Data and Safety Monitoring Guidelines - National Cancer Institute


Data and Safety Monitoring Guidelines


Background


Essential Elements


Special Circumstances


		Appendix

Page Options

	Quick Links


	Director's Corner Dictionary of Cancer Terms NCI Drug Dictionary Funding Opportunities NCI Publications Advisory Boards and Groups Science Serving People Español

Questions about cancer?


	1-800-4-CANCER

	LiveHelp online chat

	NCI Highlights


	Restructuring the NCI Clinical Trials Enterprise Clinical Trials Reporting Program Coordinating Center for Clinical Trials States Requiring Coverage of Clinical Trial Costs

	Related Pages


	Data and Safety Monitoring Example Plans Examples of NCI-approved Institutional Data and Safety Monitoring Plans, submitted by NCI-designated Cancer Centers.

Appendix

A. Trials for which NCI is also the IND sponsor (Table A and Table B)
B. Trials of an investigational agent for which NCI is not the IND holder
C. Trials involving commercially available agents only (no IND’s involved)
D. Trials involving recombinant DNA molecules (gene transfer)
E. Food and Drug Administration reporting requirements of serious adverse events for post-marketing trials of vaccines (no cancer vaccines yet in this category)
F. Trials involving behavioral or nutritional interventions that do not use an investigational agent

Appendix: Summary of Reporting Requirements for Adverse Events on NCI Trials Supported by Grant or Contract Funding —

A. Trials for which NCI is also the IND sponsor (for details, see NCI's Investigator's Handbook, available online at http://ctep.cancer.gov/handbook/index.html)

TABLE A: Expedited Reporting for Phase I Studies (including hospitalization^*)

UNEXPECTED EVENT

EXPECTED EVENT

GRADES 2 - 3 Attribution of Possible, Probable or Definite

GRADES 4 - 5 Regardless of Attribution

GRADES 1 - 3

GRADES 4 - 5 Regardless of Attribution

Grade 2 - Expedited report within 10 working days

Grade 3 - Report by phone to IDB within 24 hrs. Expedited report to follow within 10 working days.

(Grade 1 - Adverse Event Expedited Reporting NOT required.)

Report by phone to IDB within 24 hrs. Expedited report to follow within 10 working days.

This includes all deaths within 30 days of the last dose of treatment with an investigational agent regardless of attribution.

Any late death attributed to the agent (possible, probable, or definite) should be reported within 10 working days.

Adverse Event Expedited Reporting NOT required.

Report by phone to IDB within 24 hrs. Expedited report to follow within 10 working days.

This includes all deaths within 30 days of the last dose of treatment with an investigational agent regardless of attribution.

Any late death attributed to the agent (possible, probable, or definite) should be reported within 10 working days.

TABLE B: Expedited Reporting for Phase II and III Studies (including hospitalization^* )

UNEXPECTED EVENT

EXPECTED EVENT

GRADES 2 - 3 Attribution of Possible, Probable or Definite

GRADES 4 - 5 Regardless of Attribution

GRADES 1 - 3

GRADES 4 - 5 Regardless of Attribution

Expedited report within 10 working days

Grade 1 - Adverse Event Expedited Reporting NOT required.)

Report by phone to IDB within 24 hrs. Expedited report to follow within 10 working days.

This includes all deaths within 30 days of the last dose of treatment with an investigational agent regardless of attribution.

Any late death attributed to the agent (possible, probable, or definite) should be reported within 10 working days.

Adverse Event Expedited Reporting NOT required.

Expedited report, including Grade 5 Aplasia in leukemia patients, within 10 working days.

This includes all deaths within 30 days of the last dose of treatment with an investigational agent regardless of attribution.

Any late death attributed to the agent (possible, probable, or definite) should be reported within 10 working days.

Grade 4 Myelosuppression or other Grade 4 events that do not require expedited reporting will be specified in the protocol.

* For Hospitalization Only — Any medical event equivalent to CTC Grade 3, 4, 5 which precipitated hospitalization (or prolongation of existing hospitalization) must be reported regardless of requirements for Phase of study, expected or unexpected and attribution.

Expedited reporting may not be appropriate for specific expected adverse events for certain later Phase II and Phase III protocols. In those situations the adverse events that will not have expedited reporting must be specified in the text of the approved protocol. An expected Grade 3 event that is definitely related to the investigational agent is only to be reported if the patient is hospitalized using the generic reporting criteria, for instance. In a trial of an investigational agent where Grade 3 diarrhea requiring hospitalization is expected, only diarrhea requiring ICU care (Grade 4) might be designated for expedited reporting.

B. Trials of an investigational agent for which NCI is not the IND holder

The controlling regulations are those of the Food and Drug Administration (21 CFR, Part 312.32: Expedited Safety Reporting Requirements for Human Drug and Biological Products) and are available at http://www.fda.gov/cder/aers/fr07oc97.htm . They describe the responsibilities of the investigator and the IND holder. Additional sponsor or institutional requirements may be appropriate for specific agents and included in the pertinent protocol sections.

C. Trials involving commercially available agents only (no INDs involved)

Serious adverse events that occur with commercially available agents/devices are reported through Food and Drug Administration Medwatch (http://www.fda.gov/medwatch/index.html).

D. Trials involving recombinant DNA molecules (gene transfer)

In addition to the reporting requirements for investigational agents (see A or B above, as appropriate), investigators should adhere to NIH Guidelines for Research Involving Recombinant DNA Molecules (Gene Transfer).

(http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-052.html)

E. Food and Drug Administration reporting requirements of serious adverse events for post-marketing trials of vaccines (no cancer vaccines yet in this category)

Serious adverse events must be reported according to applicable FDA regulations (http://www.fda.gov/cber/vaers/vaers.htm).

F. Trials involving behavioral or nutritional interventions that do not use an investigational agent

Since there are no standard grading scales for adverse events, defining suitable grades for adverse events is the responsibility of individual investigators for each protocol. Adverse events of a psychological nature can occur with behavioral trials and should be specified for the particular intervention in question.

< Previous Section