Nicole Cowan directs IVD operations for contract research organization (CRO) ICON's Medical Device and Diagnostic Research (MDDR) business unit. Cowan has more than 15 years of experience in the clinical, academic, central lab services, and CRO space. In her role with Ireland-based ICON—which employs more than 14,000 people and is projected to generate $2.8 billion in 2019 revenue—Cowan directs cross-functional teams across multiple programs and projects, supporting manufacturers to ensure a successful program and project plan design for optimal development, in concert with budget and risk assessment, overseeing clinical study execution for each client's market access goals. Cowan recently spoke with Clinical OMICs Editor in Chief Chris Anderson about the new biomarker-driven landscape in clinical trials and the nuances of drug-diagnostic co-development programs.
Chris Anderson: Can you tell us about the evolution of in vitro diagnostics over the past 10 years and how it has changed the drug and diagnostic development landscape?
Nicole Cowan: The evolution we have seen is extremely exciting. There is an ongoing refinement in research and technology with the ultimate goal of driving the benefits to the patients through better tools, decision making, scenario planning, and better alignment of precise treatments according the patient's individual molecular and genetic drivers of disease. Biomarker strategies have become an integral part of drug development. We have evolved from that one drug-one biomarker model to biomarkers as fundamental in a combination of therapies and in combatting the heterogeneity of a patient's disease.
The evolution blends modern and more traditional methods because there needs to be a balance of optimizing the time and expense of processes. Physicians in this space now are considering a more holistic assessment [of patients] and looking at the anatomical and histological structure and function—analyzing the molecular signaling and genetic nuances, as well as the immunological subtypes to hone in on the disease drivers.
What role do diagnostics play in the drug approval process?
Cowan: The path of therapy-diagnostic co-development has been designed to select for patients who will benefit and can accelerate approval of the therapy. Companion diagnostic strategies affect the design of therapeutic clinical trial programs and lead to higher response rates when the right patients are selected for treatment. With appropriate technical, clinical and quality competencies, companion diagnostics are accelerating the introduction of new therapeutics by allowing for more efficient and targeted data collection from patients enrolled in clinical trials. In the best cases, we are increasing the data quality in smaller patient enrollment quantities, which is a powerful concept because it drives an overall reduction in the number of patients that are exposed to these investigational or experimental therapies, therefore decreasing the number of side effects and even adverse events.
How will the acquisition of molecular diagnostic developer MolecularMD help the company provide a more complete service offering to clients?
Cowan: The acquisition of MolecularMD is a tremendous addition to ICON and our abilities within the diagnostics space. As a specialty molecular and diagnostics laboratory, MolecularMD has over 12 years of experience in the successful advancement and commercialization of molecular and immunohistochemistry assays for precision oncology and therapeutic development programs. MolecularMD, and ICON as an organization, empower a number therapeutic specialties including hematology, endocrinology, infectious disease, and woman's health, in addition to oncology as MolecularMD's strong suit by legacy. With MolecularMD, ICON's abilities are amplified particularly in clinical biomarker assay development and validation, global clinical trial testing, in vitro companion diagnostic approval, and global and regional commercialization.
As diagnostics are taking a broader role in therapeutic development, how does an appropriate diagnostic or clinical trial assay speed development timelines and reduce costs?
Cowan: There is an enormous amount of investment necessary for development of biomarker strategies. As we become more educated in adapting the development, our experience in how to adjust development based on results gets faster and ultimately, in best cases, does decrease timelines. The [regulatory] agencies' positions are more than receptive to tailoring dosage and using companion diagnostics. Ultimately, it does save costs to numerous parties, because it is a more efficient and targeted approach if the process of getting the targeted data and results [sponsors] need is optimized and, at the same time, becomes more precise as the diagnostic is refined or tailored.
What do you see as the most common challenges your pharma and biotech clients face?
Cowan: A couple of challenges I have seen are connected to ensuring that the diagnostic development partner can customize the necessary support to co-develop therapeutics and associated diagnostic platforms. There are many challenges our clients face as the intellectual growth and development continues to expand. Specifically, validation—and proper validation. In some instances, lack of validation of surrogate endpoints for clinical trials and the importance of clinically meaningful outcomes for agency acceptance of various surrogate endpoints for clinical drug development approvals. Other challenges can be the clinical study design as a whole and expectations around how to adjust development based on results. The belief in the biomarker within the entire team is critical as there is a tremendous amount of investment necessary for the development of these biomarker strategies.
Much time needs to be spent on what will be done with negative biomarker readouts and if clinical development is continued to be pursued. What will be done if they get a negative biomarker readout, or if they decide to continue to pursue the clinical development? What does their strategic planning look like? Is the biomarker assay design and specifications fit for purpose? Developing a novel biomarker in parallel to a therapeutic with the expectation that the biomarker is going to be a part of the approval label is a significant challenge to ensure that both processes are in step. The endgame is the need to optimize the development and also improve the clinical trial outcomes. How do we put that vision into practice? It comes down to starting with the end in mind and that goes for everything from development to clinical trial execution.
What do you mean about starting with the end in mind?
Cowan: Ultimately, how will the therapy optimize the overall cost to the patient? How will [sponsors] demonstrate cost effectiveness in the payer space? Is it increasing effectiveness by creating safer therapy dosing and cumulatively increasing the clinical benefit? It is very difficult to see and plan for everything that is going to happen, but having those types of conversations across the board with all of the folks it takes to make this happen is critical—your pharma partner, your IVD manufacturer, your CRO—ensure that they are all coming together.
In co-development, how can you mitigate some of the challenges inherent in the process?
Cowan: The first challenge is always going to be the communication and the alignment between the pharma company and the CRO over what the sponsor's specific objectives are and the alignment on the role that each of them are going to play in the partnership—it's probably more accurate to call it a journey.
It is imperative to keep both the drug and the diagnostic programs closely linked and to understand and expect there are going to be challenges, such as gathering the evidence base that links the biomarker with the clinical endpoints, which is oftentimes underestimated.
When do sponsors typically approach ICON, and do you think they should be doing it earlier in the development process?
Cowan: It depends, of course, on the pharma company's confidence in the data to justify the investment in the companion diagnostic development. We know that, collectively, the pharma companies are averse to cost and risk. Obviously, approaches to de-risk the clinical study are preferred. In order to mitigate the cost and the risk, oftentimes the pharma company chooses to proceed as far as possible using a properly designed clinical trial assay to collect study data, for example, under an IDE with the IVD platform owner, in hopes that efficacy will subsequently justify a companion diagnostic commitment. Unfortunately, we know many trials fail. Planning for a bridging study given efficacy success could be an inherent requirement of this approach to cost and risk mitigation. I hate to say it is never too soon, but that is how I feel I would answer the question in one sentence, with the premise that if these considerations and the necessity for strategic development are in process, then you need to engage.
What do you think the future holds for ICON and the industry at large?
Cowan: It will be exciting to watch how technology advances. The convergence is here without a doubt. The ability to target treatments to a patient's specific genetic mutation or biomarker is becoming the gold standard. Technologies like sequencing, artificial intelligence, and bioinformatics are impacting this work going forward with increasingly developed digital strategies and innovation. ICON's capabilities and innovative technologies to support optimal collaboration with high-performance diagnostic providers are a key strength.
Surely, revelations in digital technology will fundamentally change the way the field of diagnostics operates from ordering tests to interpreting data and allow diagnostic testing to be more cost efficient and faster. Hopefully, these technological advances will remain complementary to each other and support process efficiency and data integrity. Rather than any one technology as a solution, a variety of technologies providing scientific insight when the data collected is able to be reviewed in a broader context against the fundamental biology of disease.
