Rationale As the pathophysiology of migraine is complex, the treatment responses of
different migraine preventives are highly heterogeneous. Therefore, migraine patients
often try out more than one preventive until an effective treatment is identified. If one
can predict individualized treatment effects of these preventives, time to effective
treatment may be reduced. We propose that ML may be used to predict individualized
treatment effects for migraine preventives (machine prescription).
We are currently developing several ML models for this purpose. The first was developed
in 2022 and uses clinical characteristics to estimate individualized treatment effects.
The second is under development and uses a combination of genetic and clinical data,
while the third will use sociodemographic data. Both of the two latter are trained to
predict the effect of commonly used prophylactics in Norway. The result is three
different ML models that use different sets of features to predict treatment effects. To
compare the performances of these models, we will conduct a pragmatic observational trial
to test and compare the models in an independent dataset. Such out-of-sample testing is
essential to establish the clinical applicability of the machine prescription models.
Objectives, Endpoints and Estimands The primary objective is to evaluate if machine
prescription can predict the treatment effect of commonly used migraine preventives at
the individual level. The endpoint for this objective will be the best machine
prescription model's ability to predict treatment response (defined as 50% reduction in
headache days) measured by ROC-AUC. Secondary objectives include investigating if
time-to-treatment-response may be reduced using machine prescription, and if machine
prescription more accurately selects the best first-line therapy for migraine at the
individual level. Additionally, we will explore developing ensemble models combining the
pre-trained models, as well as creating new machine prescription models based on the
collected data.
Overall design
This is a prospective observational trial. There will be no control method or blinding.
The study population consists of participants with episodic and chronic migraine.
Intervention will be standard migraine preventives as prescribed by the physician in care
without any interference by the researchers. Each participant will be observed for at
least 12 weeks after starting a preventive. Summarized, participation may be presented
accordingly:
Screening/inclusion including phone consultation and feature questionnaire (week 0)
Baseline (week -4 to 0) Treatment period (week 1 to 12) Follow-up phone call for outcome
assessment (week 12) Optional additional treatment period (week 13 to 24) Optional
additional follow-up phone call for outcome assessment (week 24)
Brief Summary The purpose of this study is to estimate the ability of ML models to
predict the effect of migraine preventives. This will be achieved by first identifying
sociodemographic, headache and comorbidity features of migraine patients. Headache days
will then be measured for 4 weeks before starting a migraine preventive, and this will be
compared to the number of headache days in the first 12 weeks (divided into 28-day
periods) after starting treatment. The preventive is regarded as effective if there is a
50% or greater reduction in monthly headache days. After observation of the treatment
period, the ML models will use the sociodemographic, headache and comorbidity features,
captured before treatment was initiated, to predict treatment effect for all preventives
in each participant. These predicted treatment effects will be compared to the actual
treatment effects that were observed.
Study details include:
The study duration per participant will be up to 28 weeks. The treatment duration will be
decided by the physician in care, but the treatment period in which we will monitor
headache days will be 12 weeks for each treatment, with up to two treatment periods for
each participant.
The participants will have a phone consultation at inclusion and will have a follow-up
phone call at the end of the - or possibly both - treatment period(s) of 12 weeks.
Number of Participants A maximum of 200 participants will be enrolled. Note: Enrolled
means participants', or their legally acceptable representatives', agreement to
participate in a clinical study following completion of the informed consent process [and
screening]. Potential participants who are screened for the purpose of determining
eligibility for the study, but do not participate in the study, are not considered
enrolled, unless otherwise specified by the protocol. A participant will be considered
enrolled if the informed consent is not withdrawn prior to participating in any study
activity after screening.
Study Arms and Duration There is one study arm. Study duration is described under "Brief
Summary".
Data Monitoring There will be no data monitoring committee as it is not applicable for
this study.