A watchdog group sets aside emotions to assess drugs’ value. Patients say their lives are more than a number

Health economists walk a precarious tightrope: Their analyses are quantitative and, presumably, emotion-free. But health care is intensely personal — and often, intensely emotional.

That tension between between quantitative analyses and lived experiences was on full display at a recent meeting of the Institute for Clinical and Economic Review, a nonprofit that tasks itself with determining what a drug is worth based on factors like how well it works and how much it helps patients.

ICER had set out to review evidence for three drugs that treat — but do not cure — Duchenne muscular dystrophy, a rare and fatal disease that causes affected people’s muscles to deteriorate over time. For them, the question is a basic — and, yes, quantifiable — one: Do the drugs improve the lives for these patients enough to justify the price tags, which can cost hundreds of thousands of dollars each year?

For the patient advocates who attended the meeting — most of whom were parents of children with Duchenne — even asking the question at all seemed tantamount to putting a price on their child’s life.

“It’s an extremely uncomfortable position,” said Mindy Leffler, the parent of a child with Duchenne and one of four patient advocates chosen to speak during the meeting. “How am I supposed to make some comment on the value of my son’s life?”

“I’ll be honest, that’s why we don’t have you vote,” said Stephen Pearson, the president of ICER, to Leffler and the other advocates. “We don’t think that’s fair, certainly.”

But that exchange echoes questions that have become increasingly significant to the biopharmaceutical industry — that is, what value do drugs have? And who ultimately gets a say in deciding how much they’re worth?

ICER’s analyses and decisions hinge on one metric — the quality-adjusted life year, or QALY. The higher the cost per QALY, the less cost-effective a drug is.

The idea behind QALYs is simple: measure how someone’s experience of life is changed by a particular condition. A healthy person experiences one quality-adjusted life year each year; a dead person has zero. Surveys help economists come up with numbers in the middle. Usually, those surveys ask how well someone can move around on their own and take care of themselves; they also often ask about people’s physical pain and what effects the condition has on their emotional and mental health.

To determine what kind of effect a drug might have, ICER’s team analyzes evidence to suss out if the drug actually works.

The analysis is relatively straightforward. Take eteplirsen, one of the drugs up for consideration at the recent meeting, which is also called Exondys 51. The drug’s efficacy is particularly controversial because the FDA approved the drug in 2016 over the objection of its own advisory panel.

Sarepta, which makes the drug, says it should cost about $300,000 per year. ICER spoke with insurance companies and did its own calculations, however, and determined that the product, which is dosed based on a person’s weight, could cost closer to $1 million per year.

Then it set out to determine whether it was worth it. It looked at published trial results about the drug’s efficacy, it even requested more information from the drug’s manufacturer. (Sarepta declined to share any.)

After hearing testimony from patients and experts, a panel of experts voted on a number of questions about the drug’s benefits and cost-effectiveness.

Just one person on ICER’s panel said the available evidence showed the drug improved people’s health. Similarly, just one person voted that the drug had “intermediate” long-term value for its price; the rest said it had a “low long-term value” based on its price and the available evidence.

ICER’s report concluded that “at its current price, no plausible treatment effects were found to make this treatment reach cost-effectiveness thresholds.”

ICER has no real power as a regulator; its panels’ findings and decisions are not binding. But insurance companies can still use its reports as a guidepost for decisions about what drugs to cover. Last August, for example, CVS Caremark announced it would allow its clients to use ICER’s analyses to exclude some drugs from their formularies.

The implications of that connection have distressed some patient advocates.

“It is unfathomable that after all we have gone through, a private, non-governmental group can take away access to the only treatments that exist to help my children,” wrote Jennifer McNary, a patient advocate and the mother of two children with Duchenne who attended last Thursday’s meeting.

Specifically, many advocates disagreed with how “cost-effectiveness” was defined and measured — something that advocates focused on rare diseases have brought up before at ICER meetings.

ICER’s review for Duchenne drugs segmented affected people’s lives into four categories, primarily defined by whether a person can move around on their own. Those definitions line up well with clinical trials of eteplirsen, which measured how far a person could walk in six minutes as one shorthand for how well the drug was working.

But to patient advocates, those segments — and, more broadly, the QALY metric — were inappropriate.

“Nobody cares about speedwalking,” Leffler reported her son said. Leffler, an advocate who testified at the ICER meeting, is the president and chairman of a company, Casimir, that develops new ways of collecting data for clinical trials.

She and the other advocates argued that the way individuals’ limits change over time matters more than how they perform on a more standardized test, like how far they can walk in a set time. Looking at the outer limits of a person’s abilities could show more clearly the benefits that parents have purported to see, they say.

One person may have struggled with getting into a minivan before taking the drug; a parent might have been watching to see when their child could no longer lift a fork. Christine McSherry, who is Casimir’s CEO, told the ICER panel that she believed eteplirsen was working for her son, Jett, because he was able to open a can of beer on his own.

“A parent’s daily assessment is not whether their child is walking or not, but noticing a series of thousands of tiny deaths,” said Fleur Chandler, a health economist and the mother of a child with Duchenne who spoke at the ICER meeting.

Duchenne advocates aren’t the only ones who have taken issue with ICER’s analyses. Khrystal Davis, the mother of a child with spinal muscular atrophy, told ICER in March that its models didn’t adequately account for the time she and her husband didn’t have to spend in the hospital with her son Hunter, after he began taking a drug called Spinraza. She said the drug gave her the chance to spend time with her other children, and gave her husband more time at work.

“Since beginning Spinraza in 2016, Hunter has not been hospitalized,” she said a March 2019 ICER meeting on SMA treatments. “The QALY measure fails to capture any of these significant economic aspects.” (ICER ultimately determined that Zolgesma, a gene therapy for SMA with a $2.1 million price tag, could be cost-effective, with widespread screening; Spinraza, however, which costs $375,000 annually after one more-expensive, higher-dose year, was not.)

ICER’s leaders have heard these critiques before — and they’ve tried to respond to some.

Before the report is even written, noted Pearson, ICER’s president, the nonprofit contacts advocacy groups to ask for their input — and many of the concerns that advocates expressed last Thursday were included first in a short section in the final draft report.

“We don’t know what we don’t know, and we’re going to do a review here — tell us what it’s like to live with this condition,” Pearson said ICER asks advocates. “What does value mean to you? What are the key outcomes that the studies do or don’t capture that you think we should pay attention to?”

But ICER’s reports are unlikely to stop using QALYs anytime soon. “It’s used by academics, it’s used by drug companies themselves, it’s used by countries around the world,” Pearson said of QALYs. “It’s easy to mischaracterize it,” he added.

Pearson has acknowledged that QALYs can be inherently flawed, and ICER’s recent reviews have also used another measurement that looks only at the number of years a treatment may add to a person’s life, too; the results were substantially the same.

“We don’t always get this right — and obviously, there’s no one right answer,” Pearson said at the beginning of Thursday’s meeting. “The ability to wrestle with this in public, we feel, is a very important process.”

An earlier version of this story incorrectly characterized ICER’s assessment of Zolgensma.