Data and Safety
Nancy T. Artinian ▼ Erika Sivarajan Froelicher ▼
Principal investigators have a responsibility to ensure and maintain the
scientific integrity of their research studies and to protect the safety of the partici-
pants. Data and safety monitoring is required for all types of clinical trials, and the
nature and degree of the monitoring must be related to the degree of risk involved.
This article aims to define the purpose of a data and safety monitoring
board (DSMB), to describe the functions of a DSMB and distinguish them from the
activities of an institutional review board, and to discuss the development and imple-
The literature on data and safety monitoring is reviewed, and the process and
key issues are illustrated with examples from the authors’ clinical trial and others.
The principal role of the DSMB is to monitor the data from the trial periodically,
to review and assess the performance of its operations, and to make recommenda-
tions based on interim results (e.g., modification of the study protocol, or possible
early termination of the study). Although the roles of a DSMB and institutional reviewboard complement one another, the main focus of their responsibilities is different
What Is Data and Safety
and carried out independently of one another. The members of a DSMB are selected
on the basis of their methodologic, statistical, or clinical expertise.
The multiple scientific, ethical, safety, recruitment, intervention, and bud-
getary responsibilities of a principal investigator can be complex. The role of the
DSMB is crucial and offers independent evaluation to ensure participant safety and
adverse events ⅐ data and safety monitoring ⅐ institutional review board
Nancy T. Artinian, PhD, RN, BC, FAHA,
is Professor and Director of Doctoral and
Postdoctoral Programs, College of Nurs-
ing; and Jillon S. Vander Wal, PhD, is
Assistant Professor, Center for Health
Research, Wayne State University, Detroit,
tific integrity of their studies. On June
Erika Sivarajan Froelicher, RN, PhD,
FAAN, is Professor, Department of Physi-
ological Nursing, Department of Epidemi-
ology & Biostatistics, Schools of Nursing
and Medicine, University of California San
Data and Safety Monitoring 415
TABLE 1. Criteria Used to Determine Adverse Events, the Need for Additional Safety Measures, or
the Need to Stop the Trial
1. Dropout from one study group is four times greater than the dropout rate from the other group. Attrition from each study group is expected to
2. Less than five persons recruited per month. The monthly target recruitment goal is 16.
3. Unresolved equipment failures greater or equal to 50% of the telemonitoring intervention group. Because telemonitoring is a fairly new
technology, some equipment failures are expected.
4. Adverse health event (death, stroke, myocardial infarction) rates in the telemonitoring intervention group two-fold greater than adverse health
event rates in the usual care group.
5. Level of depression in either group greater than or equal to a score of 27 as measured by the Center for Epidemiologic Studies–Depression
6. For either group, a rise in the mean systolic blood pressure (SBP) greater than or equal to 20 mm Hg or a rise in mean diastolic blood
pressure (DBP) greater than or equal to 10 mm Hg, which is maintained over a 3- to 6-month period.
7. A rise in an individual participant’s SBP to greater than 180 mm Hg or a rise in an individual participant’s DBP to greater than 110 mm Hg.
8. Differential change in systolic and diastolic blood pressure between groups.
Functions of a DSMB
tal intervention, and exceptions in eligi-
fied plans for participant retention is an
efforts begin at the time of the first con-
Data and Safety Monitoring
TABLE 2. Comparison of Data and Safety Monitoring Board (DSMB) and Institutional Review Board
Oversee participant safety; review accumulated
Assess risks and benefits of the proposed
research by reviewing the research protocol
Membership appointments determined by the PI;
Membership determined administratively at
members are approved by the study’s funding
the institution where the IRB is located
Clinicians with expertise with the specific clinical
At least five members with varying backgrounds
problem under investigation, biostatisticians
to promote complete and adequate review of
with expertise in data-monitoring methods,
research activities commonly conducted by the
and possibly medical ethicists; at least
the investigators in the institution; varying
disciplines are represented, including at least
in research design, methodologyand statistics,
one member who is a nonscientist in order to
such as an epidemiologist, who can conduct
appreciate ethical concerns from a variety of
perspectives (Penslar & Porter, 2001).
Evaluate adverse event reports (AERs) within the
Review adverse events and reassess the balance
context of the trial. Evaluate if an observed event
between the risks and the benefits to the
exceeds the expected incidence of that event in a
participants; based on provided information, the
particular population, or if the event is clinically
IRB may reconsider its approval of the study,
meaningful in the context of other medical problems
require modifications to the study, revise the
in the specified population. Provide aggregated data
continuing review time table, or even halt the
summaries to the IRB about the seriousness and
study. An IRB is poorly positioned to evaluate
relatedness of adverse events to the study
AERs owing to lack of information about the
intervention (Morse et al., 2001; National Institutes
clinical meaning of the event in the context of
other medical problems in the specified population.
integrity (Meinert & Tonascia, 1986).
A DSMB Versus an IRB
Pocock, & Julian, 1999). Unlike IRBs,
Developing Plans for Data and Safety
affiliated (Penslar & Porter, 2001). An
ducting the research ethically (Burns &
that research activities are ethical, its
Data and Safety Monitoring 417
setting potential benefit (Brass, 2001).
start of a trial, specifies a limit for the
groups (Meinert & Tonascia, 1986).
Meetings of the DSMB
their specific methodologic, statistical,
resented expertise related to statistics,
exist (O’Brien & Fleming, 1979).
ficult “stopping rule” decisions. Not
of clear evidence for a beneficial effect
also must be above suspicion of bias.
Stopping A Trial
institutional Phase 3 studies (i.e., stud-
Data and Safety Monitoring
originally planned termination date.
an angiotensin-converting-enzymeinhibitor, ramipril, on cardiovascular
Accepted for publication May 10, 2004.
events in high-risk patients. New Eng-land Journal of Medicine, 342
Preparation of this manuscript was partiallysupported by the National Institute of Nurs-
ing Research and National Center on Minor-
ity Health and Health Disparities/NIH Grant
must report their conclusions to IRBs.
Human Research Report, 14
Corresponding author: Nancy T. Artinian,
Meinert, C. L., & Tonascia, S. (1986).
PhD, RN, BC, FAHA, College of Nursing,Wayne State University, 5557 Cass Avenue,
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lowing safety concerns . . . ,” and “stop
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Cardiopulmonary Rehabilitation, 23
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