Safety in the MTN
Ensuring participant safety is of utmost importance in all Microbicide Trials Network (MTN) studies. Close cooperation between study investigators, site staff, US Division of Acquired Immunodeficiency Syndrome (DAIDS) Medical Officers and other NIH Medical Officers, DAIDS Safety Pharmacovigilance Team (SPT), Protocol Safety Physicians (CORE PSP) Clinical Research Managers (CORE [FHI] CRM), Statistical Data Management Center (SDMC) Project Managers (PMs), and other members of the study team is necessary to monitor participant safety closely and to respond to occurrences of potential harm in a timely manner.
The Three Tier Approach
The MTN uses a three-tiered approach to review safety data in order to identify potential safety concerns in a timely manner.
Tier One
The first tier of clinical and laboratory data safety review involves study participants, study site clinicians, DAIDS Medical Officers, DAIDS RCC, DAIDS SPT, DIADS Regulatory Affairs Branch (RAB), and SDMC personnel.
Site clinicians are responsible for careful participant safety assessment and reporting of relevant clinical and laboratory data and for reporting AEs that meet the criteria for expedited reporting to the DAIDS RCC.
SDMC clinical affairs staff generates and reviews protocol-specific reports on a routine basis. SDMC clinical affairs staff also apply clinical data quality control notes (queries) to data requiring confirmation, clarification, or follow-up by site clinicians. These queries are sent to sites on a regular basis for resolution.
Tier Two
A Protocol Safety Review Team (PSRT) has been established for each MTN study involving an investigational agent or otherwise requiring AE reporting. This team includes at least one CORE PSP
the DAIDS Medical Officer, Protocol Chair, SDMC Protocol Statistician, SDMC clinical affairs staff, and others, depending on the protocol design and safety considerations.
For each study, the PSRT conducts routine reviews of safety data report. The PSRT will also convene to discuss any potential safety concerns. Depending on the nature of the study, the PSRT may have additional roles such as consultation and decision-making on AE reporting, toxicity management, and study product use management.
Tier Three
Phase IIb and III studies are reviewed by the US National Institute of Allergy and Infectious Diseases (NIAID) Vaccine and Prevention Data and Safety Monitoring Board (DSMB). The DSMB examines the accumulated endpoint and safety data to make recommendations to DAIDS concerning continuation, termination, or other modifications of the study based on the observed beneficial or adverse effects attributable to the product being studied.
Protocol Safety Physicians
In support of PSRT functions, the CORE Protocol Safety Physicians review all safety data reports and prepare and distribute a summary of each report to the PSRT members. In addition, the Protocol Safety Physicians work closely with the Safety Data Management Center to query the study sites for accurate, complete, and consistent AE reporting. Finally, the Protocol Safety Physicians field safety related queries from the sites and communicate consensus PSRT opinions or guidance to the site investigators related to safety data reporting, toxicity management, and/or study product use management.
There are three Protocol Safety Physicians.
Nancy Connolly, MD
Nancy graduated from medical school in 1997 and was trained in Internal Medicine and Infectious Disease specializing in the care of patients with HIV. She is currently practicing Internal Medicine at Virginia Mason Medical Center in Seattle Washington. Prior to becoming a physician, Nancy worked with the US Peace Corps and UNICEF on Guinea Worm Eradication efforts in Benin, W. Africa for two years.
Ross Cranston, MD
Ross graduated from the University of Edinburgh Medical School.. He holds United Kingdom Boards in General Internal Medicine, a Fellowship in HIV and Sexually Transmitted Infection, and a Doctorate in Medicine based on research performed at UCSF, San Francisco. Ross works in the Pittsburgh AIDS Center for Treatment (PACT). He is interested in the HIV co-infection with sexually transmitted infection and runs the PACT Anal Dysplasia clinic that is set up to screen and treat human papillomavirus (HPV) associated anal pre-cancer. In addition to his role as Protocol safety Physician, he also a Co-Investigator of MTN 007 and the Medical Director of the Pitt Men’s Study (Pittsburgh site of the Multicenter AIDS Cohort.
Katie Bunge, MD, MPH
Katie is a board certified Ob/Gyn. She graduated from Johns Hopkins University with a combined MD/MPH degree. She completed her Obstetrics and Gynecology residency at Northwestern Memorial Hospital in Chicago, IL. After residency she pursued additional training in Reproductive Infectious Disease at the University of Pittsburgh. She is currently an Assistant Professor in the Department of Obstetrics, Gynecology and Reproductive Sciences at the University of Pittsburgh, Pittsburgh, PA. Prior to becoming a physician, Katie worked with the US Peace Corps and the Human Development Center in Thailand to implement community based HIV prevention programs.