Great post Adam! Love to see more people looking to the past to improve clinical trials. I'm curious to get your take on how the evidentiary bar might have changed over time. Is it possible that drugs approved previously wouldn't be up to stuff today? And is there a way to think of drug approval rates in "real" terms?
“What’s the smallest incentive change that would actually move behavior? (e.g., inspection expectations, sponsor–CRO contracting, liability, insurer requirements, journal norms?)” And is there a similar structure for medical device testing?
The complexity is real, but much of it is structural rather than scientific now. Every layer that got added (monitoring plans, SDV, deviation logs, query resolution, TMF completeness) created a role, and every role created a handover. On the staffing side the constraint has moved from “can we run the science” to “can we find people who can hold the whole trial in their head”. Risk-based monitoring only reduces burden if your monitors are senior enough to make judgement calls instead of ticking every box, and those people are scarce. Study startup and CRA turnover are the two costs nobody budgets properly. On how the CRA role is actually scoped in the Dutch market: https://www.sire-search.com/clinical-research-associate-cra-nederland/ (Dutch language).
It's a really great and thoughtful article. Often discussions on the economics of clinical trials don't go much beyond costing.
I work across ANZ as a physician-executive, economist and trialist.
NZ is an interesting study in minimal regulation- possibly the country with the least CT reg's of high income countries and you can't sue. Yet, trials are mostly as complicated in both countries, because of US FDA reg's.
Confession: as a PI, I find all the Governance complications reassuring. I've been an IIS site where the CPI got a negative regulatory report and contrasting investigator-led and sponsor/CRO-led is like night and day in terms of robustness.
That said, it's precisely that sort of thing that's an issue. The game results in risk and corresponding defensiveness at site, hub and sponsor level, that significantly impact timeliness to market.
Please post an update if you publish a journal article on this.
Great post Adam! Love to see more people looking to the past to improve clinical trials. I'm curious to get your take on how the evidentiary bar might have changed over time. Is it possible that drugs approved previously wouldn't be up to stuff today? And is there a way to think of drug approval rates in "real" terms?
“What’s the smallest incentive change that would actually move behavior? (e.g., inspection expectations, sponsor–CRO contracting, liability, insurer requirements, journal norms?)” And is there a similar structure for medical device testing?
The complexity is real, but much of it is structural rather than scientific now. Every layer that got added (monitoring plans, SDV, deviation logs, query resolution, TMF completeness) created a role, and every role created a handover. On the staffing side the constraint has moved from “can we run the science” to “can we find people who can hold the whole trial in their head”. Risk-based monitoring only reduces burden if your monitors are senior enough to make judgement calls instead of ticking every box, and those people are scarce. Study startup and CRA turnover are the two costs nobody budgets properly. On how the CRA role is actually scoped in the Dutch market: https://www.sire-search.com/clinical-research-associate-cra-nederland/ (Dutch language).
It's a really great and thoughtful article. Often discussions on the economics of clinical trials don't go much beyond costing.
I work across ANZ as a physician-executive, economist and trialist.
NZ is an interesting study in minimal regulation- possibly the country with the least CT reg's of high income countries and you can't sue. Yet, trials are mostly as complicated in both countries, because of US FDA reg's.
Confession: as a PI, I find all the Governance complications reassuring. I've been an IIS site where the CPI got a negative regulatory report and contrasting investigator-led and sponsor/CRO-led is like night and day in terms of robustness.
That said, it's precisely that sort of thing that's an issue. The game results in risk and corresponding defensiveness at site, hub and sponsor level, that significantly impact timeliness to market.
Please post an update if you publish a journal article on this.
Very interesting post, I enjoyed reading it and learned a couple of things too!!