Department of Health and Human Services
 

OFFICE OF 

INSPECTOR GENERAL 

THE FOOD AND DRUG 


ADMINISTRATION’S OVERSIGHT 


OF CLINICAL TRIALS
 

Daniel R. Levinson
 

Inspector General 


September 2007
 

OEI-01-06-00160
 
 

 

 

 

 

 

 

 

 

 

 

 

 

Office of Inspector General
 http://oig.hhs.gov 

The mission of the Office of Inspector General (OIG), as mandated by Public Law 95-452, 

as amended, is to protect the integrity of the Department of Health and Human Services 

(HHS) programs, as well as the health and welfare of beneficiaries served by those 

programs. This statutory mission is carried out through a nationwide network of audits, 

investigations, and inspections conducted by the following operating components: 

Office of Audit Services 

The Office of Audit Services (OAS) provides all auditing services for HHS, either by 

conducting audits with its own audit resources or by overseeing audit work done by others. 

Audits examine the performance of HHS programs and/or its grantees and contractors 

in carrying out their respective responsibilities and are intended to provide independent 

assessments of HHS programs and operations. These assessments help reduce waste, 

abuse, and mismanagement and promote economy and efficiency throughout HHS. 

Office of Evaluation and Inspections 

The Office of Evaluation and Inspections (OEI) conducts national evaluations to provide 

HHS, Congress, and the public with timely, useful, and reliable information on 

significant issues. Specifically, these evaluations focus on preventing fraud, waste, or 

abuse and promoting economy, efficiency, and effectiveness in departmental programs. 

To promote impact, the reports also present practical recommendations for improving 

program operations. 

Office of Investigations 

The Office of Investigations (OI) conducts criminal, civil, and administrative 

investigations of allegations of wrongdoing in HHS programs or to HHS beneficiaries 

and of unjust enrichment by providers. The investigative efforts of OI lead to criminal 

convictions, administrative sanctions, or civil monetary penalties. 

Office of Counsel to the Inspector General 

The Office of Counsel to the Inspector General (OCIG) provides general legal services to 

OIG, rendering advice and opinions on HHS programs and operations and providing all 

legal support in OIG's internal operations. OCIG imposes program exclusions and civil 

monetary penalties on health care providers and litigates those actions within HHS. 

OCIG also represents OIG in the global settlement of cases arising under the Civil False 

Claims Act, develops and monitors corporate integrity agreements, develops compliance 

program guidances, renders advisory opinions on OIG sanctions to the health care 

community, and issues fraud alerts and other industry guidance. 
 

INTRODUCTION 

 

 

Δ EXECUTIVE SUMMARY 

OBJECTIVE 

1.	 To determine the extent to which the Food and Drug Administration 

(FDA) conducted inspections of clinical trials from fiscal year 

(FY) 2000 to FY 2005. 

2.	 To assess FDA’s processes for inspecting clinical trials. 

BACKGROUND 

The Federal Food, Drug, and Cosmetic Act generally requires all new 

drugs and medical devices (hereinafter referred to as investigational 

products) to undergo clinical trials on human subjects to demonstrate 

the safety and efficacy of these products before they are approved for 

sale in the United States. The sponsors, clinical investigators, and 

institutional review boards (IRBs) that conduct and oversee these trials 

must comply with FDA regulations designed to protect the human 

subjects participating in them. The Office of Inspector General (OIG) 

received a congressional request to review FDA oversight of clinical 

trials after a series of news articles highlighted vulnerabilities. 

Three FDA centers regulate medical investigational products for human 

use: the Center for Drug Evaluation and Research, the Center for 

Biologics Evaluation and Research, and the Center for Devices and 

Radiological Health. FDA’s Office of Regulatory Affairs (ORA) conducts 

onsite bioresearch monitoring (BiMo) inspections of sponsors, clinical 

investigators, and IRBs as assigned by the centers. 

BiMo inspections are not required by Federal regulations; the centers 

decide when to assign them. Inspections can result in one of three 

classifications: no action indicated (NAI), voluntary action indicated 

(VAI), or official action indicated (OAI). After the inspection, BiMo 

investigators recommend a classification for the inspection, and the 

assigning center reviews the inspection report and assigns a final 

classification. Although FDA takes no additional action for inspections 

classified as NAI, it may take additional action for VAI and OAI 

inspections. 

We used seven data sources for this study: BiMo inspections data; file 

reviews of all inspections that BiMo investigators or a center classified 

as OAI; an e-mail survey of BiMo investigators; interviews with FDA 

officials; observations of BiMo inspections; analysis of the National 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS i 
 

 

 

EXECUTIVE SUMMARY 

Institutes of Health (NIH) clinical trial registry; and reviews of FDA 

policies, procedures, and guidance documents. 

FINDINGS 

Data limitations inhibit FDA’s ability to effectively manage the BiMo 

program. Because FDA does not maintain a clinical trial registry, it is 

unable to identify all ongoing clinical trials and their associated trial sites. 

Further, because FDA does not maintain an IRB registry, it is unable to 

identify all IRBs. Even though FDA maintains six databases to track 

BiMo inspections, none includes complete information needed to track all 

such inspections. For example, ORA’s database does not include complete 

information for inspection events that occur after it completes its 

inspection. The center databases do not consistently track inspection 

information. 

Other factors hinder FDA’s ability to effectively manage the BiMo 

program. Centers and ORA inconsistently classify OAI and NAI 

inspections. FDA relies on voluntary compliance to correct violations of 

regulatory significance. Uncertainty of timing and lack of coordination 

impede FDA’s ability to conduct BiMo inspections. In addition, FDA 

guidance and regulations do not reflect current clinical trials practices. 

We estimate that FDA inspected 1 percent of clinical trial sites 

during the fiscal year 2000–2005 period. FDA conducted 2,856 BiMo 

inspections that required a clinical trial site visit during the 

FY 2000–2005 period. Because FDA cannot identify the total number of 

clinical trial sites, we used the NIH clinical trial registry to estimate the 

proportion of clinical trial sites the BiMo inspections reached. The 

centers conduct more inspections that verify clinical trial data than 

inspections that focus on human subject protections. Seventy-five 

percent of the BiMo inspections during the FY 2000–2005 period were 

surveillance inspections, which generally target previously completed 

trials and often focus on verifying the quality of clinical trial data. Also, 

FDA inspected few IRBs, which offer considerable oversight of human 

subject protections. 

RECOMMENDATIONS 

To improve the BiMo information systems and processes, FDA should 

take the following actions: 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS ii 
 

 

 

 

 

 

 

 

EXECUTIVE SUMMARY 

Improve information systems and processes. 

Develop a clinical trial database that includes all clinical trials. FDA should 

develop a comprehensive internal database of clinical trials to more 

effectively identify and target ongoing clinical trials for inspection. 

Create an IRB registry. This registry would give FDA basic information 

about IRBs that it now lacks. By identifying all IRBs overseeing clinical 

trials, FDA could target IRBs more effectively for inspection. 

Create a cross-center database that allows complete tracking of BiMo 

inspections. A database that includes timely and complete information 

about all BiMo inspections would help FDA better coordinate and track 

inspections. 

Establish a mechanism to provide feedback to BiMo investigators on their 

inspection reports and findings. Improved feedback between the centers and 

BiMo investigators could lead to a common understanding of the 

regulations and guidelines that govern BiMo inspections. 

Seek legal authority to provide oversight that reflects current clinical trial 

practices. FDA should consider seeking additional authority that covers 

all of the stakeholders in the management and conduct of clinical trials. 

In particular, FDA could seek to expand its authority to include the 

colleagues and subordinates of a clinical investigator if they participate 

in the conduct of a clinical trial. 

AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 

RESPONSE 

FDA concurred with four of our five recommendations listed above. 

FDA did not address our recommendation to establish a mechanism to 

provide feedback to BiMo investigators on their inspection reports and 

findings. 

FDA pointed out that BiMo inspections make up only one part of its 

efforts to ensure human subject protections, noting that it views its 

protocol review before a clinical trial commences as the most important 

step in protecting human subjects. We recognize the important role 

that FDA’s protocol review plays in protecting human subjects. We 

note, however, that this report addresses another important part of the 

system for protecting human subjects: oversight of the trials once they 

are actually underway. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS iii 
 

EXECUTIVE SUMMARY 

The agency also highlighted the efforts of its Human Subject 

Protection/Bioresearch Monitoring Council and emphasized the 

importance of risk-based approaches to BiMo inspections. 

Where appropriate, we made changes to the report based on FDA’s 

technical comments. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS iv 
 

 

Δ TABLE OF CONTENTS 

EXECUTIVE SUMMARY ..................................... i 
 

INTRODUCTION ........................................... 1 
 

FINDINGS ................................................ 10 
 

Data limitations inhibit FDA’s ability to manage effectively .... 10 
 

Other factors hinder FDA’s ability to manage effectively ....... 13 
 

We estimate that FDA inspected 1 percent of clinical trials ..... 18 
 

RECOMMENDATIONS ..................................... 22 
 

Agency comments and Office of Inspector General response .... 24 
 

APPENDIXES ............................................. 25 
 

A: Methodology........................................ 25 
 

B: Agency comments ................................... 31 
 

ACKNOWLEDGMENTS .................................... 34 
 
 

INTRODUCTION 

 

Δ INTRODUCTION 

OBJECTIVE 

1.	 To determine the extent to which the Food and Drug Administration 

(FDA) conducted inspections of clinical trials from fiscal year 

(FY) 2000 to FY 2005. 

2.	 To assess FDA’s processes for inspecting clinical trials. 

BACKGROUND 

The Federal Food, Drug, and Cosmetic Act generally requires all new 

drugs and medical devices (hereinafter referred to as investigational 

products) to undergo clinical trials on human subjects to demonstrate 

the safety and efficacy of these products before they are approved for 

sale in the United States.1 2 FDA has promulgated regulations to 

protect the rights, safety, and well-being of the human subjects who 

participate in these trials. These regulations apply to the sponsors, 

clinical investigators, and institutional review boards (IRBs) that 

conduct or oversee clinical trials for investigational products. FDA 

inspects clinical trials to determine whether each of these groups 

complies with the relevant regulations. 

The Office of Inspector General (OIG) received a congressional request 

to review FDA’s oversight of clinical trials after a series of news articles 

highlighted vulnerabilities.3 The series identified problems with FDA’s 

oversight of clinical trials, including insufficient informed consent 

procedures, inadequate training and certification requirements for 

IRBs, limited Federal regulations, and FDA’s failure to enforce existing 

regulations. 

Clinical Trials 

Sponsors. The person or entity responsible for developing and testing 

an investigational product is the product’s sponsor. Sponsors of drug 

and biological products must file an investigational new drug (IND) 

application with FDA before they can begin clinical trials; device 

1 In some instances devices do not go through a formal approval process but go to market 

through a premarket notification and determination of substantial equivalence by FDA. In 

these instances, clinical trials may not be necessary. See Federal Food, Drug, and Cosmetic 

Act of 1938, P. L. No. 75-717, 52 Stat.1040 (1938) (amended 2004). 

21 U.S.C. § 360(o). 

2 21 U.S.C. §§ 355(i), 360(j). 

3 David Evans, Mike Smith, Liz Willen, “Drug Industry Human Testing Masks Death, 

Injury, Compliant FDA,” Bloomberg News, November 2, 2005. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 1 
 

 

 

 

 

 

 

INTRODUCTION 

sponsors submit investigational device exemptions (IDE).4 INDs and 

IDEs provide FDA with information on the study protocol, the 

qualifications of trial personnel, and assurances that trials will protect 

human subjects’ welfare, among other details.5 A sponsor may begin its 

clinical trial 30 days after FDA receives an IND or IDE, provided that 

the agency does not place the study on clinical hold.6 

FDA regulations require sponsors to select qualified clinical 

investigators to conduct the trials needed to bring an investigational 

product to the market.7 A clinical trial generally involves many clinical 

investigators working in multiple trial sites, including sites outside the 

United States. 

Sponsors must also ensure that proper monitoring occurs throughout 

the clinical trial.8 In part, this means that sponsors must ensure that 

clinical investigators comply with the relevant FDA regulations. Key 

FDA regulations pertaining to clinical trials address informed consent 

procedures, data management practices, and clinical trial oversight 

processes.9 

If the clinical trials demonstrate the investigational product to be safe 

and effective, sponsors that wish to market a product in the United 

States must submit a new product application to FDA.10 11 Provisions 

within the Prescription Drug User Fee Act of 1992 (PDUFA) and the 

Medical Device User Fee and Modernization Act of 2002 (MDUFMA) 

require FDA to expedite the process for the review of product 

applications.12 FDA reviews the clinical trial data and may choose to 

inspect facilities as part of the application review process.13 If FDA 

4 21 CFR § 312.20 (drugs and biologics); 21 CFR § 812.20 (medical devices). 

5 21 CFR § 312.23. 

6 21 CFR § 312.40 (drugs and biologics); 21 CFR § 812.30 (medical devices). 

7 21 CFR § 312.50 (drugs and biologics); 21 CFR § 812.40 (medical devices). 

8 Ibid. 

9 Ibid. See also FDA, “Compliance Program Guidance,” Chapter 48: Sponsors, Contract 

Research Organizations and Monitors Part 1—Background (February 2001). Available 

online at http://www.fda.gov/ora/compliance_ref/bimo/7348_810/default.htm. Last accessed 

on January 16, 2006. 

10 The drug development and approval process may take several years. For more 

information, see Congressional Research Service, “The U.S. Drug Approval Process: A 

Primer,” June 2001. 

11 21 CFR § 314.50 (drugs); 21 CFR § 601 (biologics); 21 CFR § 814.20 (devices). 

12 21 U.S.C. §§ 301, 379f(j). 

13 21 CFR § 314 (drugs); 21 CFR § 600.21 (biologics); 21 CFR § 814.44 (devices). 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 2 
 

 

 

 

 

INTROD U C T U C T I O N I O N 

approves a new product, sponsors can market and sell it in the United 

States. 

Clinical investigators. Clinical investigators’ responsibilities include 

recruiting subjects, supervising clinical studies of the investigational 

product, and reporting study results to the sponsor.14 Before they begin 

drug and biological clinical trials, clinical investigators must sign an 

FDA Form-1572 (Statement of Investigator).15 By signing this form, 

investigators agree to follow a research protocol that the sponsor 

provides to FDA, report any unexpected adverse outcomes to sponsors 

and IRBs, obtain informed consent from all subjects participating in the 

research, and comply with all relevant FDA regulations.16 

Institutional Review Boards. IRBs are committees that an institution 

designates to oversee clinical investigators and their research.17 IRBs 

are often affiliated with hospitals and academic medical centers, but 

they also exist in managed care organizations and Government agencies 

and as for-profit entities that are independent of the institution in 

which the research takes place. IRBs generally oversee many and 

varied clinical trials.18 

IRBs are intended to ensure that clinical investigators take appropriate 

steps to protect the rights and welfare of human subjects. All clinical 

trial research involving human subjects must be approved by an IRB.19 

Once an IRB approves a clinical trial, Federal regulations require it to 

reevaluate the trial at least once a year.20 

Food and Drug Administration Oversight of Clinical Trials 

Three centers within FDA individually regulate different types of 

medical investigational products for human use. These centers are the 

Center for Drug Evaluation and Research (CDER), the Center for 

Biologics Evaluation and Research (CBER), and the Center for Devices 

14 21 CFR § 312.60 (drugs and biologics); 21 CFR § 812.100 (devices). 

15 Although the Center for Devices and Radiological Health does not require a Form FDA 

1572, it does require an investigator agreement. See 21 CFR § 812.43(c) (devices); 

21 CFR § 312.53 (drugs and biologics). 

16 21 CFR § 50.312. 

17 21 CFR § 56.102. 

18 Larger IRBs may oversee more than 500 trials in a given year. See Institutional 

Review Boards Registration Requirements, 69 Fed. Reg. 40,556 (July 6, 2004). 

19 21 CFR § 56.109(a). 

20 21 CFR § 56.109(f). 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 3 
 

 

 

INTRODUCTION 

and Radiological Health (CDRH).21 CDER and CBER share regulations 

for the development of investigational products; CDRH has its own 

regulations.22 

The centers use onsite inspections to ensure that clinical investigators, 

sponsors, and IRBs comply with FDA regulations while developing 

investigational products. In 1977, FDA established the Bioresearch 

Monitoring Program (BiMo) to develop cross-center guidelines for these 

inspections of clinical investigators, sponsors, and IRBs (hereinafter 

referred to as BiMo inspections).23 BiMo’s objective, as it relates to 

clinical trials, is to “assure the quality and integrity of data submitted 

to FDA to demonstrate the safety and efficacy of regulated products, 

and to determine that human rights and the welfare of human and 

animal research subjects are adequately protected.”24 The “Compliance 

Program Guidance Manual” contains the current guidelines for BiMo 

inspections. 

FDA’s Office of Regulatory Affairs (ORA) conducts all onsite inspection 

activities for the agency. ORA employs about 1,300 investigators who 

conduct a total of 22,000 inspections annually. About 200 investigators 

(hereinafter referred to as BiMo investigators) have received specialized 

training to conduct BiMo inspections and have conducted these 

inspections in recent years.25 BiMo investigators work out of all 19 of 

ORA’s district offices. 

Types of Bioresearch Monitoring inspections. The centers assign two 

general types of BiMo inspections: surveillance inspections and directed 

inspections. Most surveillance inspections target concluded clinical 

trials and retrospectively review compliance with FDA regulations. 

Many directed inspections target trials that are still treating human 

subjects (ongoing trials). The centers can assign surveillance and 

directed inspections to ORA at any point during the development of an 

21 FDA’s Center for Veterinary Medicine and Center for Food Safety and Applied 

Nutrition oversee investigational products as well, but are outside the scope of our 

evaluation. 

22 21 CFR § 312 (drugs and biologics); 21 CFR § 812 (devices). 

23 21 U.S.C. §§ 355, 360(i). 

24 FDA, “Bioresearch Monitoring Program Coordination Background.” Available online 

at: http://www.fda.gov/ora/compliance_ref/bimo/background.html. Last accessed on 

February 5, 2007. 

25 Although some investigators conduct BiMo inspections exclusively, most investigators 

also conduct other types of inspections for FDA. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 4 
 

 

 

 

 

INTRODUCTION 

investigational product. Although FDA has the authority to conduct 

surveillance and directed BiMo inspections, it is not required to do so. 

Surveillance inspections are generally routine inspections that the 

centers assign to ORA to verify that a clinical investigator, a sponsor, or 

an IRB complied with FDA regulations during clinical trials for an 

investigational product. Data verification inspections are a principal 

type of surveillance inspection. Data verification inspections usually 

occur 2 to 3 years after the clinical trials for an investigational product 

conclude and focus on verifying the clinical trial data that a sponsor 

submitted to support a new product application. 

The centers assign directed inspections to ORA for a variety of reasons, 

including complaints about the conduct of a clinical trial from an 

interested party, problems noted during previous inspections, or 

problems identified at similar sites. Other factors may also lead the 

centers to assign a directed inspection of a clinical trial, such as an 

unusually high number of subjects enrolled at one site under one 

clinical investigator or a treatment that may be considered higher risk. 

Directed inspections that target ongoing clinical trials allow the centers 

and BiMo investigators to review the conduct of a clinical trial and 

advise where corrective action may be needed while the trial is still 

ongoing, thereby offering further human subject protections. 

Bioresearch Monitoring inspection process. ORA’s BiMo investigators 

conduct BiMo inspections according to the “Compliance Program 

Guidance Manual.” Also, staff at the center that assigned a BiMo 

inspection may issue additional instructions for the BiMo investigator. 

The manual’s instructions vary based on the type of inspection 

(i.e., clinical investigator, sponsor, or IRB).26 If a BiMo investigator 

identifies violations of FDA regulations, he/she records them on a Form 

FDA-483 (Inspectional Observations Report). After the inspection, the 

BiMo investigator sends the assigning center a copy of the FDA-483 and 

an Establishment Inspection Report (EIR), which includes background 

26 FDA, “Compliance Program Guidance Manual,” Chapter 48.809: Institutional Review 

Board (September 1997); Chapter 48.810: Bioresearch Monitoring—Sponsors, Contract 

Research Organizations, and Monitors (February 2001); Chapter 48.111: Clinical 

Investigators (September 2000). 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 5 
 

 

 

 

INTROD U C T I O N 

information and copies of all inspection documents. In the EIR, the 

BiMo investigator recommends a classification for the inspection.27 

Inspection classifications and actions taken. Staff at the assigning center 

classify each inspection based on the EIR and other information they 

have about the investigational product. BiMo inspections can result in 

one of three classifications: no action indicated (NAI), voluntary action 

indicated (VAI), or official action indicated (OAI). An NAI classification 

signifies few or no violations of FDA regulations. Generally, FDA takes 

no action in these cases. An inspection receives a VAI classification and 

an untitled letter when the violations are serious enough to record, but 

the center does not believe the violations cross “the threshold of 

regulatory significance.”28 FDA does not require the clinical 

investigators, sponsors, or IRBs that receive VAI classifications to 

address the violations found during the inspection. 

Centers classify inspections as OAI and issue warning letters to the 

inspected entity when investigators find violations of “regulatory 

significance.”29 FDA considers warning letters an important tool in 

ensuring voluntary compliance. If the inspection subject does not take 

corrective action to address violations cited in the warning letter, FDA 

may take enforcement actions, such as disqualifying data or barring a 

clinical investigator from conducting research. Warning letters and 

enforcement actions are publicly available on FDA’s Web site. 

FDA requests that the inspected entity respond to the violations listed 

in a warning letter by sending a justification or a corrective action plan 

to the assigning center. FDA’s “Regulatory Procedure Manual” states, 

“If necessary to ensure that corrections have been implemented, 

follow-up inspections should be conducted promptly after the agreed 

upon date of completion of the promised corrections.”30 

Recent Food and Drug Administration Initiatives 

Recently, FDA has taken steps to improve its BiMo inspection 

processes. In 2004, it created the BiMo Steering Committee to review 

27 Although most recommended classifications made by BiMo investigators are classified 

as no action indicated, voluntary action indicated, or official action indicated, BiMo 

investigators may also choose not to recommend a classification. 

28 Ibid., p. 4-27. 

29 The centers are required to get the concurrence of FDA’s Office of Chief Counsel for all 

warning and untitled letters. See FDA, “Regulatory Procedures Manual,” Chapter 4: 

Advisory Actions, p. 4-26, March 2007. 

30 Ibid., p. 4-11. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 6 
 

 

INTROD U C T I O N 

BiMo processes and make recommendations for improving them. 

During the course of our study, FDA renamed that committee the 

Human Subject Protection/Bioresearch Monitoring Council. In 2006, 

the committee issued new guidance on clinical trial conduct and policy.31 

Prior Office of Inspector General Reports 

Previous OIG reports documented weaknesses in the oversight that 

FDA and IRBs provide for clinical trials. In 1998, a series of reports 

concluded that IRBs lacked the time and the expertise to sufficiently 

monitor the research taking place under their jurisdiction.32 The 

reports found that IRBs often conducted minimal review of studies after 

the initial approval of the research. Additionally, IRBs provided little 

training for investigators and board members. 

A 2000 report documented weaknesses in clinical trial oversight. The 

report found that data integrity concerns, more than human subject 

protection, drove FDA’s oversight of clinical investigators and that the 

BiMo program lacked clear and specific guidelines.33 

METHODOLOGY 

Scope 

Our study focused on BiMo inspections of sponsors, clinical 

investigators, and IRBs in clinical trials from FY 2000 through FY 2005. 

We included all of the BiMo inspections conducted for CBER, CDER, 

and CDRH that are listed in FDA’s inspections databases for this 6-year 

period. 

Data Sources and Analysis 

We used seven data sources for this study. See Appendix A for a 

detailed methodology. 

31 In 2006, FDA issued the following new guidance: Draft Guidance: Process for 

Handling Referrals to FDA Under 21 CFR § 50.54; Additional Safeguards for Children in 

Clinical Investigations, May 2006; Guidance for Industry: Using a Centralized IRB Process 

in Multicenter Clinical Trials, March 2006; Guidance for Clinical Trial Sponsors: 

Establishment and Operation of Clinical Trial Data Monitoring Committees, March 2006; 

Information Sheet Guidances for IRBs, Clinical Investigators, and Sponsors, January 2006. 

32 Department of Health and Human Services, OIG, “Institutional Review Boards: A 

Time for Reform,” OEI-01-97-00193, June 1998; OIG, “Low-Volume Institutional Review 

Boards,” OEI-01-97-00194, October 1998; “Institutional Review Boards: Their Role in 

Reviewing Approved Research,” OEI-01-97-00190, June 1998. 

33 Department of Health and Human Services, OIG, “FDA Oversight of Clinical 

Investigators,” OEI-05-99-00350, June 2000. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 7 
 

 

 

INTRODUCTION 

Food and Drug Administration’s Bioresearch Monitoring inspections data. 

We analyzed FDA’s BiMo inspections data to evaluate how FDA tracks 

and manages BiMo inspections. We also calculated the number and 

type of inspections FDA conducts. We used data from six FDA 

databases for BiMo inspections. The three centers maintain separate 

databases to track BiMo inspections: two databases each for CBER and 

CDER and one for CDRH. ORA maintains the Field Accomplishment 

and Compliance Tracking System (FACTS). 

From each database, we analyzed the records for BiMo inspections of 

sponsors, clinical investigators, and IRBs that BiMo investigators 

conducted for the three centers during the FY 2000–2005 period. We 

excluded laboratory and bioequivalence inspections from our analysis. 

File review. Using the FDA databases, we identified and reviewed all 

BiMo inspections for which the BiMo investigator recommended OAI or 

a center classified as OAI in FY 2000–2005. We reviewed 668 files, 

including 99 CBER inspection files, 248 CDER inspection files, and 

321 CDRH inspection files. 

E-mail survey of Bioresearch Monitoring investigators. We surveyed BiMo 

investigators about their experiences with FDA guidance, classification 

recommendations, inspection followup with the assigning centers, and 

challenges conducting BiMo inspections. We received completed 

surveys from 76 percent of the BiMo investigators (170 out of 223). 

Interviews with Food and Drug Administration officials. We conducted 

telephone interviews with all 19 ORA district directors and supervisors 

of investigation branches (hereinafter referred to as supervisors). The 

interviews focused on the supervisors’ experiences with the supervisory 

role, interactions with the BiMo investigators they supervise, 

interactions with the assigning centers, classification recommendations, 

and challenges in supervising BiMo inspections. We also interviewed 

senior FDA officials in the agency’s headquarters and at each center. 

Observation of Bioresearch Monitoring inspections. We observed the 

process that BiMo investigators followed, as well as the interactions 

between the investigator(s) and the inspection subject(s). We observed 

two clinical investigator inspections and one IRB inspection. 

Clinical trials registry site estimate. From the population of trials on the 

National Institutes of Health’s (NIH) clinical trials registry as of 

February 2007, we selected a stratified random sample of 150 trials. 

Because the registry is separated by phase of the trial, the three strata 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 8 
 

 

INTRODUCTION 

used for the sample were Phase I, Phase II, and Phase III of the clinical 

trial. We excluded 43 of the sampled trials and the final sample size to 

estimate that the number of trial sites was 107. (See Appendix A, Table 

7, for our sample design.) 

Review of Food and Drug Administration regulations, guidance, policies, 

and procedures documents. We obtained and reviewed all relevant FDA 

regulations, guidance, policies, and procedures documents for 

conducting BiMo inspections. 

Standards 

We conducted this review in accordance with the “Quality Standards for 

Inspections” issued by the President’s Council on Integrity and 

Efficiency and the Executive Council on Integrity and Efficiency. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 9 
 

 

 

 

 

 

 

Δ FINDINGS 

FDA relies on BiMo inspections as 

a principal mechanism for 

Data limitations inhibit FDA’s ability to 

effectively manage the BiMo program 

overseeing clinical trials after it 

reviews the protocol. BiMo inspections help to ensure the quality and 

integrity of clinical trial data, and to determine whether sponsors, 

clinical investigators, and IRBs are complying with regulations that 

protect human subjects while they are enrolled in clinical trials. 

FDA lacks a complete clinical trial registry 

Because FDA does not maintain a clinical trial registry, it is unable to 

indentify all ongoing clinical trials and their associated trial sites. 

Limited clinical trials that are regulated by FDA can be found on a 

clinical trial registry run by NIH.34 Included within this data bank is 

information on FDA-regulated studies to treat serious or 

life-threatening diseases and conditions. Sponsors are not required to 

submit information on any other type of clinical trials that FDA 

regulates. 

FDA lacks an IRB registry 

Because FDA does not maintain an IRB registry, it is unable to identify 

all IRBs. IRBs are important because their primary purpose is to 

ensure that clinical investigators take appropriate steps to protect the 

rights and welfare of human subjects. BiMo inspections of IRBs offer 

the centers considerable oversight of human subject protections. 

Because IRBs usually oversee many and varied clinical trials, the 

centers can review numerous trials across the centers with each BiMo 

inspection of IRBs. 

The Office of Human Research Protections (OHRP) oversees all 

federally sponsored research that includes human subjects.35 OHRP 

maintains a database consisting of all IRBs that oversee this research. 

Although the OHRP database likely contains many IRBs that oversee 

some FDA-regulated clinical trials, it does not contain IRBs that oversee 

clinical trials regulated exclusively by FDA. 

34 Section 113 of the 1997 Food and Drug Administration Modernization Act directs the 

Secretary of the Department of Health and Human Services to act through NIH to establish 

and operate a databank of information on clinical trials for drugs to treat serious or lifethreatening diseases or conditions. 42 U.S.C. § 282(j)(3)(A). 

35 OHRP oversees research that is conducted or supported by HHS. See 45 CFR Part 46. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 10 
 

 

 

 

 

F I NDING S 

FDA has acknowledged the importance of creating an IRB registry and 

published a proposed rule in July 2004 for the creation of one.36 

According to FDA, the benefits of such a registry would include being 

able to identify IRBs that review clinical trials regulated by FDA, 

having a complete list of IRBs for educational and outreach purposes, 

and being able to easily identify IRBs for inspection.37 

No FDA database includes complete information for all BiMo inspections, 

hindering FDA’s ability to track BiMo inspections 

FDA maintains six databases to track BiMo inspections. Although 

ORA’s database, FACTS, includes information on all BiMo inspections, 

it does not consistently include information about inspection-related 

events that occur after an investigator submits an inspection report to 

the centers. For example, 48 percent of BiMo inspection records in 

FACTS (2,557 out of 5,312 records during the FY 2000–2005 period) 

lack the centers’ final classifications. Because of these omissions, FDA 

cannot use FACTS to track inspections from assignment through a 

center’s final action. 

Tracking BiMo inspections using data from the centers is challenging 

because of the number of databases involved and their inconsistencies. 

The three centers used five separate databases to track BiMo inspection 

data in the FY 2000–2005 period.38 

The center databases do not uniformly track inspections. First, each 

database contains different information about BiMo inspections. 

Second, when the centers track similar information, they do not do so in 

the same way. For example, each database uses different categories to 

identify the reason a center initiated an inspection.39 (See Table 1 on 

the next page.) These categories are difficult to translate across 

databases. For example, FACTS and one of CBER’s databases indicate 

whether an inspection was based on a complaint. However, the other 

databases combine complaint-based inspections with other types of 

inspections, which means that FDA cannot identify which inspections 

were prompted by complaints for all centers. Also, the databases define 

different types of inspections as surveillance and as directed. FDA 

36 Institutional Review Boards Registration Requirements, 69 FR 40,556 (July 6, 2004). 

37 Ibid., 40,557. 

38 CBER and CDER maintain two databases each to track inspections. 

39 None of the databases indicates whether an inspected trial was completed or ongoing. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 11 
 

 

 

FINDINGS 

cannot use these databases to track inspections across centers unless it 

controls for all of these discrepancies. 

Database Inspections Included Category 

Table 1: Categories Center and ORA Databases Use To Track Reason for Inspection 

All BiMo inspections ORA • Complaint (for cause, based on a complaint) 

conducts • Compliance (followup to previous violations) ORA • Surveillance (routine inspections that are not based on 

FACTS preexisting information about a firm; includes data integrity 

inspections)2 

CBER's IRB inspections • Text field (most entries in this field do not indicate reason for 

CBER inspection) 

IRB 

CBER's clinical • Complaint 

CBER investigator and sponsor • Surveillance (site selected because of high risk; includes blood, 

inspections cell, gene, vaccine, and other)2 

CISM1 

Completed inspections of • Data audit (most are based on new product application) 

trials for drug products • For cause (based on prior problems complaint) CDER 

COMIS3 

CDER inspections • For cause (based on previous problems or complaint)4 

starting in FY 2004 or • Routine data audit (based on a new product application) CDER later • Information gathering 

DSI4 • Surveillance2 

All CDRH BiMo • Routine 

inspections of IRBs, • For cause 

clinical investigators, and • Directed 

sponsors • Vulnerable population 

CDRH • Probability sampling 

• Field initiated database • Center initiated 

• Expedited review 

• Surveillance2 

• Followup inspection after OAI inspection 

1

CISM is clinical investigator, sponsor, and monitor. 2

The databases define surveillance differently. 

3

COMIS is the Center Office Management Information System. 

4

DSI is the Division of Scientific Investigations. In the CDER DSI database, inspections can be more than one type. 

Source: OIG analysis of ORA, CBER, CDER, and CDRH data, 2006. 

The five center databases do not uniformly track other important 

inspection-related data, such as (1) whether the inspection targets an 

ongoing or completed clinical trial, (2) ORA’s recommended 

classification, and (3) follow-up inspection information. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 12 
 

 

 

 

 

 

FINDINGS 

Other factors hinder FDA’s ability to effectively 

manage the BiMo program 

Centers and ORA inconsistently classify OAI and NAI inspections 

According to FY 2000–2005 CDER and CDRH data, these centers often 

disagreed when ORA recommended an OAI classification, the most 

serious classification category.40 (See Table 2.) During this 6-year 

period, CDER revised 68 percent of ORA’s OAI recommendations and 

CDRH revised 23 percent of ORA’s OAI recommendations. The centers 

reclassified most of these inspections to VAI, a classification that 

neither requires the inspected entity to formally address violations the 

center identified nor makes the classification publicly available. 

The centers do not systematically track their reasons for revising ORA’s 

recommended classifications. However, our review of 668 FDA 

inspection files identified two key reasons for changing OAI 

classifications to VAI. The most common reasons were that the center, 

in conjunction with an Office of Chief Counsel review, determined that 

the violations were not serious enough to warrant a warning letter and 

therefore an OAI classification, and that the inspection subject promised 

corrective actions. 

Table 2: CDER and CDRH Agreement With ORA Recommended Classifications, FY 2000–2005 

Center 

Percentage of All 

Recommendations 

Center Revised 

Percentage of OAI 

Recommendations Center 

Revised 

Percentage of VAI 

Recommendations Center 

Revised 

Percentage of NAI 

Recommendations 

Center Revised 

CDER 

CDRH 

14% (303 of 2,090) 

13% (193 of 1,506) 

68% (133 of 195) 

23% (62 of 271) 

2% (25 of 1,328) 

7% (47 of 688) 

26% (145 of 567) 

15% (84 of 547) 

Source: OIG analysis of CDER and CDRH data, 2006. 

CDER and CDRH also revised some of ORA’s NAI recommendations. In 

other words, center reviewers sometimes identified violations when a 

BiMo investigator found no significant violations at the inspection site. 

CDER reclassified 26 percent of the inspections that ORA identified as 

40 We could not conduct this analysis for CBER because it does not record ORA’s 

recommended classification. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 13 
 

 

 

 

 

 

F I NDING 
 S 

NAI. CDRH reclassified 15 percent of the inspections that ORA 

identified as NAI. 

These reclassifications suggest that ORA and the centers sometimes 

interpret the regulations and guidance for BiMo inspection 

classifications differently. Although the centers ultimately classify 

inspections, they rely on BiMo investigators to identify violations at the 

inspection site and collect evidence to support inspection classifications. 

If BiMo investigators interpret the regulations and guidelines 

differently than center reviewers do, they may miss evidence to support 

an OAI classification when one would be appropriate. Conversely, BiMo 

investigators may spend time gathering evidence to support an OAI 

classification that the center does not support. 

BiMo supervisors and investigators reported that a lack of feedback 

from the centers and inadequate training may contribute to the 

differences in interpreting inspection classifications. Eighteen of 

nineteen BiMo supervisors we spoke with stated that the centers rarely 

or never provide feedback on the inspection reports that the districts 

submit to the centers. Further, 19 percent of the BiMo investigators we 

surveyed (32 of 170) responded that they would like more information 

on the centers’ final classifications or feedback on their 

inspection-related performance. 

FDA relies on voluntary compliance to correct violations of regulatory 

significance 

The centers send warning letters for 70 percent of inspections classified 

as OAI. The centers can respond to OAI inspections by issuing an 

untitled letter, issuing a warning letter, disqualifying a clinical 

investigator, or disqualifying data gathered in the clinical trial. Our 

analysis of center data shows that the centers chose to respond to 

70 percent of inspections they classified as OAI during the 

FY 2000–2005 period by issuing warning letters. (See Table 3 on the 

next page.) The centers’ next most common response to OAIs was 

untitled letters, which they sent for 16 percent of OAI inspections. Less 

frequently, the centers took more formal actions, including initiating 

disqualification of inspection subjects or disqualifying data from clinical 

trials. 

Warning letters and untitled letters rely on voluntary compliance, so 

FDA must reinspect individuals who receive these letters to ensure that 

they do not repeat violations in future clinical research. If the centers 

do not track the response to warning letters and untitled letters, they 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 14 
 

 

 

FINDINGS 

cannot ensure that voluntary compliance occurs. According to FDA’s 

“Regulatory Procedures Manual,” “Warning Letters are issued only for 

violations of regulatory significance. Significant violations are those 

violations that may lead to enforcement action if not promptly and 

adequately corrected. A Warning Letter is the agency’s principal means 

of achieving prompt voluntary compliance with the Federal Food, Drug, 

and Cosmetic Act.”41 

Table 3: Centers' Official Actions for BiMo Inspections Classified as OAI 

Center 

Percentage of 

OAIs That Resulted 

in a Warning Letter 

Percentage of 

OAIs That Resulted 

in an Untitled Letter 

Percentage of 

OAIs That Resulted 

in a Disqualification 

Letter 

Percentage of 

OAIs That Resulted 

in Disqualified Data 

Unknown Action 

CBER 

CDER 

CDRH 

82% (55 of 67) 

57% (38 of 67) 

71% (151 of 214) 

6% (4 of 67) 

16% (11 of 67) 

20% (42 of 214) 

12% (8 of 67) 

18% (12 of 67) 

3% (6 of 214) 

0% (0 of 67) 

2% (1 of 67) 

1% (1 of 214) 

0% (0 of 67) 

8% (5 of 67) 

7% (14 of 214) 

Total 70% (244 of 348) 16% (57 of 348) 8% (26 of 348) 1% (2 of 348) 6% (19 of 348) 

Source: OIG analysis of CDER, CDRH, and CBER inspection files, 2006. 

Although CBER and CDER fail to track inspection followup, CDRH 

data show that that center conducts few follow-up inspections. Center 

databases fail to track whether the center conducted a followup to an 

inspection classified as VAI or OAI. CDRH’s database indicates 

whether an inspection was initiated as a followup to a prior violative 

inspection. However, the database does not link the followup inspection 

to the violative inspection. Nor does it indicate in the record for the 

violative inspection that followup occurred. CDRH data show that the 

center conducted 3 follow-up inspections for every 100 inspections 

classified as OAI or VAI in the FY 2000–2005 period (36 follow-up 

inspections for 1,048 inspections classified as OAI and VAI). 

41 FDA, “Regulatory Procedures Manual,” Warning Letter Procedures, p. 4-1-1, March 

2007. Available online at http://www.fda.gov/ora/compliance_ref/rpm. Last accessed 

April 9, 2007. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 15 
 

 

F I NDING S 

Uncertainty and lack of coordination impede FDA’s ability to conduct BiMo 

inspections 

In interviews, center and ORA staff reported that inspections triggered 

by new product applications affect the conduct and timing of other 

inspections. The centers cannot predict how many new product 

applications they will receive each year and therefore cannot plan for 

the inspections that these applications trigger. At the beginning of each 

fiscal year, the centers plan and budget for BiMo inspections. During 

the year, the centers also receive new product applications, which 

generate BiMo inspection assignments with short due dates because of 

the overall performance goals of PDUFA and MDUFMA.42 Assignments 

based on new product applications are usually retrospective reviews 

that focus on verifying clinical trial data used in the application. These 

assignments generally take priority over all other BiMo inspections. 

Because each center has a set budget for all inspections, an unexpected 

rise in new product applications may mean that the ORA districts have 

more inspections overall and more inspections with short due dates 

than they originally planned. 

Because of the uncertainties of timing and prioritization involved with 

BiMo inspections, districts sometimes must delay some of the other 

inspections that ORA conducts, particularly those with later due dates. 

In fact, 11 of 19 district supervisors we interviewed stated that 

assignments for inspections related to marketing applications create 

challenges for managing resources. Staff in five district offices reported 

asking the centers for additional time to complete BiMo inspections; two 

offices estimated that they request extensions for about 20 percent of 

BiMo assignments. Staff in four other districts reported that they have 

to cancel other inspections when they have too many unexpected BiMo 

assignments. 

Additionally, the centers generally fail to coordinate assignments with 

one another or the districts. When asked if they faced any challenges 

conducting BiMo inspections, staff from 7 of the 19 district offices 

reported that lack of planning and coordination by the centers created 

challenges for the district. For example, staff in a district that oversees 

42 PDUFA requires pharmaceutical companies to pay fees to FDA when submitting 

Preapproval Marketing Applications and New Drug Applications. These fees are dedicated 

to expediting the review of product applications for CDER and CBER. MDUFMA has the 

same requirement for device applications. The BiMo inspection serves as one step of the 

evaluation process. 21 U.S.C. §§ 379g(4), 379j. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 16 
 

 

 

 

F I NDING 
 S 

a large geographic area reported that inspection assignments for distant 

sites would be more manageable if they could combine multiple 

inspections in a single trip. However, this is not feasible without 

coordinating across the assigning centers. 

Failure to coordinate BiMo assignments across centers may also impede 

BiMo Steering Committee goals. In interviews, BiMo Steering 

Committee members reported that they want to increase the number of 

inspections of ongoing trials and inspections that focus on high-risk 

sites. One committee member we interviewed told us that the current 

system, in which each center independently issues assignments and 

tracks data, does not allow for the timely coordination necessary to 

target high-risk and ongoing inspections across centers. 

FDA guidance and regulations do not reflect current clinical trial practices 

According to interviews with center officials and ORA supervisors, 

FDA’s guidance and regulations for clinical trials have fallen behind 

industry practices. FDA officials reported that when the agency 

developed clinical trial regulations, a single investigator at a single site 

ran each clinical trial. Since then, clinical trials have grown 

increasingly complex. Trials are larger and involve multiple sites 

within and outside the United States.43 

FDA officials told us that clinical investigators frequently delegate tasks 

that include direct care to human subjects to colleagues or subordinates. 

Current FDA regulations do not address colleagues or subordinates. 

When FDA conducts an inspection and finds significant deficiencies 

related to individuals other than the clinical investigator, the agency 

may only take action against the clinical investigator. 

Finally, although sponsors increasingly conduct clinical trials outside 

the United States, FDA authority over foreign trials remains limited. 

For example, one center official estimated that 20 to 25 percent of the 

trials for products that FDA oversees occur outside the United States. 

According to the official, centers are often unaware that foreign trials 

43 Regarding the increasingly complex management structures of clinical trials, see 

Department of Health and Human Services, OIG, “The Globalization of Clinical Trials: 

A Growing Challenge in Protecting Human Subjects,” OEI-01-00-00190, September 2001. 

See also Iain M. Cockburn, “The Changing Structure of the Pharmaceutical Industry,” 

Health Affairs, 23(1) pp. 10–22, 2004; and R. A. Rettig, “The Industrialization of Clinical 

Research,” Health Affairs, 19(2), pp. 129–146, 2000. Regarding the growing size and 

complexity of clinical trials, see Institute of Medicine, “The Future of Drug Safety: 

Promoting and Protecting the Health of the Public,” Chapters 1 and 2, 2006. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 17 
 

 

 

FINDINGS 

have taken place because FDA’s investigational product regulations 

generally do not apply outside the United States. When ORA does 

inspect foreign clinical trials and finds violations, the centers can only 

disqualify data from consideration in a new product application. 

We estimate that FDA inspected 

1 percent of clinical trial sites during the 

fiscal year 2000-2005 period 

As previously noted, FDA lacks a 

complete database that includes 

information on all BiMo 

inspections. However, FDA also 

lacks registries that contain complete clinical trial and IRB information. 

Failure to track all clinical trials and IRBs limits the centers’ ability to 

oversee trials through BiMo inspections. First, the centers cannot 

assign BiMo inspections of trials and IRBs that they cannot identify. 

Second, the centers cannot identify the percentage of trials and IRBs 

that BiMo inspections reach. To identify the percentage of trials and 

IRBs that BiMo inspections reached during the FY 2000–2005 period, 

we used estimates of clinical trial and IRB populations from 

Government sources outside FDA. 

The centers reported 2,856 BiMo inspections that required a clinical 

trial site visit for the FY 2000–2005 period.44 (See Table 4 on the next 

page.) However, the centers do not have data to identify the percentage 

of trial sites that these inspections reached. Therefore, we used the 

number of INDs and IDEs the centers received as well as estimates 

from the clinical trial registry that NIH maintains to estimate the 

percentage of trial sites that the BiMo inspections reached.45 

44 We excluded IRB and sponsor inspections from this analysis because they generally do 

not take place at a clinical trial site. 

45 Section 113 of the 1997 FDAMA directs the Secretary of the Department of Health and 

Human Services to act through NIH to establish and operate a databank of information on 

clinical trials for drugs to treat serious or life-threatening diseases or conditions. Included 

within this databank is information on studies to treat serious or life-threatening diseases 

and conditions conducted under FDA IND regulations. Although the NIH registry does not 

include all the clinical trials FDA oversees, it provides the best available estimate of the 

average number of trial sites associated with clinical trials. The registry is available at 

www.clinicaltrials.gov. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 18 
 

FINDINGS 

Table 4: Centers' BiMo Inspections With Site Visits by Fiscal Year 

Fiscal Year CDER CDRH CBER Total 

2000 

2001 

2002 

2003 

2004 

2005 

296 

186 

194 

226 

219 

221 

91 

113 

153 

167 

189 

183 

143 

79 

109 

103 

75 

108 

530 

378 

456 

496 

483 

512 

Total 1,342 896 617 2,855 

Source: OIG Analysis of CDER, CDRH, and CBER data, 2006. 

W e included only clinical investigator, contract research organization, and sponsor monitor inspections. 

Although FDA cannot identify the total number of clinical trial sites 

operating during the FY 2000–2005 period, the centers did track the 

15,268 INDs and IDEs that they received during this period. However, 

each IND or IDE may involve many trial sites, so the number of INDs 

and IDEs cannot substitute for the total number of trial sites. 

Therefore, to estimate the total number of trial sites, we calculated the 

average number of clinical trial sites associated with a random sample 

of clinical trials listed on the NIH clinical trials registry. We found that 

clinical trials listed on that registry had an average of 23 sites per 

trial.46 Based on these figures, we estimate that the 15,268 INDs and 

IDEs the centers received included about 350,000 trial sites. 

Using the estimate of 350,000 trial sites, we estimate that FDA’s 

2,855 inspections reached just under 1 percent of the trial sites 

associated with the INDs and IDEs the centers received. 

46 A 95-percent confidence interval for our sample is +/- 8 trial sites, or between 15 and 

31 sites per trial. Using this range, we calculate that FDA’s 2,855 inspections reached at 

most just over 1 percent of trial sites associated with the 15,268 applications received by the 

centers. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 19 
 

 

 

FINDING 
 S 

Centers assign more surveillance inspections than directed inspections 

For the FY 2000–2005 period, 75 percent of BiMo inspections were 

surveillance inspections. Surveillance inspections generally focus on 

verifying the clinical trial data that sponsors submitted with their new 

product applications. Further, most surveillance inspections target 

completed trials. Data verification inspections serve an important 

purpose in enabling FDA to assess the quality of the data used to 

support new product applications. However, because these inspections 

take place after trials conclude, they cannot ensure that sponsors, 

clinical investigators, and IRBs are taking the necessary actions to 

protect human subjects during the trials. 

Some of the directed inspections that the centers assigned during the 

FY 2000–2005 period likely focused on ongoing trials. For example, 

CBER annually targets a high-risk category of clinical trials for 

inspection, which may include ongoing clinical trials.47 CDRH 

implemented a program in the past year to increase the number of 

inspections that focus on higher-risk clinical trials that may be ongoing. 

However, the three centers do not track whether inspections target 

ongoing trials, so we could not estimate the proportion of BiMo 

inspections that reached ongoing trials. Several senior FDA officials 

reported to us that they recognize the need to inspect more ongoing 

clinical trials to protect human subjects. 

Centers inspect few IRBs 

Our analysis of center data shows that in the FY 2000–2005 period, 

FDA conducted an average of 214 IRB inspections each year. The 

number of IRB inspections has decreased annually since 2002. (See 

Table 5 on the next page.) IRB inspections offer the centers 

considerable oversight of human subject protections. Because IRBs 

usually oversee a variety of clinical trials, the centers can review 

numerous trials across the centers with each IRB inspection. 

At most, we estimate that during the FY 2000–2005 period, the centers 

inspected an average of about 6 percent of IRBs each year, or less than 

40 percent of all IRBs in the 6-year period we evaluated. Because the 

centers do not track the total population of IRBs, we used the IRB 

database maintained by OHRP to estimate the population of IRBs. 

OHRP oversees all research that the Federal Government sponsors. 

47 Past examples include studies focusing on pediatric populations and gene therapy 

studies. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 20 
 

 

 

 

 

F I NDING S 

The OHRP database includes all IRBs that oversee research sponsored 

by the Government, so it likely underestimates the population of IRBs 

overseeing all clinical trial research. In February 2007, OHRP reported 

3,579 IRBs in its IRB database.48 

Table 5: IRB Inspections as a Percentage of Total BiMo Inspections 

Fiscal Year Number of IRB 

Inspections 

Total BiMo 

Inspections 

Percentage of Inspections That 

Are IRB inspections 

2000 

2001 

2002 

2003 

2004 

2005 

198 

187 

278 

251 

207 

163 

795 

633 

812 

854 

779 

769 

25% 

30% 

34% 

29% 

27% 

21% 

Total 1,284 4,642 28% 

Source: OIG Analysis of CDER, CDRH, and CBER data, 2006. 

IRB inspections assigned to ORA are allowed longer timeframes than 

inspections of clinical investigators or sponsors. A center’s inspection 

assignment includes a due date. In many cases, the centers allow ORA 

up to 1 year to complete IRB inspections. By comparison, ORA 

generally has 30 to 90 days to complete inspections of clinical 

investigators.

49 

Center data show that despite these longer timeframes, ORA frequently 

failed to meet the requested due dates for IRB inspections. ORA failed 

to meet CDRH’s deadlines for 60 percent of IRB inspections (214 out of 

359); 24 percent (85 of 359) were more than 60 days late. Similarly, 

ORA failed to meet CBER’s deadline for 38 percent of that center’s IRB 

inspections (24 of 63).50 

OEI-01-06-00160 

48 OHRP oversees research that is conducted or supported by the U.S. Department of 

Health and Human Services. See 45 CFR Part 46. 

49 In some cases, IRB inspections are directed because of a past OAI or some other 

concern. In these instances, the timeframes are shorter than the timeframes presented 

here. 

50 We could not determine the timeliness of CDER inspections because CDER does not 

include the inspection due date in its database. 

T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 21 
 

 

 

 

 

 

Δ RECOMMENDATIONS 

FDA conducts BiMo inspections to ensure the quality and integrity of 

clinical trial data and to determine whether sponsors, clinical 

investigators, and IRBs are complying with regulations that protect 

human subjects enrolled in clinical trials. Our evaluation identified a 

lack of comprehensive reporting and tracking systems, a lack of 

coordination among the centers and ORA, and regulations that do not 

fully reflect current clinical trial practices. 

No Federal requirements prescribe the number or type of BiMo 

inspections FDA must conduct. However, FDA relies on BiMo 

inspections as a principal mechanism for overseeing clinical trials after 

it reviews the protocol. We recognize that resource limitations may be a 

factor in determining the extent of FDA’s oversight of clinical trials 

using BiMo inspections. However, to ensure its effectiveness in meeting 

BiMo objectives, the inspection program needs comprehensive 

management and reporting systems. 

FDA has taken steps to improve the BiMo inspection program. For 

example, in 2004 it created the BiMo Steering Committee to identify 

and address weaknesses in the BiMo program. We identified additional 

steps that FDA can take to improve oversight of clinical trials. These 

changes will help FDA plan and conduct BiMo inspections more 

effectively. These changes will also help FDA meet the BiMo objective 

of “determining that human rights and the welfare of human research 

subjects are adequately protected.” 

FDA should: 

Improve Information Systems and Processes 

FDA’s BiMo inspections are a principal mechanism to ensure the 

quality and integrity of clinical trial data and to determine that human 

subjects are protected. However, the weaknesses we identified in the 

BiMo information systems and management processes inhibit FDA’s 

ability to effectively oversee and manage BiMo inspections across 

centers. To improve the effectiveness of the BiMo program, FDA should 

take the following actions: 

Develop a clinical trial database that includes all clinical trials. FDA should 

develop a comprehensive database to use as an internal management tool 

to more effectively identify ongoing clinical trials for inspection. Although 

NIH currently maintains a clinical trial registry, that registry was not 

intended to be a comprehensive listing of clinical trials. It was created to 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 22 
 

 

 

 

 

 

R E C O MMENDA T I O N S 

inform the public regarding potentially new life-saving treatments. 

Because the registry contains clinical studies to treat serious or 

life-threatening diseases and conditions conducted under FDA’s IND 

regulations, it excludes most other clinical trials subject to FDA 

regulation, such as medical device studies. 

Create an Institutional Review Board registry. By identifying all IRBs 

overseeing clinical trials, FDA could target IRBs more effectively for 

inspection. FDA has acknowledged the importance of creating an IRB 

registry and published a proposed rule in July 2004. Recently, the agency 

set a timetable of March 2008 for issuance of a final rule.51 

OHRP currently maintains an IRB registry for studies under its 

auspices.52 FDA could build upon OHRP’s existing IRB registry to 

create a larger and more inclusive database while minimizing the 

administrative burden for IRBs. 

Create a cross-center database that allows complete tracking of Bioresearch 

Monitoring inspections. FDA cannot efficiently manage BiMo inspections 

across centers without a database that includes timely and complete 

information about all BiMo inspections. A single, consistent database 

would require the centers to agree about which fields are essential and 

how they should be defined. At a minimum, the database should include: 

(1) specific information on the reason for an inspection, (2) whether the 

inspection targets an ongoing or a completed clinical trial, (3) ORA’s 

recommended classification, and (4) follow-up inspection information. 

Establish a mechanism to provide feedback to Bioresearch Monitoring 

investigators on their inspection reports and findings. Improved feedback 

between the centers and BiMo investigators could lead to a common 

understanding of the regulations and guidelines. This would minimize the 

likelihood that an investigator would miss evidence to support an OAI 

classification when one would be appropriate or spend time gathering 

evidence to support an OAI classification that the center does not 

corroborate. 

Seek legal authority to provide oversight that reflects current clinical trial 

practices. FDA should consider seeking additional authority that covers 

all of the stakeholders in the management and conduct of clinical trials. 

51 72 FR 22,520 (April 30, 2007). 

52 OHRP oversees research that is conducted or supported by the U.S. Department of 

Health and Human Services. See 45 CFR § 46. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 23 
 

 

RECOMMENDATIONS 

In particular, FDA should consider seeking authority to include the 

colleagues and subordinates of a clinical investigator if they participate in 

the conduct of a clinical trial. 

AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 

RESPONSE 

FDA concurred with four of our five recommendations. These 

recommendations aimed to improve information systems and processes 

related to the BiMo program. FDA did not address our recommendation 

to establish a mechanism to provide feedback to BiMo investigators on 

their inspection reports and findings. 

Specifically, FDA concurred with our recommendations to develop a 

clinical trial database that includes all clinical trials, to create an IRB 

registry, to create a cross-center database that allows complete tracking 

of BiMo inspections, and to seek legal authority to provide oversight 

that reflects current clinical trial practices. 

FDA pointed out that BiMo inspections make up only one part of its 

efforts to ensure human subject protections, noting that it views its 

protocol review before a clinical trial commences as the most important 

step in protecting human subjects. We recognize the important role 

that FDA’s protocol review plays in protecting human subjects and 

made several changes to our report to reflect this point. We do note, 

however, that this report addresses another important part of the 

system for protecting human subjects: oversight of the trials once they 

are actually underway. 

The agency highlighted the efforts of its Human Subject 

Protection/Bioresearch Monitoring Council in identifying key issues that 

needed to be addressed, such as coordination, tracking mechanisms, 

regulations, and guidance. FDA also emphasized the importance of 

risk-based approaches to BiMo inspections rather than committing to 

inspecting a specified percentage of clinical trials. 

Where appropriate, we made changes to the report based on FDA’s 

technical comments. 

See Appendix B for complete agency comments. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 24 
 

 

Δ APPENDIX A 

METHODOLOGY 

Scope 

Our study focused on Bioresearch Monitoring (BiMo) inspections of 

sponsors, clinical investigators, and Institutional Review Boards (IRBs) 

in clinical trials from fiscal year (FY) 2000 to FY 2005. We reviewed all 

of the inspections that BiMo investigators conducted for the Center for 

Drug Evaluation and Research (CDER), the Center for Biologics 

Evaluation and Research (CBER), and the Center for Devices and 

Radiological Health (CDRH) that are listed in Food and Drug 

Administration’s (FDA) inspections databases for this 6-year period. 

We excluded BiMo inspections that focused on the bioequivalence and 

laboratory compliance programs.53 

Data Sources and Analysis 

We used seven data sources for this study. 

Food and Drug Administration’s Bioresearch Monitoring inspections data. 

We analyzed FDA inspections data to evaluate how FDA tracks and 

manages BiMo inspections. We also calculated the number and type of 

inspections FDA conducts. 

We analyzed data from six FDA databases for BiMo inspections. Each 

center we evaluated and the Office of Regulatory Affairs (ORA) 

maintain separate databases to track BiMo inspections. CDRH and 

ORA each maintain a single database. CBER and CDER each maintain 

two databases. 

From each database, we analyzed the records for BiMo inspections of 

clinical investigators, sponsors, and IRBs for CBER, CDER, and CDRH 

during the FY 2000 to 2005 period. 

We analyzed fields in the databases that indicate the type of inspections 

that the centers conducted in the FY 2000 to 2005 period. (See Table 6.) 

Each center tracks inspections differently, so we could not gather 

information on every variable for all centers. 

53 We excluded laboratory BiMo inspections because they were not clinical in nature. We 

excluded bioequivalence BiMo inspections because they do not necessarily follow the same 

investigational product processes described in the Background on p. 2. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 25 
 

 

 

 

APPENDIX ~ A 

Using the fields listed in Table 6, we evaluated the number and types of 

inspections that FDA conducted from FY 2000 to 2005. We conducted 

all database analysis in SAS®. 

The following is a description of each of the databases: 

 Field Accomplishment and Compliance Tracking System (FACTS): 

We received FACTS data from ORA in July 2006. The FACTS data 

included 5,850 records. We removed 472 records that either 

duplicated other records or targeted subjects outside our scope (for 

example, manufacturers). We excluded 66 records that ORA coded as 

“Cancelled” or “Returned” or that the Center for Veterinary Medicine 

requested. Our analysis includes 5,312 FACTS records. 

	 CBER data: We received data from CBER’s two databases in 

July 2006. CBER dedicates one database to clinical investigator and 

sponsor inspections. This database originally contained 714 records. 

We removed records that did not fall within the scope of this study, 

including five manufacturing inspections, four inspections classified 

as “no inspection,” three inspections classified as “out of business,” 

and eight inspections classified as “washout.” We also removed 

11 inspections that did not include inspection start dates. Our 

analysis includes 683 inspection records from this database. 

CBER uses a second database to track IRB inspections. This 

database included 73 records. We used all of these inspection records 

in our analysis. 

	 CDER data: We received data from one CDER database, the Center 

Office Management Information System (COMIS), in October 2006. 

CDER uses COMIS to track closed inspections of CDER drug 

products trials that started before FY 2004. The COMIS data 

originally included 4,237 inspection records. However, many of these 

records were duplicates. After we removed the duplicate records, 

COMIS included 1,196 inspection records. 

We received data from a second CDER database, the Division of 

Scientific Investigations database (DSI), in December 2006. CDER 

uses the DSI database to track all inspections starting in FY 2004 or 

later. The DSI database originally included 1,137 inspection records. 

We removed records that did not fit within the scope of our study, 

including inspections that started after FY 2005 ended. Our analysis 

included 1,107 inspection records from the DSI database. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 26 
 

 

 

 

APPENDIX ~ A 

	 CDRH data: We received data from CDRH in November 2006. 

CDRH’s database originally included 2,762 inspection records. We 

excluded 1,168 inspection records, including records that ORA 

classified as “no inspection made” and records that CDRH classified 

as “washout,” “out of business,” or “cancelled.” Our analysis included 

1,594 CDRH records. 

Table 6: Variables Used To Analyze FDA BiMo Inspections Data 

Variable CBER CDRH CDER 

Inspection Subject Yes Yes Yes 

Reason for Inspection Not available Yes Yes 

ORA Recommended Classification Not available Yes Yes 

Center Final Classification Yes Yes Yes 

Official Actions Yes Yes 

Database 1: Not 

available 

Database 2: Yes 

Assignment Date Yes Yes Yes 

Inspection Start Date Yes Not available Yes 

Inspection End Date Yes Yes Not available 

Trial Status: Ongoing or Closed Not available Not available Not available 

Source: OIG analysis of CDER, CDRH, and CBER data, 2006. 

File review. We used FDA’s databases to identify all inspections that 

either ORA or a center classified as OAI. We reviewed 248 CDER 

inspection files, 99 CBER inspection files, and 321 CDRH inspection 

files, for a total of 668 files. 

We reviewed the files using a Microsoft Access® protocol. Our protocol 

included inspection assignment, classification, official actions, and 

correspondence between the center and the inspection subject. We 

analyzed data from the file reviews using SAS®. 

E-mail survey of Bioresearch Monitoring investigators. ORA headquarters 

provided us with a list of the 231 ORA field investigators who had spent 

100 or more hours conducting BiMo inspections in the previous 5 years. 

We removed eight investigators from the original sample because they 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 27 
 

 

 

A P P E N D I X ~ A 

no longer conduct inspections or had not conducted an onsite inspection 

in several years or we could not obtain contact information for them. 

Our survey solicited respondents’ experiences with FDA guidance, 

inspection and classification recommendations, inspection followup with 

the assigning centers, and challenges in conducting BiMo inspections. 

Before sending the survey, we solicited comments from ORA officials 

and a BiMo investigator about the survey’s content and clarity. We 

incorporated their feedback into the final survey. 

We e-mailed each investigator an introductory letter explaining the 

survey and the study in August 2006. Later in the month, we e-mailed 

the survey. In September 2006, we e-mailed a second copy of the survey 

to those who had not responded. At the end of September, we called the 

investigators who had not yet replied. We received responses from 

170 BiMo investigators for a 76-percent response rate. 

Interviews with Food and Drug Administration officials. We conducted 

telephone interviews with all 19 ORA directors of investigation (DIB) who 

oversee BiMo investigators. Several DIBs invited supervisors in their 

districts to participate in the interviews. 

The interviews focused on the DIBs’ experiences with the supervisory 

role, interactions with BiMo investigators, interactions with the 

assigning centers, classification recommendations, and their challenges 

in supervising BiMo inspections. Before the interviews, we solicited 

comments from ORA officials and a DIB about the interview guide’s 

content and clarity. We incorporated their feedback into the final 

interview guide. We conducted the interviews in October and November 

2006. At least two OIG staff participated in each interview. 

We also interviewed senior FDA officials at FDA headquarters, ORA, 

CBER, CDER, and CDRH. 

Observation of Bioresearch Monitoring inspections. We observed three BiMo 

inspections: two clinical investigator inspections and one IRB inspection. 

FDA initiated the two clinical investigator inspections because of new 

product applications. The IRB inspection was a directed inspection. 

We based our observations on a protocol that focused on the process that 

the BiMo investigator followed as well as the interactions between the 

investigator(s) and the inspection subject(s). At least two OIG staff 

participated in each inspection visit. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 28 
 

A P P E N D I X ~ A 

Clinical trial registry site estimate. To compute an estimate of the average 

number of clinical trial sites associated with a clinical trial, we used data 

from the clinical trials listed on the National Institutes of Health’s clinical 

trials registry as of February 2007. We selected a stratified random 

sample of 150 trials. Because the registry is separated by trial phase, the 

three strata used for the sample were Phase I, Phase II, and Phase III of 

the clinical trial. (See Table 7 for our sample design.) 

Table 7: Clinical Trial Registry Site Estimate Sample Design 

Stratum Population Size Sample 

Phase I 

Phase II 

Phase III 

1,866 

4,566 

4,863 

40 

50 

60 

Source: Office of Inspector General analysis of the National Institutes of Health's Clinical Trial Registry. 

We first counted the total number of clinical trial sites for each of the 

three clinical trial phases. This served as our population size. Using 

the OIG Office of Audit Service’s RAT-STATS software, we chose 

random numbers to select the clinical trial. Because each trial in the 

registry was assigned a number, we were able to use the random 

numbers to identify the sampled trial. After sampling the trials, we 

counted the number of sites associated with each sampled trial. 

We excluded 43 of the 150 clinical trials sampled. There were three 

situations in which the sampled trials were unusable and therefore had 

to be excluded. First, some of the trials appeared in the population 

multiple times because they were named Phase I/Phase II or 

Phase II/Phase III. If a trial was listed as Phase I/Phase II, it was 

counted as Phase II. Similarly, if a trial was listed as Phase II/Phase 

III, it was counted as a Phase III. Eighteen occurrences of a Phase 

I/Phase II trial in the Phase I population were excluded, as were seven 

occurrences of a Phase II/Phase III trial in the Phase II population. In 

addition, no sites were listed for 16 trials. Finally, terminated trials 

occurred twice in the sample. We used the remaining sample of 107 

trials to compute the average number of sites per trial. The sample was 

weighted using standard statistical formulas for a stratified sample. 

Based on these formulas, the estimated average number of sites for a 

clinical trial is 23. This estimate can vary by +/-8 trials at the 

95-percent confidence level. 

O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 29 
 

 

APPENDIX~A 

Review of Food and Drug Administration policies, procedures, and guidance 

documents. We obtained and reviewed all relevant policies, procedures, 

and guidance documents issued by FDA for conducting BiMo inspections. 

We used these documents to better understand the process for conducting 

inspections of clinical trials. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 30 
 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 31

Agency Comments 

ΔAPPENDIX ~ A APPENDIX B 
 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 32

APPENDIX ~ B 
 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 33

APPENDIX ~ B 
 

APPENDIX ~ B NDIX ~ B APPENDIX ~ A 

 

Δ APPENDIX~B ACKNOWLEDGMENTS 

This report was prepared under the direction of Joyce M. Greenleaf, 

Regional Inspector General for Evaluation and Inspections in the 

Boston regional office, and Russell W. Hereford, Deputy Regional 

Inspector General. 

Danielle Fletcher served as the team leader for this study. Other 

principal Office of Evaluation and Inspections staff from the Boston 

regional office who contributed include Rosemary Borck, Chris Galvin, 

and Robyn Sterling, and central office staff include Ayana Everett. 

 O E I - 0 1 - 0 6 - 0 0 1 6 0 T HE F OOD AND DRUG ADMINISTRATION ’ S OVERSIGHT OF CLINICAL T RIALS 34