https://www.wsj.com/articles/dayquil-covid-vaccine-boosters-and-fda-science-medicine-study-pill-placebo-sick-bb9e457b?mod=opinion_lead_pos6
If DayQuil never seemed to unstuff your nose, now you know why: Its core decongesting ingredient, phenylephrine, doesn’t work.
That’s what a Food and Drug Administration advisory committee unanimously concluded last week, 16 years after researchers first told the agency that evidence from the 1960s and ’70s purportedly demonstrating the ingredient’s efficacy was flawed. For decades, people have been taking what amounts to a placebo.
But unlike a sugar pill, phenylephrine can cause lightheadedness, queasiness, headaches and a rapid heartbeat. What took the FDA so long to act?
Perhaps typical bureaucratic inertia and reluctance to backtrack on “settled science.” This episode mirrors the debate over Covid boosters, which the FDA approved last week, the day before its advisory committee concluded phenylephrine is ineffective. As was the case for phenylephrine, booster recommendations are based on flawed studies and extrapolations.
The FDA concluded in 1994 that phenylephrine was “generally recognized as safe and effective” when administered orally, such as in a cold syrup, “even though the efficacy data were borderline,” according to an agency staff report. Why? Because the ingredient had proved effective when administered intranasally.
Yet studies as early as the 1930s showed that significantly higher doses of phenylephrine than are safe would be needed to have a decongesting effect, since it is mostly metabolized before reaching the bloodstream. At the time, however, the FDA credited positive evidence from poorly constructed industry studies.
When the agency revisited the issue in 2007, an industry meta-analysis of prior flawed studies showed phenylephrine was effective. But as an agency scientific adviser quipped at a regulatory briefing that March, “all meta-analysis is post facto. You only do it if you know you’re going to win.” The FDA then sought more studies to measure the efficacy of higher doses—yet the three placebo-controlled trials between 2015 and 2018 were negative.
In its recent review, FDA staff concluded that early studies demonstrating the drug’s efficacy were flawed and possibly biased. Ten, all from the same industry sponsor, had “multiple methodological and statistical issues” and apparent “data integrity” problems. Two “produced near textbook perfect results that could not be duplicated in other similarly designed studies.”
