Six Reasons to Plann Your Clinical Trial

Clinical trials are a long, tiresome and costly process, and represent the most important part of a drug development cycle. However, 85% of all clinical trials will be completed with delays¹, and this will have an immediate impact on clinical trial budgets. Delays in completing clinical trials cost pharmaceutical companies between $600,000 and $8 million on a daily basis ². It might be good to know that it is indeed possible to avoid delays, not only decrease them, and that even the most complex clinical trials can be completed on time.

The patient recruitment, which is typically recognized as the number one reason for missed study deadlines, is one of the most important parts of the clinical trial process. Besides being most challenging, this part of a clinical trial is very time consuming and takes up more than 30% of all the clinical time. Pharma and CRO companies are aware of the complexities involved in patient recruitment, however, identifying challenges is an even more difficult task, and requires time which is a sacred resource in the world of clinical trials.

Pharmaceutical and CRO companies typically invest approximately one week in performing feasibility analysis and planning for their clinical trial, if planning is performed at all. This time is not sufficient for gathering and analyzing critical information and making decisions that will enable clinical trials to be conducted and completed on time. Due to short timelines, key decisions for conducting clinical trials are often based on previously completed trials with similar design, or on the company`s experience. While experience in trials with similar design can be helpful, it can also be misleading, especially in a high-paced industry like this one, where important elements of the study protocol can easily be overlooked. Every clinical trial is unique; therefore, it would be more useful to look at the experiences gathered in previous trials with similar indication as an important piece of the puzzle – important, but still insufficient for making the right decision. The best way to get the full picture is by conducting a detailed feasibility analysis, preferably as early as possibly in the clinical trial process. The chance is 80% greater that a clinical trial planned based on a data-driven analysis will be completed on time, with no unplanned costs.

Some of the main strategies for decreasing study costs and completing trials on time will be disused below.

Selecting The Right Countries

The selection of countries (regions) is one of the key steps when it comes to clinical trial planning. Suitability of regions and countries for a particular clinical trial should be examined with special care and investigated from different perspectives. Country-specific start-up timelines, potential regulatory constraints, standards of care, acceptability of offered treatment, availability of other treatment options, competitive clinical trial landscape, availability of resources and facilities, epidemiology of the disease and availability of patients, are only few parts of the puzzle that should be reviewed in detail before getting the full picture.

However, the selection of countries is very often influenced or made based on wrong reasons. When it comes to planning clinical trials successfully, it is of utmost importance to select regions and countries that have the highest potential to recruit on time, with no delays, and with good quality. In spite of that, CRO companies very often fail to select the strongest countries only because they have no staff in certain regions, or because they need to work more in other regions. I can recall one trial for which the countries selected were not the right ones, and yet they were proposed to the client only because the client suggested them. Instead of investigating the client’ s preferences and making sure that the most efficient option was selected, the trial ended up running in countries where it was very difficult, and almost impossible to find patients. Due to the country-specific standards of care and drug reimbursement policy, patients were not interested in participating in the trial since they had better treatment available at no cost in their respective countries. Only when the trial fell behind with recruitment, it was agreed to perform a detail research and identify the most suitable countries for the trial.

Another very common mistake is selecting regions and countries that have been most frequently selected by other sponsors in the past or that are selected for ongoing trials in the same indication. Although frequent selection of the same countries by various sponsors is a strong indicator that these countries should be researched further, this is not sufficient for excluding other countries from selection. Placing clinical trial in countries with a high number of completed trials may result in having a high number of experienced investigators whose potential to complete your clinical trial successfully is higher. However, these sites might not have sufficient time and resources, their motivation and compliance may not be as high as you would want them to be, and their patient pool might be depleted. All this might decrease your chances to recruit patients on time.

The saying has it that the majority is not wise, and we should be able to think out of the box. Going to countries that have rarely been selected by sponsors in the past, and yet have qualified sites and access to patients might be a jack pot option for you.

 

Going Where The Patients Are

Access to patient population is another reason for emphasizing the region/country selection.

Instead of using the traditional approach that comprises of selecting sites and then trying to figure out ways for increasing their recruitment potential at the second stage, we suggest doing the opposite. Locating regions that have access to large patient populations and placing sites around and in those regions is the way to go. One should not be discouraged to learn that the region identified as the region with a large patient pool includes only a limited number of sites with experience in clinical trials. What I have witnessed over the years is that the sites that had never participated in clinical trials were more attentive during initiation and monitoring visits, more open to suggestions, and in the end made less mistakes than the more experienced ones.

It is recommended to conduct a thorough analysis of patient distribution between regions, countries and sometimes even between cities. For some indications, like allergies or endemic diseases, targeting regions with a high prevalence of the disease is of utmost importance for the trial success. For others, prevalence of the disease might not be as impactful; however, patients might be distributed around few big referral sites due to centralized health care structure of the country, or due to rarity of the disease.

Selecting The Right Sites

The importance of selecting the right sites can be best understood in the light of statistical data that suggest that nearly one-third of the sites performing clinical trials have never enrolled a single patient. That is more than 33% of all participating sites, and in certain geographic area the percentage is over 40%. Moreover, it is stated that, in a typical trial, more than one-third of sites under-enroll patients and roughly one-tenth of them fail to enroll even a single patient³.

Sometimes it can happen that the selected sites have access to patients; however, they do not have time or resources, or might not be motivated due to complex internal administration, or lack of research interest. Understanding the motivation and performance potential of the sites as early as possible in the process and finding ways to maximize their engagement will have multiple benefits on the success of trials.

Using Correct Recruitment Estimates

Roughly 85% of clinical trials fail to meet enrollment timelines and approximately one-third (30%) of phase III study terminations are due to enrollment difficulties.

Both CRO companies and sponsors are aware of these difficulties, and they often seek direct recommendations of site investigators for estimates of patient enrolment. The most common way to collect this information is through feasibility questionnaires. These questionnaires can be simplistic, typically focused on the number of patients who fit the study criteria treated by the investigators, and how many they believe they would be able to recruit for an upcoming trial. Or they can be the opposite, too detailed, asking questions about the site’s administration and questions that are not crucial for understanding the site`s performance, thus minimizing the motivation of investigators to complete them.

The majority of investigators tend to overestimate their recruitment potential, and CRO companies, being aware of it, will typically try to mitigate the overestimation risk by decreasing investigator estimates by 50% or 30%. Neither of these options is accurate. We would rather say that these are educated guesses, as they rely on non-bounding estimates of investigators, typically based on incomplete information provided in a rush.

The key to successful recruitment estimates lies in being able to calculate the site’s realistic recruitment potential, as opposed to relying on the investigator`s estimates.

Using Adequate Screen-out And Drop-out Rates

Successful enrollment alone does not ensure the success of the entire trial. It is only the beginning stage, and there are many more uncertainties to account for. For example, a patient recruited is not bound to stay with the trial. The reluctance of a recruited patient can be attributed to a wide variety of reasons ranging from simple logistics, to fear, or any inconvenience in adhering to the steps in the protocol, or to invasiveness of the treatment and diagnostic procedures. This reveals yet another problematic issue: patient drop-out rates in trials.

Selecting The Right CRO

In the end, have you selected the right CRO? It is known that same investigators achieve different recruitment on trials with similar design when they are managed by different CRO companies. Some CRO companies traditionally operate better in some regions, while they are not as efficient in others. Many times, this is realized only at the late stage of the clinical trial, when there is a need for “rescue”.

Instead of waiting to get in the stage when it is time for rescue, which will come at a price, it may be useful to consider combining few CRO companies, depending on their ability to perform in different regions.

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Instead Of A Conclusion

Unlike other trains, Maglev trains operate using magnetic levitation technology, floating only a few millimetres above the surface. These few millimetres enable a “floating train” to move ahead at great speed, taking advantage of the lack of friction. Maglev can compete favourably with high-speed rail and airplanes. We believe that a feasibility analysis can add these few millimetres to clinical trial planning and make the difference between clinical trials completed with delays and unwanted costs, and successfully completed clinical trials. Failing to adequately plan a clinical trial is the same as planning to fail, weather we are aware of it or not.

We hope that you will find strategies shared in this text useful, and that you might utilize them to set your trial on solid basis. Should you require any assistance with clinical trial feasibility and planning of your trial, our team will gladly support you. You can submit your question HERE.