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Ann Melvin, MD
Associate Program Director, Research Subject Advocate Program
Office: CHRMC W-7871
Mailstop W-6605
(206) 987-2535
ann.melvin@seattlechildrens.org

DSMP Example: DSMP for a Phase I study of an investigational oncology drug, which also requires an IND from the FDA

This is a risk-level IV, Phase I investigation that will be monitored according to the PBTC (Pediatric Brain Tumor Consortium) Data Safety and Monitoring Procedures (provided).

The expected risks attributable to this study agent and the procedures developed to minimize the risks are detailed in section X of this application.

All study data will be entered into the PBTC data base system on a real-time basis. The data is entered onto a password protected secure laptop computer. It is then uploaded using secure technology to the PBTC operations and biostatistics center (OBC) located at St. Jude in Memphis, TN.

Oversight for this trial at CHRMC will be provided by the PI and/or designated study personnel. They will review all inclusion/exclusion criteria and will ensure that the study is carried out according to the IRB and SAC approved protocol. They will follow all study participants on a real-time basis for the development of adverse events and study endpoints. They will monitor physical and neurologic symptoms as well as the results of hematology labs and chemistries on a real-time basis for as long as patients continue study treatment. They will assure that all adverse events are reported according to the above guidelines, that the CHRMC IRB is notified of any significant data and safety concerns which arise as the result of the study team's, monitoring committee's and/or DSMB's reviews, and that all monitoring reports are provided to the CHRMC IRB and PSAC. They will provide an annual report of all adverse events and a summary of the investigation to the CHRMC IRB and PSAC and notify the IRB and CRC within 15 days if the study has been stopped or placed on hold.

Adverse events will be graded according to the NCI Common Toxicity Criteria version 2.0 scale. For this trial, serious adverse events that will require expedited reporting include:

• Death
• A life-threatening adverse event drug experience.
• A persistent or significant disability/incapacity.
• For the purposes of this study, in-patient hospitalization or prolongation of existing hospitalization for the following reasons are not considered to be events for reporting: study drug administration, transfusional support, disease staging/re-staging procedures, concomitant radiotherapy, placement of indwelling catheter, or other elective procedures associated with conventional medical practice, unless associated with other serious adverse events.
• A congenital anomaly/birth defect.

Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered a serious adverse drug experience when, based upon appropriate medical judgment, they may jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in in-patient hospitalization, or the development of drug dependency or drug abuse.

These SAEs will be reported within 24 hours to the study chair, and the PBTC OBC and within three days to the CHRMC IRB and PSAC. The PBTC OBC will report the SAEs to the FDA. All dose-limiting toxicities will also be reported within 24 hours to the study team. All unexpected serious adverse events as defined by the ICH guidelines should be captured by the above SAE criteria, but if not, these will also be reported to the study chair, study sponsor and CHRMC IRB and PSAC according to the CHRMC IRB reporting guidelines. In addition, all toxicities (expected and unexpected) grade I and above will be reported to the operations and biostatistics center (OBC) for distribution to the study team. These will be summarized in the weekly monitoring reports given to study chairs.

Primary monitoring for this investigation will be provided by the study team. They will review accrual, adverse events and dose-limiting toxicities on a real time basis. In addition, all adverse events and study toxicities will be reviewed on a weekly basis by the PBTC Monitoring committee. Decisions regarding dose escalation, stopping accrual and concluding that the MTD has been reached (see section X) will be made by the study team. All decisions will be reviewed by the PBTC Data and Safety Monitoring Board at 6-month intervals.

Monitoring reports will generated by the DSMB on an annual basis. These will be provided to the CHRMC IRB and PSAC by the site PI or designated individual. These reports will include the date of DSMB review of the study, composition of DSMB and members participating in the review, a statement that adverse events were reviewed and that data relating to overall safety and efficacy were reviewed consistent with the study design, conclusion of the DSMB with the exception of confidential information, a statement that more information is available via the internet or by contacting the PBTC OBC, and a statement that additional information about the PBTC DSMB policy is available at the PBTC website or from the OBC.

Dr. X can be reached by calling the HemOnc clinic at X or by pager X. X is the nurse practitioner that cares for all brain tumor patients and she can be reached at extension X or by pager X. If the CRC needs to contact a physician during evening or night time hours, they may page the HemOnc fellow on call.

This protocol will be reviewed by the PBTC DSMB every six months according to Appendix 1. The composition of the DSMB is detailed in Appendix 1 and the contact information for the chair of the DSMB is available by contacting the PBTC OBC protocol coordinator X at X.