Namrata Saroj, OD, has earned a deserved reputation as a “go-to” person for companies and practices conducting clinical trials in the retina subspecialty. Dr. Saroj earned her Doctor of Optometry degree from the University of California at Berkeley. She started as a research associate at the Manhattan Eye, Ear & Throat Hospital focusing on clinical trials in retinal diseases, following which she joined the field-based medical affairs group for Lucentis at Genentech. Dr. Saroj successfully supported multiple investigator-initiated studies and research collaborations during her time there. Subsequently, Dr. Saroj led the ophthalmology medical affairs efforts at Regeneron Pharmaceuticals, supporting the commercialization of Eylea. She has recently become an independent consultant supporting companies as they develop new drugs and technologies to advance the management of retinal diseases.

Her knowledge of the nuts and bolts of planning, designing, and conducting both company-initiated and investigator-initiated clinical trials is well recognized. With retina practices showing increasing interest in conducting their own investigator-initiated trials, we asked Dr. Saroj to provide a basic primer on undertaking such an endeavor.

Q. How did you get involved in the planning and conduct of clinical trials?

A. I started my clinical research career at Manhattan Eye, Ear & Throat Hospital working with an esteemed group of retinal physicians who were leading multiple clinical trials, both company-sponsored as well as investigator-initiated. I learned how to conduct clinical trials at the site level, managing all aspects, including study designs, patient recruitment, regulatory, and legal aspects as well as data collection and analyses. I was able to further expand my experience by coordinating one of the first multicenter investigator-initiated trials, which was led by Dr. Richard Spaide as the principal investigator. This experience of running clinical trials at the site level was extremely valuable as I made my transition to industry, where I was intimately involved in clinical trials.

Q. Why are investigator-initiated trials valuable?

A. The value of investigator-initiated trials is often underappreciated. From a scientific perspective, investigator-initiated trials provide opportunities to further explore a drug or disease state. There are limitations on the extent of exploration that can be done in clinical development trials for regulatory purposes. An investigator-initiated trial represents an avenue to expand on research, which not only results in advancing the medical science, but also can provide valuable pearls in patient management. Such scientific collaborations support the symbiotic relationship between physicians and industry working together toward advances in medicine for our patients.

Q. How do individuals interested in conducting their own trials get started? How do you approach companies for support?

A. Companies generally want to collaborate with investigators who have clinical trial experience. So, the earlier you can get involved, even if indirectly, the better. One way is to assist principal investigators and coordinators with ongoing trials during medical training, and then start taking leadership as a primary investigator early on in practice. In addition to the experience, developing relationships with industry is also important. Get to know your medical and clinical liaisons for the different companies — they are the conduit to ensuring that your research ideas are communicated and reviewed. Just like for any research project, good preparation is important here as well — vet your idea with your peers, have a good scientific rationale, and provide adequate supporting documentation. All this shows you are motivated to do the study.

Q. What are the basic requirements needed at a site to conduct an investigator-initiated trial?

A. The requirements for an investigator-initiated trial are similar to any clinical trial from an equipment perspective. Most importantly, you need dedicated experienced coordinators and research managers. Unlike a company-sponsored trial, in an investigator-sponsored trial, no one is actively monitoring the study. You, as the principal investigator, are taking over all the responsibilities, and good coordinators are critical to ensure that the trials are conducted according to guidelines.

You will be responsible for developing the protocol, managing the budget and contract, submitting to the IRB and FDA (if needed), ensuring the protocol is being followed, and eventually collecting, analyzing, and publishing the data. Involving coordinators from the initial development stage is extremely helpful — they can provide input on feasibility of study assessments for the protocol as well as budget ranges that are acceptable by your institution or clinical practice.

Q. What are some pearls for designing and conducting an investigator-initiated trial?

A. Just like with any research project, start with a question or hypothesis that you would like to investigate. Explore whether this has been studied before; even if it has, you might want to answer additional questions on the same topic.

Provide a strong clinical and scientific rationale for your proposal. Keep the study design simple and streamlined — many times, I have seen investigators try to evaluate too many questions in one trial, which often results in confusing data.

Above all, follow through in a timely manner from protocol development to study activation to patient recruitment and follow-up and finally to publishing results. I have come across delays in all these aspects, and these delays can only be overcome when investigators are actively involved. It is important to understand that companies are providing funding and/or drug support for your research idea with the expectation that the investigator will complete the study and publish the results. Opportunities for future collaborations might not arise if there is a pattern of lack of follow-up with established projects.

Q. How do you lead and manage multicenter investigator-initiated trials?

A. Multicenter investigator-initiated trials are definitely more challenging than single-center trials, so an investigator should clearly identify the need for a multicenter trial before proposing one. The first thing to confirm at the primary site level is the feasibility of conducting such a trial. The investigator should establish a team that can be dedicated to this project — in addition to managing the patients at the main site, the investigator must also have administrative management and data collection from the subsites, and budget should be allocated accordingly for the same.

An investigator should also review the institution’s or clinical practice’s guidelines to confirm whether it is possible to subcontract with the subsites and if there is a mechanism to make payments to the subsites. Most companies will only contract with and make payment to the primary site. In most cases, the companies will ship the drug directly to the subsites. Additionally, a primary investigator must have confidence that the subinvestigators and their teams will conduct the study with the same integrity. The principal investigator is responsible for the data that are generated from the subsites and should make sure that all investigators are on board with the study design before initiating the study and commit to enrolling patients. I don’t usually recommend having more than 2 to 3 subsites unless it’s absolutely necessary.

Q. What are the challenges of conducting investigator-initiated trials?

A. Overall, conducting investigator-initiated trials has the benefit of autonomy, yet autonomy can be challenging as well. The investigator owns the research project, and so has the freedom to design the project. But without adequate support, owning the project completely can be difficult. The challenge can be mitigated by securing buy-in and support from the team. Sometimes things can be challenging on the company side as well. Companies have their own processes for reviews and approvals, and delays can be frustrating. Keeping an open communication with the company liaison and proactively following up through all the stages of the trial can streamline the project. RP