Reducing Post-discharge Adverse Drug Events Amongst the Elderly: a Multi-centre Electronic Deprescribing Intervention

Reducing medications and associated side effects in older adults: an electronic hospital-based intervention

Study Overview

• Status: Completed
• Conditions: Adverse Drug Event
• Intervention / Treatment: Other: Deprescribing opportunities

Detailed Description

Polypharmacy, or the concomitant use of 5 drugs or more, is a serious health concern and affects more than half of Canadians aged 65 years and older. It is the number one identifiable risk factor for adverse drug events (ADEs), which are responsible for 27,000 hospital admissions annually in Canada and up to 20% of return visits to the hospital within 30 days of discharge. Many ADEs are preventable or ameliorable through interventions to reduce inappropriate prescribing.

MedSafer, the intervention software, applies an electronic set of criteria, previously designed and piloted on one thousand (1000) hospitalized patients by a group of Quebec and Ontario internists, geriatricians, palliative care doctors and pharmacists, to identify potentially inappropriate medications (PIMs) in the hospitalized elderly and generate instructions for the patient and physician for safe discontinuation. The current study seeks to partially automate the deprescribing process and to demonstrate the efficacy of this type of intervention on adverse drug events at 30-days post hospital discharge.

At the time of hospitalization, the patient's medications, co-morbidities, and a measure of frailty will be entered into the MedSafer software which will output an individualized and prioritized deprescription plan for the most responsible physician's consideration. Any subsequent medication changes will be transmitted to relevant community physicians. The study will evaluate the impact of stopping PIMs on the occurrence of ADEs within 30 days of discharge, as compared to usual care.

This study will take place on the clinical teaching units (CTUs) at 11 hospitals from seven university hospital centres across Canada. Based on historical data, the investigators estimate a combined 5200 eligible patients per year with nearly 50% taking ten or more medications. Many will have multiple medical co-morbidities such as diabetes, heart disease, and renal insufficiency. A large portion will meet criteria for geriatric syndromes such as frailty and will be at high risk for the development of delirium, falls and functional decline. This population is ideal for a generalizable deprescribing study.

All patients aged 65 or older who meet inclusion/exclusion criteria will be enrolled. A trained research assistant will identify eligible patients and medications will be screened using MedSafer. A deprescribing plan will be generated for the CTU team containing the rationale for suggested medication changes and strategies for safe and successful deprescription. The CTU team will then decide, in conjunction with the patient/proxy and relevant consultants, whether to apply the suggested modifications.

• Study Type: Interventional
• Enrollment (Actual): 6582
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Foothills Medical Centre, Calgary
    • Edmonton, Alberta, Canada, T6G 2G3
      • University of Alberta, Edmonton
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 1Y6
      • University of British Columbia, St-Paul's Hospital
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston General Hospital
    • Ottawa, Ontario, Canada, K1Y 4E9
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • University Health Network, Toronto
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients aged 65 years and older
• patients who take five or more medications in the community
• patients who are cognitively impaired or otherwise unable to provide consent will still be included as this subpopulation of patients may be at greatest risk of ADEs because of their communication problems.

Exclusion Criteria:

• patients who take four or fewer medications in the community
• patients expected to die within 30 days or be transferred to a palliative care unit/another hospital
• patients without provincial health insurance or who normally live outside that province
• patients previously enrolled
• inability for patient or proxy to speak English or French
• no means of contacting patient or proxy post-discharge

Patients discharged from non-study units will be excluded unless that unit is a transitional care, rehabilitation, or post-acute care unit which bridges the gap between acute medical hospitalization and community services.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; All participants in the control arm will receive medication reconciliation at admission and discharge, and identical follow up, but no prioritized deprescribing list will be generated.
Experimental: Intervention; Participants in the intervention arm will be electronically screened using an electronic software "MedSafer" which will generate output of PIMs that will be brought to the attention of the CTU team via the unit pharmacist as "deprescribing opportunities". (Note that in the case of multiple recommendations, they will be limited and prioritized so as to avoid overwhelming the treating team.) Based on their own expert medical judgement, in collaboration with the patient/caregiver and other relevant clinicians, a decision will be made to deprescribe if appropriate by the patient's in-hospital doctors.	Other: Deprescribing opportunities; An electronic intervention that identifies potentially inappropriate medications (PIMs) and generates instructions for safe discontinuation, which is presented to the treating physician for their consideration.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Drug Events within 30 days post-discharge (ascertained via telephone interviewer and adjudicated via clinician reviewers)	Post-discharge telephone interview performed by trained personnel using a modification of the Australian two-step adverse reaction and drug event report. Two trained and blinded clinician reviewers will independently use the Leape and Bates approach to assess whether an ADE was present (yes/no) and if so what was the nature of the injury resulting from it using a four-point Likert scale (definitely preventable, probably preventable, probably not preventable, and definitely not preventable), and assess the probability that an event was attributable to a specific drug that was newly started, changed or continued during hospitalization. In cases of disagreement, a third trained and blinded clinician will review and determine the final assessment.	Interview performed 30-35 days post-discharge.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of potentially inappropriate medications	The absolute number of potentially inappropriate medications at discharge among patients who were identified as having a potentially inappropriate medication at admission and for who a deprescribing opportunity was generated and presented to the treating team	At hospital discharge and at 30-days post hospital discharge
Mortality within 30-days post discharge	Death following hospital discharge	30-days post hospital discharge
Proportion of participants with one or more potentially inappropriate medications deprescribed	Proportion of participants with one or more potentially inappropriate medications deprescribed at discharge between intervention and control	At hospital discharge
Quality of sleep	Quality of sleep measured by the PROMIS Sleep Disturbance 4a measured pre- and post-hospitalization compared between intervention and control	30 days post hospital discharge
Adverse events	The proportion of patients who had one or more adverse events (falls, hospitalization, death, unplanned encounter with the healthcare system	30 days post hospital discharge
Falls post hospital discharge	The proportion of patients with one or more self-reported falls post hospital discharge	30 days post hospital
Quality of life of participants	Quality of life as measured by EQ5D-5L and reported based on reported Canadian time trade-off values (from 0-1 with higher equal to better quality of life)	At 30-days post hospital discharge

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death post hospital discharge	Proportion of patients who died post-hospital discharge compared between the intervention and control groups	30-days post hospital discharge
Unplanned visits with the healthcare system	Proportion of patients with any self-reported unplanned visit with the healthcare system compared between intervention and control (emergency room visits and hospitalizations)	30-days post hospital discharge
Total number of medications at 30-days	Total number of mediations at 30 days (reported as median and interquartile range) compared between intervention and control	At 30-days post discharge
Sensitivity analysis for adverse drug events	Proportion of participants with 1 or more adverse drug events as defined by 4 or more on the 6-point Leape and Bates Likert scale	At 30-days post hospital discharge
Proportion of potentially inappropriate medications that remained stopped	Proportion of potentially inappropriate medications that remained stopped between intervention and control	30-days post hospital discharge

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Collaborators: University Health Network, Toronto; University of British Columbia; Canadian Institutes of Health Research (CIHR); University of Alberta; The Ottawa Hospital; Queen's University; Foothills Medical Centre
• Investigators: Principal Investigator: Todd C Lee, MD, MPH, McGill University Health Centre/Research Institute of the McGill University Health Centre

Publications and helpful links

General Publications

• McDonald EG, Wu PE, Rashidi B, Wilson MG, Bortolussi-Courval E, Atique A, Battu K, Bonnici A, Elsayed S, Wilson AG, Papillon-Ferland L, Pilote L, Porter S, Murphy J, Ross SB, Shiu J, Tamblyn R, Whitty R, Xu J, Fabreau G, Haddad T, Palepu A, Khan N, McAlister FA, Downar J, Huang AR, MacMillan TE, Cavalcanti RB, Lee TC. The MedSafer Study-Electronic Decision Support for Deprescribing in Hospitalized Older Adults: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2022 Mar 1;182(3):265-273. doi: 10.1001/jamainternmed.2021.7429.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2017
• Primary Completion (Actual): March 30, 2020
• Study Completion (Actual): March 30, 2020

Study Registration Dates

• First Submitted: August 31, 2017
• First Submitted That Met QC Criteria: September 1, 2017
• First Posted (Actual): September 5, 2017

Study Record Updates

• Last Update Posted (Actual): May 17, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Elderly; Polypharmacy; Frailty; Deprescribing; Adverse Drug Event; Choosing Wisely Canada; High value healthcare; Medication rationalization; Medication stewardship
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: MedSafer; CIHR Application No. 365795 (Other Grant/Funding Number: Canadian Institutes of Health Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will keep a coded, completely anonymized, database that will be made available to other researchers upon request.
• IPD Sharing Time Frame: Eighteen (18) months following the study completion.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No