Lindsay Alfano, DPT, PCS, on Designing Novel Functional Outcomes for Clinical Trials

The development of neurotherapeutics is increasing, and, therefore, it is imperative that clinical trials keep pace with regard to improving enrollment, design, and outcomes.

This will be a topic for discussion at the 144th Annual Meeting of the American Neurological Association (ANA) in October 2019.¹ Speaker Lindsay Alfano, DPT, PCS, answered our questions about her upcoming session.

Lindsay Alfano, DPT, PCS, is a physical therapist in the clinical therapies outpatient OT/PT department and a researcher in the Research Institute’s Center for Gene Therapy at Nationwide Children’s Hospital in Columbus, Ohio.

NEUROLOGY CONSULTANT: Can you tell us more about your session? What functional outcomes will you discuss?

Lindsay Alfano: My talk will be focused on factors influencing the selection of functional outcomes for use to measure change over time for clinical or research applications (more focused on research trials). Our neuromuscular physical therapy team at Nationwide Children’s Hospital works solely in our neuromuscular clinics and devotes our time and energy to reducing the burden of testing for patients and families. We focus on selection of appropriate outcomes that will provide consistent results to ensure we measure any true change occurring as a result of the natural history of a disease or investigational treatment. Outcome measure selection is multifactorial and not “one-size-fits-all.”

The most common question I receive from a clinical trialist is, “If you could pick one outcome measure, what would it be?” The answer is always, “It depends.” There are patient, study, and outcome considerations that you must fully understand to properly select an outcome that is likely to demonstrate change over time. My talk will walk through many of these considerations and the research we’ve done at Nationwide Children’s Hospital to develop novel outcomes when needed. I will discuss a variety of outcome measures, including the 100-meter timed test, 6-minute walk test, North Star Ambulatory Assessment (NSAA)/North Star for limb girdle-type muscular dystrophies (NSAD), Performance of Upper Limb (PUL), ACTIVE, ACTIVE-mini, the Neuromuscular Gross Motor Outcome (GRO).

NEURO CON: What are the benefits and pitfalls of novel functional outcomes for clinical trials?

LA: The benefit of novel outcomes is that you can design a tool specifically for your target population of interest, drug effect, etc. However, novel functional outcomes require forethought and planning to develop in preparation for use in a clinical trial. Development of a new outcome requires a full understanding of the construct you are hoping to measure (ie, walking ability, arm function, strength), the anticipated change over time (ie, loss, gain, maintenance of function), and the degree of change expected. Prior to adoption of a novel tool, sufficient research must be conducted to ensure the tool has robust psychometric properties, including assessing several forms of validity, reliability, and sensitivity to change. These studies take time and require longitudinal evaluation.

NEURO CON: How might these novel function outcomes improve clinical trial data?

LA: Novel functional outcomes have the potential to improve consistency and reliability of data collected, as we have the ability to build upon the great foundation of existing outcomes and/or learn from past issues and concerns to move the field forward. Additionally, novel functional outcomes are often developed for a target population or specific goal, rather than using an outcome designed for one population and hoping it works on the next. Novel functional outcomes also have the potential to more sensitively quantify disease-specific changes over time.

NEURO CON: What is the key take-home message from your session for neurologists and researchers?

LA: Selection of outcome measures requires thought and planning prior to initiation of a clinical trial. It is important to remember that just because an outcome has been validated for one population, it may not be useful in another. Consult your outcome measure specialist early in the planning process to ensure there is time to select the proper existing outcome or develop a novel outcome to meet your needs. 

For more information about the ANA’s Annual Meeting or to read more about Dr Alfano’s session, visit the ANA’s website: https://2019.myana.org.

Reference:

1. Alfano L. Designing novel functional outcomes for clinical trials. To be presented at: 144th Annual Meeting of the American Neurological Association; October 13-15, 2019: St. Louis, MO. https://2019.myana.org/sites/default/files/docs/2019/ana19_advanceprogram.pdf.