By Amelia Murphy

November 14, 2014

 

peanut-370470_640Food allergies are on the rise, making school, traveling, and even birthday parties risky business for many children. It’s hard to tell if children’s increased sensitivity to certain foods is due to their hyper-clean environments,1 early exposure to antibiotics,2 too little vitamin D from the sun,3 or something else. As of 2011, 1 in 13 children have a food allergy in the United States, and 40% of those children have had a severe or life-threatening reaction.4

 

What is a Food Allergy?

A food allergy is when a body’s immune system mistakes a certain food for something harmful, which leads to a potentially dangerous reaction. For example, if a person allergic to peanuts eats a peanut, her immune system overreacts and releases a chemical called histamine, which can affect the “skin, eyes, nose, airways, intestinal tract, lungs, and blood vessels.”5 This can lead to itchy eyes, wheezing, hives, itchy mouth, or a tight throat, among other things. In the worst case scenario, the allergic person may enter a state of anaphylaxis, a severe whole-body allergic reaction, which may include difficulty breathing, vomiting, swelling of parts of the body, and even death.

Anything that produces an allergic reaction in many people is called an “allergen.” Peanuts are one of the most common food allergens. Milk, eggs, fish, crustacean shellfish, wheat, soy, peanuts, and tree nuts make up 90% of the food allergens in the United States.6

Most doctors advise children and their parents to: 1) prevent a reaction by having the allergic child or adult completely avoid the food allergen;7 and 2) carry or have quick access to an EpiPen at all times in case the person is accidentally exposed and has anaphylaxis. But avoidance of problem foods isn’t always easy, for children or adults. Peanuts can be hidden in a variety of foods, such as specialty pizzas, some enchilada sauces, egg rolls, glazes, marinades, chili sauce, and candy.8 Knowing that a life-threatening allergic reaction may be one bite away is frightening for children, parents, and other adults.  

 

Can allergic reactions to food be prevented by oral immunotherapy?

Oral immunotherapy (OIT) involves training children allergic to peanuts to do what they have been trained not to do: eat peanuts! In a 2014 study of this treatment, over 80% of participants were able to eat the equivalent of about five peanuts after OIT.9 This form of treatment has the potential to make the daily lives of young peanut allergy sufferers and their parents much less stressful.

The publicly funded study, which was published in the respected medical journal The Lancet in April 2014, found that introducing peanut protein powder to children in small but increasing doses can train the body to be less sensitive over time. The year-long study included 99 children from the United Kingdom, aged 7-16, with peanut allergies. During the first 26 weeks of the study, one group of children  received peanut protein powder every day (the treatment group) and the other group did not receive the powder or any other exposure to peanuts (the control group). In the second 26 weeks of the study,  only the control group took the peanut protein powder.

After each of the two 26-week periods, all the participants were given a dessert to eat that either had peanuts or did not. Neither the researchers nor the children knew who was getting which dessert. At the end of the first 26 weeks, 84% of the children who received the peanut powder treatment could tolerate the equivalent of 5 peanuts daily. Close to two-thirds of the children in the treatment group had no reaction to the dessert at all (which contained 10 peanuts). While 38% of the children receiving the treatment had some sort of reaction to the dessert, 100% of the control group had an allergic reaction to it.

During the second 26 week period, the children in the control group received the peanut powder treatment instead. By the end, 91% of them were able to tolerate the equivalent of 5 peanuts a day. A little over half (54%) ate their dessert containing the equivalent of 10 peanuts without experiencing any reaction. The researchers concluded that the majority of the children had mild or no allergic reactions to a dessert with peanuts after the treatment.

 

Why is this study important?

This is the largest randomized controlled study ever done on oral immunotherapy for children with peanut allergies. Earlier studies were conducted on smaller numbers of children and did not compare those getting treatment to those who didn’t.  This 2014 study will pave the way for future research needed to answer many still unanswered questions, such as how long does the desensitization last, how well does it work on adults, and could this be used for other food allergies?

 

What are the drawbacks of this study?

One of the problems with this study is that 15 of the 99 participants dropped out without completing the study and were not included in the analysis. Most of the children who quit did so because they were experiencing unpleasant allergic reactions, didn’t like the taste of the powder, or were unable to increase their dose enough to take the dessert challenge. By excluding these children (who were mainly in the treatment group), the researchers may have made OIT look a little more successful than it was.  On the other hand, nearly all of the controls who received the peanut powder completed the study and achieved the same high level of desensitization as the treatment group.  What is clear from this study is that not everyone will be willing or able to undergo this form of allergy treatment.

Another shortcoming of the study was that it did not continue to follow-up with the children after the therapy was over.  The effects of OIT wear off over time, and it is expected that many will become allergic again after about 9 months if they don’t have a fixed daily dosage of peanuts.10 The researchers  suggest continuing to consume peanut powder every day for several years after treatment, but since that was not studied, there is no way to know. Some treatment centers that offer OIT instruct patients to eat 3 peanuts a day after OIT in order to stay desensitized, but this is not based on research but rather scientific guesswork.

The 2014 study does not tell us whether OIT can work for people younger than 7 or older than 16. While allergies to milk11, eggs12, and wheat13 often end up being childhood allergies that lessen or go away completely by the teenage years, allergies to peanuts, tree nuts, fish, and shellfish tend to be lifelong. Further research is needed to study the impact of this therapy for other food allergies and for adults.

 

Is OIT expensive?

Although OIT is still considered an experimental treatment, many health insurance companies will pay for it. Prices vary from one center to another, but the OIT Center in Michigan, for instance, charges about $140 per hour on the first visit, which can take up to 8 hours. Visits to increase dosage are about $110 per visit (with at least one week between dose increases) for about four months. Other centers have patients undergo OIT for longer. In other words, the cost is likely to be several thousand dollars.

 

Bottom Line

If OIT is found to work over the long-term, it could mean less reliance on EpiPens, fewer trips to the ER, less worry and greater shared enjoyment for all. This is exciting news but remember: OIT should NOT be tried at home, without a doctor’s supervision!

There are centers around the country that are beginning to offer OIT, with treatment lasting from 6 to 12 months. However, many parents will be reluctant to try OIT for their children and insurance companies may be reluctant to pay for it until more is known about how long OIT should last, what a maintenance dose should be, and how long maintenance therapy is needed.  Likewise, more research is needed before OIT can be considered promising for adults or for other food allergies.

By Heather Catallo, WXYZ Detroit

November 5, 2014

The 7 Investigators obtained records from the Food and Drug Administration (FDA) showing that the original manufacturer of a permanent birth control device, Essure, knew patients were being harmed by the device more than a decade ago.

At the time, the device was made by Conceptus. They were cited more than once by the FDA for failing to report all of the complaints about Essure within the 30 day time period allowed by law.

“I have no idea how safe this medical device is and neither does anybody else,” said Dr. Diana Zuckerman, President of the National Center for Health Research.

Essure is marketed as permanent birth control without surgery. During the procedure, two metal coils are placed inside the fallopian tubes. Over the next three months, scar tissue is supposed to amass around the coils, blocking conception. The 7 Investigators have been reporting about Essure for nearly a year, after dozens of women came forward to share their stories. Common complaints include bloating, rashes and chronic pelvic pain. Women also reported serious issues they say resulted from Essure, such as miscarriages and ectopic pregnancies. In many cases, the coils perforated the fallopian tubes and needed to be removed. Many had hysterectomies.

Conceptus was inspected twice by the FDA, in 2003 and again in 2010, according to records obtained from the FDA. In both instances, the company was issued what are called Form 483s. They are issued after an FDA inspection to firm management, “when an investigator has observed conditions that may constitute violations of the Food, Drug and Cosmetic Act…or any related acts,” according to the FDA’s website.

The FDA refused to comment on the forms, but their website describes them as a form that “notifies the company’s management of objectionable conditions.”

See the FDA’s complete response to 7 Action News below.

Dr. Michael Carome, Director of the Health Research Group for Public Citizen, told the 7 Investigators that Form 483s are relatively common and can be issued anytime an FDA inspector has found what they think is a violation of the law. Some are serious, some are less so.

The current owner of Essure, Bayer HealthCare, told 7 Action News they purchased Conceptus in June 2013 and haven’t received any observations from the FDA concerning Essure via a Form 483 since then.

See Bayer’s complete response to 7 Action News below.

The records show, in 2003 the FDA found Conceptus had procedural issues involving identifying causes of nonconforming products “and other quality problems”.

But, what got the attention of Zuckerman and Carome are records from 2010, showing the company failed to report adverse events or injuries that may have been caused by the device to the FDA.

“It’s clear that the FDA inspectors found that the company wasn’t being forthcoming in reporting problems that patients were having,” Zuckerman said.

In two observations, an FDA inspector found that a Medical Device Report “was not submitted within 30 days of receiving or otherwise becoming aware of information that reasonably suggests a marketed device may have caused or contributed to a death or serious injury.”

The records describe two complaints in which the device perforated the patient’s bowel during the procedure and 39 other complaints of perforation of the fallopian tube or uterus from July to December, 2010.

The inspector goes on to describe several instances in which the device “malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.”

The reports describe a database of complaints Conceptus provided to the FDA inspector that showed, since December, 2007, there were 168 complaints of perforation of the micro-insert. In the same time period, the FDA received only 22 complaints of perforation, pain and bleeding, the inspector wrote.

In the inspection report, women reported bleeding, pain and perforation, where the metal coil migrated out of the fallopian tube. After an incident reported in November, 2010, a patient was taken to the hospital for surgery. She eventually got a hysterectomy.

Another incident describes a patient reporting pain “immediately following the procedure,” in 2010. A CT scan “revealed the device was in 2 pieces.”

Bayer told 7 Action News they take all adverse events seriously and that most of the side effects related to Essure are known and included in the Essure Instructions for Use information. The FDA agreed with Bayer after a review of the complaints related to Essure last year.

According to Dr. Carome with Public Citizen, it’s difficult to tell how serious these issues are based on these records alone. But, he said the safety system the FDA has set up depends upon accurate reporting from device manufacturers, so these observations could potentially be very serious.

CLINICAL TRIAL QUESTIONS

These records have Dr. Zuckerman with the NCHR questioning the original clinical trials.

“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,” she said.

The FDA told 7 Action News the follow-up studies to the clinical trials have been completed. At the time the device was originally approved by the FDA in 2002, FDA spokesperson Jennifer Rodriguez said, “The FDA had one to two years of safety and effectiveness outcomes data for Essure,” and that the FDA advisory panel unanimously recommended that the device be approved.

But, Zuckerman said clinical trial studies are frequently based on too few people, studied for too short a period of time.

“The data make it look like a product is safer or more effective than it really is,” Zuckerman said.

CORRECTIVE ACTION PLANS

After a Form 483 is issued to a company, the company has to take corrective actions to address the issues at hand before the agency can determine what further action is necessary, if any.

The 7 Investigators requested the Corrective Action Plans Conceptus created as a result of these Form 483s from the FDA. We received the plans after they had been heavily redacted.

In response to the Form 483s received in 2003, Conceptus created Corrective and Preventive Action plans, but the details of those plans are blacked out in the records we received.

But, in response to the issues the FDA inspector found with reporting adverse events, Conceptus argued the point in some cases.

The company said they did, in fact, report the event in one case, but denied that the other injuries were a result of the device.

“Conceptus did not intend to conceal these types of incidents from FDA,” the records state, but the company didn’t believe those events needed to be reported.

In response to the other allegations:

  • The FDA also found Conceptus did not report events when the device “malfunctioned and would be likely to cause or contribute to a death or serious injury if the malfunction were to recur.”
  • In this case, Conceptus acknowledged the device had malfunctioned, but argued that they didn’t need to report it because the reports caused “mere ‘trivial impairment or damage”. The company didn’t believe it would be likely to cause serious injury if the malfunction occurred again.
  • Conceptus was also cited for an incomplete risk analysis process. The FDA found that Conceptus does not recognize that when the coils migrate out of the fallopian tubes and into the peritoneal cavity that is “a potential failure”.
  • Conceptus agreed to resolve this issue, but most details are redacted.
  • The FDA also found that Conceptus did not issue a corrective and preventative action and its results after materials used in the device “were taken from quarantine without having the components fully certified.”
  • Conceptus told the FDA the issue is now resolved, but details are blacked out.

Bayer’s complete response to 7 Action News:

As you are aware, Bayer acquired Conceptus in June 2013. Bayer takes all information reported on Form 483s seriously and works closely with the FDA to address any questions or observations they may have. Bayer has not received any observations from the FDA concerning Essure via a Form 483 since its acquisition of Conceptus.

We take all adverse events seriously. Most of the side effects that have been reported about Essure are known and included in the Essure Instructions for Use information. This was recently confirmed by the FDA which found that “[a]lthough there is evidence of complications, as there are with all medical devices, overall results from [a five year safety] study did not demonstrate any new safety problems or an increased incidence of problems already known.”

The information you have regarding the 5-year post approval follow up study is inaccurate. The purpose of the study you are referring to was to determine the rate of successful placements of Essure at first attempt among newly trained physicians. Positive placement data obtained within the first three years of this study prompted the FDA to allow for early termination. Safety and efficacy continued to be collected on patients in the study and was reported to the FDA.

# # #

Indication

Essure is a permanent birth control procedure that works with your body to create a natural barrier against pregnancy.

Important Safety Information

WARNING: You must continue to use another form of birth control until you have your Essure Confirmation Test and your doctor tells you that you can rely on Essure for birth control.

  • You can rely on Essure for birth control only after your doctor has reviewed your Essure Confirmation Test results. Your doctor will confirm that the inserts are properly placed and both of your fallopian tubes are blocked. If you rely on Essure for birth control before having your Essure Confirmation Test, you are at risk of getting pregnant.
  • Talk to your doctor about which method of birth control you should use for the 3 months after the procedure. Some women can remain on their current birth control. Other women, such as those using an intrauterine device or contraceptive (IUD or IUC), will need to switch to another method.
  • It can take longer than three months for the Essure procedure to be effective. In rare cases, it has taken up to 6 months. Make sure to continue using an alternate form of birth control up until your doctor has reviewed your Essure Confirmation Test results and confirmed that you can rely on Essure for birth control.

WARNING: Be sure you are done having children before you undergo the Essure procedure. Essure is a permanent method of birth control. The younger a woman is when she chooses to end her fertility, the more likely she is to regret her choice later.

During the procedure: You may experience mild to moderate pain, your doctor may be unable to place one or both Essure inserts correctly, part of an Essure insert may break off or puncture the fallopian tube requiring surgery to repair the puncture, or your body may absorb a large amount of the salt water solution. Your doctor may recommend a local anesthesia which numbs the cervix. Ask your doctor about the risks associated with this type of anesthesia. Immediately following the procedure: You may experience mild to moderate pain and/or cramping, vaginal bleeding, and pelvic or back discomfort for a few days. Some women experience nausea and/or vomiting or fainting. In rare instances, an Essure insert may be expelled from the body. During the Essure Confirmation Test: You will be exposed to very low levels of radiation, as with most x-rays. In rare instances, women may experience spotting and/or infection.

Long-term Risks: There are rare reports of chronic pelvic pain in women who have had Essure. In rare instances, an Essure insert may migrate through the fallopian tubes into the lower abdomen and pelvis. It may be necessary to surgically remove the migrated device if the patient is experiencing an adverse event. No birth control method is 100% effective. If you do become pregnant after Essure, the risks to you, the fetus, the pregnancy and childbirth are unknown. Women who have the Essure procedure are more likely to have an ectopic pregnancy if they get pregnant. Ectopic pregnancy is when the pregnancy occurs outside of the uterus. Ectopic pregnancies can be very serious or life-threatening. If you have the NovaSure® procedure, a procedure that removes the lining of the uterus to lighten or stop menstrual bleeding, after the Essure procedure, your risk of pregnancy may increase. The Essure insert is made of materials that include a nickel-titanium alloy. Patients who are allergic to nickel may have an allergic reaction to the inserts. Symptoms include rash, itching and hives.

Unknown Risks: The safety and effectiveness of Essure has not been established in women under 21 or over 45 years old. The safety and effectiveness of reversing the Essure procedure, of in vitro fertilization (IVF) after the procedure, or to you and your fetus if you get pregnant after the procedure are not known.

Adverse Events: During the procedure, the most common problem reported was mild to moderate pain (9.3%). Some of the women in the study reported moderate pain (12.9%) and/or cramping (29.6%) on the day of the procedure. A smaller percentage of women reported nausea/vomiting (10.8%) and vaginal bleeding (6.8%).

Essure inserts do not protect against HIV or other sexually transmitted diseases.

Talk to your doctor about the Essure procedure and whether it is right for you.

The FDA’s response to 7 Action News:

The FDA required Conceptus to conduct two studies as conditions of approval:

1. Post-Approval Study (PAS I): 5-year Follow-up under Essure System

2. Post-Approval Study (PAS II): U.S. Post-Approval Study for Newly Trained Physicians

PAS I evaluated the long-term follow-up (through 5 years) of the participants from the two premarket clinical investigations, and included assessment of safety, effectiveness, and patient satisfaction. The 5-year follow-up requirement was determined based on evidence available at the time of device approval and advisory panel recommendations (OB/GYN Panel Summary, 7/22/02:http://www.fda.gov/ohrms/dockets/ac/02/minutes/3881m1_summary%20minutes.pdf). This study was not terminated early—it was brought to full completion and the product label was updated with the resulting data.

PAS II was designed to document the bilateral placement rate at first attempt for newly trained physicians in the U.S. These data were used to evaluate the training procedures and to update labeling. The study was originally designed to enroll 800 women from 40 physicians in the commercial setting. Conceptus submitted a study report to the FDA in 2005, having enrolled 514 women. The sponsor used Bayesian statistics to demonstrate that enrolling additional women would not change the observed results. After reviewing the report, the FDA agreed and considered this condition of approval to be satisfied. Long-term follow-up of patients was not part of this study design.

See original article an TV interview here.

By Diana Zuckerman, PhD; Paul Brown, BA; Aditi Das, PhD

The US Food and Drug Administration (FDA) approves about 400 implanted medical devices each year through an abbreviated process called the 510(k) process, which only rarely requires clinical trials (studies of patients).  These implants include potentially high-risk devices such as heart valves, spinal implants, and hip and knee joint replacements.  In contrast, fewer than 20 implants each year are approved by FDA through the more rigorous Premarket Approval (PMA) process that requires that the impact on the patients’ health be studied in clinical trials The law requires that all medical implants sold in the U.S. provide a reasonable assurance of safety and effectiveness based on scientific evidence, even if the company doesn’t provide data from studies of patients.  The scientific evidence could include bioengineering studies, for example, to determine if the new implant is expected to be similar to older implants on the market.

This groundbreaking study examined the scientific evidence provided to the FDA and the public for 1155 medical implants. The study focuses on 50 representative medical implants newly cleared by the FDA 510(k) process from 2008-2012.  Since those implants were required to be substantially equivalent to implants already on the market, called “predicates,” the study also included the 1105 “predicates” for those 50 implants.  The implants included hip implants, surgical mesh, cardiac implants, spinal implants, and dental implants, among others. By law, every 510(k) medical device application since March 15, 1995 must provide a summary that includes “sufficient evidence” to prove that the new device is substantially equivalent to a device already on the market.  This summary must be available online, linked to a letter on the FDA website granting the company clearance to sell their device in the U.S.  If a company doesn’t provide that summary, the law requires it to provide all the same information within 30 days of a written request from anyone.  This is especially important for implants, since they can cause permanent damage or even be life-threatening if they fail while inside the human body

RESULTS:  Just 3% of the 1155 implants in the study provided scientific evidence that the implant was substantially equivalent to its predicate or that it was safe and effective.   Even when predicates had been permanently recalled because of fatalities or serious injuries, there was no evidence of how the newly cleared implant was similar or different from those predicates.  Since 2009, the FDA leadership has repeatedly focused on the need for transparency at the FDA, but even in 2012, the 3rd year of new leadership at the FDA, only 20% of the implants had any kind of publicly available scientific data. CONCLUSIONS: For the 1155 implants studied, “sufficient detail to provide an understanding of the basis for a determination of substantial equivalence,” as required by law, was unavailable to physicians, patients, providers, and others who care about patient safety or public health. Numerous newly cleared implants had predicates that had been recalled because of serious risks, calling into question the safety of the newer “substantially equivalent” implants. Regardless of how much effort physicians and providers would make to find out about the safety or effectiveness of new medical implants, they do not have access to such information for approximately 84% of medical implants that have been cleared in recent years, and more than 95% of those cleared in the last 2 decades.

IMPLICATIONS:  Previous criticisms of the FDA medical device approval process by the Institute of Medicine and public health researchers have focused on the lack of clinical trial data proving safety and effectiveness.  The FDA has repeatedly claimed that the agency has other rigorous scientific criteria for approval, such as bioengineering data proving that the new devices are so similar to the ones already on the market that they will be just as safe and effective.  This is the first study to examine the “other scientific data” that the FDA explains that it relies on.  The results indicate that either the companies are not providing solid scientific data proving that the new devices are substantially equivalent to the predicates, or that the companies are not making a sufficiently detailed summary of their scientific evidence publicly available, as required by law.  In cases where an earlier “predicate” was recalled because of serious or possibly fatal risks, the researchers found no publicly available scientific evidence to inform physicians or patients whether the newer implant would have the same potentially fatal flaw.  To safeguard the health of patients, the FDA should enforce the law.

From JAMA Internal Medicine, published online September 29, 2014.  A link to the official abstract of the article is available here. A podcast with Drs. Zuckerman and Sharfstein is available on the JAMA Internal Medicine website and can be found here. 

November 3, 2014

Good afternoon. My name is Dr. Laurén Doamekpor, and I am a senior fellow at the National Center for Health Research. Our non-profit research center is dedicated to improving the health and safety of adults and children and we do this by assessing scientific and medical data and providing objective health information to patients, providers and policy makers. Our organization does not accept funding from the fish industry, and therefore I have no conflicts of interest.

An important part of the work we do is explaining science and complicated medical jargon to people who don’t have a college degree or any scientific training. From our experience talking to consumers and answering their questions, we know that many people are frustrated and confused by what seems like conflicting information about food safety and nutrition.

Today’s example is typical. Fish is good for you, but certain kinds of fish can be dangerous – especially for children and for women who are pregnant or nursing.

How can we explain that to women in ways that are simple to understand and remember?  Of course, the biggest problem is that albacore tuna is high in mercury. Since tuna is the most popular fish, and the most affordable, how can we explain to women that they should eat fish but avoid albacore tuna if they are pregnant, might get pregnant, or nursing?

In the past, the FDA and EPA have tried to finesse that message.  That’s hasn’t worked effectively.

We believe in women’s ability to understand and remember that if they are pregnant or nursing they should avoid canned white tuna and other albacore tuna and instead consume light tuna no more than once a week. This doesn’t have to be complicated.

The draft guidance recommends that pregnant women, women who might become pregnant, and breastfeeding mothers eat at between 8 and 12 ounces per week of a variety of fish lower in mercury within their calorie needs. The advice to eat “a variety” of fish is very vague and not very helpful. It is also misleading. The truth is that these women should avoid fish that are higher in mercury, period. It should be made clear that the variety of fish consumed should come from the list of low mercury fish that also have nutritional value.

We also know that many consumers aren’t sure what 8 and 12 ounces means. It’s easy for canned fish, since that is measured by ounces.  It’s more difficult for prepared frozen fish (which might be breaded) or for fish sold by the pound.  However, there are other ways to describe portions that might be helpful. For example, one easy tip to share with consumers is that a 4 ounce fish serving is approximately the size and thickness of a deck of cards.

Incorporating diagrams and info-graphics in messaging are also effective tools for communicating information that is easier to understand.

We reviewed the proposed sound bites.  The sentences are much too long and complicated – the same information can be provided much more simply.  Terms such as “emerging science” should be avoided, instead using terms such as “the latest information.”

Please consider using a take home message that is easy to remember, such as “Rule of thumb: The smaller the fish, the safer the fish.”  However, it is also important to remember that not everyone knows that tuna is a very large fish and tilapia is a smaller fish.

In conclusion, most consumers don’t want to have a long list of exactly what kind of fish to eat and what to avoid.  If pregnant and breastfeeding women have avoided fish for themselves and for their young children it’s because the messages they were getting were confusing.  For the millions of women with smart phones, prepare a simple list of fish to choose and avoid.  Make a similar list for women without smart phones.  And come up with phrases that are easy to remember and and messages that are straightforward.

Division of Dockets Management (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

October 29, 2014

Comments of members of the Patient, Consumer, and Public Health Coalition on
Draft Guidance for Industry
“Internet/Social Media Platforms with Character Space Limitations— Presenting Risk and Benefit Information for Prescription Drugs and Medical Devices”

Docket No. FDA-2014-D-0397-0001

As members of the Patient, Consumer, and Public Health Coalition, we welcome the opportunity to provide feedback on this draft guidance regarding use of internet and social media platforms for communicating about medical products.  Patients and consumers increasingly rely on social media and the internet as sources of health and medical information that influence their decisions to seek medical care.

The draft guidance states, “Truthful, accurate, non-misleading, and balanced product promotion best serves the public health.”  We agree. But the draft guidance as written will not result in that desired goal.

The Food and Drug Administration (FDA) recognizes throughout this draft guidance the inherent difficulty in communicating adequate risk and benefit information through platforms that have very tight space limitations.  The draft guidance states, “For some products, particularly those with complex indications or extensive serious risks, character space limitations imposed by platform providers may not enable meaningful presentations of both benefit and risk.”

However, the draft guidance fails to provide any meaningful solutions to this problem.  Instead, the draft guidance simply abdicates the determination of whether such a platform is appropriate to the discretion of the sponsor.  Specifically, the draft guidance states, “If a firm concludes that adequate benefit and risk information, as well as other required information, cannot all be communicated within the same character-space-limited communication, then the firm should reconsider using that platform for the intended promotional message.”  As firms stand to benefit from information that places their product in the most favorable light, leaving this decision to them is likely to result in information that gives short shrift to safety or risk information.  The FDA has not identified any enforcement mechanisms to ensure compliance and lacks sufficient resources to adequately monitor these platforms.  If finalized, this guidance is non-binding and voluntary by nature.  On the other hand, that is almost irrelevant since this guidance leaves the most important decisions to the company that wants to sell its product.

The one major attempt to resolve the issue of space limitations comes at the cost of presenting adequate risk information.  The draft guidance states that the firm may present the “most serious risks,” and then, rather than delineating all the risk information, it could instead provide a link to the full risk information.  This plan has several fatal flaws:

  • The term “most serious” is open to interpretation, and individual patients and consumers may have different views about what risks they find acceptable.  Are the most serious risks the ones that are common and harm quality of life, such as nausea or dizziness, or the ones that might be rare but life-threatening, such as renal failure or potentially fatal blood clots?
  • It is well known among social media experts that consumers are less likely to obtain information that requires more “clicks.”  Many may not even realize that the link provides crucial, potentially life-saving information.  Allowing most risk information to be available via subsequent links clearly increases the chances that consumers will not see all the risk information that is crucial for them.

Marketing studies suggest that most consumers and patients will not follow links to additional information.  When social media are used to promote the use of medical products, they might not even realize that the presented information is only a very partial list of all possible risks. Therefore, allowing any presentation of risks that is not comprehensive opens the possibility for misinformation.

It is difficult if not impossible to think of many examples that could effectively communicate risks and benefits within strict space limitations without removing substantial amounts of risk information and relying heavily on links, given the complexity of risk and benefit information for most medical products.  As a scientific agency devoted to public health, the FDA should not consider the policies proposed in this draft guidance without collecting data on how many consumers/patients would follow links to information about risks of medical products, compared to how many would read information that does not require one or more extra clicks to access.

The draft guidance explicitly states, “Risk information should be comparable in content and prominence to benefit claims within (emphasis added) the product promotion (i.e., a balanced presentation).”  To achieve that goal, the amount of space should be comparable for risks and benefits and the reliance on links should be identical for risks and benefits.

 

Conclusions

The draft guidance notes, “The public health is best served when risk and effectiveness information about drug and device products is clearly and accurately communicated.” We agree. Unfortunately, social media platforms with character space limitations do not allow firms to provide “a balanced presentation of both risks and benefits of medical products.”   On the contrary, it is a classic case of cramming a round peg in a square hole.  This medium was not designed to provide enough information for patients to adequately access a product’s benefits and risks.

For these reasons, this draft guidance is unacceptable to those who care about public health and providing balanced information to patients and consumers.  We strongly urge FDA to completely revise this draft guidance, so that it offers the possibility of improving the public health by providing patients and consumers with risk information on the par with promotional information.

 

Annie Appleseed Project
American Medical Women’s Association
Connecticut Center for Patient Safety
Consumers Union
MISSD
Mothers Against Medical Error
National Center for Health Research
Our Bodies Ourselves
The TMJ Association
Center for Science and Democracy at the Union of Concerned Scientists
U.S. PIRG
WARS
WoodyMatters

 

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at (202) 223-4000 or at pb@center4research.org

October 16, 2014

 

Thank you for the opportunity to speak today.  I’m Dr. Diana Zuckerman, president of the National Center for Health Research.  I’m trained in psychiatric epidemiology at Yale Medical School, I’m a former faculty member at Vassar and Yale and a researcher at Harvard , and I’ve taught Research Methods courses, and those are the perspectives I bring with me today.  Our Center has no financial ties to Chantix or its competitors or to Chantix lawsuits.

We all know that smoking kills thousands of Americans and it is very difficult to quit.  That’s why we believe that Chantix should be available as an option for those who can use it safely.

At the same time, patients and their physicians need a clear black box warning for Chantix so they know to stop taking it when necessary

The challenge today is: which data should the FDA believe?  Mark Twain once said there are 3 kinds of lies: Lies, damn lies, and statistics.  I am a scientist and I believe in statistics, but I also know they can be easily manipulated to support a particular point of view.

Your task today is to make sense of conflicting data and decide which to believe.  They include:

  • Meta-analysis
  • Observation Studies based on hospital records
  • Adverse Reaction Reports from physicians
  • Reports from Patients

Meta Analysis is a valuable tool but its accuracy depends on the quality of each study and whether they fit together.  Meta analysis results can be useful or inaccurate depending on which studies you include and exclude.  No justification was given of why most studies on Chantix were excluded and only 5 were included in the meta analysis, including one study of schizophrenics, one study of depressed patients, and 3 studies of mentally healthy patients.  It is important to study schizophrenics and depressed patients, but those data should not be mixed together with 3 studies that exclude such patients.  No justification was given for that decision, but you heard from the FDA that most psychiatric events were in those two groups of mentally ill patients, clearly biasing the results.

To consider the studies showing no association between Chantix and psychiatric side effects, it is important to understand what happens to people with acute psychiatric events related to medication.  As the FDA speakers pointed out, most do not end up in hospitals or the ER.  Many of these psychiatric side effects are not reported in medical records.  Because psychiatric commitment laws depend on acts of violence, not threats of violence, many people with dramatic psychiatric symptoms end up in jail, not in hospitals.  In fact, some studies show that there are more mentally ill individuals in the criminal justice system than in psychiatric facilities — certainly those who suddenly behave violently toward others are likely to be put in jail, not in a hospital or ER.

There’s another, more positive reason why these psychiatric side effects might not be measured in a large study.  Fortunately, many stop quickly because patients or their doctors realize they should stop taking the drug, thanks to the black box.

For all these reasons, most of the studies that Pfizer is relying on are fatally flawed.

How can we make sense of the studies showing no impact in light of the thousands of reports of psychiatric side effects?

  • The studies cited did not evaluate all psychiatric side effects, they focused on depression and suicidal thoughts and behaviors
  • Those studies did not interview patients – a shortcoming of many large databases
  • They relied on hospital records, which research shows missed 82% of adverse psychiatric events
  • Some also relied on ER or medical records – which is better than hospital records, but will still miss a lot of data

What about studies showing a significant increase in psychiatric events?  We all know that adverse reaction reports are the tip of the iceberg – it’s a voluntary system of reporting.  Compared to medical records, they can have a richness of information.  And while they are far from perfect, the sheer volume of thousands of reports – many more than for other drugs – is very compelling.

I’ve spoken with some patients who took Chantix, and their reactions are distinctly different from many other drug side effects, and don’t fit neatly into the categories that most of the Pfizer studies evaluated.  For example, I spoke to a man who was so besieged with uncontrollable thoughts that he locked his door at work and wouldn’t let anyone in.  His thoughts were so terrible that he just couldn’t deal with anyone.  That psychiatric reaction would be unlikely to fit into any of the studies.  Or a man who was so frightened that he hid in the corner of his bedroom under a blanket, trying to escape the uncontrollable thoughts by being as small as possible – trying to feel safe.  What study would accurate evaluate that?

If this Advisory Committee ignores the compelling psychiatric adverse reactions that have been reported, it would discredit thousands of doctors who made thousands of reports.  It would also discredit thousands of patients who reported them.  And it would send the message to the FDA to stop their Adverse Event Reporting systems, because what is the point of having such systems in place if you ignore thousand of such reports?

We need better studies, and I hope the post-market study underway will be better.  Based on previous research, we know that such studies must include very large numbers of patients, and must follow patients for a long enough time – not all reactions are within 30 days.  And, the studies must include patients’ reports of their side effects

In conclusion:

  • The studies Pfizer is citing are fatally flawed because they omit most psychiatric adverse reactions
  • Deleting the black box would send the message that thousands of doctors’ reports don’t count, including suicides and homicides

We strongly urge you to urge the FDA to keep the black box warning to protect patients and that you strengthen rather than weaken that boxed warning.  And, since the meta analyses are fatally flawed, as I and others have pointed out, the FDA should delete the misleading meta-analyses info from the Chantix label.

 

By Jessica Rothman

October 22, 2014

 

It’s that time of year again – time to get your flu shot! Be sure to check if your office, school, or local government is giving free flu vaccines first, because this is becoming more and more common.  If not, do not worry! Most (if not all) pharmacies and doctors’ offices – even those in supermarkets – have the vaccine available in either the nasal spray or the injection. This should be free (no co-pay at all) under nearly every insurance plan, thanks to the Affordable Care Act (Obamacare), which requires health insurance companies to provide free preventive services such as flu shots. Just call first to make sure they have the vaccine you want when you are planning to be there.

 

Which should I get: the injectable vaccine or the nasal spray?

 

This year, there are two different ways to get your flu vaccine: an injection (shot) or nasal spray.  There are also two different kinds of the flu vaccine injections: the trivalent and quadrivalent versions. The trivalent contains 3 different flu strains, and the quadrivalent contains 4 different flu strains.14 The nasal spray is quadrivalent.15 Experts have no opinion whether the trivalent or quadrivalent version is better, so do not worry about which you receive (and feel free to ask if one will cost you more than the other).

The nasal spray flu vaccine should not be taken by anyone with long-term medical conditions (such as heart, kidney or breathing problems), or if you are pregnant, have a compromised immune system, have an egg allergy, or are younger than 2 or older than 49.16  Those individuals should get a flu shot instead.  Otherwise, the choice is up to you.

 

What’s new this year?

 

This year, the Centers for Disease Control and Prevention (CDC) recommended that children ages 2-8 should receive the nasal spray vaccine.  This recommendation is based on evidence that those children will be better protected against contracting the flu.  However, there are exceptions: the nasal spray vaccine is not recommended for children with asthma, have compromised immune systems, have a history of an egg allergy, or take aspirin regularly.  Those children should get the flu shot instead.17

 

Other things to remember for young children

 

Children ages 6 months to 8 years old, who have never received a flu vaccine, either the nasal spray or injection, are recommended to receive two doses.  There should be at least 4 weeks in between the two doses.  Since the components of the 2014-2015 vaccine are the same as the 2013-2014 vaccine, it is not necessary for children in this age group who were vaccinated last year to receive two doses – one dose will be enough.18 

 

If I’m over 65, is there anything different for me?

 

As we age, the flu can be more dangerous, but at the same time vaccines are less effective because our immune systems are not as strong.  That’s why individuals over the age of 65 might want to receive a high-dose version of the flu vaccine.  This is a new type of flu vaccine that is 4 times as strong as the regular flu vaccine.  However, since this is new, there is no clear evidence that the higher dose really is better, which is why the CDC recommends either the higher or the regular dose, and not one over the other.

 

What should you do if you have an egg allergy?

 

Although people with egg allergies should not use the flu vaccine nasal spray, there are several different options available using flu shots. If you have an egg allergy but can eat lightly cooked eggs, you can receive any of the vaccinations.19 If your only reaction to eating eggs is hives, and you are between the ages of 18-49, you should receive the recombinant influenza vaccine (RIV3) called FluBok.20  For those who are younger than 18 or older than 49, you can receive any of the inactivated flu shots.  You should be observed by medical professionals for at least 30 minutes after your injection to make sure you don’t get an allergic reaction.

The RIV3 (FluBok) vaccine is also an option for anyone between 18 and 49 with a serious egg allergy.  If you have a serious egg allergy and are under 18 or over 49, or if RIV3 is not available, you are still able to receive any of the other inactivated influenza shots but you should take precautions, by being vaccinated by a doctor who has experience handling severe allergic reactions.  It is unlikely that even those with a severe egg allergy will have an allergic reaction from the flu vaccine, but it is better to be more careful, just in case.21

 

What now?

 

Now that you have all the information you need, it’s time to go get your flu shot! You’ll be happy that you did once flu season starts.

 

Division of Dockets Management
Food and Drug Administration
5630 Fishers Lane, Room 1061 (HFA-305)
Rockville, Maryland 20852

October 21, 2014

Comments of the National Center for Health Research
on
“Guidance: Food and Drug Administration Safety and Innovation Act Action Plan”
Docket No. FDA-2013-N-0745-0053

The National Center for Health Research appreciates the opportunity to provide comments on the Food and Drug Administration Safety and Innovation Act (FDASIA) Action Plan. We strongly support inclusion of separate analysis of safety and effectiveness for demographic subgroups in clinical trials for drugs and devices. It is essential that methodologically sound data about how drugs and devices work in these groups be conducted and made publicly available.

Our research center along with several other non-profit, research, academic and advocacy organizations provided oral comments at the public hearing held by the FDA on April 1, 2014 on the FDA’s 907 report.  We focused our comments on what the FDA can do to ensure greater diversity in the clinical trials submitted to the agency, but underscored the importance of having large enough numbers of major demographic groups so that subgroup analyses could be performed to determine safety and effectiveness for those subgroups. Additionally, we emphasized the importance of using those subgroup analyses as a basis of approval and labeling decisions, and making those results widely available in a user-friendly format to providers, patients, and other stakeholders. Many other speakers expressed similar concerns. We are very disappointed that the FDA’s Action Plan did not incorporate more of the suggestions and recommendations voiced during the public meeting.

The Section 907 report Action Plan outlines 27 action items in three priority areas: quality, participation, and transparency. Taken together, the action items reflect the FDA’s preliminary approach to addressing the need for greater demographic inclusion in clinical trials.  However, the plan is too vague and does not adequately focus on the need for meaningful subgroup analyses.  It also fails to emphasize the regulatory role of the FDA in ensuring those analyses rather, and instead focuses on the role of the FDA as a bully pulpit with no enforcement  power.

Our specific comments are below:  

 

Priority One: Quality–Improve the completeness and quality of demographic subgroup data collection, reporting and analysis.

 

Guidance Document for Medical Products

Section 1.1 of the Action Plan states that CBER and CDER plan to “review, update, and/or finalize, as needed, relevant industry guidance and internal FDA good review practice documents to encourage greater demographic subgroup representation in clinical trials, subgroup analysis and communication of results.”   The FDA has been encouraging greater diversity and subgroup analyses for years, with limited success, and there is no evidence that more encouragement will improve the outcome.  If the FDA believes it cannot require such analyses, then they should specify that approval for a general population (e.g. not just White males under 65, or White adults 18-65) requires that the company evaluate the major demographic subgroups to determine if the drug or biologic is safe and effective for those various groups.

We support the action item that states the FDA plans to draft “a guidance document on analysis and reporting of ethnicity, race and age in medical device clinical studies. In doing so, FDA plans to explore key barriers and limitations to meaningful data analysis.”  This guidance is essential and long overdue.  We are concerned, however, about the vague and tentative tone in the use of such phrases as “Begin drafting” and “explore key barriers.”

We also support the action item that encourages “greater demographic subgroup representation in clinical trials, subgroup analysis and communication of results.”

The barriers and limitations to meaningful subgroup data analyses are very clear: Clinical studies for many drugs and most medical devices are too small to be able to assess statistical significance when conducting subgroup analyses.  This is a particularly pervasive problem regarding racial and ethnic minority patients, since the numbers of those groups are usually far too small to be analyzed separately for safety and effectiveness outcomes.  These small device studies, which often include less than 10 African American patients, should be unacceptable for a PMA process that is limited to the highest risk medical devices.

Recommendations:

  • FDA should revise and finalize the three mentioned guidance documents and explicitly require sponsors to include the appropriate subgroup analyses to determine the safety and effectiveness outcomes for each major subgroup.
  • Subgroup analyses should analyze all safety and effectiveness outcomes for each major demographic subgroup.  Too often, the only subgroup analyses available to the public are to compare the demographic traits of each subgroup; such analyses do not provide meaningful information to determine safety or effectiveness.  All subgroup analyses  should be publicly available at FDA Advisory Committee meetings and on the FDA web site for each medical product.
  • The FDA should make it clear that the agency will not approve medical products for all populations if the product was not tested for safety and effectiveness on all major demographic subgroups with meaningful subgroup analysis.

 

Training

We support the action item in section 1.3 that states that the FDA will train new clinical trial reviewers, and “offer additional education and training courses for experienced reviewers to better clarify FDA’s expectations for data collection and analysis related to demographic subgroups.”

Recommendations:

  • To strengthen this aspect of the Action Plan, training and education of FDA reviewers must be greatly improved and consistent across CDER, CBER, and CDRH.
  • The FDA should also provide training on these issues for Members of FDA Advisory Committees and Panels.  For many years, through mid-October 2014, most Advisory Committee members have shown little interest in demographic inclusion. We have attached Table 1, which provides a sample of some recent examples of drug and device Advisory Committee votes on products with very limited diversity and lacking in subgroup analyses.

 

OWH and OMH

In Section 1.5, we support the following action items:

We support the Office of Women’s Health (OWH) plans to target OWH funding to projects that answer specific regulatory research questions and emerging priorities from the product review centers.

We support the Office of Minority Health (OMH) plans to develop research projects to better understand medical product clinical outcomes in racial and ethnic demographic subgroups.

We support the OMH plans to collaborate with National Institute of Health’s (NIH) National Human Genome Research Institute in research into the role of genetics and genomics in health disparities.

Recommendation:

  • We agree that additional research is needed to better understand issues related to participation, recruitment and analyses of diverse populations. The Action Plan should specify that OWH and OMH will conduct research to better understand subgroup differences in safety or effectiveness that become apparent as a result of the new FDA policies requiring subgroup analyses of major demographic subgroups.  For example, if subgroup analyses indicate a difference in effectiveness for women compared to men or Blacks compared to Whites for one or more diabetes drugs, the OWH or OMH would conduct research to better understand those disparities.

 

Priority Two: Participation–Identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater participation.

 

We support the FDA collaborating with NIH, other Department of Health and Human Services (HHS) agencies, industry and other stakeholders to broaden diverse participation in clinical research.

We support FDA’s OMH collaborating with agencies of the HHS, NIH, Institute of Medicine and the Human Service’s Office of Minority Health to convene a 2015 meeting to better understand the barriers to participation in clinical trials by communities of color.

We strongly support the action item where FDA’s OWH will collaborate with the NIH Office of Research on Women’s Health (ORWH) on a national campaign to educate and promote clinical trial participation, focusing on women.

However, we do not believe that the major impediment to diversity in clinical trials is the lack of interest of women, people of color, or patients over 65.  We are very concerned that the FDA’s statements put the onus on patients to be recruited, rather than on companies to recruit them.  In the same way that companies recruit the best possible physicians by providing generous incentives to participate in clinical trials, companies should do the same for a diverse population of patients.  Diversity would be greatly improved if companies would improve the incentives for patients to participate in clinical trials: reimbursement for patients’ time and travel for appointments, providing free medical appointments for follow-up medical evaluations, availability of child care for mothers of young children during patient visits and follow-up, and other efforts to reduce financial disincentives and increase financial incentives.

Recommendations:

  • The FDA should gather information from companies that are successfully achieving diversity in their trials to determine the strategies they using, and compare these practices to those of companies that are not accomplishing this goal.
  • The FDA should work with individual drug and device companies to discuss the incentives needed to obtain optimal inclusion of major demographic subgroups (gender, race/ethnicity, and age) in clinical trials, as part of their ongoing conversations with the sponsors prior to final applications for approval.
  • The FDA’s OMH should collaborate with the HHS’s Office of Minority Health and companies that make medical products to create an education campaign, specifically targeting communities of color, similar to the campaign focusing on women.

 

Priority Three: Transparency–Make demographic subgroup data more available and transparent.

 

We do not support the action items in section 3.1, as currently written. We agree that it is vital to focus on transparency and it is important to make information available to patients, providers and policy makers. However, the action items under this section fall well short of that goal. The draft guidance states that the FDA will post “demographic composition and analysis by subgroup in pivotal clinical studies for FDA-approved medical products,” and for “pivotal studies” for devices.It is unclear what this means, but if it means that each subgroup will be analyzed in terms of their demographic characteristics, rather than analyzed for safety and effectiveness, that is wholly inadequate.  It is not always possible to predict how different major subgroups might respond differently to a drug or device, and for that reason is it essential that each group be analyzed to determine if the product is safe and effective for them.

Recommendation:

  • The FDA should clarify that subgroup analyses should be conducted to determine safety and effectiveness for major demographic subgroups, such as men and women; Whites, Blacks, and Hispanics; adults under 65 and adults over 65.

 

Section 3.2

We do not support the action item in section 3.2 because it is too vague. It states that the FDA intends “to work with industry, advocacy groups, risk communicators (including FDA’s Risk Communication Advisory Committee) and other stakeholders to explore potential methods for communicating meaningful information on demographic analyses to the public. It does not identify specific work that FDA will do and it does not define “meaningful information.”

Recommendations:

  • The FDA should make this section more concrete and describe the work it intends to do and define key terms.
  • Inclusion of demographic information should be required, standardized, easy-to-understand sections on the label, so that patients and doctors can quickly find this information.  If it does not exist, there should be an excellent justification that is clearly explained.
  • The FDA should require subgroup-specific analyses in language that is understandable by both health professionals and patients.

 

Conclusions

 

The FDA’s Action Plan is too vague and it is unclear whether the proposed changes would have a meaningful impact.  Nowhere in the Action Plan does the FDA state that it will require diversity in clinical trials or require subgroup analyses that evaluate safety and effectiveness.  The agency should take a firm stance of not approving medical products unless they have been adequately analyzed for safety and effectiveness on major subgroups, instead of simply recommending it.  The FDA should let sponsors know that drugs, biologics, and devices will only be approved for the general population if the major demographic subgroups were  large enough to analyze separately.  If the FDA does that, sponsors will find ways to greatly improve recruitment and all medical products that are required to have information on safety and effectiveness would provide that information for all major demographic subgroups.

The National Center for Health Research

 

Table 1- National Center for Health Research: Analysis of Sample FDA Advisory Committee Meetings (2014)

 

Product Name Company Purpose of product Pivotal Trial Sample size % (n) Subgroup Analysis Conducted? Advisory Committee Vote FDA approval?
Black Hispanic
Liraglutide Novo Nordisk Chronic weight management drug All phase 3 trials – 11% (n=575)

U.S. trial – 18% (n=476)

All phase 3 trials – 10% (n=551)

U.S. trial – 11% (n=309)

N 14-1 Overall benefit-risk assessment is favorable to support approval Pending
Nebivolol/

valsartan

Forrest Laboratories, Inc Treatment of hypertension Safety – 10% (n=411)

Efficacy – 30% (n=245)

Safety – 41% (n=1,684)

Efficacy – 24% (n=197)

Y

Safety & efficacy subgroup analyses: Black vs non Black; Hispanic vs non Hispanic; no difference in BP reduction for Black patients on new drug FDC 20/320 compared to patients on nebivolol 40 mg

6-4 in favor of approval Pending
TissuGlu Cohera Medical Reducing fluid build-up after abdominoplasty 21% (n=21) received product

22% (n=11) control

7 Hispanics total

5% (n=5) received product

4% (n=2) control

N 6-4 (one abstention) in favor – benefits outweigh the risks Pending
VBLOC MAESTRO system EnteroMedics Inc. Weight loss 5% (n=8) received device

4% (n=4) control

4% (n=6) received device

8% (n=6) control

N 6-2 (one abstention) in favor – benefits outweigh the risks Pending
Serelaxin Novartis Pharmaceutical Corp. Improve the symptoms of acute heart failure 5% (n=29) received drug

4% (n=23) placebo

10% (n=57) received drug

10% (n=57) placebo

N Unanimous vote against approval Pending
Inspire II Upper Airway Stimulator Inspire Medical Systems, Inc Treat moderate to severe obstructive sleep apnea (n=0) (n=1) N 12-0-1 (yes, no, abstain) that benefits outweigh the risks Approved
Cangrelor The Medicines Company Reduction of thrombotic cardiovascular events 3% (n=156) received drug 4% (n=196) received drug N 7-2 against approval Approval denied
Sivextro Cubist Pharmaceuticals Treat acute Bacterial Skin and Skin Structure Infections 12% (n=77) received drug 28% (n=182) received drug Y

Safety & Efficacy subgroup analyses only for Blacks; Efficacy analysis only for primary end point >20% reduction in lesion size, not for any secondary end points

14-0 That applicant provided substantial evidence of

safety and effectiveness

Approved
Dalvance Durata Therapeutics, Inc. Treat acute Bacterial Skin and Skin Structure Infections 9% (n=28) received drug Could not determine the number from the data presented Y

Efficacy for all racial subgroups but small n

12-0  That applicant provided substantial evidence of safety and effectiveness Approved

 

By Christina Silcox, PhD

October 20, 2014

 

With the Ebola situation changing daily, here’s what you need to know to stay safe.

 

WHAT IS EBOLA?

Ebola (scientific name: Zaire Ebolavirus) is a deadly virus that is spread through direct contact with the bodily fluids of a person who already has symptoms of the disease. Death is generally caused by massive organ failure. There is a 30%-50% chance of survival.

 

WHAT ARE THE SYMPTOMS?

Ebola starts as severe flu-like symptoms: a high fever, weakness, vomiting and diarrhea. Sneezing and coughing are not common symptoms of Ebola.

As the person becomes sicker, he or she may start bleeding from the eyes, ears and nose, as well as internally. This bleeding causes the person’s blood pressure to drop and the person’s organs start to fail. Death usually occurs within 2 weeks after the high fever begins.

 

HOW DOES EBOLA SPREAD?

Ebola is spread through direct human contact with body fluids, not by merely touching a person who is sick. A sick person’s blood or other bodily fluids need to pass into another person’s body through the eyes, nose, mouth or cuts or abrasions in the skin.  Ebola cannot be caught by breathing the same air as an infected person, sitting near them, or by shaking hands.

 

IF I AM AROUND AN INFECTED PERSON, AM I GOING TO GET SICK?

People who have Ebola but aren’t yet showing symptoms do not spread the virus. Even after a person has a fever, bleeding, or other symptoms, they won’t spread the Ebola virus unless their blood, mucus, vomit, feces, sweat, tears, breast milk, urine, or semen get inside a cut or other opening in another person’s body (such as getting it on one’s hands and then touching their mouth).

It’s reassuring that none of the friends or family that lived with the Liberian Ebola patient in Texas became ill, nor has anyone who visited him before he went to the hospital.  Since friends and family were not wearing the protective gear worn by hospital workers, this shows that the early stages of Ebola are not very contagious, even after the patient has already shown some symptoms.

An Ebola patient is much more likely to infect others as the disease progresses and he or she becomes very sick, and the amount of Ebola virus in the patient’s body greatly increases.  At that point, many patients are bleeding or vomiting, which also makes it easier to spread.  That is why healthcare workers treating patients with or suspected of having Ebola need to take extensive precautions, using gloves and covering their entire bodies with what look like space suits so they can’t accidentally touch a patient’s bodily fluids and then touch their mouth or eye.  Only two of the dozens of nurses and doctors who came in contact with the Liberian patient with Ebola in Texas became ill.

 

MY FAMILY MEMBER IS A HEALTHCARE WORKER. SHOULD I BE WORRIED?

Unless your family member is caring for Ebola patients, you don’t need to worry.  If your family member is treating Ebola patients, or patients that might have Ebola, they need to be trained how to use and remove protective gear and to follow directions exactly in order to protect themselves. The CDC and the Department of Defense has also committed to sending a “rapid-response” team of experts to any hospital that admits a patient with Ebola to help with logistics and training.22

 

HOW LONG AFTER A PERSON IS INFECTED WILL THEY GET SICK?

A person will start to get sick between 2 and 21 days after he or she is infected by an Ebola patient who is already showing symptoms of the disease.  The 21 days has already ended for the friends and family members of the Liberian Ebola patient in Texas, and none of them became ill.

 

CAN ANIMALS GET OR SPREAD EBOLA?

Experts believe that fruit bats spread the disease to humans in Africa.  When pigs, horses, and goats have been infected in experimental studies, they did not get seriously ill and did not spread the disease.

There have been no reports of dogs or cats getting sick with or spreading the Ebola virus, on the African continent or any other continent.  In previous Ebola outbreaks, dogs have been exposed to Ebola and have developed antibodies to it, but have not gotten sick.

There is no evidence that mosquitoes or other insects can transmit Ebola virus.23

 

HOW LONG DOES THE VIRUS LIVE OUTSIDE THE BODY?

The Ebola virus can live for several days outside the body in blood or other body fluids. However, once the fluid dries, the virus will only survive a couple of hours and then will no longer be dangerous. Bleach and other hospital-grade disinfectants will kill Ebola, as will careful incineration at high temperatures.

 

WHAT IS THE TREATMENT?

Currently, there is no known cure for Ebola. People who are infected with this strain of Ebola have a 30%-50% chance of survival (BMC).  The healthier the patient is when they get infected, the more likely they are to survive.

When a patient is admitted to the hospital and diagnosed with Ebola, blood pressure and blood oxygen levels are carefully monitored and maintained. It is especially important not to make sure the patient doesn’t get dehydrated. Other symptoms are treated as soon as they appear.  These treatments increase the chances of recovery. (CDC)

 

WHAT ABOUT EXPERIMENTAL TREATMENTS?

Experimental treatments and vaccines are being used for a small number of patients, but we do not know how effective they are.  Some patients have survived after getting experimental treatments, but others have died.

An experimental drug called ZMapp made headlines when three American health workers who got Ebola while treating patients in Liberia were treated with it. Although it had only been tested on a small number of monkeys and never in humans, the FDA allowed it to be used on these patients through a special humanitarian policy for people in urgent need of treatment.  Of the 7 patients who are reported to have gotten ZMapp, 5 survived and 2 died. It is impossible to know if the drug worked or if those patients would have lived even without the experimental treatment. As of August, the company that makes ZMapp has said they do not have any more of the drug and it takes a long time to manufacture. The US government has announced it will pay millions of dollars to several advanced laboratories to start producing it.

Another experimental drug named TKM-Ebola, which is still being studied to determine if it is safe or effective, has also been used to treat some patients. Two vaccines are also in development.

Another treatment is made from antibodies in the blood of people who have survived Ebola. Nicknamed “gold in the blood”, there is no conclusive proof that it works. However, several small experiments have shown the treatment has promise and the World Health Organization (WHO) has endorsed its use during this epidemic.  It has been used by at least one of the Texas nurses who got sick.

 

By Ed Silverman, The Wall Street Journal

October 17, 2014

Cigarette_smokingIn a setback for Pfizer PFE -0.07%, an FDA advisory panel yesterday voted overwhelmingly to maintain the most serious warnings on its Chantix smoking cessation pill.

The drug maker had sought to remove a so-called Black Box warning noting the risk of psychiatric side effects, such as suicidal thoughts and behavior, in hopes reviving the fortunes of a medicine that was once seen as a blockbuster, but has since sputtered among sensational news accounts and litigation.

Shortly after Chantix was approved in 2006, the pill became associated with stories of suicide and violence, which dampened use. Sales fell to $648 million last year from $846 million in 2008. And Pfizer spent hundreds of millions of dollars to settle hundreds of lawsuits.

Last month, however, the FDA altered another portion of the Chantix label portion of the Chantix label to indicate the pill may not carry the risks of suicidal thoughts and behavior. That change was part of an effort by Pfizer to lessen concerns about prescribing and usage, which have fallen since the Black Box was issued in 2009.

To persuade the FDA panel, Pfizer pointed to a meta-analysis of five studies the drug maker says did not show an increase in suicidal activity compared to those on a placebo. Pfizer also cited four observational studies involving thousands of patients the drug maker claimed did not show an increased risk  (see hereherehere and here).

But 11 members of an FDA advisory panel voted to recommend the agency maintain the Black Box warning, while six members voted to strengthen the labeling, suggesting that references to sleep disturbances, for instance, should be added. Only one panel voted in favor of removing the Black Box.

The panel also recommended that any further thought to changing the warnings should not be considered until after Pfizer completes a promised post-marketing study, which the drug maker expects to finish in the third quarter of 2015.

The panel, essentially, took the same position as FDA staffers, who questioned the designs of the observational studies. Several consumer groups recently cited both the study designs and thousands of side effect reports to petition the FDA to increase the Chantix warnings.

“I think Pfizer took quite a chance trying to get the box deleted. They obviously wouldn’t have done it if they thought they could convince people, but they failed completely,” says Diana Zuckerman, the president of the National Center for Health Research, a non-profit think tank.

“They had the best presentation money could buy – very good analyses and complicated statistics to prove their point. And the company trotted out these studies and tried to make a very strong case for why the Black Box should be deleted, but only one person voted their way.

“Pfizer took a big chance, but I think they did so because they were afraid the next study wouldn’t be so favorable and maybe they could get rid of the Black Box warning now. Remember, if it were removed, it would be hard to get it reinstated later, even if a post-marketing study showed risk.”

Pfizer is not flinching. “The completion of our currently ongoing safety study will represent one more step forward in the process of accurately characterizing the neuropsychiatric safety of this important medication,” says Steven Romano, a Pfizer senior vp who heads the medicines development group.

Read original article here.