The following are examples of how a strategic clinical innovation process helps solves problems.
Case study #1 - Innovation Thinking

PROBLEM:
The sponsor needed a clinical plan for their lead compound (a biologic) that was the second on the market for the rare disease indication. Given the high cost of development and product manufacturing, a “me too” product would not be acceptable. Special challenges were provide by:

  • Presence of a very similar product on a monopoly market for about 15 years
  • Small number of patients available worldwide due to the orphan disease status

    A Key Opinion Leader meeting was called with the five most accredited academic disease experts worldwide. Sponsor walked away from the meeting very confused. Each of the academic disease experts had proposed very complex study designs with several treatment arms. Furthermore, no consensus was found either on the study design or on the primary endpoint.

    SOLUTION:
    It was important that a unique and defined strategy be implemented. This strategy must effectively gain critical knowledge from Key Opinion Leaders and funnel it into a clinical trial design with endpoint selections that would focus on collecting only useful data to evaluate the product. Dr. Fratazzi, in charge of developing the unique clinical plan and trial designs, started by collecting information regarding

  • Standard of care and disease progression at diagnosis
  • Unmet medical needs and prescriber evaluation criteria
  • Patients’ distribution worldwide
  • Trial design options
  • Endpoint selection link to progression of disease
  • Regulatory “must have” requirements
  • Differentiation factor for the market place

    With the above information, a draft synopsis was created together with a list of questions to allow critical review and refinement of the study protocol. Given the high complexity of the task, several meeting were needed to finalize the study design and agree on the overall clinical development plan that included also a long-term safety trial. Both trial design and development plan were successful, leading to product approval, introduction and market success.

    Case study # 2 - Clinical and Regulatory Analysis

    PROBLEM:
    Sponsor developed a new class drug up to the first in man study. The drug proved to have a safe “safety profile” during the phase 1 studies in healthy volunteers. Sponsor started to evaluate a clinical development plan. In order to identify the disease in which to perform proof of concept, sponsor invested into a marketing analysis that resulted in an eight diseases list. Each of the indications looked very exciting at a first glance. Nevertheless, sponsor felt uncertain about the cost-benefit of developing each of the proposed indications and lack of clarity on the clinical development strategy. Sponsor decided to hire BBCR to create a roadmap by analyzing clinical and regulatory pros and cons for each of the indications on the list, to be jointly evaluated with market size, competition and resources constraints.

    SOLUTION:
    When BBCR first reviewed the list, it was noted that the indications on the list were very different among themselves. The only factor they had in common was an established or possible inflammatory component. BBCR felt drug specifications were not appropriately matched with diseases. In order to create a prioritization of the indications on the list, we established the factors that we wanted to include in the first level analysis versus those ones that could be include in a secondary phase.

    First Level Analysis Factors:

  • Highlight aspects of the disease that could be treated with the sponsor drug and those that were not related
  • Analyze clinical models and challenges associated to the development of drugs, for the selected indication, with similar mode of action
  • Review available biomarkers, possibility of surrogate, clinical and composite endpoints.
  • Regulatory review of appropriate models followed by integrated challenges and opportunities analysis completed the evaluation for each of the selected indications.

    Sponsor was able to recognize the value of clinical experts in roadmap creation. Secondly, Sponsor appreciated the “innovation thinking” that was generated and the value to perform an integrated product- indication analysis.

    Case study #3 - Strategic Vision

    PROBLEM:
    A small molecule with antiviral activity was to be developed for an influenza like disease call “RSV”. In a previous clinical trial, in which patients were randomized on symptoms, approximately 35% of patients enrolled were not infected with RSV due to late virus load detected by PCR. The confusion created by this patients’ selection process was the cause of:

  • Missed primary endpoint due to dilution of study power and efficacy effect
  • Lack of balance in the randomization groups due to uncontrolled distribution of the RSV negative patients
  • Ethical issue linked to anti RSV administration in non RSV infected patients
  • Additional 35% of trial cost and enrollment time Sponsor involved Dr. Fratazzi to find an alternative approach and solve this problem.

    SOLUTION:
    The clinical challenge offered in this case was:

  • Risk associated to enrolling the subjects on symptoms only
  • Need to enroll patients within 72 hours from the start of symptoms.

    Timing of treatment in upper respiratory viral infection is crucial. Clinical symptoms present with several hours delay after the infection and viral replication start. Therefore, in order to shorten the duration of symptoms and reduce the possible chance of lung complication, it is critical to administer anti-viral treatment almost immediately after the start of symptoms.

    Based on this knowledge and in order to truly test the anti viral treatment effectiveness we needed to:

  • Keep track of the seasonality and viral infection spread within any geographical area
  • Educate the patients about the importance of seeing the doctor with the very early symptoms
  • Being able to enroll only PCR positive patients and have the PCR results back on time for treatment
  • Start the antiviral treatment within 72hours from the start of the early symptoms

    With this project, the challenge was the development of a companion diagnostic named real-time PCR. Collaboration was established between the sponsor and a small laboratory that had developed an RSV-PCR test and agreed to develop a real-time PCR. After the companion diagnostic development was completed, patients were enrolled and randomized base on real-time PCR positivity that was confirmed, at a later time, with the validated standard assay. The development of this companion diagnostic saved the product development and solved all the problems above listed.