Hi (again) Reg,
IMO you're on a key point that a lot of people miss. There's an absolute dearth of research articles, or scholarly works generally, about label extension
from paediatric indications
to adult indications by
extrapolation. Rarer than hen's teeth. I've been doing research on it for a few days now, so I feel I'm at the cutting edge. Ha.
Almost always the label extension path is from adults to paediatrics.
Why? Because the adult trials can be run very rigorously in terms of science. They can produce the very best possible evidence of efficacy & safety - without having to worry about e.g. the ethics of child consent, or the inability of the patient/ participant to communicate their experience adequately for themselves. Also, the impact of treatments on diverse minority groups in society can be best explored in as large a scale trial as is possible, & in the West the larger group in a given population is sure to be the adult population.
So, against that background, & in the context of label extension from adults to paediatrics, what is common is what regulators call '
paediatric (pediatric) extrapolation'. I recommend that everyone look this thing up for themselves so that they understand what Reg & I are
NOT rabbiting on about. This is where a regulator find a statistical way to help kids with an approval based on adult population research outcomes (IFF a sponsor has no or very limited paediatric data to support possible treatments). The FDA even has a draft Guidance on it - link
here.
So you'd think OK, it might/ should work the other way round then, eh? But it seems the concept of 'pediatric extrapolation' shouldnt be assumed to be a bidirectional thing i.e. equally amenable to some concept of '
adult extrapolation'.
See para. 2 above. The regulators say, point blank, it's not the same - because the acceptability of the process is driven (in the case of the kids) by a need
incapable of being met any other way, whereas trying to persuade the FDA kids mini-trial evidence is good enough evidence for whole of population indication approvals in the case of adults, the FDA's overwhelmingly likely to say IMO 'meh...just do the trial...no excuses for you lot, you adult, consenting humans you'.
The FDA is struggling with making the US Pediatric Research Equity Act (PREA) work at the moment. They'd love to see adult and pediatric trials wrapped up in one. But it's not happening. It's all about money, of course.
This article puts the problem & all the challenges into perspective IMO:
https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1002/cpt.1886So, in the meantime, for adult indications we will need adult studies/ trials.
Cheers
GLTA(LT)H
(20min delay)
