Frequently Asked Questions about Project Management of a Clinical Trial in a PBRN
Clinical Trial Development Phase
Clinical Trial Conduct Phase
Clinical Trial Close-out Phase
Clinical Trial Dissemination Phase
Clinical Trial Development Phase
Practice-based research is distinctive because PBRN and practice representatives (e.g., PBRN investigators, Practice Lead Physicians/Clinicians) are essential members of the research project team. These PBRN and practice representatives are critical in the planning stage of a clinical trial. They provide critical feedback on the feasibility of implementing the trial protocol in practices given their specific local requirements. Early engagement of these team members is essential for implementation of the trial protocol. (Graham 2007)
Most clinical trials involving PBRNs will include the following team members, although the titles and responsibilities may differ in each PBRN:
Principal Investigator (PI): The individual who is responsible for oversight and direction of the clinical trial. This is usually a faculty member at an academic institution, but could be a physician who is in a leadership role at a PBRN. This individual is responsible for the management and integrity of the design, conduct, and reporting of the clinical trial and for managing, monitoring, and ensuring the integrity of any collaborative relationships. This individual is responsible for communicating research project updates, changes, or problems to research project team members and funders (as appropriate), and for communicating with research project consultants.
PBRN Director: The PBRN Director is usually a clinician or researcher who has responsibility for PBRN operations and for overall PBRN management, and sets the direction for the PBRN mission, goals, oversight, opportunities and collaborations. The Director identifies research investigators to work with the PBRN, reports to a governing board, and reports to any other entities to which the PBRN is responsible (e.g., University). The PBRN Director frequently serves as a research project PI or co-PI. The Director communicates regularly with PBRN Coordinator and other PBRN staff.
PBRN Coordinator: The PBRN Coordinator, sometimes known as the Network Coordinator, is a member of the PBRN core team, and is responsible for managing the daily operations of the PBRN. This includes primary hiring, training and oversight of staff; and assignment of staff to research projects. This individual is responsible for communicating with other PBRN core team members about the status of research projects in the PBRN. The PBRN Coordinator communicates regularly with PBRN Director. The PBRN Coordinator often serves the role of PBRN Research Project Manager.
PBRN Research Project Manager: The PBRN Research Project Manager is a member of the PBRN core team and the PBRN central research project team who manages and organizes the PBRN-based activities of an individual research project. This may include the following types of activities, all specific to the research project: hiring, training and supervising PBRN research project team staff; maintaining communications across the PBRN research project team; assigning tasks to research project staff; coordinating roles to complete the PBRN-based research project; ensuring adherence to research project procedures and timelines; overseeing research project recruitment and follow-up activities. The PBRN Research Project Manager serves as the PBRN central research project team contact for both participating practices and the academic research project team and/or PI. If the PBRN is the prime organization for a research project, then the PBRN Research Project Manager may manage and organize the research project overall.
PBRN staff: Staff such as Practice Liaisons/Research Project Coordinators and Research Assistants are vital to completing clinical trials in a PBRN. These roles may overlap with that of the Practice Facilitator (see next). These staff members are generally supervised by the PBRN Research Project Manager.
Practice facilitators (PF): Practice Facilitators are members of the PBRN on-site research project team. The role of the PF in conducting practice-based research and the relationship the PF maintains with the PBRN practices make PBRN studies unique. Within the PBRN, the PF can function as a Research Project Coordinator or Research Assistant, and as a practice enhancement resource to practices. PFs also function in a manner similar to an agricultural extension agent, sharing ideas and successes across practices within the region served by the PF. Practice Facilitators are generally supervised by the PBRN Research Project Manager. Not all research project teams include practice facilitators.
Practice Lead Physician/Clinician: Practice Lead Physicians/Clinicians are physicians or clinicians practicing at PBRN sites who are responsible for communicating information regarding all phases of the research project with other practice providers and staff. They work closely with the PBRN central research project team (e.g., PBRN Research Project Manager) and on-site staff involved in the research (e.g., Practice Liaison/Research Project Coordinator, Research Assistants, Practice Facilitators). The Practice Lead Physician/Clinician serves as a leader for the research project at the practice. Some multisite trials designate this person as the "Site PI."
Site Principal Investigator (PI): In a PBRN, this role in a multisite clinical trial is generally held by the Practice Lead Physician/Clinician (see above), and sometimes by a PBRN Investigator/Senior Scientist, depending on the organizational structure of the PBRN.
The PBRN Director and PBRN Coordinator will offer the grant writing team critical feedback on the effort required by the PBRN central research project team and its affiliated practices to implement the clinical trial. Additional activities may include:
- Providing the grant writing team with standard descriptions (e.g., PBRN descriptions, research environment, and resources)
- Advising and negotiating payments to the practices
- Working with the budget office or its designee and/or collaborators to finalize the budget
- Reviewing draft research plans and making revisions
- Obtaining letters of support (e.g., practices, community stakeholders, institutional officials).
3) How should tasks be divided between the academic research project team, PBRN central research project team, and PBRN on-site research project team members?
Responsibilities will differ for each clinical trial. Prior to the start of the trial, it is imperative to determine whether the academic research project team, the PBRN central research project team, or the PBRN on-site research project team will perform tasks such as the following:
- Develop and submit IRB/regulatory paperwork
- Generate list of potential patients for the trial
- Mail/e-mail recruitment letters
- Conduct telephone screening calls
- Conduct informed consent process with patients (paper or electronic, on-site or remotely)
- Collect surveys (clinic, mail, telephone, on-line)
- Conduct trial procedures (labs, radiology, clinical exams)
- Enter data
- Monitor the conduct of the trial (adherence to consent procedures and study intervention, assessment of data quality)
- Provide financial payments (to patients, practices)
Clinical Trial Conduct Phase
The PBRN central research project team plays a key role in the ongoing conduct of the clinical trial because of its established research relationships with the practices. For most studies, a PBRN Research Project Manager will be assigned to coordinate clinical trial implementation with the academic research project team. Specifically, the PBRN Research Project Manager would have the following roles:
- Attend (and if necessary convene) clinical trial team meetings
- Communicate with other PBRN central research project team members and PBRN on-site research project team members about trial implementation
- Communicate requests for information to participating practice staff as required by the trial
- Serve as the PBRN central research project team contact for both participating practices and the academic research project team and/or PI
- Assist, as necessary, with creation of practice-friendly clinical trial protocols and procedure manuals, and any additional trial documents (e.g., fliers, posters, one-page overviews).
- Maintain trial documentation (electronic and hard copies)
- Complete IRB applications as necessary
- Monitor compliance with human subjects training of key trial personnel (including PBRN staff and practice staff)
- Monitor the informed consent process for the practice site
- Advocate for participating practices during the trial
- Assist the PI with other duties as assigned
The PBRN Research Project Manager and PBRN central research project team may manage the trial directly or they may work closely with an on-site Practice Liaison/Research Project Coordinator who manages on-site trial implementation. The Practice Liaison/Research Project Coordinator is the key practice contact for the PBRN central research project team. This person should:
- Understand the mission of the PBRN
- Maintain timely and ongoing communication with the PBRN central research project team
- Complete trial-specific and general PBRN-related tasks as assigned
- Oversee implementation of PBRN clinical trials on-site, ensuring completion and accuracy of all trial tasks
- Promote importance of conducting PBRN trials with clinicians and other practice staff
- Assist with scheduling PBRN meetings and trainings at the practice
- Attend trial-specific training and meetings and other PBRN meetings as required
The first step is to create a Manual of Protocol Procedures. The purpose of the Manual is to outline all trial procedures that the PBRN and Practice Liaison/Research Project Coordinators should follow to ensure intervention fidelity and quality of data collected. This should include, as appropriate or needed:
- Plan for completing IRB continuation applications
- Plan for completing IRB reportable event forms
- Recruitment plan
- Trial procedures/timelines
- An overview of major steps and procedures/protocols for the trial, including when each step takes place, what is to be done, and which trial personnel are involved and/or responsible.
- Documentation of trial procedures/protocols such that any trial personnel joining the team after trial inception could easily understand trial flow and major steps.
- Display of trial procedures/protocols in the form of a graphical representation of timeline with key milestones
- Copies of forms to be used for documentation of IRB and protocol training
- Plan for data and database management
All collaborators (e.g., lead academic institution, PBRN central research project team, and practices) on a trial should take part in designing a data use agreement. Furthermore, a participating practice or community partner may request access to data collected within a PBRN for local dissemination purposes (e.g. to present the results from their practice or community at local meetings or newsletters).
Each trial should create a regulatory binder. This binder may be managed by the PBRN Research Project Manager or by a Practice Liaison/Research Project Coordinator who has received full IRB training. Depending on the type of trial, this binder may include:
- Trial protocol
- Regulatory forms
- Curriculum Vitae (CV) of the clinical trial investigators
- Approved consent forms/waivers
- IRB approvals and correspondence
- Trial logs
- Documentation regarding Adverse Events
- Laboratory protocols
- Drug/device accountability
Quality management involves detailed documentation of trial progress and maintenance of organized trial files; this is required when a trial is audited by an external monitor. The PI is responsible for developing and implementing a process for managing the quality of the trial. A member of the academic research project team will monitor the quality of the trial and inform the PBRN central research project team when monitoring visits to the PBRN central research project team office and individual practices will occur.
The first step is to create a clinical trial quality management plan. This should outline:
- Responsibilities of key members of the clinical trial team for maintaining quality
- Communication plan for quality issues
- Plan for program and systems audits
- Plan for data management and data quality audits
- Plan for documentation processes
- Plan for correcting problems
Then the following should occur according to the review timeline developed in the trial protocol:
- Review plan periodically to assess if it needs revision/update
- Monitor data quality frequently
- Ensure appropriate documentation and form completion
- Present pertinent findings to the trial team and PBRN partners (as appropriate)
- Develop and disseminate solutions to issues discovered as part of the quality management review
- Ensure solutions are implemented
Communication is key to keeping PBRN on-site research project team members engaged. The academic research project team should work with the PBRN central research team to create and disseminate the communication materials. Below is an outline of good communication practices:
- Schedule regular meetings with PBRN on-site research project team members (weekly initially and decreasing frequency as appropriate)
- Schedule meetings far in advance and cancel if not needed, as it can be difficult to schedule meetings with individuals from the practices
- Provide agendas for meetings
- Provide PBRN on-site research project team members with trial recruitment updates, e.g., number consented or enrolled
- Distribute minutes of all meetings to all interested parties
- Identify action steps and person responsible to complete actions; include due dates if possible.
- Provide regular trial recruitment updates and other communications to participating practices. The trial update can be the same as that given to the PBRN on-site research project team, or a shortened version with only the enrollment information and trial timeline, and removal of the trial-specific procedures that are not pertinent to the practices.
Another way to keep PBRN on-site research project team members engaged is to offer the opportunity for additional training. Opportunities for training and professional development enable staff to further develop interests and skills that may benefit their role within the PBRN, propel career goals, and lead to increased personal fulfillment.
Clinical Trial Close-out Phase
The clinical trial close-out phase may be conducted if the following are completed:
- Enrollment is completed.
- Trial-related intervention is completed.
- Participant follow-up is completed.
- Data are de-identified.
- Biological specimens are de-identified.
- Trial sponsor agrees to close the trial.
The following are required during the clinical trial close out phase:
- Submit an IRB project closure form, terminating the trial.
- Determine how long documents need to be kept.
- Label and store paper copies of materials (i.e., informed consent documents) in locked storage according to agency and local IRB policy.
- Shred paper files of patient identifiers linked with data.
- Ensure that electronic files containing patient identifiers have been deleted.
- Ensure that e-mails containing patient identifiers have been deleted.
- Notify PBRN research project team and PBRN practices of study closure.
- Provide preliminary study findings to participating PBRN practices.
- Destroy investigational products and maintain documentation of the destruction.
- Provide final reports to regulatory authorities and funding agency.
- Financial close out with accounting office.
Responsibilities will differ with each study, but it is important to decide who will be responsible for the following tasks prior to the start of the clinical trial:
- IRB final report
- Resolution of queries related to the database (e.g., inconsistencies, out of range values)
- Final payment to subjects and practices
- Final financial reports (e.g., to federal agencies)
Clinical Trial Dissemination Phase
PBRNs strive to report their important results in peer-reviewed publications and presentations. Publications that align with the PBRN mission are important to advance the PBRN and its reputation.
In addition to the PBRN central research project team members, it is ideal for PBRNs to engage one or more PBRN governing/advisory committee representatives during study execution and data analysis to gather feedback from a different perspective (non-research clinician or community representative).
Include PBRN central research project team members who contributed significantly to the study as authors.
Ensure a PBRN governing/advisory committee representative and a member of the PBRN leadership reviews each manuscript to ensure alignment with the PBRN mission and, if appropriate, PBRN publication guidelines.
Individuals from the PBRN central research project team who may have made some contribution to a publication, but who do not meet the criteria for authorship, should be listed in an acknowledgement and/or contributorship section of the work.
It is important to keep the participating practices and patients in the loop by providing information on trial results and publications through letters, e-mail or newsletters. See Frequently Asked Questions about Communication when Collaborating on a Clinical Trial with a PBRN for more detail.
Literature cited: Graham DG, Spano MS, Stewart TV, Staton EW, Meers A, Pace WD. Strategies for planning and launching PBRN research studies: a project of the Academy of Family Physicians National Research Network (AAFP NRN). J Am Board Fam Med. 2007 Mar-Apr;20(2):220-8. [full text]
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