CEO Itescu needs to go, page-95

Hi @MJC73,

regarding your Post #: 69184113,

just by way of clarification, in my note to @LeftYahoo I asked the same question - 'study' or 'trial' - because one instinctively thinks it is an important question. And one might go as far as to reasonably consider a 'trial' to be a more 'serious' thing than a mere 'study'. I was trying to draw @LeftYahoo to comment on that, because his posts are inevitably insightful and well worth reading.

But the scientific fact is that it's a question that doesn't have an easy answer. Even from the FDA's point of view. Look again at the extract which I posted from John Colcato's image as used in his NEJM article.

You'll see that an 'Externally Controlled Trial' can at the same time be a 'Non-Randomized Interventional Study' - in the eyes of the FDA's RWE division itself!

Here's an extract from Colcato's article which, IMO, shines a light for us on the relevance of RWE issues for the FDA when it comes to MSB's approval:

" ...The second misconception is that a simple dichotomy between randomized, controlled trials (RCTs) and observational studies delineates the entire landscape of study design.

Although randomization of treatment assignment is a key strength of RCTs, not all clinical trials are randomized; rather, their defining feature is assignment of treatment according to an investigational protocol.

For example, in single-group trials, investigators assign participants to receive an intervention without randomization — and face challenges similar to those in observational studies in determining whether differences in clinical outcomes between the protocol-driven group and a comparator (“control”) group represent actual treatment effects..."

and again:

" ...Also, although the terms “clinical trials” and “observational studies” have clear meanings when used properly, the terms “interventional studies” and “non-interventional studies” have advantages in describing whether the treatment of interest was administered according to a study protocol.

These conceptual distinctions were less pertinent when causal inferences regarding therapeutic effectiveness relied mainly on interventional studies with primary data collected in traditional RCTs. Increasingly, however, RCTs incorporate RWD, and when randomization isn’t feasible for ethical or other reasons, externally controlled trials include a comparator group derived entirely from a source of secondary data (“external” to the treatment group). Conversely, noninterventional studies that analyze primary data collected from registries are being conducted more often.

Notwithstanding confusion regarding these terms and concepts, we at the FDA continue to evaluate RWD and RWE as we consider regulatory decisions...".

Hope this assists with your question.

Cheers & GLTAH