BPCA  also provides mechanisms for pediatric drug studies that drug sponsors  decline to conduct. FDA cannot extend pediatric  exclusivity in response to written requests for any drugs for which the  drug sponsors declined to conduct the requested pediatric drug studies. First, when drug sponsors decline written requests for studies of on-patent  drugs, BPCA provides for FDA to refer the study of those drugs to FNIH  for funding. Second, to further the study of off-patent drugs, NIH—in consultation with  FDA and experts in pediatric research—develops a list of drugs, including  off-patent drugs, which the agency believes need to be studied in children. FDA may  determine that the drug is not approved for use by children, which would  then be reflected in any labeling changes. Drug Sponsors Agreed to Study the Majority of On-Patent Drugs with Written Requests under BPCA, but No Studies Were Conducted When Drug Sponsors Declined the Written Requests

Most of the on-patent drugs for which FDA requested pediatric drug  studies under BPCA were being studied, but no studies have resulted  when the requests were declined by drug sponsors. From January 2002  through December 2005, FDA issued 214 written requests for on-patent  drugs to be studied under BPCA, and drug sponsors agreed to conduct  pediatric drug studies for 173 (81 percent) of those. Analyses of two national  databases shows that about half of the 10 most frequently prescribed  drugs for children were studied under BPCA. FDA referred 9 of these 41 written  requests (22 percent) to FNIH for funding, but as of December 2005,  FNIH had not funded the study of any of these drugs. Few Off-Patent Drugs Have Been Studied under BPCA

Few off-patent drugs identified by NIH as in need of study for pediatric use  have been studied. By 2005, NIH had identified 40 off-patent drugs that it  believed should be studied for pediatric use. NIH funded pediatric drug studies for 7 of  the remaining 15 written requests declined by drug sponsors through  December 2005. Most Drugs Granted Pediatric Exclusivity under BPCA Had Labeling Changes, but the Process for Making Changes Was Sometimes Lengthy

Most drugs that have been granted pediatric exclusivity under BPCA— about 87 percent—have had labeling changes as a result of the pediatric  drug studies conducted under BPCA. Pediatric drug studies conducted  under BPCA showed that children may have been exposed to ineffective  drugs, ineffective dosing, overdosing, or side effects that were previously  unknown. The labeling for these drugs was changed to reflect these  study results. For the remaining  18 drugs (about 40 percent), FDA took from 238 to 1,055 days to complete  the scientific review process and approve labeling changes.
Why GAO Did This Study

About two-thirds of drugs that are prescribed for children have not been studied and labeled for pediatric use, placing children at risk of being exposed to ineffective treatment or incorrect dosing. The Best Pharmaceuticals for Children Act (BPCA), enacted in 2002, encourages the manufacturers, or sponsors, of drugs that still have marketing exclusivity--that is, are on-patent--to conduct pediatric drug studies, as requested by the Food and Drug Administration (FDA). If they do so, FDA may extend for 6 months the period during which no equivalent generic drugs can be marketed. This is referred to as pediatric exclusivity. BPCA also provides for the study of off-patent drugs. GAO was asked to testify on the study and labeling of drugs for pediatric use under BPCA. This testimony is based on Pediatric Drug Research: Studies Conducted under Best Pharmaceuticals for Children Act, GAO-07-557 (Mar. 22, 2007). GAO assessed (1) the extent to which pediatric drug studies were being conducted under BPCA for on-patent drugs, (2) the extent to which pediatric drug studies were being conducted under BPCA for off-patent drugs, and (3) the impact of BPCA on the labeling of drugs for pediatric use and the process by which the labeling was changed. GAO examined data about the drugs for which FDA requested studies under BPCA from 2002 through 2005 and interviewed relevant federal officials.

What GAO Found

Drug sponsors have initiated pediatric drug studies for most of the on-patent drugs for which FDA has requested such studies under BPCA, but no drugs were studied when sponsors declined these requests. Sponsors agreed to 173 of the 214 written requests for pediatric studies of on-patent drugs. In cases where drug sponsors decline to study the drugs, BPCA provides for FDA to refer the study of these drugs to the Foundation for the National Institutes of Health (FNIH), a nonprofit corporation. FNIH had not funded studies for any of the nine drugs that FDA referred as of December 2005. Few off-patent drugs identified by the National Institutes of Health (NIH) that need to be studied for pediatric use have been studied. BPCA provides for NIH to fund studies when drug sponsors decline written requests for off-patent drugs. While 40 such off-patent drugs were identified by 2005, FDA had issued written requests for 16. One written request was accepted by the drug sponsor. Of the remaining 15, NIH funded studies for 7 through December 2005. Most drugs granted pediatric exclusivity under BPCA (about 87 percent) had labeling changes--often because the pediatric drug studies found that children may have been exposed to ineffective drugs, ineffective dosing, overdosing, or previously unknown side effects. However, the process for approving labeling changes was often lengthy. For 18 drugs that required labeling changes (about 40 percent), it took from 238 to 1,055 days for information to be reviewed and labeling changes to be approved.