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Ruben van Eijk @rpavaneijk.bsky.social · 05/12/2025

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

Ruben van Eijk @rpavaneijk.bsky.social · 22/05/2025

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!

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Ruben van Eijk @rpavaneijk.bsky.social · 13/12/2024

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

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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).

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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.

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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.

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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."

pubmed.ncbi.nlm.nih.gov

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...

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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...

academic.oup.com

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

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Ruben van Eijk @rpavaneijk.bsky.social · 10/12/2024

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.

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