While 60 percent of serious diseases occur among children, just 12 percent of clinical drug trials are pediatric trials, according to a research study presented at the Pediatric Academic Societies 2012 annual meeting in Boston.
Researchers at Harvard Medical School measured the level of federally and privately supported research activity devoted to the top 10 "high burden" pediatric diseases and listed in ClinicalTrials.gov between 2006 to 2011. The medical conditions included asthma, bipolar disorder, depression, diarrheal illness, HIV/AIDS, lower respiratory infection, malaria, migraine headaches, and schizophrenia.
"We found that there is a large discrepancy between global disease burden in children and the amount of clinical trial research devoted to this population," Florence Bourgeois, MD, MPH, Harvard Medical School
"Children suffering from both acute and chronic diseases are not well-served by the current drug development and approval processes," said Kenneth Mandl, MD, MPH, associate professor at Harvard Medical School and senior author of the study.
A lack of financing is one reason for the discrepancy, according to a statement from Florence Bourgeois, MD, MPH, an assistant professor at Harvard and one of the researchers. "We found that 58.6 percent of pediatric drug trials were conducted without any industry funding, relying solely on nonprofit organizations. In contrast, the majority of adult drug trials (64.7 percent) received industry funding."
The discrepancy in the number of trials involving adults and children was highest in middle- and low-income countries, said the researchers.
Bourgeois suggests more incentives are needed to encourage pharmaceutical companies and nonprofits to increase the number of pediatric drug trials. "It is critical that drugs are studied that are most likely to benefit children, particularly children in developing countries who appear to be most neglected in the current research portfolio," said Bourgeois.
The researchers also found that pediatric and adult trials are designed differently. Studies that enroll adults were more likely to focus on safety outcomes and to be multi-center trials than those that enrolled pediatric patients.
Legal and Ethical Considerations
Some pediatricians have concerns that many trials involving children don't factor in how different stages of human development can affect trial outcomes. The FDA, researchers and medical groups are working to develop guidelines and protocols for pediatric trials where they don't currently exist.
In 2010, the American Academy of Pediatrics updated its Guidelines for the Ethical Conduct of Studies to Evaluate Drugs in Pediatric Populations. The guidelines state that a committee tasked with monitoring data collection and safety should be in place for all phase III trials, and for phase I and II trials when the trial includes blinding. In addition, the association states that it is unethical to repeat trials unnecessarily in children, and that all trials should be registered and published.
In May 2011, the Pediatric Ethics Subcommittee of the FDA's Pediatric Advisory Committee discussed the ethics of giving children smaller doses of drugs that are effective and approved for adults as part of an investigational new drug (IND) study. The advisory committee meets quarterly and makes recommendations to the FDA commissioner regarding pediatric research priorities, the ethics, design, and analysis of clinical trials, labeling issues, adverse event reports, and other issues relating to enrolling children as drug trial subjects.
The FDA's current guidance on pediatric trials call for enrolling children in trials only when scientific or public health goals can't be met through adult trials; allowing pediatric trial subjects to be exposed to only minimal risk unless there is a direct benefit to the child; and avoiding situations that put a pediatric patient at a disadvantage either through participation in a trial or failure to get needed medical care.
Current regulations concerning pediatric studies are found in the Best Pharmaceuticals for Children Act (BPCA) passed in 2002 and the Pediatric Research Equity Act (PREA) passed in 2003.
Joel Finkelstein outlined some of the obstacles facing industry researchers attempting pediatric clinical trials in a 2005 article published in the Journal of the National Cancer Institute.
He wrote that pharmaceutical companies and the FDA grapple with designing study protocols where no standard therapeutic options currently exist for children. In rare diseases, such as some childhood cancers, researchers have trouble finding adequate numbers of trial participants which means that it can take years longer to complete a pediatric study than a comparable study in adults.
Bourgeois FT, et al. Abstract 1135.8.Clinical Drug Trials: A Paucity of Pediatric Representation Mismatched to Global Disease Burden. April 28, 2012, Pediatric Academic Societies 2012 Annual Meeting.
Finkelstein, JB, Pediatric Drug Trials Facing Some Obstacles, Journal of the National Cancer Institute, Oxford University Press 2005. DOI: 10.1093/jnci/dji441
Shaddy RE, et al. Clinical report guidelines for the ethical conduct of studies to evaluate drugs in pediatric populations. Pediatrics 2010; 125: 850-60. Doi: 10.1542/peds.2010-0082