A Duke University study published in the journal Pediatrics (abstract below) examined the effects of the Pediatric Exclusivity Provision of FDAMA (enacted in 1998). FDAMA provides six months of patent exclusivity to pharmaceutical companies to conduct safety and efficacy studies of drugs in children.
The findings confirm that Big Pharma is conducting most pediatric drug trials offshore–including developing or transitioning countries in Eastern Europe, Asia, Africa, and South and Central America–where ethical standards, oversight, and legal protections against children’s exploitation are least reliable (if they exist at all).
Of the 174 published trials that indicated the study location, 65% were conducted offshore, 38% were conducted in a developing country, and 11% did not include any sites in the US.
The authors note that “It’s much cheaper, easier, and less time consuming to conduct research outside the U.S.”
Indeed, they found that the Pediatric Exclusivity Provision has led to an estimated $14 billion in profits to pharmaceutical companies.
The authors raise concerns about the validity of 150 pediatric label changes that (presumably) resulted from these offshore trials:
“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 Dr. Sara 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.”
And they note the ethical issue of exploitation of poor children in trials testing products they will not have access to.
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
We would add an additional requirement: that FDA not accept data from pediatric trials conducted at sites not inspected by the agency during the course of the trial.
Vera Hassner Sharav
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Published online August 23, 2010
PEDIATRICS (doi:10.1542/peds.2010-0098)
Globalization of Pediatric Research: Analysis of Clinical Trials Completed for Pediatric Exclusivity
Sara K. Pasquali, MDa,b, Danielle S. Burstein, BSa,b, Daniel K. Benjamin, Jr, MD, PhDa,b, P. Brian Smith, MD, MHS, MPHa,b, Jennifer S. Li, MD, MHSa,b
aDepartment of Pediatrics, Duke University Medical Center; and
bDuke Clinical Research Institute, Duke University, Durham, North Carolina
Objective We evaluated the setting of published studies conducted under the US Pediatric Exclusivity Provision, which provides economic incentives to pharmaceutical companies to conduct drug studies with children.
Methods Published studies containing the main results of trials conducted in 1998–2007 under the Pediatric Exclusivity Provision were included. Data were extracted from each study and described, including the therapeutic area of drug studied, number of patients enrolled, number of sites, and location where the study was conducted, if reported.
Results Overall, 174 trials were included (sample size: 8–27 065 patients); 9% did not report any information regarding the location or number of sites where the study was conducted. Of trials that did report such information, 65% were conducted in 1 country outside the United States, and 11% did not include any sites in the United States. Fifty-four countries were represented, and 38% of trials enrolled patients in 1 site located in a developing/transition country, including more than one-third of infectious disease, cardiovascular, and allergy/immunology trials.
Conclusions The majority of published pediatric trials conducted under the Pediatric Exclusivity Provision included sites outside the United States, and more than one-third of trials enrolled patients in developing/transition countries.
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Statement By Duke Medicine News and Communications
Questions Abound as Pediatric Clinical Trials Move Overseas
Aug. 23, 2010
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.