Research Article: Global migration of clinical research during the era of trial registration

Date Published: February 28, 2018

Publisher: Public Library of Science

Author(s): Paul K. Drain, Robert A. Parker, Marion Robine, King K. Holmes, Srinivas Murthy.

http://doi.org/10.1371/journal.pone.0192413

Abstract

Since the site of human subjects research has public health, regulatory, ethical, economic, and social implications, we sought to determine the global distribution and migration of clinical research using an open-access trial registry.

We obtained individual clinical trial data including location of trial sites, dates of operation, funding source (United States government, pharmaceutical industry, or organization), and clinical study phase (1, 1/2, 2, 2/3, or 3) from ClinicalTrials.gov. We used the World Bank’s classification of each country’s economic development status [“High Income and a Member of the Organization for Economic Co-operation and Development (OECD)”, “High Income and Non-Member of the OECD”, “Upper-Middle Income”, “Lower-Middle Income”, or “Low Income”] and United Nations Populations Division data for country-specific population estimates. We analyzed data from calendar year 2006 through 2012 by number of clinical trial sites, cumulative trial site-years, trial density (trial site-years/106 population), and annual growth rate (%) for each country, and by development category, funding source, and clinical study phase.

Over a 7-year period, 89,647 clinical trials operated 784,585 trial sites in 175 countries, contributing 2,443,850 trial site-years. Among those, 652,200 trial sites (83%) were in 25 high-income OECD countries, while 37,195 sites (5%) were in 91 lower-middle or low-income countries. Trial density (trial site-years/106 population) was 540 in the United States, 202 among other high-income OECD countries (excluding the United States), 81 among high-income non-OECD countries, 41 among upper-middle income countries, 5 among lower-middle income countries, and 2 among low-income countries. Annual compound growth rate was positive (ranging from 0.8% among low-income countries to 14.7% among lower-middle income countries) among all economic groups, except the United States (-0.5%). Overall, 29,191 trials (33%) were funded by industry, 4,059 (5%) were funded by the United States government, and 56,397 (63%) were funded by organizations. Countries with emerging economies (low- and middle-income) operated 19% of phase 3 trial sites, as compared to only 6% of phase 1 trial sites.

Human clinical research remains concentrated in high-income countries, but operational clinical trial sites, particularly for phase 3 trials, may be migrating to low- and middle-income countries with emerging economies.

Partial Text

Research involving human subjects has evolved over millennia–from an observational study in the Old Testament [1] to the first randomized clinical trial in 1944 [2]. Historically, clinical research has been financed by pharmaceutical companies and conducted in affluent regions, but rising drug development expenditures have increased demand for faster and cheaper trial results [3]. Currently, over 3,000 clinical research organizations (CROs) operate worldwide with total combined market revenues exceeding $21 billion [4–6]. Since researchers, including CROs, use global networks to accelerate patient recruitment and reduce costs, we sought to quantify the global distribution and migration of clinical research [4,6,7].

Over the 7-year period, 89,647 clinical trials operated 784,585 trial sites in 175 countries, contributing 2,443,850 trial site-years of observation (Table 1). Among those, 652,200 trial sites (83%) and 2,052,126 trial site-years (84%) were operating in the 25 high-income OECD countries. Conversely, the 125 countries with emerging economies accounted for 115,684 trial sites (15%) and 342,053 trial site-years (14%). As expected, the distribution of clinical trial sites was very heterogeneous between economic development categories (Fig 1).

Using a large global repository of open-access clinical trial data, we demonstrated that the vast majority of clinical trials remain concentrated in high-income countries. Although annual growth rates were highest among low and middle-income countries with emerging economies for both aggregate measures and when stratified by clinical study phase, there remained a relative underrepresentation of phase 1 trials as compared to phase 3 trials in countries with emerging economies. The majority of clinical research was funded by organizations and the pharmaceutical industry; organization-sponsored trials have been increasing. This overall global migration of operational clinical trial sites—particularly for phase 3 trials—to low- and middle-income countries with emerging economies has numerous implications.

 

Source:

http://doi.org/10.1371/journal.pone.0192413

 

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