By Robert Lowes, Medscape

December 31, 2015

Hammered for its regulation of medical device safety, the US Food and Drug Administration (FDA) today proposed telling the public about “emerging signals” of possible device risk before it determines whether the risk actually exists.

Such early warnings already are issued for drugs through the FDA Adverse Event Reporting System (FAERS), a database on adverse event and medication error reports submitted to the agency. A dramatic fall-off in the number of drugs flagged for potential risk signals in FAERS since 2012 prompts FDA critics to wonder whether a similar system for medical devices will benefit the public.

In today’s proposal, the FDA explained that it historically has alerted the public about safety concerns that crop up after a device goes on the market, and usually after it has determined what to do about them. Agency responses include recommendations for the “device user community” and possible regulatory action.

However, the FDA said there is a need to notify the public “about emerging signals that the agency is monitoring or analyzing, and for which the agency does not yet have specific recommendations.” […]

Diana Zuckerman, PhD, president of the National Center for Health Research, a think tank focused on children and adults, said she does not believe that the downward trend line means that the FDA has been receiving fewer adverse event reports. Rather, the process of disseminating possible risk signals has become “moribund.”

“We think FAERS information is not being made public in a timely manner,” Dr Zuckerman toldMedscape Medical News. She cites lack of regulatory and political will as the reason. FDA user fees collected from drug manufacturers “are dependent on speed of review for drug approvals, not on timely FAERS information,” she said. “Similarly, Congress has complained about the speed of drug and device approvals, not on the speed of warning safety signals.

“Unfortunately, safety is not currently a priority at the FDA or Congress,” Dr Zuckerman said. […]

To see original article, click here.

Carolyn Johnson, Washington Post

November 24, 2015

To patients grappling with incurable diseases, new therapies can’t come quickly enough. A bill that hopes to address this need sailed through the House in the summer with the goal of getting more “21st Century Cures” through the drug approval pipeline. But a pair of new studies found that speeding up this process could put drugs that are ineffective or harmful on the market.

At least for complex neurological diseases, such as Alzheimer’s, Parkinson’s and depression, recent history suggests that approving drugs faster based on biomarkers — early signs that a drug could be working — might make drugs that ultimately don’t work available to patients, two teams of researchers found.

These early biomarkers are one of several ways the House bill could speed up the drug approval process. A Senate version of the bill is expected to be presented soon, with many wondering how similar it will be to the House version. The Food and Drug Administration has said the House legislation wouldn’t override its ability to approve safe and effective drugs.

[…] A second study published in the British Medical Journal this week examined three Alzheimer’s drugs that progressed to late-stage trials based on positive data in earlier stage trials that suggested the drugs were working. In each case, the team found that the phase two trials suggested the drugs would work — two showed encouraging decreases in measurements of beta amyloid, a protein that builds up in the brains of Alzheimer’s patients. One drug, semagacestat, was then tested in 1,537 patients and was found to cause skin cancer and even worsen patients’ ability to perform activities of daily life. The other two drugs looked promising in intermediate trials, but also failed once tested in large numbers of patients.

The researchers projected that if the semagacestat had been approved based on its encouraging results in intermediate trials, the treatment would likely have cost thousands of dollars a year, treated 234,000 patients, and caused 19,000 cases of skin cancer.

“This is just yet another example where, if you look at these very reasonable surrogate endpoints …  you can get results that are completely different when you look at things you really care about, which, in this case, is memory loss and the ability to function, day-to-day,” said Diana Zuckerman, president of the National Center for Health Research.

[…] Read full article here.

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.

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.

[…]

“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.”

[…]

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.

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.

[…]

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.

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.

[…]

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.

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.

[…]

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.

[…]

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.

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.

[…]

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.