Tag Archives: Drug approval

Beleaguered FDA in talks for drug-company funding

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Eleanor Laise, Marketwatch: July 13, 2021

Amid a firestorm over its approval of a new Alzheimer’s treatment, the Food and Drug Administration is holding closed-door meetings with companies it regulates — talks that critics say allow drug and device makers to exert outsize influence over the agency’s operations, threatening to erode public trust in the agency at a critical moment.

The talks focus on “user fees” that pharmaceutical and medical-device companies pay to the FDA annually and when applying for approval of new products. The FDA in recent years has become increasingly reliant on such payments, which funded nearly half of the agency’s total spending in fiscal year 2020. In exchange for the fees, the FDA agrees to certain deadlines for reviewing new-product applications, the type and frequency of meetings with companies submitting applications, and other commitments. The medical-product user-fee agreements are generally renegotiated every five years — a process that’s happening now, in advance of the current agreements’ expiration next year — and submitted to Congress for authorization.

Although the FDA is required by law to consult with patient and consumer advocacy groups on the discussions and make minutes of its industry meetings public, the meat of the talks often remains hidden, observers say. Since September of last year, the FDA has held more than 150 meetings with industry to discuss fee agreements for brand-name prescription drugs, generics, medical devices and biosimilars (products similar to branded biologic drugs), which together are expected to generate nearly $2 billion for the agency this fiscal year. Yet consumer advocates and other outside groups attempting to track the discussions say they remain in the dark about most of the details. FDA summaries of some recent meetings have been posted months after the fact or sum up a discussion in a single sentence. Medical-product safety experts say they’ve repeatedly asked for more access and details on the negotiations, to no avail.

“We simply can’t get a view into this process, and the lack of transparency is deliberate,” says Madris Kinard, a former public health analyst at the FDA and CEO of Device Events, which tracks medical-device adverse-event reports.

Details about the negotiations that have trickled out raise alarms among some medical-product safety experts, academic researchers and consumer advocates that the industry’s leverage in these talks ultimately puts patients at risk. User fees are speeding more products to market without a corresponding increase in resources to track the safety of those products, critics say. Yet in the current round of negotiations, FDA efforts to allocate more user fees toward monitoring the safety of medical products already on the market have met industry resistance.

[….]

The main idea behind the user-fee programs was to speed up FDA review of medical-product marketing applications — and they’ve delivered on that front. The median time to approval for standard new-drug applications was 10 months in fiscal 2018. In the years before user fees were first enacted, the median FDA application review time was nearly three years, according to a study by Kesselheim and colleagues at Harvard and Brigham and Women’s Hospital.

[….]

But user-fee deadlines can have serious side effects, some experts say. As the opioid crisis was exploding, “there was a question of ‘Why does the FDA keep approving the opioids?’ ” says a former FDA official. “One reason was that they had applications and had user-fee obligations to review the applications.” So long as an application met the standard requirements, “it would be approved,” he says. “That’s an example of the mindset” created by the deadlines.

Several studies have linked faster drug-approval timelines to safety issues. A 2014 study in Health Affairs found that drugs approved after user fees were enacted were more likely to get new black-box warnings or be withdrawn from the market than drugs approved in the pre-user-fee era. Other studies have found that, compared with drugs approved at other times, drugs given the green light shortly before their user-fee deadlines were more likely to have subsequent safety issues.

[….]

In the current round of medical-device user-fee negotiations, one of the FDA’s goals is to improve device safety, including through increased funding for surveillance of devices already on the market, the agency says. That proposal met stiff resistance from the industry, according to outside groups that have received FDA briefings on the talks. At an April 7 negotiation meeting, the industry expressed the view that fees “should be solely for the premarket review process,” according to a summary posted by FDA. Medical-device trade group AdvaMed didn’t respond to requests for comment.

At the start of the prescription-drug user-fee negotiations, the FDA also emphasized its hope of improving the Sentinel Initiative, a system for assessing the safety of approved medical products. But a related proposal advanced by the FDA during the negotiations was shot down by the industry, a December meeting summary notes.  

[….]

Revolving doors

“There’s not a lot of friction between the industry and the agency” in prescription-drug user-fee negotiations, says a former FDA official. “The industry knows it’s getting good value.”

A sign of the amicable relations: One FDA official leading the current round of prescription-drug user-fee negotiations left the agency in April of this year, according to her LinkedIn profile, to become vice president of science and regulatory affairs at BIO — one of the industry groups she’d just been negotiating with. The former FDA official, Khushboo Sharma, participated in a user-fee negotiation meeting with BIO and other industry representatives as recently as Feb. 12, according to meeting summaries posted by the agency. “That is obviously an outrageous situation and clearly undermines the integrity” of the process, says Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank.

Asked for comment, the FDA sent a link to its post-employment restrictions, which say in part that current employees who have begun seeking employment outside the federal government must immediately recuse from certain matters that affect “the discrete industry, economic sector, or other defined class of organizations in which the prospective employer operates.” BIO didn’t respond to a request for comment. Sharma says that she worked with FDA ethics officials “to ensure I was recusing myself from all appropriate activities. I started seeking post-employment opportunities after negotiations had concluded.”

When the agency’s position does conflict with an industry’s, the FDA “is not going to come out on top,” says Lisa McGiffert, a patient-safety advocate at the nonprofit Patient Safety Action Network. Given the industry’s track record of snagging many items on its wish list, some observers are concerned that the current round of negotiations could chip away at FDA standards for approving new drugs. One issue: the use of “real-world data,” which can come from insurance claims, medical records, disease registries and other sources beyond the bounds of clinical trials. In an August 2020 letter to the FDA about user-fee reauthorization, PhRMA said that real-world data and evidence “may, in some circumstances, be adequate on their own to satisfy the substantial evidence criteria for demonstrating effectiveness” of drugs.

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Janet Woodcock revolutionized the way the FDA reviews cancer drugs, inspiring her supporters and raising concerns for detractors

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Nicholas Florko, STAT News: March 1, 2021

In 2000, the Food and Drug Administration approved just three cancer drugs. Last year, even with the agency laser-focused on the coronavirus pandemic, much of its staff teleworking, the agency still approved a record-breaking 17 different cancer therapies — more than in any other category. That’s the legacy of FDA drug center chief Janet Woodcock. Woodcock, a 36-year veteran of the agency, is infamous for pushing the FDA to loosen its standards for drugs for rare conditions like Duchenne muscular dystrophy. But Woodcock’s most lasting impact at the FDA is her transformation of the way the agency approaches cancer drug approvals….. Now the nation’s top cancer doctors are emerging as Woodcock’s most vocal backers in her campaign to become President Biden’s FDA commissioner.

Critics say Woodcock’s cancer crusade has come at a cost. With the speed has come an erosion of the agency’s high standards and an increasing willingness to greenlight drugs that haven’t actually been proven to extend a patient’s life. … Their complaint mostly revolves around Woodcock’s willingness to accept studies testing drugs based on so-called surrogate endpoints, measures like the shrinkage of a tumor, rather testing a drug based on how long it keeps a patient alive. ….It’s a view that even some former FDA officials hold; one described Woodcock as pushing “flexibility even at the expense of science.”

[.…]

“For many cancers there is an improvement in survival, the question is which drugs are responsible for that and which ones aren’t, that’s the big unknown and that’s what’s so frustrating,” said Diana Zuckerman, the president of the National Center for Health Research. The end result of this confusion, critics argue, is that doctors and patients are left guessing whether a drug is truly effective, or worth the money.

 [….]

Read the full article here.

Does the FDA Have a High Enough Standard for Drug Approvals?

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Shayla Love, STAT News: September 28, 2015

Is the FDA ’s approval process broken? […] Here are some excerpts of the conversation, edited for clarity.

Let me start off by asking: What do you think needs to be improved in the FDA approval process?

Zuckerman: I am increasingly concerned when the standards and criteria for what’s safe and what’s effective is moving more from the pre-market stage, before approval decisions are made, to the post-market stage. More drugs and devices are being approved on a basis of preliminary data, smaller samples, shorter time frames, and sometimes lacking control groups, as what recently happened with Duchenne muscular dystrophy. When that happens, it has a chilling effect on those who are trying to develop treatments and cures. Why would a company spend all of its energy working to do the best possible research if they can get an approval based on a shorter-term study, less definitive data, as long as they encourage patient groups to advocate and lobby for them?

What about the notion that patients and parents living with the disease are really the only ones who can understand what that’s like, and they should be in a position to assess the benefit and risk?

Zuckerman: I think patient perspectives absolutely should be factored in. And they should be factored in at every level. It’s not just important for patients who are wanting a treatment, it’s also equally important for the patients who get harmed. There are some folks in this room who have been harmed by unsafe medical products. They feel like FDA doesn’t listen to them. It’s really important to listen to patients, both the patients who can talk about the benefits of the drugs, or devices, but also the patients who can talk about the risks and the complications.

[…]

Going forward, why wouldn’t we be concerned that other companies won’t be emboldened to try and put an application in, and then force the issue? What we saw with this Duchenne episode is that when you have an effective pressure campaign, that can have an effect. And I’m not saying that’s necessarily a bad thing, that introduces a very human element into the discussion, and it can provide additional information.

[…]

Zuckerman: I want to get into the specifics of why this particular decision concerned us so much. The scientists all said this drug isn’t proven to work, we don’t know if it works, and therefore it doesn’t meet the legal standards that FDA is supposed to use to make a drug approval decision.

The company said they didn’t have a control group because it would be unethical to have a control group. That is a very frightening statement. If you think that it is not ethical to have a control group to study a drug that you don’t know whether it works or not, then you will never be able to find out if the drug works. You have to have a control group, particularly if you have a small sample like that.

Another big issue is the company announced the same day of the approval that this drug is going to cost $300,000 a year. This is a drug that has to be taken every year for the rest of these boy’s lives. It’s not a cure, it’s management. Now, these patients who have been getting this drug, presumably, for free as part of a clinical trial will somehow have to come up with $300,000 a year to continue to get the drug. I don’t know if insurance companies are going to pay for it, considering that the data show there’s not evidence that it works.

[…]

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Obama Extends Controversial Program for Rare Pediatric Drugs

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Ed Silverman, STAT: September 30, 2016

Despite objections from his own regulators, President Barack Obama Friday signed into law a bill that will briefly extend a voucher program that rewards drug makers for rare pediatric medicines.

As a result, the program will run through Dec. 31 while Congress attempts to further extend the effort for another few years. […]

“This is important because if he hadn’t signed this extension, there would have been a gap in the program,” said Nancy Goodman, who is executive director of Kids v Cancer, a patient advocacy group. “And we need to maintain incentives for companies to develop these types of drugs.”

At issue is the pediatric review program, which was created in 2012 and awards a voucher to a drug maker that wins approval of a treatment for a rare pediatric disease, an area of drug development that was seen as neglected at the time.

The vouchers have gained notice in the pharmaceutical industry because they are valuable – companies can later redeem them when seeking approval from the US Food and Drug Administration for another medicine to treat any illness. […]

Moreover, the newly signed law appears to expand the potential for awarding vouchers. How so? The language may widen the patient population for which a drug may be used by broadening the definition of a rare pediatric disease to include symptoms that emerge any time before 18 years of age.

The language reflected an effort to modify the approach taken by the FDA for viewing certain diseases, according to Paul Melmeyer, associate director of public policy with the National Organization for Rare Disorders. This could also become a boon to drug makers. As the FDA Law Blog noted, “diseases that are extremely severe in childhood but tend to be less severe in adulthood may qualify” for vouchers.

Nonetheless, the voucher program is not universally embraced.

[…] the FDA strongly objects to the program.

FDA officials told the GAO they have not seen any evidence the program has encouraged increased development of drugs for rare pediatric diseases. They also maintained the program hinders their ability to set priorities because agency staff must provide priority reviews of new drugs that would not otherwise qualify.

Nonetheless, the push for an extension is also a timing issue. “It’s just before the election, so it’s not surprising for Congress or the White House” to support the extension, said Diana Zuckerman, who heads the National Center for Health Research, a nonprofit think tank.

Read the original article here.

Clinical evidence in FDA drug approvals varies widely, study finds

News Stories & Editorials,
by Sabriya Rice, Modern Healthcare
January 21, 2014

Not every new drug approved by the U.S. Food and Drug Administration has undergone the rigorous clinical testing that physicians and their patients might expect, according to new research.

A study published Tuesday in the Journal of the American Medical Association finds that the FDA has “flexible standards” for approving of new therapies. Using publicly available information from the FDA drug database, investigators identified 188 novel therapies for treating 206 conditions approved between 2005 and 2012. Of these, 37% were approved on the basis of a single clinical trial, 38% on the basis of two trials and 25% had been tested in three or more trials.

Although most therapies were supported by at least one randomized, double-blind trial—the gold standard for clinical research—there was wide variation in the duration, size and completion rates. Comparative-effectiveness data was available for less than half of the indications.The purpose of the study, according to its authors, was not to suggest that the FDA is not rigorous in its approach to drug reviews. The regulatory flexibility allows for a customized approach, and the agency can rapidly approve potentially effective therapies for life-threatening diseases and those for which there is no existing, effective treatment, such as orphan diseases, said Dr. Joseph Ross, assistant professor of general internal medicine at Yale University School of Medicine and one of the study authors.

According to Ross, the drug approval variability is problematic in the sense that both patients and physicians feel the research is the same across all drugs approved.

The FDA, in a statement responding to the findings, explained that drugs may be tested in clinical trials that enroll hundreds of participants, while others, particularly those seeking to treat rare diseases, may be tested in trials that enroll only a handful of participants. “In all cases, however, the statutory standards of safety and efficacy must be met in order for the drugs to be marketed in the United States,” the agency said.

Whether or not the process has become too lenient has become a topic of debate among advocates.

The Progressive Policy Institute, a center-left think tank, acknowledged in a policy brief (PDF) that the FDA must strike a difficult balance. “If it is too lenient, (the FDA) will allow the sale of drugs and medical technology that could harm vulnerable Americans. Too tight, and the U.S. is being deprived of key innovations that could cut costs, increase health, and create jobs.”

Some argue, however, that physicians don’t have time to sift through statistical data on every new drug approved, and when they do, there is little information to choose from as they make decisions about the safety of new therapies.

“With new drugs, there is often an exaggeration of the benefits and underreporting of the risks,” said Diana Zuckerman, president of the National Research Center for Women & Families, who has testified at several hearings on drug safety. “There’s so much emphasis on drugs being the latest, the most innovative and novel—but unfortunately this usually means it’s just new, not necessarily better,” she said.

Zuckerman conceded that it’s a given that the FDA should have the flexibility to provide access to new treatments when there are no available options. “But the FDA shouldn’t be rushing studies for diseases that have good alternatives. It’s better to have an old treatment that is proven to be safe and effective than a new treatment that we don’t know is safe and may not improve health.”

“I think we can all agree that if you have a disease for which there are no available treatment options, that is the time to be flexible, although you’d still want the best possible research,” she said.

Ross, the Yale researcher who worked on the study, encourages physicians to be more nuanced with how new treatments are presented to patients. When prescribing newly approved drugs that have limited trial data, he said physicians should be clearer with patients about what the research shows. The physician should say, “There are not a lot of options, this drug was just approved, but we don’t know if it extends your life,” rather than giving the patient the impression the drug does things for which it has not been tested.

To view the original article in Modern Healthcare, click here.