Engaging Patients to Promote Deprescribing
Phase: NA
Conditions: Medical Overuse, Inappropriate Prescribing, Deprescriptions
Sponsor: VA Office of Research and Development

Official Title: Engaging Patients to Promote Deprescribing  
NCT Number: NCT04294901 
Document Date: July 18, 2023 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Study overview 
We propose a multi-site, mixed-methods, quasi-experimental Hybrid Type I effectiveness implementation 
trial of a patient-centered intervention. A Hybrid Type I trial “tests a clinical intervention while gathering 
information on its potential for implementation in a real-world situation.” Modeled on our Institutional Review 
Board (IRB)-approved pilot study procedures1, Veterans at three intervention sites will each receive a 
medication-specific brochure adapted for VA prior to a scheduled primary care appointment. For the up to 
6,800 subjects, we will use pharmacy dispensing data to measure deprescribing (primary outcome).  
 
Intervention design 
The intervention is an evidence-informed practice: a medication-specific brochure (adapted from Canadian 
Deprescribing Network EMPOWER brochures) designed to educate and activate patients. 2,3 These brochures 
provide detailed medication information, allow self-testing of indications for use, prompt reflection of 
experiences with potential side effects, discuss alternative therapies (medication and non-pharmacologic 
options), and provide a vignette of a patient who successfully stopped the medicine. They were designed for a 
6th grade reading level and were based upon theories of patient activation, adult learning, and cognitive 
dissonance. The visually appealing brochure repeatedly emphasizes that patients should not make any 
medication changes without first consulting their health care provider.  
As we did in our pilot study, we will adapt the brochures to tailor the presentation to a Veteran population 
and to align with current VA initiatives. We will change images and names to be more representative of 
Veterans to promote relatability. Importantly, to mirror efforts of the Whole Health initiative, we will add the 
following two questions to prompt reflection by the Veteran: 1) “How does staying on (medication name) help 
me reach my personal health goals?” and 2) “How does stopping (medication name) help me reach my personal 
health goals?”  
This proposed intervention will not directly deprescribe medications; we will not be randomizing patients to 
medication discontinuation. Instead, we are testing an intervention to prompt consideration of a clinical 
decision, analogous to a clinical reminder in the electronic health record prompting the provider to consider 
appropriate care. We propose an innovative approach to promote medication use review that starts by contacting 
the patient, not the clinician, yet the ultimate decision remains with the patient-provider dyad. 
 
Study Aim 
 
The study primary aim is to examine the impact of a patient-centered intervention to change provider 
prescribing (the primary outcome), as determined by the frequency with which medications are either 
deprescribed or de-escalated. Our primary outcome will be the composite of deprescribing and de-escalation of 
target medications, identified in pharmacy dispensing records of the Corporate Data Warehouse (CDW). 
 
Hypothesis 
The hypothesis is deprescribing will be greater for Veterans receiving the intervention brochure than for 
those in the historical control group.  
 
Study sites 
We will target Veterans at three primary care sites who meet eligibility criteria and are prescribed the target 
medication at the time of their scheduled primary care visit (in-person, video technology-based, or telephone 
clinics). These sites were selected based upon ability to recruit adequate samples, geographic variability, and 
patient population. We will include all PCPs at VA Medical Centers (VAMCs) and Community Based 
Outpatient Clinics (CBOCs), except for resident clinicians, as these trainees are likely to turn over during the 
intervention.  
 
Randomization 
Previous research, including our pilot study, revealed differences in deprescribing tendencies across 
providers. Thus, although our intervention intends to engage patients, our study design prioritizes comparisons 
of patients within the same provider to maximize power. At each intervention site, individual PCPs will be 
randomized to the sequence of medication cohorts. We will randomize PCPs to one of the three medication 
groups at the beginning of the first (month 1) and second (month 7) window and assigned them to their 

remaining medication group at the start of the third (month 13) window. Our primary comparisons are between 
“brochure-intervention” patients and “baseline” patients (matched in terms of eligibility) from the same 
provider. Each patient will only have one opportunity to receive a brochure, even if they subsequently meet 
eligibility criteria for receipt of a second, different brochure. This allows equal exposure to the intervention for 
all Veterans since the impact of a second brochure might be influenced by the first brochure.  
Although our primary comparison is between patients of the same provider pre- and post-intervention, 
we will also collect data at non-equivalent control sites matched by geography who will not receive the 
intervention; all data on control patients will be from the Corporate Data Warehouse (CDW). Including 
additional control sites will allow us to address potential temporal trends in deprescribing over the timeframe of 
our study that are not due to our intervention. The use of separate control sites (rather than randomizing some 
PCPs at each intervention site to control conditions) was preferred due to concerns about potential 
contamination across intervention and control conditions within sites. For both the control sites and the pre-
intervention baseline period, we will identify patients who would have been eligible for the study; patients 
meeting criteria for multiple cohorts will be randomly allocated to only one. 
 
Study Cohorts 
The intervention cohort will consist of eligible patients in one of the three medication groups with an 
upcoming PCP appointment during the study enrollment period. We will create a comparison historical control 
cohorts comprising eligible patients in each medication group who were seen by the same PCPs at the same 
sites as our intervention cohort eighteen months to one year before our intervention cohort window to allow for 
comparable follow-up time before the intervention commenced. Patients in the intervention cohorts will be 
excluded from the historical control cohorts.  
 
Medication Groups 
To be enrolled in the study intervention or control cohort, patients needed to meet eligibility criteria for one of 
three medication-based groups. We have selected three medication-based patient groups based upon variations 
in 1) type of potentially inappropriate use, 2) medication factors (potential benefit and harms of continued use), 
and 3) anticipated interest in deprescribing by patients and providers.  
 
1. Proton Pump Inhibitor Cohort (PPI) 
The PPI cohort will be defined as patients with prescriptions for any PPI at any dose for 90 consecutive 
days in patients of any age.  
 
2. Diabetes – Hypoglycemia Risk (DM-HR) 
To create diabetes cohorts, we identify overly-controlled patients with diabetes based upon International 
Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes, most 
recent HbA1c <7%, as well as one or more of the following criteria: 1) age 65 or older, 2) renal 
insufficiency defined as creatinine >2 mg/dL, or 3) cognitive impairment defined by a diagnosis of 
cognitive impairment and/or prescription for an acetylcholinesterase inhibitor (e.g., donepezil). Patients 
in the DM-HR group needed to have a current prescription for either insulin or sulfonylurea with at least 
90 consecutive days on the medication in the prior year.   
 
3. Gabapentin (Gaba) 
 The gabapentin cohort will include patients prescribed a total daily dose of gabapentin >1800mg for a 
minimum of 90 days.  
 
Subject Exclusion Criteria  
We will not exclude women or minorities, but children will not be eligible for participation. 
 
1. Proton Pump Inhibitor Cohort (PPI) 
In response to feedback from our pilot study, we will exclude diagnoses for which PPI continuation 
would be appropriate (e.g., Barrett’s esophagus, or those prescribed chronic glucocorticoids or 
NSAIDs).  

 
2. Diabetes – Hypoglycemia Risk (DM-HR) 
 
No exclusion criteria. 
 
3. Gabapentin Cohort (Gaba) 
We will exclude patients with recommended indications for gabapentin, including documented 
neuropathic pain using established criteria, those with seizure disorders, documented neuropathic pain, 
and cancer-related pain.  
 
Recruitment 
As we did for our IRB approved pilot study, we are requesting a waiver of informed consent and a waiver of 
HIPAA authorization to identify eligible Veterans to whom we will mail brochures.  
 
Note about Patients with Cognitive Impairment – Due to the eligibility criteria for the Diabetes cohort, it 
is possible that patients with cognitive impairment will be recruited. Veterans with cognitive impairment 
represent a population at potentially increased risk for worsened outcomes associated with overtreatment 
of diabetes, especially for hypoglycemia (low blood sugar). Thus, it is important to understand the effect 
of promoting deprescribing on this vulnerable population. Veterans with mild cognitive impairment may 
still comprehend the brochure well enough to ask their primary care provider about the need for diabetes 
medication. Veterans with more severe cognitive impairment may not interact with the brochure, but a 
caregiver may on their behalf. Veterans with cognitive impairment significant enough to not interact 
with the brochure are likely at greater risk of harm from potentially inappropriate medication use and 
subsequent risk for hypoglycemia than they are from hyperglycemia should they decide to stop taking 
their medication prior to discussing with their PCP.  
 
Data Collection/ Study Measures 
 Data collection procedures 
Before starting the trial and mailing medication-specific brochures, using material similar to that in our pilot 
study, we will inform clinicians (attending physicians, nurse practitioners, physician assistants, and clinical 
pharmacy specialists) and staff via either Outlook or Enterprise Feedback Management (Verint)-managed email 
about the project, describe an overview of deprescribing, and provide them with deprescribing algorithms and 
guidelines available online. The intention is to prepare providers to respond to a patient engaged by the 
medication-specific brochure, as the patient is the focus of the proposed intervention. When the patient cohort 
changes, prescribers will receive “refresher” emails, for a total of three points of contact during the intervention. 
 
Chart review – We will conduct chart reviews on a sample of subjects; this activity will assess the 
concordance of the medication dispensing data obtained from CDW with that of both electronic health record 
documentation. 
 
Study Measures 
We will query CDW for 6 months following the date of each scheduled primary care visit to assess our 
primary outcome of deprescribing. Based upon findings in our pilot study, medication orders may not be 
discontinued in electronic health records even if discussions occur in the clinic visit (e.g., the PCP tells the 
patient to deprescribe but does not change the order). Notably, because our primary objective is to improve safe 
prescribing and reduce PIMs, pharmacy dispensing data best reflects our deprescribing outcome. As per our 
definition, either complete cessation or dose reduction will be fulfillment of our primary outcome. 
Modeling our approach after the methods of Steinman, Sussman, and Martin, we will use non-refill of the 
medication in the 6 months following the primary care appointment as our a priori definition of cessation, based 
upon dispensing dates. 4,5 Per VA Pharmacy policy, medications are only refilled upon request, and therefore, 
non-refill of a medication can indicate that it was discontinued, it expired (typically one year after it was 
ordered), or the patient did not refill it. If the medication continues to be dispensed, we will determine any 
reduction in the total daily dose, indicating de-escalation (one component of our deprescribing definition). An 

exception to the de-escalation rule will be for insulin, where only complete cessation will qualify since dose 
changes are less likely to be reflected in the order compared to oral medications.  
Consistent with our conceptual framework, we will also assess patient and provider factors that may 
influence deprescribing. Patient factors will be obtained from CDW, and will include age, race, sex, Elixhauser 
comorbidities in the two years prior to the scheduled primary care visit. Provider factors include sex, discipline, 
age, and site.  
To assess potential ADWEs, we will ascertain if the deprescribed medication is subsequently restarted or 
returns to original dosing. We will then query CDW for diagnoses of GI bleeding for the PPI cohort, diabetic 
ketoacidosis or hyperosmolar hyperglycemic state for the DM cohort, and seizure for the gabapentin cohort in 
the year following the index visit.  Note, we consider substitution to a lower potency medication (e.g., 
histamine-2 receptor antagonist for a PPI) to be a neutral or desirable event and not an ADWE.  
 
Statistical Analysis Plan (see attached statistical analysis plan for greater detail) 
 
Our Aim 1 primary quantitative outcome will be binary: deprescribing versus not, assessed via pharmacy 
dispensing data. To investigate the impact of the medication-specific brochure on deprescribing, we will use 
Hierarchical Generalized Linear Modeling (HGLM) to account for the nesting of patients within providers. This 
approach will provide information not just about the average effectiveness of the intervention, but also about 
how much variation there is in the intervention impact across providers. In all models, Level 1 (patient-level) 
intercepts and slopes will be treated as random effects, and parameters will be estimated with robust standard 
errors. We will conduct all analyses using SAS software. 
Using this approach of nesting patients within providers, for our primary analysis, we will compare the 
likelihood of deprescribing among patients in the pre-intervention period to that for patients in the intervention 
periods for providers at the intervention sites only. We predict that intervention patients will be significantly 
more likely to have deprescribing than patients in the pre-intervention period with the same eligibility criteria. 
We will then examine whether the intervention effectiveness is moderated by the target medication. We do not 
expect a discontinuation rate of 100%, as many patients could still have an indication to remain on the 
medication.  
Provider Effects – Although our intervention is designed to target and engage patients, it is possible that the 
intervention may be more effective with certain PCPs. If we find significant variance in the average 
effectiveness of the intervention across PCPs in our primary analyses, we will use HGLM to explore how 
provider characteristics by accessing CDW data (e.g., age, race, discipline) impact intervention effectiveness.  
Patient-Level Effects – We will again use HGLM analyses to assess the extent to which patient factors 
collected from CDW (e.g., age, race, sex, comorbidities) are associated with deprescribing among patients who 
receive the intervention.  
 
Ethical Issues 
Risks 
 Risk of the intervention – It is important to note that the decision to deprescribe or not remains in the purview 
of the patient-provider dyad; we are not randomizing patients to have medications withdrawn. The primary 
intervention is distribution of information directly to patients. As such, this study involves a low level of risk to 
all human subjects.  
It is possible that Veterans could feel discomfort receiving information about their medications, expressing 
their beliefs and perspectives, or have concerns that their subsequent health care services will be affected. 
Bringing the issue of potential medication overuse to Veterans’ attention may also lead them to worry that they 
are taking too many medicines or that the targeted medications (PPIs, diabetes medications, or gabapentin) may 
have caused them harm. 
The intervention could lead to the actual discontinuation of unnecessary medications as intended; 
nonetheless, there is a slight possibility that the intervention could unintentionally lead to discontinuation of 
medications that are necessary or that the discontinuation of medications perceived as unnecessary could 
actually result in adverse drug withdrawal events. It is also possible that patients will stop a medication after 
receiving the brochure but without consulting their primary care provider.  

The risks of deprescribing medications include, but are not limited to, adverse drug withdrawal reactions 
and return of a medical condition. Adverse drug withdrawal reactions are rare, especially in comparison to 
adverse drug events. It is more common for patients to experience a return of symptoms for which the 
medication was initially prescribed. Serious adverse events resulting from inappropriately discontinuing a 
medication include upper gastrointestinal bleeding for the PPI cohort, diabetic ketoacidosis or hyperosmolar 
hyperglycemic state for the DM cohort, and seizure for the gabapentin cohort. 
 Risk from breach of confidentiality – The risk to participants includes potential compromise of confidential 
information; however, the use of VA data in research analyses similar to those proposed is standard practice and 
there are no viable alternatives to obtain this quantity and quality of data. We will take all actions required to 
protect the security and integrity of confidential and personal health information.  
 
Procedures to Minimize Risk  
Veterans receiving the intervention (brochure) and survey – Exclusion criteria have been carefully 
incorporated to help minimize Veteran risk prior to enrollment. Further, as noted, we are not randomizing 
patients to have medications withdrawn. The primary intervention is distribution of information directly to 
patients. It is important to note that the decision to deprescribe or not remains in the purview of the patient-
provider dyad. We will provide a brief cover letter when sending the medication-specific brochure to patients, 
and the medication-specific brochure states multiple times to not decrease or discontinue a medication without 
first consulting with a clinician. We are also mailing the brochures two weeks prior to a primary care visit, so if 
patients decide they want to stop a medication, they will already have an appointment scheduled. Taken 
together with the fact that patients and providers already have the ability to make deprescribing decisions, the 
risk of this study is not greater than current standard practice. 
 Risk from breach of confidentiality – In order to assure appropriate research subject selection and high-
quality data collection, all study personnel will undergo training in the study protocols. We will take all 
necessary steps to ensure the protection of confidential information in accordance with VA regulations and 
other applicable laws. All identifiable data will be protected from improper use or disclosure. Only research 
team members will have access to data. We will enter survey data into an electronic database with a unique 
identifier, removing any Protected Health Information (PHI). We will store all electronic data entirely within 
the VA network, which is protected by firewalls. User identification codes limit access to specific directories 
and files. We will not include names on audio-recordings or transcriptions, and publications will not identify 
individual participants or the sites from which they were recruited. We will not disclose identifiable information 
to any other person or entity outside VA, except as required by law, for authorized oversight of this research 
study, or for approved use in another study by an IRB. We will store physical data in locked cabinets within the 
Section of General Internal Medicine and Center for Healthcare Organization and Implementation Research 
(CHOIR) offices at VA Boston 
 
Potential Benefits 
Veteran participants of the intervention may benefit from the attention focused on considering their 
medication regimens and potential discontinuation of medications that are unnecessary or place them at risk for 
harm. The concept of deprescribing is gaining increased recognition as an important component of standard 
clinical practice. The study intervention primarily provides the patient with an opportunity to learn more about 
their medication and encourages them to contemplate the role of medication within their overall health goals, 
and thus may lead to a more knowledgeable, activated patient. The proposed research, taken together with 
future research efforts, has the potential to reduce the prescribing of non-indicated medications and reduce 
associated adverse effects, improving the care and safety of Veterans nationally. 
 
Analysis of Risks in Relation to Benefits 
Given the high prevalence of adverse drug events, any successful reduction in the use of inappropriate, non-
indicated, or unnecessary medications has the potential to reduce medication-related errors and associated 
adverse events. Further, within any system with constrained resources, reducing low-value care will enable 
resources to be focused more efficiently on those practices which are considered high-value. This study will 
determine the effectiveness of a low-tech patient-centered intervention on changing prescribing patterns. We 
will also understand the actions patients take after receiving this type of intervention, and how it enhances 

ownership of their health care. The value of the knowledge gained outweighs the minimal risk to subjects of 
compromised patient or clinician data. 
 
Stopping Rules 
A participant may always withdraw their participation at any time.   
The study has no stopping rules.  
 
Safety Monitoring Plan   
Per instructions of the VA HSR&D Program, the full Data Analysis Plan has been submitted to the Data 
Safety Monitoring Board (DSMB) using the Just-In-Time (JIT) document manager. Because the intervention 
described is an educational outreach to patients, there is minimal risk since clinical providers retain complete 
authority to deprescribe, de-escalate, and resume medications per their clinical judgement. However, it is 
possible that deprescribing could lead to adverse drug withdrawal. We expect these to be extremely rare 
occurrences, as we are identifying Veterans likely to be over-treated and further excluding populations for 
whom the medications are indicated. Thus, we will assess for serious adverse drug withdrawal events, 
specifically looking for emergency department and hospital visits for upper gastrointestinal bleeding for the PPI 
cohort, diabetic ketoacidosis or hyperosmolar hyperglycemic state for the DM cohort, and seizure for the 
gabapentin cohort on a quarterly basis for all recruited subjects.   
Monitoring progress reports will be submitted to regulatory bodies (e.g., IRB) as requested and/or required. 
This will serve as a method for identifying systematic problems and allow the study team to identify and resolve 
problems and continuously maintain and improve data quality and Veteran safety.  Additionally, we will 
schedule weekly team meetings to be led by the study PI and include all study personnel directly involved in 
enrollment, data collection, data entry and the intervention protocol.  These team meetings will allow the study 
PIs to keep track of enrollment numbers, data integrity (e.g., reasons for missing data), and protocol 
implementation challenges that need to be addressed in a timely manner.  
 
Adverse Event/Unanticipated Problems Reporting Plans 
 
The Principal Investigator at VABHS will report Unanticipated Problems, Adverse Events, and safety monitors’ 
reports to the IRB in accordance with VHA Handbook 1058.01 and VABHS IRB SOP.  This is a multi-site 
study, but all procedures will be conducted at VABHS and thus oversight remains with the VABHS IRB.  
 
References 
1. 
Linsky AM, Kressin NR, Stolzmann K, et al. Direct-to-consumer strategies to promote deprescribing in 
primary care: a pilot study. BMC Primary Care. 2022/03/22 2022;23(1):53. doi:10.1186/s12875-022-01655-5 
2. 
Tannenbaum C, Martin P, Tamblyn R, Benedetti A, Ahmed S. Reduction of Inappropriate 
Benzodiazepine Prescriptions Among Older Adults Through Direct Patient Education: The EMPOWER Cluster 
Randomized Trial. JAMA Internal Medicine. 2014;174(6):890-898. doi:10.1001/jamainternmed.2014.949 
3. 
Canadian Medication Appropriateness and Deprescribing Network: Patient Handouts. (2023). 
https://www.deprescribingnetwork.ca/patient-handouts 
4. 
Sussman JB, Kerr EA, Saini SD, et al. Rates of Deintensification of Blood Pressure and Glycemic 
Medication Treatment Based on Levels of Control and Life Expectancy in Older Patients With Diabetes 
Mellitus. JAMA Intern Med. Dec 2015;175(12):1942-9. doi:10.1001/jamainternmed.2015.5110 
5. 
Lam KD, Miao Y, Steinman MA. Cumulative Changes in the Use of Long-Term Medications: A 
Measure of Prescribing Complexity. JAMA Internal Medicine. 2013;173(16):1546-1547. 
doi:10.1001/jamainternmed.2013.7060