Ruben van Eijk

That would work, thank you!

Is there a preferred term we should use in study materials?

Thank you for inviting me, it was great to hear about your important work! Great effort to develop methods for using real world data in drug development for #ALS #MND, including synthetic controls with the potential to reduce placebo & trial duration!

Remote monitoring of amyotrophic lateral sclerosis using wearable sensors detects differences in disease progression and survival: a prospective cohort study The results serve as motivation to incorporate accelerometer-derived outcomes in clinical trials, which is essential for further validation of these markers to meaningful endpoints.

@rpavaneijk.bsky.social & colleagues conducted a multi-year prospective cohort study of 97 patients with #ALS. Their findings: an #accelerometer -based measure is predictive of disease progression and related to patient-reported functioning: www.thelancet.com/journals/ebi...

Our study on the safety and tolerability of Trimetazidine in #ALS @braincomms.bsky.social
Trimetazidine reduced oxidative stress markers and energy expenditure, warranting a follow up study

@rpavaneijk.bsky.social @fredsteyn.bsky.social @ammaralchalabi.bsky.social

academic.oup.com/braincomms/a...

Dropout & attrition in #ALS #MND trials is a major challenge. We have created an #open-access calculator to estimate attrition rates for a given study duration, which can used to guide trial design and sample size calculations (tricals.shinyapps.io/Attrition/); the accompanying paper: rdcu.be/d3n36

Yes as prognostic factor it works great, could be used as eligibility criteria to leave out slow progressors, but correlation NFL - progression is not 1 to 1 and comparative data is sparse yet how well this works (and how much better it is than simpler methods based on FRS/clinics).

Regarding NFL, most programs include it as secondary objective now. I have some reservations still around NFL as probably small effects like Riluzole will not show a large change and would be difficult to assess in non-randomised studies.

You are right, the riluzole example is an RCT for patients who can't participate in the main RCT, which I believe is similar for EAP (only those not eligible for trial?). Think you need some control to make the data insightful.

Thanks! I would be interested in the starter pack as well!

A study of riluzole in the treatment of advanced stage or elderly patients with amyotrophic lateral sclerosis - PubMed Treatment with the neuroprotective drug riluzole has previously been shown to increase the probability of survival in patients with amyotrophic lateral sclerosis. This report describes a placebo-contr...

Maybe redesign how we use EAPs. I like the approach riluzole used - they did a controlled EAP study, which provided useful data (pubmed.ncbi.nlm.nih.gov/12021952/): "The primary objective was to enable access to treatment to patients excluded from the pivotal trial which was run in parallel."

Rethinking phase 2 trials in amyotrophic lateral sclerosis There is a long history of ALS therapies being promoted on the basis of Phase 2 data, which then fail to translate into meaningful benefits in Phase 3 tria

New paper to reflect on the main challenges in phase 2 #ALS #MND trials. Key issues relate too short study durations, reliance on the wrong outcome measures, absence of biomarkers, statistical issues, over-interpretation of 'clinical trends' and miscommunication. academic.oup.com/brain/articl...

Good points; EAP could evaluate safety and tolerability, but it is difficult to determine drug benefit in EAP. OLE (or ATE - active treatment extension - as I was told over the weekend) holds value to get some efficacy data, especially if there is a delayed effect, but doesn't replace a placebo.