The Lowering of the Bar for Drug Approval: Is Evidence Being Ovepowered by Anecdotes?

Category Technology

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A new drug was granted conditional approval by the US Food and Drug Administration (FDA) based on weak clinical trial evidence, likely as a result of anecdotes overpowering evidence in decisions on drug approval. We desperately need to question how these decisions are made and who should be involved in the decision-making process as biotechnology quickly advances.

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Max was only a toddler when his parents noticed there was "something different" about the way he moved. He was slower than other kids his age, and he struggled to jump. He couldn’t run. Blood tests suggested he might have a genetic disease—one that affected a key muscle protein. Max’s dad, Tao Wang, a researcher for a climate philanthropy organization, says he and his wife were initially in denial. It took them a few months to take Max for the genetic test that confirmed their fears: he had Duchenne muscular dystrophy. Duchenne is a rare disease that tends to affect young boys. It’s progressive—those affected generally lose muscle function as they get older. There is no cure. Many people with the disorder require wheelchairs by the time they reach their 20s. Most do not survive beyond their 30s.

The majority of people affected by Duchenne muscular dystrophy are boys, although it can affect girls.

Max’s diagnosis hit Wang and his wife "like a tornado," he says. But eventually one of his doctors mentioned a clinical trial that he was eligible for. The trial was for an experimental gene therapy designed to replace the missing muscle protein with a shortened, engineered version that might help slow his decline or even reverse it. Enrolling Max in the trial was a no-brainer for Wang. "We were willing to try anything that could change the course [of the disease] and give us some hope," he says.

Duchenne is the most common childhood form of muscular dystrophy.

That was more than two years ago. Today, Max is an active eight-year-old, says Wang. He runs, jumps, climbs stairs without difficulty, and even enjoys hiking. "He’s a totally different kid," says Wang. The gene therapy he received was recently considered for accelerated approval by the US Food and Drug Administration. Such approvals, reserved for therapies targeting serious conditions that lack existing treatments, require less clinical trial data than standard approvals.

Duchenne muscular dystrophy is caused by mutations in the dystrophin gene which encodes the dystrophin protein.

While the process can work well, it doesn’t always. And in this case, the data is not particularly compelling. The drug failed a randomized clinical trial—it was found to be no better than a placebo.

Still, many affected by Duchenne are clamoring for access to the treatment. At an FDA advisory committee meeting in May set up to evaluate its merits, multiple parents of children with Duchenne pleaded with the organization to approve the drug immediately—months before the results of another clinical trial were due. On June 22, the FDA granted conditional approval for the drug for four- and five-year-old boys. This drug isn’t the only one to have been approved on weak evidence. There has been a trend toward lowering the bar for new medicines, and it is becoming easier for people to access treatments that might not help them—and could harm them. Anecdotes appear to be overpowering evidence in decisions on drug approval. As a result, we’re ending up with some drugs that don’t work.

It is one of the nine types of muscular dystrophy which can affect children and adults.

We urgently need to question how these decisions are made. Who should have access to experimental therapies? And who should get to decide? Such questions are especially pressing considering how quickly biotechnology is advancing. Recent years have seen an explosion in what scientists call "ultra-novel" therapies, many of which involve gene editing. We’re not just improving on existing therapies, we’re making entirely new ones. Suddenly, we’re facing a world of innovation that wasn’t even conceivable a few decades ago.

The US FDA requires two successful clinical trials for drug approval.

Of course, we should make sure that these treatments are safe and effective, but regulations on drug approval put many of these treatments out of reach, and ethical gray areas only muddy the waters. With so many lives in the balance, it’s hard to know what the right course of action is.

The story of Max is a heartening one. His brothers and sisters with Duchenne may never be as lucky. In a world of weak evidence and new medicines, we need to take a close look at the way in which decisions about drug approval are made. There’s a lot at stake.

Gene therapy is a type of treatment that alters the activity of genes or introduces new genes into the human body.

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