March 4, 2015

My name is Dr. Margaret Dayhoff-Brannigan and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.

Thank you for the opportunity to speak here today.

I completed my Ph.D. in Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health. I bring a perspective as both a researcher and an advocate for public health here today.

An effective flu vaccine is critical for public health. Antiviral medications have very limited efficacy, so for many people the flu vaccine is the best line of defense to protect against infection. The CDC’s latest report calculated a 19% vaccine efficacy this year. That is simply not good enough. More importantly, this is not just one bad year. Four of the last 10 years the vaccine has been less than 40% effective.

When the flu vaccine does not work well, people think they should not bother to get it. This is bad for both for the pharmaceutical companies who have unused doses of vaccine, and for the general public that is less protected.  It is important that we implement strategies to improve the efficacy of the influenza vaccine.

According to the briefing information, a new strain of influenza A(H3N2) was detected in March 2014, after last year’s vaccine production had already begun. Nothing was changed in response to these new data. We urge the FDA to consider changing the timeline for selecting strains for the vaccine to allow more time. We understand there are tight deadlines, but there should at least be a strategy for making a last minute change to one of the strains selected for inclusion, if it is found that there is a newer circulating strain within a certain time frame. In response to the 2009 H1N1 pandemic, vaccines were produced in an accelerated timeline, so we know that it is possible. While these strategies may cost more to implement, the increased cost is worth it if efficacy could be substantially improved. More effective vaccines will save lives, and will save money in reduced sick days taken, doctors visits, and hospitalizations.

Currently, there are few incentives for pharmaceutical companies to implement strategies to improve vaccine effectiveness. For example, military, health care and childcare workers will all be required to get the flu vaccine next season regardless of how ineffective the vaccines have been this season.

In addition, the FDA should look carefully at whether the live attenuated influenza vaccine (nasal spray) should still be approved, since for the second year in a row it has shown considerably lower efficacy than the standard flu shot. At the very least, the nasal spray labels should specify how ineffective they are compared to flu shots.

We urge the FDA to require new protocols to ensure that the best and most effective vaccine is produced each year.

Thank you for your time.

By Elizabeth Cohen, CNN

March 3, 2015

Exterior view of the Ronald Reagan UCLA Medical Center during their Ebola virus readiness drill (closed to the media) to test their ability to diagnose and treat Ebola patients in Los Angeles on October 17, 2014.  The United States and Canada announced stepped-up airport screening measures to look for passengers carrying Ebola, as the deadly virus killed a man in Texas and the worldwide toll has passed 4,500.             AFP PHOTO/Mark RALSTON        (Photo credit should read MARK RALSTON/AFP/Getty Images)

Exterior view of the Ronald Reagan UCLA Medical Center during their Ebola virus readiness drill (closed to the media) to test their ability to diagnose and treat Ebola patients in Los Angeles on October 17, 2014. The United States and Canada announced stepped-up airport screening measures to look for passengers carrying Ebola, as the deadly virus killed a man in Texas and the worldwide toll has passed 4,500. AFP PHOTO/Mark RALSTON (Photo credit should read MARK RALSTON/AFP/Getty Images)

(CNN) — CNN has learned that the manufacturer of the endoscope involved in two superbug deaths at UCLA never obtained permission to sell the device, according to an official at the Food and Drug Administration.

Olympus started selling its TJF-Q180V duodenoscope in 2010, but the FDA didn’t notice until late 2013 or early 2014 that the company had never asked for clearance to put it on the market, according to Karen Riley, deputy director of strategy for the FDA’s Office of External Affairs.

“Why didn’t we notice it? I don’t know,” Riley said.

“Can you imagine a prescription drug getting out on the market that didn’t go through the approval process?” asked Dr. Steven Nissen, the chief of cardiovascular medicine at the Cleveland Clinic, who’s testified to Congress about device safety problems. “Devices need to be regulated more vigorously. This is really disturbing.”

Mark Miller, a spokesman for Olympus, did not respond to calls and emails from CNN seeking comment for this story.

Outbreak started at UCLA

Seven hospital patients at Ronald Reagan UCLA Medical Center were infected with the deadly superbug CRE — also known as carbapenem-resistant Enterobacteriaceae — between October and January, according to hospital officials. Two of those patients died.

The patients caught CRE after routine endoscopic treatments. Hospital officials believe two medical scopes that still carried the deadly bacteria even after disinfection guidelines were followed were the cause of the superbug outbreak.

The medical center has contacted 179 others who had endoscopic procedures between October and January and is offering them home tests to screen for the bacteria.

In a separate outbreak on the other side of the country, 18 people contracted CRE in North Carolina, and one of those died.

Not safer

According to FDA rules, a manufacturer must seek clearance for a new model if it includes changes that “could significantly affect the safety or effectiveness of the device.”

The TJF-Q180V duodenoscope, used to check out ducts in the gastrointestinal system, includes a modification to the exact part of the device that’s been implicated in the superbug outbreaks.

With this new model, Olympus sealed up that part of the device, known as the elevator channel, hoping to make it more impervious to infection.

“The company clearly made these modifications to make the device safer, but it seems to be that it wasn’t safer,” Riley said.

Last year, at the FDA’s request, Olympus applied for permission to sell the scope. That application is still pending.

Riley emphasized that duodenoscope procedures can be lifesaving, so the agency doesn’t want to take them off the market.

“More than 500,000 of these procedures are done every year in the U.S., and the risk of bacterial transmission is actually really very, very low,” she said. “We believe the risks outweigh the benefits.”

Riley noted that the other two duodenoscope manufacturers, Pentax and Fujifilm, did apply for and were granted clearance to market models similar to Olympus’ TJF-Q180V.

Not clean enough

Now the FDA is asking all three companies to submit evidence that the scopes can be thoroughly cleaned — and so far it’s not going well.

Riley said twice the companies have submitted data that failed to show that cleaning could get rid of 99.9999% of all microbes on the scope — the FDA’s standard for disinfection.

“We’re still working with them to get good data,” she said.

Riley said she doesn’t know if the FDA will penalize Olympus for selling the device without permission.

Diana Zuckerman, a device safety expert, said they should.

“It’s like with kids. How do you teach your children to behave if there are no consequences when they misbehave?” she said.

See original article here.

Lobbyists have blanketed the U.S. Congress to demand a repeal to the 2.3% medical device tax.  The lobbyists claim that the tax is a terrible burden on medical device companies and is causing the companies to cut jobs – thus harming each Senator’s and Representative’s constituents.  As scientists, we decided to determine the facts behind these claims.

The tax is an essential component of the Affordable Care Act; the funds help to make this important legislation affordable, by offsetting the costs of health insurance for those who otherwise could not afford it.  Without the device tax, the subsidies would have $29 billion less in funding.

Our State fact sheets provide information on the total number of medtech jobs in the state and compares that to the total number of state residents who need key benefits of the Affordable Care Act.  The Fact Sheets are linked below:

Alabama

Alaska

Arizona

Arkansas

California

Colorado 

Connecticut

Delaware

Florida

Georgia

Hawaii

Idaho

Illinois

Indiana 

Iowa

Kansas

Kentucky

Louisiana 

Maine

Maryland 

Massachusetts 

Michigan 

Minnesota 

Mississippi

Missouri 

Montana 

Nebraska

Nevada 

New Hampshire

New Jersey

New Mexico

New York

North Carolina

North Dakota

Ohio

Oklahoma

Oregon

Pennsylvania 

Rhode Island 

South Carolina 

South Dakota

Tennessee

Texas

Utah 

Virginia

Vermont 

Washington 

West Virginia

Wisconsin

Wyoming

For additional information, see our report on the Device Tax.

 

February 2015

This is a very brief summary of the concerns of coalition members.  Our more detailed analysis of concerns and support of specific provision is available from Paul Brown at pb@center4research.org 

The purpose of federal regulations is to protect the U.S. public from harm by implementing reasonable safeguards.  The purpose of U.S. public health agencies is to support scientifically sound research and protect the integrity of the scientific enterprise.  Even our current regulatory oversight has failed to protect hundreds of thousands of patients from unsafe drugs and defective devices, as evidenced by the needless deaths linked to Vioxx and serious injuries from metal on metal hips. Voluntary safeguards are not sufficient, nor is reliance on public/private negotiations to develop research agendas or scientific research safeguards.

The American taxpayer is the customer for U.S. public health agencies, not private industry. 

We are very concerned that the 21st Century Cures Discussion Draft focuses almost exclusively on speeding new medical products to market, largely ignoring whether those products are safe or effective, or more beneficial than products already proven safe and effective. It would drastically reduce patient safeguards that the U.S. Congress and the FDA have developed on the basis of decades of experiences such as the thalidomide tragedy of the 1960s, the AIDS crisis of the 1980s, the Vioxx recall of 2004, or the metal-on-metal hip recalls of 2011.  Even more worrisome, the legislation would respond to 21st century challenges such as software platforms and social media by taking away the authority that the FDA already has, de-regulating devices that millions of Americans depend on and de-regulating industries direct-to-consumer advertising and promotional activities.

Many provisions in the 21st Century Cures discussion draft also would greatly weaken the regulatory authority of the FDA and the decision-making authority of the NIH, replacing unbiased scientific decision-making with micromanagement from Congress, placing private industry in the driver’s seat, and putting patients’ lives at risk.

 

Medical Devices

Despite recent high profile device-related health tragedies such as power morcellators, metal-on-metal hip implants, and surgical mesh, the safety or effectiveness of medical devices are hardly mentioned in the 21st Century Cures discussion draft. Patients want safe and effective devices cleared in a timely matter—not the fastest device out of the lab. Safety is not mentioned once in three device sections and is mentioned only twice in the large medical device reforms section.

Patients want to be able to trust that will improve their health or survival.  The discussion draft would be less burdensome to device companies but would move that burden to patients and physicians.  Neither patients nor their physicians would have confidence that new devices are safe or effective.  Approximately 18% of moderate to high-risk devices are recalled under the current standards.1 Lower standards are likely to result in more harm to patients.  The proposed micromanagement of the already under-resourced Center for Devices and Radiological Health (CDRH) staff would create significant morale and resource problems, creating unnecessary burdens and potentially overruling scientific judgment for inappropriate reasons.  This could lead to a mass exodus of the agency’s best scientific staff, and would make those remaining less able to meet the review deadlines imposed by FDASIA.

While improved communication between industry and the agency is a laudable goal, the inherent role of a regulatory agency is to be in charge and make decisions without undue pressure from Congress or the companies it regulates. Provisions in this discussion draft tip the balance in ways that would greatly weaken FDA’s authority and autonomy and require enormous additional resources at CDRH – resources that neither Congress nor the device industry has been willing to provide in appropriations or user fees.

 

Drugs

A key focus of the numerous provisions on drug approvals is to lower FDA approval standards by pushing for shorter and smaller clinical trials.

The provisions on biomarkers and surrogate endpoints dangerously undermine the authority of the FDA, essentially privatizing a crucial regulatory function. Surrogate markers – a laboratory value or event that is anticipated to predict a patient outcome – often do not reliably predict the impact of a drug on actual patients.2, 3 By expanding the use of surrogate markers without adequate safeguards, it would put millions of patients at risk.  By including industry experts in the evaluation of surrogate markers, and offering a new appeals process when an industry request for approval of a surrogate marker is denied, the provisions would waste FDA resources and greatly increase opportunities for bias stemming from financial conflicts of interest and political interference.

Although surrogate markers are intended to predict meaningful health outcomes, such as survival or improved health, many surrogate markers are poor predictors.  Despite the well-known problems in accurately selecting effective surrogate endpoints, the draft bill proposes to use surrogate markers much more widely, without adequate safeguards. Drugs should not be approved based on preliminary data unless they are urgently needed, but the draft would pressure the FDA to do just that.  The provisions on surrogate endpoints should be deleted in their entirety.

The provisions on breakthrough therapies encourages FDA to approve drugs that have not been tested in Phase 3 clinical trials, if the drugs are intended to treat serious or life-threatening diseases or conditions.  This would not be limited to drugs that meet unmet needs.  Approving a wide range of drugs on the basis of the more preliminary Phase 2 trials poses many risks to patients.  Many drugs that are promising in Phase 2 trials are found to be unsafe or ineffective in Phase 3 trials.  Once approved under the proposed new mechanism, however, the companies would be able to advertise and sell the product widely and have no incentive to conduct phase 3 studies in a timely manner.  This would eviscerate the powers of the FDA to ensure the drugs we use are safe and effective, powers granted after the thalidomide disasters of the early 1960s.  Accelerated approval mechanisms already exist to achieve the goals in this section of the bill, and compassionate use mechanisms make experimental drugs and devices available to patients.

Since the FDA does not control the practice of medicine, and since this legislation would make it easier for drug companies to advertise new drugs for unproven treatments, this provision would put millions of patients in danger.  This section needs to be greatly revised or deleted to preserve the balance between speed and safety.

The bill’s provisions to encourage smaller clinical trials to expedite approval directly contradicts the provisions in FDASIA aimed at increasing the number of women, people of color, and adults over 60 in clinical trials.  Smaller clinical trials would make it impossible to conduct subgroup analyses to determine if a new medical product is safe or effective for women, men, people of color, and older adults.

Instead the bill would push the requirements of proving that a drug (or device) is safe or effective from the approval application to studies that are required after the product is approved.  Unfortunately, research shows that such unproven drugs are likely to be sold to patients for a decade or longer before those post-market studies are completed.4,5 Moreover, despite requirements to do so, post-approval studies often fail to include the diverse populations that the company promises to study; companies have no incentive to ensure diversity once their drug/device has already been approved for the general population.

 

Antibiotic Resistance

The proposed Antibiotic Drug Development legislation purports to solve the problem of antibiotic resistance but would fail to do so.  It contains so many loopholes and insufficient safeguards to protect patients or to protect the efficacy of new or existing antibiotics by reducing overuse.  The newly introduced HEAL Act (H.R. 931) would be a much more effective strategy to encourage antibiotic drug development targeted to the patients who most need new antibiotics.

 

Conflicts of Interest

The discussion draft creates many advisory committees, working groups and other structures that do not adequately restrict the participation of members who have significant financial ties to industries that will benefit from relaxed regulations.

 

Advertising in social media

This draft would enable companies to promote their drugs and devices without informing the audience about the product’s risks. This would mislead patients and providers and would be dangerous for many patients.

 

February 20, 2015

Thank you for the opportunity to speak today. I am Dr. Christina Silcox, I have a PhD in Medical Engineering and Medical Physics from MIT, and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. Those are the perspectives I bring with me today. We do not accept funding from device companies and therefore I have no conflicts of interest.

Lumbar spinal stenosis is the most common indication for spine surgery in patients older than 65, and its prevalence in the United States is expected to rise 59% by the year 2025. That means that the FDA’s decision about whether or not to approve this device will affect the lives and health of many men and women. The Superion IDE trial shows that the Superion ISS Device is non-inferior to the X-Stop device. But does that mean it should be approved?

We have two major concerns. First, we agree with FDA scientists that the 16.3% spinous fracture rate is likely to have clinical significance, despite the sponsor’s claim that it doesn’t.  We base that on the fact that the hypothesized mechanism of action depends on intact spinous processes.  The Sponsor’s executive summary itself states that part of the purpose of the Superion IDE was to validate the device’s mechanism of action. We are concerned that the similar successful clinical outcomes for the patients with and without spinous process fractures means that the mechanism of action is not understood. Is it possible that the adjacent soft tissues and musculature is playing more of a role than previously thought? If so, what are the potential long-term effects? 68% of the Superion fractures were unhealed at 24 months, compared to 59% for X-Stop. Is the device placement preventing healing? What are the long-term potential effects if so? This is a device that is being proposed for use in patients as young as 45 years old. It is essential to understand the mechanism of action in order to understand the long-term effects of this permanent implant and to avoid the risks of revision surgery in the future.

Our second concern is the effectiveness data.  The committee is being asked whether this product should be approved based on its demonstrated non-inferiority to the X-Stop device. However, the FDA’s advisory committee recommended again approval of the X-Stop device because of its questionable benefits.  That Advisory Committee thought the data from the pivotal trial did not demonstrate that the benefits outweighed the risks. The FDA approved the device anyway, and since that time, real world evidence has clearly shown that the X-Stop is even less beneficial than the pivotal study indicated. In the study presented today, successful outcomes were only found in approximately 50% of patients in both arms and more than 25% of Superion patients had to have revision surgery by 36 months.

It is common for studies submitted to the FDA to have more favorable outcomes than surgical devices will have in the real world.  That’s because the surgeons are the best that the sponsor can identify and the patients are carefully selected according to a protocol that is unlikely to be followed in the real world.  For that reason, we can expect that in the real world, the Superion ISS Device will be even less beneficial than it was in the study by the sponsor. Given that Superion found a correlation between the spinous process fracture risk and the spinous process placement of the device during surgery, this is a particular concern.

I do not know why the FDA ignored the previous Advisory Panel recommendation and approved the X-Stop anyway, but I do know that in 2004 the FDA had lower standards for PMA approval than they have today.  The FDA leadership has changed and efforts have been made to be more consistent.

If you consider the higher standards of evidence currently used for this very important indication, and the real world data indicating that the X-Stop device has risks that outweigh its benefits for most patients, if you were considering the X-Stop today it is very likely that this Advisory Committee would again recommend AGAINST approval and this time the FDA would agree.

HOWEVER, the task today is to focus on the Superion ISS and whether its benefits outweigh the risks of surgery without the device.  It does not make sense to approve another device meant for the same population that does not demonstrate superiority even when the best surgeons and most appropriate patients are selected for the study. Even more importantly, when the X-Stop was approved 11 years ago, it filled a gap between open surgery and non-surgical treatments that were not very effective. Since then, minimally invasive surgery techniques have become much more common.

In summary:

  1. The mechanism of action is not clear, making the long-term benefits and risks unknown
  2. This device is no better than the X-Stop and inferior to surgery without the device – even under the ideal circumstances of a clinical trial.  It is likely to be even less beneficial in the real world.
  3. The X-Stop was approved because it filled a need for patients who could not undergo open surgery.  That need has been met because other, more effective minimally invasive surgeries have been developed.

We urge you to vote NO because the data are insufficient to prove that the benefits outweigh the risks or a reasonable assurance of safety or effectiveness.

 

 

By Lauren Gilger and Maria Tomasch, ABC15

February 25, 2015

A CLINICAL TRIAL PARTICIPANT’S STORY

Kimberly Lira said she’s lived in nearly constant pain for fifteen years.

The mother of three was a patient in the original clinical trial to get Essure permanent birth control approved by the Food and Drug Administration (FDA).

“Every single day I have bloating,” she said. “Every single day, I have pain.”

In 2001, Lira reported to the Women’s Health Research clinic in Phoenix to have the device implanted. Essure consists of two metal coils placed inside the fallopian tubes to block conception permanently.

Essure, then known as STOP 2000, is marketed as a surgery-free alternative to tubal ligation, or getting your tubes tied.

“They told me that it was just a really easy procedure, and just a few minutes were all it took,” she said.

Lira said almost immediately after the procedure she was in pain. “Day three, right after the surgery, I wanted it out already,” she said.

Lira recently obtained all of her medical records related to the trial and shared them with the ABC15 Investigators.

“The stress that I get to look through those,” she said, “it’s crazy. It makes me very emotional.”

Throughout the trial, records show Lira consistently reported health issues associated with the device. Though, Lira said the nurse continuously told her that these were normal symptoms.

“I kept hearing her say this, ‘Oh, honey, that’s normal, everything is normal’.”

Lira said she also noticed some questionable notations in her records from the trial.

Like, when she reported “excessive menstrual bleeding,” it was categorized on her records as “unlikely” that it was related to the device.

And, when she reported “severe menstrual cramping,” the word “severe” was crossed out.

“Somebody dated and initialed that, like they were making a correction to what I’m telling them,” Lira said. “Why would somebody cross out my own word when I’m telling them it’s severe? Who is a nurse or whoever signed this to say it wasn’t severe?”

On the same form where Lira reported she was experiencing “severe” pain, “a lot more” unusual pain, and “pelvic tenderness,” it was reported that her comfort with the device is “excellent.”

Her records also show that she asked researchers to remove the device. Lira said that from day three until she broke down crying in 2003, she asked them to remove it numerous times. At one point, she said she went into the clinic desperate to get the device taken out. She told them she wanted to become pregnant again.

“I was crying, I told them I wanted them taken out and they told me that there was no reversal,” she said. “This is permanent.”

When Conceptus, the original manufacturer of the device, got approval from the FDA for Essure in 2002, it was reported that “there were no requests for removal of the device.”

The summary of minutes of the Obstetrics and Gynecology Devices Panel that approved the device said 92 percent of women in the trial were “very satisfied” with the device after three months of wearing it and 95 percent were “very satisfied” after one year.

“I think it undermines what I am going through,” Lira said. “It undermines the pain that I am going through.”

Bayer Health Care, Inc. bought Conceptus in 2013 largely because of the Essure device.

A Bayer spokeswoman told ABC15 they cannot comment on any individual clinical trial participant, but said numerous trials and independent studies involving thousands of patients have shown consistent results with those seen in the pivotal clinical trial for Essure.

See Bayer’s complete statement below.

The clinical trials for Essure began with 745 women; 567 women completed it according to the FDA.

Lira wasn’t one of them.

A form in her medical records shows she was “lost to follow-up” in late 2003. The form said she returned a letter withdrawing her participation in the trial.

Lira denies ever seeing a letter like that, and there’s no such letter in her medical records.

The form also said she was a no-show for a visit in 2004 and numerous attempts to reach her went unanswered.

But Lira thinks she was removed from the trial for a different reason.

“I think I became a thorn in their side,” she said. “They didn’t care. I wasn’t giving them the happy results that they wanted.”

Bayer told ABC15 in an email that all data collected on every clinical trial participant is reported to the FDA, regardless of whether they left the trial.

FLAWED CLINICAL TRIALS?

“The data makes it look like a product is safer or more effective than it really is,” said Dr. Diana Zuckerman, President of The Center for Health Research in Washington, DC.

She said clinical trials are often flawed especially when it comes to medical devices like Essure because there are fewer legal standards for them.

“Usually the scientists at FDA are very well aware that the studies are inadequate and that patients can be put at risk,” Zuckerman said. “And, yet, decisions are being made to rush these products to get them approved quickly because there’s so much pressure to do that.”

Essure birth control received premarket approval from the FDA in 2002 after two preliminary trials and 12 months of a pivotal clinical trial, according to the FDA.

The device went through the Premarket Application (PMA) process which according to the FDA is their “most stringent regulatory pathway.”

“Like a new drug, devices approved under a PMA undergo a thorough regulatory and scientific examination of all available scientific data before FDA makes an approval decision,” FDA spokesman Eric Pahon wrote in an email statement.

In a review conducted after our stories first aired, the FDA maintains the product is safe and is 99.83 percent effective.

ADVERSE EVENT REPORTS CLIMBING

There are now more than 4,500 adverse event reports filed with the FDA by patients and doctors describing problems with or side effects from the device.

Those reports include deaths linked to the device.

Last year, the ABC15 Investigators found an adverse event report detailing the death of a woman with the device.

Now, there are three late-term miscarriages categorized as deaths in the FDA’s database.

In one report, a woman writes that she had to deliver her son after becoming pregnant while having Essure implanted, “but he had already died in utero three to four days prior,” the report said.

Another adverse event report describes premature lungs in a baby born at 26 to 32 weeks. The manufacturer’s narrative of those events concluded there was not enough information provided to suspect a quality defect in the product. The device was not returned to the manufacturer to determine if it had malfunctioned.

third report describes a premature miscarriage after a woman with Essure became pregnant. “She couldn’t have Essure removed and in the 25th week of the pregnancy it broke and migrated, perforating the amniotic fluid. The child didn’t make it,” the report read.

The manufacturer’s narrative said this is a “non-medically confirmed, spontaneous case report” that was received from a social media website.

A Bayer spokeswoman told ABC15 they do not comment on any individual adverse events, but they take them all seriously and report them to the FDA as required.

Dr. Zuckerman has helped the more than 14,600 members of the Essure Problems Facebook page get their cause heard in Washington.

“When you see data that looks so great and you talk to women who have used the product whose experience is completely different, you have to question whether the studies were really done appropriately,” Dr. Zuckerman said.

Lira also questions the clinical trial. She doesn’t want anyone else to have to experience the pain she feels every day.

“Do I want to be pain free? I would love it,” she said, crying. “I would love to know who that Kim is. I would love to know who I could be.”

A Bayer spokeswoman told ABC15, “If clinical trial participants have questions, they should call 888-84-BAYER.”

Complete statement from Bayer Health Care:

Patient safety is our top priority at Bayer. We are saddened to hear of any serious health condition affecting a patient using one of our products, regardless of the cause. Although we do not comment on individual adverse events, we take all adverse events seriously, and report them to the FDA as required.

Per you question on clinical trials, all data collected on every clinical trial participant are reported to the FDA.   

Numerous well-controlled trials along with many independently sponsored studies involving thousands of patients have demonstrated results consistent with those seen in the pivotal study. We cannot comment on the experience of an individual clinical trial participant. If clinical trial participants have questions, they should call 888-84-BAYER.

Read original article here.

February 24, 2015

My name is Dr. Margaret Dayhoff-Brannigan and I am a senior fellow at the National Center for Health Research. Our research center scrutinizes scientific and medical data and provides objective health information to patients, providers and policy makers. We do not accept funding from device companies, and therefore I have no conflicts of interest.

Thank you for the opportunity to speak here today.

I completed my Ph.D. in Biochemistry and Molecular Biology at the Johns Hopkins School of Public Health. Prior to receiving my doctorate, I conducted research at the Wilmer Eye Institute at Johns Hopkins.  I bring a perspective as both a researcher and an advocate for improved safety of medical devices here today.

It is clear that patients suffering from Keratoconus or Corneal ectasia need treatment options. The risk-benefit analysis may support approval of corneal cross-linking for those patients, however we are very concerned about the data presented here showing limited efficacy. More than 25% of patients treated showed Kmax values that did NOT improve or stabilize. We are also extreemly concerned about off-label use of this risky technology. The incidence of adverse events from the cross-linking procedure is very high, so this procedure should NOT be used except for those diseases/conditions. We are already seeing Lasik procedures that include cross-linking in Europe, where standards are lower than in the US. This puts patients at unnecessary risk.   Approving cross-linking could be a slippery slope that we need to avoid in our country to keep patients safe.

If cross-linking is approved, there are a few ways to prevent or at least greatly reduce off label use:

  1. A black box warning that specifies that the benefits are not proven to outweigh the risks for Lasik patients, and that the device is only approved for progressive Keratoconus or corneal ectasia.  The black box should explain the risk of decreased vision, eye pain, irritation, infection, and severe chronic dry eyes. It should also explain that at least 25% of patients have NO improvement after treatment.
  1. FDA approval should be limited to patients over 16. Adolescence is a time of rapid eye development, and it is inappropriate to extrapolate the results from adults to adolescents.
  1. We urge the committee to recommend that FDA strictly limit the marketing of the cross-linking procedure to its approved purposes: progressive keratoconus and corneal ectasia on patients over 16.

The FDA has the authority to provide a black box warning warning about off label use.  I urge you to ask the FDA this question: Can the FDA limit and enforce advertising, including in-office marketing?

In addition, we strongly recommend two other safeguards:

  1. FDA should require data on the off label use of this device.
  2. FDA should require the company to immediately start a post approval study to determine the long-term effect of the treatment particularly on teens and young adults. The data presented by Avedro cannot confirm if the procedure merely delays progression of the disease, or if it is a permanent solution. If the procedure is not a permanent solution, then it is important that patients use that information in determining if the risk of adverse events is worth the delayed progression.

In conclusion, it is crucial that patients have a safe and effective treatment option for progressive keratoconus and corneal ectasia.  But the evidence indicates this treatment would do more harm than good for Lasik patients.

To protect the patients who would benefit and those who are likely to be harmed, the FDA needs to use a black box warning and minimize the off-label use of the product. Post market approval studies will also provide valuable information about the risk benefit for undergoing the procedure.

Thank you for your time.

 

Committee Vote:

First indication, Keratoconus: 10 Yes, 4 No, 1 Abstain

Second indication, Corneal ectasia: 6 Yes, 4 No, 4 Abstain, 1 No Voting

By Amelia Murphy

February 23, 2015

News about Alzheimer’s disease and other dementias is rarely uplifting, but a 2014 study shows that something as simple as exposure to light during the day may improve life for people with the condition. Alzheimer’s and other dementias affect millions of people, causing mild to severe memory loss, which makes it difficult to carry out daily activities such as remember simple things or have a conversation.As many as 5 million Americans over the age of 65 are living with dementia. Unless significant advances are made, this number is expected to almost triple by 2050.6

Currently, there is no known cure.  The Center for Diseases Control (CDC) suggest that caregivers try to manage patients’ symptoms, prevent triggers that upset the person, and arrange the environment to ensure his or her safety.  Although it is possible to slow the worsening of some of the symptoms, nothing can completely stop the disease’s process.7 One important way to improve the quality of life for those with dementia is to modify their environment so that they are less likely to become agitated.

Agitation, which means the person is restless or worried, can cause pacing, sleeplessness, or aggression, and it is one of the major complaints by caregivers of dementia patients.8 People with dementia often sleep for large parts of the day and are awake for about 40% of the night. Being awake at night increases the likelihood that they will get out of bed and fall in the dark. Perhaps because of this, people with dementia are three times more likely to fall than other older adults.9 Sleep problems also lead to increased agitation and more problems with memory, as shown by worse scores on tests of recognition and recall.10  Moreover, nighttime waking and poor sleep are a leading cause for patients to enter long-term care facilities.

There’s some research to suggest that the sleep problems that people with dementia have may predate and even contribute to the development of the disease. At least one study found that poor sleep was linked to the presence of a molecule that leads to the formation of plaque in the brain—the same kind of plaque found in people with Alzheimer’s disease.11 If people with Alzheimer’s can sleep better, they may be able to feel and function better and perhaps even slow the progression of their disease. And while there’s no research yet to support this: It’s possible that improving sleep in people who haven’t yet shown any signs of developing Alzheimer’s might prevent the disease or delay its onset.

Can Installing Lights Improve Sleep Quality and Help Alzheimer’s Patients?

alz light bedThe September 2014 study,12 funded by the National Institute on Aging, included 14 participants who had an average age of 87. They all lived in long-term care facilities in Albany, NY, had mild to moderate dementia, and suffered from sleep and agitation problems. Fluorescent lamps with low level blueish-white light were installed in each participant’s room. A timer turned them on between 6 and 8am, and off at 6pm. If the timer didn’t detect movement in the room for 20 minutes, it turned the lights off. These lights were designed to imitate daylight, telling the body when to be awake.

Researchers collected information about the participants at three points: before these new lights were installed, after 4 weeks with the new lights, and 4 weeks after the lights were removed. Participants wore small devices on their wrists, called Daysimeters, for 7 days at each of these three points to continually record light and participants’ activity levels. The primary caregivers filled out questionnaires about the sleep quality and daily living activities of the participants as well as noting their levels of, depression and agitation.

Results

Just by regulating participants’ exposure to this special light that simulates daylight, researchers found a significant increase in sleep quality (the average sleep time increased by 30 minutes per night). Caregivers reported a significant decrease in depression and agitation in the participants after the lights were installed. Daysimeters showed that participants were more active during light hours and more at rest during dark hours. The increase in daytime activity was especially apparent after lunch. Four weeks after the lights were removed from the rooms, participants’ agitation and depression rose to be closer to that experienced before light installation. Sleep quality decreased after the lights were removed, but not significantly.

Though these are promising results, it’s important to remember that this study was small and only 4 weeks long. There was no comparison group of Alzheimer’s patients who didn’t have the new lights in their room, so we can’t be absolutely sure that these positive changes were a result of the new lights. Also, the caregivers filling out the questionnaire could see that lights had been installed (they didn’t know the goal of the study), so this could have affected the way they scored their patients’ sleep and agitation.

Other weaknesses in the study: Only 10 of the 14 participants used the Daysimeter, and data for the full 7 days was only usable from 6 of those subjects. Wearing the Daysimeter on the wrist presented problems since it was often covered by clothes or a blanket, making data collection difficult. Due to this difficulty, researchers could not evaluate the information from the Daysimeters at the point 4 weeks after the lights were removed. Lastly, the questionnaires were not completed at all three stages for all 14 participants.

The Bottom Line

Researchers only tested the effect of the lighting for 4 weeks. Based on the results, they recommended that future studies look at using the lights for 6 months. Installation of these new lights would be low cost (a light costs about $24 and light timers are around $15). If a more expensive “wall washer” (about $200) is installed with the light, the light is directed toward the ceiling, giving the room an even, diffuse illumination which  uses less energy and minimizes glare. So far, the effect of light on people with Alzheimer’s disease has only been studied in long-term care facilities. If caregivers want to try this at home, they should install the lights in the room where the person with Alzheimer’s spends most of his or her day. If the person is very mobile and moving from room to room or spending regular time outdoors, installing these lights might not provide any additional benefit. Figuring out how to apply these findings to private homes will require more study. Regardless, using a short-wave white light such as this one during the day may be a low cost, no harm way to help Alzheimer’s and related dementias patients get more sleep. This could decrease their agitation and depression, improve their quality of life and lessen the burden on caregivers. Based on this research, caregivers might consider using these lights for any older person with limited mobility and difficulty sleeping.

 

By Noam N. Levey, Chad Terhune, and David Willman, LA Times

February 19, 2015

Duodenoscopes linked to superbug at UCLA

Duodenoscopes like this one have been linked to the superbug outbreak at a UCLA hospital. The scopes are commonly used by physicians to diagnose and treat cancer, gallstones and other conditions. (Liz Martin/The Gazette)

A commonly used medical scope linked to a deadly bacterial outbreak at UCLA may be so flawed it cannot be properly cleaned, federal officials conceded Thursday. But they stopped short of recalling the device or outlining any new sterilization procedures.

The U.S. Food and Drug Administration has known about the potential problems for more than two years, and took action only after The Times reported this week that two patients died in a new superbug outbreak at UCLA’s Ronald Reagan Medical Center. At least five other patients have tested positive for the drug-resistant bacteria, and 179 others may have been exposed.

Critics immediately complained about the FDA’s failure to act.

“FDA didn’t do its job,” said Diana Zuckerman, president of the nonprofit National Center for Health Research.

An FDA spokeswoman said that the devices’ benefits outweighed the risks.

“If we pulled the devices from the market, we would prevent hundreds of thousands of patients from accessing a beneficial and life-saving procedure,” said the spokeswoman, who, like other agency officials, spoke on condition she not be named. “So at this time, the continued availability of these devices is in the best interest of the public health.”

The devices, called duodenoscopes, which feature a tiny camera mounted on the end of a tube that is threaded down a patient’s throat and into the digestive tract, are commonly used by physicians to diagnose and treat cancer, gallstones and other conditions. Nationally, about half a million patients each year undergo the procedure, called ERCP, or endoscopic retrograde cholangiopancreatography.

Duodenoscopes are considered much less invasive and risky than surgery. And doctors credit them with saving lives through early detection and treatment.

The infections at UCLA are the latest in a series of outbreaks linked to duodenoscopes in recent years that have sickened patients at hospitals in Pennsylvania, Illinois and Seattle.

The FDA said Thursday that from January 2013 to December 2014, it received reports of 135 patients potentially infected by contaminated scopes.

But medical experts and safety advocates have been reporting potential design flaws for years.

In October, a study in the Journal of the American Medical Assn. linked bacterial infections to duodenoscopes at an Illinois hospital, even though researchers found no cleaning lapses.

The FDA acknowledged this problem in its new warning: “Some parts of the scopes may be extremely difficult to access, and effective cleaning … may not be possible.”

The agency noted that moving parts in the scopes contain microscopic crevices that can’t be reached with a cleaning brush and may harbor residual body fluids and organic debris that could expose subsequent patients to serious infections.

One type of bacteria, known as CRE, are particularly dangerous because they can’t be treated with most antibiotics, leading to mortality rates of up to 50%, according to the Centers for Disease Control and Prevention.

Unless regulators give hospitals and physicians better guidance or the scopes are redesigned, more patients will get sick, said hospital safety consultant Lawrence Muscarella.

“There are no corrective actions that tell me how to address the problem,” he said

Sen. Patty Murray (D-Wash.), who urged the FDA to update its safety guidance after a Seattle hospital reported that 11 patients died in a similar bacterial outbreak, also said more should be done to ensure patients’ safety. Murray is the senior Democrat on the Senate Health Committee.

FDA regulators urged medical providers Thursday to carefully follow manufacturers’ cleaning instructions and talk to patients about the benefits and risks of undergoing procedures that involved duodenoscopes.

“The FDA’s move is a step in the right direction, but it doesn’t have a lot of guidance about how to reduce the risk beyond what was already known,” said Dr. Jeffrey Duchin, an epidemiologist who oversaw the Seattle-King County investigation of the recently disclosed bacteria outbreak at Virginia Mason Medical Center in Seattle.

“Many clinicians and people I work with in the public health community are frustrated by the pace at which the issued is being addressed,” he said.

Nancy Foster, vice president for quality and patient safety at the American Hospital Assn., called the FDA’s guidance “problematic.”

“We want to be able to rely on the guidance to get the result that we want, and what we want is a clean endoscope,” she said.

Olympus, the market leader in duodenoscopes, said in a statement Thursday that it was making available to its customers supplemental educational materials, including an interactive checklist with video demonstrations. “We are working with the FDA, relevant medical societies and our customers regarding these concerns,” the company reported.

FDA officials were reluctant Thursday to discuss what other steps they may take, but the spokeswoman said the agency was trying to determine what it could do to limit infections.

UCLA has said it changed its decontamination procedures after discovering CRE in a patient in late January. It also alerted county and state health authorities at that time. No new cases have been found since UCLA began using gas sterilization. The gas, which is highly toxic, carries its own risks, however.

Many medical centers are looking for alternatives.

Some hospitals now quarantine their endoscopes for 48 hours after cleaning to check for bacterial growth. That system has drawbacks for busy hospitals because the scopes are unavailable for an extended period.

See original article here.

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