Category Archives: In the News
The 21st Century Cures Act could be a harmful step backward
Susan F. Wood and Diana Zuckerman, The Washington Post
November 19, 2015
Precision medicine is the next big thing in health care, and it’s also one of the few health goals that Congress and the White House agree on. But while we await treatments targeting the precise genetic makeups of individuals and diseases, medical researchers still are not paying enough attention to the most important kinds of differences among patients: those of sex, age and race.
A clear example of this disconnect is the 21st Century Cures Act, which was passed overwhelmingly by the House of Representatives and is being scrutinized by the Senate. The stated goal of the bill is wonderful: to stimulate the development of new cures for a range of diseases. Many medical schools and patient organizations are supporters, since the proposal would provide almost $9 billion more for the National Institutes of Health — including a boost for precision medicine. The 360-page bill offers other potential benefits as well. But an immediate impact would be to ignore how differences between men and women and younger and older patients influence the safety and effectiveness of many medical products.
Throughout the 20th century, most medical research was conducted on relatively young, healthy men. In recent years, researchers have realized that treatments often affect women and older patients differently than men or younger patients. These differences can affect safety and effectiveness. The sleeping pill Ambien, for example, makes women drowsier for longer periods than it does men, putting them at risk if they drive the next morning. Since most medications are taken by people older than 65 and women of all ages, it makes sense to analyze the effects of age and sex on the drugs’ safety and effectiveness before they can be sold.
But the 21st Century Cures Act is based on the assumption that there will be more cures if drugs and devices are studied more quickly by testing them on fewer patients — in some cases, on just a handful. Unfortunately, such studies would be too small to allow safety and effectiveness findings to be broken down for subgroups such as men, women, young adults and seniors.
This embrace of smaller, more preliminary studies could drastically lower scientific standards. When fewer people are studied, it is more likely that a drug will seem safe and effective even if it has dangerous side effects for many patients — who may not have been included in those small studies.
In addition to allowing smaller studies, the House bill would encourage the Food and Drug Administration to determine a drug or device’s effectiveness based on “clinical experience,” which the bill defines to include the experience of one or more doctors or patients. Scientists call these anecdotes and note that just because one doctor has had success treating a few patients with a particular drug does not prove it is either safe or effective. Worse, the bill specifies that after studying only small groups of patients, drug manufacturers could sell a new treatment to anyone, even if the patient was not among the types studied. In fact, hospitals would be paid extra to make it financially feasible to prescribe more expensive new drugs to Medicare patients, even if the drugs were never studied on patients older than 65 (the age of most Medicare patients).
Similarly, lifesaving medical devices, such as heart valves, could be approved based on case histories, which are written descriptions of the experiences of just one or two patients. They are unlikely to be good predictors of how a treatment helps or harms most patients.
The recalls of drugs such as Vioxx and devices such as metal-on-metal hips in recent years have made clear that inadequate testing can produce ineffective and harmful products. And since new drugs tend to be much more expensive than older ones, the costs of widely used, unproven medical products can be enormous in both human and economic terms.
These sections in the 21st Century Cures Act go in the opposite direction of the push for precision medicine and what we’ve learned about differences between male and female and older and younger patients. The General Accountability Office has concluded that the NIH needs to make a priority of analyzing data related to sex differences. Just three years ago, the House and Senate overwhelmingly passed legislation that directed the FDA to ensure that men and women, old and young, are studied, with results analyzed to see which treatments are safest and most effective for whom. Why is Congress undermining that law?
Congress should surely increase funding for research to find 21st-century cures, but the price should not be returning to early-20th-century standards, when unproven medical products were widely available and often put all Americans at risk.
See the article here.
Senate counterpart to 21st Century Cures bill is struggling
BRETT NORMAN, POLITICO
OCTOBER 25, 2015
The Senate’s companion effort to the House-passed 21st Century Cures is struggling to navigate a dramatically different political reality than the one that helped rocket the medical innovation bill through the lower chamber over the summer.
The HELP Committee is aiming to release its draft of the Innovations for Healthier Americans Act next month, but it missed earlier targets in September and October. If it’s not out soon, it won’t be possible to gather feedback and mark it up by the end of the year – the goal Chairman Lamar Alexander (R-Tenn.) has set.
It will make fewer changes to how FDA reviews medical treatments – and will likely be less expensive – than the Cures bill the House overwhelmingly passed in July.
Since the summer, the debate over high prescription drug costs has intensified and complaints from public safety groups about Cures’ FDA reforms have grown louder. That’s drawn added scrutiny from Democrats to provisions viewed as pharma-friendly, as well as pressure to address drug prices, a highly partisan topic on the Hill.
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“You have a House bill that has many negative aspects from a public health point of view and has one big positive aspect – a lot of additional money for NIH,” said Diana Zuckerman, president of the National Center of Health Research, and a critic of the House Cures bill. “You have a Senate that cannot create that same big pay-for. You can see why it’s not moving that quickly.”
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The Senate is a very different place. The bill moved so quickly through the House that “by the time the criticism started coming out, it had already passed,” Zuckerman said.
Read the full article here.
Approved but not proven: what’s up with FDA, cancer drugs?
Nick Mulcahy, Medscape Medical News
October 22, 2015
In approving new cancer drugs, the US Food and Drug Administration (FDA) is now heavily relying on surrogate markers of effectiveness, such as tumor shrinkage, instead of proof that an agent improves survival, according to a new analysis.
The investigators conclude that this might be having a deleterious effect on patients, public health, and healthcare costs.
“Our results suggest that the FDA may be approving many costly, toxic drugs that do not improve overall survival,” write Chul Kim, MD, MPH, from the National Cancer Institute (NCI), and Vinay Prasad, MD, MPH, from the Knight Cancer Center at the Oregon Health and Sciences University in Portland.
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Lack of follow-up is part of the problem here.
Postmarketing studies with results are missing for about one-third of the drugs approved with surrogates. This means that the survival effect of 13 of the 36 drugs approved on the basis of surrogate markers is still untested or without reported results.
Enforcement of postmarketing studies is of “critical importance,” Drs Kim and Prasad write.
Their study is timely, given Congressional debate on how the FDA approves drugs and medical devices. In July, the House passed the 21st Century Cures Act, which encourages the use of surrogate markers as one way to speed new drugs to market. Opponents of the legislation, however, say that its lax standards would permit unsafe and ineffective products to reach the marketplace. The Senate is deliberating its own version of the House bill.
Surrogate markers, especially tumor response rate, should not be used to approve cancer drugs, according to a critic of the approval process for cancer drugs in the United States.”It’s outrageous that tumor shrinkage is a basis of approval,” said Diana Zuckerman, PhD, from the National Center for Health Research in Washington, DC, who was asked for comment.”Cancer drugs are good at killing cancer cells,” Dr. Zuckerman told Medscape Medical News. Thus, tumors respond to the toxic agents and die or shrink, which is typically captured by radiographic imaging and is reported as an overall rate in clinical trials. But the problem is that they also kill healthy cells, and overall survival might not improve.
“It’s important to know if the patient will live longer,” she said.
In their study, half the drugs (18 of 36) approved on the basis of surrogate markers were eventually found to not improve survival, Drs Kim and Prasad report.
Pharmaceutical companies have “no incentives” to speed up the survival discovery process, unless early signs of survival improvement are obvious, said Dr. Zuckerman, whose nonprofit think tank receives funding from individuals and foundations and focuses on the safety, efficacy, and quality of healthcare in the United States.
But the FDA has incentives to approve drugs on standards less stringent than improved survival, she noted.
“The FDA is trying so hard to please Congress and industry that they are approving drugs on the basis of flimsy evidence, and patients are being harmed,” she said.
Agency budget is one of the motivators for the FDA to loosen its standards, Dr. Zuckerman explained.
The use of surrogates in cancer drug approval seems to be here to stay, she said, citing a personal conversation she had with an ex-FDA official. There is no real debate about using progression-free instead of overall survival. “That ship has sailed,” she said, repeating her source’s comments.
The NCI has also transitioned to emphasizing progression-free survival as a primary outcome in its funded studies, she observed.
However, some of the drugs approved using surrogates during the study period have been hailed as practice-changing and have led to dramatic improvements. For example, vismodegib (Erivedge), which was approved in 2012 for locally advanced or metastatic basal cell carcinoma on the basis of treatment response rate, was called “the greatest advance in therapy yet” in an editorial published that year in the New England Journal of Medicine (2012;366:2225-2226).
Dr. Zuckerman was not swayed. “Some patients have been helped by approvals using surrogates, but the vast majority have not,” she opined. As Drs Kim and Prasad report, half of the drugs did not improve survival despite approval, and only five of 36 have been proven to improve survival, she added.
Read the full article here.
Cancer and Military Service
Nicholas J. Jury, PhD and Diana Zuckerman, PhD
2015
Cancer has many causes. The main ones that experts can identify are linked to heredity and environment. Members of the military and their family members have the same risks from heredity as others do, but are sometimes at higher risk of certain cancers because of exposures in their environment.
Can Military Service in Afghanistan and Iraq Increase Cancer Risk?
Are Gulf War veterans more likely to get brain cancer or lung cancer than other veterans? Are troops returning from Iraq and Afghanistan likely to become ill from chemicals spewing from open air pits where garbage was burned on military bases? Since the garbage includes tires and other products made of materials that can be toxic when burned, the Cancer Prevention and Treatment Fund is urging safety measures to prevent toxic exposures on military bases and studies of the health risks. This is a situation where common sense should prevail: open air pits that burn toxic materials are dangerous to the health of those nearby.
Camp Lejeune and Contaminated Drinking Water
Contaminated drinking water at the Marine Corps Base Camp Lejeune in Jacksonville, North Carolina put military families and civilians who lived or worked there from the 1950’s through the 1980’s at risk for cancer and other serious diseases.
- Men living or working on the base from the mid-1950s until 1987 have been much more likely to develop breast cancer than other men. Breast cancer is rare among men, and men often do not recognize the symptoms and so delay treatment.
- Pregnant women who were exposed to more contaminated drinking water at Camp Lejeune were 4 times as likely to give birth to children with serious birth defects compared to women who were less exposed. Their children were also slightly more likely to develop childhood cancers such as leukemia.
We have been strongly urging U.S. officials to continue investigating how contaminants at Camp Lejeune have harmed children and adults in letters to Congress and in public statements.
Agent Orange and Vietnam War Veterans
Agent Orange was used by the U.S. military during the Vietnam War to clear vegetation to make it easier to see enemy soldiers. Agent Orange was contaminated with dioxin, making it much more dangerous. Nearly 1.5 million veterans were exposed when 20 million gallons were sprayed over Vietnam.
- New research indicates Agent Orange may increase the chance of developing a cancer of the bone marrow called multiple myeloma.
- The Institute of Medicine has concluded that people exposed to Agent Orange are more likely to develop chronic B-cell leukemia, chronic lymphocytic leukemia, Hodgkin disease, Non-Hodgkin disease, prostate cancer, respiratory cancers, and soft tissue sarcoma. They are also more likely to develop Type 2 diabetes, high blood pressure, stroke, Parkinson disease, heart disease, and peripheral neuropathy.
For more information, see Agent Orange and Serious Diseases including Multiple Myeloma.
Would Washington’s FDA fix cure the patients or the drug industry?
Alec MacGillis, ProPublica
October 20, 2015
This might seem to be a rough political patch for the pharmaceutical and medical device industries. The exponential price increases of several drugs have brought scrutiny to the overall rise in drug costs and have prompted several 2016 candidates, most notably Hillary Clinton, to vow action to rein in the industry. Meanwhile, thousands of complaints are pouring into the Food and Drug Administration about a contraceptive implant made by Bayer.
In Congress, however, things are looking better for the manufacturers. Legislation is advancing that would speed up the FDA’s approval process for medications and medical devices, offering a rare example of how major initiatives can get traction even in today’s gridlocked Washington.
The industry has mounted a major lobbying and public relations push for the 21st Century Cures Act. The bill, in turn, has garnered an unusually broad range of support, ranging from Republican lawmakers and conservative think tanks to the White House, patient advocacy groups, Democrats and nonprofit organizations that are typically leery of deregulatory efforts by industry. One reason: Lawmakers softened up the usual opponents of looser rules with a big carrot — billions of dollars in new federal medical research funding for the National Institutes of Health. After years of austerity, that money is awfully difficult to turn down.
But the enthusiasts have left a small band of critics warning that bipartisan consensus does not necessarily affirm the bill’s worth. Far from showing that Washington can still get big things done, they say, it shows how a lobby can blow past skeptics if the pot of resources is sweet enough. They maintain that the bill, which easily passed the House in July and has a counterpart soon to be introduced in the Senate, hasn’t received the scrutiny that such sweeping legislation deserves.
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The promised NIH money also brought on board major universities, which carry out about $15 billion of all NIH-funded research. “It was the investment in NIH that led everyone to get behind it,” said Atul Grover, chief public policy officer at the Association of American Medical Colleges. “As soon as we talked about innovation, people said, look, you can try to grease the skids on the approval process, but if we’re not investing as a nation in research, then this other stuff is not going to make much difference. You have to invest in cures to get them.”
The list of entities lobbying on the bill now runs to about 1,800 quarterly entries in the Senate’s lobbying database, with more than 1,100 lobbyists registered as working on it, which is staggering even by the standards of Washington. And what has been so beneficial for the legislation is that the vast majority of those entities are not companies or trade associations, which are motivated by bottom-line demands, but patient groups and universities, which have a far more neutral sheen.
“Members of Congress who wouldn’t be responsive to pharma’s lobbying did respond to universities’ lobbying or to patients’ lobbying,” said Diana Zuckerman, president of the National Center for Health Research, an advocacy group that has spoken out against the legislation. “It was a perfect storm of lobbying.”
Read the full article here.
Pharmaceutical industry, under scrutiny for prices, has history of big political wins
Brianna Gurciullo, OpenSecrets Blog at Center For Responsive Politics
October 2, 2015
Soaring drug prices already had customers unhappy. The pharmaceutical industry hardly needed a new poster boy to add volume and passion to the complaints.
But that’s just what it got last week when Martin Shkreli, the CEO of Turing Pharmaceuticals, made a name for himself after he hiked the price of a drug for AIDS and cancer patients by more than 4,000 percent. Now, some lawmakers are scrutinizing another company, Valeant Pharmaceuticals, for increasing the price of two heart drugs this year.
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There’s work to be done, for sure, but the industry has never lacked for resources to amplify its voice in politics and policy making. Since 1999, pharmaceuticals/health products has poured more money annually into lobbying than any other industry, including $229 million last year alone. PhRMA led the group, plowing $16.6 millioninto helping advance drugmakers’ priorities in Washington.
Pharmaceutical company employees and PACs have also given big to politicians. During the last presidential cycle, federal candidates, political parties and outside spending groups received $51 million – the largest-ever total from the industry. In last year’s midterms, it provided $32.1 million.
What’s been the return on this substantial investment? For one thing, dodging a number of bullets bearing PhRMA’s name. One of the industry’s greatest victories has been preventing Medicare from being able to negotiate drug prices with pharmaceutical companies. That was ensured when Congress passed and President George W. Bush signed the Medicare Modernization Act of 2003, which expanded Medicare to cover outpatient prescription drugs. The law also prohibited drug re-importation from Canada and Europe, where prices are often lower.
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Recently, pharmaceutical companies have set their sights on the 21st Century Cures Act, a bill to accelerate new drug approval by the Food and Drug Administration. Castellani has said that the legislation would help “ensure biomedical advances continue and are available to the patients who need them to live longer, healthier lives.”
Critics like Diana Zuckerman, the president of the National Center for Health Research, argue that speeding up the process means smaller studies that fail to show whether a drug correlates with not only short-term changes – like, for example, a tumor shrinking over a few months – but also living longer, spending less time in the hospital and experiencing a better quality of life.
Psst! Industry has taken over FDA
By Jim Dickinson, Medical Device and Diagnostic Industry
September 17, 2015
Just six years ago, the industry-at-arm’s-length tradition held sway—as it had throughout FDA’s history—when Califf was passed over in Obama’s hunt for a commissioner.
The reason? The Duke University researcher of numerous drug industry clinical trials was then viewed as being too close to the pharmaceutical industry—the same reason that had for decades kept other similarly situated candidates from being chosen to lead the world’s premier health regulatory agency. New York health commissioner Margaret Hamburg was chosen instead.
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No matter how sincere a commissioner might be—and Hamburg was—in divesting him or herself from all potential appearances of possible conflicts of interest before taking on the job, suspicions will linger in the minds of people and groups ready to provoke investigations that cost taxpayer dollars.
That is exactly what seems to be developing in the case of Califf’s nomination.
In a press release, Public Citizen said the Senate should reject it because of Califf’s close ties with industry over the years. “During his tenure at Duke University, Califf racked up a long history of extensive financial ties to multiple drug and medical device companies, including Amgen, AstraZeneca, Eli Lilly, Johnson & Johnson, Merck Sharp & Dohme and Sanofi-Aventis, to name a few,” the group said. “Strikingly, no FDA commissioner has had such close financial relationships with industries regulated by the agency prior to being appointed.”
Echoing similar concerns, National Center for Health Research president Diana Zuckerman said Califf could have a bias toward industry after working in tandem with companies that funded clinical research at Duke.
When Califf joined the agency last February as deputy commissioner for medical products and tobacco—a step widely seen as grooming him to become commissioner—Zuckerman told Time that his “interdependent relationships” may bring into question his “objectivity and distance.” In the Time article, she pointed out that research has shown that scientists may unknowingly be swayed by their industry relationships.
Read the full article here.
Califf nomination for FDA chief gets mostly high marks
By Joyce Frieden, Medpage Today
September 16, 2015
WASHINGTON — The nomination of Robert Califf, MD, as FDA commissioner is getting good reviews from most health policy and cardiology experts.
“He has a very good understanding of industry and academia, and think that will serve him well,” Caleb Alexander, MD, co-director of the Johns Hopkins Center for Drug Safety and Effectiveness in Baltimore, told MedPage Today in a phone interview. “He built and grew the Duke Clinical Research Institute into a behemoth, so he has deep experience in drug development. On the medical products side, he has a deep and comprehensive understanding … from manufacturers and academia, so I think he’ll be very well suited there.”
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Califf was nominated on Tuesday by President Obama; he is currently serving as FDA’s deputy commissioner for medical products and tobacco. Prior to that appointment, Califf was vice-chancellor for clinical and translational research at Duke University in Durham, N.C., where he also co-chaired the Clinical Trials Transformation Initiative, a public-private partnership co-founded by Duke and the FDA to identify and promote practices that will increase the quality and efficiency of clinical trials.
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One area that might cause controversy with Califf’s nomination is his ties to the pharmaceutical industry. “His very close ties to industry [are] his greatest weakness from a public health point of view,” Diana Zuckerman, PhD, president of the National Center for Health Research, a think tank here that researches the safety of medical products for consumers, said in an email. “That’s why Republicans have supported his nomination and many Democrats have opposed it. Those ties have also been a source of great concern to public health experts across the country.”
“If he is confirmed, he will need to show his independence from industry in order to protect the safety of patients and the integrity of the FDA as a public health agency,” she said. “This will be especially important because the 21st Century Cures Act, which passed the House overwhelmingly and is being revamped in the Senate, has the strong support of pharmaceutical and device companies, as well as academic researchers who depend on industry funding, as Dr. Califf did when he was at Duke.”
Read the full article here.
Michael Milken, from junk bonds to legislative advocate
By Sheila Kaplan, Boston Globe via STAT
September 14, 2015
WASHINGTON — Nearly 1,200 lobbyists roamed the halls of Congress this year, trying to shape legislation to speed up the federal approval of new drugs and expand medical research. But the advocate who arguably has had the biggest impact on the process isn’t a registered lobbyist at all. It’s onetime junk bond king Michael Milken.
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He has pushed his agenda with a muted public presence, one that stresses quiet messaging over press releases and networking over campaign contributions. His goal is passage of the 21st Century Cures Act, a bill that would accelerate regulators’ review of new medical treatments and boost funding for the National Institutes of Health by nearly $9 billion over five years.
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Not everyone is pleased with Milken’s behind-the-scenes advocacy. While supporters say the Cures Act, a version of which was passed by the House in July, would make it cheaper and faster to get cutting-edge drugs and medical devices to patients, critics warn that it would create dangerous regulatory shortcuts. They fear that Milken is doing the bidding of the Pharmaceutical Research and Manufacturers of America, the drug industry’s main trade group.
“This is a bill that has many provisions that are exactly what PhRMA wants and what the device companies want,” said Diana Zuckerman, president of the National Center for Health Research, a nonprofit think tank in Washington.
Please see full article here.