It’s Halloween, let’s cue the scary music! You know the theme, the single note on the high end of the piano played repeatedly. Yeah, that one. Being a sponsor of a global clinical trial is not for the weak-hearted! What makes a sponsor’s hair stand on end? Interviews reveal the biggest terrors sponsors experience with their service providers is clinical study startup delays. On-time study startup challenges can cause delays and curse your entire clinical trial by:
- Delaying site initiation visit (SIV) and first-patient-in (FPI)
- Missing enrollment timelines including last patient first visit (LPFV) and other targets
- Losing ground with compliance and attrition issues including last patient last visit (LPLV)
- Struggling with the complexities of increasingly global clinical trials
- Checking out that strange sound you heard in the basement when you should just leave
Global on-time study startup challenges are sinister, and they grow and grow! Don’t panic, your trial isn’t doomed. Just be very careful, keep your eyes open, and plan, plan, plan. Don’t wait for the zombies to arrive before you start planning. Here are some helpful tips.
Beware of the unexpected!
There are well-known causes of delay in the execution of a study. Delays caused by the following matters are usually expected and rarely come as a surprise:
- Site contracting
- IRB/EC approvals
- Protocol amendments
- Patient enrollment
- Patient retention
But what about the causes of delay that are lurking in the shadows? Trials haunted by hidden causes of delay usually lack planning around these vital activities:
- Ancillary supplies and equipment (getting the right supplies and getting them to sites on time)
- Study materials and approvals (recruitment materials, dosing diaries, etc.)
- Translations (materials translated accurately into local languages)
- Recruitment planning
- Global logistics
These components hide well (and they’re good at suppressing their sinister giggling) because they aren’t always part of a sponsor’s planning process. Yet they can cause major problems when left out. Identifying each of these elements and giving them a sense of urgency in the planning process is critical to ensuring on-time trial execution.
Common gaps prior to study startup
Activities leading up to study kickoff and site initiation typically fall short in taking these three things into account:
- Protocol requirements
- Site needs and wants
- Local considerations
Let’s explore examples of each of these gaps in high-definition detail:
Protocol requirements
The specific requirements in a protocol can create special challenges, especially in multinational trials. For example, a protocol may stipulate that specific brands of equipment are required because the sponsor needs consistency across the board to ensure consistent data.
Different types of equipment are regulated in certain countries. In our experience, sponsors don’t always fully consider the location of where equipment or supplies will be used. Trying to ship a given brand of equipment into a country where it is not approved is a recipe for disaster.
Electronic devices require a power cord (pro tip: don’t trip on these when trying to escape the monster). The power cord has to accommodate each country’s specific sockets and voltages. Anyone who has traveled internationally has experienced this firsthand.
If the sponsor has not conducted compatibility testing on alternate items, they will find themselves in a bind trying to get like items capable of being used in the study.
While this can present challenges with procuring items, especially given today’s supply chain problems, the issue can actually be much bigger. Having compatibility testing done in advance on alternate items gives you flexibility if the initial items desired aren’t available or will be significantly delayed. Due to persistent regional conflicts and other geopolitical factors, simply finding the supplies needed to run a trial is a lengthy and frustrating process.
Another common example of protocol issues that can cause on-time study startup challenges is when the study drug needs to be kept within a specific temperature range. This affects how you’re going to store, package, and transport the drugs, and it is a complex undertaking.
Site needs and wants
This is where a lot of boxes need to be checked off. What do sites need and want to get started and to be able to conduct the study successfully? What will they need to comply with protocol requirements and conduct the study effectively? Don’t leave your sites alone in the wilderness.
Do your sites have all the equipment that’s necessary to conduct the trial? They might have outdated equipment, or it might not be calibrated appropriately. Are all sites able to capture information in the same way to get consistent and accurate input and data from the tests that will be conducted?
Different sites often want different materials to conduct the study. Some may want, for example, a pocket protocol they can carry with them, or a laminated guide that has the site process and specific recruitment materials that they would prefer. These individual preferences need to be identified and shipped to the sites. Sites are not one-size-fits-all. More on this in the next section.
Local considerations to prevent on-time study startup challenges
Most phase 3 trials are conducted internationally. Differences in local requirements from country to country make multinational studies especially challenging. Customization is required to conduct the study at a local level. This includes maintenance, calibration, disposition, customs clearance and import regulations, technology infrastructure, regulated devices, instructions for use, and translations.
Here is a common issue: once you choose a particular software platform, you must further investigate to determine whether all sites have the capability to use that software. Another issue is whether sites have the equipment and bandwidth to use the software.
Again, the logistics challenge rears its head. Specific brands are just part of the issue. The way you label and package those items can have a direct impact on whether they will be allowed through customs. Trying to get these through regulatory bodies, through different distribution channels, and through customs so they can reach the study site on time presents another set of issues that must be considered.
When these issues are not properly planned and accounted for, and are then fed through the bottleneck of global logistics, teams find themselves weighed down with significant headaches and unexpected delays.
Translation is another issue critical to study conduct. It can impact recruitment, consent, and retention. It goes beyond just getting the words translated and onto the page. There is an incredible amount of nuance that is involved with translating for effectiveness, including local dialect-related finessing, cultural considerations, and more.
Too often, teams think of translation too late and then discover that turn times are much longer than expected. Imagine reporting to management, investors, and your customer that the study start is on hold because you are waiting for translations. The devil is in the details when it comes to creating delays.
Considering impact
Here are typical timelines for different elements of study conduct.
These steps generally take place in the order listed. And when one gets delayed, it can maniacally impact every next step – for example, materials must be written before they can be translated.
Individually and cumulatively, these gaps in planning destroy study timelines and add ghastly costs. Ignoring them, or setting them aside to sort out later, is an invitation to failure.
To sum it all up: Don’t be a study startup victim. Don’t be like a group of teens facing danger! Make good choices!
The Imperial Advantage
Don’t venture into the study startup woods alone! Sink your fangs into study startup success by calling on Imperial.
Though we are mere mortals, our teams will whip up what you need to deal with on-time study startup challenges and ensure study success with wizard-like perfection.