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!

@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!

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."

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.