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Pediatric Update


Pediatric Update

Spring 2008

UCLA Expands Drug Clinical Trials Involving Children


Less than one-fourth of the drugs approved by the U.S. Food and Drug Administration (FDA) are labeled for pediatric use, due to historic disincentives for pharmaceutical companies to include children in clinical trials. “For every day that a drug doesn’t reach the market, the company behind it is losing millions of dollars,” says Edward R.B. McCabe, M.D., Ph.D., professor and executive chair of the UCLA Department of Pediatrics and physician-in-chief of Mattel Children’s Hospital UCLA. “Expanding clinical trials to include children increases the cost and introduces the risk that you will see side effects that you don’t see in adults, further delaying the time to market.”

Thus, in pediatrics most drugs have been used off-label—prescribed without having been tested in a controlled setting. This introduces several concerns, notes Theodore Moore, M.D., pediatric hematologist-oncologist at Mattel Children’s Hospital UCLA. “Children metabolize drugs differently than adults,” he says. “You can’t just say a child is 20 pounds so I’ll give him onetenth the dose I would give a 200-pound adult. In addition, children are actively growing—their bones are forming, their neurologic system is developing—so a drug may affect them differently than adults.”

Adds Dr. McCabe: “In effect, pediatricians have been forced to conduct unsupervised clinical trials. In that sense, it takes a lot longer to identify serious side effects, because no one is tracking the data.”

That has begun to change. In 1997 the Food and Drug Administration Modernization Act was signed into law. Reauthorized in 2002 as the Best Pharmaceuticals for Children Act, it gives companies an extra six months of marketing exclusivity on their patent if they perform appropriate studies for children showing an indication for their drug. This provision, endorsed by the American Academy of Pediatrics, has resulted in more than 100 drugs being approved for pediatric use.

Mattel Children’s Hospital UCLA has also been a major supporter, taking steps to increase the number of clinical studies involving children. In 2006, Dr. McCabe established an Office of Clinical Trials within the Department of Pediatrics, aimed at increasing clinical research within the department by providing resources to assist and support faculty. The office, under the leadership of Erica Stanley, J.D., is designed to encourage more clinical research by faculty in collaboration with industry and government sponsors.

Researchers are assisted in all administrative functions, with Stanley serving as a liaison between the faculty and the university’s contracting offices as well as providing support in dealings with the institutional review boards. Those pursuing clinical studies receive support in developing budgets and tracking payments. An educational component is also being developed for research study staff.

In addition to ensuring that approved agents have undergone appropriate tests for dosing and side effects in children, the push to increase clinical trials within the department is driven by the need for new drugs for diseases in which the current standard of care is inadequate. This is particularly true in cancer. “There are more than 400 anticancer drugs in the pipeline of drug companies, almost none of them developed with children in mind,” says Dr. Moore. The reason is simple, he notes. Approximately 14,000 pediatric cancers are diagnosed each year; by comparison, breast cancer alone is diagnosed in 50,000 adults each year. “A drug company is not going to make a profit off of just treating children with cancer,” Dr. Moore explains.

And yet, the need for new treatments is substantial. “We need more clinical trials to investigate new therapies for children, because we are still unable to cure all patients with pediatric tumors,” says Kathleen Sakamoto, M.D., Ph.D., pediatric hematologist-oncologist at Mattel Children’s Hospital UCLA. She notes that despite significant strides, approximately 20 percent of pediatric cancer patients relapse or have resistant disease. “We must take the reins and find new therapies for these children,” Dr. Sakamoto says. “In addition, although we are giving chemotherapy and 80 percent of children who get cancer today are cured, we are now realizing that many of our children have long-term complications from their treatment. So we also must find ways that we can treat these children without producing longterm complications.”

With the Best Pharmaceuticals for Children Act as an impetus, clinical researchers such as Drs. Moore and Sakamoto have been involved in a variety of efforts to team with drug companies in ways that will bring new pediatric cancer drugs to market. In many cases, that has meant getting appropriate existing drugs that have been developed and tested for adult cancers into trials for pediatric tumors. Mattel Children’s Hospital UCLA is one of five institutions across the country that have partnered with the Glaser Pediatric Research Network to bring new clinical therapies for pediatric diseases; as part of this effort, Dr. Moore collaborated with the manufacturer of rituximab to conduct a pediatric study for a drug that had only been tested in adults. Dr. Moore’s team is also part of the Children’s Oncology Group, a multi-institutional collaborative group leveraging its status as a consortium in an effort to spur development of new drugs and clinical trials for pediatric tumors.

“Most drugs that pediatricians are using have still not had the appropriate studies done in children,” concludes Dr. Moore. “The new incentives for drug companies are an important step. As pediatricians, we all need to continue to support efforts to have more clinical trials that include children.”

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