First Slice of Long-Term “100K” Study: Useful Data, No Health Outcomes

Xconomy Seattle — 

It’s easy to find hope that new biomedical technologies, from genetic sequencing to wearable fitness trackers, will lead to a healthier populace. It’s harder to find evidence. There has even been caution about the idea of analyzing the DNA of seemingly healthy people.

But a small study in Seattle called the Pioneer 100 Wellness Project, published in the August issue of Nature Biotechnology, aims to build evidence that comprehensive testing of healthy people can stave off disease. Study leaders include genomics pioneer Leroy “Lee” Hood (pictured above, center), who for years has pushed for a data-intensive form of healthcare described with four P’s: predictive, preventive, personalized, and participatory.

The data published yesterday take small steps toward that goal, but the number of participants—108 joined the nine-month course, one did not complete it—makes the Pioneer study more like a pilot project. It demonstrates that sizable amounts of personal health data can be stored, tracked, and analyzed; that comprehensive testing might provide some early warnings of ill health; and that researchers mining the data might find new clues to pursue with future experiments. (For example, the authors note that lower levels of the blood protein cystine might point to higher risk of inflammatory bowel disease.)

But the short study was not designed to track health outcomes—the ultimate measure of whether a technology, service, or product is actually making people better. While it seems reasonable that testing people for hidden signs of disease should keep them healthier longer, it’s not so simple. The problem of over-diagnosis has prompted experts to rethink some guidelines, such as those for prostate and breast cancer screening. Tests can return false positives, or can lead to more procedures like invasive biopsies that carry their own risk.

Anecdotal details from the Pioneer project have been available for some time: One participant caught his high mercury levels and cut back on raw tuna; another discovered he had hemochromatosis, an iron disorder. The study leaders have been using those stories to tout a startup, Arivale, which was spun out of the project two years ago with $36 million in private funding from Arch Venture Partners and others. (Arch’s Bob Nelsen, an Arivale board member, is pictured with Hood above, right.) Hood and his colleagues at the Institute for Systems Biology, in Seattle, have a financial stake in Arivale. (Hood, ISB’s founder, is stepping down as president at the end of this year; he is now chief science officer at Providence St. Joseph Health, a medical network in seven western states.)

Participants in the Pioneer study received comprehensive health workups that included a whole-genome sequence, blood, stool, and saliva sample analysis, FitBit monitoring of physical activity, and check-ins with a behavior coach to guide the participant through the results. The idea was to find early signals of a person shifting from a healthy to an unhealthy state, then change their behavior to shift them back.

For example, 95 of the participants began with levels of vitamin D considered outside the healthy range. The study found that at least some participants at the outset were out of range for 31 other proteins and biological markers, including insulin, zinc, mercury, and various cholesterol indicators. For nearly all markers, participants on average showed improvements toward normal range during the study.

Some participants had their conditions flagged and went to see a doctor. While it’s generally recognized in a few cases that changing an underlying marker, like cholesterol for heart disease, leads to better health outcomes, the study was too short to measure whether participants actually got healthier, says Arivale chief translational science officer Jennifer Lovejoy.

Showing those health outcomes is the next step. Arivale and the ISB will each continue down different paths. With more private funding in process, according to regulatory filings, Arivale has begun a three-year study of 1,000 people who have signed up for its service through a large employer. (Arivale sells its service to individuals for $3,499, but it also goes through larger employers looking to lower healthcare costs.)

Arivale will compare the impact on their health insurance costs to the costs of non-Arivale customers who work for the same employer. Arivale declined to name the employer, but Lovejoy said the study will not be a randomized controlled trial.

CEO Clayton Lewis said earlier this year that Arivale is aiming for 5,000 customers by the end of 2017.

Meanwhile, ISB will press on separately beyond its study’s first 100 participants, with a goal of recruiting 100,000 people by 2020. Asked how it would get there so quickly, spokeswoman Gretchen Sorensen said some recruits would come through trials run jointly with the Providence St. Joseph network, and others would come from other as-yet-unidentified partners.

Both Arivale and ISB will have to improve upon the 100 Pioneer study’s lack of diversity. It recruited people only from Seattle and Northern California, and 89 percent were of European ancestry. Even more were non-smokers.

Other groups are pursuing long-term health studies with a smorgasbord of tests. Verily, formerly known as Google Life Sciences, is recruiting people in California and North Carolina for its Baseline study; the federal government has begun All of Us, part of the Obama administration’s Precision Medicine Initiative that, for now, remains intact under Donald Trump.

For the PMI’s All of Us cohort, recruiting a diverse set of Americans is critical. The long- term goal is to have 75 percent of the volunteers from groups traditionally underrepresented in biomedical research, according to All of Us director Eric Dishman. Extrapolating results from white European men and applying them to women or non-white groups “can cause harm,” Dishman told Xconomy in May.

Photo by Xconomy Seattle editor Ben Romano.