Role Of A Biostatistician In Drug Development Programs Impact Beyond Clinical Studies

ROLE OF A BIOSTATISTICIAN IN DRUG DEVELOPMENT PROGRAMS

Impact beyond clinical studies

By Natasa Rajicic

Statisticians contribute to clinical study design, conduct, analysis and reporting - where their involvement has been well established. They are typically part of a larger biometrics team where they work closely with clinicians, data managers and programmers, and contribute to the study design, protocol writing, dataset formats and monitoring plans. For example, one of the main deliverables for a statistician working on a clinical study is the completion of a Statistical Analysis Plan (SAP) where they detail the statistical considerations. These include the planned sample size, statistical approaches for the evaluation of endpoints and testing the stated hypothesis, definitions of the analysis populations and estimands, and the treatment of missing observations, to name just a few.

However, the input from a statistician with broad experience in different quantitative strategies goes beyond sample size considerations, creation of the SAP document, and summaries of the results. When they are given the room to work closely with clinical pharmacologists, data scientists and other types of quantitative strategists, statisticians can take a broad view of the clinical development plan to synthesise existing information and consider the range of pathway options. They can help detect any knowledge gaps, identify the right data needed for present and future needs, and help manage the risks along the way. The best statisticians are knowledgeable both about a product and its clinical development pathway, and about a whole range of quantitative approaches and strategies that can be employed to better inform decisions made along the development path. Their contribution can add to data-driven decision-making at every stage of the development. Their evaluation of the existing data can feed into the design of the trial through historical controls, help identify a high-value sub-population, or evaluate the collection of patient-centric measurements. They

can help forecast a more realistic enrollment schedule, use optimisation tools to characterise different clinical pathways, or help plan smarter resource allocation.

During the drug development phase, companies naturally tend to concentrate on a single audience: a regulatory agency who will ultimately review the submission package and decide on a marketing approval. Yet the regulatory agency is only one of many stakeholders for whom the drug developers need to generate and present evidence and data. Therefore, if the data is accounted for throughout the program, rather than mainly concentrating solely on agency approval, companies have a golden opportunity to gather valuable evidence that could speak to all future stakeholders which, at a minimum, includes prescribers, patients, payers (stakeholders of the healthcare sector who are involved in the budget allocations and payment for medicines etc.), and the public.

To be able to do this, statisticians need to be brought in as equal partners early enough in the process. Often, they are introduced after a study design has already been settled on, with their input reduced to simply the sample size considerations and the execution of the analysis plan. That could be an opportunity missed. Instead, they should be involved in the broader planning

for the overall development plan and beyond, so they can use their quantitative skills and strategies to help identify data gaps, help gather evidence needed for the key stakeholders mentioned above, to allow for better informed decisions in ‘real-world’ settings. Therefore, clinical development teams need to re-evaluate how to optimally employ the skills of various quantitative strategists, including the statisticians, across the whole product lifecycle. Statisticians remain core members of clinical study teams. However, keeping them out of the overall strategic planning is an opportunity missed and has some considerable risks that may not become apparent until it’s too late. As I heard one of my former non-statistical colleagues say at one point, it is essential to have a statistician included at all times, you don’t always know when a statistician’s input and perspective is what you’re missing.

Natasa Rajicic, ScD Principal, Strategic Consulting Cytel Inc