Nu530501.qxd

Data and Safety
Monitoring During
Randomized
Controlled Trials
of Nursing
Interventions
Nancy T. Artinian ▼ Erika Sivarajan Froelicher ▼ Background: 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.
Objectives:
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- Methods: 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.
Results: 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 Monitoring?
on the basis of their methodologic, statistical, or clinical expertise.
Conclusion: 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 Key Words: 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 Nursing Research
Nursing Research
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- 416 Data and Safety Monitoring
Nursing Research
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
Monitoring
affiliated (Penslar & Porter, 2001). An ducting the research ethically (Burns & that research activities are ethical, its Nursing Research
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
DSMB Membership
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- 418 Data and Safety Monitoring
Nursing Research
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(3), 145- DSMB Reports
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(10), 3.
Corresponding author: Nancy T. Artinian, Meinert, C. L., & Tonascia, S. (1986).
PhD, RN, BC, FAHA, College of Nursing,Wayne State University, 5557 Cass Avenue, monitoring. In C. L. Meinert & S.
Tonascia (Eds.), Clinical trials: Design, such as “continue trial without modifi- conduct, and analysis (pp. 208-216).
cation,” “continue trial with specific References
Moody, L. E., & McMillan, S. (2002).
tion,” “stop the study due to the fol- lowing safety concerns . . . ,” and “stop Heart disease and stroke statistics— ized clinical trials. Nursing Research, ping rule for efficacy.” In a report from Morse, M. A., Califf, R. M., & Sugarman, Armstrong, P. W., & Furberg, C. D.
safety during clinical research. JAMA, constitution. Circulation, 91(3), 901- National Institutes of Arthritis and Mus- culoskeletal and Skin Diseases (2003).
Generic monitoring plan for trials tained at each follow-up date (i.e., 3, 6, requiring a data and safety monitoring a general clinical research center. Jour- board. Retrieved March 6, 2003, from nal of Investigative Medicine, 49(6), Burns, N., & Grove, S. K. (2001). Ethics National Institutes of Health.AQ (1998).
and research. In N. Burns & S. K.
NIH Policy for Data Safety Monitor- Grove (Eds.), The practice of nursing ing. Retrieved February 11, 2003, from research (pp. 191-222). Philadelphia: DeMets, D. L., Pocock, S. J., & Julian, D.
in monitoring of clinical trials. Lancet, 8).AQ Data and safety monitoring exam- ple plans. Retrieved March 12, 2004 O’Brien, P. C., & Fleming, T. R. (1979). A C. D. Furberg, & D. L. DeMets (Eds.), Fundamentals of clinical trials (pp. 246- trials. Biometrics, 35(3), 549-556.
Penslar, R. L., & Porter, J. P. (2001, June Froelicher, E. S. (1996). Tracing patients 21). IRB Guidebook. Retrieved March 5, Conclusion
St. Jude Children’s Hospital Cancer Cen- Froelicher, E. S., Miller, N. H., Buzaitis, A., Pfenninger, P., Misuraco, A., Jordan, Whitehead, J. (1999). On being the statis- sion and/or social isolation. Journal of Board. Statistics in Medicine, 18(24), Cardiopulmonary Rehabilitation, 23(4),

Source: http://digilib.bc.edu/reserves/nu821/pulc/nu821176.pdf