Department of Health and Human Services 

OFFICE OF 

INSPECTOR GENERAL 

DATA AND SAFETY MONITORING 

BOARDS IN NIH CLINICAL 

TRIALS: M EETING GUIDANCE, 

BUT FACING SOME ISSUES 

Daniel R. Levinson 

Inspector General 

June 2013 

OEI-12-11-00070 
 

EXECUTIVE SUMMARY: DATA AND SAFETY MONITORING BOARDS IN 

NIH CLINICAL TRIALS: MEETING GUIDANCE, BUT FACING SOME ISSUES 

OEI-12-11-00070 

WHY WE DID THIS STUDY 

A Data and Safety Monitoring Board (DSMB) is a committee of experts responsible for 

reviewing clinical trial data on an ongoing basis to ensure the safety of study subjects and 

validity and integrity of the data. Members should be independent, with no vested 

interest in a specific treatment. A DSMB reviews evidence of adverse events and interim 

treatment outcomes to recommend whether trials should be continued, altered, or 

terminated. To do so, a DSMB must have access to “unmasked” data during the course 

of a trial, meaning that members know which subjects are in which treatment group. This 

study seeks to determine the extent to which DSMBs met National Institutes of Health 

(NIH) guidance, identify any challenges to DSMB effectiveness, and contribute to the 

Office of Inspector General’s body of work concerning clinical trials and human subject 

protections. 

HOW WE DID THIS STUDY 

We reviewed the extent to which DSMBs met NIH guidance and identified any 

challenges to their effectiveness. According to general NIH guidance, DSMBs (which 

are composed of relevant experts) should meet regularly to review interim trial data and 

make recommendations concerning the trials’ continuation or termination. Our findings 

are based on the population of 44 NIH-funded Phase III multi-site clinical trials 

completed in 2009 and 2010 that entailed potential risk. We reviewed NIH guidance and 

DSMB policies; documentation regarding DSMB meetings, including membership 

rosters and recommendations; surveyed DSMB members and principal investigators; and 

interviewed NIH staff and DSMB stakeholders. 

WHAT WE FOUND 

DSMBs met general NIH guidance. They met regularly, and 91 percent of meetings 

resulted in a recommendation to NIH. DSMB members represented multiple disciplines 

and had significant experience. Most DSMB members identified themselves as either 

clinicians or as clinical trial experts. However, DSMBs face some issues. NIH 

participation in closed DSMB meetings diminishes the appearance of independence; not 

all Institutes and Centers (IC) policies reference DSMB access to unmasked data; and 

NIH faces challenges in recruiting and training DSMB members. 

WHAT WE RECOMMEND 

NIH should (1) direct ICs to articulate the circumstances in which IC staff should 

participate in DSMB meetings, (2) direct ICs to explicitly reference DSMB access to 

unmasked data in their DSMB policies, and (3) identify ways to recruit and train new 

DSMB members. NIH concurred with all three recommendations. 
 

TABLE OF CONTENTS 

Objectives ....................................................................................................1 

Background..................................................................................................1 

Methodology................................................................................................4 

Findings........................................................................................................7 

DSMBs are meeting NIH guidance in their roles as trial 

monitors ...........................................................................................7 

DSMBs face some issues that may affect their ability to fulfill 

their roles .........................................................................................9 

Conclusion and Recommendations ............................................................12 

Agency Comments and Office of Inspector General Response .....13 

Appendix: Agency Comments ..................................................................14 

Acknowledgments......................................................................................17 
 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 

 

 

 

 

 

 

 

OBJECTIVES 

1.	 To determine the extent to which Data and Safety Monitoring Boards 

(DSMBs) met National Institutes of Health (NIH) guidance in carrying 

out their responsibilities to monitor trials. 

2.	 To identify any challenges to DSMB effectiveness. 

BACKGROUND 

Clinical trials test experimental drugs, devices, and treatments to 

determine whether they are safe and effective. DSMBs are advisory 

committees of experts responsible for reviewing ongoing trial data. They 

play a unique role in ensuring the safety of human subjects enrolled in 

trials. They also play a critical role in ensuring the merit of these trials.1 

To carry out these functions, DSMBs must have direct access to 

“unmasked” data during the course of a trial, meaning that members know 

which subjects are in which treatment group—something the researchers 

and subjects themselves do not generally know. NIH requires DSMBs to 

monitor all Phase III multi-site trials that entail potential risk.2 

DSMBs serve as independent bodies of experts that have no vested 

interest in a specific treatment. DSMBs approach trial monitoring with 

uncertainty regarding whether the intervention or drug being tested will be 

superior to existing treatments or at all effective until proven otherwise.3 

DSMBs review evidence of study-related adverse events and interim 

treatment outcomes to recommend whether trials should be continued, 

altered, or terminated. This study seeks to explain the important role that 

DSMBs play in NIH-sponsored research involving human subjects, and to 

contribute to the Office of Inspector General’s (OIG) significant body of 

work concerning clinical trials and human subject protections. 

NIH 

NIH is the largest source of funding for medical research in the world; it 

had a budget of $30.9 billion in fiscal year (FY) 2012.4

 NIH comprises 

the Office of the Director and 27 Institutes and Centers (IC), each with a 

specific research agenda. 

1

 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov
 

on January 15, 2013.
 2

 Ibid. 

3 This approach is known as practicing “clinical equipoise.”
 4

 NIH, Operating Plan-Budget Mechanism. Accessed at 

http://officeofbudget.od.nih.gov on December 18, 2012. 

 1 
 

 

 

Clinical Trials 

A clinical trial is a controlled study to determine whether an experimental 

drug, treatment, or device is safe and effective. Drugs, treatments, and 

devices generally undergo three phases of clinical trials. Phase III trials 

typically involve several hundred to several thousand human subjects. 

These trials are used to confirm the effectiveness of a treatment, monitor 

its side effects, compare it to commonly used treatments, and collect 

information on safe usage. Phase III clinical trials also typically involve 

multiple trial sites where human subjects receive an experimental 

intervention.5 All multi-site clinical trials involving interventions that 

pose potential risk to the participants require a DSMB.6 

Grantees, principal investigators, and DSMBs are involved in Phase III 

NIH clinical trials. A grantee is an organization or individual awarded a 

grant or cooperative agreement by NIH. The grantee is accountable for 

the use of funds and for the performance of the clinical trial. Grantees 

typically include academic centers or pharmaceutical and device 

companies. To direct the trial, a grantee designates a principal investigator 

who is accountable to the grantee and NIH for the trial’s proper conduct.7 

A DSMB is a group of individuals with pertinent expertise that regularly 

reviews accumulating data from one or more ongoing clinical trials. A 

DSMB functions as a monitor of the trial to ensure the safety of study 

subjects and validity and integrity of the data. Independence is critical for 

DSMBs. Without independence, their recommendations could be biased, 

and the ability of the DSMB to fulfill its mission would be compromised. 

DSMBs make recommendations to NIH, Institutional Review Boards 

(IRBs), and/or the principal investigator regarding continuing, altering, 

suspending, or terminating a trial. 8, 9 For instance, a DSMB may 

recommend terminating a trial if the results are so overwhelmingly 

positive or negative that the ultimate conclusion can be readily predicted 

or if the trial appears futile (e.g., no difference emerged between the 

treatment groups). 

DSMBs meet in open and closed sessions. They generally first meet in an 

open session attended by voting DSMB members, IC staff, principal 

5

 NIH, Glossary. Accessed at http://grants.nih.gov on January 15, 2013. 6

 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov on 

January 15, 2013.
 7

 NIH, Glossary. Accessed at http://grants.nih.gov on January 15, 2013. 8

 An IRB is a committee set up to ensure the protection of the rights and welfare of 

human subjects. Each clinical trial must be covered by an IRB. IRBs are typically 

site-specific. 

9

 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov on 

January 15, 2013.
 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 2 
 

 

 

 

 

 

 

 

 

 

investigators, and industry representatives.10 During an open session, 

principal investigators or their designee(s) typically provide an update on 

trial progress and answer questions. Following the open session, the 

DSMB convenes a closed session to review emerging trial data (including 

potentially unmasked data). Closed sessions are attended by voting 

DSMB members and sometimes by study statisticians and other IC staff.11 

These closed meetings also include a review and discussions of adverse 

events, participant risk versus benefits, and trial sites. 

NIH DSMBs 

Potential grantees who apply for funding must submit a clinical trial 

protocol, which is a detailed study plan that includes the objectives, 

methodology, and statistical plan for the trial. The protocol must include a 

data and safety monitoring plan (DSM plan). For multi-site Phase III 

clinical trials that involve risk to participants, the plan must involve a 

DSMB.12 

NIH allows ICs flexibility in implementing the DSMB guidance for data 

and safety monitoring. Each IC should have its own DSMB policy. 

However, NIH does specify responsibilities related to DSMB composition, 

reporting, and conflict of interest.13 

Composition. DSMBs should consist of experts in all scientific disciplines 

needed to interpret the trial data and ensure patient safety. They may 

include clinical trial experts, biostatisticians, bioethicists, and clinicians 

knowledgeable about the disease and treatment under study.14 ICs are 

responsible for ensuring that DSMB members have the appropriate 

expertise required for each specific trial.15 

Reporting Recommendations. A DSMB must make recommendations to 

the IC after each meeting concerning the continuation or conclusion of the 

trial. The IC should review all recommendations and ensure that they are 

addressed and shared with the principal investigator and the IRB.16 

Conflict of Interest. To preserve the group’s independence, individual 

DSMB members should not be associated with the trial, meaning that they 

should have no financial or professional interests in the trial. ICs should 

10 NIH, Policy for Data and Safety Monitoring, 1998. Open sessions can be public or
 

private, as decided by the IC. Accessed at http://grants.nih.gov on January 15, 2013. 

11 Ibid. 

12 Ibid. 

13 NIH, Glossary. Accessed at http://grants.nih.gov on January 15, 2013. 14 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov 

on January 15, 2013.
 15 Ibid. 

16 Ibid. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 3 
 

 

 

 

evaluate whether the potential DSMB members have conflicts of interest 

with or financial stakes in the research outcomes; when conflicts exist, ICs 

must have policies for managing them in a reasonable manner.17 Although 

it is not explicitly required, ICs may require that DSMB members disclose 

a conflict or sign a document maintaining that they are free of any conflict 

of interest. 

Related Reports 

In 1998, OIG issued a series of reports on IRBs.18 This report is a followup on the recommendations from that series regarding the use of DSMBs. 

OIG recommended that NIH and the Food and Drug Administration 

(FDA) define the types of trials for which DSMBs would be required and 

set forth requirements for the composition of DSMBs.19 In response, NIH 

required DSMBs for all Phase III multi-site trials and published guidance 

about their composition.20 FDA released nonbinding recommendations 

regarding the use of DSMBs. Like NIH, FDA defines a DSMB as a group 

of individuals with pertinent experience that reviews accumulating data 

from one or more ongoing clinical trials. FDA allows trial sponsors to 

determine when a DSMB may be useful for study monitoring.21 

METHODOLOGY 

This study reviewed the extent to which DSMBs for NIH-funded Phase III 

multi-site clinical trials met NIH guidance. The findings are based on data 

collected on the population of Phase III multi-site clinical trials completed 

in 2009 and 2010 that entailed potential risk. NIH identified a total of 44 

trials funded by 10 ICs that met these criteria. 

We used several data sources to answer our study objectives: (1) NIH 

guidance and IC DSMB policies; (2) DSM plans; (3) documentation 

regarding DSMB meetings, including membership rosters and 

recommendations; (4) a survey of DSMB members, (5) a survey of 

principal investigators; (6) structured interviews with staff from the 

10 ICs; and (7) interviews with DSMB stakeholders. These sources are 

described below. 

17 Ibid. 

18 OIG, Institutional Review Boards: Their Role in Approved Research, OEI-01-97-

00190, June 1998; Institutional Review Boards: Promising Approaches, OEI-01-97-

00191, June 1998; Institutional Review Boards: The Emergence of Independent Boards, 

OEI-01-97-00193, June 1998; Institutional Review Boards: A Time for Reform, OEI-01-

97-00193, June 1998. 

19 OIG, Institutional Review Boards: A Time for Reform, OEI-01-97-00193, June 1998. 20 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov 

on January 15, 2013.
 21 FDA, Guidance for Clinical Trial Sponsors: Establishment and Operation of Clinical
 

Trial Monitoring Committees, 2006. Accessed at www.fda.gov on March 7, 2013. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 4 
 

 

 

 

NIH Guidance and IC Policies 

We reviewed NIH’s 1998 Policy for Data and Safety Monitoring to assess 

NIH guidance on DSMBs. Because each IC has flexibility in 

implementing this guidance as appropriate for its specific clinical research 

activities, we also reviewed the 10 ICs’ DSMB policies. 

DSM Plans 

We collected DSM plans from ICs for each of the 44 clinical trials. From 

these we gathered information about the DSMBs’ composition and the 

frequency of their meetings. 

Documentation Regarding DSMB Meetings 

We received documentation regarding closed DSMB meetings for 39 of 

the 44 trials in our population (a total of 399 meetings).22 For each closed 

meeting, we received meeting attendance records, a summary of the 

meeting (including any minutes), and DSMB recommendations. 

Survey of DSMB Members 

In April 2012, we surveyed DSMB members about their experiences on 

DSMBs and whether they had enough information to make 

recommendations. We identified 322 DSMB members through the DSMB 

membership rosters provided by NIH for our population of 44 studies. Of 

the 322, we ultimately surveyed 251.23 We made up to three attempts to 

elicit responses and ultimately received 180, 72-percent response rate. 

Survey of Principal Investigators 

In November 2012, we surveyed principal investigators about their 

perceptions regarding the representation of scientific disciplines on 

DSMBs and their overall experiences with DSMBs. NIH provided us a 

list of all 91 principal investigators associated with our population of 

44 trials (some trials had multiple investigators). Of the 91, we ultimately 

surveyed 69 principal investigators.24 We made up to three attempts to 

elicit responses and ultimately received 30, 43-percent response rate. 

Given this response rate, our results may not reflect the opinions of all the 

principal investigators associated with the 44 clinical trials in our 

population. 

22 One IC accounted for the five trials for which we did not receive meeting minutes. 

This IC stated that it does not receive DSMB meeting documentation. 23 Thirty-five email addresses were no longer active; 21 DSMB members were listed
 

more than once; 5 DSMB members were deceased; and 3 individuals stated that they did 

not serve on a DSMB and were incorrectly identified.
 24 Seventeen email addresses were no longer active; four individuals confirmed they were 

not the principal investigator for the trial; and one principal investigator was deceased. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 5 
 

 

Structured Interviews With NIH Staff 

We interviewed staff from the 10 ICs associated with 2009 and 2010 trials. 

We asked IC staff about their oversight of DSMBs, including any training 

provided to members and the recruitment process. We also asked about 

the IC staff’s review of DSM plans and DSMB recommendations. 

Interviews With Stakeholders 

We interviewed 11 experts with DSMB experience either as DSMB 

members (e.g., biostatistician, clinician) or a principal investigator. These 

experts were not directly associated with any trials in our population and 

were identified through research and individual recommendations. 

Conversations focused on the independence of DSMBs, DSMB members’ 

access to unmasked data, and recruitment and training of DSMB members. 

Limitations 

Given our response rates and the possibility that nonresponding DSMB 

members or principal investigators may have responded differently to our 

questions than responders, our results may not reflect the opinions of all 

DSMB members or principal investigators associated with the 44 clinical 

trials in our population. Also, given that responses were anonymous, we 

are unable to determine the specific trials with which respondents are 

associated. 

Standards 

This study was conducted in accordance with the Quality Standards for 

Inspection and Evaluation issued by the Council of the Inspectors General 

on Integrity and Efficiency. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 6 
 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 7 

FINDINGS 

DSMBs are meeting NIH guidance in their roles as 

trial monitors 

According to NIH guidance, DSMBs should meet regularly to review 

interim trial data and make recommendations to ICs concerning the 

continuation or conclusion of the trial. DSMBs should be composed of 

experts in all scientific disciplines needed to interpret the data and ensure 

patient safety. For NIH trials completed in 2009 and 2010, we found that 

DSMBs met this general guidance. 

DSMBs met regularly and made recommendations about the 

continuation of the trials 

Clinical trials span many years; therefore the DSMBs must meet over 

many years. The 39 trials for which we had meeting records met for 

4.5 years on average, ranging from 21 months to 8.5 years. Almost all 

members reported that their DSMBs met frequently enough to fulfill their 

mission. Most DSMBs met semiannually (45 percent) or annually (42 

percent). The remainder met quarterly. 

DSMBs’ initial meetings were usually in person, but over half of the 

subsequent 360 meetings were by teleconference. IC staff reported that 

meeting via teleconference reduced the burdens of time and travel. 

At the conclusion of closed sessions, DSMB members vote on 

recommendations regarding trial continuation. Making such 

recommendations is a primary responsibility of the DSMB. The great 

majority of meetings (91 percent, 365 of 399) resulted in 

recommendations.25 According to meeting records we reviewed, the 

DSMBs recommended stopping seven trials. Four of these 

recommendations were based on findings that the treatments under study 

were ineffective; the other three were based on findings that the trials 

could not accrue enough subjects in the allotted time to yield useful 

results. All seven trials were subsequently terminated. 

The great majority of DSMB recommendations were to continue the 

studies with no changes; 20 percent of the recommendations were to 

continue the studies with changes. Recommended changes included 

pretrial changes to the protocol, altering the informed consent form or 

process, changing enrollment, or changing treatment. 

25 Those that did not were often the final meetings at the close of the trial or a specific 

meeting solely on enrollment updates or a protocol modification. 
 

 

DSMB members represented multiple disciplines and have 

significant experience with DSMBs 

The effectiveness of a DSMB depends in large part on the strengths of its 

members. Members volunteer their expertise and time to ensure trial 

integrity and patient safety. According to IC staff and DSMB 

stakeholders, DSMB members are experienced professionals respected in 

their scientific fields. 

The DSM plans and DSMB policies we reviewed generally called for 

members from the disciplines necessary to carry out the task of a DSMB. 

On the basis of our review of the DSMB rosters, DSMBs met this general 

requirement. DSMBs were composed of clinicians, clinical trial experts, 

biostatisticians, bioethicists, and patient advocates. On average, each 

DSMB had seven members. Membership ranged from 4 to 11 per trial. 

More than two-thirds of DSMB members identified themselves as either 

clinicians knowledgeable about the disease and/or treatment relevant to 

the trial or as clinical trial experts. The vast majority of DSMB members 

and principal investigators reported that these disciplines were adequately 

represented on DSMBs. DSMB members and principal investigators also 

reported that biostatisticians were adequately represented. 

Bioethicists may be warranted on some DSMBs to provide bioethical 

perspectives on the progress of trials. However, one-third of DSMB 

members and principal investigators reported that bioethicists were 

underrepresented. Bioethicists were the least represented discipline of 

those members we surveyed (15 of 180). Staff from two ICs said that 

bioethicists are especially difficult to recruit to DSMBs given their limited 

experience with clinical trials. 

Seventy-five percent of DSMB members reported that they had served on 

more than one DSMB. On average, they reported serving on five DSMBs 

throughout their careers. Twenty-six of thirty principal investigators 

surveyed reported that the DSMB members had enough experience to 

fulfill their roles. 

Standing DSMBs may account for the large percentage of individuals 

serving on multiple DSMBs. A standing DSMB is one that meets for a 

number of different trials within the same IC in which the same disease or 

treatment is being studied. Eight of the ten ICs use standing DSMBs for 

some or all of their trials. Staff stated that the main advantage to using 

standing DSMBs is having a ready-made, experienced pool of members 

familiar with the roles and responsibilities of a DSMB. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 8 
 

 

 

 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 

 

DSMBs face some issues that may affect their ability

to fulfill their roles 

DSMBs met NIH’s general guidance by having relevant experts who met 

regularly to offer recommendations to NIH. To fulfill their roles, however, 

DSMBs must also maintain their independence, be assured access to 

unmasked data, and have a qualified pool of experts from which to recruit 

DSMB members. DSMBs face issues in all three of these areas. 

IC participation in closed DSMB meetings diminishes the 

appearance of independence 

According to NIH, ideally, individuals are in no way associated with the 

trials they monitor.26 Association with a trial could take many forms. For 

instance, DSMB members could have conflicts of interest, meaning 

personal or financial stakes in the outcome of a trial. However, we found 

that conflict-of-interest paperwork was generally submitted to ICs, as 

required. 

Additionally, IC staff have interests in the trials because the ICs fund the 

trials. Staff from 9 of the 10 ICs attended closed DSMB meetings at 

which interim data were reviewed. DSMBs generate recommendations 

regarding trial continuation from the interim data review. 

We did not assess whether any DSMB recommendations were subject to 

bias. However, the extent to which IC staff participated in closed 

meetings diminishes the appearance of independence. Half (15 of 30) of 

principal investigators responded that IC staff should not participate in 

closed DSMB meetings. Six of the eleven expert stakeholders expressed 

concern about the extent to which ICs participate in closed DSMB 

meetings. One stakeholder said that such participation hindered 

independence. Another referred to IC participation as a “delicate balance” 

between the IC obtaining information and the DSMB maintaining 

independence. 

A few DSMB members and principal investigators did not agree that their 

DSMBs maintained their independence from NIH. Specifically, 14 (of 

180) DSMB members and 3 (of 30) principal investigators did not believe 

that DSMBs maintained their independence. 

On the other hand, IC staff, most DSMB members, and most principal 

investigators agreed that DSMBs maintained their independence from 

NIH. In fact, one DSMB member noted that the IC’s participation in the 

DSMB was important to help the DSMB make informed decisions; a 

26 NIH, Policy for Data and Safety Monitoring, 1998. Accessed at http://grants.nih.gov 

on January 15, 2013. 

 9 
 

 

 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 10 

stakeholder noted that the DSMBs benefit from the closer relationship the 

ICs have with the principal investigators. Others also cited the importance 

of having an IC staff attend closed meetings to serve as an executive 

secretary, thereby facilitating note taking, scheduling, and other related 

functions. 

IC staff involvement in DSMB meetings is addressed in each IC’s DSMB 

policy. However, the policies did not always clearly restrict participation 

in closed meetings or define the role of IC staff in closed meetings. For 

example, one IC policy appears to include no restrictions, stating that 

“during closed sessions of the DSMB meetings only DSMB members and 

IC program staff may attend.” Another policy states that “closed sessions 

will be restricted to voting and ad hoc members ... and IC staff as 

appropriate.” In a third example, the policy is clearer, restricting IC staff 

participation in closed session (when unmasked data would be discussed) 

to the IC executive secretary and statistician. 

Not all IC policies reference DSMB access to unmasked data 

DSMBs are typically the only clinical trial oversight entity with direct 

access to unmasked data during the course of the trial, meaning that 

members know who is in the control group versus the treatment group. 

Many experts and almost all principal investigators agreed that to fulfill 

their roles, DSMB members must have access to these data if they request 

them.27 

Only 4 of 10 IC policies referenced DSMB access to unmasked data. One 

IC policy makes clear that members should “review masked or unmasked 

data as needed and appropriate.” In another example, the policy is very 

clear regarding members’ access to unmasked data and states that “the 

DSMB decides in their first meeting if DSMB members will be unmasked. 

If the DSMB decides to remain masked, they should consider assigning 

one DSMB member to be unmasked to treatment assignment.” The 

remaining six IC policies were silent on the issue of DSMB member 

access to unmasked data. 

A small number of DSMB members (17 of 180) did not believe they had 

access to unmasked data. Additionally, DSMBs for 14 of 39 trials 

reviewed only masked data at each meeting.28 We do not know whether 

they requested unmasked data. 

27 One expert argues that monitoring a trial without access to unmasked data “denies the 

monitors the key information they need to perform in a competent fashion, and 

incompetent monitoring poses a risk to research subjects.” (Curtis Meinert , “Masked 

Monitoring In Clinical Trials: Blind Stupidity?” The New England Journal of Medicine. 

338, 19. May 7, 1998.) 

28 This analysis is based on the 39 trials for which we have meeting minutes. 
 

 

ICs face challenges in recruiting and training DSMB members 

The participation of experienced professionals is essential to ensure that 

DSMBs are effective, and ICs must maintain a pool of qualified 

individuals from which to recruit and train new members. According to 

staff from all 10 ICs, however, recruiting is a challenge. Membership in a 

DSMB is a voluntary commitment that lasts many years, with little 

reimbursement. Some DSMB members noted the onerous nature of the 

conflict-of-interest disclosures. For example, former collaborations with 

the study sponsor can be considered a disqualifying conflict. Furthermore, 

the ICs noted that bioethicists can be challenging to recruit, especially 

because they lack clinical trial experience. 

The ICs reported facing challenges in recruiting DSMB members despite 

the prestige associated with serving on an NIH-sponsored trial DSMB. 

The ICs touted the qualifications of their DSMB members as representing 

the best of the best, and the DSMB members cited their DSMB service as 

not only professionally satisfying but also as an important way to 

contribute to scientific advancement. 

ICs benefit from the depth of experience of their DSMB members. 

However, sustaining that level of experience is a challenge for the ICs 

because those with the most experience eventually retire. We found that 9 

of 10 ICs do not offer any formal training to DSMB members and, in fact, 

ICs and stakeholders noted that the best form of training is on-the-job 

experience. ICs offer informal training such as online reading materials 

and a review of the DSM plan during the first meeting. Many DSMB 

members responding to our survey noted that formal training would have 

benefitted them most only at the outset of their DSMB experiences to 

create a common understanding of the role of a DSMB. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 11 
 

 

 

CONCLUSION AND RECOMMENDATIONS 

DSMBs play a critical role in ensuring the safety of human subjects and the 

merit of clinical trials. They fulfill their mission to monitor trials by making 

use of the significant strengths of their members’ experience. However, 

DSMBs face three issues that could compromise their effectiveness. The first 

lies in ensuring their independence—and appearance of independence. The 

second lies in ensuring their access to unmasked data. The third lies in 

maintaining a pool of qualified individuals to serve on DSMBs. We 

recommend that NIH: 

Direct ICs To Articulate the Circumstances Under Which IC Staff 

Participate in Closed Meetings 

The extent of IC staff involvement in closed DSMB meetings and the lack of 

clarity concerning the ICs’ expected roles in meetings could diminish the 

appearance of independence. ICs should clearly describe the circumstances in 

which it is appropriate for specified IC staff to attend closed DSMB meetings, 

and the role of these staff during the meetings. For instance, IC policies could 

outline that IC executive secretaries will attend closed meetings to take 

minutes and provide appropriate followup. IC policies provide an appropriate 

platform to set these expectations. 

Direct ICs To Explicitly Reference DSMB Access to Unmasked 

Data in Their DSMB Policies 

DSMB members may not always have access to unmasked trial data. The 

ability of DSMBs to monitor trial progress and ensure the safety of patients 

may be compromised without access to unmasked data. ICs should ensure that 

DSMB members have access by directing ICs to reference this access in their 

DSMB policies. 

Identify Ways To Recruit and Train New DSMB Members 

According to staff from all 10 ICs, recruiting is a challenge. In addition, 9 of 

10 ICs do not offer any formal training to DSMB members. Experienced 

professionals are essential to ensure that DSMBs are effective. 

To help recruit and train new DSMB members, NIH could create a forum for 

DSMB issues to be shared and discussed across ICs. A forum in which IC staff 

can discuss challenges and solutions—such as how to address recruitment 

issues, including the underrepresentation of bioethicists—could be highly 

beneficial for the effective use of DSMBs. An online forum is one option for 

ICs to share information and network. NIH could also sponsor an in-person or 

Webinar conference. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 12 
 

 

In addition, NIH could create a pool of potential DSMB members by 

expanding each DSMBs’ membership to include one nonvoting member who 

has not previously (or recently) served on a DSMB. 

AGENCY COMMENTS AND OFFICE OF INSPECTOR GENERAL 

RESPONSE 

NIH concurred with all three of OIG’s recommendations. NIH stated that it is 

organizing a trans-NIH working group to review the report and to ensure that 

ICs’ DSMB policies and practices are optimal. 

Although NIH agreed with our first recommendation, it did not find that the 

presence of IC staff constituted a conflict of interest. However, we found that 

the presence of IC staff at closed DSMB meetings did create the appearance of 

a conflict of interest for at least some DSMB members, principal investigators, 

and stakeholders. NIH did state that IC policies should make staff roles and 

responsibilities transparent; clarify why their participation does not affect the 

independence of DSMB-decision making; and delineate instances in which the 

program staff take on additional roles that would constitute a conflict of 

interest. 

In response to our second recommendation, NIH specified that all IC policies 

should state that DSMBs have access to unmasked data. 

In response to our third recommendation, NIH stated that ICs are actively 

exploring ways to enlarge their pools of experts and ensuring that DSMB 

service is appropriately credited and recognized. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 13 
 

 

 

APPENDIX A 

Agency Comments 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 14
 
 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 15
 

 

APPENDIX A 

Agency Comments (cont.)
 
 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 16
 

APPENDIX A 

Agency Comments (cont.)
 
 

 

 

ACKNOWLEDGMENTS 

This report was prepared under the direction of Joyce Greenleaf, Regional Inspector 

General for Evaluation and Inspections in the Boston regional office and Russell 

Hereford, Deputy Regional Inspector General. 

Anne Gavin served as the team leader for this study. Amy Glynn served as the lead 

analyst. Other principal Office of Evaluation and Inspections staff from the Boston 

regional office who contributed to the report include Shreya Patel; central office staff 

who contributed include Debra Roush, Talisha Searcy, Jacquelyn Towns, and Sherri 

Weinstein. 

Data and Safety Monitoring Boards in NIH Clinical Trials (OEI-12-11-00070) 17 
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 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. These evaluations focus on preventing fraud, waste, or abuse and promoting 

economy, efficiency, and effectiveness of departmental programs. To promote impact, OEI 

reports also present practical recommendations for improving program operations. 

Office of Investigations 

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

of fraud and misconduct related to HHS programs, operations, and beneficiaries. With 

investigators working in all 50 States and the District of Columbia, OI utilizes its resources 

by actively coordinating with the Department of Justice and other Federal, State, and local 

law enforcement authorities. The investigative efforts of OI often lead to criminal 

convictions, administrative sanctions, and/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 for OIG’s internal operations. OCIG represents OIG in all civil and 

administrative fraud and abuse cases involving HHS programs, including False Claims Act, 

program exclusion, and civil monetary penalty cases. In connection with these cases, OCIG 

also negotiates and monitors corporate integrity agreements. OCIG renders advisory 

opinions, issues compliance program guidance, publishes fraud alerts, and provides other 

guidance to the health care industry concerning the anti-kickback statute and other OIG 

enforcement authorities.