Introduction

Multicenter impactful small trials (MISTs) have become increasingly common in the urology literature. Their adoption likely stems from multiple reasons—most obviously as an expeditious means to completing studies. However, other less obvious benefits include sharing of resources, cross-pollination of ideas, internal review process, financial benefits, and fostering collegiality. Here we are excited to share our key elements and common barriers encountered when designing a MIST working group. A sample list of operational working groups within the field can be found in the Table.

Table. Urology Research Working Groups

	Name of group	No. publications	Logo
SWOG	Southwest Oncology Group	5349
PCCTC	Prostate Cancer Clinical Trial Consortium	400+
LURN	Symptom of Lower Urinary Tract Dysfunction Research Network	35
EDGE research consortium	Endourology Disease Group of Excellence	32
PLUS	The Prevention of LUTS Research Consortium	30
TOWER	Endourologic Society	27
SUO-CTC	Society of Urologic Oncology Clinical Trials Consortium	27
USDRN	Urinary Stone Disease Research Network	17
NASQoL Consortium	North American Stone Quality of Life Consortium (WISQOL)	14
PIONEER Consortium	PIONEER Consortium	11

Key Elements

While there are many ways to complete a MIST, we present some suggested best practices when designing and carrying out these types of studies, as corroborated from MIST leaders within the field of urology.

Study leadership

According to Vaneet Gauhar, MD (Ng Teng Fong General Hospital, Singapore, email, July 2023), “There has to be one key person is necessary to take initiative and be persuasive.” Alternatively, a core group of individuals can lead the initiative. The leader(s) ensures clear conception, implementation, and execution. For selecting the research question, the acronym FINER (feasible, interesting, novel, ethical, relevant) can be helpful.¹ The leadership maintains the broad overview while ensuring milestones are accomplished.

Center recruitment

Center recruitment involves taking advantage of one’s network within the field. After a list of candidate sites are created, a discovery meeting then permits an open discussion among potential sites. Social media can be a tool to promote exposure of the research idea and facilitate center recruitment, though personal relationships are a more natural method to collaborate. Site selection might be the single most important component of this process. A single site’s failure can lead to mission failure. Thus, the vetting process cannot be overemphasized, as it is better to have a few engaged sites than many sites with unclear motivation.

Follow-up and progress tracking

Periodic multicenter meetings to track progress, maintain morale, and communicate updates are critical. Having a meeting “on the books” maintains a cadence. While in-person working group meetings may be scheduled at annual national or regional meetings, telephone or video-based meetings are convenient. Kristina L. Penniston, PhD, RDN, CD, FAND (University of Wisconsin, Madison, email, July 2023), a MIST leader, recommends compiling and disseminating periodic progress reports including enrollment, data, etc, to all participants to maintain working group engagement.

Scholarship and authorship

The multi-institutional nature of the study necessitates clear, open, and honest communication regarding expectations. Authorship should be decided for each publication prior to study inception. Ground rules should be established at one of the first meetings and reinforced at subsequent meetings. Communications should be documented in written form and distributed to all centers. Given that submission for many journals now requires documentation of each author’s specific contributions, maintaining these records prospectively facilitates this process.

Barriers to an Effective Multicenter Working Group

Communication issues

Communication issues can pose a significant barrier to success. Again, the vetting of reliable sites that communicate well avoids this problem. Challenges such as different time zones, geographical distances, cultural differences, language barriers, and time-consuming meetings can also impede effective communication. However, these barriers are surmountable when sites agree up front to communicate well.

Figure. Keys to an effective multicenter impactful small trial working group. IRB indicates institutional review board.

Regulatory compliance

Managing multicenter trials unfortunately carries increased administrative burdens, predominantly due to institutional review board (IRB) requirements. IRB can either be conducted at individual sites or performed through a central site—either through a principal site IRB or commercial IRB (eg, Western IRB, BRANY IRB, Sterling IRB, Advarra, National Cancer Institute Central IRB). While maintaining IRB compliance within a MIST may seem daunting, utilization of shared resources can effectively cut the time and effort required. Moreover, the IRB process permits an internal review of the methodology, potentially avoiding post-IRB approval changes. As part as their leadership role, the central data collection/coordination center should draft the IRB protocol and provide IRB materials to other sites (Penniston, July 2023). Additionally, pursuing IRB expedited review or exemption can dramatically reduce lag time in the project.

Data quality and standardization

Data quality and standardization present challenges. Variations among participant baseline characteristics, operational resources, and data collection methods can undermine data quality. However, use of online clouds (eg, Research Electronic Data Capture [REDCap]) where data is entered with dropdown/radio buttons keeps the data clean—minimizing write-in answers (which can increase complexity of data and risk of entry errors/missing data). Online clouds can then be transformed into analyzable data. Additionally, these tools are often HIPAA (Health Insurance Portability and Accountability Act of 1996) compliant and maintain patient privacy. We recommend avoiding storing data on local computer drives as they are typically not as secure and risk data loss or compromise.

Statistics and power analysis

Statistics and power analysis encounter hurdles due to differences in disease incidence across centers, which complicates sample size calculation. Variability in recruitment rates and participant retention among centers can adversely affect a study’s statistical power and its ability to derive meaningful conclusions. We have found that subject enrollment can be a very rate-limiting step. Sites may underestimate how difficult it is to accrue subjects. Competing studies also affect enrollment. Again, this principle reinforces vetting the sites.

Funding

Funding is not always possible and not even necessary depending on the complexity of the study design. However, securing funding does provide advantages, such as covering IRB costs, clinical research coordinator coverage, and laboratory/device charges. Investigators should thoroughly seek both institutional or extramural funding options (governmental, industry based, or even philanthropy based). Governmental funding is excellent for large studies but clearly competitive. Industry- or even philanthropy-based support can be easier entry-level support. The authors view application submission helpful even when grant support is not approved, since it demonstrates investigator interest and the potential for future approval.

Conclusion

Multicenter small trials are an excellent method for conducting studies. The principles of success (Figure) include vetting reliable partners, up-front expectations, frequent communication, clean data, and creative funding. The rewards of such an undertaking not only lead to meaningful research, but also create relationships that are the basis for future collaborations.

Support

Boston Scientific funding for a joint UC San Diego–Kaiser Permanente Laparoscopic-Endourology fellowship.

Conflict of Interest Disclosures

The Authors have no conflicts of interest to disclose.

Acknowledgments

We thank Kristina L. Penniston, PhD, RDN, CD, FAND, of the University of Wisconsin in Madison and Vaneet Gauhar, MD, of Ng Teng Fong General Hospital in Singapore for their contribution of ideas to the article.