Children on losing end of access to new drugs
New initiatives should help
Only five of 14 recently approved AIDS drugs have been tested in children and no protease inhibitors are approved for pediatric patients under age 2, causing difficult ethical and clinical dilemmas for treating the estimated 500 children born with HIV infection each year in this country. New legislation, however, coupled with an ambitious initiative to improve pediatric HIV care, should help the well-being of infected children, say pediatric HIV experts.
"Children are on the losing end of access to new drugs," said David Harvey, MSW, executive director of the AIDS Policy Center for Children, Youth, and Families in Washington, DC. "Nearly 80% of all [AIDS] drugs on the market have not been tested in this population."
As a result, pediatricians are forced to prescribe AIDS medication for off-label use, he reported, relying solely on clinical judgment that these drugs will be as safe and effective in children as they are in adults.
Moreover, the development and testing of new HIV drugs in children has decreased in recent years as the success of AZT preventive therapy has reduced perinatal transmission in this country from about 2,000 cases prior to standard use of the regimen to about 500 cases today. With a smaller cohort of infected children, it has become more difficult to conduct pediatric HIV trials, said Mark Kline, MD, associate professor of pediatrics at Texas Children’s Hospital in Houston.
"Answering critical research questions will require novel study designs and a willingness to look beyond clinical research settings for answers," he explained.
Responding to this inequity, the Clinton administration issued a proposed rule last summer that would require pharmaceutical companies to test more drugs in children and submit data to the FDA at the same time or shortly after a drug is approved for adults. The proposal also would require pediatric testing for some drugs already approved.
In addition, the Better Pharmaceuticals for Children Act, part of recent FDA reform legislation, would complement the president’s proposed rule by providing marketing incentives for pharmaceutical companies to increase the testing of drugs in children.
While these developments bode well for pediatric HIV, the AIDS Policy Center and other children’s groups are concerned that the numerous waivers in the rule weaken the proposal and will give manufacturers loopholes to jump through. For example, if the drugs are not expected for use in a substantial number of children or a pediatric formulation cannot be developed through reasonable efforts, the drug can be exempt from pediatric testing.
A model illustrating that a drug company can develop a pediatric formulation for AIDS drugs if it has the will power is Agouron Pharmaceuticals, Inc., which decided to test its protease inhibitor nelfinavir in children even though there were economic incentives not to, Harvey noted.
How to assure compliance
Concerns about pediatric HIV treatment is not just limited to access to new drugs, however. A major problem is what safeguards are in place that will assure children adhere to therapy regimens, Harvey noted. Without comprehensive family-centered care that recognizes the needs of both parents and children, and offers them necessary social support services, compliance with most regimens will be difficult, he said, adding that the large majority of children with HIV are from indigent families.
Kline listed four areas of improvement needed in pediatric HIV research. First, pediatric formulation of all HIV drugs must be developed. Second, clinical trials on the use of these pediatric formulations, especially in combination with other drugs that have been shown beneficial in adults, must be undertaken. Third, HIV clinicians need greater access to treatment information on pediatric infection. And fourth, access to presently approved pediatric drugs should be guaranteed regardless of the financial status of the child’s parents or caretakers.
Long concerned that children were getting short shrift in AIDS treatment advances, the International Association for Physicians in AIDS Care is launching an ambitious initiative that will address many of the concerns about pediatric HIV drug testing and treatment, Kline reported at the IAPAC conference in Washington.
A demonstration project called "Children First" will begin soon in several targeted states, with the goal of expanding it to all states by 2000. The overall goal of the project is to develop resources and structures for assuring that HIV-infected children have access to all HIV drugs within three years, Kline said.
As a first step, IAPAC has organized a first-ever meeting of drug companies, clinicians, and government health officials to set an agenda for pediatric HIV treatment research both in the United States and internationally. The meeting, to be held in 1998, will be sponsored by the Pediatric AIDS Foundation.
As a second step, the project will develop a pediatric HIV mentor program. The association will assist in the professional development of clinicians with little experience in pediatric HIV infection by assigning them to pediatric HIV specialists who would serve as mentors.
IAPAC also intends to develop a pediatric HIV resource center that will assist in timely distribution of HIV treatment and management of children. The center will develop reports on pediatric HIV clinical management presented at conferences as well as from peer review literature. A vehicle for this information will be a new pediatric HIV journal it plans to launch that will include original research on pediatric HIV treatment and management, Kline said.
In efforts to increase access to drugs, IAPAC also proposes the appointment of a national pediatric HIV drug coordinator who would oversee the demonstration project and identify existing programs through which drugs could be obtained, such as supplemental state funds or pharmaceutical industry indigent drug programs.
"While the association realizes some of these services are already available through existing community HIV service organizations, cutbacks in funding for such organizations and lack of appropriate organizations in some communities justifies the appointment of a drug coordinator as a safety net," Kline explained.
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