Multisite Clinical Trials in PBRN Toolkit
> Executive Summary
Nationally, there is increased interest in pragmatic, multi-center clinical trials to answer questions in real world, community settings about:
- Clinical effectiveness – Is a treatment beneficial?
- Comparative effectiveness – Are two treatments equally beneficial? and
- Safety – Are there harms to treatment(s)?
Pragmatic clinical trials (PCTs) measure the effectiveness that a community-, clinical-, or system-level intervention produces in routine clinical settings. (Concannon 2014). In these trials the unit of randomization can be an individual patient or provider, the practice, the health system, or a
practice-based research network (PBRN).
Primary Care PBRNs are an ideal setting for these PCTs. PBRNs are composed of community- and/or academically-affiliated practices that are committed to improving medical care on a range of health problems by conducting primary care research, engaging understudied populations, and accelerating adoption of new knowledge and best practices. Well over 100 PBRNs are registered with the Agency for Healthcare Research and Quality. In 2011 these PBRNs had a median of 32 practices and 219 physicians, and served a median of over 150,000 patients (Peterson 2012).
A number of PBRNs have conducted PCTs in community-based primary care
practices to evaluate treatment effectiveness and behavioral interventions for
chronic conditions (Bosworth 2009, Svetkey 2009,
Yawn 2012). For those PCTs, the lead investigator approached the PBRN leadership for assistance with trial design, procedures, and budgeting (during the proposal submission phase); practice recruitment, participant recruitment, and communications (during the enrollment phase); management of the trial (during the trial conduct phase); and interpretation of trial results, manuscripts, and presentations (during the closeout and dissemination phase). PBRN engagement was evident throughout the trials and acknowledgement of the PBRN contributions (including opportunities for co-authorship) was included in dissemination products.
This set of FAQs was created to guide researchers who are interested in conducting a PCT in a PBRN setting. They will help researchers understand how best to work with PBRNs and PBRN core teams, which, because of the trusted relationships they have developed with practices, is critical to a PCT's success. In addition, these FAQs will assist
PBRN directors and their teams in communicating with researchers about their PBRN’s project-specific needs. The
Glossary of Terms for PBRN Research Project Teams contains general descriptions of PBRN personnel and their roles to convey the methods for working with PBRNs on PCTs. However, PBRNs can have subtle differences in their network structure and governance that some of the terminology and procedures will vary across networks. Researchers should be aware of this inter-PBRN variability when they collaborate with more than one PBRN for their PCT.
Suggestions for additional content, revisions, or updates to content
should be sent to
Laura-Mae Baldwin, MD, MPH.
Suggested Citation: Baldwin L-M, Graham D, Schmit K, Dolor RJ, Fox C, Pace W. Toolkit for Developing and Conducting Multi-site Clinical Trials in Practice Based Research Networks.
http://www.dartnet.info/ClinicalTrialsBPRNToolkit.htm. Accessed on (insert date).
This toolkit was developed in collaboration with the DARTNet
Institute Research Steering Committee and the Clinical Translational
Science Award (CTSA) Practice Based Research Network Workgroup of the
Community Engagement Key Function Committee. The authors solicited
feedback from workshop attendees at the 2013 North American Primary Care
Research Group (NAPCRG) PBRN meeting. Please see the
Acknowledgements section for contributors to this toolkit.
Summary Table to Recommendations
|Recruiting, Engaging, and Maintaining Practices for a Clinical Trial in a PBRN
- Including a PBRN core team member on the academic research project team is critical to facilitate recruitment of practices to a trial.
- A simple one-page information sheet about the trial is extremely helpful for the recruitment process and for informing participating practices about the trial details, how it will impact the practice and what value it provides to the practice.
- Utilize different forums (e.g., PBRN meetings, e-mail, newsletters) to advertise the trial.
- Target practices in which there is already an interest in the trial’s topic and provide incentives (e.g., continuing medical education, financial incentives, quality improvement).
- Consider practical factors such as size of practice, scope of practice, and resources available when determining appropriate practices to approach.
- Involve primary care practices in the design of the trial and engage them in an ongoing advisory or participatory role.
- For each trial, minimize the work required by the practice and design the intervention to cause as little disruption to clinical care as possible.
- Provide adequate funding to the practices and reduce their burden of regulatory requirements.
- Provide adequate training for key practice clinicians and staff at the start of and as needed throughout the trial.
- Keep PBRN personnel involved in all the steps that involve the practices to maintain trusting relationships.
- Maintain ongoing communication between the
PBRN Research Project Manager and a key contact at each participating practice.
- At the completion of the trial, make sure to recognize the accomplishments and contributions of the participating practices.
• Keep the trial fun and interesting.
|Budgeting a Multisite Clinical Trial in a PBRN
- Although the budget process may vary among PBRNs, the most important aspect of budget development is to include the PBRN core team in the process to ensure that the budget is appropriate and realistic.
- Deciding who will hold the primary budget and who will serve as subcontractors will depend on whether the PBRN and/or the
Principal Investigator sit in an academic institution or a non-profit organization.
- Ideal timing for a rough draft of the budget is no later than 6 weeks before a grant proposal due date and a final budget, including sub-contracts, no later than three weeks before the due date.
- Non-profit PBRNs may provide budgeting advantages to a grant, such as lower indirect cost rates or efficient strategies for paying incentives and honoraria to patients and practices.
- It is important that a trial budget includes costs that are particular to working in a PBRN (e.g., practice honoraria, PBRN infrastructure costs, site visits).
- Linking practice payments to milestones is a good way to structure a budget.
- When budget cuts or changes are required, it is important that both the academic research project team and the PBRN core team make these decisions together.
- It is critical that the academic research project team meets its obligations to both the PBRN and the practices participating in the trial to maintain willing practice partners for future trials.
|Project Management of a Clinical Trial in a PBRN
- PBRN and practice representatives are essential members of the research project team, and it is important to involve them in all aspects of a clinical trial.
- The PBRN
central research project team members offer critical feedback and advice on how best to work with the member practices.
- PBRN research project personnel will vary depending on the particular PBRN and the specific clinical trial.
- Responsibilities for PBRN research project personnel will also differ for each trial so it is important to clarify who is responsible for which activities before the trial starts.
- For most studies, a
PBRN Research Project Manager will work closely with the academic research project team during all phases of trial implementation.
- In some studies an on-site
Practice Liaison/Research Project Coordinator will help to facilitate implementation of the trial within a practice.
- For a trial to run smoothly, it is imperative to create a Manual of Protocol Procedures that will clearly outline all trial procedures.
- It is important to develop a data sharing agreement that addresses issues such as data ownership prior to the commencement of a trial.
- Each trial should also use a regulatory binder to manage important documents.
- Ensuring quality requires detailed documentation of trial progress and maintenance of organized trial files.
- A clinical trial quality management plan can help to make sure that all issues that affect trial quality are being appropriately addressed.
- Regular communication between the academic research project team, the
PBRN on-site research project team and the participating practices is key to keeping all team members engaged in the trial.
- Offering opportunities for training and professional development is another strategy for keeping PBRN on-site research project team members engaged.
- It is important to understand all the steps necessary for closing out a trial and clarify who will be responsible for which steps.
|Communications when Collaborating on a Clinical Trial with a PBRN
- Given the number of collaborators involved with most studies involving PBRNs, it is important to establish clear lines of communication to ensure that a trial runs smoothly.
- Engaging the PBRN core team and/or PBRN
central research project team in communications with the practices at all phases of the trial is crucial.
- All research project team members should promote good communication, but the PBRN Coordinator often oversees this task with the help of the
Practice Liaison/Research Project Coordinator.
- Communication should be ongoing and updates should occur frequently.
- Effective communication should be multi-directional, recognizing and respecting the expertise that all collaborators bring to a trial.
- There are several different methods of communication (e.g., in-person, e-mail, phone conferences), and they should be tailored to the preferences of the collaborators.
- All trial-related communications should be stored on a secure server or website to facilitate access for members of the PBRN
central research project team and participating practices.
- It is important to engage PBRNs in publication and presentation opportunities when appropriate and to acknowledge the contribution of the PBRN and the
PBRN research project team members who are not authors in publications and presentations.
Bosworth HB, Olsen Mk, Grubber JM, Neary AM, Orr MM, Powers BJ, Adams MB, Svetkey LP, Reed SD, Li Y, Dolor RJ, Oddone EZ. Two self-management interventions to improve hypertension control: A randomized trial. Annals of Internal Medicine 2009;1515:687-695.
Concannon TW, Guise JM, Dolor RJ, Meissner P, Tunis S, Krishnan JA, Pace WD, Saltz J, Hersh WR, Michener L, Carey TS. A National Strategy to Develop Pragmatic Clinical Trials Infrastructure. Clin Transl Sci. 2014 Jan 28. doi: 10.1111/cts.12143. [Epub ahead of print]
Peterson KA, Lipman DB, Lange CJ, Cohen RA, and Durako S. Supporting better science in primary care: a description of practice-based research networks (PBRNs) in 2011. J Am Board Fam Med 2012;25:565-571.
Svetkey LP, Pollak KI, Yancy WS, Dolor RJ, Batch
BC, Samsa G, Matchar DB, Lin P. Hypertension Improvement Project (HIP):
Randomized Trial Of Quality Improvement For Physicians And Lifestyle
Modification For Patients. Hypertension 2009; 54:1226-33.
Yawn BP, Dietrich AJ, Wollan P, Bertram S, Graham D,
Huff J, Kurland M, Madison S, Pace WD. TRIPPD: a practice-based network
effectiveness study of postpartum depression screening and management.
Ann Fam Med. 2012 Jul-Aug;10(4):320-9.