Clinical trial NCT03826758: Enhanced Dynamic Clinical Decision Support System Pragmatic Trial (E-DYNAMIC)
Official title: E-DYNAMIC - Enhanced Dynamic Clinical Decision Support to Identify Patients With Chronic Kidney Disease and Improve Cardiovascular Health
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Chronic Kidney Diseases
Keywords: chronic kidney disease
clinical decision support
health informatics
pragmatic clinical trial
Lead sponsor: Loyola University
Sponsor class: OTHER
First posted: 2019-02-01
Enrollment: 8000
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Pragmatic randomized clinical parallel trial with two arms
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Chronic kidney disease (CKD) is a highly prevalent, poorly recognized and undertreated and increases risk of atherosclerotic cardiovascular disease (ASCVD) and mortality. ASCVD risk interventions such as statin medications are not effective if initiated when kidney disease is advanced. Thus, early recognition of CKD is important for effective ASCVD risk management. Patient centered medical homes (PCMH)s (clinics which include nurse educators, dietitians, pharmacists and social workers) were designed to address gaps in care for complex chronic diseases such as CKD by increasing availability of ancillary services for patients. However, PCMH models have not been shown to improve the recognition and treatment of CKD and its associated ASCVD risk. The E DYNAMIC CDS retrieves real-time patient data from the electronic health record (EHR) every 24 hours to help primary care providers (PCP) identify patients with CKD and assess ASCVD risk and provide appropriate treatment. E-DYNAMIC also delegates CKD care with utilization of an opt-out approach for nurse education and dietitian referral. The overall objective of this pragmatic trial is to examine whether the E-DYNAMIC CDS increases PCP recognition of CKD and use of ASCVD risk management interventions when implemented within a PCMH. This pragmatic trial will be conducted within the Hines VA Hospital and community-based outpatient clinics designed as PCMH called teamlets. Teamlets include several PCPs, a nurse educator, a dietitian, a pharmacist, and a social worker. We will randomize 51 teamlets to the E-DYNAMIC CDS or to standard care. This pragmatic trial will address the following aims: 1) Determine the difference in PCP diagnosis of CKD stage 3-5 non-dialysis dependent CKD by allocation to the E-DYNAMIC CDS; 2) Determine the difference in PCPs ASCVD risk management of patients with stage 3-5 non-dialysis dependent CKD by teamlet allocation to the E-DYNAMIC CDS; 3) Determine the difference in patient use of ASCVD risk interventions and patient activation measures by their teamlet allocation to the E-DYNAMIC CDS. The primary outcomes of the pragmatic trial will be ascertained from the EHR. The E-DYNAMIC CDS tool may be transferred into other health systems that utilize an EHR and improve the diagnosis and management of CKD.

Detailed description: The E-DYNAMIC trial a pragmatic randomized two-arm parallel trial that will randomize 51 teamlets at the Hines Veterans Affairs (VA) hospital outpatient and community based outpatient clinics to either the E-DYNAMIC CDS vs. standard care. The E-DYNAMIC CDS will be activated for PCPs who practice in teamlets allocated to the E-DYNAMIC CDS group and this CDS will be kept active for 18 months to maximize the number of patients with potential CKD who complete a clinic visit with teamlets enrolled in the trial.The index date represents the first visit with the PCP after the date of switching on E-DYNAMIC CDS in intervention and standard care groups. E-DYNAMIC will be active for 18 months to maximize the number of index visits of CKD patients with their PCP during the trial; patients with early stage 3 CKD may not visit their PCP annually.

Randomization Scheme: The unit of randomization will be at the teamlet level. PCPs within a teamlet provide coverage for each other's patients so randomization of teamlets will help prevent contamination. We will match the teamlets in pairs based on their potential patients volumes, # of PCPs, and location (hospital based clinic vs. community based outpatient clinic). A computer generated randomization scheme will then be used by the biostatistician to randomize the pairs to either intervention or control. We will analyze the data for all three aims at the patient level, clustered by teamlets; therefore, our analyses will account for intra-cluster correlation among patients within the randomized cluster (PCPs practicing in teamlets).

After randomization, we will turn on the E-DYNAMIC CDS for the PCPs working within teamlets allocated to the E-DYNAMIC CDS. The E-DYNAMIC CDS will be seen by the PCPs at the point-of-care for their highly likely chronic kidney disease (CKD) patients identified by up-to-date laboratory data. Teamlets assigned to the standard care group will have no change to their clinical practice. The trial is not blinded and PCPs will be aware if they receive the E-DYNAMIC clinical decision support (CDS). Written individual consent will not be obtained from the providers or patients. All PCPs working in eligible teamlets which could be randomized to the E-DYNAMIC CDS will be contacted several months before trial initiation to inform them of the study and provide them with opportunity to opt-out of the study. All providers who do not opt-out will be eligible to be randomized to the E-DYNAMIC CDS or standard care groups.

1. Study cohort: Our PCP cohort includes all PCPs practicing in PACT teamlets. Our analyses will include patients ≥ 50 years old with two eGFR \< 60 mL/min/1.73 m2 for ≥ 3 months apart with no intermittent eGFR\> 60 mL/min/1.73 m2 in the electronic health record because these patients have confirmed CKD. Patient level data from administrative records will be queried to obtain information on PCP prescribing practices and patient use of medications and services for 12 months before trial initiation and for 12 months after trial initiation. We will ascertain patient demographics; co-morbidities; mention of CKD in the problem list or an international classification of disease (ICD 9/10) code for CKD, prescription and proportion of days covered (PDC) for statin medications and angiotensin converting enzyme inhibitors, angiotensin receptor blockers (ACE/ARB); and prescription and use of nurse education services, medical nutrition therapy (MNT) from a dietitian, PharmD consult for medication management, nurse visit for blood pressure check and smoking cessation by social worker for smokers.
2. Data sources: Patient level data will be obtained from the following administrative national Veterans Health Administration (VHA) datasets including the corporate data warehouse (CDW), Veterans Affairs Vital Status File, and Managerial Cost Accounting National Data Extracts where information on medication prescriptions are stored. Our analyses will exclude patients receiving dialysis or with a kidney transplant. In order to identify patients receiving dialysis or with a previous kidney transplant, we will link data files with the United States Renal Data System (USRDS) database to further identify these patients. Patient demographics, patient co-morbidities, CKD status based on laboratory data and CKD diagnoses (in the problem list or ICD 9/10 code) and statin and anti-hypertensive medication prescriptions will all be obtained from the CDW, VA Vital Status File and Managerial Cost Accounting National Data Extracts. Reason(s) for not prescribing statins will be collected with E-DYNAMIC and will be saved in the CDW as a health factor for future analysis. Because a small percentage of patients receive their medication from non-VA pharmacies, we will also use data from the Center for Medicare \& Medicaid Services (CMS) Medicare Part D 'Slim' file obtained from the VA Information Resource Center to capture statins and anti-hypertensive medications including medications dispensed from non- VA pharmacies. The VA Status Files is updated quarterly.
3. Patient surveys: Using data from the CDW, we will identify eligible patients receiving care at the Hines VA hospital and community based outpatient clinics who have upcoming PCP (in the trial teamlets) appointment in the next 0-6 months. We will stratify the patients by teamlet and use random number generator to select equal number of patients from each teamlet for a total number of 750 eligible patients to participate in the survey (pre-test). These same patients will be followed up for 6 months from the Index visit date and contacted again to re-take the survey (post-test). Our sampling strategy will account for patients who will not show up for their appointments (20%), non-response (20%) and loss to follow-up during post-test (30%). We anticipate that 400 Veterans will complete the pre and post surveys. We will mail a short, informational letter explaining the purpose of the survey, their role and the voluntary nature of participation. We will inform the patient that our study coordinator will contact them in the next couple of weeks to conduct the survey. Patients will be provided a phone number to call to opt-out of the survey. We will use a verbal consent script to obtain verbal consent before proceeding with patient surveys. The survey instruments will consist of the standardized and validated Patient Activation Measure (PAM). Survey will also include questions about statin and/or ACE/ARB use and other hypertension use, and why the patient thinks the doctor prescribed them and if they have received CKD education from a nurse or attended a group CKD education class.
4. Provider perception surveys: We will conduct provider (PCP and nurse) perception surveys to evaluate E-DYNAMIC only in the intervention arm after one year of trial enrollment. The survey will be available via-email, on paper in the clinic or by phone whichever is convenient to the provider. The survey instrument will include short battery of statements asking providers to indicate on a 5 point scale how strongly they agree or disagree with statements regarding experiences about the E-DYNAMIC CDS (PCPs) and the trial (PCPs and nurses), followed by limited number of open ended questions asking for their feedback and recommendations for improvement. We will use a written consent script at the beginning of the provider surveys and assume consent if the provider proceeded to take the on-line survey.

Statistical analysis and hypothesis testing

1. primary outcomes:The data analysis for the outcomes will be conducted at the patient level clustered by teamlets; therefore, our analyses will account for intra-cluster correlation among patients within the randomized cluster (PCPs practicing in teamlets). All the primary outcomes in this study are binary (1-Yes/ 0-No). We will assess the outcome variables for each patient at two time points: during 12 months prior to the index date and postintervention 12 months after the index date. The preintervention data will be used as a covariate to adjust for differences in baseline values. For all three aims, we propose to use the two-level mixed-effect logistic regression model to analyze the data with patients at level 1 nested within clustered teamlets (PCPs) as level 2. Although some teamlets may have more than 1 PCP, the PCPs will not be treated as a different level since PCPs within the same teamlets share the same patients and the same clinical nurses. In addition, the associations between teamlets within hospitals are assumed to be very minimal and ignorable given that the E-DYNAMIC system is turned on specifically and limited to PCPs in the randomized intervention group. We will formulate the probability of a positive outcome (1- Yes) for a given patient in a given clustered teamlet using the multilevel mixed effect model. The analysis will be adjusted for patient level (e.g. age, gender, race, and baseline CKD stage or presence of diabetes, hypertension, ASCVD) and teamlet level (e.g. proportion of baseline CKD recognition, number of providers in teamlet, average PCP age in teamlet, median years in practice of teamlet PCPs) covariates to eliminate potential impact on outcomes.
2. Patient surveys: In the initial analyses, we will analyze the raw scores (0-100) from the PAM survey and answers to the medication awareness and education participation. We will use the difference in differences approach to compare change in patient activation level from pre to post between intervention and control groups. A mixed-effect regression model will be applied to account for the intra-cluster correlations. Our analyses will control for patient demographic and medical characteristics.
3. Provider perception surveys: We will use descriptive statistics to describe results from the provider surveys separately for nurses and PCPs and report summary descriptive statistics. Established qualitative analytic techniques will be used to examine results from the open-ended questions, albeit staff answers may be brief, it will involve identifying key themes and concepts emergent from the data to generate meaningful categorization.

Sample size justification

1. Primary outcomes: An estimated 7,825 patients with CKD in 51 teamlets receive care from the Hines VA based clinics and its associated 6 CBOC clinics. We have conducted power calculations under various scenarios for changing the effect size (proportion difference in the outcome between intervention and standard care groups) and the outcome level in the standard care group. To test the primary outcomes in 3 specific aims, the significance level of alpha was decreased to 0.0167 accounting for the multiple hypothesis testing in each aim. As such, a total sample size of 50 clustered teamlets (25 in each group) and 4000 patients in each clustered teamlet is anticipated to have 82% power to detect at least a 10% difference in the outcome between the two groups, with an intra-cluster correlation of 0.05 and 20% of patients with the outcome in the control group. Our study will also be powered at 80-90% to detect a 20% difference in the outcome between the intervention and control groups with the half available number of clusters (20 clusters).
2. Patient surveys: For the patient surveys, at a significance level of 0.05, and accounting for an intra-cluster (teamlet) correlation coefficient (ICC) of 0.01, a sample size of 400 patients \[10 clusters in each group (intervention and control) and 20 patients in each cluster\] is estimated to achieve enough power (at least 90%) to detect a difference of 5 points (with SD =10 ) change in the pre- and post-intervention score of PAM-13 survey between the intervention and standard care control groups.

Eligibility criteria: Inclusion Criteria:

* All patients with chronic kidney disease (50 years and older, non-dialysis dependent and who had not received kidney transplant) seen by the primary care providers during the study period will be included in this study.
* Practicing primary provider at any of the Edward Hines Jr. hospital outpatient clinics or community based outpatient clinics
* Willing to be involved in the E-DYNAMIC clinical trial

Exclusion Criteria:

- Provider not willing to be involved in the E-DYNAMIC clinical trial

Primary outcomes:
measure: Proportion of a primary care providers' patients with chronic kidney disease (CKD) with clinically recognized chronic kidney disease (CKD).
timeFrame: 12 months follow-up after the index primary care visit
measure: Proportion of a primary care providers' patients with CKD prescribed at least two of the atherosclerotic cardiovascular disease- (ASCVD) CKD care metrics.
timeFrame: 12 months follow-up after the index primary care visit
measure: Proportion of patients who utilize at least two of the ASCVD-CKD care interventions.
timeFrame: 12 months follow-up after the index primary care visit
Secondary outcomes:
measure: Patient activation
timeFrame: One month before and 6 months after the index primary care visit
measure: Proportion of patients who used ancillary care
timeFrame: 12 months follow-up after the index primary care visit
Other outcomes:
Locations:
city: Hines
country: United States
facility: Edward Hines Jr. Hospital and associated Community Outpatient Based Clinics
state: Illinois
Study officials:
affiliation: Loyola University Chicago
name: Holly J Mattix-Kramer, MD MPH
role: PRINCIPAL_INVESTIGATOR
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