Inflammatory bowel disease clinical studies – where do we go from here?

Inflammatory bowel disease (IBD), incorporating Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing-remitting inflammatory disorder of the gastrointestinal tract.1 There is currently no cure for IBD and available treatments (e.g. aminosalicylates, immunosuppressant, biologics) have variable degrees of efficacy and tolerance. As a consequence, there is a large focus upon the development of new drugs for the treatment of IBD. While this is undoubtedly a welcome fact for patients and their families, the current level of research activity brings logistical challenges when conducting clinical trials.

The competitive trial environment for IBD is extremely crowded. As of October 2018, there were globally approximately 76 and 99 industry-sponsored, phase II-III CD and UC studies, respectively, that are planned or open to enrollment (plus a further nine CD studies and 11 UC studies that are ongoing but closed to recruitment).2 These studies not only compete for patients within each indication but also for site resources both within and across indications.

It is reported that over 1.5 million and 2 million people suffer from IBD in North America and Europe, respectively.3 Based on this fact, there should be no shortage of patients for recruitment into clinical studies across all phases. However, the reality is that sites within these two regions are saturated with IBD studies which are consequently requiring more sites than historically observed and are taking significantly longer to recruit.

Changes in the global incidence of IBD may offer a partial solution to this challenge. IBD has traditionally been considered a disease of the western world. The incidence of IBD in the western countries increased significantly during the latter half of the 20th century.3 This increase in incidence has been linked to a number of factors including genetics and urbanization. However, incidence rates in the western world are now showing signs of plateauing or even decreasing.3 In contrast, although still lower than western countries, incidence rates in Asia and Latin America (LATAM) are on the rise. This rise appears to be following the rapid industrialization/urbanization within specific areas of these regions,3,4 including China, Hong Kong, Japan, India and Brazil.4,5

So, has the industry started to follow this trend by placing more studies/sites in Asia and LATAM? The answer is yes – see Figure A. In comparison to the period 2008 to 2012, between 2013 and 2017 there was an increase of approximately 30% and 72% in the number of sites participating in IBD clinical studies in Asia and LATAM, respectively.6 While these increases appear large, they are based upon a low starting point, i.e. during the period 2008 to 2012, approximately 10% and 2% of sites participating in IBD studies were in Asia and LATAM, respectively. Although not the topic of this blog, it is also worth highlighting that the number of sites participating in IBD studies has also increased in Eastern Europe.

We now have to ask, is there room for further increase in the number of sites participating in clinical studies in Asia and LATAM? It’s reasonable to believe the answer to this question is yes, despite the fact that IBD incidence is still relatively low in comparison to western regions. This lower incidence rate is, to some extent, counter-balanced by the immense populations of most of the aforementioned Asian and LATAM countries, even accounting for signs that incidence rises are more typical in metropolitan areas.3 To highlight the potential to further increase the number of participating sites in Asia and LATAM, Citeline Sitetrove currently has 47 IBD sites listed in China, 59 in India and 46 in Brazil – this in comparison to the UK (having a vastly lower population) which has 98 listed IBD sites.

Figure A: Percentage of Listed Sites Participating in Phase II-III IBD Clinical Studies

Data source: Citeline Sitetrove
MENA = Middle East & North Africa; RSA = South Africa

Including more sites in Asia and LATAM in IBD studies will clearly not entirely solve the patient recruitment challenges created by the current competitive environment. However, as part of a multi-faceted recruitment initiative, it has the potential to somewhat ease the trial burden on North America and Europe.

If you are currently planning an IBD clinical study, we have the global infrastructure and access to unique proprietary databases allowing for optimized country and site selection, aligned with your specific target patient population and ensuring that recruitment meets your expectations. To highlight our experience in these regions, at this point in time (October 2018) and across all therapeutic areas, we are currently managing >180 studies and >2100 sites in Asia (including UC) and >60 studies and >750 sites in LATAM. Data quality in the regions is excellent as testified by no critical findings across the 13 sponsor inspections and the 53 Investigator inspections over the past 12 months.

This article was authored by:

Martin Knight BSc (Hons), Dip Clin Sci
Senior Director, Strategy & Planning
Inflammation, Infectious Disease & General Medicine (iiGM)
Global Clinical Development 

Katerina Cooper
Medical Director
Inflammation, Infectious Disease & General Medicine (iiGM)
Global Clinical Development

Susanne Greutter-Urban
Senior Director, GenMed Therapeutics
Project Management
Global Clinical Development