Coalition Letter Opposing the “Right to Try” Law

July 31, 2017

Dear Senator:

The time is at hand for a momentous decision in the Senate which could greatly affect how patients get access to experimental drugs.  We are writing as members of the Patient, Consumer, and Public Health Coalition, representing millions of Americans, because we are very concerned about the controversial legislative measure that Senator Ron Johnson (R-WI) is trying to insert as an amendment to the Senate version of the FDA’s user fee legislation.  The User Fee bill must pass soon to avoid mandatory layoffs at the agency.

This bill, S. 204, the Trickett Wendler Right To Try Act of 2017, purports to help dying patients gain access to experimental treatments that can save their lives.  However, patients already have access to the FDA’s Expanded Access Program, which gives patients compassionate access to experimental drugs if their doctor believes it is appropriate and the company which makes the drug agrees to provide it for that use.

The Expanded Access program is not a restrictive program; FDA grants these requests more than 98% of the time.  A recent GAO report affirmed the FDA’s appropriate handling of their Expanded Access Program and outlined agency efforts to improve it and streamline its requirements for eligibility.  Also, please keep in mind that the experimental drugs provided through the FDA program are almost always free.  In contrast, Sen, Johnson’s proposal would remove FDA from the process, allow companies to charge whatever they want, not allow FDA to consider any harm that the experimental drug causes when used under the Right To Try auspices, and thus eliminate the safeguards and monitoring that otherwise are done to determine whether the patient has been helped or harmed by the experimental drug.

We strongly support the need for terminally ill patients to receive the best medical treatments as quickly as possible.  Unfortunately, the right to try approach of this legislation would have the following dangerous outcomes:

➢     Hinder patients from obtaining the experimental drugs that are more likely to help them.

➢     Enable companies to charge extremely high prices for experimental drugs, instead of providing them for free in clinical trials.

➢     Reduce or eliminate the incentive of pharmaceutical companies to perform scientific studies to prove that their experimental medications are safe and effective, and for whom.  Why would drug companies agree to spend time and money researching their product when they can instead spend that money on marketing to desperate patients?

➢     The resulting lack of patients participating in clinical trials for these experimental drugs could make it difficult, if not impossible to determine if the medication will make the patient feel better or live longer, and what dosage the patient should take.

➢     Make it nearly impossible to prove if the risk outweigh the benefits for these drugs dispensed without any oversight.

new study published last week in BioMed Central found that 76% of the drugs provided through FDA’s current compassionate use program eventually received FDA approval.  This indicates that while 3 out of 4 experimental drugs being made available through the current program have benefits that outweigh their risks for many (though not all) patients, one out of every four is not.  Since the loosening of safeguards in the proposed Right to Try law would lower those odds, probably substantially, study authors bioethicist Dr. Arthur Caplan and his colleagues concluded, “allow the FDA to retain its oversight and approval role for these programs, in order to help mitigate safety risks for patients.”

There is no scientific evidence that Right To Try programs already operating in a number of states are helping patients survive longer or have a better quality of life.  Nobody has studied how many patients were harmed by these programs, and the proposed legislation would not allow such studies either.  Desperate patients will be vulnerable to false or misleading promises.  Drug companies which now agree to supply free experimental drugs under FDA’s Expanded Access Program may refuse to do so when there is no oversight.

The proposed law would potentially harm many patients and family members, including seriously ill patients who could be harmed by scam artists or unconventional medical practitioners who will take advantage of them. This legislation could open the floodgates to undermine the scientific and carefully-monitored medical requirements that made FDA approval the gold standard for the world.  Please oppose this amendment or any other efforts to have this legislation become law.

Sincerely,

National Center for Health Research
Breast Cancer Action
Breast Cancer Consortium
Jacobs Institute of Women’s Health
MedShadow
MRSA Survivors’ Network
National Consumers League (NCL)
National Organization for Women (NOW)
National Physicians Alliance (NPA)
National Women’s Health Network (NWHN)
Our Bodies Ourselves
Treatment Action Group (TAG)
Washington Advocates for Patient Safety (WAPS)
Woodymatters
For more information, please contact Jack Mitchell at jm@center4research.org.

Letter of Opposition to Trickett Wendler Right to Try Act of 2017 (S. 204)

clip_image002February 24, 2017
United States Senate
Washington, DC 20510

Dear Senator:

As members of the Patient, Consumer, and Public Health Coalition, we are writing to thank you for not co-sponsoring the Trickett Wendler Right to Try Act of 2017 (S. 204), introduced by Sen. Ron Johnson (R-WI).  We urge you to strongly oppose this measure.

This bill purports to help dying patients gain access to experimental treatments that can save their lives.  However, patients already have this access through the FDA’s Expanded Access Program, which gives patients access to experimental drugs if their doctor believes it is appropriate and the company making the drug agrees to provide it for that use.  The bill instead does something much more dangerous: It would remove the FDA’s role in protecting many millions of patients from unsafe or ineffective treatment options – patients who already have safe and effective treatment options.

While we all greatly sympathize with the need for terminally ill patients to receive the best medical treatments as quickly as possible, the right-to-try approach of this legislation would:

➢    Hinder patients’ ability to obtain the experimental drugs that are more likely to help them.

➢    Enable companies to charge for experimental drugs, instead of providing them for free in clinical trials.

➢    Reduce or eliminate the incentive of pharmaceutical companies to do scientific studies to prove that their medications are safe or effective, and for whom.  Why would companies agree to spend time and money researching their product when the company can spend that money on marketing it instead?

➢    Due to the lack of incentive to conduct clinical trials, could make it impossible to scientifically prove if a medication will make the patient feel better or live longer, and what dosage the patient should take.

➢    For the same reason as above, could make it impossible to scientifically prove if the side effects are so debilitating or dangerous that they outweigh the risks for most patients.

This scenario would take us back to the early twentieth century, when “snake oil salesman” peddled untested home remedies and “cures” to patients who had no access to information about whether the product would help or harm them.  Indeed, tragedies arising from those “right to try” laissez faire and harmful medical policies were the very reason that the FDA was created.

While this Senate and House legislation calls for access to experimental drugs which have completed Phase 1 clinical trials, and remain under investigation in a clinical trial approved by FDA, Phase 1 trials are conducted with only small groups of healthy volunteers or patients to determine safe dosage range and identify relatively frequent, short-term side effects.  These very preliminary trials are only the beginning of safety testing, and do not test for effectiveness.

As noted above, the FDA already has a program in place to expedite access to experimental and unapproved drugs for which there is some evidence of safety and efficacy and some knowledge about the appropriate dosage.  The FDA Expanded Access Program routinely utilizes what the agency terms “compassionate use” for patients when doctors request such access.  As would also be the case under all Right-to-Try laws, access to the treatment is determined by the company; if the company doesn’t want to provide the experimental treatment to the individual patient, it does not have to do so.  Under current law, when the company agrees to provide the drug to the patient, the FDA quickly agrees to allow the patient access more than 95% of the time.  Moreover, in urgent circumstances, the FDA had made such a decision within 1 or 2 days.

Currently, the most difficult part of the process is for doctors to obtain permission from the company.  The FDA is working to facilitate access by ensuring that companies make it easier for doctors and patients to quickly identify the contact person or persons at each company who is in charge of the Expanded Access Program.  The drug companies are also asked to make their policies regarding access to specific experimental drugs easily available to the public.

It is important to note that insurance companies generally do not pay for experimental treatments.  This is not a problem in clinical trials or under the FDA’s Expanded Access Program, because in those cases, treatment is almost always free.  However, there is reason to be concerned that pharmaceutical officials will be unwilling to make experimental treatments available for free if they are more frequently requested under the proposed Right to Try Act.

No Evidence that Lives Will Be Saved

In addition to other problems with the legislation, it does not clearly define “terminally ill” patient, or who makes that determination.  How many patients with cancer or heart disease would be considered terminally ill, since those serious illnesses can cause death?  It is not always possible to predict how long a seriously ill person will live, and patients could be easily manipulated by scam artists and others who are motivated by financial gain to convince patients to “try” the “latest” experimental treatment.  Such problems have long been documented regarding unproven treatments sold at outrageously high prices in Mexico, where patients have been irreparably harmed by such treatments.

Bioethics experts and many physicians also point to the following problems with the law:

✓    Desperate patients will be vulnerable to false or misleading promises about likely benefits and failed to be warned about the risks, which may include dying earlier and more painfully than they would without the experimental treatment.

✓    Despite patients’ hopes, there is no evidence that access to experimental treatments through humanitarian exemptions helps more patients than it harms.

✓    There is no evidence that various state right–to-try laws have saved lives or improved patient outcomes.

✓    A survey conducted by Modern Healthcare in late 2015 found no evidence of patients receiving an experimental therapy as a result of state right-to-try laws, despite the fact that more than 20 states already had such laws in place.

✓    If a federal Right to Try Act were to become law, even small companies that make prescription drugs would need to develop complex policies to make such treatments available.

We urge you to strongly oppose S. 204 because it would undermine the successful program already in place to enable patients to have access to experimental drugs for free or at cost.  The proposed law would potentially harm many patients and family members, including seriously ill patients who could be harmed by scam artists in a treatment environment with no checks and balances. This legislation could open the floodgates to undermine the scientific requirements that made FDA approval the gold standard for the world.

Sincerely,

National Center for Health Research
American Medical Women’s Association (AMWA)
Association for Medical Ethics (AME)
Breast Cancer Action (BCA)
Breast Cancer Consortium
Breast Implant Victim Advocacy
Center for Medical Consumers
DES Action
Jacob’s Institute of Women’s Health
MedShadow
MISSD
Mothers Against Medical Error (MAME)
MRSA Survivors Network
National Consumers League (NCL)
National Physicians Alliance (NPA)
National Women’s Health Network (NWHN)
Our Bodies Ourselves
Quinolone Vigilance Foundation
TMJ Association
Washington Advocates for Patient Safety
WoodyMatters
For more information, please contact Jack Mitchell at jm@center4research.org.

Coalition comments to the FDA on voluntary sodium reduction goals

October 17, 2016

 

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

 

 

Comments of members of the Patient, Consumer, and Public Health Coalition on Voluntary Sodium Reduction Goals: Target Mean and Upper Bound Concentrations or Sodium in Commercially Processed, Packaged, and Prepared Foods

[Docket No. FDA-2014-D-0055]

 

 

As members of the Patient, Consumer, and Public Health Coalition, we strongly support the Food and Drug Administration’s voluntary sodium reduction goals.  We agree that high sodium consumption “is a contributory factor in the development of hypertension, which is a leading cause of heart disease and stroke.”[1]

 

We support FDA’s approach to lowering sodium content by avoiding “large, abrupt changes to individual products that might result in noticeably altered taste, greatly reduced shelf life, or other undesirable product outcomes.”[2]

 

We also support FDA’s “plan to monitor the levels of other nutrients (e.g., added sugars and saturated fat) … to ensure that no broad trends emerge that negatively affect the nutritional quality of the foods.” [3] This has happened in the past when processed food manufacturers lowered the fat content of products such as cereals, yogurts, and snacks but then spiked the sugar levels to improve taste.[4]

 

The overall goal of this guidance is to reduce sodium intake in the general population to 2,300 mg/day from the current average adult level of 3,400 mg/day.[5] More than three-quarters of sodium that Americans consume is added when the food is manufactured or commercially prepared. By encouraging manufactures, retailers and food service to reduce sodium, consumers have more access to healthier choices.

 

Research provides important information that should be used to help determine how best to reduce salt intake. A recent study by the U.S. Department of Agriculture found wide variation in the amount of sodium in similar types of products, which suggests that current food manufacturing practices and food preferences vary enough that sodium levels could be reduced in some types of foods relatively easily, and without reducing consumers’ enthusiasm for those products.[6] Others have examined the amount of sodium in the same or similar items from the same fast food restaurants in different countries or in the US over time. Again there were wide variations in the amount of sodium, suggesting that gradual changes in salt levels would not have a negative impact on consumer preferences.[7] [8]

 

We support the FDA’s approach of using mg/ 100g as a standard way to monitor changes in the sodium in various foods independent of changes in serving size or other nutrient levels. However, it would be helpful for consumers and health professionals to also see what these changes mean in units that are found in the marketplace. This would increase transparency and allow outside monitoring.

 

We also want to encourage caution with the development of new or expanded use of food additives and other substances for food preservation or salty flavor. Any such chemicals or substances should be sufficiently studied to ensure that they do not have a negative impact on health in the short-term or long-term.

 

By making healthier options more available, consumers are able to choose foods based on what is important to them. We believe that many consumers will choose healthier options when they become available and as lower sodium levels become the norm. Current initiatives by individual companies, New York City, and the United Kingdom have shown that large reductions in sodium content are attainable and attractive to consumers.

 

We reject the claim that some target levels for sodium might be low enough to be unhealthy. “More than 75 percent of the sodium in the average American Diet comes from salt added to processed foods,” according to the American Heart Association.[9] Consumers can continue to add salt to their food, if they choose to do so, since  able salt is plentiful and inexpensive in the United States. Currently, it is difficult for individuals to lower the sodium in their diet because the salt is added before the consumer purchases it. Reducing the sodium in processed and restaurant foods gives individuals greater control over the amount of sodium that they consume.

 

In summary, we strongly support the FDA’s effort to reduce sodium levels in foods, while monitoring foods to ensure that sodium reductions are not offset by unhealthy changes in nutrients such as increased saturated fat or sugar. The FDA must also ensure that methods to compensate for the reduction do not include substances that could harm consumers. Reducing sodium levels in processed and prepared food would provide consumers with more control over the amount of sodium they consume and thus make it easier for individuals to choose a lower sodium diet and lower the risk for hypertension, heart disease, and stroke.

American Medical Student Association

American Medical Women’s Association

Jacobs Institute of Women’s Health

MRSA Survivors Network

National Center for Health Research

National Physicians Alliance

Washington Advocates for Patient Safety

WomenHeart: The National Coalition for Women with Heart Disease

WoodyMatters

 

[1] FDA DG (June 2016).

[2] Food and Drug Administration (June 2016). Draft guidance, Voluntary Sodium Reduction Goals: Target Mean and Upper Bound Concentrations or Sodium in Commercially Processed, Packaged, and Prepared Foods [Docket NO. FDA-2014-D-0055].

[3] FDA DG (June 2016).

[4] Nguyen PK et al  (2016) A systematic comparison of sugar content in low-fat vs regular versions of food. Nutrition & Diabetes 6:e193.

[5] FDA DG (June 2016).

[6] Ahuja, JKC et al (2015) Sodium content of popular commercially processed and restaurant foods in the United States. Preventive Medicine Reports 2:962-967.

[7] Dunford E et al (2012) The variability of reported salt levels in fast foods across six countries: opportunities for salt reduction. CMAJ 184(9):1023-1028.

[8] Rudelt A et al (2012) Fourteen-year trends in sodium content of menu offerings at eight leading fast food restaurants in the USA. Public Health Nutrition 17(8):1682-1688.

[9] American Heart Association (December 8, 2015). Processed Foods: Where is all that salt coming from?

Coalition Letter Protesting 21st Century Cures

November 29, 2016

The Honorable ________
United States House of Representatives
Washington, DC 20515

Dear Senator/Congressman ____:

The undersigned nonprofit organizations represent members of the Patient, Consumer and Public Health Coalition, which includes more than 6 million healthcare providers, public health experts, and consumer and patient advocates.  We are writing to urgently express our strong opposition to the newly revised 21st Century Cures Act, both in terms of the process of trying to pass a bill without adequate time for public debate, and for specific provisions in the bill that would harm patient safety.  Passing a complicated health bill in the rush of a lame-duck session is always problematic.  Passing a 996-page bill that was negotiated behind closed doors and includes provisions that were never voted on before represents the kind of legislative sausage that Congress should reject.

While the bill includes some positive measures, the most important ones – funding for the National Institutes of Health (NIH) and the Opioid bill that previously passed – are not guaranteed in this legislation.  Unlike the earlier version of the 21st Century Cures Act that was passed in 2015, the funding is not mandated in the new version.  In exchange for the hope of additional funding, the bill contains dangerous measures that would lower safety and approval standards for drugs and medical devices at the Food and Drug Administration (FDA).  This would put all patients and consumers at risk.

For example, the bill would allow antibiotics to be approved based on minimal evidence of safety and effectiveness through a “limited population” approval pathway.  The bill would not require that the antibiotics be studied on the target population that the new drugs would be approved for.  In other words, it is possible that the antibiotics would not meet the urgent need that they are intended for.  Unfortunately, these antibiotics could then be widely advertised and used by patients who are not likely to benefit, and could be seriously harmed by them.  In the long run, that would contribute to antibiotic resistance.  While the Senate version had several restrictions designed to help protect patients, the 21st Century Cures version released this past weekend does not.

The MEDTECH section of the bill would deregulate electronic medical records and decision support software.  A study by the National Center of Health Research (NCHR) found that these types of health IT devices can cause life-threatening problems when they miscalculate incorrect drug dosages for chemotherapy drugs and other treatments.  The Breakthrough Devices (Sec. 3051) encourages shorter and smaller clinical trials for medical devices. These smaller studies make it impossible to include sufficient numbers of women, men, seniors, and racial and ethnic minorities.  Moreover, a recent study of high-risk medical devices found that the median number of participants is currently only 65 patients, which is already too small a cohort to adequately evaluate safety and effectiveness for both men and women, let alone for elderly men and women compared to young adults, or for minority populations.

The bill would also drastically lower standards by allowing companies to provide FDA with summaries of their data, instead of the data itself, as now required, when they want to sell drugs for new indications (treatments).  It also encourages the FDA to make approval decisions based on “real world evidence” that is not necessarily scientifically sound.  The FDA currently reviews and scrutinizes scientific data provided by companies, which is necessary to make sure the benefits outweigh the risks for any approved indication.  Providing summaries would also reduce information about the possible risks to particular demographic groups, such as women or patients over 65.

The Accelerated Approval for Regenerative Advanced Therapies (Sec. 3033), creates an expedited review pathway for ‘regenerative medicine.’  This section has been promoted by extensive campaign contributions, was not in any previous version of the Cures legislation, and should not be rushed through without adequate discussion and debate.

The bill also allows off-label promotion of medical products under certain circumstances, which reduces the incentive for companies to conduct scientific research to prove that their products are safe and effective for new indications.

By lowering standards for approval of drugs and devices, and in some cases eliminating them, the bill would increase the cost of healthcare and pharmaceuticals at a time when such costs have become a grave threat to affordability of health insurance and to the survival of Medicare.  The implications for patients’ health and the affordability of medical care can’t be overstated.  Researchers at the best medical schools in the country already have shown that many ineffective and unsafe drugs have already been approved by FDA on the basis of the kind of preliminary data encouraged by 21st Century Cures.

This situation would worsen under the bill.  For example, the National Center for Health Research assessed the cost of new, ineffective cancer drugs and found that they cost the same or more as cancer drugs that are proven to work.  In addition, the bill would continue the existing pediatric priority review voucher program, even though a recent GAO review of the program concluded that the program has questionable benefit.  This increases the cost of medications and undermines FDA’s ability to set its work priorities based on public health needs.

The extensive and expensive lobbying efforts in favor of 21st Century Cures have been designed to make every aspect of the bill seem bipartisan and non-controversial.  If that were true, however, the bill would not have been negotiated behind closed doors and released during the Thanksgiving holiday weekend.  That is why dozens of patient, consumer, physician, labor, and public interest groups, as well as former Members of Congress, have asked the Congress to delay consideration of the bill.

Thank you for your consideration of our views on this legislation.  We must ensure that patients can trust their drugs and medical devices to improve their health rather than harm it.

Sincerely,

National Center for Health Research
American Medical Student Association
American Medical Women’s Association
Annie Appleseed
Association for Medical Ethics (AME)
Advocating Safety in Healthcare E-Sisters (ASHES)
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
ISMP
Jacobs Institute
Mothers Against Medical Errors
MISSD
MRSA Survivors Network
National Physicians Alliance
National Women’s Health Network
Our Bodies, Ourselves
Quinolone Vigilance Foundation
TMJ Association
Treatment Action Group
Union of Concerned Scientists
Washington Advocates for Patient Safety (WAPS)
WomenHeart: The National Coalition for Women with Heart Disease
WoodyMatters

 

For more information, please contact Jack Mitchell at jm@center4research.org.

Coalition Comment on Conflicts of Interest

Untitled

Comments of members of the Patient, Consumer, and Public Health Coalition on
“Procedures for Evaluating Appearance Issues and Granting Authorizations for Participation in Food and Drug Administration Advisory Committees; Draft Guidance for the Public, Food and Drug Administration Advisory Committee Members, and Food and Drug Administration Staff; Availability; Extension of Comment Period”

Docket No. FDA-2016-D-1399

As members of the Patient, Consumer, and Public Health Coalition we are writing to respond to the FDA’s draft guidance for comments on appearances of conflicts of interest. In our view, there are troublesome inconsistencies in the way that the FDA considers financial conflicts of interest and how they consider appearances of conflicts of interest. Moreover, there are also troubling inconsistencies in how the FDA perceives such appearances for public health and consumer advocates and how they are considered for clinicians.

FDA defines financial conflicts of interest as financial ties during the previous 12 months, so even extensive financial ties in the recent past – or even 12 months plus one day earlier — do not require a waiver. And yet, FDA’s determinations of appearances of conflicts of interest seem to last for years, even decades, if the latter involves a person who previously expressed concerns about a company or a product. On the other hand, Advisory Committee members who previously favored a product are often considered to have important knowledge and experience, rather than having an appearance of a conflict of interest.

The FDA advisory committee that met in 2011 to discuss whether Yaz oral contraceptives are too risky to stay on the market is a perfect example of the one-sided way FDA considers these appearances of conflicts of interest. Dr. Sidney Wolfe was not allowed to vote because he had previously expressed concerns about Bayer’s Yaz. On the other hand, Advisory Committee members with extensive financial ties to Bayer that were more than a year prior voted in support of Yaz (and Yasmin, Beyaz, and other contraceptives made with the hormone drosperinone). This shifted the vote to keep these pills on the market. In other words, many conflicted advisory committee members weren’t counted as “conflicted” because their financial ties were more than a year old. In addition, doctors who had previously prescribed Yaz and other contraceptives made with drosperinone, or who had stopped prescribing it, were allowed to be voting members of the Advisory Committee. In our view, those treatment decisions reflect potential sources of bias or knowledge (whichever interpretation that you prefer) that predates the meeting, that was no less than bias or knowledge that Dr. Wolfe might have had prior to the meeting.

Similarly, at the 2016 Advisory Committee meeting on Chantix, consumer representative Kim Witczak was removed from committee because the FDA identified the appearance of conflicts of interest based on incidents that were well over a year old – in fact, one of the two conflicts FDA cited was over 10 years old. The one that was just over a year old consisted of her speaking during a public comment period during the previous FDA Advisory Committee meeting on the same topic. And yet, 11 of the 27 members of the Committee had previously voted for or against warnings about Chantix at that same meeting. Why was Ms. Witczak’s 3 minutes of public comment disqualifying as a conflict of interest, but comments and votes from previous Committee members were not considered disqualifying? Why was it assumed that Committee members would be open-minded enough to consider new evidence, but Ms. Witczak was not considered open-minded enough to do the same?

For committee meetings reconsidering safety issues for popular products such as Vioxx, Avandia, Yaz, osteoporosis drugs, surgical mesh, hip joints, and breast implants, advisory members who have frequently prescribed or implanted the products being reviewed are not considered biased and also do not need to have waivers. Isn’t the fact that the doctors prescribed a product an indication of an appearance of a conflict of interest in favor of the product? These potentially more knowledgeable but possibly less objective members influence how others vote at least as much if not more than a public health expert or researcher who has previously spoken about or written about the risks or benefits of a medical product.

The National Center for Health Research did a study of FDA Advisory Committee meetings and members of this coalition have attended dozens of them. It is clear from these meetings that many Advisory Committee members are clinicians who want more treatments to be available, making comments such as “if this drug can help one patient, we should get it on the market.” FDA’s responsibility is to make decisions based on scientific evidence that patients are more likely to be helped than harmed by a new medication or medical device. They are asked to provide their perspectives based on objective analysis of the information provided, not on speculation or wishful thinking about whether a drug might “help at least one patient.” Those hopes can appear to be a conflict of interest.

Whether FDA Advisory Committee members have financial conflicts of interest or other types of bias, the standards in terms of the numbers of years should be identical. One year is too short, and 10 years is too long. In industry and academia, 3-5 years is generally considered to be an appropriate amount of time to consider such conflicts. Equally important, bias in favor or opposed to a product should be equally disqualifying; either the Advisory Committee members are able to have an open mind to consider new information, or they aren’t. Disqualification on the basis of an “appearance” of a conflict of interest should not depend on whether the sponsor is opposed to having that person on the Committee.
Thank you for the opportunity to share our concerns regarding the Draft Guidance.

Sincerely,

National Center for Health Research
Association for Medical Ethics (AME)
Breast Cancer Action
Center for Medical Consumers
Connecticut Center for Patient Safety
Mothers Against Medical Error (MAME)
MRSA Survivors Network
National Women’s Health Network
Our Bodies Ourselves
Quinolone Vigilance Foundation
Washington Advocates for Patient Safety (WAPS)
WoodyMatters

For more information, please contact Jack Mitchell at jm@center4research.org.

Testimony to FDA panel on consideration of off-label promotion of medical devices

November 10, 2016

Thank you for the opportunity to speak today.  My name is Jack Mitchell, and I’m the director of government relations for the non-profit National Center for Health Research, which performs public health research and conducts patient advocacy.  This morning I’m speaking on behalf of the Patient, Consumer and Public Health Coalition, to which NCHR belongs and helps to coordinate.

The Coalition includes both large and small nonprofit organizations across the country that are united to ensure that medical treatments are safe and effective, and to enhance the scientific and public health focus of the FDA.  We represent millions of patients, consumers, researchers, and medical professionals.

Our coalition has opposed previous efforts to allow the promotion of off-label use, and we still continue to strongly oppose it.

There are valid reasons for doctors to prescribe treatments off-label.  Many drugs are prescribed off-label as common, accepted practice. However, doctors and patients should discuss the use of these treatments with a clear understanding of the level of evidence, the doctor’s reasoning, and the risks.

Patients should have informed consent, which includes signing a piece of paper that explains that the product is not approved by the FDA for the indication that the product is being prescribed for.  It should also include a discussion of what that means regarding the lack of objective evidence that the benefits outweigh the risks for most patients.  That is the critical calculus that the FDA must always balance.

We are concerned that the FDA does not have the resources to monitor such increased off-label promotion and patients will be harmed.

In our view, the off label promotion for medical devices has one primary goal: To increases the use of medical products for conditions and indications for which the product is not approved by the FDA.  It is not approved because the sponsor has not adequately proven to the FDA that the product is safe and effective for that particular indication.  The result can be that:

  1. Patients will be more likely to be prescribed treatments that are not effective or safe for their specific condition.
  2. Patients also may be more likely to be prescribed treatments that are may be more likely to harm than to help them.

It is virtually impossible for FDA or any other agency to ensure that off-label communications are uniformly truthful and scientifically sound.  That would be an extremely resource-intensive task at an agency where resources are often stretched to the very limit.

Representatives from our collation have testified at FDA advisory committees regarding medical products.  Some of these products have looked promising in the companies’ presentations trials, but then FDA reviewers identified key problems that raised major concerns about the study or the underlying data.  In other words, the entire FDA process is based on the assumption that a sponsor’s analysis is not always unbiased and of sufficient scientific quality to merit FDA approval.  That is why we believe in the critical importance of FDA’s role and why we oppose the promotion of medical products for off-label uses.

As I mentioned, off-label uses are already widespread and commonplace.  For many drugs and devices, in fact, a significant proportion of use is off-label.  Unfortunately, research shows that off-label uses increase the number of adverse events.  If promotion of off-label usage is allowed, we believe, more patients will inevitably be harmed.

Increasingly, FDA is approving drugs and devices based on smaller, preliminary studies.  In the case of medical devices, the vast majority are not required to do any clinical trials.  Frequently, the apparently promising results of small exploratory studies or clinical experiences fail to be confirmed when further tested with a larger, controlled trial.  Sponsors already have few, if any, incentives to robustly test their product once it is on the market, either for its approved indication or for other indications.

Some observers have suggested that increased transparency or data sharing about clinical trials could allow practitioners and patients to evaluate clinical trials themselves.  Supposing that there is sufficient data for us to evaluate the data and that it is not selectively released, we believe that many medical professionals and nonprofit organizations have neither the time nor the expertise to do so.

Those advocating for off-label promotion of their products contend that such claims are protected as free speech and that restriction off-label promotion is an unfair abridgement of that free speech.  As a lapsed and recovering journalist, I’m a big fan of the First Amendment.

However, if it is true that not allowing promotion of off-label uses of medical devices is a restriction of free speech, then why do companies which settle lawsuits with patients who have been harmed insist on non-disclosure agreements that make it impossible for those patients to exercise their own free speech?  Why are patients who settle lawsuits so frequently not allowed to speak publicly about what happened to them?  We believe such restrictions are also another barrier or impediment to identifying patterns of adverse events involving medical devices.

Companies don’t have an incentive to disseminate clinical trials that show that their product does not work.  It’s relatively easy to find cases where a product worked for at least one or a few patient with a simple internet search.  Such information is more difficult to find where patients were harmed, because it is either not published or not promoted.

The history of promoting off-label use in the pharmaceutical world has been dismal.  This list of major violations includes almost all of the major drug firms.  Each has been successfully sued for improper off-label marketing tactics.  Collectively, they’ve been fined hundreds of millions, if not billions, of dollars.

As former chief of oversight and investigations for the Senate Special Committee on Aging. I’ve seen the devastating human impact of the over-use and massive off-label prescribing of antipsychotic drugs in nursing homes, for which multiple pharmaceutical companies have been fined hundreds of millions of dollars.

Nevertheless, those hefty fines and legal settlements have not discouraged off-label promotional practices, and many violations have been made by repeat offenders.  Neither FDA nor the Justice Department has been able to curb these abusive off-label practices with lawsuits and huge fines.  It is hard to believe that legitimizing off-label promotion for devices will not make these type of abuses even more widespread.

Proponents of device of-label promotion have argued that FDA should allow promotion of off-label uses, but that the agency must insure that it is “scientifically sound, responsibly presented, and provides as full an understanding as possible about the limitations of the available evidence.”  That sounds reasonable but it apparently assumes that the clinical trial results that the company is distributing are truthful and aren’t distorted by selectively reporting information, or have serious flaws that may not be apparent.

In summary, we strongly oppose allowing the promotion of device products for off-label uses. We believe that there are not adequate safeguards to allow such promotion to be limited to only scientifically sound, complete, and unbiased data.

While admittedly some off-label use is accepted and has positive outcomes, as you are hearing from patients’ testimonies at this meeting, many have been harmed by off-label use.  The patient Jeremy Lew related yesterday the painful details of coming very close to death or complete paralysis because a device was surgically inserted into his neck which was not approved by FDA for that purpose, but was advertised as being approved.  As you’ve heard, this is not an academic or legal debate only—there are huge human costs and immense suffering.

Our concern, simply stated, is that allowing off-label promotion will cause more patients to be harmed than helped.  When companies submit data to the FDA, agency reviewers have the expertise and responsibility to thoroughly review such data.  That careful process is what has kept Americans more safe from medical harm since the creation of FDA more than seventy-five years ago.

Allowing off-label promotion conflicts with that delicate balance and tends to remove an important incentive for companies to complete high-quality clinical trials for new indications; which would produce reliable data of both efficacy and safety.

I worked in the FDA Commissioner’s office for seven years, and I know the dedication that agency employees have.  They will get the job done when they have access to the appropriate resources and information necessary to do perform their life-critical responsibilities.   Thank you.

Letter to Senators on the Innovation for Healthier Americans bills

November 8, 2016

United States Senate
Washington, DC 20510

Dear Senator _____:

The undersigned nonprofit organizations represent members of the Patient, Consumer and Public Health Coalition, which includes more than 6 million healthcare providers, public health experts, and consumer and patient advocates.  We respectfully urge you to not advance the Senate’s Innovation for Healthier Americans bills or the House’s 21st Century Cures Act during the lame duck session of Congress.  While the House version of the legislation provides additional funding for the National Institutes of Health (NIH), both the House and the Senate versions contain more controversial measures which would lower safety and approval standards for drugs and medical devices at the Food and Drug Administration (FDA).

A number of leading medical experts, including a former Commissioner of the FDA, Dr. David A. Kessler, believe that the bill “could lead to the approval of drugs and devices that are less safe or effective than existing criteria could permit”. We believe that the far-reaching measures described below will significantly impact public health and safety and should therefore not be rushed into law in the final brief weeks of this Congress.

For example, the PATH Act, in both the House and Senate versions, would allow antibiotics to be approved based on minimal evidence of safety and effectiveness through a “limited population” approval pathway.  Unfortunately,  these antibiotics could then be widely advertised in order to increase sales, even though they may be much less safe or effective than older, less expensive antibiotics.

The MEDTECH Act, also in both Senate and House (Section 2241)  versions, would prevent the FDA from collecting adverse events caused by flawed electronic medical records and decision support software.  A study by the National Center of Health Research found that these types of health IT devices can cause like-threatening problems when they miscalculate incorrect drug dosages for chemotherapy drugs and other treatments.

The Advancing Breakthrough Devices for Patients Act, versions of which are in both House and Senate bills, would encourage shorter and smaller clinical trials for medical devices. These smaller studies make it impossible to include sufficient numbers of women, men, seniors, and racial and ethnic minorities. Moreover, a recent study of high-risk medical devices found that the median number of participants is currently only 65 patients, which is already too small to adequately evaluate safety and effectiveness for both men and women, let alone for elderly men and women compared to young adults, or for people of color. The House bill is even worse; for example, Section 2221 would permit companies that manufacture life-saving devices such as heart valves and stents, to be modified without submitting the new devices for FDA approval, as is now required.

Alarmingly, the bill in its current form also allows anecdotal and easily manipulated sources of health data to be used to approve new drugs (Section 2121).   It effectively would eliminate clinical trial drug testing for new medical uses (called “indications’ in the bill).  This measure also would result in the widespread use of medications for uses that are not approved by FDA, causing inevitable patient harm.  (Section 2012: Facilitating responsible communication of scientific and medical development).

In addition to the extensive dilatory effects on FDA’s ability to protect the public health, the bill also extends exclusivity provisions for the pharmaceutical industry, discouraging the use of cheaper generic drugs, and having the practical effect of increasing or maintaining higher drug prices, at a time when the vast majority of Americans are frustrated with and angered by rapidly increasing drug prices.  For example, the Advancing Hope Act, passed by the Senate, would continue the existing pediatric priority review voucher program through 2022. A recent GAO review of the program concluded that the program has questionable benefit.  And, by allowing drug makers to buy a priority review, the bill undermines FDA’s ability to set its work priorities based on public health needs.

There also is serious concern concerning whether the additional $550 million dollars allocated to FDA by the House version of the bill would be sufficient to carry out the extensive mandates outlined by the legislation.  FDA already is severely under-funded and cannot absorb unfunded mandates without dire consequences to its regulatory effectiveness and ability to protect public health.

The House version of the bill also weakens reporting requirements for the bipartisan Physician Payments Sunshine Act (“Sunshine”), a medical payments disclosure measure which is being successfully administered by the Centers for Medicare and Medicaid (CMS).  The Sunshine Internet data base has provided the public with a useful and readily accessible transparency tool that can be used to discover which physicians and surgeons are accepting payments from the pharmaceutical and medical device industry, how much, and for what purpose.

Until the Sunshine data base was established a few years ago, doctors were accepting hundreds of millions of dollars annually in undisclosed payments from industry, much of which was intended to influence drug prescribing practices and the physicians’ brand choice of medical devices.  The Sunshine Act does not prohibit or discourage these payments, merely makes them part of the public record, and allows patients and consumers to decide whether such payments influence their own medical treatment and choice of physicians.

In addition to weakening safeguards for patients and increasing the availability of treatments that are not proven either safe or effective, neither the House nor Senate bills include provisions to lower drug prices.  A recent study by a researcher at the National Cancer Institute found that most cancer drugs approved during a recent 5-year period are not proven to improve the health of cancer patients.  The National Center for Health Research assessed the cost of those ineffective drugs and found that they cost the same or more as cancer drugs that are proven to work.  A recent letter to Congress by a coalition of more than a dozen labor and public interest groups asked the Congress to delay consideration of the Cures/Innovation bills until there are measures included to lower drug prices.  We agree, but we also point out that several provisions in these bills would have the opposite impact, since many new drugs would be sold without clear evidence of efficacy, and yet those new drugs will inevitably cost more than older, more effective and less expensive treatments.

Sincerely,

National Center for Health Research
American Medical Student Association
American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Breast Cancer Coalition
Center for Medical Consumers
Connecticut Center for Patient Safety
Institute for Safe Medication Practices
Jacobs Institute of Women’s Health
Mothers Against Medical Error
MRSA Survivors Network
National Physicians Alliance
National Women’s Health Network
Our Bodies Ourselves
Quinolone Vigilance Foundation
TMJ Association
Washington Advocates for Patient Safety
WomenHeart
Woody Matters

For more information, please contact Jack Mitchell at jm@center4research.org.

FDA should require device makers to include more diverse populations in their analysis of clinical trials

September 19, 2016

 

Comments of Patient, Consumer, and Public Health Coalition

 on “Evaluation and Reporting of Age, Race, and Ethnicity Data in Medical Device Clinical Studies: Guidance for Industry and Food and Drug Administration Staff”

Docket No. FDA-2016-D-0734

 

Members of the Patient, Consumer, and Public Health Coalition have substantial concerns about the weaknesses of the draft guidance “Evaluation and Reporting of Age, Race, and Ethnicity Data in Medical Device Clinical Studies.”  It does not go far enough to improve the proportion of medical devices that are as safe and effective as possible for all subgroups included in an indication for approval.

The purpose of the guidance is to outline FDA’s expectations for the evaluation and “reporting of age, race and ethnicity [subgroups] data in medical device clinical studies.”  FDA evaluated the subgroup “sex” in a previous guidance.[1] 

We agree with the guidance’s recommendation that “clinical trials include diverse populations that reflect the intended populations,” but strongly disagree with the caveat “especially when clinically meaningful differences in safety, effectiveness…or benefit-risk profile are expected across these groups.”   We oppose that caveat because in many cases when the risk-benefit ratio differs, those differences were not expected.

We agree that sponsors (device makers) “should develop a strategy to enroll diverse populations.”  We also agree that these data are needed because “historically many medical device clinical studies” have not included subgroups in proportions that reflect “disease distribution in the affected [subgroup] population.”[2]  In fact, members of our coalition have worked on this issue for many years. For example, at a 2014 FDA AC meeting for a weight-loss device, National Center for Health Research (NCHR) noted that even though four out of five Black women in the U.S. are overweight or obese and Hispanic women are more likely to be overweight compared to White women as well, the clinical trial was 93% White. Only 11 patients were Black and only 2 were Hispanic.  Although the Advisory Committee members voiced their concerns about the mostly white sample, they voted for approval of this device anyway.  This shows two problems: 1) the FDA is not requiring diversity in clinical trials and 2) when companies fail to include sufficient numbers of minority groups to conduct subgroup analyses, the FDA is not providing instructions to their Advisory Committee members that such diversity is essential for FDA approval and for public health.

Several of our members also spoke at the April 2014 Section 907 hearing on this issue.  We noted the importance of including women, minorities and the elderly in clinical studies of safety and effectiveness for drugs and devices. We recommended that subgroup analyses be used as a basis for approval, in labeling decisions, and that the information be made available to patients and providers.

This draft guidance addresses many of the concerns raised previously by coalition members, and we are concerned that the FDA has continued to approve devices that were not analyzed in subgroup analysis proving that benefits outweigh the risks for women, people of color, and people over 65.  If FDA continues to approve/clear devices without subgroup data, then many medical device companies will ignore this guidance, as they often have in the past.  While guidances are not enforceable, FDA has the authority to refuse to approve medical products that have not been adequately tested on representatives of the population that will rely on them.  For example, if the FDA clearly states that a sponsors’ applications will be rejected — or perhaps approved only for the population that was adequately tested in subgroup analyses of safety and effectiveness, we are confident that companies will find a way to comply.

 

Below are our specific comments on the guidance:

 

Analyses should focus on each subgroup independently

Analyses should focus on whether a device is safe and effective for each subgroup independently, rather than whether there is a difference between groups.

Differences in safety and effectiveness between subgroups are much less important than whether benefits outweigh the risks for each subgroup.  For example, in a study of 20,000 patients, it is possible that a small difference between racial groups would be statistically significant for a device that is very effective for both all races.  But, for patients, that small difference would not matter.  What matters is not that they differ, but whether or not the device is useful for all racial groups.

Another reason why comparisons between or among groups is not sufficient is that smaller sample sizes result in wider confidence intervals. Therefore, the subgroups with fewer patients have a greater chance of appearing not significantly different from the other groups.  This would mask much of the meaningful information about safety and effectiveness in specific subgroups.  The guidance recommends device makers engage in “consultation with FDA” when sample sizes are not large enough.  This unfortunately will result in subjective case-by-case reviews, which can result in bias as well as being labor and resource-intensive for CDRH, which is under-funded. If the FDA believes such case-by-case reviews are needed, industry should pay for them through generous user fees.  Such “consultations” should not be funded by appropriations that are already inadequate for CDRH.

 

Analysis by age

The guidance notes that different age populations are “often underrepresented” in clinical trials for medical devices, and it cited the 2013 FDASIA 907 report that found “only 40%” of approved PMAs “reported an age based analysis of outcome data” and that age information was inconsistent and not detailed enough.  Medical device companies must provide more and better data. The guidance states that “older patients may have age-related covariates” (less bone density, slower metabolisms, and digestion issues) “that could affect the performance of medical devices.”   It also notes that pediatric subgroups are affected differently by medical devices “due to the size of the implant,” and that they are more “radiosensitive than adults.”

We agree with the guidance’s recommendation that studies should use more discrete age categories in performing subgroup analyses.  Even though FDA does not define a specific age for the geriatric population, we strongly urge that devices intended to be used by older patients should include an analysis of patients who are over 65 separately from younger adults.  FDA has expressed an interest in harmonizing with the Centers for Medicare & Medicaid Services (CMS), and since most Medicare patients are 65 and older, research evidence that a device is safe and effective in this age group would benefit patients, companies, and CMS.

 

Analysis by race, and ethnicity

The guidance notes that the U.S. population is becoming more diverse, yet subgroup representation in clinical trials “remains a challenge and inconsistent analysis and reporting contributes to persistent lack of publicly available data on device performance in diverse ethnic and racial groups.” The FDASIA 907 Report showed that “only 27% of the studies reviewed contained a race or ethnicity subgroup analysis and only 16% had public statements” regarding the subgroups.  Recent analyses by the National Center for Health Research found that this continued to be a problem for devices FDA reviewed in 2015.  It is critical that racial and ethnic subpopulations be adequately represented in clinical trials in order to ensure that the tested product is safe and effective for all the subpopulations that are likely to use that product.

 

Postmarket submissions

The guidance states that “consideration should be given to whether market approval/clearance is supported for the general population, with postmarket studies to gain further information regarding any observed…subgroup differences.” We urge FDA to require subpopulation data be analyzed before the device is marketed and that the focus be on benefits outweighing risks for each subgroup, rather than comparing subgroup differences.

Once a device maker has its product on the market, there is no incentive for them to do postmarket studies in a timely manner (or to complete them at all) since their device has already been approved/cleared by the FDA.  Additionally, the guidance notes there are “concerns about disproportionate dropout and loss to follow-up [which] are potential barriers to diverse study representation of minorities and older patients.”  For that reason, companies need to create incentives to keep patients in their studies.  If those studies are not completed appropriately, the FDA should rescind approval.

 

Unplanned subgroups analyses

We agree with the guidance that “unplanned subgroup analyses or those with inadequate sample size are generally not considered to be adequate to support statements in the labeling regarding the safety or effectiveness of the device.”  We suggest deleting the word “generally” from that sentence.

 

Device labeling

We agree with the guidance that “when clinically relevant differences in treatment effect are anticipated across age, race, or ethnic groups, these effects should be considered in the study design and…device labeling.”  However, as stated above, it is not sufficient to only consider such issues when subgroup differences are anticipated – they should always be considered.  In addition, also as stated above, subgroup differences are not the key issue; what matters to patients and providers is how safe and how effective devices are for patients in each subgroup.

In addition, we are concerned that patients will never see the label for the devices implanted in their bodies (hips and knees, for example).  Even more disturbing, surgeons have told us that they do not see the medical device labels either. FDA should investigate whether or not surgeons actually see and read the device labels, or if the labels are removed before surgeons receive the devices in the operating room.

 

“Snapshots” for medical device trials

Although it is beyond the scope of this guidance, the FDA should consider creating an equivalent to the FDA Drug Trials Snapshots for medical devices. This would make demographic subgroup data more available and transparent to the public.

 

Conclusions

To ensure that medical devices intended for use by the entire U.S. population are safe and effective for all relevant subgroups, FDA needs to require device makers to include more diverse populations in their analysis of clinical trials, and needs to require that subgroups be large enough to analyze to determine how safe and how effective a device is for each major subgroup population.   If a device is not safe and effective for all target groups, then labels should say that and approval indications should be restricted to those populations for whom benefits outweigh the risks.  Otherwise, doctors and patients will not have the information needed to make decisions about whether to use the device for treatment.

We are disappointed that this guidance, like other FDA documents, continues to miss the essential issues regarding subgroup analyses: to answer the question of how safe and how effective is this device for each major subgroup.   We strongly urge the FDA to require that safety and effectiveness be analyzed separately for each subgroup instead of just comparing safety or effectiveness between or among subgroups.  Companies need to collect sufficient information to evaluate the benefit/risk profile for each subgroup independently.  That will make it possible to determine if medical devices are sufficiently safe and effective for anyone who uses them.

Without these changes, the guidance will not help ensure that patients and providers have the information they need to determine if a device is likely to be safe or effective for a wide range of patients in terms of age, race, and ethnicity.  Moreover, it is crucial that FDA hold device makers accountable by not approving devices for all Americans if it has not been proven to have benefits that outweigh the risks for all major subgroups that will use those devices.

 

American Medical Student Association

American Medical Women’s Association

Breast Cancer Action

Breast Cancer Consortium

Connecticut Center for Patient Safety

MRSA Survivors Network

National Center for Health Research

National Organization for Women

Our Bodies Ourselves

The TMJ Association

Washington Advocates for Patient Safety

WoodyMatters

 

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

[1] Food and Drug Administration (2014).  Guidance: Evaluation of Sex Specific Data in Medical Device Clinical Studies. http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm283707.pdf

[2] Food and Drug Administration (2016).  Draft guidance: Evaluation and Reporting of Age, Race, and Ethnicity Data in Medical Device Clinical Studies. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM507278.pdf

Coalition strongly urges the FDA to ban the use of certain phthalates in food packaging

September 19, 2016

 

Division of Dockets Management (HFA-305)

Food and Drug Administration

5630 Fishers Lane, Rm. 1061

Rockville, MD 20852

 

 

Comments of members of the Patient, Consumer, and Public Health Coalition

on

The Food Additive Petition Filed by Breast Cancer Fund, Center for Environmental Health, Center for Food Safety, Center for Science in the Public Interest, Clean Water Action, Consumer Federation of America, Earthjustice, Environmental Defense Fund, Improving Kids’ Environment, Learning Disabilities Association of America, and Natural Resources Defense Council;

  [Docket No. FDA-2016-F-1253]

 

Members of the Patient, Consumer, and Public Health Coalition strongly support the food additive petition to amend or revoke food additive regulations regarding food processing and packaging involving specific  phthalates.[i]  We strongly urge the FDA to ban the use of these ortho-phthalates for use in the production, storage, and packaging of food.

 

More commonly known as phthalates, ortho-phthalate metabolites are detectable in nearly everyone in the U.S.,[ii] primarily because of the food we eat.[iii] While exposures to specific phthalates may be low for many individual foods, they are present in a wide variety of foods and so the cumulative level is much higher.[iv], [v], [vi]

 

Phthalate exposure can have diverse and long-lasting harms. Phthalates such as DEHP are probable human carcinogens.[vii] Exposure before birth and during early life has been linked to numerous problems with brain development. These include Attention Deficit Hyperactivity Disorder (ADHD) related behaviors, impaired social behavior, aggression, depression, and lower IQ.[viii] Increased exposure causes reproductive problems for both sexes, including abnormal testicle development and preterm birth.[ix]

 

Eleven phthalates have been found to affect reproductive, developmental and endocrine health, and the remaining substances do not have sufficient evidence to judge their safety As such, it is impossible to conclude that there is “reasonable certainty of no harm.” We agree with the petitioners that phthalates should be addressed as a class because if phthalates are considered on an individual basis, one harmful phthalate will likely replace another harmful one. Phthalates contaminate food at different stages of production and storage.[x] We support the extensive scope of the petition to cover all of the steps in processing and packaging of food.

 

We note that government agencies have already banned or limited the use of certain phthalates covered by this food additive petition. The Consumer Product Safety Commission has banned the use of six of these phthalates from children’s toys and other products due to these health concerns for this vulnerable population.[xi] The FDA already limits/warns about the use of DEHP in medical devices[xii] and DEHP and DBP in drugs.[xiii] Clearly, the same chemicals in our food is potentially even a greater risk.

 

Conclusions

Our Coalition and member groups have commented or testified to the FDA on phthalates and food contact issues for several years. In 2010, members of our coalition submitted comments in support of the FDA’s proposed rule regarding allowable DEHP levels in bottled water (see Docket NO. FDA-1993-N-0259).

 

The National Center for Health Research’s Dr. Anna Mazzucco spoke at the December 9, 2014 FDA meeting on expanding the Redbook to enhance the safety of food and products. Dr. Mazzucco noted that “Current evaluation of food additives for carcinogenic activity is narrowly focused on genotoxic mechanisms of action.  She added that the FDA should add tests for endocrine disruption to its toxicological evaluation of food contact substances and additives to ensure that all food contact substances, both old and new, are safe.”

 

In summary, we agree with the March 18, 2016 letter from the Natural Resources Defense Council and other groups to the Center for Food Safety and Applied Nutrition. The letter states that “there is no longer a reasonable certainty of no harm for the food contact use of the 30 phthalates.” We echo their concerns that exposure levels to U.S. citizens of these phthalates are above the tolerance for the class of chemicals. The FDA should ban the use of phthalates for use in the production and storage of food.

 

American Medical Student Association

American Medical Women’s Association

Breast Cancer Action

Breast Cancer Consortium

Mothers Against Medical Error

MRSA Survivors Network

National Center for Health Research

National Consumers League

National Organization for Women

Our Bodies Ourselves

Washington Advocates for Patient Safety

 

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

[i] Federal Register (May 20, 2016). Food and Drug Administration, notice of petition. Breast Cancer Fund, Center for Environmental Health, Center for Food Safety, Center for Science in the Public Interest, Clean Water Action, Consumer Federation of America, Earthjustice, Environmental Defense Fund, Improving Kids’ Environment, Learning Disabilities Association of America, and Natural Resources Defense Council; Filing of Food Additive Petition.

[ii] National Health and Nutrition Examination Survey (NHANES) (October 2014). Phthalates and plasticizers metabolites- Urine (PHTHTE_G); years of content 2011-2012. http://wwwn.cdc.gov/Nchs/Nhanes/2011-2012/PHTHTE_G.htm

[iii] Consumer Product Safety Commission (July 2014). Chronic Hazard Advisory Panel On Phthalates and Phthalate Alternatives.https://www.cpsc.gov/PageFiles/169876/CHAP-REPORT-FINAL.pdf

[iv] Sathyanarayana S et al (2013). Unexpected results in a randomized dietary trial to reduce phthalate and bisphenol A exposures. J Expo Sci Environ Epidemiol. 23(4):378-384.

[v] Schecter A et al (2013). Phthalate concentrations and dietary exposure from food purchased in New York State. Environ Health Perspect. 121(4):473-479. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620091/

[vi] Serrano SE, Braun J, Transande L, Dills R, Sathyanarayana S (2014). Phthalates and diet: a review of the food monitoring and epidemiology data. Environ Health 13:43.

4 Agency for Toxic Substances and Disease Registry (2002).  Toxicological profile for di (2-ethylhexyl) phthalate.  Update. Atlanta, GA:  U.S. Department of Health and Human Services, Public Health Service.

[viii] Ejaredar M, Nyanza EC, Ten Eycke K, Dewey D (2015). Phthalate exposure and children’s neurodevelopment: A systematic review. Environ Res 142:51-60.

[ix] Marie C, Vendittelli F, Sauvant-Rochat MP (2015) Obstetrical outcomes and biomarkers to assess exposure to phthalates: A review. Environ Int. 83:116-136.

[x] Fierens T, Van Holderbeke M, Willems H De Henauw S, Sioen I (2013). Transfer of eight phthalates through the milk chain — A case study. Environ Int. 51:1-7.

[xi] US Consumer Product Safety Commission. (July 2015). Phthalates. http://www.cpsc.gov/en/Business–Manufacturing/Business-Education/Business-Guidance/Phthalates-Information.

[xii] US Food and Drug Administration (July 2002). FDA public health notification: PVC devices containing the plasticizer DEHP. http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/PublicHealthNotifications/ucm062182.htm.

[xiii] US Food and Drug Administration (December 2012). Limiting the use of certain phthalates as excipients in CDER-regulated products. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm330792.htm

Comments to FDA against removal of the black box warning for Chantix

Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings and I am speaking on behalf of many members of the Patient, Consumer, and Public Health Coalition. The Coalition includes nonprofit organizations representing millions of patients, consumers, researchers, and doctors united to ensure that medical treatments are safe and effective.  The coalition does not have paid staff and does not accept funding from any outside sources, so I have no conflicts of interest.

Pfizer is once again asking the FDA to remove the black box warning that Chantix is associated with serious adverse events such as depression, hostility, agitation, suicidal thoughts, attempts, and completions. They want to replace it with the statement that these are associated with quitting smoking. They also want to remove the warning that there may be an increased risk for patients with a psychiatric illness. GlaxoSmithKline wants to remove REMs requirements for Zyban. They based these changes on one large, poorly executed clinical study.

It is important to point out that these black box warnings were initiated because of the enormous number of extremely serious psychiatric adverse events, including suicide and aggressive behaviors, associated with these smoking cessation products.  Research has also confirmed that some patients have extreme psychiatric responses that can be deadly to themselves and to others.  The purpose of these warnings is to let patients know that if they seem to be having uncontrollable feelings when on these drugs, that there is a good chance that getting off the drugs will solve the problem almost immediately.

Pfizer’s study concludes that Chantix does not have these risks but the FDA reviewers have clearly shown that there are extensive problems with how the data were collected and analyzed:

#1: The study measured psychiatric problems with something called the Neuropsychiatric Adverse Event Inventory (NAEI).  This is not a validated test so it was only supposed to be used to start the conversation about psychiatric symptoms.  Instead, it was used as a unvalidated checklist, which contributed to inaccurate data.  For example, it did not identify cases of suicidal behaviors that were identified by validated scales.

#2.  When patients reported psychiatric problems, those problems were not coded consistently.  The FDA pointed out that the staff doing interviews and coding were not always trained mental health professionals and didn’t seem to understand some of the categories they were coding.  Even worse, their very subjective measures of severity were sometimes completely incorrect: such as a patient who became severely depressed being coded as having a mild problem from taking Chantix.

#3: Since 70% had tried to quit smoking previously using one of these drugs, the study was biased toward people that had previously tolerated the drug.  This would drastically underestimate the percentage having serious adverse reactions.   In addition, anyone with suicidal thoughts or behaviors in the past year or anyone with self-injuring behaviors were excluded. While these patients should not be treated with a drug that could make these worse, this could again bias the results to make the drugs seem safer than they really were.

In summary, patients deserve access to smoking cessation treatments, but they also deserve warnings about the risks.  There remains considerable credible evidence that some patients are severely harmed by Chantix and Zyban, and those patients’ lives depend on warnings about the risks, so they will recognize that sudden suicidal, paranoid, or violent thoughts are side effects of the drugs.

Thank you for your time and consideration of our views.