First-in-human – this phrase often causes a visceral reaction that is some combination of frustration, terror, and exhilaration depending on your personal history. Regardless of your experience, applying your new technology to the diagnosis or treatment of an actual human being for the very first time can be a major source of trepidation. In large companies, a feasibility study is often the culmination of years of research, involving a substantial financial and human resource investment. In start-ups, it is the first step into product viability and if that is not scary enough, current and future funding of the company almost certainly depends on the results.
In either case, there is a great deal of pressure to succeed and yet questions abound. What if a patient is injured? What if the technology doesn’t work? Almost as frightening – what if it does work? Are you ready to move to the next stage? How quickly can the study get started? These questions all factor into the approach to early feasibility studies. The biggest challenge however, is that this stage of product development often involves much uncertainty and uncertainty breeds risk. While risk tolerance is different for different companies, the less risk there is in a feasibility study, the better it is for all involved. A master’s thesis could be written on how to identify and mitigate/minimize the various risks associated with early studies, but here I will simply identify several questions you should be asking yourself and your team; ideally, before you start to work on a feasibility study.
How you start your clinical experience may depend on how your technology got started. Was the technology developed in collaboration with physicians or did key physician advisors aid in development? If so, it may be important to ensure their involvement in the study – either performing cases or in proctoring/training. Having Investigators who know something about the technology can sometimes be a very efficient way to get product feedback.
However, in some cases, you may not want them involved to avoid any bias or appearance of bias in the study results. Are there key opinion leaders that are the de facto collaborators in this clinical arena? Sometimes it is obvious who should conduct the study because there is only a small number of pioneers in the field. While this may make the decision simple, it may not make the execution as simple because your competitors want access to those same experts, so timely access may be a challenge along with keeping your stealth project under the radar.
Impact of the Technology
The complexity of the technology being tested will have an enormous impact on your study. Is your device a single-use, simple disposable or is it a high-technology computerized piece of capital equipment? Does it involve special safety or compatibility factors such as radiation or magnetic fields? How easy is your product to use? How much training is involved in using the product? These factors will feed into the pre-clinical testing required for your product and will impact the complexity of study elements like your study protocol, the regulatory approval pathway for the study, required training of clinical site personnel, logistics for device packaging, shipping, setup, and installation, additional site inspections or reviews beyond ethics reviews, and company personnel needed to support the study.
Another technology impact factor is its viability. How much testing has been done on the product? If only safety testing has been performed, what level of detail is needed in the performance and usability data to be collected in your study? In other words, how much are you expecting to learn in your feasibility study? Is the study expected to simply confirm pre-clinical testing because it is a “me-too” device or is this the first time this type of test or procedure is ever being performed anywhere in the world? The complexity of regulatory and clinical oversight, the procedural detail in the protocol, and the training required will generally be proportionate to the complexity of your technology.
Also, think about how the technology will impact the use of the study data. Is the technology in its final form or is it in an interim stage? This is particularly important if study data will be used to support any type of regulatory submission. Typically, regulatory agencies or notified bodies want to see testing performed on the product that is going to be marketed. Justification is often needed for test data obtained using prototypes or “near-final” configurations of product. Most companies don’t plan to use early feasibility study results to support a regulatory submission – until the study is wildly successful. Suddenly, that data originally meant to simply determine technology feasibility needs to be robust and pristine. Don’t forget to plan for success.
Location, Location, Location
The location of your feasibility study site(s) will play a vital role in the execution of the study. Sometimes, this may be pre-determined, as mentioned above with a physician collaborator. When it is not – and sometimes, even if it is – there are many questions that must be answered. Which investigator(s) should be involved? Will the study be at a single site or multiple sites? Will it be in a single country or in multiple countries? These questions, along with the complexity of technology will determine most of the regulatory requirements for the study.
Some countries have become popular for first-in-human studies because of rapid regulatory approval timelines. However, these countries may present travel or logistical challenges for geographic reasons. In addition, they may not have the required key opinion leaders, so you’ll need to investigate whether these countries and/or hospitals allow bringing physician collaborators with you.
In other cases, specific physicians or hospitals attract certain products or procedures because they are leaders in the field, but they may have challenges such as being in countries with onerous regulatory requirements that lead to unacceptable study timelines. Keep in mind, however, that the quickest feasibility study start date does not always lead to the fastest or most efficient product approval. Make sure to take the project’s long-term goals into account when planning your feasibility study.
Regional logistics also play a factor in site selection. Quite often, early feasibility studies are performed in a country or at a hospital with which your company has little or no experience, so what should be simple logistical tasks can take days or weeks to coordinate. Local language (spoken and written), shipping, storage, customs requirements, personnel travel requirements (e.g., visa requirements for one or more of your team), and other local challenges may create frustratingly long delays. Frequently, it can help to have local “boots on the ground.”
So, as with most things in product development, the questions above and their answers need to be planned and assessed with the understanding that there are rarely obvious choices in how to execute your feasibility study. These decisions must take your specific circumstances into account and must strike a balance between timeline, regulatory requirements, cost, Investigator/site expertise, and resources required to get started. Make sure you take all these elements into account when planning your feasibility study and start having these discussions with your product development team early in the clinical development process.