The much-touted arrival of “precision medicine” promises tailored technologies that help individuals and may also reduce health care costs. New research shows how pregnancy screening can meet both of these objectives, but the findings also highlight how precision medicine must be matched well with patients to save money.
The study involves cfDNA screenings, a type of blood test that can reveal conditions based on chromosomal variation, such as Down Syndrome. For many pregnant women, though not all, cfDNA screenings can be an alternative to amniocentesis or chorionic villus sampling (CVS) — invasive procedures that come with a risk of miscarriage.
In examining how widely cfDNA tests should be used, the study reached a striking conclusion.
“What we find is the highest value for the cfDNA testing comes from people who are high risk, but not extraordinarily high risk,” says Amy Finkelstein, an MIT economist and co-author of a newly published paper detailing the study.
The paper, “Targeting Precision Medicine: Evidence from Prenatal Screening,” appears in the Journal of Political Economy. The co-authors are Peter Conner, an associate professor and senior consultant at Karolinska University Hospital in Sweden; Liran Einav, a professor of economics at Stanford University; Finkelstein, the John and Jennie S. MacDonald Professor of Economics at MIT; and Petra Persson, an assistant professor of economics at Stanford University.
“There is a lot of hope attached to precision medicine,” Persson says. “We can do a lot of new things and tailor health care treatments to patients, which holds a lot of promise. In this paper, we highlight that while this is all true, there are also significant costs in the personalization of medicine. As a society, we may want to examine how to use these technologies while keeping an eye on health care costs.”
Measuring the benefit to “middle-risk” patients
To conduct the study, the research team looked at the introduction of cfDNA screening in Sweden, during the period from 2011 to 2019, with data covering over 230,000 pregnancies. As it happens, there were also regional discrepancies in the extent to which cfDNA screenings were covered by Swedish health care, for patients not already committed to having invasive testing. Some regions covered cfDNA testing quite widely, for all patients with a “moderate” assessed risk or higher; other regions, by contrast, restricted coverage to a subset of patients within that group with elevated risk profiles. This provided variation the researchers could use when conducting their analysis.
With the most generous coverage of cfDNA testing, the procedure was used by 86 percent of patients; with more targeted coverage, that figure dropped to about 33 percent. In both cases, the amount of invasive testing, including amniocentesis, dropped significantly, to about 5 percent. (The cfDNA screenings are very informative, but not fully conclusive, which invasive testing is, so some pregnant women will opt-for a follow-up procedure.)
Both approaches, then, yielded similar reductions in the rate of invasive testing. But due to the costs of cfDNA tests, the economic implications are quite different. Introducing wide coverage of cfDNA tests would raise overall medical costs by about $250 per pregnancy, the study estimates. In contrast, introducing cfDNA with more targeted coverage yields a reduction of about $89 per patient.
Ultimately, the larger dynamics are clear. Pregnant women who have the highest risk of bearing children with chromosome-based conditions are likely to still opt for an invasive test like amniocentesis. Those with virtually no risk may not even have cfDNA tests done. For a group in between, cfDNA tests have a substantial medical value, relieving them of the need for an invasive test. And narrowing the group of patients getting cfDNA tests lowers the overall cost.
“People who are very high-risk are often going to use the invasive test, which is definitive, regardless of whether they have a cfDNA screen or not,” Finkelstein says. “But for middle-risk people, covering cfDNA produces a big increase in cfDNA testing, and that produces a big decline in the rates of the riskier, and more expensive, invasive test.”
How precise?
In turn, the study’s findings raise a larger point. Precision medicine, in almost any form, will add expenses to medical care. Therefore developing some precision about who receives it is significant.
“The allure of precision medicine is targeting people who need it, so we don’t do expensive and potentially unpleasant tests and treatments of people who don’t need them,” Finkelstein says. “Which sounds great, but it kicks the can down the road. You still need to figure out who is a candidate for which kind of precision medicine.”
Therefore, in medicine, instead of just throwing technology at the problem, we may want to aim carefully, where evidence warrants it. Overall, that means good precision medicine builds on good policy analysis, not just good technology.
“Sometimes when we think medical technology has an impact, we simply ask if the technology raises or lowers health care costs, or if it makes patients healthier,” Persson observes. “An important insight from our work, I think, is that the answers are not just about the technology. It’s about the pairing of technology and policy because policy is going to influence the impact of technology on health care and patient outcomes. We see this clearly in our study.”
In this case, finding comparable patient outcomes with narrower cfDNA screenings suggests one way of targeting diagnostic procedures. And across many possible medical situations, finding the subset of people for whom a technology is most likely to yield new and actionable information seems a promising objective.
“The benefit is not just an innate feature of the testing,” Finkelstein says. “With diagnostic technologies, the value of information is greatest when you’re neither obviously appropriate or inappropriate for the next treatment. It’s really the non-monotone value of information that’s interesting.”
The study was supported, in part, by the U.S. National Science Foundation.
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