In Drugwatch’s 2015 investigation, How the FDA Let Women Down, we highlighted issues with drug and medical device approvals that posed greater risks to women.
Now, we’re diving deeper into regulatory processes to highlight how far they’ve come — and where the administration still falls short in terms of device testing and clinical trials for medical products marketed toward women.
The FDA’s 510(k) clearance process is still allowing moderate-risk devices on the market without clinical trials. Some of these products, such as pelvic mesh, continue to hurt women.
The agency has also been working to approve drugs faster than ever, offering fast-track options for new drugs for serious illnesses such as cancer.
However, mistakes can lead to devastating outcomes when drugs are approved based on lower-quality data. In some cases, the FDA proposed using one clinical trial with patients instead of two to approve drugs faster.
More recently, the FDA has championed AI to help achieve faster drug approvals, but AI has been known to produce false data.
As health care evolves, so do women’s needs and safety concerns. Stronger data and testing requirements can help protect women from dangerous medical devices and drugs.
Medical Approval Processes May Fall Short
While the FDA requires clinical trials for drugs to hit the market, a large number of medical devices are sold without trial data — exposing women and men to health risks.
The 510(k) clearance process allows medium-risk (Class II) medical devices like surgical mesh, some hip implants, catheters, pregnancy tests and others on the market without clinical trials as long as they are similar to devices already on the market.
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Drug approvals, on the other hand, require more testing and clinical data for the FDA to approve them. However, in some cases, the quality of the data submitted may be an issue, and drugs could be approved based on lower standards.
Medical Devices: Inadequate Testing, Conflicts of Interest and Delayed Warnings
Donna Miser’s doctor implanted a surgical mesh bladder sling that was supposed to help her with stress urinary incontinence (SUI), a condition that causes urine to leak when there’s increased pressure on the bladder. Exercising, sneezing or coughing can all trigger these leaks. SUI affects 1 in 3 women.
But no one told her about the risks of mesh.
The implant is supposed to be permanent, but after a few years, the mesh eroded into her bladder and vaginal walls and cut into her urethra in multiple places. She’s since had several surgeries to remove the mesh.
“Someone’s really dropped the ball. I do not understand how so many women got implanted with [this] product. That surgeon looked at me with a smile on his face, telling me, ‘I have got the answer. I’ve got the cure for you. We’re going to put this in you,’” Miser told Drugwatch. “It wasn’t tested. It wasn’t approved.”
The issue with 510(k) approvals is that products can enter the market based on similarities to decades-old devices. This was the case with the surgical mesh implanted in women for SUI or pelvic organ prolapse (POP), a condition where organs slip down and bulge into the vagina.
Another, more rigorous (but less frequently used) path to device approval, Premarket Approval (PMA), requires more scientific evidence. The PMA is intended for high-risk Class III medical devices, such as pacemakers or defibrillators.
Mesh implanted through the vagina for POP has since been reclassified to a Class III device and now requires more testing before it’s sold, but SUI mesh remains a Class II.
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“Missing Safety Device Data May Delay FDA Warnings
The FDA’s Manufacturer and User Facility Device Experience (MAUDE) system is a searchable database for medical device complications. The FDA uses it to flag safety data and determine if it needs to take action.
Madris Kinard of Device Events used to work at the FDA as an adverse events subject matter expert for devices and unique device identification (UDI). Kinard spoke to Drugwatch and cited a report on a problematic birth control device called Essure. With Essure, doctors implanted two metal coils into the fallopian tubes. This caused scar tissue to develop, blocking the tubes and preventing sperm from reaching the egg.
Women reported thousands of complications from Essure that led them to get it surgically removed.
Kindard’s FDA database analysis showed that about 32,000 device complaints from inspections of Essure’s manufacturer in 2011 and 2013 hadn’t made it into the FDA’s database. Kinard said it’s not clear whether these complaints contained adverse event reports because the details haven’t been made public. The FDA still hasn’t responded to her Freedom of Information Act (FOIA) request.
If that data had been added to MAUDE, it might have given the FDA more information to warn women about Essure sooner.
“That set them back by probably 10 years in identifying these problems,” Kinard said.
Drugs: Poor Evidence for Approval, Improper Doses for Women and Underrepresentation in Clinical Trials
Unlike the 510(k) clearance pathway for medical devices, drugs require more clinical trial data for approval. One of the most important parts of the drug approval process is when the FDA looks at the risks and benefits from clinical trial data submitted by a manufacturer. The FDA expects the manufacturer to conduct two well-designed clinical trials, but in some cases, it will accept one.
To determine if drugs work safely, the FDA uses four minimum criteria to judge whether manufacturers have provided enough evidence for drug approval.
The report revealed that the FDA approved these drugs without clinical trials that met the minimum four criteria of having a control group, blinding, replication or clinical endpoints.
“More medical products have been allowed on the market in the last decade based on skimpier research, or research studying biological markers that patients can’t feel (such as plaques on the brain or bone density) rather than meaningful health benefits such as living longer or spending less time in a hospital,” Diana Zuckerman, President of the National Center for Health Research and a project advisor for The Lever, told Drugwatch.
“We knew going in that the FDA had relaxed its scientific standards over the years and that the result was drugs getting on the market without adequate evidence that they work,” Lenzer told Drugwatch. “We didn’t know just how bad it was.”
Lenzer and Brownlee were also surprised by how many cancer drugs in the data they pulled made it to the market without adequate proof they work. The exact cancer medications are included in the table above.
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Improper Dosing Can Lead to More Side Effects For Women
Women experience side effects nearly twice as often as men, and one of the reasons is that medications take longer to leave women’s bodies.
Even with researchers recommending dose reductions for women, the FDA hasn’t taken meaningful action to require sex-specific dosing information on drug labels.
One study in Biology of Sex Differences looked at 86 drugs and found that (when compared to men), women generally had higher blood concentrations of the drugs, and the medications took longer to leave their bodies. This led to higher rates of side effects in women in 96% of cases.
The findings in this study suggest that women may have been prescribed higher doses of drugs than necessary, even when they take the dose recommended on the drug’s label or as directed.
Medications studied included common OTC and prescription medications such as aspirin and Zoloft (sertraline).
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When we interviewed Zuckerman in 2015, she highlighted the lack of women, people of color or people over age 65 in clinical trials. Over the past 10 years, the FDA has increased the number of women in clinical trials, but still lags behind with women of color and older women.
“Most trials submitted to the FDA include quite a few women, but they are not women of color or women over 65, even though many diseases are more common on people over 65 and at least as prevalent in people of color,” Zuckerman told Drugwatch.
While it’s great that more women are finally included in trials, the benefits might not be seen for a few years. Most drugs on the market today were approved during older clinical trials. The data from these trials were primarily gathered from men, leaving a gap in safety data for women.
Expert Opinion: How Can the FDA Improve Drug Safety?
When it comes to drug safety, the FDA needs to require more stringent clinical trial evidence before allowing drugs onto the market.
“The problem for the agency is it is now hamstrung by Congress, which has, over the years, steadily eroded the statutes governing drug regulation,” Lenzer said. “In addition, we believe that PDUFA has to be repealed.”
The PDUFA, or Prescription Drug User Fee Act, allows the FDA to collect fees from drugmakers in exchange for expediting their medications’ reviews and approvals.
“Nobody wants to talk about that because it would almost certainly require public funding, but an agency that is paid by the industry it is supposed to regulate — almost by definition — cannot be independent. What that means for the FDA is it no longer protects the public health and patients because it’s too busy protecting the commercial interests of its benefactors,” Brownlee added.
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