Practical Advice for Investigator-Initiated Trials

Practical Advice for Investigator-Initiated Trials 1024 363 Lauren Dembeck

Investigator-initiated trials play a crucial role in advancing medical research and contributing to evidence-based medicine. These trials are initiated, designed and conducted by researchers, often physicians or scientists, rather than by pharmaceutical or biotechnology companies. They allow researchers to explore specific hypotheses, novel interventions or unique patient populations that may not be addressed in industry-sponsored trials.

Samantha Sharpe, CCRP, clinical research project manager at Nationwide Children’s

“The field of investigator-initiated studies is growing, and it is a beautiful opportunity to engage study participants with clinical research in a meaningful way,” says Samantha Sharpe, CCRP, clinical research project manager at Nationwide Children’s Hospital.

Investigator-initiated trials present a multitude of challenges for the investigator. Over the last decade, Sharpe has refined her expertise in clinical research management. She has presented internationally on best practices for developing investigator-initiated trials since 2018.

“When we’re talking about investigator-initiated studies, it is like building a house from the ground up — all planning and operation is directed by the investigator,” explains Sharpe. “It requires them to think comprehensively about all aspects of the study, checking all the ‘blind spots’ that are often overlooked and can hinder swift execution of study deliverables and scientific progress.”

Investigators also need to think backward about the possible outcomes of the study and what data will be needed to draw those conclusions.

“Truly successful studies are built on detailed planning before implementation,” says Sharpe. “While deadlines often make investigators feel the need to rush, it is important to be thoughtful at the beginning of the planning process. Those initial weeks of planning increase the probability of success throughout the rest of the study.”

Institutional Support For Investigator-Initiated Trials

Institutional support is vital for investigator-initiated trials. At Nationwide Children’s, this is reflected in the strategic plan of integrating clinical care and research, building new facilities and augmenting infrastructure capabilities, investing in both new and ongoing research areas, and funding investigators via an intramural funding program.

Cynthia Gerhardt, PhD, chief clinical research officer at Nationwide Children’s

“Our goal is to continue to build infrastructure that expedites clinical trials and catalyzes discoveries, so we can offer cutting-edge innovations and treatments to our patients faster,” says Cynthia Gerhardt, PhD, chief clinical research officer at Nationwide Children’s. “It’s very important that the institution supports investigators by providing resources, training, and funding for their trials under development.”

Dr. Gerhardt also highlights the importance of collaborations with other institutions via multicenter and decentralized trials. Both allow for increased numbers of participants, enabling investigators to draw more robust conclusions. These are particularly important in pediatrics research because many pediatric conditions are rare, making it difficult for a single center to recruit enough patients to trials.

“The future of clinical trials is about collaborating with providers in the community,” says Dr. Gerhardt.

Tip No. 1: Make a Detailed Schedule

When writing the study schedule of events, think through every single step, considering the smallest of logistical details. This can be achieved by imagining a mock run of what it would take to implement all the visits of the study.

During this planning phase, special consideration should be given to recruitment and retention of study participants. When the estimated sample size target is not met, researchers can be challenged to draw valid conclusions or discern differences between treatment groups, compromising the scientific validity of the study.

To aid participant recruitment and retention, study protocols should be designed with a patient-centric approach, incorporating the needs and concerns of the participants and, in the case of pediatric studies, their parents or caregivers. For example, in pediatrics, will the study require the children to miss school and the parents to miss work? How will siblings be accommodated during visits? How long will each follow-up visit last?

“We have to be intentionally mindful, taking a holistic view when considering participant recruitment. The needs of the participants can get missed in the desire to capture large amounts of study data. There has to be a balance,” says Sharpe.

Another area that deserves special consideration is regulatory and compliance requirements and local guidelines. While some institutions have dedicated regulatory departments or teams, investigators without those resources can hire regulatory specialists to help them conduct their study in a compliant manner and develop consent and assent forms.

Tip No. 2: Make a Manual of Operations

“The study protocol is the scientific idea, and the manual of operations is essentially the directions of how to have that idea realized,” explains Sharpe.

A manual of operations should include how each step of the study will be carried out — moving ideas to implementation. This process includes engaging with potential team members and discussing the study (e.g., finance, regulatory and clinical research teams). The feedback gained during this process not only solidifies the manual of operations but can also help the investigator refi ne the study protocol, potentially avoiding any changes that can impact study completion. For example, if collecting peripheral blood samples is indicated in the protocol, the manual of operations should address where the collection tubes can be obtained; who will collect the samples; whether the blood draw is happening as part of routine care, and how samples will be transported and processed.

Tip No. 3: Don’t Forget Your Budget

For an investigator-initiated study, the investigator is also in charge of detailing all costs of the study. This includes appropriately compensating any staff members performing duties outside of their usual clinical care requirements and determining how much to compensate participants for their time. Study costs can also include support services, specimen processing, research procedures and numerous other operational fees. In the example above, it is important to define clearly if the study is paying for the time and supplies for the blood draw.

This article appeared in the Fall/Winter 2023 issue. Download the full issue.

About the author

Lauren Dembeck, PhD, is a freelance science and medical writer based in New York City. She completed her BS in biology and BA in foreign languages at West Virginia University. Dr. Dembeck studied the genetic basis of natural variation in complex traits for her doctorate in genetics at North Carolina State University. She then conducted postdoctoral research on the formation and regulation of neuronal circuits at the Okinawa Institute of Science and Technology in Japan.