It was May 20, 2021 when we introduced Dr. Juna de Vries . Click here for last year’s post where we learned about her, her study plans and how her project would help patients and families affected by AE.
In the 2021 AEA Community Seed Grant Final Report, Dr. de Vries explains the outcomes of her project, Patient Reported Outcomes while Manipulating the Immune System in autoimmune Encephalitis. .
Over the past year, we have built a foundation for disease-specific outcome measures for (autoimmune) encephalitis. As a first step we dedicated a literature review to previously applied cognitive and patient-reported outcome measures in the literature on encephalitis and encephalopathy. We have systematically reviewed the literature on patient-reported outcome measures (PROM’s) for autoimmune encephalitis as well as infectious encephalitis and (i.e. metabolic) encephalopathy. Although there is limited to no PROM’s developed for and validated in the encephalitis population specifically, various tools have been applied to obtain relevant information on different aspects of ‘outcome’, including daily functioning and quality of life. An article on this systematic literature review is to be submitted soon (deliverable).
First, all items (~200) were scored for relevance to measure the outcome of autoimmune encephalitis by three investigators independently and items with different relevance scores were assessed to reach consensus (content validity, milestone, accomplished). The next step was to return to the existing measuring instruments to evaluate what part of the instrument was deemed to be relevant. Instruments with at least 50% relevant items, were included in total for the first data collection and analysis. Instruments with less than 50% relevant items, were excluded as an instrument, although the individual relevant items were included separately. As an exception, we did include at least one total instrument per construct, in preparation for the analysis of construct validity in a later stage of the study.
In addition to the previously applied instruments and individual items, we have added items based on a focus group discussion. We organized two meetings of 8-12 patients of different ages, gender, ethnicity and socio-economic status and with different antibodies. We had an open discussion about relevant concepts of outcome and what deficits the patients had experienced since the autoimmune encephalitis, i.e. fatigue, the capability of social interaction and independency regarding activities of daily living and transportation. Although most items were already incorporated in the selected items and instruments, we added 12 additional items, either from other instruments or we have created new items (milestone, accomplished).
We have incorporated all selected items and instruments in a digital survey package in Castor and have started the cross-sectional collection of the patient-reported survey data as well as clinical and cognitive outcome data in the PNS cohort study. We have also implemented a structured follow-up of newly diagnosed patients.
Due to the COVID-19 pandemic, we could not start with the inclusion of patients as promptly as we wished for. Since the beginning of this year, we are accelerating the inclusion rate. Today, we have seen over 100 Dutch patients with an autoimmune encephalitis – mainly anti-NMDAR and anti-LGI1 encephalitis patients – for an structured interview, neurological examination, MOCA, antibody- and neuropsychological testing. All patients also complete questionnaires regarding quality of life, fatigue, mood and level of handicap (median time to complete this survey is 30 min.). We aim to include 200-250 patients in total for this study (deliverable, in progress).
We will perform a quantitative analysis of the validity, reliability, redundancy and difficulty of the items. This will create a (shorter) psychometrically robust disease-specific (set of) outcome measure(s). The discriminative ability of the developed measure(s) will be evaluated. In a subgroup of 20 patients we will ask to complete the developed instruments two times, with an interval of two weeks, to establish test-retest reliability.
With the longitudinal data from the prospective patients, we will evaluate the longitudinal responsiveness of the measuring instrument. Through our validation studies of these data, we aim to refine the items further to create a shorter, more targeted questionnaire to further minimalize the effort of outcome measurement for future patients.
Future deliverables will be the following publications on 1) Long-term clinical outcome and disease burden in anti-NMDAR encephalitis patients; 2) Long-term clinical outcome and disease burden in anti-LGI1 encephalitis patients; 3) Long-term clinical outcome and disease burden in anti-Caspr2 encephalitis patients; 4) The development and validation of a new composite PROM for autoimmune encephalitis patients.
The results of this study will determine the residual disease burden with regard to cognitive impairments, altered behavior and fatigue in auto-encephalitis patients. By using the data from this study, we will be able to develop a disease specific PROM that is valid in the way it determines clinical outcome and disease burden on multiple domains.
Due to this project’s awareness, I was invited to give a talk about clinical outcome measures on the European TREAT AIE networking conference (Florence, April 29-30, 2022). Within this meeting, we started a European collaboration, and my position within this projects puts me amongst the inner circle of starting this endeavor.
By using this PROM as a new outcome measure in clinical trials or patient registry comparisons, relevant clinical outcome will be measured in a more standardized way. Herewith studies will be able to include less participants, as the PROM will be more sensitive and has more statistically powerful.
By estimating the clinical outcome and disease burden in autoimmune patients, awareness is raised for the residual symptoms these patients suffer. This will lead to more targeted rehabilitation programs to support patients and their families as best as possible.
This AEA community seed grant provided me with more time to guide our two PhD-candidates, who are currently working on the PROMISE study.
The funding made it possible to hire Dr. Melissa Mandarakas, a methodologist with experience in developing patient reported outcome measures for 1 day per week for a period of 6 months to improve the PROMISE research protocol and to collaborate with us writing the systematic literature review.
Furthermore it has improved my research profile, increasing my chances in generating more funding for clinical research in autoimmune encephalitis in the future.
Thank you, Dr. Juna de Vries for your research and your commitment to improving the lives of patients and families impacted by AE.
Thank you to the entire AE Alliance Community for contributing during the 2020 Research Network Month which assisted in funding this seed grant project.
Thank you for your contributions this year to fund future research!
Together, we are changing the course of AE.