Two randomized controlled trials of nudges to encourage referrals to centralized pharmacy services for evidence-based statin initiation in high-risk patients: Rationale and design of the SUPER LIPID program

Abstract

Background: In patients with or at risk for atherosclerotic vascular disease, statins reduce the incidence of major adverse cardiovascular events, but the majority of US adults with an indication for statin therapy are not prescribed statins at guideline-recommended intensity. Clinicians' limited time to address preventative care issues is cited as one factor contributing to gaps in statin prescribing. Centralized pharmacy services can fulfill a strategic role for population health management through outreach, education, and statin prescribing for patients at elevated ASCVD risk, but best practices for optimizing referrals of appropriate patients are unknown.

Study design and objectives: SUPER LIPID (NCT05537064) is a program consisting of two pragmatic clinical trials testing the effect of nudges in increasing referrals of appropriate patients to a centralized pharmacy service for lipid management, conducted within 11 primary care practices in a large community health system. In both trials, patients were eligible for inclusion if they had an assigned primary care provider (PCP) in a participating practice and were not prescribed a high- or moderate-intensity statin despite an indication, identified via an electronic health record (EHR) algorithm. Trial #1 was a stepped wedge trial, conducted at a single practice with randomization at the PCP level, of an interruptive EHR message that appeared during eligible patients' visits and facilitated referral to the pharmacy service. For the first 3 months, no PCPs received the message; for the second 3 months, half were randomly selected to receive the message; and for the last 3 months, all PCPs received the message. Trial #2 was a cluster-randomized trial conducted at 10 practices, with randomization at the practice level. Practices were randomized to usual care or to have eligible patients automatically referred to centralized pharmacy services via a referral order placed in PCPs EHR inboxes for co-signature. In both trials, when a patient was referred to centralized pharmacy services, a pharmacist reviewed the patient's chart, contacted the patient, and initiated statin therapy if the patient agreed. The primary endpoint of both trials was the proportion of patients prescribed a statin; secondary endpoints include the proportion of patients prescribed a statin at guideline-recommended intensity, the proportion of patients filling a statin prescription, and serum low-density lipoprotein level.

Conclusions: SUPER LIPID is a pair of pragmatic clinical trials assessing the effectiveness of two strategies to encourage referral of appropriate patients to a centralized pharmacy service for lipid management. The trial results will develop the evidence base for simple, scalable, EHR-based strategies to integrate clinical pharmacists into population health management and increase appropriate statin prescribing.

Clinical trial registration: clinicaltrials.gov; NCT05537064.

Figure 1:. Design of SUPER LIPID

SUPER LIPID consists of two pragmatic randomized controlled trials of nudges to increase referrals to a pharmacist service for initiation of high- or intermediate-dose statins in appropriate patients who were not treated with statins at baseline. Panel A depicts Trial #1, a stepped wedge trial, conducted in a single primary care clinic with randomization at the PCP level, of an interruptive pop-up notification that is delivered to the PCP when an eligible patient is seen in clinic and, as a default action, facilitates referral to the pharmacy service. Panel B depicts Trial #2, a cluster randomized trial conducted at 10 primary care clinics, with randomization at the level of the clinic, of sending a referral order for pharmacy services to PCPs for co-sign without regard to the timing of an in-person clinic visit. For both trials, the primary endpoint is the proportion of patients prescribed a statin during the study period, among all eligible patients seen in clinic during the study period for Trial #1, and among a randomly selected subset of all patients assigned to the clinic that meet study inclusion criteria for Trial #2.