How Studies Are Created and Monitored

The Pediatric Heart Network (PHN) is a cooperative effort between participating medical centers, a data coordinating center, an independent Network chair, and National Heart, Lung, and Blood Institute (NHLBI) staff. All entities work together to:

• Propose pertinent and timely research ideas
• Develop protocols
• Conduct research studies
• Monitor patient safety and data
• Disseminate the research findings

Study Proposals

Principal Investigators and affiliated investigators propose new areas of research to the PHN Steering Committee for review and consideration as Network Studies. New ideas emerge from formal and informal discussion among the PHN Steering Committee members, co-investigators at participating institutions, and also from outside investigators who wish to propose an idea to the PHN. A written proposal is composed by the investigator(s) and is presented to the entire PHN Steering Committee during an in-person meeting or conference call. Issues such as selection of a meaningful study endpoint, feasibility of proposed study procedures, availability of adequate numbers of patients, clinical center support, and clinical relevance of the study are discussed extensively. Study proposals approved by the PHN Steering Committee are then developed into a full study protocol.

Protocol Development

Following approval by the PHN Steering Committee, a subcommittee is established to develop the full study protocol. One investigator from each medical center, at least one nurse/study coordinator, a biostatistician and project manager, as well as NHLBI staff participate on the protocol subcommittee. If additional sites outside of the PHN are chosen for a particular study, the new investigators will work on the existing subcommittee with the other PHN investigators to develop the study protocol. The subcommittee defines the primary and secondary endpoints, the study procedures, data collection and analysis, and also provides the PHN Steering Committee with regular updates (during monthly conference calls) throughout the development process.

Protocol Review Committee (PRC)

After the study protocol is completed by the subcommittee and approved by the PHN Steering Committee, the protocol is reviewed by the PRC. The PRC is an independent group appointed by NHLBI and made up of experts within the fields of pediatric cardiology, pediatric cardiothoracic surgery, pharmacology, clinical trial design and analysis, ethics and genetics. The responsibility of the PRC is to provide scientific peer review of protocols developed within the Network. They assess the protocol based on the following criteria:

• Importance of the question being asked
• Need for a multi-center design to meet the objectives
• Merit of design and controls
• Adequacy of patient population
• Appropriateness of recruitment strategies
• Adequacy of data collection and overall monitoring

The PRC may recommend that a protocol be approved as written, request certain changes to the protocol, or recommend that the concept not be considered for further development.

Data Safety and Monitoring Board (DSMB)

After approval by the PRC, the protocol, model consent forms, and data collection forms are then reviewed by the DSMB . The purposes of this NHLBI supervisory board are to ensure the safety of study subjects and to provide advice on the ethical and safe progression of studies conducted by the PHN. Modifications to the study protocol may be requested by the DSMB. Once the final study protocol is approved by the DSMB, the protocol is ready to go to the Institutional Review or Research Ethics Boards at the individual clinical centers.

Monitoring Patient Safety

Institutional Review Board (IRB)/Research Ethics Board (REB)
Each clinical center submits the protocol, consent forms, patient education materials, advertising materials, and other required documentation to their IRB/REB . These boards are chosen by an institution to review and approve the new research studies and to provide on-going review of the conduct of these studies. Their primary purpose is to assure the protection of human subjects. The board may ask that changes be made before allowing the research team to begin the study at their hospital or clinic.

Data Safety and Monitoring Board (DSMB)
As indicated above, the DSMB reviews each study on a regular basis to make sure that participants are safe and that the study data is reliable. The PHN DSMB meets every six months (or more often if needed) to:

• Assess how well each clinical site is performing
• Review adverse events
• Suggest possible early termination of the study because of lack of attainment of study objectives, safety concerns or poor recruitment
• Recommend possible modifications to the protocol

Training/Certification
One or more training sessions are held for the research staff (study coordinators, technicians, etc…) prior to the start of any study conducted by the PHN. Each center must complete certain certification requirements including familiarity with study procedures, methods of endpoint measurement, use of the database system and designation of staff who will conduct the study.

Site Visits
Site visits are routinely made to assess the medical center’s proficiency in executing the study protocols, to assess data quality and completeness, and to provide consultation in identifying and solving problems. The site visit team will generate a formal written report of the site’s areas of excellence and recommendations for improvement. Problem areas will be identified and timelines will be given to the clinical site for documentation of improvement.