The majority of pediatric clinical trials conducted under a Congressional provision granting patent extensions to pharmaceutical companies in exchange for performing research on drug safety and efficacy in children involve sites outside the United States, raising scientific and ethical questions, according to researchers at Duke Clinical Research Institute.

The study, published in the journal Pediatrics, is the first to examine pediatric research moving overseas, which is a trend that has been previously reported in adult clinical research.

Among the findings of the new study is that the majority of the pediatric trials evaluated enrolled patients in at least one country outside the United States. More than one-third of trials included patients in developing or transitioning countries, and 11 percent were conducted exclusively outside the United States.

“There are potential benefits to the globalization of pediatric research, such as reducing the cost and time line for drug development, fostering global clinical innovation, and improving access to therapies and the health of children worldwide,” says Sara Pasquali, MD, the study’s lead author and assistant professor of pediatrics at Duke. “However, globalization also raises certain ethical and scientific concerns.”

The Pediatric Exclusivity Provision provides six months of patent exclusivity to pharmaceutical companies to conduct safety and efficacy studies of drugs in children. This program has resulted in more than 150 drug label changes for children’s medications, and led to an estimated $14 billion in profits to pharmaceutical companies.

“The original objective of the program was to encourage research that enables the FDA to label drugs for appropriate use in children in the U.S.,” says Pasquali. “Whether it’s valid to extrapolate the results from trials conducted in other countries is not known. The efficacy of a medication may depend on genetic background and access to health care resources, among other factors, which may differ across countries.”

The research team analyzed 174 trials published since the program began in 1998 through those published in 2007. They note that about half of the studies conducted under this program are not published, so the analysis may underestimate the globalization of pediatric trials.

The studies included sites in 54 countries, including developing or transitioning countries in Eastern Europe, Asia, Africa, and South and Central America.

Similar to the trend observed in adults, Pasquali says these findings are likely due to the lower costs of conducting research overseas and fewer regulatory requirements. Pediatric diseases are often more rare, so including numerous sites also can expedite the research process.

“It’s much cheaper, easier, and less time consuming to conduct research outside the U.S.” Pasquali says.

The article raised ethical concerns regarding research conducted in developing nations, including whether the research was being conducted in sync with the health needs of the population and whether the treatments studied would be readily available to children in these countries after the study had ended.

The authors also expressed concern for how children and families in the developing world may have been induced to participate in trials. They noted that participation in the study may be the only access a family has to medical care and compensation for trial participation can be significant. Ensuring adequate informed consent may also be difficult in countries with widespread illiteracy.

The authors put forth several recommendations for reforming the conduct of pediatric trials conducted outside the United States. These include:

• Requiring pharmaceutical companies to describe how the proposed study population matches the intended market for the drug being tested
• Requiring all studies conducted under the program be published and include specific data regarding the setting and location of the trial
• Improving mechanisms of global regulatory oversight with input from all stakeholders

Study co-authors include Danielle Burstein, Daniel K. Benjamin, P. Brian Smith, and Jennifer S. Li.