Author: Connor Brenna, MD
The Daily Dose
Published clinical trials often appear straightforward. They present a focused research question, organized methods, and clearly reported findings. However, the final publication rarely reveals the failed approaches, funding rejections, regulatory delays, recruitment problems, and strategic decisions that occurred behind the scenes.
A session at the 2026 IARS and SOCCA Annual Meeting examined the practical challenges of leading a first multicenter or industry-funded clinical trial. The speakers emphasized that successful research requires more than an important question. It also demands strong mentorship, careful planning, teamwork, protected time, adaptability, and persistence.
Leading a First Multicenter Trial
Jessica Spence, MD, PhD, discussed lessons learned while leading the B-Free trial.
B-Free was a pragmatic, multiple-period, cluster-randomized crossover trial conducted at 20 cardiac surgical centers in North America. The trial included 19,768 patients and compared liberal with restrictive intraoperative benzodiazepine administration.
Restricting benzodiazepine use did not significantly reduce postoperative delirium. Although the primary clinical finding was important, the experience of coordinating such a large trial also provided valuable lessons for early investigators.
Find the Right Mentors
A new investigator should develop relationships with several mentors rather than relying entirely on one person.
Different mentors may provide expertise in:
• Study design
• Statistics
• Grant applications
• Clinical trial operations
• Regulatory requirements
• Leadership and career development
• Scientific writing
Mentors can help investigators avoid common mistakes, but the research question must ultimately belong to the investigator.
Choose a Question You Truly Care About
A first trial should address a question that the investigator believes is important.
Clinical trials may take years to design, fund, conduct, analyze, and publish. A researcher who is only working on a mentor’s project may have difficulty maintaining enthusiasm when delays and setbacks occur.
Personal commitment to the research question can provide the motivation needed to continue through rejection, recruitment difficulties, and operational problems.
Keep the Trial Simple
Simplicity is especially important in multicenter trials.
Every additional procedure, assessment, data field, or protocol requirement increases the possibility of:
• Staff confusion
• Protocol violations
• Missing information
• Recruitment delays
• Increased costs
• Differences among participating centers
A trial should collect the information necessary to answer the research question without creating unnecessary burdens for patients or participating sites.
Seek Feedback From Multiple Sources
Investigators should seek advice not only from senior researchers but also from research coordinators, statisticians, clinicians, patients, and participating centers.
Patients may identify burdens or concerns that researchers have overlooked. Coordinators may recognize operational problems that are not apparent in the written protocol. Participating centers may determine that certain study requirements are unrealistic within ordinary clinical workflows.
Early feedback can prevent major problems after the trial begins.
Build the Right Team
Clinical research is a team activity.
A successful trial may require:
• Clinicians with relevant subject-matter knowledge
• Statisticians and methodologists
• Research coordinators
• Regulatory specialists
• Data-management personnel
• Patient representatives
• Participating-site leaders
• Administrative and financial support
Formal qualifications are valuable, but practical experience is equally important. Team members who have previously managed recruitment, consent, data collection, and regulatory submissions can help translate a research protocol into a functioning trial.
Select Participating Sites Carefully
A prestigious institution is not automatically a productive trial site.
Partner centers should have genuine interest in the research question, appropriate patient volume, local leadership, available personnel, and the ability to follow the study protocol.
Before choosing a site, investigators should evaluate:
• Expected recruitment volume
• Availability of research staff
• Institutional support
• Previous trial performance
• Local regulatory timelines
• Enthusiasm from clinical leaders
• Competing studies
A smaller, highly committed center may outperform a larger institution without sufficient local engagement.
Do Not Take Delays or Rejection Personally
Grant rejection, regulatory delay, slow recruitment, and unsuccessful submissions are normal parts of clinical research.
Investigators should evaluate criticism objectively, revise the project when appropriate, and submit again. Rejection does not necessarily mean that the research question lacks importance.
Persistence is often what separates an abandoned idea from a completed trial.
Write Frequently and Clearly
Clinical investigators must become effective writers.
Writing is required for:
• Study protocols
• Ethics submissions
• Grant applications
• Statistical-analysis plans
• Investigator manuals
• Presentations
• Manuscripts
• Responses to reviewers
Researchers should consider publishing trial protocols and methodological papers in addition to the final study results. These publications improve transparency and allow investigators to receive academic credit throughout a lengthy research program.
Protect Time for Deep Work
Major research projects cannot be completed entirely during brief intervals between clinical responsibilities.
Investigators need protected periods for concentrated thinking, writing, data review, and strategic planning. Without protected time, urgent clinical and administrative demands may repeatedly displace important research work.
Leading a First Industry-Funded Trial
Ashish Khanna, MD, MS, discussed lessons from ATHOS-3, his first major industry-supported trial.
ATHOS-3 evaluated angiotensin II in patients with vasodilatory shock that did not adequately respond to conventional vasopressors. The study demonstrated that angiotensin II could increase blood pressure in these critically ill patients.
The trial also presented substantial recruitment and operational challenges because eligible patients had severe shock and required urgent treatment. Decisions regarding enrollment and consent therefore had to occur under difficult clinical conditions.
Be Nimble
Industry-funded trials may progress rapidly and may not wait for ideal academic circumstances.
Investigators must be prepared to respond quickly to:
• Protocol changes
• Sponsor requests
• Regulatory deadlines
• Recruitment problems
• Safety concerns
• Data questions
• Operational changes
Flexibility is essential, but changes should never compromise patient safety or scientific integrity.
Anticipate Problems Before They Occur
Trial leaders should identify potential obstacles during the planning stage.
Questions to address include:
• Will eligible patients be available?
• Can informed consent be obtained in time?
• Is the protocol compatible with clinical workflow?
• Are treatments and equipment available around the clock?
• Who will enroll patients during nights and weekends?
• What competing trials may reduce recruitment?
• How will protocol deviations be addressed?
• What happens if a participating center underperforms?
Proactive planning is more effective than repeatedly reacting to preventable problems.
Aim for Excellence
A high-quality trial does not occur accidentally.
Investigators should establish high standards for recruitment, data completeness, protocol adherence, communication, and scientific analysis.
This does not mean that a first trial must be the largest study in the field. It means that every aspect of the project should be performed as carefully and reliably as possible.
Understand and Own the Data
Trial leaders should understand the underlying data rather than focusing only on the final results.
Investigators should know:
• How variables were defined
• How information was collected
• Which data are missing
• How protocol deviations were handled
• Whether outcomes were consistently measured
• Which analyses were planned in advance
• Whether unexpected findings are clinically plausible
Industry sponsors, statisticians, and contract research organizations may assist with data management, but the clinical investigator remains responsible for understanding the study.
Build a Continuing Research Program
Dr. Khanna recommended following a “plan-grant-next” cycle.
Each trial should contribute to a larger scientific program:
- Plan and conduct the current study.
- Use the findings to support publications and new grant applications.
- Identify the next question that follows logically from the results.
ATHOS-3 became the beginning of a broader translational research program rather than an isolated project.
A sustained research career is often built through a connected series of studies in which each project provides experience, preliminary data, collaborators, and questions for the next investigation.
Managing Industry Partnerships
Industry collaboration can provide funding, medication, technology, logistical support, and access to large research networks. However, investigators must maintain scientific independence and understand the contractual terms of the partnership.
Important issues include:
• Access to the complete dataset
• Publication rights
• Control over the statistical analysis
• Disclosure of conflicts of interest
• Safety reporting
• Intellectual-property provisions
• Sponsor involvement in manuscript preparation
• Procedures for resolving disagreements
Industry partnership can advance important research, but transparency and clearly defined responsibilities are essential to maintaining credibility.
The Real Process Behind a Successful Trial
The challenges involved in coordinating multiple institutions or working with industry are not separate from clinical research. They are central parts of the process.
A successful first trial requires:
• A meaningful and manageable question
• Multiple experienced mentors
• A committed multidisciplinary team
• Carefully selected research sites
• Clear and practical study procedures
• Strong writing and communication skills
• Protected research time
• Regulatory and operational planning
• Understanding of the complete dataset
• Persistence after delays and rejection
The final published article may make a trial appear inevitable. In reality, most successful studies are shaped by repeated revisions, difficult decisions, unsuccessful applications, and operational setbacks.
Early-career investigators should not interpret these obstacles as evidence that they do not belong in research. False starts and complications are normal parts of becoming an effective trialist.
The most important qualities are the willingness to learn, adapt, seek advice, maintain high standards, and continue working when the initial plan does not succeed.
Thank you to The Daily Dose and the International Anesthesia Research Society for allowing us to summarize this important educational session.