This transcript has been edited for clarity.
Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.
Milestone birthdays are always memorable — those ages when your life seems to fundamentally change somehow. Age 16: a license to drive. Age 18: You can vote to determine your own future and serve in the military. At 21, three years after adulthood, you are finally allowed to drink alcohol, for some reason. And then… nothing much happens. At least until you turn 65 and become eligible for Medicare.
But imagine a future when turning 30 might be the biggest milestone birthday of all. Imagine a future when, at 30, you get your genome sequenced and doctors tell you what needs to be done to save your life.
That future may not be far off, as a new study shows us that screening every single 30-year-old in the United States for three particular genetic conditions may not only save lives but be reasonably cost-effective.
Getting your genome sequenced is a double-edged sword. Of course, there is the potential for substantial benefit; finding certain mutations allows for definitive therapy before it's too late. That said, there are genetic diseases without a cure and without a treatment. Knowing about that destiny may do more harm than good.
Three conditions are described by the CDC as "Tier 1" conditions, genetic syndromes with a significant impact on life expectancy that also have definitive, effective therapies.
These include mutations like BRCA1/2, associated with a high risk for breast and ovarian cancer; mutations associated with Lynch syndrome, which confer an elevated risk for colon cancer; and mutations associated with familial hypercholesterolemia, which confer elevated risk for cardiovascular events.
In each of these cases, there is clear evidence that early intervention can save lives. Individuals at high risk for breast and ovarian cancer can get prophylactic mastectomy and salpingo-oophorectomy. Those with Lynch syndrome can get more frequent screening for colon cancer and polypectomy, and those with familial hypercholesterolemia can get aggressive lipid-lowering therapy.
I think most of us would probably want to know if we had one of these conditions. Most of us would use that information to take concrete steps to decrease our risk. But just because a rational person would choose to do something doesn't mean it's feasible. After all, we're talking about tests and treatments that have significant costs.
This week, appearing in the Annals of Internal Medicine, Josh Peterson and David Veenstra present a detailed accounting of the cost and benefit of a hypothetical nationwide, universal screening program for Tier 1 conditions. And in the end, it may actually be worth it.
Cost-benefit analyses work by comparing two independent policy choices: the status quo — in this case, a world in which some people get tested for these conditions, but generally only if they are at high risk based on strong family history; and an alternative policy — in this case, universal screening for these conditions starting at some age.
After that, it's time to play the assumption game. Using the best available data, the authors estimated the percentage of the population that will have each condition, the percentage of those individuals who will definitively act on the information, and how effective those actions would be if taken.
The authors provide an example. First, they assume that the prevalence of mutations leading to a high risk for breast and ovarian cancer is around 0.7%, and that up to 40% of people who learn that they have one of these mutations would undergo prophylactic mastectomy, which would reduce the risk for breast cancer by around 94%. (I ran these numbers past my wife, a breast surgical oncologist, who agreed that they seem reasonable.)
Assumptions in place, it's time to consider costs. The cost of the screening test itself: The authors use $250 as their average per-person cost. But we also have the cost of treatment — around $22,000 per person for a bilateral prophylactic mastectomy; the cost of statin therapy for those with familial hypercholesterolemia; or the cost of all of those colonoscopies for those with Lynch syndrome.
Finally, we assess quality of life. Obviously, living longer is generally considered better than living shorter, but marginal increases in life expectancy at the cost of quality of life might not be a rational choice.
You then churn these assumptions through a computer and see what comes out. How many dollars does it take to save one quality-adjusted life-year (QALY)? I'll tell you right now that $50,000 per QALY used to be the unofficial standard for a "cost-effective" intervention in the United States. Researchers have more recently used $100,000 as that threshold.
Let's look at some hard numbers.
If you screened 100,000 people at age 30 years, 1500 would get news that something in their genetics was, more or less, a ticking time bomb. Some would choose to get definitive treatment and the authors estimate that the strategy would prevent 85 cases of cancer. You'd prevent nine heart attacks and five strokes by lowering cholesterol levels among those with familial hypercholesterolemia. Obviously, these aren't huge numbers, but of course most people don't have these hereditary risk factors. For your average 30-year-old, their genetic screening test will be completely uneventful, but for those 1500 it will be life-changing, and potentially life-saving.
But is it worth it? The authors estimate that, at the midpoint of all their assumptions, the cost of this program would be $68,000 per QALY saved.
Of course, that depends on all those assumptions we talked about. Interestingly, the single factor that changes the cost-effectiveness the most in this analysis is the cost of the genetic test itself, which I guess makes sense, considering we'd be talking about testing a huge segment of the population. If the test cost $100 instead of $250, the cost per QALY would be $39,700 — well within the range that most policymakers would support. And given the rate at which the cost of genetic testing is decreasing, and the obvious economies of scale here, I think $100 per test is totally feasible.
The future will bring other changes as well. Right now, there are only three hereditary conditions designated as Tier 1 by the CDC. If conditions are added, that might also swing the calculation more heavily toward benefit.
This will represent a stark change from how we think about genetic testing currently, focusing on those whose pretest probability of an abnormal result is high due to family history or other risk factors. But for the 20-year-olds who are watching this, I wouldn't be surprised if your 30th birthday is a bit more significant than you have been anticipating.
For Medscape, I'm Perry Wilson.
F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his new book, How Medicine Works and When It Doesn't, is available now.
Image 1: F. Perry Wilson, MD, MSCE
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Cite this: The 30th-Birthday Gift That Could Save a Life - Medscape - May 09, 2023.