In no way is a single arm trial superior to an RCTLet's be...

In no way is a single arm trial superior to an RCT

Let's be honest here for a moment. There are instances where single arm trials may be preferred over a RCT (especially in rare diseases, life threatening diseases with minimally effective/ or very toxic SOC).

Single arm trials may be preferred:

1. Ethical reasons - patients/ physicians may have a preference for the investigational therapy and may not wish to participate in a randomised trial if the standard therapy is considered inferior. I would assume so even more for children where there is no alternative approved therapy (or current therapies considered not very effective or toxic).

2. Shorter timeframe to completion - therefore shorter timeframe for efficacy outcomes. Let's not dismiss the cost side of things when running a trial. IMO there would be less drug development innovation from smaller companies (or companies in the rare disease areas) if RCT were essentially mandatory for getting FDA approval due to significant additional cost/timeframes involved (with the potential downstream problem of less innovative therapies on the market if this were a blanket rule).

3. For rare diseases a smaller RCT may not ideally match patient characteristics between treatment and placebo groups as eloquently put by @WesM in above posts. In this instance an external control group may be a beneficial methodology to overcome the limitations of the RCT design. This is important because intergroup variation (e.g. based on disease severity, age, sex, race) will be less if matched to an appropriate historical control (e.g. MAGIC Database) than if just randomly assigning patients to Drug or Placebo group.

Of course RCT are considered gold standard in most instances. But I disagree that they are superior in all ways (and therefore in all circumstances) like you stated.

IMO the regulators would benefit from access to RCT data, real world evidence, case controlled data when assessing a new drug applications. However this is not always feasible (or in some instances ideal) in the real world and hence why drug approvals can be given (and are increasingly given) without the need for a Randomised Controlled Trials (especially in the field of Oncology and/or rare diseases).

What's more, at the end of the day it's up to the FDA to decide if there is a clear medical need and the benefit to risk ratio is favourable based on the data provided (I am confident that this will be the case) assuming now the potency assays... have been adequately addressed.

Nearly there folks!