Human Research Protection Program: Policy

 

Review of Data and Safety Monitoring in Research

 

 

Adopted By: All Campus IRB

Adoption Date: December 8, 2005

Purpose:  This document describes when UW-Madison IRBs require data and safety monitoring as part of a research study and how the IRBs evaluate the adequacy of the monitoring plan.

Policy

I.      Before approving a research protocol, federal regulations require that IRBs determine whether data and safety monitoring is necessary and, if so, whether the research protocol makes adequate provision for monitoring the data collected to ensure the safety of participants. [45 CFR §46.111(a)(6) and 21 CFR §56.111(a)(6)]

A.  UW-Madison health sciences IRBs require data and safety monitoring plans (DSM plans) for all protocols involving more than minimal risk.

B.  All research conducted or supported through the UW Comprehensive Cancer Center (UWCCC) requires a DSM plan.

C.  All research conducted or supported through the Clinical and Translational Research Core (CTRC) of the University of Wisconsin-Madison Institute for Clinical and Translational Research (UW-ICTR) requires a CTRC Data and Safety Monitoring Plan (DSMP).

 

1.  In general, protocols that are deemed high risk by the Research Subject Advocate must also have a Data and Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC).  

 

2.  PIs working with an outside DSMB (such as the Cancer Center DMC or Study Sponsor DSMB) need only ensure that the Advocate receives all reports to and from the DSMB or DMC to maintain CTRC documentation.

 

3.  For low-risk studies, without an outside DSMB or DMC, the CTRC will provide supervision through the RSA and the CTRC Data and Safety Monitoring Committee (DSMC).

II.     UW-Madison IRBs may determine that data and safety monitoring of research conducted under the jurisdiction of the UW-Madison may be appropriately performed by the investigator, the sponsor (e.g., medical monitor or monitoring committee) or an independent Data and Safety Monitoring Board (DSMB) or Committee.

Procedure

III.    Submission of Information

A.  Social and Behavioral Science IRB (SBS IRB) and Education Research IRB (ED IRB): Investigators are asked to provide the following information in the Application for Initial Review of Research:

 

1.       An assessment of the types and level of each type of risk

2.       Steps that will be taken to minimize risks

3.       If there are no risks, a statement to that effect

4.       Safeguards to protect confidentiality, as needed, or why confidentiality is not an issue in the study

5.       Provisions for ensuring necessary medical or professional intervention in the event of adverse effects to the participants

B.  Health Sciences IRB (HS IRB) and Health Science Minimal Risk IRB (MR IRB):  Investigators are asked to provide the following information in the Application for Initial Review of Research:

 

1.       The potential risks to subjects of participation in the study, including the expected frequency, severity, and reversibility of the major risks identified and possible late effects of participation (e.g., secondary cancers).

2.       If the study is more than minimal risk, a description of the data and safety monitoring plan.

3.       If a formal Data Safety Monitoring Board or Data Monitoring Committee exists, a general description of the committee or board’s membership e.g. number of members, expertise, and whether the members are independent of the sponsors/researchers) and the expected frequency of their meetings.

IV.   Review of Data and Safety Monitoring Plans

A.  The SBS IRB and ED IRB may consider the following issues when evaluating whether a data and safety monitoring plan is necessary:

 

1.       Whether protocol presents risks of breach of confidentiality and privacy.

2.       Whether it can be anticipated that the research may reveal a risk of suicide or homicide by a research participant, based either on the population being studied or the nature of the questions being asked.  The protocol should describe the procedures that will be followed if the research reveals such a risk.

3.       Whether it can be anticipated that the research may reveal neglect or abuse of a vulnerable individual, based either on the population being studied or the nature of the questions being asked.  The protocol should describe the procedures that will be followed if the research reveals such a risk.

B.  The SBS IRB and ED IRB may consider the following issues when evaluating the adequacy of data and safety monitoring measures described in the protocol:

 

1.  Protection of confidentiality of data and privacy of participants

a.  The sensitivity of the data being collected:

a.  Where the data will be stored?

-        Locked room

-        Secure server

b.  Whether and how the data will be coded?

c.  Who will have access to the data?

 

2.  Risk of suicide and/or homicide

a.  What procedures will be followed by research staff

b.  Whether the consent form includes a warning to participants that any information they provide suggesting a risk of suicide or homicide may be disclosed to proper authorities and may not be entitled to confidentiality.

 

3.  Risk of abuse or neglect of vulnerable individual

a.  What procedures will be followed by research staff

b.  Whether the consent form includes a warning to participants that any information they provide suggesting a risk of abuse or neglect of vulnerable individual may be disclosed to proper authorities and may not be entitled to confidentiality.

C.  The HS IRB and MR IRB may consider the following issues when evaluating whether a DSM plan is necessary and appropriate:

 

1.  Level of risk of the research

a.  If the study is more than minimal risk, a DSM plan is required.  The IRB may require a monitoring board consisting of a physician and a biostatistician.

b.  Inclusion in the research of a vulnerable population may require DSM plan.

    

2.  Phase of the study, if it involves drugs, biologics or devices

a.  NIH guidelines require a formal independent Data Safety Monitoring Board or Data Monitoring Committee for all Phase III studies.

b.  UW-Madison IRBs require a protocol specific DSM plan for Phase I and Phase II studies.

 

3.  Whether the study is blinded or unblended

a.  If blinded, a formal independent Data Safety Monitoring Board or Data Monitoring Committee may be required.

b.  If unblinded, a protocol specific DSM plan may be sufficient.

 

4. Size of the study

a.  Physician-initiated or single site studies that involve more than minimal risk studies require a DSM plan and may require a formal, independent Data Safety Monitoring Board or Data Monitoring Committee.

b.  If a multi-center study, UW-Madison IRBs may ask for a protocol specific DSM plan and may ask for a formal, independent DSMB or Committee.

D.  HS IRB and MR IRB may consider the following issues when evaluating whether a DSM plan is adequate:

 

1.  Reporting mechanisms:

a.  Who will make reports to IRB

b.  How often IRB will receive reports

c.  Contents of reports

 

2.  The frequency of the monitoring

 

3.  Who will conduct the monitoring, such as a data monitoring committee, data and safety monitoring board, medical monitor, investigator, independent physician, or IRB

 

4.  The data to be monitored, and

 

5.  Procedures for communication from the data monitor to the IRB and sites.

a.  DSM plans should provide for reports to be made by the investigators to the IRB on an annual basis and immediately if monitoring reveals a problem with the research requiring re-evaluation of protocol.

b.  If a report is not adequate, the IRB may request an affirmative statement from the DSMB or DSM Plan monitor that there are no problems with the research.

E.  Special considerations with regard to data and safety monitoring by sponsor

 

1.  The IRB recognizes that conflicts of interest are inherent when data and safety monitoring are conducted by monitors chosen by research sponsor.

 

2.  If the IRB believes a sponsor’s DSM plan is inadequate, the IRB may:

a.  Request changes by the sponsor

b.  Request the investigator to conduct additional data and safety monitoring, or

c.  Not approve the protocol.