In June I had the privilege of publishing and presenting the following research at DIA Annual Global meeting in Philadelphia. The analysis was completed using BrackenData tools, from which we also used the visuals you see. Learn more about our tools here.

My team is continually analyzing clinical trial data on a global scale, and identifying interesting trends to share. One look at aggregate numbers will show you that global clinical trial activity has been growing steadily over the last 5 years. However, when we mapped this out to identify the biggest growth centers what surprised us wasn't any particular place of extreme growth, but that amidst such growth there are three regions in the world where clinical trial activity is rapidly declining. These three regions are Africa, South America, and the Middle-East. I'll tell you how we pin-pointed this, and why we think this decrease is taking place, but first I’d like to explain how we came to this conclusion.

Method

Firstly, we sourced our data from ClinicalTrials.gov (CT.g), the NIH’s online registry for clinical trials. This is the world’s largest public source of clinical trial records, as I’m sure most of our readers are aware. However, the CT.g dataset contains a number or errors – mainly human error on the misspelling of country names – that we needed to clean up with the use of a filtering and logic process. We then compiled all the Phase 3 studies in the last 6 years and looked at the mean and median number of studies per year. In Fig 1,  in red, we can see the count of NCT numbers (the unique identifier for a clinical trial on CT.g) per year and the average enrollment.

 

Results

 Fig 1

Fig 1

Although the graph looks dramatic, the relative numbers are not that different from year to year.  Since we were evaluating the number of countries being used for recruitment, we deleted all studies which were recruiting from only one country.  This has the effect of providing a clearer signal where n > 1. Fig 2  provides the actual number of phase 3 trials per year, and the mean number of countries with median number in brackets, that were used for conducting these studies since 2010, where the number of countries is greater than 1.

 Fig 2

Fig 2

The number of phase 3 trials and the median number of countries stays consistent over the last 5 years. If we were to look only at these numbers, there would be no implication of steady growth or decrease of phase 3 activity across the globe. But once we actually map where these phase 3 trials are taking place a different story develops. The aggregate numbers are misleading because the dramatic decrease in some regions is offsetting steady growth in the rest of the world. We created geographical heat maps of the countries involved in clinical trials over the years.  Look for the areas where the number of studies is decreasing and it was very apparent where the decreases were occurring..

 Fig 3

Fig 3

The three areas I’d like to highlight are Africa, South America, and the Middle-East. This is where there has been nearly a 50% decrease in number of studies over the last four years, but especially in the last year. Exact numbers are in Fig 4.

There is a clear decrease in trial activity in Africa, shown by the amount of white space (that signals zero activity).  A similar picture emerges in the  Middle-East and South America. Again, we have the numbers to back this up in fig 4, but the pictorial representation of our data makes it rapidly apparent.

Conclusion

Our hypothesis as to why these decreases are happening have to do with political and public health factors, though further work will need to be done to confirm this. The decrease in trials in Africa and the Middle-East correlate with conflicts in those areas; the Arab Spring in North Africa and the Syrian Crisis in the Middle East in particular. South America also has some political unrest, but we hypothesize that fear of the Zika virus has contributed to the lack of desire to travel or conduct clinical studies there.

Since publishing this data, we have received confirmation of these global findings from a large pharmaceutical company.  The main reason for the decrease in clinical trials in South America, according to this source, is that the cost of doing business and getting product into the various countries makes it economically and logistically challenging.

A limitation of our study is the assumption that all Phase 3 studies are registered on CT.g. However registering a trial on CT.g, in order to receive an NCT number, is a required step for any clinical operations team that wants to ensure information about the trial can be used in publications.  Therefore we believe that the data from CT.g captures 95% of all the multi-center, multi-country clinical trials

In conclusion this research proves useful in giving insight into the geopolitical aspects of recruiting subjects into multi-centers for phase 3 clinical trials. For the first time in six years we’ve observed a decline in countries where clinical trials have been conducted. This suggests that political changes across the globe have a profound effect on the recruitment of clinical trial subjects.

Do you have any data or insight into our hypothesis to share? Please add to the conversation by leaving a comment.

Acknowledgements: I’d like thank and acknowledge my co-author Emmanuel Olart for providing his data science expertise.

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