Reports on an FDA approval should be considered just the beginning when it comes to coverage of new drugs. Journalists need to keep watch on safety issues that show up only in “real world” populations when a drug is marketed to the wider public. It also helps to understand how clinical trials are conducted and delve into the nuts and bolts of published clinical trials to see who was tested and for how long.

The “breakthrough” status of certain hepatitis C drugs gained the medications a lot of positive coverage when nine new drugs came on the scene starting in 2013. They were deemed highly effective — even a “cure” — for a disease that had few effective treatment options. But now serious side effects are coming to light in a new report issued by a drug safety watch group and the addition of FDA “black box” warnings.

A report from the non-profit Institute for Safe Medicine Practices (ISMP) released yesterday states that Sovaldi and Harvoni, marketed by Gilead Sciences, and Janssen’s Olysio, among others, were among antiviral hepatitis C drugs named in hundreds of reports of side effects provided to the FDA after the drugs came on the market. Acute liver failure, reactivation of hepatitis B, encephalopathy, liver transplants and deaths were found in the follow-up adverse event reports.

The drugs cost can cost anywhere from $55,000 to $120,000 per patient, the ISMP notes. “Our data show the need for further investigation into the negative consequences of these expensive and important new drugs,” according to the report.

Why is the public just now hearing about safety issues with hepatitis C drugs?

You might also be wondering why black box warnings often occur after a drug is approved, and why serious side effects don’t emerge during clinical trials.

“Just because the FDA approves a drug that’s not the end of the story,” says Christopher Labos, MD, a Toronto cardiologist and HealthNewsReview.org contributor who writes frequently about health and drug safety issues.

The drugs were welcomed for their ability to work quickly in suppressing hepatitis C infection, says Labos. But unanticipated side effects, including reactivation of dormant hepatitis B in some patients, didn’t show up until after the drugs had been on the market and given to hundreds of thousands of patients since their launch one to two years ago.

“Side effects are very hard to see in clinical trials because they have a very homogeneous, highly selective group of patients,” explains Labos. In the case of hepatitis C drug trials patients with hepatitis B and other potential complications were removed from the group. It’s common for drug sponsors to exclude volunteers with other medical conditions from drug trials.



Where the new data come from

When side effects emerge after they’ve been approved for the market it’s because a broader audience has been exposed. The FDA requires drug makers to report adverse events after the drug is launched as a condition of its approval. Post-market surveillance data, sometimes referred to as phase 4 data, is captured through the FDA Adverse Event Reporting System (FAERS). In many ways, the FDA’s post-market surveillance system works, says Labos.

The FAERS is where the ISMP gathered the data for its quarterly report.

STAT Plus (behind a paywall), FiercePharma, the New York Times and others are now reporting the serious side effects from these drugs, all based on the ISMP report.

We won’t likely be getting much additional insight from the FDA, particularly under a new administration that – by all indications – will keep the release of information tightly controlled. The agency told the New York Times’ Denise Grady: “The F.D.A. does not typically comment on specific studies, but evaluates them as part of the body of evidence to further our understanding about a particular issue and assist in our mission to protect public health.”

These drugs all received expedited FDA approval under its “breakthrough” review process. Keep in mind that the FDA’s definition of “breakthrough” may not be what the typical consumer thinks it means.

On its fact sheet on breakthrough therapies the FDA states: “If a drug is designated as breakthrough therapy, FDA will expedite the development and review of such drug. All requests for breakthrough therapy designation will be reviewed within 60 days of receipt, and FDA will either grant or deny the request.”

Journalists can help track harms found after a drug has been approved

As fast-tracked drug approvals become the norm, and they are, journalists should be paying close attention to post-approval reports of adverse effects. Anyone is free to access the FAERS data, but it can be unwieldy.

The usefulness of the FAERS data “really depends on the journalist’s knowledge and experience in reporting on the risks and benefits of drugs, and on what specific FAERS data they are using,” ISMP’s senior scientist Thomas Moore wrote in an email. “It is a challenge and very time consuming to download the relational database and use it properly. I do know news organizations that have done this successfully.”