FDA Could Be Sustainable AND PREVENT Harm

The FDA Could Earn Over $60 Million A Day From Enforcing The Law

Stuart Buck

October 14, 2015

Many clinical trials on medicines and devices are subject to a 2007 federal law that requires the results to be publicly disclosed on a federally sponsored website within a year after the clinical trial is over. The reason for this requirement is simple: to give doctors and patients full information so that they can make educated decisions about a given treatment. If disappointing clinical trial results remain hidden, while only the most positive results are published and presented in the media, doctors and patients can be wildly misled.

Unfortunately, investigators have found that over half the time, clinical trial sponsors fail to abide by the law, sometimes failing to disclose results even after five years have elapsed. Even more unfortunately, the Food and Drug Administration (FDA) has never once imposed the legally authorized $10,000-per-day fine for failure to disclose a clinical trial’s results.

Compliance With Reporting Requirements

The most recent investigation was published in the New England Journal of Medicine (NEJM) in March 2015. The authors identified 13,327 clinical trials that were registered on ClinicalTrials.gov, that were completed between 2008 and 2012, and that were subject to the 2007 federal law requiring full disclosure. A mere 13.4 percent of the clinical trials actually disclosed their results within the 12 months required by law, and even after up to four years had elapsed, only 50.5 percent had disclosed the results or asked for a delay (see Figure 2 in the NEJM article).

In a twist that ought to embarrass academics, industry-funded trials were more likely to disclose results than the National Institutes of Health (NIH)-funded trials, which were in turn more likely to disclose results than academic medical centers. The authors found 6,599 clinical trials that were overdue on reporting results.

Increasing Fda Enforcement

If the FDA imposed a $10,000 per day fine on each of these 6,599 outstanding trials, clinical trial sponsors would be responsible for $66 million in payments in the first day alone, adding up to over $24 billion per year.

Although the $24 billion figure shows the size and scope of the problem, the collective fines would never reach that amount because as soon as the FDA actually begins enforcing the law, the researchers who conducted these 6,599 trials would finally be incentivized to report the trials’ results.

Why doesn’t the FDA enforce the law? Some have argued that ClinicalTrials.gov is an antiquated and difficult-to-use website. True enough, but given that 38 percent of trials do disclose their results at some point, it is clearly not impossible to do so. This is not a reason to leave the federal law completely unenforced.

The NEJM article states that one reason for lack of enforcement is that a new rule on clinical trial report is still pending. But the 2007 law itself requires basic reporting of results; the only point of a new rule is to expand the requirements to include other items, such as protocols. The mere fact that a rule may be expanded in the future is no reason to leave the current requirements unenforced. Yet another possibility is that the FDA does not want to get bogged down in lawsuits from companies or universities that have a valid reason for delay. But this argument would suggest, at most, that the FDA ought to levy a fine only when truly merited, not that the FDA should never enforce the fine at all.

My proposal: as an experiment, the FDA should give the 30-day notice required by statute, and then set aside a single week in which it will levy the $10,000-per-day fine on all overdue trials. Assuming that there are around 6,600 overdue trials that don’t come into compliance within the 30-day grace period, the FDA would end up imposing over $460 million in fines within a week’s time. In so doing, it would make a strong statement that disobeying the law and hiding clinical trial results is no longer acceptable.

And within a week, compliance with the law would likely shoot up astronomically, and we would have more complete knowledge about how well or how poorly drugs actually work. In turn, we could all make better decisions about how to improve our nation’s health.

http://healthaffairs.org/blog/2015/10/14/the-fda-could-earn-over-60-million-a-day-from-enforcing-the-law/

Gummy Bear Breast Implants

Perfecting Bodies Through Chemistry?

February 22, 2013 Written by Diana Zuckerman  FiDA highlight

Do you like your body?   If there was a simple way to change it, with no risks, would you do it?

If making that change meant you would put your health at risk and have multiple surgeries for the rest of your life, would you hesitate?

Most women say they don’t like their bodies, and research shows that dissatisfaction usually starts during the middle school years and may never go away.  For many of us, it eases up a little in young adulthood as we come to appreciate our attributes and accept any “flaws,” but insecurities rev up again as aging takes its toll.  It seems ironic that we long to regain the body that seemed so imperfect when we were younger.

In the U.S., there are thousands of products and procedures that feed on women’s insecurities.  Most are ineffective – the pills and products that promise to melt fat away without diet or exercise, or to make cellulite or wrinkles disappear.  But only a few are actually dangerous to our health.  Breast implants are one of those.

The FDA just approved a new kind of breast implant, which many plastic surgeons promise will be safer and better than other kinds of breast implants.  It is made of thick silicone gel (nicknamed “gummy bear implants” for its consistency), which is supposed to prevent it from breaking, leaking, or wrecking havoc with your body.

What’s the proof that this product is safer, or even safe at all?  Apparently, that’s a secret.

When breast implants were first sold in the U.S. in the 1960s, no testing was required to make sure they were safe.  For the next 30 years, more than a million women in the U.S. got breast implants, not realizing that studies on women had never been done to prove they were safe or to determine how many months or years they would last.

In 1990, I was working as an investigator in the U.S. House of Representatives when a Senate staffer called me.  She told me that her mom had gotten breast implants after a mastectomy, which had resulted in terrible problems including silicone leaking out of her nipples.  Her mom was cured of cancer but the implants had put her through hell.  I was sure that the FDA had very strict rules about safety testing, but I promised I’d look into it.

I found out that I was wrong: the FDA had never required clinical trials for breast implants.  We held a Congressional hearing, I continued my investigation, and soon my office – and the media – was full of horror stories about women whose health had been ruined by breast implants.

Thanks to Congressional and media pressure, the FDA changed their policies.  They eventually required breast implant companies to conduct studies on hundreds of women with breast implants, to find out how safe their products were.  Public meetings were held so that women could testify about their experiences, scientists could openly discuss the research, and the media could report what was said.  Some companies failed to do the newly required research and their implants were no longer allowed to be sold in the U.S.  And, although all breast implants were found to have high complication rates, the FDA, under tremendous pressure from implant companies and plastic surgeons, decided that women were capable of making an informed choice about the risks they were willing to take.

I have no doubt that women are capable of making an informed choice.  But the FDA is still not providing the full information that women need to make an informed choice, and neither are the plastic surgeons.

In a giant step backwards, some FDA officials are reverting to their old ways.  They approved “gummy bear” implants with no public meeting and they have not made the study findings public.  Instead, in a press release that the agency quietly released on February 20, they report that the new breast implants have the same kind of complications as other types of implants – such as hard, painful, or lopsided breasts and the need for additional surgery – but don’t say how often those complications occur.  They also reported a new complication: the silicone gel in these new implants can crack.  What happens to women when that happens?  The FDA isn’t saying.

Since I did my investigation in 1990, I have been one of the FDA’s strongest critics and biggest fans.  I have often been horrified by some of the decisions FDA makes to approve unsafe or inadequately tested medical products, but I also know that when the FDA does its job well, it can save millions of lives.

When I did the Congressional hearing on breast implants, I was 7 months pregnant.  My son is now a college senior.  In those 22 years, the FDA regained and is now again at risk of weakening its public health focus, as Congressional pressure on the FDA to protect patients has been replaced by Congressional pressure to get products to market as quickly as possible and thus “create jobs.”  Whether it is breast implants, riskier birth control pills, TB drugs that do more harm than good, or sleeping pills with questionable benefits, the FDA is allowing drugs to be sold that do a lot of harm.  And when the FDA fails to hold medical products to a high standard, it is women – the consumers of most medical products – who are harmed the most.

For more information about the FDA’s recent decision on Allergan breast implants, see Statement of Dr. Diana Zuckerman on FDA approval of new Silicone-Gel Breast Implant Natrelle 410 and for more information about the risks of breast implants, see www.breastimplantinfo.org

Diana Zuckerman is the president of the National Research Center for Women & Families. She received her PhD in psychology from Ohio State University and was a post-doctoral fellow in epidemiology and public health at Yale Medical School.  After serving on the faculty of Vassar and Yale and as a researcher at Harvard, Dr. Zuckerman spent a dozen years as a health policy expert in the U.S. Congress and a senior policy adviser in the Clinton White House.  She is the author of five books, several book chapters, and dozens of articles in medical and academic journals, and in newspapers across the country.

Fodder for TV: The Good Wife highlights failed medical device trial

LINK

Sit down with a glass of wine and experience the medical and legal purgatory of the harmed patient.  This one has a Hollywood ending . . .  The Good Wife  "Get A Room" Season 3 Episode 3

http://www.cbs.com/shows/the_good_wife/video/2149721418/the-good-wife-get-a-room

More scientific rigor picking out a garbage disposal!

http://ctwatchdog.com/health/more-women-need-to-be-involved-in-medical-device-trials

More Women Need To Be Involved In Medical Device Trials

June 8, 2012

By Ct Health I Team

Written by Rochelle Green  (FiDA blog bold added)

Hundreds of thousands of women at risk for irregular heart rhythms have a battery-powered, iPod-sized gadget embedded in their chests. The implantable cardioverter defibrillator (ICD) can be a lifesaver, shocking a dangerously fast heartbeat back to normal.Yet the actual benefit to women is uncertain, because ICDs were approved by the Food and Drug Administration (FDA) based on clinical trials made up mostly of men.  That’s typical of testing of many high-risk devices, according to medical reports. And even in the clinical device trials that do include women, generally the outcomes aren’t reported by sex.

The result is a critical gap in the data doctors rely on when making decisions about a treatment’s benefits and risks for women. It can also pose troubling dilemmas later on, said cardiologist Rita F. Redberg, a professor of medicine at the University of California, San Francisco. That was the case in 2009, when data pooled from clinical trials showed that ICDs were no better than drugs at reducing a woman’s risk of death.

“The time to collect data in both sexes is before FDA approval,” said Redberg. “Especially with implanted devices, where there’s no going back.”

Only recently has the FDA proposed guidelines to improve the representation of women in clinical device trials. Intended for the medical device industry, which sponsors most of the research submitted for review, the guidelines are expected to become final by year’s end. Similar standards for drug testing were put in place some 20 years ago, following a long period during which women of childbearing age were explicitly excluded from most studies.

The proposed FDA guidelines are nonbinding, however, and some experts who favor the new recommendations are skeptical that the medical device industry will comply.

“Industry is always most attentive to the bottom line,” said Christine Carter, vice president for scientific affairs at the Society for Women’s Health Research (SWHR) in Washington, D.C. “So companies will continue to lament that trials are expensive and that recruiting more women is a problem.” Device makers will change their study protocols just enough to meet FDA requirements, Carter predicted, but protocols will be “less than ideal for those of us concerned with sex differences and women’s health.”

SWHR and other groups have urged the FDA to strengthen the document by finalizing it as a rule. The debate highlights the competing interests that the agency struggles to balance, with industry and some lawmakers in one camp, demanding faster approvals and “less burdensome” regulation, and health advocates in another, warning that patient safety is at risk.

To U.S. Rep. Rosa DeLauro, the issue is science, not politics. “We know there are real medical distinctions between genders that must be recognized when the government is deciding whether to approve a new device,” she said.

Opening A Window On Women’s Health

Until the mid-1980s, clinical trials were practically a men’s only club. Studies funded by the National Institutes of Health (NIH) and pharmaceutical firms—the largest contributors to biomedical research in the United States—drew subjects primarily from a pool of white males. The first randomized trial using estrogen to prevent heart disease consisted entirely—and counter-intuitively—of men.

Women were considered too complicated to study, given their cycling hormones and the chance that those of childbearing age could expose a fetus to unintended risk, said SWHR’s Carter. Gender wasn’t yet recognized as a factor in health and illness, and it was assumed that study results in men would be just as useful for women.

As biomedical research advanced, however, women began to suspect that their health needs were being left behind, experts say. The results of clinical trials in men weren’t always extended to women, depriving them of powerful new treatments like cholesterol-lowering drugs, according to an Institute of Medicine report. And the male model didn’t always correspond to women’s experience of health and disease.

In the early 90s, women’s health advocates began to mobilize, according to Carolyn Mazure, director of Women’s Health Research at Yale. “They took it to Congress,” she said, educating key legislators about the exclusion of women from medical research and the lack of information about gender differences related to health.

In 1993, Congress passed legislation requiring that women and minorities be included in all NIH clinical research. The FDA reversed its policy barring women of childbearing age from certain drug studies, encouraging their inclusion in all clinical drug trials. The measures also required study results to be analyzed by sex.

As an NIH researcher at the time, Mazure witnessed history in the making. “The idea that we now needed to include women and minorities in our research—we found it revolutionary,” she recalled. Her program at Yale promotes research on gender differences in health by providing seed money to get innovative projects off the ground.

In the past 20 years, scientists have discovered that sex differences are significant at every stage of life and at every biological level, from the single cell to the whole body. Gender influences how people experience disease, metabolize drugs, respond to pain, and much more. While the findings support the need for sex-based research, the going is slow, said Carter.

“There’s still only 30 percent—maybe up to 40 percent—of women involved in clinical trials, and too often their data isn’t analyzed separately from men’s,” she said.

A major challenge is changing the mindset of researchers, she said.  She described how, at a recent SWHR roundtable with more than a dozen Alzheimer’s disease experts, she had asked about the sex differences they had found in their research. Almost all responded that they hadn’t looked at the data that way.

“We’re finding this over and over, with experts in different fields,” she noted. “If you’re not aware that there are biological differences between the sexes, you don’t look for it in your data.” With each roundtable, however, she convinces more scientists to look at outcomes based on sex. “It’s time to make this more mainstream,” she said.

In the meantime, the effects of the old mindset are still in evidence: in one example, women account for just 30 percent of subjects in the clinical trials supporting the American Heart Association’s 2007 guidelines for cardiovascular disease prevention in women. Twenty of the 156 studies were men-only, according to a published gender analysis of the studies from which the guidelines were drawn.

The paucity of women “wasn’t a big surprise,” said Dr. Chiara Melloni, assistant professor of medicine at the Duke Clinical Research Institute in Durham and lead author of the analysis. But it’s a reminder to design studies with gender differences in mind, she said.

Bringing Device Studies Up To Speed

If the FDA’s device center has been slow to tackle the gender gap, its new guidelines are a prescription for change, agency officials say.

In a key provision, researchers are advised that men and women should be enrolled in proportions that reflect the gender distribution of the underlying disease. Cardiovascular device studies, for example, should enroll men and women in equal numbers, since each sex is equally at risk for the disease. Until now, most such studies have included just half as many women as men, according to an FDA review of cardiovascular devices approved in a recent five-year period.

Since medical device studies have traditionally been small, the new enrollment goals will likely require more women, and possibly bump up the number of subjects overall. The guidelines provide strategies for recruiting female subjects, and advice on examining data for potential differences by sex. And they call for sex-specific outcomes to be reported on device labels, a practice that consumer health groups have been advocating for years.

In practice, the vast majority of medical devices reviewed by the FDA are cleared for use without human testing, if they are deemed “substantially equivalent” to devices already on the market. Only 1 percent of devices undergo rigorous review and clinical trials before they can be marketed.

Even so, the new guidelines for device trials are an important advance, experts say. Dr. Patrice Desvigne-Nickens, a program director at the National Heart, Lung, and Blood Institute, praised the FDA for alerting device makers to the new imperative in clinical research. “To not look for gender differences is unacceptable,” she said.

Joleen Chambers on June 11, 2012 at 4:14 pm

Thank you for this excellent and informative article. Sadly, if a woman researches any implanted medical device she will find that data is hidden behind a barrier of “proprietary” claims by the industry. She is more likely to find hard data about any kitchen appliance than an implanted medical device. Gender clinical studies are another layer of insufficient scientific rigor.