Investigator Initiated Studies: The Why, When, How and So What
Many MSLs are working on pipeline molecules and are therefore involved in clinical studies liaising with key opinion leaders (KOLs). Oftentimes these clinical studies are the company sponsored trials. However, MSLs are also the first point of contact to start discussing KOLs’ own clinical research study ideas using the company’s (pipeline) molecules. These KOLs’ investigator initiated studies are known by different acronyms in pharma/biotech: investigator initiated studies (IIS), investigator sponsored studies (ISS), investigator sponsored trials (IST) or externally sponsored research (ESR) to just name a few. We will call them IIS to clearly indicate they are investigator initiated, as an MSL is not allowed to proactively initiate an IIS discussion, as it is off-label.
WHY do pharma companies run IIS rather than classic company-led clinical trials?
KOLs are extremely knowledgeable when it comes to patients’ unmet medical needs. They know which patient groups are poorly responding to currently available treatments or patient groups that are excluded from larger company sponsored trials (i.e. elderly patients, patients with certain co-morbidities, or certain cancer mutations) and have therefore very limited to no treatment options available to them. Because KOLs know the disease mechanism(s) and signaling pathways inside out, they often formulate strong rational to use a certain compound in a patient group that pharma companies might not have thought of. Having this targeted or personalized approach often increases the likeliness of success of such an IIS.
From the pharmaceutical company perspective, it is a practical way to test the efficacy of their compounds in a new patient group at a relatively low cost without having to do all the logistics and monitoring of a company sponsored trial.
WHEN during the drug development process are IIS commonly run?
Usually, KOLs (and pharma) are interested to run IIS after the phase 1 studies are completed. At this stage the safety, optimal route of administration, optimal dose and dosing schedule of a given compound have been assessed in dedicated phase 1 centers that are equipped to running these complex phase 1 company sponsored studies. A KOL can then use the phase 1 study result and combine it with his/her own ideas to treat a specific patient group. Because of this, most IISs are earlier phase and smaller studies, such as phase IIa or IIb studies.
HOW does an IIS get up and running?
KOLs approach a pharma company - usually the MSL - to start a discussion about an IIS proposal. Often a short proposal (A4) is shared with the MSL for review by the medical team. When it is of interest, a more comprehensive (full) proposal is submitted by the KOL and will undergo a full review by the medical department to assess the scientific, clinical and medical merit. The company also reviews the proposal at a strategic level, i.e. is this the best use of the company’s resources and research budget. Then the MSL often pitches his/her KOL’s IIS proposal in a (evening/midnight) teleconference to the senior global medical leaders of the company. If the study is approved, the investigator will receive the drugs and/or the budget to conduct the IIS.
An important role of the MSL is to manage expectations of the KOL. There are many (similar) IIS proposals globally being put forward and there is often a limited amount of budget. Other IIS proposals might be more competitive in their offering and the cost, so as an MSL it is important to manage expectations of the KOL to get funding for the proposal.
If an IIS is successful, it can pave the way to start a larger company led registrational (phase 3) trials to obtain regulatory approval for the drug to be used in that (new) patient group. Interestingly, an IIS can sometimes provide enough evidence to obtain regulatory approval, and saving the cost of running a phase 3 trial.
Therefore, picking the right IIS as an MSL and the pharma company can give you a competitive advantage over other companies.
As an MSL – having the first point of contact discussing an IIS proposal with those KOLs - you are playing an essential role in potentially allowing patients to get access to drugs that they would normally not have access to.
IIS is an important topic that is discussed in most Advisory board meetings to plan the data generation of the product. Do you want to become a master in running Advisory Boards? Then start our "Advisory Board Masterclass" training today.