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.1 The nasal spray is quadrivalent.2 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 49.3  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.4

 

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.5 

 

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.6 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.7  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.8

 

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.9

 

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.10

 

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.

By Harold Bishop, Wolters Kluwer Law & Health Blog

October 15, 2014

 

Even though the FDA has recently proposed a new program to provide earlier market access to high-risk medical devices, FDA Commissioner Margaret Hamburg nevertheless came under fire for the agency being to slow to approve medical devices at the annual conference of the Advanced Medical Technology Association (AdvaMed) in Chicago. The implication of her inquisitors was that FDA delays are driving the medical device business to Europe, where device approval standards are more lax. Other health industry research groups disagree, believing that the FDA is acting responsibly, while Europe may be reexamining its lower approval standards.

New Expedited Program

The new FDA program was announced on April 22, 2014, through the issuance of a draft guidance entitled “Expedited Access for Premarket Approval Medical Devices Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or Conditions.” The Expedited Access PMA or EAP program is designed to provide earlier access to high-risk medical devices that are intended to treat or diagnose patients with serious conditions whose medical needs are unmet by current technology and are subject to premarket approval (PMA) applications. The program features earlier and more interactive engagement with FDA staff during device development and more interactive review of investigational device exemption (IDE) applications. The FDA also intends to work interactively with the sponsor to create a data development plan specific to the device.

In addition to the EAP program, the FDA published a separate draft guidance outlining the agency’s policy on when data can be collected after product approval and what actions are available to the FDA if approval condidtions, such as postmarekt data collection, are not met. Entitled “Balancing Premarket and Postmarket Data collection for Devices Subject to Premarket Approval,” the draft guidance also includes advice on the use of surrogate or independent markers to support approval, cimilar to the data points used for accelterated prescription drug approval.

AdvaMed Discussion

In response to reports that slow FDA approvals have sent medical device startups and clinical trials to Europe, Commissioner Hamburg responded (as reported in MedCityNews) that “It’s not a race to who’s first – it’s a race to get the best possible product to people.” Hamburg continued that “approval in Europe doesn’t mean it’s broadly available in the healthcare systems of those countries,” adding that Europe is “in a moment of examination of their regulatory system for devices” due to the emergence of some safety issues.

One example of this “moment of examination” may involve the European Union recall of tens of thousands of defective breast implants. According to an article in Reproductive Health Matters (RHM), “In the U.S., breast implants are regulated as high-risk medical devices that must be proven reasonably safe and effective in clinical trials and subject to government inspection before they can be sold. In contrast, clinical trials and inspections have not been required for breast implants or other implanted devices in the EU; approval is based on other information. As a result of these differing standards, the PIP [Poly Implant Prothese] breast implants that were recalled across Europe had been removed from the market years earlier in the U.S., a decision U.S. government health agencies can point to with pride.”

In an interview with Wolters Kluwer, Diana Zuckerman, PhD, President of the National Center for Health Research, and co-author of the RHM article, indicated she supported Commissioner Hamburg’s position on this issue. According to Zuckerman, recent studies show that devices get on the market in the U.S. about as fast as they do in other countries. In addition, “It is much easier to get insurance coverage for devices in the U.S.  In most other countries, the national health plans won’t pay for devices unless they are proven safe and effective and sometimes need to be proven cost-effective.  In the U.S., such requirements have been  rare.  It is very easy to get devices on the market in Europe and other countries, but difficult to get coverage until studies prove the device’s value.  For that reason, and because devices cost so much more in the U.S. than other countries, device companies are always going to want to sell their products in the U.S.  Whether their headquarters are in the U.S. or not, they need FDA approval to sell in the U.S.  So, that is not going to influence whether a U.S. company moves to another country.”

From a follow-up discussion at the AdvaMed conference, The Boston Globe quotes Mark Deem, managing partner of the medical device startup The Foundry LLC, as stating that “the horse has already left the barn. It’s gotten to the point where entrepreneurs are just moving all their early stage medical device activities lock, stock, and barrel overseas.” With regard to the FDA’s EAP program, MedCityNews further opines that “Deem worries that it has taken so long for the FDA to realize it’s been shellacked by Europeans that it could be too little, too late.” Zuckerman, however, disagrees.  According to Zuckerman, “the decision of some device companies to leave the U.S. is clearly related to the tax advantages of doing so, not related to the FDA approval process or standards for clinical trials in the U.S.”

Opposition to the EAP Program

Lest anyone think that the FDA’s new EAP program has full support, on July 22, 2014, members of the Patient, Consumer, and Public Health Coalition sent comments to the FDA indicating their lack of support for the program. While the coalition members sympathize with patients who suffer from life threatening or irreversibly debilitating disease, they believe that “the standards for PMA are already substantially lower than for prescription drugs…and yet, the [EAP program] lowers the bar for certain PMA medical devices even further.” The coalition believes “there is no guarantee that the [program] benefits would outweigh the risks for patients.” While the members indicate their support the program’s emphasis on earlier interactive communication between sponsors and the FDA, they also believe the program “gives undue emphasis on postmarket studies that are poorly monitored, have high loss to follow-up, and are rarely conducted in a timely manner that provides useful results.”

Read original article here.

By Diana Zuckerman, PhD

American Association for the Advancement of Science

October 14, 2014

One of the most pressing scientific issues facing Congress today is the risk that antibiotic resistance presents to human health. Unlike other political-scientific hot potatoes, such as global warming, the House and Senate crossed the aisle to pass a bipartisan bill to speed new antibiotics to market, and are working on a new bill to make FDA approval even easier.

Unfortunately, there is an enormous gap between what the science tells us is needed and the Congressional approach.

In addition to the obvious biological cause of antibiotic resistance, two major problems contribute to antibiotic resistance—lack of new antibiotics to fight resistant bacteria and misuse and overuse of existing antibiotics.

Congress has focused on the first by creating financial incentives for companies to develop new antibiotics, and changing the scientific criteria for FDA approval to make it easier to get new antibiotics approved. The GAIN (Generating Antibiotic Incentives Now) ACT, passed in 2012 as part of a larger law, provides an additional five years of patent protection for certain antibiotics and makes them eligible for fast-track review by the FDA.

Congress is currently considering the Antibiotic Development to Advance Patient Treatment (ADAPT) Act, which offers companies an even easier pathway to FDA approval for antibiotics used by “a limited population of patients” who urgently need new drugs. But ADAPT contradicts that purpose by specifying that doctors have the authority to prescribe these drugs for any patient under any circumstances. The bill also encourages FDA to approve these drugs based on smaller studies, Phase 2 rather than controlled Phase 3 trials, and surrogate endpoints rather than meaningful health outcomes.

In contrast, the Center for Disease Control and Prevention has stated that, “Perhaps the single most important action needed to greatly slow down the development and spread of antibiotic resistant infections is to change the way antibiotics are used.” Unfortunately, neither GAIN nor ADAPT does anything to discourage the overuse of new or old antibiotics.

Human misuse includes prescribing antibiotics for colds, flu and other viral infections for which antibiotics are ineffective. It also includes widely prescribing new antibiotics when older antibiotics would be just as effective, instead of saving new antibiotics for when they are most needed. Changing doctors’ prescribing habits is difficult, however, despite recent efforts such as the “Choosing Wisely Campaign.”

The most important issue missing from these legislative efforts isn’t human-centered at all—it is the routine use of antibiotics in animals. The FDA reports that 80 percent of antibiotics in the U.S. are used for food-producing animals, not for humans, and that many are used to promote animal growth in cows, sheep, chickens and hogs, rather than to keep them healthy. The resulting resistant bacteria can spread from animals to humans.  And yet, a bill to address that problem, introduced by Rep. Louise Slaughter and other House members in every Congress since 1999, has never had a hearing or vote in the House. Nor has Sen. Dianne Feinstein’s recent companion bill in the Senate. In fact, a much weaker bill introduced by Rep Henry Waxman last year, which would merely require data collection on use in farm animals, attracted only 10 co-sponsors and never had a hearing, vote or Senate companion bill.

Provisions to reduce human misuse of antibiotics were in the GAIN Act, but deleted before it was passed. Earlier this year, the FDA proposed strategies to reduce the use of antibiotics in livestock—unfortunately, they are voluntary and unenforceable.

Last month, however, the President’s Council on Advisors on Science and Technology issued a report on antibiotic resistance that takes a very different approach than Congress or the FDA. Rather than focusing on financial incentives and reducing the research burden on pharmaceutical companies, this report includes a range of scientific insights and strategies about what kind of research is needed to develop antibiotics that will save lives. The challenge now is to translate those complex and evidence-based ideas into a bill that can pass Congress.

Read original article here.

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

October 14, 2014

Comments of Members of the Patient, Consumer, and Public Health Coalition
on Draft Guidance
“De Novo Classification Process (Evaluation of Automatic Class III Designation)”
[Docket No. FDA-2011-D-0689]
October 14, 2014

As members of the Patient, Consumer, and Public Health Coalition, we have serious reservations about the use of the de novo classification process for implants, life-sustaining, and life-saving devices. We believe that all such high-risk devices should be Class III devices reviewed through the more rigorous PMA process.  That is why we urge CDRH to revise the draft guidance to explicitly state when the de novo process may be used and when it cannot be used.

We strongly support language in the draft guidance that states the de novo process should be used for devices that are “low to moderate risk” (Class I or Class II devices).  We also support language that states, “The de novo should include all (emphasis added) information and evidence regarding the safety and effectiveness of the device,” and “provide data demonstrating that general controls or general and special controls support a classification of Class I or Class II.” However, we urge the FDA to revise the second sentence to read: “provide publicly available scientific data and test results demonstrating that general controls…support a classification of Class I or Class II.”

We support the draft guidance section on “Supporting Protocols and/or Data.” It recommends that an applicant “Provide a summary of all performance and clinical testing” and that “the summary should include the objective of the testing, a description of study design, and a description of results.” If companies fail to provide this information, FDA should deny their de novo application. In the National Center for Health Research’s recent study of cleared 510(k) implants, researchers found companies provided no scientific data in 4 out of 5 recent 510(k) applications, because they either did not provide summaries or their summaries provided vague information such as “all required testing was completed and the results were satisfactory.”11  This is very disturbing since current law states that the summary must include “sufficient detail to provide an understanding of the basis for a determination of substantial equivalence.” 12

 

Devices ineligible for de novo

We strongly support the following language that clearly states that a device is ineligible for the de novo process, if the “device falls under a class III classification regulation, or if it is a direct de novo and the device is not low-moderate risk, we [FDA] intend to decline your de novo.”   However, we disagree with the restriction that a de novo review would not be considered “if a likely predicate device exists.”  In many cases, implanted devices are listed as predicates even when they differ in size, shape, materials, or mechanism of action from new devices, and a de novo review would be a better choice than a 510(k) review.

The draft guidance states that if general and special controls are “insufficient to provide reasonable assurance of safety and effectiveness or…the data provided in the de novo are insufficient to determine…a reasonable assurance of safety and effectiveness, we [FDA] will decline the de novo and you may not legally market the device.”  We are concerned about this wording, however, because the FDA’s definition of sufficient evidence is often very subjective and this has resulted in terrible harm to patients when based on assumptions that have proven to be incorrect, such as for Vena Cava filters (product code DTK).

Regarding the final sentence of the draft guidance, it states “All information posted to the FDA website will be redacted to protect any confidential commercial, trade secret, or personal privacy information.” FDA should delete the first word, “all” because the intent of the language is not to redact all information, which is how it currently reads.  Moreover, we strongly urge the FDA to err on the side of transparency when redactions take place.  In the past, information that is publicly available elsewhere has been redacted from documents by the FDA.

 

Conclusions

The de novo process should be used to strengthen the approval standards for low-to-moderate risk devices by replacing the 510(k) process.  It should not be used to lower the approval standards for high risk (Class III) devices, which should always be reviewed through the more stringent PMA process. We strongly urge the FDA to revisit their classifications of many implants, 95% of which now go through the 510(k) process, according to recent research.1  We also urge the FDA to reconsider the Class II classifications of many other life-sustaining and life-saving devices that have also been cleared through the 510(k) process based on predicates that differ substantially from the new devices in ways that have clear implications for safety and effectiveness, such as surgical robotic systems that were cleared as substantially equivalent to surgical tools.  To protect public health and ensure that medical devices provide a reasonable assurance of safety and effectiveness, the draft guidance must unambiguously describe when the de novo process may and may not be used to clear a medical device.

 

Annie Appleseed Project
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
National Center for Health Research
Our Bodies Ourselves
Center for Science and Democracy at the Union of Concerned Scientists
WoodyMatters

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

 

Division of Dockets Management (HFA-305)
Food and Drug Administration
5600 Fishers Lane, Room 1061
Rockville, MD 20852

October 14, 2014

Comments of Members of the Patient, Consumer, Public Health Coalition
on the Draft Guidance
“Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications [510(k)] with Different Technological Characteristics”
[Docket No. FDA-2014-D-0900]

As members of the Patient, Consumer, and Public Health Coalition, we strongly oppose the draft guidance Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications [510(k)] with Different Technological Characteristics.  The three major shortcomings of the guidance are as follows:

  1. It focuses on benefits and risks that cannot be accurately measured in the absence of large, long-term, well-designed clinical trials.  Such studies are never available for new devices being considered for 510(k) clearance.  In fact, even small, short-term, well-designed clinical trials are almost never available.
  1. The wording of the guidance is vague and rather than clarifying the criteria for substantial equivalence, the guidance illustrates the very subjective decisions that the Food and Drug Administration (FDA) relies on.  The lack of consistent, clear standards is unfair to device companies and physicians and harmful to patients and the public health.
  1. The specifics regarding surrogate endpoints, emphasis on postmarket data, and patients’ perspectives on risk assessment would further reduce the already extremely limited safeguards available to ensure the safety and effectiveness of new medical devices cleared through the 510(k) process.

 

Principal Benefits and Risk Factors for Performance Data

This section states that the FDA will assess “on a case-by-case basis” what it may find acceptable in a substantial equivalence decisions. We oppose these subjective judgments made on case-by-case assessments because they do not foster a standardized approach.  The Center for Devices and Radiological Health (CDRH) should be able to make clear guidelines about what substantial equivalence means and how it needs to be proven scientifically.

 

Assessment of the Benefits of Devices

The FDA takes into account the following four factors in assessing information provided in a 510(k) submission: Type of benefits, magnitude of the benefits, probability of the patient experiencing one or more benefits, and the duration of effects.

Type of benefits

The draft guidance list of benefits includes patient health, patient satisfaction, quality of life, and probability of survival among other benefits.  It then adds that “these endpoints denoting clinical benefit…may be demonstrated by use of validated surrogate endpoints.”  The word “validated” is not defined.  The FDA should avoid using surrogate endpoints because the FDA’s judgment of what is validated has been very subjective.  Patients want improved health, relief from symptoms, longer life, and improved quality of life.  Even if surrogate endpoints correlate with any of those outcomes, the surrogate endpoints would need to be scientifically validated for specific demographic subgroups, such as women, men, Whites, Blacks, Hispanics, and people over 60.  The CDRH does not have a good track record on surrogate endpoints or subgroup analysis, unfortunately.

Magnitude of the benefits

The draft guidance states, “The change in clinical study subjects’ condition or clinical management” allows the FDA to assess the benefits patients receive from the treatment. However, a recent study showed that only about 6% of 510(k) implant applications—including implants with different technological characteristics than the predicate device—mention the existence of clinical data in their summaries, whereas many more mention the use of non-clinical data.13  If the FDA is using clinical data as the basis of substantial equivalence decisions, the law requires that information to be publicly available “in sufficient detail.”14

Probability of the patient experiencing benefits

The guidance does not explain the evidence that will be used to determine patient benefits.  Since 510(k) applications so rarely include any clinical data, and those that are included tend to be a small study, it is misleading to claim that the FDA can determine the “[d]emonstration of a large benefit experienced by a small proportion of subjects [which] may raise considerations that differ from those in instance where a small benefit is experienced by large proportion of subjects.”  The key question is, given the small or non-existent clinical studies of new devices included in virtually all 510(k) applications, how can the proportion of subjects who experience a large benefit be identified or targeted? This would require that accurate diagnostics be available to identify populations that would benefit the most from the device, which is often not the case.

Regarding the assessment of probable risks and harms by reviewing factors individually and in the aggregate, we agree that “When multiple harmful events occur at once, they have a greater aggregate effect.”  However, we are concerned that the draft guidance use of “number and rates” of harmful events associated with a device is not practical, since it is commonly known that Manufacturer and User Facility Device Experience (MAUDE) undercounts adverse events.  The same can be said for device-related non-serious adverse events and procedure-related complications.  In the absence of clinical trials or registry data for the vast majority of 510(k) devices, CDRH does not have accurate reporting mechanisms currently functioning to accurately reflect these numbers. The FDA is still years away from using unique device identifiers (UDIs) and device registries on enough devices to accurately measure adverse events.

Regarding the probability of a harmful event, the draft guidance states, “FDA would factor whether an event occurs once or repeatedly into the measurement of probability.” In the absence of long-term clinical trials, accurate measurement of repeated harmful events is not possible.  Even if it were possible, it would not weigh the seriousness of an event. For example, death happens only once.  The draft guidance also states that the FDA may be able to predict which patients “may experience a harmful event.” Again, this seems unlikely given that very few 510(k) devices have clinical trial data and those that do usually have relatively few patients, little diversity, and no subgroup analyses.

Duration of effects

The draft guidance states that some devices can cause temporary or minor harms, others can cause repeated but reversible harm, and others can cause permanent, debilitating injury.  The FDA plans to consider the severity and duration of the harm. Again, in the absence of clinical trials or more accurate adverse reporting systems, the FDA is not able to accurately evaluate the likelihood or severity of harms. Moreover, the FDA and patients may have different definitions for “reversible harm.” For example, when metal-on-metal hips were recalled, the FDA classified the recall as Class II, “moderate risk” recalls.  And yet, removal of those implants required multi-hour surgery that could cause permanent harm or death, and revision hip surgery almost always leaves patients with disabilities or limited abilities compared to the first hip surgery.  A failed revision surgery can result in patients losing mobility and thus having to move from independent living to a nursing home.

 

Patient tolerance for risk

The draft guidance states that the FDA may consider the patient’s perspective and notes that some patients are “willing to accept a higher level of risk to achieve a higher probable benefit.” There are two major fallacies with that statement:

  1. Patients may say they are willing to accept a higher risk, but when they have a negative outcome they inevitably wonder why the FDA allowed such an unsafe product on the market, and why this terrible harm happened to them.
  1. A 510(k) device is cleared for everyone, not just those willing to accept a higher risk. Also, the device can then be used as a predicate for a new device, which will also be used by patients who did not choose to accept the high level of risks.  By catering to those patients who say they are willing to accept higher risks, the FDA by default makes all patients who may use the device accept higher risks.

 

Risk mitigation

The draft guidance states that if a new device has an increased risk, the FDA may approve it, “if the risk is appropriately mitigated.” The draft guidance recommends “appropriate information within labeling (e.g., warnings, precautions, contraindications)” to mitigate risks. What evidence does the FDA have to conclude that health care professionals read the labels, are influenced by warnings on them, or share that information with their patients?  On the contrary, in our work with thousands of patients, most tell us that their physicians did not ask even simple questions about allergies or illnesses that were listed on the label as contraindications.  Our work with physicians has clearly shown that many do not read device labels and that surgeons often do not ever see the labels on the devices they use in the operating room.

 

Degree of uncertainty and innovative technology

We oppose the statement, “FDA may accept a greater degree of premarket uncertainty regarding a device’s benefit-risk profile through a greater reliance on postmarket controls…if FDA’s overall assessment is sufficiently balanced by other factors…”  This is too vague to provide meaningful guidance. Moreover, it is the FDA’s mission to provide reasonable assurance of safety and effectiveness before a device is put on the market, not to wait years after millions of patients may have used it.  A recent review of postapproval studies for medical devices found that “small sample sizes, delays in reaching protocol agreement, and lack of availability of findings may hinder their ability to be clinically useful.”15

Regarding innovative technology, the draft guidance states that the FDA “may accept greater uncertainty” in assessing benefits and risks compared to the predicate device when the technological improvements are “important for public health.”  We oppose this statement because the phrase “important for public health” is too vague and subjective, especially when combined with the other statement in this section that the FDA will evaluate innovative changes on a “case-by-case basis.”

 

Conclusions

We oppose the draft guidance as written and strongly urge the FDA to rewrite it.  The current draft guidance relies on vague wording and subjective judgments, not science or technological assessments.  When it is more specific, it promotes the use of surrogate endpoints and the risk tolerance of a small number of patients whose views come to the FDA’s attention.

American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
MISSD
National Center for Health Research
National Consumers League
The TMJ Association
WARS
WoodyMatters

The Patient, Consumer, and Public Health Coalition can be reached through Paul Brown at 202-223-4000 or pb@center4rersearch.org

By Matthew Perrone

AP article that appeared on ABC News and many other websites

October 8, 2014

Public safety advocates are asking the federal government to strengthen warnings on Pfizer’s anti-smoking drug Chantix, even as the drugmaker prepares to argue that a bold-letter warning about psychiatric problems should be removed from the medicine’s label.

Five advocacy groups petitioned the Food and Drug Administration on Wednesday to expand Chantix’s boxed warning, calling for more detailed language about potential side effects like suicidal behavior, hostility and depression. The groups also say that the prominent warnings should include information about blackouts, convulsions and other problems reported in some patients.

“It would be illogical to discount the reports of thousands of consumers who told of frightening or destructive experiences with Chantix,” states the petition, filed by Consumer Reports, Public Citizen, the National Center for Health Research, National Physicians Alliance and the Institute for Safe Medication Practices.

The groups urge the FDA to revisit the boxed warning, first added in 2009, arguing that it “substantially underestimated the psychiatric adverse effects and accident risks of Chantix.” They also argue that Chantix should be contraindicated for people working in critical or hazardous occupations, like pilots, air traffic controllers, police and military personnel. The petition notes that the Federal Aviation Administration and the Department of Defense already restrict the use of Chantix among certain employees.

A spokesman for Pfizer Inc. noted that the petition is based on patient reports of injury “which have several limitations, including missing data, reporting biases, and no ability to determine that the adverse event was caused by the drug.” The company reiterated that its own studies “do not show evidence of an increased risk of serious neuropsychiatric events” in patients taking Chantix, versus other smoking-cessation products.

The move by safety advocates comes just over a week before the FDA meets publicly to review Chantix’s risks. Pfizer has conducted several studies showing no link between its drug and suicidal behavior and the FDA added information from those studies to the drug’s label last month. Company executives say they plan to use next Thursday’s FDA advisory panel meeting to argue that the boxed warning is no longer warranted. The FDA will hear input from the company, a panel of outside experts and members of the public.

New York-based Pfizer has paid roughly $300 million to settle more than 2,500 lawsuits alleging that Chantix caused various psychiatric problems, injuries and suicides. Two experts who studied Chantix for the Institute for Safe Medication Practices — one of the petitioning groups — also served as paid expert in the litigation against Pfizer.

The FDA first began investigating potential side effects with Chantix in 2007, the year after it hit the market.

The drug’s labeling tells patients to stop taking Chantix immediately if they experience agitation, depressed mood, suicidal thinking and other behavioral changes. Doctors are advised to weigh the drug’s risks against its potential benefit of helping patients quit smoking.

Pfizer’s drug works by binding to the same spots in the brain that are activated by nicotine when people smoke. The drug, known chemically as varenicline, blocks nicotine from binding to those spots and prevents the release of “feel-good” brain chemicals that make smoking so addictive.

Chantix had global sales of $648 million last year. That was down about 26 percent from the drug’s peak sales of $883 million in 2007.

Pfizer shares rose 59 cents to $29.38. Its shares are down more than 4 percent in the year to date.

Read original article here.

Read our citizen’s petition here.