By contrast, independent experts who have expressed concerns about individual drugs or devices have been charged with “intellectual conflicts” and excluded from FDA panels. In November of 2004, the FDA barred adviser Curt Furberg from serving on the panel considering the safety of a class of pain-relieving medicines known as cyclooxygenase-2 (COX-2) inhibitors.208 Prior to the panel meeting, Furberg had been quoted in the New York Times as saying that “Bextra is no different than Vioxx, and Pfizer is trying to suppress that information.” (Both drugs belong to the same class, COX-2 inhibitors.) The FDA cited his statement as evidence that he wasn’t “impartial.”209 In the end, the advisory panel vote was closely split, but Bextra was withdrawn from the market. Furberg’s involuntary recusal was in contrast to the substantial numbers of experts with financial ties to the manufacturer of devices and drugs under review who are frequently appointed to FDA advisory panels.210 If panelists with financial conflicts of interest had been recused from panels, such as the panel that voted to keep the birth control pill Yaz on the market, the vote would have been reversed and Yaz pulled from the market.211–213
Hamburg’s recommendation to include more industry representatives on advisory panels caused a public furor, and she ultimately backed away from her position. But she did manage to push through rules allowing faster drug approvals, a move loudly applauded by industry.
The proclivity of presidents to name industry-friendly leaders to head agencies like the FDA shouldn’t be surprising, given that politicians across the board increasingly rely on industry, especially the drug and device industries, to support their campaigns. During the 2012 presidential campaign, Barack Obama and Mitt Romney each received more than $19 million from the healthcare industry.214 This was no departure from the norm: industry generally funds politicians on both sides of the aisle in order to curry favor with whichever candidate wins. All sectors of the industry get into the act. In 2014, the top two health insurance groups, Blue Cross Blue Shield and America’s Health Insurance Plans, contributed $12 million and $9.2 million respectively to politicians. With the FDA reliant on budgetary support from presidents and congressional leaders who, in turn, depend on the healthcare industry for campaign money, it’s not surprising that the agency should tend to be cautious about thwarting the plans of companies in the medical-industrial complex.
The FDA depends on corporate support in other, less widely known ways. It receives money from industry through the Prescription Drug User Fee Act (PDUFA), passed in 1992, and the FDA’s Center for Devices and Radiological Health (CDRH) first began receiving direct industry funds through the Medical Device User Fee and Modernization Act (MDUFMA) of 2002. The device center also receives support for its programs indirectly through the virtually unknown Reagan-Udall Foundation, which “advance[s] the mission of the FDA by advancing regulatory science and research.”215 The foundation received more than $4.1 million in 2013 from drug and device manufacturers. Overall, 43 percent of the FDA’s budget and 28 percent of the CDRH’s budget come from industry user fees.216
According to a November 2012 report by Partnership for Public Service sponsored by Pew Charitable Trusts, “large sums” of money from drug and device companies “in many ways influence how the FDA will spend the money,” thereby forcing FDA officials to “deal with current political realities.” The authors concluded that those realities were affecting the number of people hired for new drug reviews as well as the timelines for reviews and approvals, which in turn have “distorted the structure of the FDA’s workforce, creating the potential for expertise gaps.”217
In other words, money to speed up approvals was forthcoming. Money to tighten up safety…well, that wasn’t on the agenda.
FDA review times of high-risk devices are indeed faster since 2006. And industry funding not only speeds up the approval process, it also may be playing a role in ensuring that devices win approval. During fiscal year 2015, the FDA approved 98 percent of all high-risk device applications.216 That’s up from 86 percent in 2014.
It’s not hard to point to specific examples of how regulatory capture plays out in the daily operations of an agency like the FDA. Numerous devices have been pushed through the FDA approval process with scant to no evidence of benefit or safety. Some have been deadly. The Sprint Fidelis defibrillator, which was implanted in hundreds of thousands of heart patients, was recalled in May of 2009, after it was found to misfire, seriously harming and killing numerous patients. John Mandrola, a cardiologist, said that when the device misfires most patients can tolerate the first 750-volt shock, but “almost no one can tolerate multiple shocks…after a second or third shock, anxiety…progresses quickly to near terror.”218 The harm is particularly disturbing given that, according to cardiologist Rita Redberg, “many, if not most” defibrillator implants are unnecessary.14
Other cases include the 1999 recall of ProtoGenmesh, which was implanted during surgeries to support internal organs and tissues, after it was found to have caused bowel perforations, bleeding, and at least seven deaths.219
In 2008, the FDA cleared Menaflex, a device made of bovine cartilage and used to repair or replace a torn or damaged knee meniscus. The maker of Menaflex, a New Jersey–based company named ReGen, had pushed for fast-track clearance through the 510(k) pathway, claiming their device was “substantially equivalent” to surgical mesh. FDA scientists rejected the company’s request three times, concluding that Menaflex wasn’t effective, that it caused multiple adverse events in 42 percent of patients, and that the device wasn’t substantially equivalent—after all, surgical mesh doesn’t have to stand up to pounding as it would in a joint like the knee, nor is it made of cow cartilage.141, 220
Faced with rejection, ReGen did an end run around the FDA scientists. They approached their friends in Congress, after which three New Jersey Democrats met with then FDA commissioner Andrew von Eschenbach, who in turn complied with several of ReGen’s requests, including that he put Daniel Schultz, then director of the CDRH, in charge of a new hearing (Schultz was widely perceived as a friend of industry). Eschenbach also required that the agency bar its own scientists from the hearing (ReGen charged that they were “biased”) and agreed to appoint five outside experts recommended by ReGen to the new panel. In fact, Eschenbach not only named Schultz to head the review, he also named Gerald E. Bisbee Jr., who was ReGen’s president and CEO at the time, to the panel.141
Eschenbach was so eager to assist ReGen that FDA attorneys had to tell him to cut a comment he made in a draft of a letter to the company because it could get the agency in hot water by revealing the favoritism shown to the company.141
Unsurprisingly, the new panel Eschenbach appointed overruled the FDA’s own scientists and approved the device without explanation.
In 2010, on the heels of a congressional investigation launched by Senator Chuck Grassley, the FDA acknowledged it had yielded to political pressure, and the agency rescinded its clearance of Menaflex.221 But ReGen appealed the agency’s decision, and on September 26, 2014, an appellate court ruled in favor of ReGen. Ivy Sports Medicine bought out ReGen and now sells Menaflex as the Collagen Meniscus Implant (CMI).222
Donna-Bea Tillman, former director of the Office of Device Evaluation, was criticized for caving to political pressures in the Menaflex case. She left the agency after seventeen years, and in a talk sponsored by the University of Michigan Medical School, she coached device entrepreneurs on the nuances of the 510(k) pathway:
[The] 510(k) is the pathway that most people who are developing new medical devices are likely to run into, and it is the pathway that requires you to identify a predicate device, which is a legally marketed device, [to] show that your new device is substantially equivalent. So that’s what you need to do. And it’s kind of interesting because what I find is that a lot of my clients and a lot of people developing new devices, they want to say, “Oh, my device is novel and it’s new and there’s nothing else like it out there.” And that is absolutely not what you want to tel
l FDA, because you want to be able to say to FDA, “Well, yes, even though I may have some new features or a slightly different technology, it’s substantially equivalent to what’s already out there.” Because that’s what enables you to go through this 510(k) pathway, which is a lot less costly and expensive and burdensome than going down the PMA pathway.223
This double-edged sword of being different while simultaneously claiming substantial equivalence has created a logical loophole exploited by industry, which the Institute of Medicine concluded can’t be repaired. Despite the IOM’s 2011 recommendation to eliminate the 510(k), there has been no movement in that direction. Indeed, industry has been pushing for even fewer restrictions on their march to market.224
In chapter 4, I described how Cyberonics managed to win approval to market the VNS device to treat depression despite the unanimous protests of nine scientists on the FDA’s review panel who considered this approval inappropriate and ill advised. We know what happened in this case because the scientists involved chose to take a public stand—a stand that cost several of them their jobs.
In 2008 and 2009, “the FDA Nine” wrote to Congress, and then to President Obama, complaining about corruption at the agency and political interference.225 In their letters, they cited the Menaflex and VNS cases as examples of the way corruption and political influence at the FDA were trumping science. The scientists also described other questionable FDA rulings. For example, they said that FDA scientists had unanimously recommended against approval of a digital mammography machine. But their recommendation was overturned following a call from Congressman Christopher Shays, who represented the district where equipment for the device is manufactured, to Dr. Donna-Bea Tillman, then the director of the Office of Device Evaluation. (Shays told the New York Times that he called the FDA simply to demand a final decision—not to force approval.)
The FDA Nine also cited approval of a CT colonography device after scientists declined to approve it. One of the Nine, Julian J. Nicholas, MD, PhD, concluded that there was no “demonstrable evidence” that screening with CT colonography would reduce deaths. He also warned that the device wasn’t safe, because a single examination delivers a radiation dosage equivalent to eight hundred chest X-rays—a dose that could cause cancer in between one in seven hundred and one in one thousand screened individuals.226
When Nicholas refused to clear the device, FDA managers indicated they would clear it anyway. Nicholas then asked another medical officer at the FDA, Dr. Robert C. Smith, to independently review the device. Smith agreed and concluded that “the device should not be cleared,” and that if cleared, “it would pose a serious public health risk.”
When it became clear that the FDA was going to approve the device regardless, Nicholas and Smith contacted various legislators, journalists, and a whistle-blower organization in an attempt to forestall approval. When their concerns were published in the New York Times and other media outlets, General Electric, manufacturer of the colonography device, complained to the FDA, suggesting that the FDA Nine were guilty of releasing “proprietary and confidential” information.
Claiming that they needed to monitor any leak of proprietary information, FDA managers spied on the scientists’ private and encrypted Yahoo and Gmail accounts and, according to their whistle-blower lawsuit, “stole the whistleblowers’ confidential communications” with their attorneys, members of Congress, and the US inspector general regarding “allegations of serious wrongdoing by the agency.”
Eventually the FDA fired four of the FDA Nine, and FDA managers asked the Office of the Inspector General (OIG) to initiate criminal proceedings against the FDA Nine. Despite repeated requests by the managers, the OIG declined, each time stating that the FDA Nine had the right to raise their concerns with Congress and the media.
Despite the ruling by the OIG, FDA managers and the agency’s director of the Center for Devices and Radiological Health (CDRH), Jeffrey Shuren, continued their secret spy operation against the FDA Nine for at least two years. But Shuren took the spying to another level: despite the OIG’s assurance that the FDA Nine’s communications with Congress and the media were protected, Shuren filed criminal charges against at least two of the FDA Nine, charging that they may have leaked confidential information to the New York Times.
The FDA Nine countered that the FDA actions violated their constitutionally protected communications with Congress.
After learning of the spy operation, and after six of the nine suffered harassment and retaliatory firings, those six scientists filed suit against the FDA and its managers, including Margaret Hamburg and William Maisel, for interfering with their First Amendment right of free speech. The suit was dismissed in September of 2014 by US District Court judge Reggie B. Walton, who ruled that although the spy operation was “troubling,” the plaintiffs had failed to exhaust administrative remedies prior to filing suit.
Despite the agency’s claimed concern that the FDA Nine were leaking commercially protected information, FDA managers never demanded that the scientists stop their communications or return the documents they shared with Congress or the media—undermining the managers’ claims that the information was actually proprietary.
The FDA’s spying produced no intelligence regarding leaked proprietary information. Instead, according to Stephen Kohn, executive director and attorney with the National Whistleblower Center, who is representing the scientists, they followed the officers’ whistle-blowing activities, using screen shots and minute-to-minute recordings of each keystroke on their computers.142
One of the FDA Nine, Robert C. Smith, the former radiology professor at Yale University who was a device reviewer at the FDA until July of 2010, when his contract wasn’t renewed, told the Washington Post, “Who would have thought that they would have the nerve to be monitoring my communications to Congress? How dare they?”
Michael Carome, deputy director of the public-interest organization Public Citizen Health Research Group, urged the FDA in 2012 to tighten its lax oversight of medical devices. Citing device failures such as a “surgical clip designed to clamp off arteries that pops off, causing patients to bleed to death, and [a type of] artificial hip that shreds metal fragments…causing extreme pain and limited mobility,” Carome said that the “massive lobbying effort” by the device industry was threatening the public health.
One might think that regulators would be moving to close loopholes and tighten restrictions on industry in order to stem the flow of faulty products that reach the market. Unfortunately, the evidence suggests that the FDA is working hand in hand with industry to dismantle even the weak protections currently in place, a problem that has greatly accelerated with the Trump administration.
The history of entanglements between industry and the top brass at the FDA should make the recent scandals unsurprising. In 2005, the FDA commissioner at the time, Lester M. Crawford, mysteriously resigned just two months after being confirmed. His resignation may have been tied to a Justice Department finding that he had illegally withheld information about his financial ties to companies that the FDA regulates.
Daniel Schultz, CDRH director from 2004 to 2009, resigned in the middle of the Devicegate scandal. Schultz was sharply criticized during a Senate investigation by Senator Chuck Grassley for overruling FDA medical officers’ unanimous recommendation not to approve ReGen’s Menaflex knee device and Cyberonics’ VNS device for the treatment of depression. AdvaMed, a trade association for device manufacturers, had praised Schultz for ensuring that the CDRH obtained a constant flow of industry funding.
Jeffrey Shuren, the current director of the CDRH, became acting director in September of 2009. Shuren is so cozy with industry that he had secret meetings with AdvaMed to shape the 21st Century Cures Act, which lowers the bar for evidence needed to approve devices. In December of 2015, Inside Health Policy, an online news service, obtained e-mails and documents under the Freedom of Information Act revealing that Shuren and AdvaMed “met regularly during the legislative p
rocess and that the agency and the device lobbying arm had jointly written legislative text.” The news service wrote that during a meeting on August 7, 2015, AdvaMed “thanked Dr. Shuren and the Center for Devices and Radiological Health team for meeting with AdvaMed regularly during the legislative process for getting the 21st Century Cures Act passed.”
The 21st Century Cures Act, signed into law by President Obama in December of 2016, severely curtails FDA oversight of the medical device industry. The act, says Diana Zuckerman, president of the National Center for Health Research, instructs the FDA “to help drug and device companies get their products on the market more quickly. Unfortunately, it does that by loosening and lowering the very scientific standards that have made FDA approval the gold standard for countries around the world.”227
The act includes provisions that allow the use of what industry likes to call real-world evidence, which could include individual case reports, observational studies, and even speculation based on post hoc subgroup analyses.228 But such low-level evidence is unreliable and has misled doctors and the public in the past—sometimes with disastrous results. Consider the use of high-dose chemotherapy for breast cancer. For decades doctors subjected women to highly toxic doses of chemotherapy and bone marrow transplants in the belief that they were saving lives. But that belief was based on case reports and observational data. When five randomized controlled trials were finally completed in 1999, it was clear that the brutal treatment was no more effective than conventional chemotherapy and caused far more devastating side effects, including heart failure and death.90
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