Clinical Research

Before you plan your next study, please read this first.

Planning and conducting a clinical trial presents numerous challenges, and we find that many sponsors and CROs repeatedly miss important areas when planning their studies. These planning gaps result in:

• Delayed clinical study startup
• Missing key enrollment timelines
• Retention and compliance issues

I will explore delayed study startup in this blog post and address the other gaps in future blogs.

Sponsors regularly tell us that delayed clinical study startup is their number one source of frustration. When the study eventually begins, it is on a bad footing. Late starts have a reverberating effect that negatively impacts the entirety of the trial.

Expected and well-known causes of delay include:

• Site contracting (the number 1 cause of delay in trials)
• IRB/EC/regulatory approval
• Protocol amendments

These are well-known causes of delay in executing a trial, but what about the hidden causes?

Hidden causes of delayed clinical study startup

Advance planning of every detail is essential, and lack of planning around these important activities often occurs:

• Preparation of protocol-related site materials and shipment to study sites (reference documents, data collection tools)
• Preparation of recruitment and retention materials with on-time shipment to study sites (recruitment materials, dosing diaries, etc.)
• Translations (patient-facing study materials translated accurately into local languages), getting the materials shipped into these countries, along with local review prior to going for IRB/EC approval
• Ancillary trial supplies and equipment (getting the right supplies and getting them to sites on time)
• Training site staff
• Development of proactive recruitment and retention plans

I call these components hidden because they aren’t always part of a sponsor or CRO’s planning process, yet they require a huge amount of steps and time. Identifying each of these elements, and giving them a sense of urgency in the planning process, is critical to on-time trial execution.

Common gaps that occur prior to clinical study startup

Activities leading up to study kickoff and site initiation requires direct support in three areas:

• Protocol requirements
• Site needs and wants
• Local considerations

Let’s explore examples of each of these gaps:

Protocol requirements

The specific requirements in a protocol can create special challenges, especially in multinational trials. For example, a protocol will often stipulate that specific brands of ancillary supplies and equipment are needed 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 and CROs 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.

And oftentimes, an electronic device has a power cord. 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/CRO 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 in the event that the initial items desired aren’t available or will be significantly delayed. Due to zero-Covid policy manufacturing shutdowns in China, as well as the war in Eastern Europe and other geopolitical factors, simply finding the supplies needed to run a trial is a lengthy and frustrating process.

Another common example of protocol challenges is when the study drug needs to be kept within a specific temperature range. This affects how you’re going to store, package, monitor, and transport the drugs, and it is a complex undertaking.

Site needs and wants

This is where a lot of boxes need to get checked off. What do sites need and want to get started and conduct the study successfully? What will they need to comply with protocol requirements and perform the study effectively?

Do your sites have all the equipment necessary to conduct the trial? They might have outdated equipment, or it might not be calibrated appropriately. Are all sites trained and able to capture information in the same way to get consistent and accurate input and data from the study testing?

Various sites often want different materials to conduct the study. Some may prefer, for example, a pocket protocol they can carry with them or a laminated guide with the site process or preferred specific recruitment materials. 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

Most phase 3 trials are international. 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.

Software

Here is a common issue: once you choose a particular software platform, you must further investigate to determine whether all sites have the capability and equipment to actually use that software.

Logistics

Again, the logistics challenge comes up. Specific brands are just part of the issue. The way you label and package those items can directly impact whether they will be allowed through customs. Trying to get these through regulatory bodies, different distribution channels, and customs, so they can reach the study site on time presents another set of issues for consideration.

 When these issues are not properly planned and accounted for and then fed through the bottleneck of global logistics, teams find themselves weighed down with significant headaches and unexpected delays.

Translation

Getting clinical trial materials translated 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. Clinical study materials require translators experienced in life sciences to precisely convey protocol-specific elements and the nuances of the local dialect and culture. Effective and experienced translation project management also helps keep the translation process on track.

Too often, teams think about translation too late and find that reasonable turn times are much longer than expected. Imagine reporting to management, investors, and your customer that clinical trial startup is on hold because you are waiting for translations. The devil is in the details when it comes to on-time studies.

Conclusion

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 impact every next step – for example, writing materials has to occur before translation.

Individually and cumulatively, these gaps in planning destroy study timelines, delay clinical study startup, and add extraordinary costs. Ignoring, or setting them aside to sort out later, is an invitation to failure.

To sum it all up: plan, plan, plan.

In my next post in this series, I will write about planning enrollment timelines and meeting the first patient in and last patient/first visit goals.