Alzheimer Disease
Conditions
Keywords
Deprescribing, Dementia, Medication Safety
Brief summary
Potentially inappropriate prescribing includes the use of medications that may no longer be necessary or that may increase the risk of harm. Inappropriate prescribing can increase the overall symptom burden, and negatively affect health-related quality of life and function. The inappropriate prescription of certain drug categories such as sedative/hypnotics, antipsychotics, and strong anticholinergic agents poses particular risks for older adults, and may be more common among those with Alzheimer's disease and Alzheimer's disease- related dementias (AD/ADRD) due to a higher prevalence of multimorbidity and more frequent prescription of five or more medications. The D-PRESCRIBE-AD (Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer's Disease) study will test a health plan-based intervention using the NIH Collaboratory's Distributed Research Network, which employs the Food and Drug Administration (FDA) Sentinel System infrastructure. The overarching goal of this randomized controlled trial is to assess the effect of a patient/caregiver- centered, multifaceted educational intervention on potentially inappropriate prescribing in patients with AD/ADRD. The research hypothesis is that education on inappropriate prescribing among patients/caregivers and their providers can reduce medication-related morbidity in patients with AD/ADRD and improve medication safety for this vulnerable population. The study population will include community-dwelling patients with AD/ADRD, identified based on diagnoses codes of AD/ADRD or use of a medication for Alzheimer's Disease, who have evidence of potentially inappropriate prescribing the three drug classes above. The trial will evaluate the effect of educational interventions designed to spur patient/caregiver-provider communication about medication safety (versus usual care) on the proportion of patients with inappropriate prescribing, the primary outcome of this study. The trial will be conducted in two large, national health plans.
Interventions
OTHEREducational Materials
Educational materials on inappropriate prescribing and deprescribing.
Sponsors
National Institute on Aging (NIA)
Harvard Pilgrim Health Care
Humana Co.Ltd.
Elevance Health
HealthCore, Inc.
University of Massachusetts, Worcester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
The study design will be a prospective, randomized, open-label educational intervention trial with three arms: (1) a combined patient/caregiver and provider educational intervention; (2) a provider only educational intervention; and (3) usual care.
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient Inclusion Criteria: 1. Diagnosis of AD/ADRD based on a combination of AD/ADRD codes or treatment with a pharmacologic therapy used for AD (e.g., donepezil, rivastigmine, galantamine, and memantine) in the 365 days prior to or on cohort entry date. 2. Evidence of potentially inappropriate prescribing with antipsychotics, sedative-hypnotics, and strong anticholinergics within the past 3 months 3. Age ≥50 years of age as of cohort entry date 4. Continuous medical and pharmacy insurance coverage for at least the prior year Patient
Exclusion criteria
1. Evidence of residing in a nursing home or skilled nursing facility or receiving palliative care. 2. Incomplete/missing prescriber ID or incomplete contact information for either patient or prescribing provider. 3. On do not contact list
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Dispensing of Inappropriate Medication Prescription | 6 months | The primary outcome will be defined as dispensing of the targeted inappropriate prescription class from day 91 to day 270 during the 6 months observation period following receipt of intervention, or days 91-270. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Polypharmacy | 6 months | Polypharmacy was defined as being dispensed 5 or more unique prescription medications, assessed on the last day of the 6-month study observation period. Polypharmacy was based on medications administered by any route (including topical or ocular medications) and included AD medications and the 3 medication classes targeted for deprescribing. A combination drug was considered a single medication for the purpose of this analysis. |
| Percentage of Participants With Ambulatory Encounters | 6 months | We assessed the occurrence of any ambulatory encounter over the 6-month observation period. |
| Percentage of Participants Who Died | 6 months | We assessed all-cause inpatient mortality in all study participants (n=12,787) during the 6-month study observation period. |
| Dose Reduction | 6 months | Dose reduction was measured as the percentage of patients who achieved a reduction in the patient-specific and medication-specific mean daily dose of the medication targeted for deprescribing of 50% or more during the 6-month study observation period compared with the mean daily dose for the 6-month period immediately preceding the date of mailing of the educational materials. Mean daily dose was calculated using days of supply, dispensed quantity, and unit strength of all dispensings occurring during the 6-month period of interest (either the 6-month study observation period or the 6-month period immediately preceding the date of the mailing). |
| Percentage of Participants With Emergency Department Encounters | 6 months | We assessed the occurrence of any emergency department encounters over the 6-month observation period. |
| Percentage of Participants With Hospitalizations | 6 months | We assessed the occurrence of any hospitalizations over the 6-month observation period. |
| Percentage of Participants With Non-acute Institutional Admissions | 6 months | We assessed the occurrence of any non-acute institutional admissions over the 6-month observation period. |
| Switching Within Classes | 6 months | Switching of agents within the following targeted drug classes: sedative/ hypnotics, antipsychotics, highly anticholinergic agents. |
Countries
United States
Participant flow
Recruitment details
Patients with 1 year of health plan coverage who met the following criteria: 1\) AD/ADRD, defined as either presence of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for AD/ADRD associated with 2 different claims or as 2 dispensings for an agent used for AD in the 365 days prior to or on cohort entry; (2) age 50 or older; and (3) a dispensing of any of the 3 targeted drug classes in the 3 months prior to or on cohort entry.
Pre-assignment details
To address the potential for within-prescriber contamination, only 1 randomly selected eligible patient was randomized per prescribing clinician.
Participants by arm
| Arm | Count |
|---|---|
| Patient-Provider Both patients and providers will receive educational materials on inappropriate prescribing and deprescribing.
Educational Materials: Educational materials on inappropriate prescribing and deprescribing. | 4 |
| Provider Only Only providers will receive educational materials on inappropriate prescribing and deprescribing.
Educational Materials: Educational materials on inappropriate prescribing and deprescribing. | 4 |
| Usual Care Usual care - no intervention. | 4 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Died or disenrolled during blackout period | 239 | 278 | 273 |
| Overall Study | Removed prior to mailing | 289 | 306 | 270 |
Baseline characteristics
| Characteristic | Total | Patient-Provider | Provider Only | Usual Care |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11501 Participants | 3855 Participants | 3803 Participants | 3843 Participants |
| Age, Categorical Between 18 and 65 years | 1286 Participants | 431 Participants | 427 Participants | 428 Participants |
| Age, Continuous | 77.3 Years STANDARD_DEVIATION 9.4 | 77.4 Years STANDARD_DEVIATION 9.3 | 77.3 Years STANDARD_DEVIATION 9.4 | 77.2 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 12787 Participants | 4286 Participants | 4230 Participants | 4271 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 18 Participants | 1 Participants | 8 Participants | 9 Participants |
| Race (NIH/OMB) Asian | 84 Participants | 32 Participants | 27 Participants | 25 Participants |
| Race (NIH/OMB) Black or African American | 1341 Participants | 451 Participants | 447 Participants | 443 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 111 Participants | 40 Participants | 31 Participants | 40 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2976 Participants | 983 Participants | 1000 Participants | 993 Participants |
| Race (NIH/OMB) White | 8257 Participants | 2779 Participants | 2717 Participants | 2761 Participants |
| Region of Enrollment United States | 12787 Participants | 4286 Participants | 4230 Participants | 4271 Participants |
| Sex: Female, Male Female | 8742 Participants | 2971 Participants | 2860 Participants | 2911 Participants |
| Sex: Female, Male Male | 4045 Participants | 1315 Participants | 1370 Participants | 1360 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 51 / 4,286 | 59 / 4,230 | 51 / 4,271 |
| other Total, other adverse events | 0 / 4,286 | 0 / 4,230 | 0 / 4,271 |
| serious Total, serious adverse events | 0 / 4,286 | 0 / 4,230 | 0 / 4,271 |
Outcome results
Primary
Time to Dispensing of Inappropriate Medication Prescription
The primary outcome will be defined as dispensing of the targeted inappropriate prescription class from day 91 to day 270 during the 6 months observation period following receipt of intervention, or days 91-270.
Time frame: 6 months
Population: Modified intention to treat cohort.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Time to Dispensing of Inappropriate Medication Prescription | 76.7 Percentage of Cumulative Incidence |
| Provider Only | Time to Dispensing of Inappropriate Medication Prescription | 77.9 Percentage of Cumulative Incidence |
| Usual Care | Time to Dispensing of Inappropriate Medication Prescription | 77.5 Percentage of Cumulative Incidence |
Comparison: For the primary analysis, we combined all three targeted medication classes (antipsychotics, sedative/hypnotics, or strong anticholinergics). We calculated Kaplan-Meier curves and performed log-rank testing, and estimated hazard ratios using Cox proportional hazards modeling, censoring at death or disenrollment from the health plan, or at the end of the 6-month study observation period, whichever came first. The index date for the survival analysis was the end of the 3-month blackout period.p-value: 0.7695% CI: [0.94, 1.04]Log Rank
Secondary
Dose Reduction
Dose reduction was measured as the percentage of patients who achieved a reduction in the patient-specific and medication-specific mean daily dose of the medication targeted for deprescribing of 50% or more during the 6-month study observation period compared with the mean daily dose for the 6-month period immediately preceding the date of mailing of the educational materials. Mean daily dose was calculated using days of supply, dispensed quantity, and unit strength of all dispensings occurring during the 6-month period of interest (either the 6-month study observation period or the 6-month period immediately preceding the date of the mailing).
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Dose Reduction | 25.8 percentage of participants |
| Provider Only | Dose Reduction | 24.2 percentage of participants |
| Usual Care | Dose Reduction | 24.8 percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.33Chi-squared
Secondary
Percentage of Participants Who Died
We assessed all-cause inpatient mortality in all study participants (n=12,787) during the 6-month study observation period.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants Who Died | 1.2 Percentage of participants |
| Provider Only | Percentage of Participants Who Died | 1.4 Percentage of participants |
| Usual Care | Percentage of Participants Who Died | 1.2 Percentage of participants |
p-value: 0.66Log Rank
Secondary
Percentage of Participants With Ambulatory Encounters
We assessed the occurrence of any ambulatory encounter over the 6-month observation period.
Time frame: 6 months
Population: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants With Ambulatory Encounters | 94.2 Percentage of participants |
| Provider Only | Percentage of Participants With Ambulatory Encounters | 93.8 Percentage of participants |
| Usual Care | Percentage of Participants With Ambulatory Encounters | 94.5 Percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.47Chi-squared
Secondary
Percentage of Participants With Emergency Department Encounters
We assessed the occurrence of any emergency department encounters over the 6-month observation period.
Time frame: 6 months
Population: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants With Emergency Department Encounters | 31.7 Percentage of participants |
| Provider Only | Percentage of Participants With Emergency Department Encounters | 33.0 Percentage of participants |
| Usual Care | Percentage of Participants With Emergency Department Encounters | 33.6 Percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.19Chi-squared
Secondary
Percentage of Participants With Hospitalizations
We assessed the occurrence of any hospitalizations over the 6-month observation period.
Time frame: 6 months
Population: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants With Hospitalizations | 12.0 Percentage of participants |
| Provider Only | Percentage of Participants With Hospitalizations | 12.9 Percentage of participants |
| Usual Care | Percentage of Participants With Hospitalizations | 12.8 Percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.46Chi-squared
Secondary
Percentage of Participants With Non-acute Institutional Admissions
We assessed the occurrence of any non-acute institutional admissions over the 6-month observation period.
Time frame: 6 months
Population: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants With Non-acute Institutional Admissions | 7.2 Percentage of participants |
| Provider Only | Percentage of Participants With Non-acute Institutional Admissions | 6.9 Percentage of participants |
| Usual Care | Percentage of Participants With Non-acute Institutional Admissions | 6.8 Percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.79Chi-squared
Secondary
Percentage of Participants With Polypharmacy
Polypharmacy was defined as being dispensed 5 or more unique prescription medications, assessed on the last day of the 6-month study observation period. Polypharmacy was based on medications administered by any route (including topical or ocular medications) and included AD medications and the 3 medication classes targeted for deprescribing. A combination drug was considered a single medication for the purpose of this analysis.
Time frame: 6 months
Population: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patient-Provider | Percentage of Participants With Polypharmacy | 81.3 Percentage of participants |
| Provider Only | Percentage of Participants With Polypharmacy | 82.3 Percentage of participants |
| Usual Care | Percentage of Participants With Polypharmacy | 82.0 Percentage of participants |
Comparison: Secondary outcomes were analyzed only for those patients who were not censored due to health plan disenrollment or death over the 6-month study observation period (n = 10 424). For analyses of secondary outcomes, we compared the 3 arms using chi-square testing for dichotomous outcomes.p-value: 0.55Chi-squared
Secondary
Switching Within Classes
Switching of agents within the following targeted drug classes: sedative/ hypnotics, antipsychotics, highly anticholinergic agents.
Time frame: 6 months
Population: Data were not collected on this measure.