Effect of an Educational Intervention on Therapeutic Inertia in Neurologists With Expertise in Multiple Sclerosis: A Randomized Clinical Trial

Abstract

Importance: Therapeutic inertia (TI) is the failure to escalate therapy when treatment goals are unmet and is associated with low tolerance to uncertainty and aversion to ambiguity in physician decision-making. Limited information is available on how physicians handle therapeutic decision-making in the context of uncertainty.

Objective: To evaluate whether an educational intervention decreases TI by reducing autonomic arousal response (pupil dilation), a proxy measure of how physicians respond to uncertainty during treatment decisions.

Design, setting, and participants: In this randomized clinical trial, 34 neurologists with expertise in multiple sclerosis (MS) practicing at 15 outpatient MS clinics in academic and community institutions from across Canada were enrolled. Participants were randomly assigned to receive an educational intervention that facilitates treatment decisions (active group) or to receive no exposure to the intervention (usual care [control group]) from December 2017 to March 2018. Participants listened to 20 audio-recorded simulated case scenarios as pupil responses were assessed by eye trackers. Autonomic arousal was assessed as pupil dilation in periods in which critical information was provided (first period [T1]: clinical data, second period [T2]: neurologic status, and third period [T3]: magnetic resonance imaging data). Data were analyzed from September 2018 to March 2020.

Interventions: The traffic light system (TLS)-based educational intervention vs usual care (unexposed). The TLS (use of established associations between traffic light colors and actions to stop or proceed) assists participants in identifying factors associated with worse prognosis in MS care, thereby facilitating the treatment decision-making process by use of established associations between red, green, and yellow colors and risk levels, and actions (treatment decisions).

Main outcomes and measures: Pupil assessment was the primary autonomic outcome. To test the treatment effect of the educational intervention (TLS), difference-in-differences models (also called untreated control group design with pretest and posttest) were used.

Results: Of 38 eligible participants, 34 (89.4%) neurologists completed the study. The mean (SD) age was 44.6 (11.6) years; 38.3% were female and 20 (58.8%) were MS specialists. Therapeutic inertia was present in 50.0% (17 of 34) of all participants and was associated with greater pupil dilation. For every additional SD of pupil dilation, the odds of TI increased by 51% for T1 (odds ratio, 1.51; 95% CI, 1.12-2.03), by 31% for T2 (odds ratio, 1.31; 95% CI, 1.08-1.59), and by 49% for T3 (odds ratio, 1.49; 95% CI, 1.13-1.97). The intervention significantly reduced TI (risk reduction, 31.5%; 95% CI, 16.1%-47.0%). Autonomic arousal responses mediated 29.0% of the effect of the educational intervention on TI.

Conclusions and relevance: In this randomized clinical trial, the TLS intervention decreased TI as measured by pupil dilation, which suggests that individual autonomic arousal is an indicator of how physicians handle uncertainty when making live therapeutic decisions. Pupil response, a biomarker of TI, may eventually be useful in medical education.

Trial registration: ClinicalTrials.gov Identifier: NCT03134794.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Saposnik is supported by the Heart and Stroke Foundation Career Scientist Awards following an open peer-reviewed competition. Dr Saposnik has received personal compensation for consulting or CME activities from Hoffman LaRoche, Celgene, and Servier Canada. Dr Oh has received research funding from the MS Society of Canada, the National MS Society, Brain Canada, Sanofi-Genzyme, Roche, and Biogen. Dr Oh has received personal compensation for consulting or speaking from EMD-Serono, Genzyme, Biogen, Novartis, Celgene, and Roche. Dr Ruff received research funding from the Swiss National Science Foundation (grant 100019L_173248). Dr Tobler received research funding from the Swiss National Science Foundation (grants PP00P1_150739 and 100014_165884) and Pfizer. No other disclosures were reported.

Figures

Figure 1.. CONSORT Flow Diagram

TLS indicates traffic light system (use of established associations between traffic light colors and actions to stop or proceed).

Figure 2.. Study Design and Time Period Illustration

A, Participants answered demographic and practice-based questions and provided risk and ambiguity preferences. Next, they listened to simulated case scenarios. Each scenario was followed by 6 therapeutic choices, which remained on the screen until the participant selected 1 of them. After the first 10 simulated case scenarios (pre-intervention), participants were randomized to the intervention or the control group. All participants performed another 10 simulated case scenarios. B, The black dots represent the peak pupil size within each period used to compute pupil responses (pupil peak for each period minus mean baseline at period 0 (T0). Peaks were determined similarly for both groups across all periods and case scenarios. T1 indicates first period (critical clinical information); T2, second period (neurological status of the patient); T3, third period (critical brain imaging information); and T4, fourth period (standardized questions were asked).

Figure 3.. Effects of Intervention and Group Randomization on Pupil Responses

Pupil-linked autonomic arousal responses (peak minus mean baseline) are shown separately for intervention and control groups, stratified by the intervention period. Lower responses in the intervention group extend to T4, in which no critical information was provided, which may suggest that the protective effect of the intervention extends into the period when participants made decisions in the context of uncertainty. T1 indicates first period (critical clinical information); T2, second period (neurological status of the patient); T3, third period (critical brain imaging information); and T4, fourth period (standardized questions were asked). aP < .01 for the comparison of pupil responses between control and intervention groups.