Q&A 19 - Mavenclad, AHSCT & evidence-based medicine

Mavenclad has been tested only once versus a placebo. How was this kind of trial made possible and allowed? Can we speak of collective bias?

Questions

Dear Prof G

Here are a few questions about the scientific conditions that led oral cladribine (Mavenclad) to be labelled and available for RRMS.

Q1: Within the evidence-based medicine (EBM) paradigm, any new drug must be tested within a randomised trial and compared to available treatment(s). When effective treatments are already available, using a placebo to test the new DMT efficacy is unethical. However, as far as I know, Mavenclad has been tested only once versus a placebo.

Could you please kindly explain:

Q2: How was this kind of trial made possible and allowed?

Q3: Whereas the EBM pyramid has not been respected (no randomised trial involving another DMT), how come a scientific consensus was reached to rate Mavenclad as a "highly effective DMT", same as Ocrevus, Lemtrada or HSCT?

Despite a poor level of evidence (according to EBM requirements), Mavenclad is regularly prescribed, whereas, despite substantial scientific literature and data, many neurologists keep asking for more evidence (through randomised trials) for HSCT.

Q4: Can we speak of collective bias? Is it only because of the HSCT mortality rate?

Thank you for your attention.

I am looking forward to your reply.

NOTE: General substack newsletters and microsite are free; only Q&A sessions are restricted to paying subscribers. I can't run and maintain the MS-Selfie microsite, hence the need to pay people to help do the work for me. If people want to ask medical questions unrelated to the Newsletters or Podcasts, they either need to become paying subscribers or email (ms-selfie@giovannoni.net) to request a complimentary subscription.

Answers

Q1: Within the evidence-based medicine (EBM) paradigm, any new drug must be tested within a randomised trial and compared to available treatment(s). When effective treatments are already available, using a placebo to test the new DMT efficacy is unethical. However, as far as I know, Mavenclad has been tested only once versus a placebo.