Electronic health record nested pragmatic randomized controlled trial of a reminder system for serum lithium level monitoring in patients with mood disorder: KONOTORI study protocol

Abstract

BackgroundThe weaknesses of classical explanatory randomized controlled trials (RCTs) include limited generalizability, high cost, and time burden. Pragmatic RCTs nested within electronic health records (EHRs) can be useful to overcome such limitations. Serum lithium monitoring has often been underutilized in real-world practice in Japan. This trial aims to evaluate the effectiveness of the EHR-nested reminder system for serum lithium level monitoring in the maintenance of therapeutic lithium concentration and in the improvement of the quality of care for patients on lithium maintenance therapy.MethodsThe Kyoto Toyooka nested controlled trial of reminders (KONOTORI trial) is an EHR-nested, parallel-group, superiority, stratified, permuted block-randomized controlled trial. Screening, random allocation, reminder output, and outcome collection will be conducted automatically by the EHR-nested trial program. Patients with a mood disorder taking lithium carbonate for maintenance therapy will be randomly allocated to the two-step reminder system for serum lithium monitoring or to usual care. The primary outcome is the achievement of therapeutic serum lithium concentration between 0.4 and 1.0 mEq/L at 18 months after informed consent.DiscussionThe KONOTORI trial uses EHRs to enable the efficient conduct of a pragmatic trial of the reminder system for lithium monitoring. This may contribute to improved quality of care for patients on lithium maintenance therapy.Trial registrationUniversity Hospital Medical Information Network (UMIN) Clinical Trials Registry, UMIN000033633. Registered on 3 July 2018.

Electronic Health Record–Nested Reminders for Serum Lithium Level Monitoring in Patients With Mood Disorder: Randomized Controlled Trial

“…At the follow-up, 38 (69.1%) patients in the reminder group and 33 (60%) patients in the usual care group achieved therapeutic serum lithium levels, but the difference in the proportions was not significantly different between the 2 groups (adjusted OR 2.14, 95% CI 0.82-5.58, P=.12; risk difference 0.136, 95% CI -0.017 to 0.288, P=.08; risk ratio 1.17, 95% CI 0.94-1.47, P=. 16). With multiple imputation, the result was consistent but more conservative than that of the primary analysis (adjusted OR 1.22, 95% CI 0.73-2.06, P=.45) (Table 2).…”

“…This trial was conducted at the Department of Psychiatry of Toyooka Hospital, a tertiary-care community hospital in Toyooka City, Hyogo, Japan. The details of the trial design have been previously published (University Hospital Medical Information Network Clinical Trials Registry: UMIN000033633) [ 16 ].…”

Data I

“…For an example of a pragmatic trial nested within an EHR, take a look at the protocol for the study by Seki et al (2019) which used an EHR within a psychiatric department of a hospital in Japan. The EHR provided the data framework for assessing eligible patients for this study, which randomized physicians caring for eligible patients taking lithium carbonate to receive a two-stage reminder for the patient to have a blood test for lithium levels or to receive no such reminder (usual care).…”

Three recommendations for addressing the ongoing lithium underutilization crisis in bipolar disorder

“…At present, EHRs can facilitate comprehensive review of medications and promote side effect monitoring through clinician prompts. Reminders can be built to promote adherence to guidelines, including around serum lithium level 5 and renal and thyroid monitoring. Clinician to clinician collaboration can also be enhanced, and through use of EHR integrated and smartphone friendly electronic portals, communication with patients between appointments can be readily facilitated, including via wearable technology programmed to provide increased patient medication support, including reminders to take lithium and obtain trough serum levels at specific times.…”