Investigator Initiated Trials - when are they appropriate?
Investigator-initiated trials (IITs) are clinical studies in which the principal investigator—typically a physician or academic researcher—takes the lead in designing and conducting the study. Unlike sponsor-initiated trials, which are primarily funded and managed by pharmaceutical or biotech companies, IITs are conceived and overseen by independent researchers.
IITs can certainly play a role in advancing clinical evidence for a new or existing therapy. The question I often get when putting together a clinical strategy is where and when IITs make sense within a given program. The answer to that question is not normally straightforward, as it depends on several factors, including but not limited to the phase of development the therapy is in, whether the IIT goal aligns with the organization’s goals, and the intended use of the data after the study.
While oversimplifying the consideration of utilizing the IIT option, let us approach it from a development phase perspective for this discussion. There are two phases that an ITT may make sense in – the early and late phases. Often, start-ups consider IITs as an “easy” way to do that first proof-of-concept (POC) study, and certainly, there is some truth to that. Instead of the company, the site must deal with regulatory submission, resourcing the study, running the study, and summarizing the study. All that takes a lot of work off a company that may have limited resources. However, all those benefits introduce the inherent risk(s). Often, the Sponsor company needs this study to be run well and with high confidence in the data coming out of the study, as the data will drive future funding efforts and drive the direction of the company. With the requirement that the Sponsor company be arms-length from the design and execution of the study, there is little control and, therefore, less confidence in the data. Along these lines, it is critical during the contract process that the Sponsor company clearly understands who will own the data in the end. For an IIT, the site (especially if an academic center) will require that they own the data and have free and open publication rights. This means that the Sponsor will not have open access to the data and that the site can publish however and whenever they would like – neither of these is likely in the best interest of a start-up company. Finally, there is the belief that an IIT will be cheaper. If the study is done right, this often is not the case, at least not to the point of making up for the risks of an IIT at this stage of development. Refer to my previous blog on how different resourcing and geographic options can mitigate the costs of early-phase trials. All this is not to say that an IIT may be a good early-phase option, but the risks need to be well understood and mitigated.
Where an IIT often can make sense is with post-market data efforts. The opportunities here are rather endless and may include efforts to collect additional on-label data to drive adoption and/or further understand the therapy within the patient population, or early data for labeling expansion, as examples. Many of the same considerations need to be understood as with an early phase trial, but those risks may be more tolerable post-market or even once a company is further along in its lifecycle (e.g., has an approved therapy and revenue).
One aspect of IITs that many organizations may not fully understand is what makes a study an IIT vs. an industry-sponsored study. For a study to be an IIT, the study idea and protocol needs to come from the Investigator and be executed by the Investigator. Funding can come from several places, including the site itself, the therapeutic company, and grants, to name a few. Regardless of where the funding comes from, the therapeutic company is meant to be arm’s length throughout the execution of the study. This is not to say there can’t be milestones that may be tied to study funding, but the day-to-day execution should be with the site (or a CRO that the site hired). If these basic benchmarks are not maintained, then regulatory agencies may (and have) considered the therapeutic company the actual sponsor and all that comes with that designation. I have built IIT processes for several organizations, and I am happy to discuss further what this looks like.
As I conclude this, I realize that it may come across as if I am not a proponent for ITTs. This is far from the truth as I have utilized IITs many times in the past and believe, despite these challenges, IITs remain a vital component of clinical research. I also do not believe they are the golden ticket to easy clinical evidence that they are sometimes credited for. Organizations simply need to ensure at a minimum that they are understand what they want to get from the study, how they intend to use the data and whether the study is appropriate for that, what they will get from the study (including data quality), and the terms of the study contract with the Investigator.
If you are considering IITs as part of your clinical program, reach out for a discussion.
