Study Design: We conducted a prospective parallel randomized controlled trial (RCT) with patients as the unit of randomization, with allocation ratio 1:1. The rationale and protocol for this RCT have been reported previously.[40]
Setting: We included 7 community neurologist (CN) practices across Edmonton, Alberta, Canada and the tertiary MS Clinic at the University of Alberta Hospital.
Ethics Approval:
The study was performed in accordance with the Declaration of Helsinki, and was approved by the Health Research Ethics Boards of the University of Alberta (approval number Pro00069595). This trial was registered retrospectively on clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04388592, 14/05/2020).
New Clinical Tools and Procedures:
The introduction of the NP into community general neurologist care for PwMS is novel. However, NP care for PwMS is standard at tertiary care centres and MS Clinics in optimizing care for PwMS.
Consent to Participate:
Informed consent was obtained from all participants to participate in the study, prior to being randomized to participate within the study, and before completing baseline measures.
Population: Patients were included in the study if they were adults (≥ 18 years) who had a diagnosis of MS as per the McDonald 2010 criteria,[41] were followed by a private-practice general neurologist and/or family doctor, willing to give consent, able to complete questionnaires and to attend outpatient visits with NP, English-speaking, and able to use a computer.
We excluded patients if they were unable to provide consent, unable or unwilling to attend appointments, referred to, or followed by neurologists within the tertiary setting, or had other central nervous system inflammation disorders.
Recruitment: Participants were recruited through advertisements and computer tablets were placed in the waiting rooms of the seven CN practices. Interested patients completed the EQ5D [42] on a tablet and were encouraged to self-register for the study and discuss their results with their CN. We also accepted direct referrals from family physicians to the NP. Details about the recruitment process are available elsewhere.[40] All participants provided informed consent to participate in the trial.
Randomization and blinding: After being enrolled in the study, patients were randomized in a 1:1 ratio to either the intervention or control groups.[51] Due to the nature of the intervention, blinding of providers or patients was not possible. The EPICORE Centre randomly randomized and allocated consented participants using a centralized secure website. Further details can be found in the study protocol publication.[40]
Intervention: Patients in the intervention group received a comprehensive NP consultation. This included 1) patient history, 2) physical examination, 3) individualized symptomatic strategies (e.g., lifestyle strategies, mobility issues, fatigue, spasticity, bladder and bowel concerns, depression or anxiety, and medications), 4) exploration of the MS patient’s local community, 5) discussion of resources to optimize mood and QoL, and 6) regular follow up visits at 3, 6 months either in-person, via telehealth, or via phone call (Figure 1).
Control: Patients randomized to the control group received usual care from CN practices, which included MS registered nurses (part of the tertiary MS clinic setting but going to community neurologists’ offices as outreach). This care was delivered according to standard practices. Follow-up visits were conducted according to the individual standard care practices (Figure 1). Patients in the control group were offered the NP intervention after six months.
Outcomes: The primary outcome was the difference in change in HADS-D and HADS-A scores between intervention (NP-led care) and control (Usual care) groups at 3 months. Secondary outcomes included difference in change in a) HADS-D and HADS-A scores at 6 months, b) EQ5D at 3 and 6 months, and c) Modified Fatigue Impact Scale (MFIS) score at 3 and 6 months and patient satisfaction with care as measured by the validated Consultation Satisfaction Questionnaire (CSQ).[43-46]
Sample size calculation: Using the information from Honarmand and Feinstein48 [Baseline scores and standard deviation (SD)] and the following assumptions 80% power and a two-sided alpha of 0.025, a total sample size of 200 (100 in each group) was required to detect 1.5 difference [48] between the intervention and the control groups. We calculated the same size for both HADS-A and HADS-D and used the sample size for HADS-A, as it required a larger sample size and to ensure there was sufficient power for both HADS-A and HADS-D. This sample size was inflated to 220 to account for possible dropouts, losses to follow-up and withdrawals of consent.
Statistical analysis: Data analysis was performed using R 3.4.0 computer software (Vienna, Austria; https://www.R-project.org/) and SAS 9.4 software (SAS Institute Inc. Cary, NC, USA). Patient demographic and clinical characteristics were analyzed using descriptive statistics. Categorical variables were reported using frequency and percentage and continuous variables were reported using mean (SD) or median [Interquartile range (IQR)] as appropriate. The primary outcome of difference in change of HADS-D and HADS-A from baseline to three months was analyzed using independent T-test. An independent T-test was also used to assess the difference in change between HADS-D and HADS-A between baseline and six months as well as the other questionnaires - EQ5D and MFIS. The CSQ Likert scales were analyzed as continuous variables, with the overall satisfaction score being calculated as a sum of the scales of each question and analyzed using an independent t-test to determine a difference between the intervention and control groups.
Data were analyzed according to the intention-to-treat principles. Trial and Data Management was completed by EPICORE Centre (www.epicore.ualberta.ca).