Intrinsic capacity, a measure of a person’s physical and mental abilities used to evaluate drugs targeting aging, lacks a measurement standard, says John Beard, who led the WHO work that introduced the concept

Intrinsic capacity, a measure of a person’s physical and mental abilities used to evaluate drugs targeting aging, lacks a measurement standard, says John Beard, who led the WHO work that introduced the concept

On October 19, Longevity.Technology published an interview with Beard, a professor at Columbia University.

WHO distinguished a person’s own abilities from the support their surroundings provide. “To sit and talk with you, I need a chair,” Beard explains. These abilities were termed intrinsic capacity and grouped into five domains: cognition, mobility, psychological capacity, sensory capacity, and vitality (energy).

Drug developers need the measure to obtain results sooner. Detecting a drug’s effect on disease would take about twenty years, whereas a rigorous, sensitive measure of intrinsic capacity could theoretically detect gradual changes in midlife and earlier, Beard argues. ARPA-H, the US agency that funds high-risk medical research, is building its PROSPR program around this measure. Program manager Andrew Brack said the program would combine information from 20 datasets into a single “PROSPR IC” score and seek FDA recognition so that any developer could use it.

“I don’t think we have standardization of intrinsic capacity, and that is a major problem,” Beard says. Most studies, he says, use tests drawn from large surveys of older adults, whose cognitive assessments may be designed primarily to detect dementia rather than gradual changes. In many studies, he adds, abbreviated tests for individual domains are simply added together to produce a single score, even though “losing a little hearing or needing glasses is very different from losing a substantial amount of cognitive function, yet they may produce the same score.” Many researchers use “very inappropriate, poor measures” to validate biomarkers of aging. Unless this is corrected, he warns, “the whole field will be destroyed. It will lose credibility.”

An ARPA-H working group that included Beard also identified the gap in calculating an overall score. Its May 18 document for the FDA states that there is no generally accepted scoring method for trials. The group describes its proposed tests and scoring rules (version 1.0) as “a starting point rather than a final standard” and recommends measuring the five domains separately. A review of 53 studies also found substantial variation in measurement methods.

WHO introduced a clinical version of the measure through its ICOPE program, which was designed as an entry point to care for older adults and uses a whisper test to assess hearing. Trials need a different measure, Beard says, because this test “will not help detect gradual change.” He proposes a tiered approach comprising a full set of rigorous tests, brief tests, and biomarkers. “There is a lot of work to do, but it could be done in a few years with investment.”

Asked whether a trial of GLP-1 drugs (such as semaglutide) had used this measure, Beard answered “no.” Pharmaceutical companies are interested, he says, and once a measurement method is agreed upon, including it in a trial would be “relatively straightforward.” According to its organizers, such a trial within PROSPR is already recruiting participants. VITAL-H compares semaglutide and another drug with placebo in generally healthy people aged 60–75 and, according to Brack, will test whether the drugs improve intrinsic capacity over three years.

Beard says researchers need to “pause and say that there must be a standard for measuring these outcomes if we are going to validate some of the biomarkers and interventions we are studying. At present, there is no such standard.”