A poorly designed and improperly executed trial can « kill » a product

A poorly designed and improperly executed trial can « kill » a product

A poorly designed and improperly executed trial can « kill » a product

An interview with Régine Rouzier, president of the CRO Cap Research

What is the central issue to successfully perform a phase I trial?

The success of a phase I study depends on the speed in execution and the excellence and quality of returned work. These are the two fundamental pillars of a clinical trial.
Phase I studies are conducted with healthy volunteers, but proof of concept is often performed with patients with the targeted disease. Quality of the studies on healthy volunteers will have a strong impact on these trials that are also early stage studies. The choice of the clinical investigation center is therefore decisive because you have to be sure of the quality of the results. You have to carefully select your Phase I center and it’s also important to be sure that your study isn’t one among so many others. So you can see that several factors interact to ensure the success of a phase I trial.

What kind of  factors play a fundamental role?

Studies in healthy volunteers are fairly standardized. But further operations relating to the proof of concept can be more complicated and the range of pathologies is very broad: diabetes, AIDS, hepatitis C, lupus, cancers …. It is therefore very important for the investigator not only to have experience with healthy volunteers but also with patients. Many people believe that you have to open many centers to quickly achieve a proof of concept. This could be the case for rare diseases, but in many situations, one or two centers with a a high-level of patient recruitment are enough. It is easier to manage and it needs lower spending on personnel, equipment and overall functioning. Finally, it can be very stimulating for a human-size CRO. The relationship with the promoter is very close and each client is unique and very important.
Properly define what you are looking for and what you want to demonstrate, so your phase I trial will be successful. The protocol is a key element and it must be designed with all the stakeholders (investigator, promoter and CRO). A good relationship and trust between the partners are therefore important. Experience is also required to accurately assess the feasibility of a protocol. We often see errors, « copy/paste » between protocols and unnecessary examinations at an early stage of the development of a product candidate. Eligibility criteria for a healthy volunteer must not be confused with criteria required for a patient for example. At the end of the day product development can be delayed if the selection criteria are too restrictive and if the purpose of the research is not well targeted. It can also create unnecessary additional costs.
Promoters are often tending to measure too many parameters in phase I. But we must remain realistic and understand that we can’t ask too many examinations to a volunteer. If too many examinations are planned, especially invasive investigations such as lumbar punctures or biopsies, the need for all these tests must be weighed very carefully. One must also know how to tell to the promoter : « Put yourself in the patient’s shoes and think of the people accompanying him/her during the test ». The patient must also be very participative. This is a guarantee of success and this can only happen when the investigator can spend time with his patient …
Moreover, the accumulation of examinations leads to a plethora of results. These data are sometimes hard to interpret at an early stage of development, without being directly useful for the study. It’s important to be effective and it is also the role of the CRO to warn the promoter to protocol’s feasibility and problems that could arise with patients and healthy volunteers.

What major pitfalls can be found in planning a phase I protocol?

I would stress once more the particular importance of having inclusion and exclusion criteria clearly defined. Often, when your study includes healthy volunteers, you have no pathology markers to check the effectiveness of the product. Conversely, you can’t ask patients with disease markers to have the same check-up than healthy volunteers.
Protocol design must involve three types of stakeholders: the scientist who knows the product, the medical specialist who knows the pathology to be treated and the clinical trial specialist who knows how to conduct and to manage a study. Each of them has a role to play and each of them can provide significant experience. In the event of satisfactory outcomes, you have also to foresee that your Phase I product will advance into a Phase II trial and this transition needs to be planned from the start of the Phase I.
Let’s not forget that a poorly designed and improperly executed Phase I trial can l « kill » a product. It is therefore essential to choose the right people and the right CRO, to take the time to draft a suitable protocol designed for the product and for the targeted pathology. If you can create these conditions, you could consider a quick transition to Phase II. And I will reply in the words of Talleyrand to his valet: « Go gentlly Jean, I am in a hurry ».