Male | 121 Participants | 118 Participants | 108 Participants | 347 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 14 / 396 | 7 / 394 | 6 / 356 |
| other Total, other adverse events | 0 / 396 | 0 / 394 | 0 / 356 |
| serious Total, serious adverse events | 0 / 396 | 0 / 394 | 0 / 356 |
Outcome results
Primary
Change in Inappropriate Prescribing
This outcome is measured as a composite of 1) discontinuation of study high-risk medications (i.e., active discontinuation or lack of an order during follow-up) or 2) ordering a dose taper (for benzodiazepine or sedative hypnotics) using EHR data by the primary care provider included in the study arm. If any of these actions occurred by the primary care provider, then the patient was considered to have had a change in prescribing (i.e., a reduction in inappropriate prescribing). This outcome was measured as a binary outcome.
Time frame: Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant
Population: Patients who met eligibility criteria for inclusion in the analysis (adults ≥65 years, who were prescribed ≥90 pills of benzodiazepine, strongly anticholinergic medication, or sedative hypnotic in the last 180 days and had an office or telemedicine visit with a primary care provider who was assigned to a study arm), as measured from EHR system data.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| No Alert (Usual Care) | Change in Inappropriate Prescribing | 106 Participants |
| Open Encounter + Pre-commitment | Change in Inappropriate Prescribing | 145 Participants |
| Open Encounter + Follow-up Booster | Change in Inappropriate Prescribing | 122 Participants |
Comparison: Outcomes were evaluated using generalized estimating equations with a log link and binary errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 0.00295% CI: [1.1, 1.78]Regression, Logistic
Comparison: Outcomes were evaluated using generalized estimating equations with a log link and binary errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 0.03995% CI: [1.01, 1.57]Regression, Logistic
Secondary
Cumulative Lorazepam Milligram Equivalents Prescribed
This outcome is measured on the patient level as the number of lorazepam milligram equivalents of benzodiazepine and sedative hypnotic (Z-drug) prescribed to patients by providers over the follow-up, measured within the EHR system. This outcome was measured as a continuous outcome.
Time frame: Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant
Population: Patients who met eligibility criteria for inclusion in the analysis (adults ≥65 years, who were prescribed ≥90 pills of benzodiazepine, strongly anticholinergic medication, or sedative hypnotic in the last 180 days and had an office or telemedicine visit with a primary care provider who was assigned to a study arm), as measured from EHR system data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Alert (Usual Care) | Cumulative Lorazepam Milligram Equivalents Prescribed | 238.7 lorazepam milligram equivalents | Standard Deviation 461.6 |
| Open Encounter + Pre-commitment | Cumulative Lorazepam Milligram Equivalents Prescribed | 220.1 lorazepam milligram equivalents | Standard Deviation 413.9 |
| Open Encounter + Follow-up Booster | Cumulative Lorazepam Milligram Equivalents Prescribed | 259.7 lorazepam milligram equivalents | Standard Deviation 601.3 |
Comparison: Outcomes were evaluated using generalized estimating equations with an identity link and normally-distributed errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 0.65795% CI: [-74.5, 47]Regression, Linear
Comparison: Outcomes were evaluated using generalized estimating equations with an identity link and normally-distributed errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 0.69695% CI: [-60.7, 91]Regression, Linear
Secondary
Quantity of High-risk Medication Prescribed
This outcome is measured on the patient level as the number of pills of high-risk medications prescribed to patients by providers over the follow-up, measured within the EHR system. This outcome was measured as a continuous outcome.
Time frame: Each patient was assessed beginning from the date in which they were identified as eligible (i.e., meeting the inclusion criteria) until the end of a 16-month follow-up; the outcome time frame varied by participant
Population: Patients who met eligibility criteria for inclusion in the analysis (adults ≥65 years, who were prescribed ≥90 pills of benzodiazepine, strongly anticholinergic medication, or sedative hypnotic in the last 180 days and had an office or telemedicine visit with a primary care provider who was assigned to a study arm), as measured from EHR system data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Alert (Usual Care) | Quantity of High-risk Medication Prescribed | 398.6 Number of pills | Standard Deviation 439.4 |
| Open Encounter + Pre-commitment | Quantity of High-risk Medication Prescribed | 422.5 Number of pills | Standard Deviation 470.9 |
| Open Encounter + Follow-up Booster | Quantity of High-risk Medication Prescribed | 437.9 Number of pills | Standard Deviation 481.6 |
Comparison: Outcomes were evaluated using generalized estimating equations with an identity link and normally-distributed errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 0.38695% CI: [-36.6, 94.6]Regression, Linear
Comparison: Outcomes were evaluated using generalized estimating equations with an identity link and normally-distributed errors, adjusting for provider-level clustering and Holm-Bonferroni multiple comparisons.p-value: 27295% CI: [-29.9, 106.1]Regression, Linear