Report to Congressional Committees 

United States General Accounting Office 

GAO 

September 2003 PEDIATRIC DRUG 

RESEARCH 

Food and Drug 

Administration Should 

More Efficiently 

Monitor Inclusion of 

Minority Children 

GAO-03-950 
Compared with the proportions of children from racial and ethnic minority 

groups in the U.S. population, smaller proportions of children from minority 

groups were included in the pediatric clinical drug studies requested by FDA 

before the enactment of BPCA that GAO reviewed. However, FDA required, 

and drug sponsors included, larger proportions of African American children 

in clinical studies for hypertension drugs because there is evidence that 

hypertension is more prevalent and more severe among African Americans. 

Furthermore, FDA has requested that forthcoming studies for certain drugs 

include larger proportions of minority children. 

Studies of some drugs that may be used to treat diseases or conditions that 

disproportionately affect minorities have been completed and additional 

such studies have been requested by FDA. From January 4, 2002, through 

March 6, 2003, FDA granted additional exclusive marketing rights to four 

drugs that may be used to treat conditions such as hypertension, type II 

diabetes, and sickle cell anemia—conditions or diseases that 

disproportionately affect minority children. During that time, FDA also 

issued written requests for studies of six drugs for these conditions. 

FDA does not have a system in place to serve as a single source of data to 

allow the agency to efficiently determine the extent of participation of 

children by racial and ethnic group under the pediatric exclusivity provision. 

GAO found that some study reports submitted to FDA from drug sponsors 

did not specify the race and ethnicity of all study participants. Across all the 

studies for drugs granted additional exclusive marketing rights that GAO 

reviewed, 86 percent of study participants were identifiable by race or 

ethnicity, but the race or ethnicity of 14 percent of study participants was 

unknown. In January 2003, FDA issued draft guidance recommending that 

drug sponsors use standard definitions for race and ethnicity in drug studies. 

However, drug sponsors are not required to use these definitions. FDA has 

also begun to develop an agencywide system to monitor demographic 

characteristics of study participants, such as age, sex, and race. 

FDA agreed with the GAO recommendation to specify the categories that 

sponsors should use to report minority representation as well as GAO’s 

findings regarding the efficiency of its data collection systems. FDA 

expressed concerns about the GAO comparison of the proportion of 

minorities in drug studies to their proportion in the U.S. population. 

However, FDA had previously used the methodology GAO employed in its 

analyses of adult study participants. 

Drug effectiveness and adverse 

events can vary between children 

and adults and among racial and 

ethnic groups. The Food and Drug 

Administration (FDA) is authorized 

under the pediatric exclusivity 

provision to grant drug sponsors 

6 months of additional exclusive 

marketing rights for conducting 

clinical drug studies in children. 

The Best Pharmaceuticals for 

Children Act of 2002 (BPCA) 

expanded this provision to require 

FDA to take into account the 

adequacy of minority 

representation in pediatric 

exclusivity studies. BPCA also 

directed GAO to evaluate the 

representation of minorities in such 

studies. GAO examined the extent 

to which minority children are 

represented, whether drugs that 

treat diseases disproportionately 

affecting minority groups are 

studied under the provision, and 

FDA’s monitoring of the 

representation of minority children 

in the studies. GAO reviewed 

related FDA documents, FDA 

requests for pediatric studies and 

final study results, and interviewed 

FDA officials and other experts. 

GAO recommends that FDA specify 

that drug sponsors use the 

standard racial and ethnic group 

definitions described in FDA’s 

January 2003 draft guidance to 

identify study participants. FDA 

concurred with the 

recommendation. 

www.gao.gov/cgi-bin/getrpt?GAO-03-950.

To view the full product, including the scope 

and methodology, click on the link above. 

For more information, contact Janet Heinrich 

at (202) 512-7119. 

Highlights of GAO-03-950, a report to the 

Committee on Health, Education, Labor 

and Pensions, U.S. Senate, and the 

Committee on Energy and Commerce, 

House of Representatives 

September 2003

PEDIATRIC DRUG RESEARCH 

Food and Drug Administration Should 

More Efficiently Monitor Inclusion of 

Minority Children 
Page i GAO-03-950 Pediatric Drug Research 

Letter 1

Results in Brief 4

Background 6

Smaller Proportions of Minority Children Were in Studies for 

Additional Marketing Exclusivity Requested before BPCA 11

Drugs of Importance to Minority Children Are Being Studied in 

Response to Pediatric Exclusivity Provision Requests 14

FDA Monitoring of Data on Minority Representation Needs 

Improvement 16

Conclusions 18

Recommendation for Executive Action 18

Agency Comments and Our Evaluation 19

Appendix I Scope and Methodology 21 

Appendix II The Number of Children by Racial and Ethnic 

Group in Studies for Drugs Granted Exclusive 

Marketing Rights 23 

Appendix III Comments from the Food and Drug Administration 25 

Appendix IV GAO Contact and Staff Acknowledgments 29 

GAO Contact 29

Acknowledgments 29

Tables 

Table 1: Children, by Racial and Ethnic Group, in Clinical Studies 

for Drugs Granted Additional Exclusive Marketing Rights, 

January 4, 2002, through March 6, 2003 12

Table 2: Children, by Racial and Ethnic Group, in Clinical Studies 

for Three Drugs for Which FDA Required Mixed Race 

Participation, and for All Other Drugs Granted Additional 

Exclusive Marketing Rights, January 4, 2002, through 

March 6, 2003 13

Contents 
Page ii GAO-03-950 Pediatric Drug Research 

Table 3: Estimated Prevalence of Diseases or Conditions in 

Minorities That May Be Treated by Drugs for Which FDA 

Issued Written Requests or Granted Exclusive Marketing 

Rights, January 4, 2002, through March 6, 2003 15

Table 4: Children of Racial and Ethnic Groups, by Drug Class, in 

Clinical Studies for Drugs Granted Exclusive Marketing 

Rights, January 4, 2002, through March 6, 2003 24

Abbreviations 

ACE angiotensin converting enzyme 

AIDS acquired immunodeficiency syndrome 

BPCA Best Pharmaceuticals for Children Act 

DIDR Demographic Information and Data Repository 

FDA Food and Drug Administration 

HHS Department of Health and Human Services 

NICHD National Institute of Child Health and Human Development 

NIH National Institutes of Health 

HIV human immunodeficiency virus 

NDA new drug application 

sNDA supplemental new drug application 

This is a work of the U.S. government and is not subject to copyright protection in the 

United States. It may be reproduced and distributed in its entirety without further 

permission from GAO. However, because this work may contain copyrighted images or 

other material, permission from the copyright holder may be necessary if you wish to 

reproduce this material separately. 
Page 1 GAO-03-950 Pediatric Drug Research 

September 26, 2003 

The Honorable Judd Gregg 

Chairman 

The Honorable Edward M. Kennedy 

Ranking Minority Member 

Committee on Health, Education, Labor and Pensions 

United States Senate 

The Honorable W.J. “Billy” Tauzin 

Chairman 

The Honorable John D. Dingell 

Ranking Minority Member 

Committee on Energy and Commerce 

House of Representatives 

While children can be stricken with many of the same diseases afflicting 

adults and are often treated with the same drugs, only about one-third of 

drugs in use today have been studied and labeled for pediatric use.1

 A drug 

used to treat children that has not been tested or labeled for pediatric use 

may place children at risk of under- or overdosing, and when ageappropriate formulations of the drugs do not exist, such as liquids or 

chewable tablets, the drug may be improperly administered to children. To 

help address these concerns, in 1997 Congress passed a law that gives 

sponsors 6 months of additional exclusive marketing rights for their 

products in return for conducting clinical drug studies in children, 

commonly known as the pediatric exclusivity provision.2

 The Food and 

Drug Administration (FDA), the federal agency that approves drugs for 

marketing, is responsible for administering the law and has procedures for 

ensuring the study of drugs in pediatric patients. Specifically, if FDA 

officials believe that studying a drug may lead to health benefits for 

children, FDA issues a formal “written request” for clinical drug studies in 

 1

R. Roberts and others, “Pediatric Drug Labeling: Improving Safety and Efficacy of 

Pediatric Therapies,” Journal of the American Medical Association, vol. 290, no. 7 (2003). 

2

Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105-115, §111, 111 

stat. 2296, 2305. Drug manufacturers may obtain marketing exclusivity through patents, 

patent term extensions to compensate for regulatory delays, approval of drugs containing 

new chemical entities, or approval of orphan drugs. 

United States General Accounting Office

Washington, DC 20548 
Page 2 GAO-03-950 Pediatric Drug Research 

pediatric patients to the drug sponsor. If the sponsor agrees to comply 

with the terms of the written request and submits final study results to 

FDA that meet the terms of the request, FDA will grant the sponsor 6 

months of additional exclusive marketing rights. Pediatric drug research 

has increased substantially since the enactment of the pediatric exclusivity 

provision.3

FDA officials are concerned that drug effectiveness and adverse effects 

can vary among children from different racial and ethnic groups. Although 

FDA has requested race and ethnicity data on subjects in clinical drug 

trials, no formal evaluations have assessed the extent to which children of 

different racial and ethnic groups are represented in clinical studies of 

new drugs, thus the extent to which these drugs have been tested on 

children in minority groups is unknown. Concern exists that if children 

from racial and ethnic minority groups are not included in adequate 

numbers in clinical studies of drugs, the administration of the drugs to 

children in these groups may result in atypical responses or unexpected 

side effects. In addition, no formal evaluations have assessed the extent to 

which drugs that were studied under the pediatric exclusivity provision 

may be used to treat diseases or conditions that disproportionately affect 

minority children. 

To ensure that children of racial and ethnic minority groups are included 

in clinical studies for new drugs, the Best Pharmaceuticals for Children 

Act of 2002 (BPCA) expanded the pediatric exclusivity provision to 

require, among other things, that FDA “take into account adequate 

representation” of children from racial and ethnic minority groups when 

negotiating written protocols with the study sponsors of pediatric drugs.4

In addition, the act required that we study the adequacy of minority 

representation in studies covered by the pediatric exclusivity provision. As 

agreed with the committees of jurisdiction, we addressed the following 

questions: (1) to what extent are children of racial and ethnic minority 

groups represented in clinical studies for drugs granted exclusive 

marketing rights, (2) are drugs that are used to treat diseases that 

 3

U.S. General Accounting Office, Pediatric Drug Research: Substantial Increase in 

Studies of Drugs for Children, But Some Challenges Remain, GAO-01-705T (Washington, 

D.C.: May 8, 2001).

4

Pub. L. No. 107-109, § 18, 115 Stat. 1408, 1423. The pediatric exclusivity provision sunset on 

January 1, 2002. BPCA, which took effect on January 4, 2002, reauthorized the provision 

through October 1, 2007. BPCA, § 8, 115 Stat. 1414. 
Page 3 GAO-03-950 Pediatric Drug Research 

disproportionately affect racial and ethnic minority groups being studied 

for safety and effectiveness in children under the pediatric exclusivity 

provision, and (3) does FDA have appropriate management systems to 

monitor the representation of children of racial and ethnic groups in 

studies submitted for additional exclusive marketing rights? 

To answer these questions, we reviewed recently completed and requested 

pediatric studies for inclusion of children from racial and ethnic minority 

groups and FDA’s data systems, regulations, and guidance used to 

implement the pediatric exclusivity provision. To quantify the 

participation of racial and ethnic groups in completed pediatric clinical 

studies, we reviewed FDA pediatric study documents and collected data 

about racial and ethnic group representation in study participants for the 

23 drugs that were granted additional exclusive marketing rights during 

the period January 4, 2002, through March 6, 2003.5

 All of the studies for 

these drugs had been requested by FDA before BPCA took effect on 

January 4, 2002, and thus were not subject to the expanded pediatric 

exclusivity provisions under the law. The time lag between an FDA written 

request and a sponsor’s submission of final study results ranges from 1 to 

4 years. To determine the representation and reporting requirements that 

FDA required drug sponsors to follow concerning the participation of 

racial and ethnic minorities in pediatric studies since BPCA took effect, 

we reviewed the 22 written requests for pediatric drug studies that FDA 

issued from January 4, 2002, through March 6, 2003. To determine if drugs 

used to treat conditions disproportionately affecting minorities are being 

studied, we obtained data on the prevalence of selected diseases or 

conditions that disproportionately affect minorities. We then examined the 

list of drugs for which FDA had either issued study requests or granted 

additional exclusive marketing rights from January 4, 2002, through 

March 6, 2003, to determine if any of the drugs may be used to treat these 

diseases or conditions. To evaluate FDA’s monitoring of data on 

demographic traits, such as race, in drug studies, we reviewed relevant 

documents and interviewed FDA officials. We also interviewed 

pharmacology experts and pediatric clinicians, including members of the 

American Academy of Pediatrics and the Pharmaceutical Research and 

 5

We collected clinical study participation data for three racial groups (African American, 

Asian, and Caucasian) and one ethnic group (Hispanic) because these categories were 

commonly used in the clinical study documents that were submitted to FDA for exclusive 

marketing rights. The term pediatric study is defined as including at least one clinical 

investigation and may include studies on the absorption, distribution, metabolism, and 

excretion of a drug in pediatric age groups in which a drug is expected to be used. 
Page 4 GAO-03-950 Pediatric Drug Research 

Manufacturers of America. (For additional information on our 

methodology, see app. I.) We conducted our work from October 2002 

through September 2003 in accordance with generally accepted 

government auditing standards. 

Compared with the proportions of children from racial and ethnic minority 

groups in the U.S. population, smaller proportions of children from 

minority groups participated in clinical drug studies for additional 

exclusive marketing rights that FDA requested before BPCA took effect. In 

clinical studies for the 23 drugs granted 6 months of additional exclusive 

marketing rights from January 4, 2002, through March 6, 2003, 

approximately 7 percent of study participants were African American, 5 

percent were Hispanic, and 1 percent were Asian, whereas these groups 

comprised 15, 17, and 3 percent, respectively, of U.S. children under 18 

years of age in 2000. However, FDA required, and drug sponsors included, 

larger proportions of minority children in studies for hypertension drugs 

because there is evidence suggesting a difference in drug metabolism or 

response in adult minority groups. Specifically, hypertension is more 

prevalent and more severe in African Americans, and African American 

children represented 22 percent of pediatric study participants in studies 

for three hypertension drugs. Similarly, FDA written requests for certain 

drugs issued since BPCA took effect require sponsors to increase minority 

representation. Specifically, in 4 of the 22 requests FDA required sponsors 

to increase the number of minorities in the study or analyze the effects of 

race and ethnicity for drugs that may affect minority groups differently. In 

11 of the 22 requests, FDA directed drug sponsors to report the 

representation of pediatric patients of ethnic and racial minority groups 

when submitting final study results, and 7 written requests made no 

mention of race or ethnicity. 

Some drugs that may be used to treat diseases that disproportionately 

affect minorities are being studied under the pediatric exclusivity 

provision. During the period January 4, 2002, through March 6, 2003, FDA 

granted exclusive marketing rights for four drugs and issued written 

requests for pediatric studies of six drugs that may be of particular 

importance to children in minority groups. For example, drug sponsors are 

either conducting or have completed studies on drugs to treat children 

with hypertension, type II diabetes, and sickle cell anemia—conditions or 

diseases that disproportionately affect children of racial and ethnic 

minority groups. 

Results in Brief 
Page 5 GAO-03-950 Pediatric Drug Research 

FDA does not have a system in place to serve as a single source of data to 

allow the agency to efficiently determine the level of participation of 

children by racial and ethnic group under the pediatric exclusivity 

provision. In addition, FDA lacks standard definitions for study sponsors 

to use in reporting racial and ethnic group participation in studies, and 

sponsors have reported these data using their own definitions for racial 

and ethnic groups. For example, in the completed studies for the 23 drugs 

granted additional exclusive marketing rights that we examined, the race 

or ethnicity of 86 percent of study participants was identified, but study 

sponsors did not specify the race or ethnicity of 960 children, or 14 

percent of the studies’ populations. FDA has taken action to start to 

address these issues. In January 2003, FDA issued draft guidance 

recommending that sponsors of drug studies use the definitions for race 

and ethnicity that the Department of Health and Human Services (HHS) 

has adopted for data collection and reporting systems funded or supported 

by HHS. However, FDA’s guidance is not legally binding on clinical study 

sponsors. FDA has also begun to develop an agencywide system to 

monitor demographic variables, such as race, age, and sex in clinical 

studies. 

We are recommending that FDA revise the format of its written requests to 

specify that study sponsors must use the racial and ethnic categories 

described in FDA’s January 2003 draft guidance to identify study 

participants in their reports to the agency. FDA can refuse to grant 6 

months of additional exclusive marketing rights under the pediatric 

exclusivity provision for sponsors that do not fairly respond to FDA’s 

written requests. 

In commenting on a draft of this report, FDA concurred with our 

recommendation and reported that it has already begun to implement it. 

FDA also reaffirmed the importance of testing drugs used to treat children 

in clinical studies of that population and agreed that the agency needed to 

improve the efficiency of its system for tracking demographic information 

about study participants. However, FDA raised concerns about three 

aspects of our draft report. First, FDA was critical of our comparison of 

the proportions of minority children study participants to the proportions 

of minority children in the population. FDA commented that it would have 

been more appropriate for us to compare the proportions of minority 

children in clinical drug studies with the proportions of minority children 

with the specific condition each drug is intended to treat. We agree that 

such a comparison would have been useful, but both FDA and we found 

that the information needed for such comparisons was not available. 

Further, FDA has previously used the methodology we employed in its 
Page 6 GAO-03-950 Pediatric Drug Research 

analyses of adult study participants. Second, FDA was concerned about 

what it regards as the implications of our finding that the proportions of 

minority children in pediatric studies requested by FDA before the passage 

of BPCA were less than their proportions in the general population. Our 

report does not make any recommendations about the preferred study 

populations for any clinical drug trial. Third, FDA noted that the race or 

ethnicity of a high percentage of study participants was identified even 

before BPCA was enacted. While our findings agree with that assessment, 

we believe that FDA should have been able to identify the race or ethnicity 

of every study participant. 

Congress passed the pediatric exclusivity provision as part of the Food 

and Drug Administration Modernization Act of 1997 to address a longstanding concern about the low percentage of prescription medications on 

the market that had been tested and approved for use in children. BPCA, 

which reauthorized the pediatric exclusivity provision, also included a 

requirement that FDA take into account adequate representation of race 

and ethnicity in the development of patient groups in pediatric drug 

studies. FDA is responsible for administering the law and has procedures 

for ensuring the study of drugs in pediatric patients as well as guidance 

that encourages (1) the inclusion of children from minority groups and 

(2) the collection and analysis of race-related study data. In this role, FDA 

must balance its policy of minimizing the number of children exposed to a 

drug during clinical trials with the need to maintain adequate sample sizes, 

including adequate representation of minority children, for effectively 

assessing a drug. 

In May 2001, we testified before the Senate Committee on Health, 

Education, Labor and Pensions that, since enactment of the pediatric 

exclusivity provision, both the numbers of new drugs studied in children 

and the number of therapeutic classes these drugs represent have 

substantially increased.6

 We reported that hundreds of studies were being 

done on drugs that are important to pediatric patients because the drugs 

treat a variety of diseases or conditions that afflict children. Some were 

tests on relatively small numbers of pediatric patients to determine the 

correct dose for a specified age group, while other tests were on larger 

numbers of pediatric patients and were more complex and costly 

 6

GAO-01-705T. 

Background 

Improvements Resulting 

from the Pediatric 

Exclusivity Provision 
Page 7 GAO-03-950 Pediatric Drug Research 

evaluations of a drug’s safety and effectiveness in children of various 

ages.7

 BPCA reauthorized and expanded the provision for 5 more years 

through October 1, 2007. 

The process for obtaining exclusive marketing rights can be initiated 

either by a drug sponsor or by FDA. A sponsor may submit a proposal to 

FDA to conduct drug studies. If FDA officials believe that studying a drug 

may produce health benefits for children, FDA issues a formal written 

request to the drug sponsor that includes, among other things, the type of 

studies to be conducted, the study design and goals, and the formulations 

and age groups to be studied. As of March 31, 2003, FDA had issued 272 

written requests for pediatric studies. Of these, 220 were issued in 

response to sponsors’ proposals. FDA may issue a written request without 

the sponsor’s proposal if FDA identifies a need for pediatric data. FDA has 

issued 52 written requests without sponsors’ proposals. A written request 

may require more than 1 study of a drug; the 272 requests covered 631 

studies, and could involve more than 37,150 pediatric patient participants 

if they were all completed. Regardless of the final study results, if FDA 

determines that the data submitted fairly responds to the written request 

and the studies were conducted properly, it will grant the sponsor 6 

months of additional exclusive marketing rights. From enactment of the 

pediatric exclusivity provision in 1997 through April 30, 2003, FDA granted 

an additional 6 months of additional exclusive marketing rights for 74 

drugs. Sponsors are not required to include minority children in studies for 

pediatric exclusivity. 

Findings from these studies have led to labeling changes for pediatric use 

for 50 drugs. For example, a study of fluoxetine (an antidepressant) 

confirmed its effectiveness to treat major depressive disorders in children 

8 to 17 years of age and obsessive-compulsive disorder in children 7 to 17 

years of age. In addition, studies for a new asthma drug—montelukast—

led to new information on dosing and a new oral formulation permitting its 

use in children from the ages of 12 months to 5 years. 

 7

More recently, FDA officials reported that the pediatric exclusivity provision has 

stimulated pediatric clinical studies resulting in improved understanding of drugs 

prescribed in pediatric medicine, important dose changes, and improved safety for children 

taking certain drugs. See R. Roberts and others, “Pediatric Drug Labeling: Improving Safety 

and Efficacy of Pediatric Therapies.” 

FDA Procedures for 

Ensuring the Study of 

Drugs in Pediatric Patients 
Page 8 GAO-03-950 Pediatric Drug Research 

FDA also has a process in place to encourage pediatric studies of drugs 

that manufacturers choose not to conduct. For drugs on which the patent 

or exclusive marketing rights have expired, commonly referred to as offpatent drugs, the National Institutes of Health (NIH) in collaboration with 

FDA annually develop a list of drugs for which pediatric studies are 

needed and publish it in the Federal Register.8

 FDA may select a drug from 

this list, issue a written request to the manufacturer that holds the 

approved application for the drug, and, if the manufacturer does not 

respond within 30 days, forward the written request to NIH to issue a 

contract to conduct the study. In fiscal year 2003, HHS announced that 

NIH would set aside $25 million from its budget to conduct pediatric 

studies of off-patent drugs from this list. Similarly, if FDA issues a written 

request for a drug that is on-patent but the drug sponsor declines to test 

the drug in children, FDA can ask the Foundation for the National 

Institutes of Health, which supports the mission of NIH,9

 to test the drug 

with funds raised from the private sector. 

 8

The purpose of this list is to promote studies of pharmaceuticals in pediatric populations 

that would normally not be studied under the pediatric exclusivity provision. These include 

drugs that do not have specific patent protection or exclusive marketing rights that could 

be prolonged under BPCA. 

9

Originally established by Congress as the National Foundation for Biomedical Research, 

the Foundation was incorporated in 1996 as a nonprofit organization funded through 

private donations. In 1998 Congress changed its name to the Foundation for the National 

Institutes of Health. 
Page 9 GAO-03-950 Pediatric Drug Research 

An important reason to include minorities in pediatric drug studies is to 

examine the effect of race or ethnicity on the disposition and effects of 

drugs in children. In adults, the activity of some drug-metabolizing 

enzymes varies with race or ethnicity.10 For example, one commonly 

prescribed drug used to treat gastric conditions, esomeprazole (Nexium), 

is partly metabolized by the CYP2C19 enzyme. Studies have shown that 

from 15 to 20 percent of Asians lack the enzyme CYP2C19. As a result, 

some Asians metabolize the drug poorly and require lower doses because 

their bodies do not clear the drug as rapidly as individuals with this 

enzyme.11 Also, compared with Caucasians, certain Asian groups are more 

likely to require lower dosages of a variety of different antipsychotic drugs 

used to treat mental illness. 

Research in adults over the past several decades has further characterized 

significant differences among racial and ethnic groups in the metabolism, 

clinical effectiveness, and side-effect profiles of many clinically important 

drugs. These differences in response to drug therapy can be traced to 

differences in the distribution of genetic traits that produce these 

differences among racial and ethnic groups.12 These naturally occurring 

variations in the structures of genes, drug metabolism enzymes, receptor 

proteins, and other proteins that are involved in drug response affect how 

the body metabolizes certain drugs, including cardiovascular agents (betablockers, diuretics, calcium channel blockers, angiotensin coverting 

 10An FDA review of demographic data for 185 new molecular entities approved between 

January 1, 1995, and December 31, 1999, found that labeling for 45 percent of the drugs 

contained a statement that race may affect how a patient responds to the drug, although in 

only 8 percent were any differences in response related to race described. For this small 

subset of drugs, information on differences in the drugs’ effects among racial and ethnic 

groups noted that 50 percent were related to how drugs are processed in the body, 39 

percent were related to efficacy, and 11 percent were related to safety. However, only one 

drug label, for a drug used to treat hypertension, recommended a change in dosage based 

on racial differences. It recommended that physicians increase the initial dose for African 

American patients. See B. Evelyn and others, FDA, Office of the Commissioner, Office of 

Special Health Issues, Participation of Racial/Ethnic Groups in Clinical Trials and RaceRelated Labeling: A Review of New Molecular Entities Approved 1995-1999 (Rockville, 

Md.: 2001). http://www.fda.gov/cder/reports/race_ethnicity/race_ethnicity_report.htm 

(downloaded Oct. 29, 2002). 

11H. Xie and others, “Molecular Basis of Ethnic Differences in Drug Disposition and 

Response,” Annual Review of Pharmacology Toxicology; Vol. 41 (2001), 815-850, and 

R. Weinshilboum, “Inheritance and Drug Response,” New England Journal of Medicine, 

vol. 348 (2003), 529-537. 

12Institute of Medicine, Unequal Treatment: Confronting Racial and Ethnic Disparities in 

Health Care (Washington, D.C.: 2002). 

Evidence Shows That Drug 

Effectiveness and Toxicity 

Can Vary among Racial 

and Ethnic Groups 
Page 10 GAO-03-950 Pediatric Drug Research 

enzyme (ACE) inhibitors, and central nervous system agents 

(antidepressants and antipsychotics).13

BPCA requires that FDA take into account adequate representation of 

children from ethnic and racial minority groups when issuing written 

requests to drug sponsors. FDA regulations have required that in new drug 

applications, “effectiveness data (safety data) shall be presented by 

gender, age, and racial subgroups and shall identify any modifications of 

dose or dose interval needed for specific subgroups.”14 Other FDA 

guidance encourages the participation of racial and ethnic groups in all 

phases of drug development, recommends collection of race-related data 

during research and development, and recommends the analysis of the 

data for race-related effects.15

FDA officials told us that if there is scientific evidence documenting 

possible mechanisms causing variation in drug response in minorities, 

such as a higher or lower prevalence of a specific drug metabolizing 

enzyme or drug receptor, then FDA’s written request will require the study 

sponsor to increase minority representation in the study. The officials told 

us that it is particularly important to consider racial differences in 

pediatric patients under two circumstances: (1) when there is a possible 

difference in drug metabolism or response demonstrated in adult clinical 

studies or documented in the scientific literature or (2) if a drug is used to 

treat a disease that disproportionately affects minorities. Absent these 

conditions, the officials told us that FDA does not require that sponsors 

include particular numbers or proportions of minority children in its 

studies. 

 13There are over 100 examples in the medical literature in which inherited individual traits 

that contributed to atypical, exaggerated responses to drugs or to unusual effects or 

ineffectiveness of drugs. See for example, V.J. Burroughs, R.W. Maxey, and R.A. Levy, 

“Racial and Ethnic Differences In Response to Medicines: Towards Individualized 

Pharmaceutical Treatment,” Journal of the National Medical Association, vol. 94, no. 10, 

Supplement (2002). 

1421 C.F.R. 314.50 (d)(5)(v) and (vi) (a) (Content and format of an application for approval 

to market a new drug). 

15Food and Drug Administration, Guideline Format and Content of Clinical and 

Statistical Sections of an Application (Rockville, Md.: July 1988); Food and Drug 

Administration, Population Pharmacokinetics (Rockville, Md.: 1999); Food and Drug 

Administration, Content and Format of the Adverse Reactions Section of Labeling for 

Human Prescription Drugs and Biologics (draft) (Rockville, Md.: 2000). 

FDA’s Efforts to Account 

for Minority Children in 

Clinical Drug Studies 
Page 11 GAO-03-950 Pediatric Drug Research 

According to FDA officials, FDA’s policy is to minimize the number of 

children exposed to a drug during clinical studies, while maintaining an 

adequate sample size to draw clinically meaningful conclusions. Most 

pediatric studies for extension of exclusive marketing rights are designed 

to give health care providers information on the appropriate dosage or 

formulation of a drug in a pediatric population.16 As a result, most pediatric 

clinical drug studies generally are on a smaller scale than the clinical 

studies drug sponsors conduct to gain FDA approval to market a new 

drug. FDA officials told us that both the small number of patients in most 

pediatric studies as well as the fact that most studies seek to determine 

the appropriate dosage and safety for pediatric patients have precluded 

any definitive conclusions about racial or ethnic differences in drug 

response among children. No completed studies under the pediatric 

exclusivity provision to date have led to findings or labeling changes 

specific to any racial or ethnic group. 

Compared to their proportions in the U.S. population, smaller proportions 

of children of racial and ethnic minority groups were included in the 

clinical drug studies we reviewed for additional exclusive marketing rights 

that FDA requested before BPCA took effect. However, for hypertension 

drugs where differences in racial response have been documented in adult 

drug studies, FDA required, and drug sponsors included, larger numbers of 

children from specific racial and ethnic groups. Most of FDA’s written 

requests for studies that have been issued since BPCA took effect required 

drug sponsors to report the number of racial and ethnic minorities in their 

final study results. In addition, some requests required drug sponsors to 

analyze the effects of race and ethnicity or increase minority 

representation for certain drugs where differences in racial response have 

been documented in adult drug studies. 

 16FDA officials told us that about one-third of the studies requested under the pediatric 

exclusivity provision are for efficacy. 

Limitations of Pediatric 

Drug Studies 

Smaller Proportions 

of Minority Children 

Were in Studies for 

Additional Marketing 

Exclusivity Requested 

before BPCA 
Page 12 GAO-03-950 Pediatric Drug Research 

Compared with their proportions in the U.S. population, smaller 

proportions of African American, Hispanic, and Asian children were 

included in clinical studies for the drugs that were granted 6 months of 

additional exclusive marketing rights by FDA from January 4, 2002, 

through March 6, 2003. Across all clinical studies for the 23 drugs we 

examined, 7 percent of pediatric patients were African American, 5 

percent were Hispanic, and 1 percent were Asian. Most pediatric patients 

were Caucasian—69 percent—and the race and ethnicity were unknown 

for 14 percent. Compared with the frequency distribution of African 

American and Hispanic children under 18 years of age for the U.S. 

population as a whole in 2000, the proportions of these two groups 

included in clinical drug studies were 8 and 12 percentage points lower, 

respectively, than their proportions in the U.S. population. The proportion 

of Asian children in clinical drug studies was 2 percentage points lower 

than their proportion in the U.S. population (see table 1). (See app. II for 

the number of children in racial and ethnic groups included in clinical 

studies for drugs granted additional exclusive marketing rights from 

January 4, 2002, through March 6, 2003.) 

Table 1: Children, by Racial and Ethnic Group, in Clinical Studies for Drugs Granted 

Additional Exclusive Marketing Rights, January 4, 2002, through March 6, 2003 

Race/ethnicity 

Number in 

clinical studies 

Percentage in 

clinical studies 

Percentage in U.S. 

population under age 18 

African American 488 7 15

Asian 94 1 3

Caucasian 4,783 69 69

Hispanic 355 5 17

Other 272 4 NA

Unknown 960 14 NA

Total 6,952 100 104a

Sources: FDA and Department of Commerce. 

Notes: GAO analysis of final study reports for the 23 drugs granted additional exclusive marketing 

rights; and U.S. Bureau of Census, Census 2000 Summary File 1, “Total Population by Age and Sex 

for the United States: 2000.” 

NA means not applicable. 

a

Individual entries do not sum to 100 percent because the Department of Commerce, in collecting 

U.S. Census data, permitted individuals to report that they belonged to multiple race groups. 

Consequently, the total of all race groups exceeds the population total. 

The Proportions of 

Children in Racial and 

Ethnic Minority Groups in 

Clinical Studies for 

Exclusive Marketing 

Rights Were Lower Than 

Their Proportions in the 

U.S. Population 
Page 13 GAO-03-950 Pediatric Drug Research 

FDA required that sponsors increase representation of children of ethnic 

and racial minority groups in clinical studies for drugs used to treat 

diseases that disproportionately affect children in such groups or where 

evidence from studies on adults suggests that for certain classes of drugs 

differences in metabolism or response for racial or ethnic groups exist. 

For example, because hypertension is more prevalent and more severe in 

African Americans than in Caucasians, and adult responses to some 

hypertension therapies appear to be different in African American and 

non-African American populations, FDA’s written requests for these drugs 

require that the patient recruitment protocol be designed to ensure a 

mixture of African American and non-African American patients. 

Therefore, in pediatric clinical studies for three cardiovascular drugs used 

to treat hypertension, African American children represented 22 percent of 

study participants (see table 2). 

Table 2: Children, by Racial and Ethnic Group, in Clinical Studies for Three Drugs 

for Which FDA Required Mixed Race Participation, and for All Other Drugs Granted 

Additional Exclusive Marketing Rights, January 4, 2002, through March 6, 2003 

 Numbers in percent 

Race/ethnicity 

In clinical studies for 

3 drugs when mixed 

race required 

In all other clinical 

studies 

In U.S. population 

under age 18 

African American 22 6 15 

Asian 1 1 3 

Caucasian 54 70 69 

Hispanic 17 4 17 

Other or unknown 6 19 NA 

Total 100 100 104a

Sources: Department of Commerce and FDA. 

Notes: GAO analysis of 23 new drug applications (NDAs) or supplemental new drug applications 

(sNDAs) and FDA medical officer reviews and Department of Commerce, Bureau of the Census, 

Census 2000 Summary File 1, “Total Population by Age and Sex for the United States: 2000.” 

NA means not applicable. 

a

Individual entries do not sum to 100 percent because the Department of Commerce, in collecting 

U.S. Census data, permitted individuals to report that they belonged to multiple race groups. 

Consequently, the total of all race groups exceeds the population total. 

Pediatric Studies for 

Hypertension Drugs 

Included More Children of 

Racial and Ethnic Minority 

Groups 
Page 14 GAO-03-950 Pediatric Drug Research 

For some written requests issued since BPCA took effect, FDA required 

sponsors to increase the participation of minority children. Specifically, 4 

of the 22 written requests for such studies directed sponsors to increase 

the proportion of minority children participants or to analyze the effects of 

race and ethnicity. In 11 of the 22 requests, FDA directed drug sponsors to 

report the representation of pediatric patients of ethnic and racial minority 

groups when submitting final study results, but did not request that 

sponsors include a particular proportion of minority children or analyze 

the effects of race and ethnicity. The remaining 7 written requests made no 

mention of race or ethnicity. 

FDA’s four study requests that directed sponsors to increase the 

proportion of minority children participants or to analyze the effects of 

race or ethnicity took varied approaches. One written request by FDA 

required that the sponsor include a mixture of African American and nonAfrican American patients for a study of a drug used to treat hypertension. 

Two other requests, for diabetes drugs, required the study sponsors to 

ensure that 50 percent of the study populations were composed of African 

American, Native American, and Hispanic patients because of a greater 

prevalence of diabetes in these groups. In the fourth written request, for a 

drug used to prevent bone loss, FDA required that the study sponsor 

examine potential demographic covariates, such as race. 

Some drugs that may be used to treat diseases or conditions that 

disproportionately affect children of racial and ethnic minority groups are 

being studied under the pediatric exclusivity provision. In response to 

FDA written requests, drug sponsors are conducting or have completed 

pediatric studies on drugs that might be used to treat hypertension, type II 

diabetes, sickle cell anemia, and other conditions that disproportionately 

affect minorities. 

From January 4, 2002, through March 6, 2003, FDA granted exclusive 

marketing rights or issued written requests for studies of 10 drugs that 

might be used to treat diseases or conditions that disproportionately affect 

minority children. Specifically, 4 of the 23 drugs for which FDA granted 

additional exclusive marketing rights might be used to treat diseases or 

conditions that are more prevalent in minorities, such as asthma and 

hypertension (see table 3). In addition, 6 of the 22 written requests for new 

studies that FDA issued to drug manufacturers during this period also 

included treatments for diseases or conditions disproportionately affecting 

minorities, such as type II diabetes, hypertension, sickle cell anemia, HIV, 

and hepatitis B. 

FDA Written Requests 

Issued since BPCA Require 

Sponsors to Increase 

Minority Representation 

for Certain Drugs 

Drugs of Importance 

to Minority Children 

Are Being Studied in 

Response to Pediatric 

Exclusivity Provision 

Requests 
Page 15 GAO-03-950 Pediatric Drug Research 

Table 3: Estimated Prevalence of Diseases or Conditions in Minorities That May Be Treated by Drugs for Which FDA Issued 

Written Requests or Granted Exclusive Marketing Rights, January 4, 2002, through March 6, 2003 

Disease/condition 

Estimated prevalence among selected racial and 

ethnic groups Drug(s) Study status 

Asthma Asthma prevalence of 82/1,000 in African American 

children compared to 76/1,000 in Hispanic and 65/1,000 in 

Caucasian children.a

Budesonide Exclusive rights granted. 

Diabetes mellitus 

(type II diabetes) 

National age-adjusted rates for all types of diabetes show 

that it is more frequent in African Americans and Hispanics 

than Caucasians.b

 In addition, one study found that over 

70 percent of type II diabetes cases among children were 

in African Americans.c

Metformin 

Pioglitazone 

Written request issued. 

Written request issued. 

Hepatitis B Age-adjusted rates of Hepatitis B in African Americans are 

more than 2.5 times greater than in Hispanics and 4.5 

times greater than in Caucasians.d

Adefovir Written request issued. 

HIV infection and AIDS Prevalence rate of 1.4/100,000 African American children 

was 7 times greater than in Hispanics and 14 times 

greater than in Caucasians and Asians.e

Tipranavir Written request issued. 

Hypertension A study found that a sample of African American children 

in California had higher blood pressure than Caucasian 

children.f

Losartan 

Quinapril 

Fosinopril 

Metoprolol 

Exclusive rights granted. 

Exclusive rights granted. 

Exclusive rights granted. 

Written request issued. 

Sickle cell anemia Occurs in 1 out of every 700 African American births, 1 of 

every 46,622 Hispanic births, and 1 of every 158,127 

Caucasian births.g

Hydroxyurea Written request issued. 

Sources: FDA and publications identified below. 

a

L.J. Akinbami and K.C. Schoendorf, “Trends in Childhood Asthma Prevalence, Health Care 

Utilization, and Mortality,” Pediatrics, vol. 110, no. 2 (2002), 315-322. 

b

Age-adjusted rates from the National Center for Chronic Disease, Diabetes Public Health Resources, 

available at http://www.cdc.gov/diabetes/statistics/index.htm#prevalence (downloaded Apr. 11, 2003). 

c

A study in Arkansas found that 74 percent of type II diabetes in children was in African Americans. 

C. Scott and others, “Characteristics of Youth-onset Noninsulin-dependent Diabetes Mellitus and 

Insulin-dependent Diabetes Mellitus at Diagnosis,” Pediatrics, vol. 100, no.1 (1997), 84-91. 

d

Age-adjusted rates from the National Health and Nutrition Examination Survey III (1988-1994) in 

G.M. McQuillan and others, “Prevalence of Hepatitis B Virus Infection in the United States: The 

National Health And Nutrition Examination Surveys, 1976 through 1994,” American Journal of Public 

Health, vol. 89, no. 1 (1999), 14-18. 

e

Based on a total of 175 AIDS cases reported in children aged 13 and younger in December 2001, 

from National Center for HIV, STD and TB Prevention, 

http://www.cdc.gov/hiv/stats/hasr1302/table18.htm#tab18 (downloaded Apr. 11, 2003). 

f

M.L. Cruz and others, “Insulin Sensitivity and Blood Pressure in Black and White Children,” 

Hypertension, vol. 40, no. 1 (2002), 18-22. 

g

A. Ashley-Koch, Q. Yang, and R.S. Olney, “Sickle Hemoglobin (Hb S) Allele and Sickle Cell Disease: 

A HuGE Review,” American Journal of Epidemiology, vol. 151, no. 9 (2000), 839-845. 
Page 16 GAO-03-950 Pediatric Drug Research 

FDA does not have a system in place to serve as a single source of data to 

allow the agency to efficiently determine the extent of minority enrollment 

in drug studies under the pediatric exclusivity provision. Further, we 

found that some study reports submitted to FDA from drug sponsors did 

not specify the race and ethnicity of study participants. For example, in 

the completed studies for the 23 drugs granted additional exclusive 

marketing rights that we examined, the race or ethnicity of 86 percent of 

study participants was identified, but study sponsors did not specify the 

race or ethnicity of 960 children, or 14 percent of the studies’ populations. 

Recently, FDA issued draft guidance to improve drug sponsors’ reporting 

of racial and ethnic minority representation data, and FDA is planning to 

develop a database to monitor demographic variables in drug trials across 

the agency. 

There is no single data source at FDA to allow the agency to tabulate the 

overall numbers of racial and ethnic minorities in clinical studies. For 

example, to quantify the participation of racial and ethnic groups in 

studies for the 23 drugs granted additional exclusive marketing rights 

since January 2002, FDA had to extract and tally race data from about 50 

separate final study reports that included nearly 7,000 children. 

Final study results submitted to FDA from sponsors do not always fully 

describe the race and ethnicity of children who participated in clinical 

drug studies. In addition, FDA has not established uniform definitions for 

reporting racial and ethnic minorities in drug studies. In reviewing the 

study results for the 23 drugs granted additional exclusive marketing rights 

from January 4, 2002, through March 6, 2003, we found wide variation in 

how study sponsors presented and defined data regarding minority 

participation. Study sponsors reported minority representation according 

to non-standard definitions, which were often ambiguous. For example, 

one study classified its 200 participants as “mostly Caucasian” and 

included no further data on the remaining population. Similarly, in studies 

included in three applications involving more than 1,500 children, 

sponsors only identified the number of Caucasian patients and did not 

identify the racial or ethnic groups of non-Caucasian children. Across all 

studies for drugs granted exclusive marketing rights from January 4, 2002, 

through March 6, 2003, the race or ethnicity of 960 children, or about 14 

percent of all study participants, was unknown. Eighty-six percent of 

study participants were identified by race or ethnicity. Further, we could 

identify the specific race or ethnicity for only 30 of the 268 subjects 

classified as “other” in study reports. FDA officials told us that they do not 

FDA Monitoring of 

Data on Minority 

Representation Needs 

Improvement 

There Is No Single Source 

of Data about Minority 

Representation 

Reporting of Minority 

Representation Data Is Not 

Standardized 
Page 17 GAO-03-950 Pediatric Drug Research 

know which populations are included in the “other” category and that it 

likely includes children whose race was not determined. 

Recently, FDA has begun to take steps to address data management 

issues. In January 2003, FDA issued draft guidance for industry17

recommending that study sponsors collect and report racial and ethnic 

representation using definitions developed by the Office of Management 

and Budget, which HHS adopted for use in HHS funded and sponsored 

data collection and reporting systems.18 FDA stated in its draft guidance 

that using uniform categories would enhance the consistency and 

comparability of data across studies and other HHS agencies, as well as 

promote the early identification of differences in physiological response 

among racial and ethnic groups. FDA’s draft guidance recommended that 

sponsors collect race and ethnicity data for clinical study participants 

using five racial groups (African American/Black, American Indian/Alaska 

Native, Asian, and Native Hawaiian/Other Pacific Islander, and White) and 

two ethnic groups (Hispanic/Latino and not Hispanic/Latino). However, 

FDA guidance is not legally binding for either FDA or the sponsor. 

In addition, FDA has started to develop an agencywide system called the 

Demographic Information and Data Repository (DIDR) to electronically 

manage information regarding demographic characteristics of clinical trial 

participants, including age, sex, and race.19 DIDR is part of FDA’s response 

to a congressional report requesting that FDA monitor the representation 

 17See Food and Drug Administration, A Guidance for Industry: Collection of Race and 

Ethnicity Data in Clinical Trials (Rockville, Md.: January 2003) 

http://www.fda.gov/cber/gdlns/racethclin.htm (downloaded Jan. 28, 2003). 

18See Department of Health and Human Services, A Policy Statement on Inclusion of Race 

and Ethnicity in DHHS Data Collection Activities (Washington, D.C.: October 1997). 

19In a prior report, we recommended that FDA develop management tools to ensure that 

the collection, presentation, and analyses of data related to sex differences are addressed 

and monitored. See U.S. General Accounting Office, Women’s Health: Women Sufficiently 

Represented in New Drug Testing, but FDA Oversight Needs Improvement, GAO-01-754

(Washington, D.C.: July 6, 2001).

FDA Is Taking Steps to 

Improve Data Management 
Page 18 GAO-03-950 Pediatric Drug Research 

of women in clinical studies.20 The conference report accompanying FDA’s 

2002 appropriations identified a $500,000 increase in funding for FDA’s 

Office of Women’s Health to begin work on this system. FDA officials told 

us that it would be several years before the system is operational. 

To have optimal effectiveness for all children, a drug should be tested in 

clinical studies that include pediatric patients representing the full range 

of population groups likely to receive the drug once it is marketed. In 

addition to age, genetic factors related to race and ethnicity may play 

important roles in the variability of patients’ responses to a drug. Pediatric 

clinical drug studies with sufficient representation of minority groups are 

necessary to detect the presence or absence of differences in responses to 

certain drugs. The changes under BPCA to the pediatric exclusivity 

provision require that FDA take into account the adequate representation 

of children of racial and ethnic minorities in written requests for drug 

studies. However, it is too early to tell whether FDA’s written requests 

issued since enactment of BPCA will result in better reporting or a broader 

mix of participants. Currently, FDA is unable to accurately determine 

whether and to what extent minority groups are accounted for in final 

study results because it does not require sponsors to use uniform 

definitions. Though FDA’s draft guidance on standard definitions for 

reporting race and ethnicity is helpful, sponsors will not be obligated to 

use these categories to identify study participants unless FDA requests 

that they do so. The standardized collection of demographic data, such as 

race and ethnicity, would help ensure that FDA’s forthcoming DIDR will 

have the required data needed to evaluate the risks and benefits of a drug 

in specific demographic groups. 

To help the agency more efficiently monitor the participation of children 

of racial and ethnic groups in studies for additional exclusive marketing 

rights, we recommend that the Commissioner of FDA specify in written 

requests that study sponsors must use the racial and ethnic categories 

 20The conference report for the 2002 FDA appropriations act expressed concern that FDA 

has paid insufficient attention to gender-based research and directed the agency to develop 

an agencywide database focused on women’s health activities to include demographic data 

on clinical trials. See H.R. Conf. Rep. No. 107-275, at 82-83 (2001) (accompanying Pub. L. 

No. 107-76, making appropriations for Agriculture, Rural Development, Food and Drug 

Administration, and Related Agencies programs for the Fiscal Year Ending September 30, 

2002, and for other purposes). 

Conclusions 

Recommendation for 

Executive Action 
Page 19 GAO-03-950 Pediatric Drug Research 

described in FDA’s January 2003 draft guidance to identify study 

participants in their reports to the agency. FDA can refuse to grant 6 

months of additional exclusive marketing rights under the pediatric 

exclusivity provision for sponsors that do not fairly respond to FDA’s 

written requests. 

FDA comments on a draft of this report reaffirmed the importance of 

clinical studies of drugs used to treat children. FDA agreed that the agency 

needed to improve the efficiency of its system for tracking demographic 

information about study participants. FDA also agreed with our 

recommendation and reported that it has already begun to implement it. 

FDA raised concerns about three aspects of our draft report. First, FDA 

was critical of our comparison of the proportions of minority children 

study participants to the proportions of minority children in the 

population. FDA commented that it would have been more appropriate for 

us to compare the proportions of minority children in clinical drug studies 

with the proportions of minority children with the specific condition each 

drug is intended to treat. We agree that such a comparison would have 

been useful, but both we and FDA found that the information needed for 

such comparisons—the racial and ethnic group distributions of children 

with many of the specific conditions treated by the drugs studied for 

additional exclusive marketing rights—was not available. Further, FDA 

has previously used the methodology we employed in its analyses of adult 

study participants.21

Second, FDA was concerned about what it regards as the implications of 

our finding that the proportions of minority children in pediatric studies 

requested by FDA before the passage of BPCA were less than their 

proportions in the general population. FDA incorrectly suggested that we 

advocate that “the percentage of children in each clinical drug trial would 

or should track the percentage of children in the general population.” Our 

report does not make any recommendations about the preferred study 

populations for any clinical drug trial. Further, we did not disagree with 

FDA’s current policy requiring larger proportions of children from racial 

and ethnic minority groups when a studied drug treats a condition that 

 21For example, see B. Evelyn and others, Participation of Racial/Ethnic Groups in 

Clinical Trials and Race-Related Labeling: A Review of New Molecular Entities Approved 

1995-1999. 

Agency Comments 

and Our Evaluation 
Page 20 GAO-03-950 Pediatric Drug Research 

disproportionately affects minorities or when it is known from adult 

studies that the effects of a drug may be different in persons from different 

racial or ethnic groups. 

Third, FDA noted that the race or ethnicity of a high percentage of study 

participants was identified even before BPCA was enacted. Our findings 

agree with that assessment—we reported that the race or ethnicity of 

study participants was identified for 86 percent of study participants—but 

we believe that FDA should have been able to identify the race or ethnicity 

of every study participant. 

FDA’s written comments are reprinted in appendix III of this report. FDA 

also provided technical comments, which we considered and incorporated 

where appropriate. 

We are sending this report to the Commissioner of FDA and to other 

interested persons. We will also provide copies to others upon request. In 

addition, the report will be available at no charge on GAO’s Web site at 

http://www.gao.gov. 

If you or your staffs have any questions about this report, please contact 

me at (202) 512-7119. Another contact and major contributors to this 

report are listed in appendix IV. 

Janet Heinrich 

Director, Health Care—Public Health Issues 
Appendix I: Scope and Methodology 

Page 21 GAO-03-950 Pediatric Drug Research 

To assess the extent to which children of racial and ethnic groups are 

represented in clinical studies for drugs granted exclusive marketing 

rights, we reviewed data for the 23 drugs that were granted exclusive 

marketing rights from January 4, 2002, through March 6, 2003. For these 23 

drugs, we determined the total number of children in four racial and ethnic 

groups enrolled in each study from Food and Drug Administration 

summary documents, and new drug applications (NDA) or supplemental 

new drug applications (sNDA) submitted to FDA for this time period. We 

collected clinical study participation data for three racial groups (African 

American, Asian, and Caucasian) and one ethnic group (Hispanic) because 

drug sponsors commonly used these categories.1

 However, the clinical 

studies included in the NDAs or sNDAs submitted during this period were 

conducted before the effective date for the Best Pharmaceuticals for 

Children Act of 2002 because the time lag between when FDA issues a 

written request for a pediatric study and when sponsors submit final study 

results ranged from 1 to 4 years. To assess the extent to which FDA 

required drug sponsors to take into account the adequate representation 

of children of racial and ethnic groups in clinical studies for drugs for 

which written requests have been issued since BPCA took effect, we 

reviewed the 22 written requests issued for pediatric drug studies by FDA 

from January 4, 2002, through March 6, 2003. 

To determine whether drugs used to treat conditions or diseases 

disproportionately affecting minorities are being studied under the 

pediatric exclusivity provision, we obtained data on the prevalence of 

selected diseases or conditions that disproportionately affect minorities 

and examined the list of drugs for which FDA has either granted exclusive 

marketing rights or issued study requests from January 4, 2002, through 

March 6, 2003, to determine if any of these drugs may be used to treat 

these diseases or conditions. We compiled data on the estimated 

prevalence of the diseases and conditions by race and ethnicity from the 

National Centers for Health Statistics, National Center of HIV, STD, and 

Tuberculosis Prevention, and research in scientific journals reporting the 

prevalence of these diseases and conditions in minority children. We 

interviewed National Institutes of Health officials, pharmacology experts, 

and pediatric clinicians, including members of the American Academy of 

 1

We classified as “other” any study participants that were specified by some other race or 

ethnicity. If no race was indicated, we classified those participants as “unknown.” For 

example, one study classified its 200 participants as “mostly Caucasian” and included no 

further data on the remaining population. We classified the entire study population as 

unknown. 

Appendix I: Scope and Methodology 
Appendix I: Scope and Methodology 

Page 22 GAO-03-950 Pediatric Drug Research 

Pediatrics and the Pharmaceutical Research and Manufacturers of 

America to gain their perspectives on the representation of minorities in 

drug studies and the study of drugs of importance to these populations. 

To evaluate FDA’s management of pediatric clinical study data on minority 

representation and its guidance to sponsors on reporting such data, we 

reviewed FDA’s policies, guidance, and rules for inclusion and reporting of 

minority representation in drug studies. We interviewed FDA officials 

within the Office of Counter-Terrorism and Pediatric Drug Development to 

determine how they interpret and implement these policies for the 

pediatric exclusivity program. We spoke with officials in the Office of 

Women’s Health who were responsible for establishing a database to 

monitor demographic variables to determine how an agencywide 

demographic database might affect the monitoring of minority 

participation in drug studies. We also reviewed FDA’s response to a 

congressional request to develop an agencywide demographic database.2

We conducted our work from October 2002 through September 2003 in 

accordance with generally accepted government auditing standards. 

 2

“Response to Congressional Request on FY 2002 Funding to Develop an Agency-wide 

Database Focused on Women’s Health Activities,” Conference Action, Pub. L. No. 107-76, 

FDA, June 2002. 
Appendix II: The Number of Children by 

Racial and Ethnic Group in Studies for Drugs 

Granted Exclusive Marketing Rights 

Page 23 GAO-03-950 Pediatric Drug Research 

We obtained the number of children by race or ethnic group who 

participated in the clinical drug studies for the 23 NDAs or sNDAs for 

exclusive marketing rights in our sample by reviewing the portions of final 

study reports that provide information on the demographic representation 

in the study. Table 4 represents the number of children of racial and ethnic 

groups, by drug class, in clinical studies for drugs granted exclusive 

marketing rights from January 4, 2002, through March 6, 2003. It is 

important to recognize that the FDA written requests outlining the study 

design for the 23 NDAs or sNDAs that we examined preceded the passage 

of BPCA on January 4, 2002. The time between when FDA issued written 

requests for pediatric studies and sponsors conducted and submitted final 

study results for FDA review and approval ranged from 1 to 4 years. 

Appendix II: The Number of Children by 

Racial and Ethnic Group in Studies for Drugs 

Granted Exclusive Marketing Rights 
Appendix II: The Number of Children by 

Racial and Ethnic Group in Studies for Drugs 

Granted Exclusive Marketing Rights 

Page 24 GAO-03-950 Pediatric Drug Research 

Table 4: Children of Racial and Ethnic Groups, by Drug Class, in Clinical Studies for Drugs Granted Exclusive Marketing 

Rights, January 4, 2002, through March 6, 2003 

Drug Indication African American Asian Caucasian Hispanic Other Unknown Total

A Allergic Rhinitis 6 0 46 0 5 398 455

B Allergic Rhinitis 47 2 146 0 24 0 219

C Allergic Rhinitis 51 0 222 0 33 0 306

D Cancer 0 0 30 0 0 45 75

E Cancer 13 4 151 10 7 0 185

F Cancer — — 26 — — 112 138

G Cancer 1 0 12 6 5 0 24

H Cardiovascular 3 3 172 0 9 0 187

I Cardiovascular 0 0 311 6 2 0 319

J Cardiovascular 2 6 203 0 3 24 238

K Hypertensiona 52 5 152 35 9 0 253

L Hypertensiona 50 3 54 21 8 0 136

M Hypertensiona 33 0 125 48 21 0 227

N Ophthalmologic 3 2 89 0 40 0 134

O Ophthalmologic 3 2 89 0 40 0 134

P Psychiatric 16 49 265 34 12 0 376

Q Psychiatric 6 0 1,101 0 4 249 1,360

R Psychiatric 52 4 391 48 23 0 518

S Psychiatric 0 0 367 0 0 89 456

T Psychiatric 86 8 583 72 19 43 811

U Other 18 1 86 26 1 0 132

V Other 5 2 15 5 1 0 28

W Other 41 3 147 44 6 0 241

Total 488 94 4,783 355 272 960 6952

 Percentage of children in 

clinical studies 7 1 69 5 4 14 100

 Percentage of U.S. population 

under age 18 15 3 69 17 NA NA 104b

Sources: Department of Commerce and FDA. 

Notes: GAO analysis of 23 NDAs or sNDAs and FDA medical officer reviews; and U.S. Bureau of 

Census, Census 2000 Summary File 1, “Total Population by Age and Sex for the United States: 

2000.” 

NA means not applicable. 

a

Drugs are those for which FDA required greater minority representation. 

b

Individual entries do not sum to 100 percent because in collecting U.S. Census data, the Department 

of Commerce permitted individuals to report that they belonged to multiple race groups. 

Consequently, the total of all race groups will exceed the total population. 
Appendix III: Comments from the Food and Drug Administration 

Page 25 GAO-03-950 Pediatric Drug Research 

Appendix III: Comments from the Food and 

Drug Administration 
Appendix III: Comments from the Food and Drug Administration 

Page 26 GAO-03-950 Pediatric Drug Research 
Appendix III: Comments from the Food and Drug Administration 

Page 27 GAO-03-950 Pediatric Drug Research 
Appendix III: Comments from the Food and Drug Administration 

Page 28 GAO-03-950 Pediatric Drug Research 
Appendix IV: GAO Contact and Staff 

Acknowledgments 

Page 29 GAO-03-950 Pediatric Drug Research 

Martin T. Gahart, (202) 512-3596 

Gloria E. Taylor, Sharif Idris, George Bogart, and Elizabeth T. Morrison 

also made major contributions to this report. 

Appendix IV: GAO Contact and Staff 

Acknowledgments 

GAO Contact 

Acknowledgments 

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