Metrics that Matter
Assessing “quality of life” in clinical research
Think back on the resolutions you made at the beginning of the new year, the goals you set, the dreams and desires whispered from your heart. Odds are high that if you established objectives as the calendar year flipped at least one of them had to do with health, whether improved mental health (45% of goal-setters), improved fitness (39%), or weight loss and a better diet (37% and 33%, respectively).[1] As temperatures rise, schools let out, and plans are made for the summer, the presence of swimsuits, tank tops, and shorts mean that this time of year, both New Year’s Eve goal-setters and the suddenly motivated are thinking about their physiques and larger health picture.
Some metrics are simple — do the scale and tape measure say what you want them to? If you live with conditions often associated with dramatic improvement through lifestyle management, such as blood pressure or diabetes,[2] are you now able to work with your physician to reduce or stop medications? Do the values on your bloodwork and other lab tests reveal a healthier physical system? Are you stronger, more coordinated, more limber? These things are easy to measure — numbers tell us whether progress is being made and as the adage goes, the numbers don’t lie. But what about considerations that might be impacted by improved health — how do we assign a number to whether you are sleeping or walking better; how much better? What if you tighten up your diet and your finances improve, where do those numbers go? What is the value of being able to capitalize upon improved energy by pursuing a new profession, or improved personal relationships? On and on the questions go, ad infinitum. To add a little more difficulty, how about this one: if you set a goal for weight loss and did not achieve it, but gained better muscle and skin tone through diet and exercise modification and feel great in that bathing suit you just tried on, did you succeed or fail?
If you’re starting to feel like a conversation about pool-side physique goals is becoming a philosophy class, you’re on the right track. How we determine what constitutes success or failure, and how we approach defining each term, reflects a philosophical commitment to underlying values. In the clinical research space, part of applying for Food and Drug Administration (FDA) authorization requires clearly identifying what will be measured, when, and how in the proposed protocol. Research nearly always focuses on safety, efficacy (another word for “effectiveness”), or some combination thereof. By definition, however, pursuit of something first-of-class means no one knows exactly what will improve, over what timeline, and in what sequence. Aristotle teaches “those who wish to succeed must ask the right preliminary questions.”[3] How, then, do we decide what to ask; i.e., what to measure? Well, start just the way Aristotle did — with philosophies.
At Hope Biosciences Research Foundation (HBRF) we are privileged to work predominantly with a particular type of adult stem cell therapy, mesenchymal stem cell therapy, that since discovery 50 years ago has become one of the most widely studied cellular therapeutics by industry and academia, with an established and accepted safety profile. HBRF’s focus is on sustained high-volume administration of cells cultured to an unprecedented degree of cell viability; HBRF is most intrigued by questions about how the stem cells we study will act in the body, to what degree, and over what period of time. This constitutes a completely unexplored area of research, an opportunity to study MSCs at work in new disease conditions, with data-supported hope that an unprecedented degree of progress may occur in conditions commonly considered uncurable, including complete eradication of symptoms in some cases.
HBRF’s first philosophy, our first commitment, is to patients and caregivers. As we begin protocol design, deciding what to measure, we ask patients and caregivers what they hope for. We ask them how their lives have been impacted to date by their current health condition, and what they desperately hope and pray to change. Their answers are often illuminating — a person with a central nervous system condition wants to be able to write a grocery list or note to a loved one clearly; someone in pain daydreams about being able to play easily with children or grandchildren again; an individual with facial paralysis wishes they could find a job without being told during the interview process their lack of expression is off-putting; a spouse wants to be held; a caregiver wants to see their loved one drive again. HBRF often conducts expanded access research — that is, studies in a single individual or small group who would not otherwise quality for participation, often to complex disease conditions with co-morbidities, or age — prior to larger studies. Expanded access brings with it opportunities to truly get to know patients well, and often allows the Hope team a clearer window into the intricacies of living with a particular condition, than does research far removed from a living, breathing person with thoughts and feelings, willing to share about the experience of that condition in a way not readily gained apart from lived experience.
HBRF’s second philosophical commitment is to collaboration. So, we call doctors and researchers who specialize in the condition HBRF intends to study. We ask what assessment tools they are using real-time, today, right now in their practice. We ask what, in their clinical experience, are the strengths and challenges associated with each tool. HBRF’s location only twenty minutes’ drive from the largest medical complex in the world, the Texas Medical Center, is an incredible boon in this regard.
A third, related, philosophical commitment by HBRF is to FDA authorization, as part of making our first pledge to patients a practical reality. We call them, too. We talk to them about what we are hearing from patients and physicians, seeking points of connection between what we are learning from real people doing the work now, and FDA’s guidance on quality of life (QoL) assessments.[4]
In clinical research, “QoL” refers to all the things that make a patient’s life better or more difficult, but are challenging to measure with scales, tape measures, or blood values. QoL scales exist in many disease conditions, usually developed by researchers dedicated to a particular disease and well-versed in it, who observe certain trends in that disease’s progression. Some measures ask patients narrative questions. Some ask patients to assign numerical values to self-assess their current state of function and well-being; others, called Visual Analog Scales (VAS assessments), require participants to depict status in lines instead of numbers, that can then be measured and compared. QoL scales in mental health can be included, to add a dimension to our understanding of how cell therapy in a certain disease condition in a truly wholistic manner. At HBRF we also employ photography and videography, including video interviews, to capture unique elements of personal story and progress.
HBRF cares deeply about QOL assessments because these are the things most true to the experience of a given disease state. In clinical research, we are always measuring, weighing, comparing, analyzing. This is important because measurable, or “quantitative,” data is what moves science forward to a scope and scale that will impact many patients. But someone who suffers a spinal cord injury that leaves them in a wheelchair does not tend to care so much about their measurable levels of nerve function, important thought those values are; they want to walk. That is the story we want to tell, too, and careful selection of QoL assessments forms a powerful part of the narrative.
[1] Sarah Davis, “New Year’s Resolution Statistics 2023,” Forbes Health.
[2] WC Willet, Koplan, Nugent, et al. “Prevention of Chronic Disease by Means of Diet and Lifestyle Changes” in Disease Control Priorities in Developing Countries, Second Edition. DT Jamison, JG Breman, AR Measham, et. al., editors. Washington, D.C.: The International Bank for Reconstruction and Development, The World Bank. New York: Oxford University Press, 2006.
[3] Aristotle, Metaphysics, II, (III), i.
[4] See FDA’s “Focus Area: Patient-Reported Outcomes and other Clinical Outcome Assessment,” “Core Patient-Reported Outcomes in Cancer Clinical Trials,” and related guidance available through fda.gov.
