At Clinical Accelerator we are always looking to the future for new innovations and advances in technology. But what will that future be like? In this post I discuss the increasingly globalized clinical trials market and the challenges this poses, as well as the technologies, which may change the nature clinical trials over the coming years.

Clinical trials today: ClinicalTrials.gov data analysis

The ClinicalTrials.gov is web site maintained by the National Library of Medicine at the U. S. National Institute of Health. The site has 176 696 clinical trial studies listed across America’s 50 states and in 187 other countries worldwide (as of October 15, 2014) (1).

On average ClinicalTrials.gov receives more than 112 million page views per month, with 57 000 unique visitors daily (as of July 2014) (1).

According to their data, 45% of all studies registered on the portal are non-U.S. trials (1), while U.S. studies constitute 40% of total, with the remaining 5% in unspecified locations (1). The data also reveals that the locations of recruiting clinical trials are also split, with 51% conducted in non-U.S. sites, 43% in the U.S. and 6% in both U.S. and non-U.S. locations (1).

Of the trials registered, interventional studies account for 80% of total number of registered studies, while observational studies constitute only 18 % of total (1).

It is particularly noteworthy that only 14,770 (8%) of all registered trials have their results publically posted (1). This surprisingly low percentage can be explained as a consequence of the fact that it is not mandatory to publish results for all types of studies (1).

We can see from the ClinialTrials.gov data that there is a trend for an increasing number of clinical trials registered on the site year on year. Two factors contributing to this are: (1):

• The International Committee of Medical Journal Editors (ICMJE) requirement for trials to be registered as a condition of publication (September 2005),
• The Food and Drug Administration Amendment Act of 2007 (FDAAA) expanded registration requirements (December 2007).

The majority of clinical trials are registered in America, with California, Texas and New York contributing the greatest number of sites. Europe also conducts large numbers of clinical trials, with Germany, France and United Kingdom the highest ranking countries, and Montenegro, Albania and Luxembourg the lowest.

In addition to the ClinicalTrials.gov portal, there are a number of other active registries, which are listed in the WHO Registry Network (5), including:

•  The European Clinical Trials Register – 24,141 clinical trials with EudraCT protocol (3)
• The Australian New Zealand Clinical Trials Registry – 9801 studies (6)
• The Chinese Clinical Trial Registry – 5195 studies (7)
• ReBEC (Registro Brasileiro de Ensaios Clínicos) – 2483 studies (8)

Clinical trials in an increasingly globalized market

Clinical trials have traditionally been carried out in wealthy countries (4). However this is changing, with clinical trials sponsored by pharmaceutical and device companies increasingly being conducted in emerging regions (4).

Discovery, development and research are becoming increasingly globalized (4). This shifting business model inevitably creates regulatory challenges, from areas such as product development, all the way to customer use (4). There are several factors influencing the globalization of clinical trials:

• Finance – The industry looks to regions and countries that can lower operational costs, by reducing expenditure in resources, salaries and rental costs (4).
• Recruitment – Organizations are attracted to locations in which patient enrollment and retention rates are high (4), such as Central and Eastern Europe.
• Contract research organizations (CROs) – A number of CROs focus on global trials further globalizing the market (4, 11).
• Logistics – Changes that act to reduce regulatory barriers, simplifying contracts and cutting bureaucracy, and promoting faster recruitment rates and shorter trial timelines, stimulate the globalization of clinical trials (4).
• Good Clinical Practice (GCP) – Greater adoption of ICH-GCP guidelines worldwide as well as strong intellectual property protection also give sponsors greater confidence to fund clinical trials in an increasingly wide range of locations. (4).

Challenges to progress

There are however, still obstacles that stand in the way of change. To move forward the clinical trials industry must face a number of regulatory challenges.

There is a need to create appropriate resources to allow efficient GCP inspections in many parts of the world (4). It is also essential for many countries to build sufficient knowledge of medical practice legislation and the various medical qualifications (4). There are still differences in the definition of legitimate “consent”, based around issues of illiteracy and legal rights relating to gender and age, in some countries (4). There are also wide disparities in the standard of care, access to healthcare, and availability of medicinal products across the world (4). Genetic diversity of patient populations as well as cultural issues, also pose a challenge (4).

References:

1. http://clinicaltrials.gov/ct2/resources/trends
2. http://clinicaltrials.gov/ct2/search/map
3. https://www.clinicaltrialsregister.eu/ctr-search/search;jsessionid=rSoo935D_vEy308nOXCRMNw_kf3W6iA96WzqrpTtl_HczC9jhIuo!-376466626
4. http://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM378499.pdf
5. http://www.who.int/ictrp/network/en/
6. http://www.anzctr.org.au/docs/Monthly%20Website%20Reporting_Statistics%20Sep14.pdf
7. http://www.chictr.org/en/registry.aspx
8. http://www.ensaiosclinicos.gov.br/about/
9. http://www.fda.gov/downloads/Training/ClinicalInvestigatorTrainingCourse/UCM378499.pdf
10. http://www.fda.gov/scienceresearch/specialtopics/personalizedmedicine/default.htm
11. http://www.totalbiopharma.com/2014/07/03/top-5-trends-clinical-partnering-outsourcing/
12. http://www.totalbiopharma.com/2014/06/10/social-media-compromising-clinical-trials/