What Clinical Wishes Supply Did Better – And How To Close The Gap: Part 2 – Where Assumptions Break Trials
By Rachel Grabenhofer, Chief Editor, Clinical Supply Leader
Not all clinical supply breakdowns come from poor timing or communication, which we covered in part 1 of this series with Elena (Ella) Sinclair, principal consultant at FlexPoint Bio – who served in clinical trial and operations management and director roles for five years at Sangamo Therapeutics after 17+ years in clinical research at UT Southwestern Medical Center.
Some are built into the study from the beginning — through assumptions that go unchallenged.
“What I very rarely hear is: what kind of assumptions did we make that are going to break that study?” Sinclair highlights.
Those assumptions show up in subtle ways:
- Reusing plans from previous studies
- Assuming systems will behave as expected
- Treating supply challenges as straightforward
“Just because this plan worked on another study doesn’t mean that it will work exactly the same on the current study,” she says. “The patient profile, the sites, the protocol will all differ.”
Comparator drugs are one of the clearest examples.
“If a comparator is being planned, the right people need to be aware of that ahead of time. It’s just as trivial as that.” She’s observed several cases where this has failed. “The planning body thought, ‘Well, it’s standard of care — you just go into the pharmacy and buy it.’ That’s not how it works.”
Per Sinclair, companies need permission from the patent holder to use the comparator drug in a study. Comparators also require special labeling to anonymize them, so they appear similar to the drugs being tested. “Oftentimes, it takes six to nine months to procure that comparator,” she explains.
Another example is when the digital management system is misconfigured.
“Studies that use systematic tools such as IRTs to track the use of drug, the enrollment, etc. are set up to replenish a site with a particular frequency. But if they are not aligned with the projections of the protocol, this is a problem – and one that comes up frequently,” Sinclair observes.
She explains how IRT is generally considered part of the supply chain. And oftentimes the platform is selected based solely on: I used this company before, the platform worked fine, let's just bring it in. “But sometimes, things change,” Sinclair adds. “Especially in contemporary trials. Clinical trials are progressing, moving away from fixed designs and structures; for example, instead of bringing in a patient for every single visit, we’re moving visits to patients’ homes.”
It’s about adaptive design, and the actual supply will depend on which arm of the study it is moving toward. If the platform cannot adapt to that, or if the programming wasn’t well thought through, then you start having issues.
At the very least, Sinclair feels that clinical operations and supply chain should be brought together to determine the right technology to implement. “Especially considering that clinical operations is the one working with the sites and bringing patients in,” she explains.
If clinical operations has projections for how quickly to replenish drug at a site, but the site then lags in enrollment or is higher performing, as long as the IRT setup is known, those settings can be adjusted to keep up with the change in enrollment. Because ultimately, no one wants drugs sitting, expiring and being wasted.
Choose Sites Wisely and Give Easy, Clear Instruction
There are also several supply-related assumptions that create avoidable issues at the site level, when it comes to biomarkers, biosamples, and novel endpoints.
“The assumption is that site coordinators will figure out how to order kits. How to run a particular sample collection. How to ship everything. I can tell you 100%: They will not,” Sinclair emphasizes.
She explains this is especially the case because studies are becoming more complex, with more challenging biomarkers than ever before. “It’s not uncommon to have 40, 50 different biomarkers on a single study,” Sinclair says.
Ultimately, Sinclair advises, don’t make this assumption. Give them the instruction they need – and make it simple. “If a site can choose between working on a poorly designed clinical trial from a sponsor who is not really working with them, and another sponsor who has their ducks in a row, they will always choose the latter,” she suggests, highlighting that sites will also allocate the best coordinators and more time to sponsors that have their plan in order.
Sinclair additionally recommends, especially for complex clinical trials, choosing sites that are experienced. “They have been there, done that – so they have other comparative studies.”
To make it even easier, Sinclair believes in designing trial kits with the actual user experience in mind. “For kits or IP packaging, this is not usually the case, but it should be,” she says. “Especially if you have a very complex collection of samples or very complex processing.”
For example, if you require timed collection for your pharmacokinetics, “design kits like nesting dolls,” she envisions. “You open your first one with the tubes for your 15-minute collection, then inside there's another one for your 30-minute collection.”
She describes the desired experience as something like what Apple would create. “They go into detail and the product is easy to use. So, it is less a training issue and more a design issue — how intuitive the process is for those who are executing it under real-world constraints.
“Also, make sure you provide instructions – and not just here's your lab manual, follow it and figure it out,” she continues. “If you provide instructions that are very simple, that are written not for the scientist at the bench, but for someone who has just five minutes to figure things out… that’s critical.”
For example, explain that at week 24, here is what they need to prepare, what tool to use, where to ship it, and what it looks like. “Almost like IKEA-style instructions,” she says. “It works. I’ve used it at several sites and improved site compliance by over 80% just by switching to this approach.”
These challenges don’t end at planning. They carry forward into execution, where changing conditions make alignment harder to sustain.
