Are Friday Drug Safety Alerts Deadly?

 What happens if a drug safety alert goes out and no one pays attention?

Something like that appears to be happening at least one day of the week — and research shows that more patients could experience drug-related side effects as a result.

The Friday Effect

At the end of the work week, people mentally check out and pay less attention to the news.

For that reason, Friday has been known as the day of choice for businesses and governments to release unflattering reports about themselves.

For years, Friday was also when the US Food and Drug Administration (FDA) tended to issue its drug safety communications, researchers found.

But alerts released on a Friday were shared 34% less often on social media, were 12% to 51% less likely to be covered in print media, and were mentioned in 23% to 66% fewer news articles than alerts on other days, according to their study.

When the researchers compared how adverse event reporting and use of medications changed before and after a safety announcement from the FDA, they found that alerts on Fridays had less of an effect on medication consumption and submissions to a key drug-safety database.

The so-called "Friday Effect" is so pronounced that withholding an alert and waiting to release it the following week would be the better course of action, according study author Luis Diestre, PhD, a professor of strategy at IE Business School in Madrid, Spain. The extra attention on other days would more than make up for the delay, he said.

Avoidable Harm?

To examine whether medication safety alerts on Fridays have less of an impact, Diestre and his colleagues studied 441 FDA safety alerts from 1999 to 2016. They looked at data from the FDA's Adverse Event Reporting System (FAERS) to gauge whether alerts led to decreases in reported side effects, presumably because doctors and patients used a drug less often after learning about a new safety issue.

The FAERS database includes incidents of possible side effects associated with medications that were reported by clinicians, pharmacists, manufacturers, and patients. The agency monitors submissions for unexpected safety consequences. FAERS has various limitations, according to the FDA, such as the inclusion of unverified self-reports. As a result, the database on its own cannot be used to determine whether a drug caused a particular adverse event.

Diestre and his coauthors focused on reports of adverse events that listed a drug in a safety alert as the primary suspect and assessed whether the number of reports decreased 1, 3, and 6 months after FDA issued the alert. Did the extent of the reduction depend on whether the safety issue was announced on a Friday vs another weekday?

The answer was clear.

"[M]oving a Friday alert to any other weekday would reduce all drug-related side effects by 9% to 12%, serious drug-related complications by 6% to 15%, and drug-related deaths by 22% to 36%," they write.

The effect was smaller with larger time windows, which "is consistent with the idea that Friday alerts are disseminated more slowly, and thus it takes more time for doctors and patients to be informed," the researchers note.

Financial Influence?

The researchers also found that lobbying activity might play a role in the Friday effect. For drugmakers that lobbied the FDA, Fridays were by far the most common day for safety alerts. About one-third of their safety alerts were announced on that day.

But for companies that did not lobby the FDA, alerts were more evenly spread throughout the work week, with Thursdays equally as likely as Fridays, and Tuesdays and Wednesdays close behind.

"We do not know the extent to which firms and the FDA are aware of the Friday effect and its consequences," the study authors write. "Accordingly, why firms and the FDA behave like they do, and the ethical implications of their behavior, is something we do not and cannot answer in our study."

An Easy Fix?

Diestre and his colleagues reported their findings in 2019 in Management Science.

Anupam B. Jena, MD, PhD, a professor at Harvard Medical School, Boston, and the host of the Freakonomics, M.D. podcast, discussed the researchers' paper on his show about a year ago and revisited the issue last month.

Jena featured the study on his podcast "not only because the study's findings were so intuitive and interesting but because unlike most issues in healthcare, there seemed to be an easy fix," he told Medscape Medical News. "Don't report safety news about medical products on Fridays."

Have regulators have gotten the message?

"We checked with the FDA both during the initial broadcast and the re-broadcast and it was not clear that they were aware of the study's findings or the potential for a 'Friday effect,'" Jena said. "They continue to release alerts on Fridays the last we checked."

The FDA says it releases information as soon as possible, no matter the day of the week.

For whatever reason, however, Friday no longer seems to be as common a day for drug safety announcements.

Diestre sees that apparent trend as welcome news.

"I took a quick look at alerts announced in the last 2 to 3 years and it is true that there are not that many Friday alerts," Diestre said, adding that a careful statistical analysis would be required to confirm the observation. "I don't know if this is thanks to our paper or not, but in any case, I think this is great news given what we find in our study."

Diestre said he understands the FDA's inclination to release alerts as soon as possible, but avoiding Fridays has merit.

The FDA issues drug safety communications (DSCs) "to communicate new and emerging postmarket drug safety issues or adverse events to the public, patients, and/or healthcare professionals," according to Charles Kohler, a press officer for the agency's Center for Drug Evaluation and Research.

Notifications might include information about serious or life-threatening adverse events discovered after a drug is on the market, additional details about a known adverse event, a new contraindication, previously unknown drug interactions, or medication errors that could cause serious reactions, Kohler said.

When weighing whether to issue an alert, FDA officials consider whether information about an adverse event might alter the drug's risk-benefit balance, aid prescribing decisions, or affect a patient's decision to use a drug. Officials also look at whether there are ways to avoid or minimize harm from a drug, the strength of the evidence, and the severity of the adverse event, Kohler said.

DSCs appear on the FDA's website and can be shared on other channels such as MedWatch Safety Alerts, email newsletters, podcasts, and social and traditional media. They are "distributed to more than 500,000 subscribers to email distribution listservs and more than 1.6 million followers to FDA social media accounts," Kohler said.

Officials also work with other federal agencies like Veterans Affairs and regulatory agencies in other countries to keep them informed about safety issues, Kohler said.

"It has been our policy to issue drug-safety alerts as soon as we have all the available information," Kohler said. "Time is a critical factor in drug safety and we can't delay or hold on to critical safety information."

An Art and a Science

Joseph Ross, MD, MHS, of Yale School of Medicine, New Haven, Connecticut, appeared on the Freakonomics, M.D. episode.

While he doesn't doubt that the Friday effect is real, "I do not think that the day of the alert is nearly as important or influential as there being an alert in the first place," Ross told Medscape.

News alerts inform clinicians and pharmacists, who can notify patients. Prescriber resources and electronic health records incorporate the updated information. Eventually, professional guidelines take the safety data into account, which takes the longest and "will not be impacted by whether the alert is released on a Friday or a Monday," Ross said.

Ross's research has found that postmarket safety events are common.

Of 222 novel therapeutics approved by the FDA between 2001 through 2010, 32% were affected by a postmarket safety event, according to one study. Biologics, drugs indicated for the treatment of psychiatric disease, medications that received accelerated approval, and those that were approved close to the FDA's deadline for making an approval decision were more likely to have postmarket safety events.

G. Caleb Alexander, MD, MS, an internist and epidemiologist with Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, said risk communication is "an art and a science."

"Unfortunately, there are many risks about prescription drugs that are learned only after the drugs have been approved," he said.

Alexander has studied the impact of FDA drug safety communications, and found that it's "hard to predict what the precise effect of a given risk communication will be," he said. "Frankly, risk communications can become risks unto themselves."

He pointed to a recent FDA notification about cooking chicken in NyQuil as an example of an alert that could have unintended consequences.

"The FDA's communication about this may have elevated rather than reduced the likelihood of individuals undertaking this misadventure," Alexander said.

Diestre's study was partially funded by the Spanish Ministry of Economy and Competitiveness Project and by the European Regional Development Fund. Ross disclosed research support from the FDA and from Johnson & Johnson through Yale University. Alexander is a former chair and current member of an FDA advisory committee. Jena disclosed ties to pharmaceutical companies.

https://www.medscape.com/viewarticle/981857