Coalition Comments on FDA Draft Guidance for Generic Abuse-Deterrent Opioids

May 24, 2016

Comments of members of the Patient, Consumer, and Public Health Coalition on “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products: Guidance for Industry”

Docket No. FDA-2016-D-0785

Thank you for the opportunity to comment on the draft guidance, “General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products: Guidance for Industry.” Development of such products is of great public health importance as a strategy to help make pain medications more affordable to those who truly need them while also reducing opioid abuse.

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The comments and recommendations of the members of the Coalition follow:

  1. Avoid use of the misleading term “abuse-deterrent”

While the guidance does not specifically address labelling, we urge FDA to avoid use of the term “abuse-deterrent” since it is often misinterpreted to mean “addiction-deterrent.” In fact, a recent study found that nearly half (46%) of physicians think that abuse-deterrent formulations make these medications less addictive than others.[1] Instead, labelling language that more accurately captures the product’s abuse-deterrent properties should be used. For example, if a pill has been made difficult to crush, it should be labeled “crush-resistant.” It is important to use precise language because “abuse” and “addiction” are often used interchangeably.

  1. Provide guidance for all types of abuse-deterrent technologies

The draft guidance includes recommendations to industry on the studies needed to show that a generic opioid is no less abuse-deterrent than the brand-name (or reference) drug, with respect to all potential routes of abuse. It provides testing recommendations for four of the seven categories of abuse-deterrent technologies described in FDA’s “Abuse-Deterrent Opioids: Evaluation and Labeling” guidance: solid oral opioid drug products formulated to incorporate physical or chemical barriers, agonist/antagonists, aversive agents, and combinations of two or more of these technologies. Since this field is continually evolving, we urge the FDA to also develop guidance for products in the remaining three categories so that patients have access to a variety innovative pain management therapies that are also safe and effective.

  1. Require the generic product to show it is not less abuse-deterrent than the reference product with respect to all potential routes of abuse

We agree with FDA that it is necessary for a generic manufacturer to provide studies that show that their product is not less abuse-deterrent than the reference product with respect to all potential routes of abuse. This will help minimize the risk of shifting abuse to another potentially more dangerous route of abuse (e.g. oral abuse to intravenous abuse). It will also prevent the approval of a generic opioid product that is less abuse-deterrent than the reference drug, which could lead opioid abusers to preferentially seek out and abuse generics. It is critical that, in attempting to solve one problem, we avoid creating a new one.

  1. Include a control product in tampering studies

Since the abuse-deterrent properties of currently approved drug products can eventually be compromised, it is important to have a good understanding of the type of manipulation or tampering that renders the opioid non-abuse-deterrent. Therefore, we agree with FDA’s recommendation to include a control product (i.e. a non-abuse-deterrent version of the reference product) in studies of abuse-deterrence. This will help provide a more accurate understanding of the product’s ability to deter abuse.

  1. Apply extra scrutiny to Tier 1 studies

As stated in the draft guidance, FDA recommends that applicants follow a tier-based approach when comparing a generic product to a reference product. This tier-based approach allows for hierarchical testing, starting with simple and gentle manipulations of the product (Tier 1) and progressing to more destructive mechanical and chemical manipulations (Tiers 2, 3, 4, etc.). Using this method, all of the null hypotheses in Tier 1 must be rejected before testing the null hypotheses in higher tiers. For that reason, it is essential that Tier 1 studies are rigorously conducted and documented. We urge FDA to apply extra scrutiny to these Tier 1 studies to ensure the statistical integrity of the tier-based approach.

  1. Enforce post-marketing real-world epidemiological study requirements for reference opioids

While not specifically addressed in this guidance, we strongly urge the FDA to enforce post-market study requirements for reference drugs. Since generic abuse-deterrent opioid formulations use the branded product as the reference for actual ability to deter abuse, it is critical that FDA follow through on its requirement for real-world post-marketing studies. An unsafe and ineffective reference product will result in unsafe and ineffective generic products. Sponsors of brand name products with approved abuse-deterrent labeling must complete the required long-term epidemiological studies to assess their effectiveness in reducing abuse in practice or risk having their approval revoked.

Conclusions

In summary, we applaud the FDA for providing guidance to industry to advance the regulatory science behind abuse-deterrent oral opioid formulations. We agree with many of the recommendations in the guidance and urge the FDA to consider our recommendations regarding the use of the term “abuse-deterrent”, the development of guidance addressing additional abuse-deterrent technologies, the scrutiny applied to Tier 1 studies, and the enforcement of post-marketing study requirements for reference products.

Sincerely,

American Medical Women’s Association

Cancer Prevention and Treatment Fund

Connecticut Center for Patient Safety

MedShadow Foundation

National Consumers League

The TMJ Association

Washington Advocates for Patient Safety

 

References

[1] Hwang CS, Turner LW, Kruszewski SP, et al. Primary Care Physicians’ Knowledge And Attitudes Regarding Prescription Opioid Abuse and Diversion. Clin J Pain. 2016 Apr;32(4):279-84.

 

 

 

 

Coalition’s Comment the Black Box Warning and Patient Decision Checklist for Essure Birth Control System

May 3, 2016

 

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

 

Comments of members of the Patient, Consumer, and Public Health Coalition
on the Draft Guidance “Labeling for Permanent Hysteroscopically-Placed Tubal Implants [the Essure System] Intended for Sterilization”

 

As members of the Patient, Consumer, and Public Health Coalition, we appreciate the efforts of the FDA to improve the information available to women and physicians considering the Essure System for Permanent Birth Control, through a “Boxed Warning” (black box warning) and a “Patient Decision Checklist” as part of the product labeling.  However, we believe that the draft guidance is not sufficient.

 

The purpose of the draft guidance is to ensure that women receive and understand information about the risks and benefits of permanent devices (hysteroscopically-placed tubal implants intended for sterilization). The Essure System is the only type of these devices marketed in the U.S.

 

We agree with the FDA that in order to make patients aware of the risks associated with the Essure System, there needs to be “accurate product labeling and effective messaging of that labeling.” We agree with FDA that a boxed warning and patient decision checklist should be included in the labeling sections of the Federal Food, Drug, and Cosmetic Act (FD&C Act).

 

The FDA is seeking comment on this draft guidance regarding the wording and content of the black box warning and the patient decision checklist. Our specific comments are below:
The Boxed Warning

This section of the draft guidance has two bullets. The first covers adverse events associated with the device and its insertion or removal, and the second bullet declares that a statement “noting these risks should be conveyed to the patient during the women’s decision-making process.” This short section is augmented by example of a Boxed Warning included in Appendix A of the draft guidance. The example lists several adverse events that may occur from the use of Essure.

 

We have two concerns about the Black box warning:

 

  • We believe that the phrase “some patients” will be misconstrued as “not many patients.” This is not consistent with the thousands of women who have reported their problems from Essure to the FDA.  We suggest you delete the word “some” or replace it with “Many” or “numerous.”

 

  • Most patients will probably not see the device’s boxed warning. To make it clear to patients that the implants are associated with serious adverse events, the black box warning and a description of why the device has one, should be added to the Patient Checklist.

 

Possible text for the Patient Checklist could read:

 

“I understand that the Essure device has received a black box warning, which is used to call attention to serious or life-threatening risks. I acknowledge that my provider has discussed these risks with me and that I understand those risks.”

 

Patient Decision Checklist

We support the FDA’s requirement that physicians provide women considering Essure or similar implants with a list of risks that the FDA has found to be linked to the device.

 

Women can and do make good decisions about the risks and benefits of drugs and medical devices when they have good information. However, the Patient Checklist needs to be easier to understand and more succinct in order to maximize the likelihood that most patients will read and understand it.

As drafted, the Patient Checklist is too long, the language is at a level that seems designed for college graduates rather than the 6th-8th grade reading level that is recommended by health educators, and the check list emphasizes the permanent nature of the device rather than the risks of the device.  In its current form, it is unlikely that most women will read more than the first few points.  The checklist needs to be completely rewritten.  It should also use the term “sterilization” rather than “permanent birth control.”  Essure patients have advised us that the term “permanent birth control” is confusing.

Some specific language in the example checklist needs to be changed.  On page 12, lines 407-411, it says: “These types of events, although not reported in clinical trials supporting device approval, have been reported to FDA by women implanted with the Essure System.”  We request that you delete: “although not reported in clinical trials supporting device approval.” The inclusion of that line downplays the thousands of serious adverse events reported by women from their real world experience.  For example, the National Center for Health Research study of 1104 women with Essure problems found that 86% reported pain (mostly pelvic or abdominal), 34% reported excessive bleeding (some bled every day of the month instead of a regular period), 22% fatigue, 16% hair loss, 12% hysterectomy, 12% depression, and  7% allergies. While these are not a random sample of Essure patients, they indicate the clear pattern of complications that women report. It is important to note that about 35% had Essure removed and about half of those had a complete recovery.  Only 5% of those who had them removed reported no improvement in symptoms.1

 

In addition, it is essential that the checklist be completed at least one week prior to the Essure procedure, so that the patient is provided the information prior to scheduling the surgery or at the least at a time that she can cancel the surgery if she decides it is not a good idea for her.

 

Additional Research Study

We fully support FDA requiring a “clinical study for Essure to determine heightened risks for particular women.” During the 2015 FDA Advisory Committee meeting, it became clear that many women have been harmed by Essure and it is not known if the risks are higher for some subgroups of women or not.

 

Requiring an additional research study be conducted as soon as possible is essential so that providers and women to make more evidence-based decisions. We urge the FDA to require a study of sufficient size and inclusive of diverse populations (including women of color, women of diverse reproductive ages, body size, for example). The study as a whole and the subgroups must be of sufficient power to detect increased risks for certain women and conducted in a way that short-term and long-term complications are well-documented.

 

Conclusions

Members of the Patient, Consumer, and Public Health Coalition strongly support a Boxed Warning and a Patient Decision Checklist for the Essure Permanent Birth Control device.  However, both need to be improved, and the latter needs to be rewritten to be suitable for the average reading skills in the U.S.

 

One final point, we are very concerned about how the FDA discusses Essure in the press. FDA made a statement on February 29, 2016 that “Essure remains an appropriate option for the majority of women seeking a permanent form of birth control” (emphasis added).2 Until better research is conducted, it is not possible to say what percentage of women or which subgroups of women are most likely to benefit and least likely to be harmed by Essure compared to other alternatives.
Breast Cancer Consortium
MISSD
National Center for Health Research
Washington Advocates for Patient Safety
WoodyMatters

 

 

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The coalition can be reached through Paul Brown at (202) 223-4000 or at pb@center4research.org.

Coalition’s Comments on FDA’s Efforts to Improve Diversity and Analyses in Clinical Trials

April 29, 2016

 

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

 

Comments of members of the Patient, Consumer, and Public Health Coalition on FDA’s Efforts to Improve Diversity and Analyses in Clinical Trials Docket No. FDA-2015-N-4952

 

We are writing as member organizations of the Patient, Consumer, and Public Health Coalition, to express our views on the need for diversity and subgroup analyses in clinical trials.

 

We support efforts to improve the safety and effectiveness of drugs and medical devices for ALL patients that are likely to use them. Women, people of color, and patients over the age of 65 have often been under-represented in clinical trials. Just as that was improving in recent years, efforts to speed drug approval have resulted in smaller clinical trials. So, the numbers of patients in those groups are again shrinking, making it impossible to do meaningful analysis of safety or effectiveness.

 

For example, cancer is most common in the elderly, but many cancer drug trials include very few elderly patients. Cancer drugs are often more toxic and less effective in the elderly. But with so little information on elderly patients when a drug is approved, it can be years later that we learn that elderly patients are more likely to be harmed if approved dosing information is followed.

 

The National Center for Health Research recently examined drugs reviewed by FDA Advisory Committees in 2014. They found that, for the 24 drugs the committees reviewed, 7 sponsors did not even tell FDA how many patients in their studies were 65 and older. That is a crucial subgroup for Medicare to make coverage decisions, and should always be analyzed separately. An additional 2 sponsors included fewer than 30 patients 65 and older. In other words, over onethird of the drugs were not studied on enough patients over 65 to draw even the most preliminary conclusions about safety or efficacy.

 

Similarly, over a quarter of the drugs did not include at least 30 African Americans – some didn’t even include 10! It is impossible to conduct meaningful subgroup analyses with such a small number of patients.

 

And although women were always included when appropriate, 23% of drugs did not include a subgroup analysis to determine if the drug was safe for women.

 

Here’s one egregious example. FDA did not require subgroup analysis of Blacks when the company submitted clinical trials for Singulair for asthma in 2014, despite previous evidence that the drug did not work for Blacks.

 

The FDA should make it clear that the agency will not approve medical products for all populations if meaningful subgroup analysis for safety and effectiveness were not conducted for major demographic groups.

 

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. Inconvenient locations are a major impediment, however. Companies have not done a better job of recruiting because they know FDA will approve their drugs even when adequate subgroup analyses are not conducted.

 

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 to make participation in clinical trials possible and affordable (and even attractive) for patients of limited financial means or with limited resources.

 

Most important, the FDA needs to make it clear to companies that if they want their drugs approved for women and men, whites and people of color, and adults of all ages (and especially Medicare beneficiaries), they need to study sufficient numbers of those patients in subgroup analyses to make sure the drugs are safe and effective for them in the short-term and long-term.

 

American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
Breast Cancer Consortium
Center for Medical Consumers
National Center for Health Research
National Organization for Women Foundation
Our Bodies Ourselves
Washington Advocates for Patient Safety
WoodyMatters

 

 

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The coalition can be reached through Tracy Rupp at (202) 223-4000 or at tr@center4research.org

Coalition’s Comments on FDA’s Direct-to-Consumer Advertising Survey

April 29, 2016

 

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

 

Comments of members of the Patient, Consumer, and Public Health Coalition
on the “National Direct-to-Consumer Advertising Survey
Docket No. FDA-2016-N-0544

As members of the Patient, Consumer, and Public Health Coalition, we appreciate the opportunity to comment on the “National Direct-to-Consumer Advertising Survey.” In general, we support this survey, which will update information from surveys completed in 1999 and 2002.

 

The objective of this research is to gain information from the public about “their experiences with and attitudes toward direct-to-consumer (DTC) advertising of prescription drugs.” 3 Topics covered by the survey include consumer’s knowledge of FDA’s authority over DTC ads, how often they’re exposed to DTC ads, their beliefs and attitudes about DTC ads and the influence of DTC advertising on patient-doctor interactions. The survey will measure other characteristics such as demographics, insurance coverage, and prescription drug use. We want to make sure that the questions about beliefs and attitudes will include gathering information about consumers’ views on how information about the benefits and risks is provided, if it could be provided in a more unbiased way, and how it influences their views of the product being advertised. Ideally, you can provide short DTC videos for respondents to watch and ask them questions about what benefit-risk information they recall from those ads.

 

The new study of DTC ads is designed to reach a wider range of respondents than the previous surveys by weighting the data to make it nationally representative. We agree that the survey should represent the demographic makeup of the United States in sufficient numbers to analyze subgroups based on race, ethnic backgrounds, and sex. The survey should be skewed to include a disproportionate number of Americans over 50, since they are the target of vast majority of DTC ads and are also the most likely to be exposed to those ads on TV and in magazines. Of course, younger adults (18 and over) should also be included. Ideally, the study would include a sufficient number of teenagers who are 14-18 years old, to gather meaningful information about that age group.

 

We agree with the FDA that the DTC advertising landscape has changed since the previous surveys. We are concerned that extremely brief social media ads will not include sufficient information about risks. Since DTC ads focus primarily on selling products, it is unacceptable for the risks of a product to be listed through a link that consumers may not click or the often-used phrase, “for more information, see this month’s issue” of a particular magazine. The survey should directly ask respondents how much information about the risks of the medical products they notice from social media ads.

 

Regarding the survey procedures, we support the mixed-mode methodology where households will be asked to complete a 20-minute online survey with a paper questionnaire sent to those who do not respond on-line. The paper option will ensure that respondents who are not internet savvy will still be included. The survey is designed to have as many as five contacts sent by mail to adults aged 18 and older and this should ensure that the FDA achieves at least its 35 percent response rate for both the pilot study and the main study. These estimated response rate percentages are lower than the telephone surveys conducted in 1999 (65 percent or 960 respondents) and in 2002 (53 percent or 944 respondents) 4 but the total number of respondents (1,765) is estimated to be higher for the new survey.

 

FDA also plans to compare responses between this survey and FDA’s 2002 survey. In 2002, “60 percent [of respondents] felt that ads do not provide enough information about risks.”2 That is a high percentage. We want to know if that percentage has gone up or down, and what steps FDA and industry are taking to provide more information about the risks of medical products. We are particularly interested in the number of people searching the internet for drug and health information, which jumped from 18 percent in 1999 to 38 percent in 2002. Back then, most people were looking for information about risks associated with the medical products.2 The new survey should ask people how often they search the internet regarding medical products and what information they are inquiring about.

 

Conclusions

We are very concerned about the impact of DTC ads on prescriptions, and are especially disappointed at the FDA’s failure to follow through on the agency’s previous proposals to put risk information on a more equal footing with information about benefits. Due to the FDA’s continued acquiescence to companies’ proposed ads, DTC ads use the power of an expensive advertising campaign to persuade patients to use medical products that may not be safe or appropriate for them. Rather than empowering consumers, direct-to-consumer ads expose consumers to the most effective persuasion that money can buy. To truly protect consumers, and reduce unnecessary healthcare costs, Congress and the FDA need to do more than survey the public about DTC ads. They need to propose laws and rules to limit the persuasive power and unbalanced information provided in DTC ads, especially for drugs that have not been tested for long-term safety on a large population.

American Medical Women’s Association
Breast Cancer Action
Connecticut Center for Patient Safety
MAME
MISSD
MRSA Survivors Network
National Center for Health Research
National Organization for Women Foundation
National Physicians Alliance
National Women’s Health Network
Quinolone Vigilance Foundation
The TMJ Association
Washington Advocates for Patient Safety
WoodyMatters

 

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The coalition can be reached through Paul Brown at (202) 223-4000 or at pb@center4research.org.

Establishing Paid Sick Leave for Federal Contractors

April 12, 2016

Establishing Paid Sick Leave for Federal Contractors

Proposed Rule

RIN 1235–AA13

[Docket No. 2016-03722]

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of patients, consumers, health-care professionals, scientists, and public health experts.   As members of the coalition, we strongly support the proposed rule (Federal Register Docket #2016-03722) based on President Obama’s Executive Order 13706, Establishing Paid Sick Leave for Federal Contractors, which requires that employees that work on federal contracts are entitled to earn at least seven days or 56 hours of paid sick leave per year.

The federal government provides paid sick leave to its employees, but not those who work indirectly for the federal government as contractors. This rule would extend sick leave for an estimated 828,000 employees, including providing paid sick leave for the estimated 437,000 that currently do not receive any.   Currently, these men and women must choose between getting a pay check (and possibly retaining their job) and taking the time off to recover from an illness, get preventative care, or care for a family member.

Paid sick leave improves health and productivity of employees.  It enables those who have physical or mental illnesses to take the time to recover when sick, to get preventative care, to deal with injuries, and to care for sick or injured family members.   At the same time, it reduces the chances that their work colleagues will become sick as a result of their contagious illnesses.  For all those reasons it results in greater productivity in the work place.

Paid sick leave improves community health as well. Employees that cannot afford to take an unpaid sick day unwillingly expose co-workers, clients, and even those they are in contact with on public transportation or other public places to their illness. When employees’ ill children cannot stay home from school, they also expose classmates. Enabling employees to stay home when sick reduces the transmission of illnesses throughout the community.

Providing paid sick leave also helps employers. Besides reducing productivity loss due to the spread of illness through the workforce and “presenteeism” losses1, 2, research shows that paid sick leave increases employee retention and overall productivity3. It also reduces the likelihood of workplace injuries4.

The benefits of paid sick leave for communities are well established and currently 5 states, 22 cities, and one county have passed laws requiring paid sick leave.  A study of six of these jurisdictions found that these laws have not hurt most businesses in the region nor the local economy5.

In conclusion, paid sick day policies like those in the Department of Labor’s proposed rule will save employers, taxpayers and families money, and promote healthier workplaces and communities. We urge you to proceed with implementation without delay.

American Medical Women’s Association
Annie Appleseed Project
Breast Cancer Action
MISSD
MRSA Survivors Network
National Center for Health Research
National Consumers League
National Organization for Women
National Women’s Health Network
Our Bodies Ourselves
Washington Advocates for Patient Safety
WoodyMatters

 

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

1 Kumar, S., Grefenstette, J. J., Galloway, D., Albert, S. M. & Burke, D. S. (2013). Policies to Reduce Influenza in the Workplace: Impact Assessments Using an Agent-Based Model. American Journal of Public Health. 103(8), 1406-1411. www.ncbi.nlm.nih.gov/pmc/articles/PMC3893051

2 Johns, G. (2010) Presenteeism in the workplace: A Review and Research Agenda. Journal of Organizational Behavior. 31, 519-542. onlinelibrary.wiley.com/doi/10.1002/job.630/epdf

3 Hill, H. D. (2013). Paid Sick Leave and Job Stability. Work and Occupations. 40(2), 143-173. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825168

4 Asfaw, A., Pana-Cryan, R. & Rosa, R. (2012). Paid Sick Leave and Nonfatal Occupational Injuries. American Journal of Public Health, 102(9), e59-e64. www.ncbi.nlm.nih.gov/pmc/articles/PMC3482022

5  National Partnership for Women & Families. (2015, November). Paid Sick Days: Low Cost, High Reward for Workers, Employers and Communities. Retrieved March 2, 2016, from www.nationalpartnership.org/research-library/work-family/psd/paid-sickdays-low-cost-high-reward.pdf

Coalition Supports Proposal to Notify the Public About Emerging Safety Issues with Medical Devices

Comments of members of the Patient, Consumer, and Public Health Coalition
on the Draft Guidance
Public Notification of Emerging Postmarket Medical Device Signals (“Emerging Signals”)
[Docket No. FDA-2015-D-4803]

 

As members of the Patient, Consumer, and Public Health Coalition, we support the draft guidance, Public Notification of Emerging Postmarket Medical Device Signals (“Emerging Signals”).  The draft guidance addresses a serious problem: the delay between early signals that a device is less safe or less effective than expected, and the development of confirming evidence that the FDA would like to have before making recommendations.  But in the months or even years during that delay, patients can be and too often have been seriously harmed.

The FDA draft guidance is a step in the right direction, and we look forward to working with the CDRH to ensure that it is implemented in ways that provide easy-to-understand and widely accessible information to patients and their health care providers.  Below are our specific comments on the draft guidance.

We support FDA’s precise description of the term “emerging signal,” which is new information about medical devices used in clinical practice that meets four criteria including information that may “alter the known benefit-risk profile of the device.”5

We agree with the FDA that the public needs to be notified about emerging signals “even when the information has not been fully analyzed, validated or confirmed” by the FDA.  If this draft guidance had already been policy, then hundreds of thousands6 of patients might have been spared from suffering adverse events from medical devices such as surgical mesh, metal-on-metal hips, power morcellators, contaminated endoscopes, and Essure, to name a few.  The FDA has handled the early signals for these five types of devices in different ways, some more successfully than others. In each of these cases, accurate information about risks was not generally known for months or years after persuasive evidence began to emerge. Without any warnings from the FDA that there could be greater risks than those that were officially proved, patients and their doctors could not make informed treatment decisions.

We agree with the FDA that new information about the safety and effectiveness of medical devices “often becomes available once the device is more widely distributed and used under real-world conditions.”  We encourage CDRH to consider how often this happens because of the lack of meaningful safety or effectiveness data provided through the 510(k) review process, and how improvements of that review process could reduce problems stemming from lack of definitive information about safety or effectiveness.  Shifting the evidence requirement for safety and effectiveness of medical devices from premarket to postmarket allows time for more people to use these devices, which may cause harm.   This means that emerging signals including from subpopulations (such as sex-specific, age, ethnic, and racial information) gathered from real-world conditions will become even more important.

The draft guidance cautions about unintended consequence of communicating emerging signals and states that “a beneficial device’s use may be avoided or inappropriately stopped.”  Given the slow response of the medical community to new data regarding standard treatments, we believe this risk is relatively minor. For example, patients’ serious problems related to surgical mesh started receiving widespread media coverage in 20087 but after the FDA’s first safety communication in 2008 the use of surgical mesh actually increased (from 21% of all procedures in 2008 to 30% in 2011).  Only after FDA released a second more strongly worded safety warning in 2011 did mesh use decrease to 23% in 2013, which was still above the 2008 percentage.8  With that in mind, the FDA can appropriately address this issue by recommending that an emerging signal be “based on reliable data, [so that] the benefits of providing early information to the public outweigh these risks.”1  We also note that the draft guidance specifically defines emerging signals, and lists nearly a dozen specific considerations for determining if the FDA will issue a public notification about an emerging signal.  These notifications will be made in a deliberate manner, which should limit negative consequences.

However, the draft guidance on when to communicate and what to say to the public is too restrictive.  It states that the FDA should communicate about emerging signals when all of the following statements apply:

  1. The information represents a new, potentially causal association, or a new aspect of a known association (e.g., increased rate or severity of event or reduced benefit), between a medical device and one or more adverse events of clinical outcomes;
  2. The available information is reliable and supported by sufficient strength of evidence; and
  3. The information could have important clinical implications for patient management decisions and/or could it significantly alter the known benefit-risk profile of the device.

Recommending that all of the statements must apply could stop FDA from alerting the public about emerging signals in a timely manner, and this would be harmful to patients and unfair to healthcare providers.  If the first two apply, we strongly urge that be sufficient to require the FDA to release a public communication.  Also, in #3, the phrases “important clinical implications” and “significantly alter the known benefit-risk profile” are not clearly defined.  That could lead to endless arguments between industry and the FDA, which would delay or have a chilling effect on FDA communicating to the public about possible hazards from a medical device.

We agree with the FDA that when a decision is made not to communicate emerging signals to the public, it should be reassessed within 30 days of the FDA receiving new information regarding safety signals of the device.

We support FDA’s efforts to provide consistency in communicating medical device emerging signals and we support the format, which provides six data points including the name of the device and a summary of the emerging signal.  We suggest that FDA add three more items: the device’s 510(k) or PMA number, its UDI number, and a “recall” line.  The recall line would show if the device is currently being recalled or has been recalled in the past.  In our examinations of recalled devices, it has not been unusual to find a device that has been recalled more than once.  Knowing that a device has been modified to address safety or effectiveness issues could help the FDA and the public to focus on possible emerging signals.

Conclusions

For the above reasons, the following members of the Patient, Consumer, and Public Health Coalition support the draft guidance on emerging signals.

Breast Cancer Action
Connecticut Center for Patient Safety
Consumers Union
Jacob’s Institute of Women’s Health
Mothers Against Medical Error
National Center for Health Research
National Consumers League
National Women’s Health Network
Our Bodies Ourselves
Quinolone Vigilance Foundation
The TMJ Association
WomenHeart: The National Coalition for Women with Heart Disease
WoodyMatters

 

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

Comments on FDA’s Proposed Reclassification of ECT Devices for Treating Severe Major Depressive Episodes

Coalition comments
on the Proposed Order
Reclassification of Electroconvulsive Therapy Devices
[Docket No. FDA-2014-N-1210]

 

As members of the Patient, Consumer, and Public Health Coalition, we are writing to strongly oppose the split classification of electroconvulsive (ECT) devices. This reclassification would make ECT devices used for treatment-resistant major depression or depression requiring a rapid response class II (special controls) and all other psychiatric indications class III.

An ECT device applies a brief intense electrical current to a patient’s head to intentionally induce a major motor seizure.9  These devices have only short-term benefits and are known to have serious risks and should only be used when the benefits are likely to outweigh the risks.  That requires clinical trials, inspections, and other safeguards that are part of the PMA review process.  Allowing any ECT devices to be cleared by the FDA through the 510(k) process for any indication puts patients at risk.

ECT can cause cardiac complications, prolonged or delayed onset seizures, and death.10 This risk for harm is not any less when the devices are used to treat depression versus other psychiatric diagnoses.  Eleven of the 14 risks identified by the FDA would be mitigated exclusively by labeling.  However, it is widely known that many doctors do not read the labels on devices carefully, if at all.

Even when the labeling and other controls are followed, the current treatment protocols for ECT devices still carry substantial risks for patients’ cognitive impairment.11 12 13 Studies demonstrate that the percentage of patients with complaints about ongoing memory problems even years after treatment ranges from 29 % to 67%.14 15 16 These memory deficits greatly affect patients’ lives, and an unknown proportion of these patients suffer very severe, persistent memory problems.17 18 19 20  Unfortunately, the percentage of patients who suffer severe memory problems is unknown because the FDA has not required such research. It is not possible to predict the extent to which patients will be affected by a given device and protocol or which patients will develop severe memory problems. 21 22

It would be very dangerous to patients if new ECT-like devices are approved without clinical trials. The strength of the current or voltage, as well as the length, pattern and waveform of the pulse affect the effectiveness and the extent of cognitive impairment.23 24  For example, cognitive impairments are less severe when a brief pulse or ultrabrief pulse is used as opposed to a sine wave because less energy is required to induce a seizure.

Once an ECT device is cleared as a 510(k) class II device, it would serve as a predicate for many other potentially dangerous devices.  In addition, if an ECT device can be cleared through the 510(k) process, device manufacturers have no incentive to apply for approval through the PMA process.  To pretend otherwise is fundamentally dishonest, since the devices could be used off-label for treatment of indications other than depression. The only way to ensure that the benefits outweigh the risks for any indication for which it is approved is to require a PMA review for these obviously high-risk devices.

In conclusion, ECT devices are potentially high-risk devices and should remain as class III and should be subject to PMA review for all indications. The risks for patients associated with down classification of ECT devices for depression greatly outweigh any presumed benefit.

American Medical Women’s Association
Connecticut Center for Patient Safety
MISSD
National Organization for Women
National Women’s Health Network
The TMJ Association
Washington Advocates for Patient Safety
WoodyMatters

 

The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The coalition can be reached through Stephanie Fox-Rawlings, Ph.D. at sfr@center4research.org or (202) 223-4000. 

 

 

 

Coalition Strongly Supports FDA’s Proposal to Regulate Over-the-Counter Sunscreens

Comments of members of the Patient, Consumer, and Public Health Coalition
on the FDA Draft Guidance entitled “Over-the-Counter Sunscreens: Safety and Effectiveness Data”
 Docket No. FDA-2015-D-4021
 
 
As members of the Patient, Consumer, and Public Health Coalition, we appreciate the opportunity to comment on the draft guidance entitled “Over-the-Counter Sunscreens: Safety and Effectiveness Data.” As members of the coalition, we strongly support the safety and effectiveness clinical and nonclinical testing requirements to obtain generally recognized as safe and effective (GRASE) status, as they are articulated in the draft guidance. Americans are using sunscreens more frequently and on a more long-term basis than ever before. Our safety and efficacy standards must reflect that Americans of all ages rely on these products to protect them from skin cancer.

 

We need clear evidence that sunscreen products are safe and effective for long-term use, particularly for infants, children, and pregnant women. Although current sunscreens are marketed for skin cancer prevention, we have very little evidence that they are effective for this purpose. In fact, major public health authorities, including the FDA, National Cancer Institute, and the International Agency for Research on Cancer, have concluded that the available data do not support the assertion that sunscreens alone reduce the rate of skin cancer.25, 26, 27  The safety and effectiveness testing requirements proposed in the draft guidance will provide the level of evidence that we need to be able to trust our sunscreen products to protect us and not harm us.

 

We strongly support the FDA’s proposal to require that active ingredients be tested for carcinogenicity and developmental and reproductive toxicity prior to marketing. These studies must be carefully designed to mimic the conditions of real-life sun exposure, including temperature and humidity.28  Additionally, the National Institute of Environmental Health Services has concluded that endocrine-disrupting agents often have greater risks at low doses so dose-response testing is not appropriate for these studies.29  Without well-designed studies, children and other vulnerable groups could be harmed by hormone-altering ingredients.

 

Infants and children are more vulnerable to unsafe chemicals, because they use sunscreen more often and are more susceptible to the risks of chemicals in sunscreen. Although children are at disproportionate risk of harm from unsafe sunscreen products, we have very little data on the safety of these products in this young population. For those reasons, we strongly urge the FDA to stipulate that clinical studies must provide demographic subgroup analyses of these and other susceptible populations before the products are allowed to be marketed for widespread use.

 

Sunscreens are not “just cosmetics” and should not be regulated as such. Sunscreen chemicals may lose their effectiveness when exposed to light, or, worse yet, may actually cause cancer rather than prevent it.30  It is important that manufacturers provide clear scientific evidence proving the product remains active when exposed to sunlight for a reasonable length of time.

 

There is also evidence that certain active ingredients demonstrate potentially carcinogenic activity when exposed to UV light, such as generating free radicals that damage DNA and cause harmful mutations.31  Testing for carcinogenic activity should be done under conditions that reflect real-world use as closely as possible, e.g., during UV light exposure. Without such information, products intended to help prevent cancer may do just the opposite.

 

Several sunscreen ingredients currently on the market have endocrine-disrupting or carcinogenic activity.32  For example, oxybenzone is a widely used sunscreen ingredient and, with up to 10% absorption through the skin, it is found in the blood of nearly every American as well as in breast milk.33  Research has shown it acts like an estrogen in the body, is associated with endometriosis in women, and alters sperm production in animals.34  This ingredient should be banned from sunscreen and FDA must not let this mistake be repeated by allowing new sunscreen ingredients to be marketed without sufficient safety testing.
 
Finally, we strongly agree with the proposal to require testing of the active sunscreen ingredient with each vehicle (e.g. cream, spray, etc.) in which it will be delivered. Different product formulations that are more water or lipid soluble may change the properties or absorption of active ingredients in ways that could affect safety or efficacy of the final product. For example, alcohol-based formulations appear to increase sunscreen absorption and some sunscreen chemicals may enhance the skin absorption of other sunscreens when applied in combination.35

 

In conclusion, the safety and effectiveness testing requirements for new sunscreen chemicals proposed in the draft guidance will assure our country’s most vulnerable that the products will protect them from skin cancer and not cause unintended harm. We understand the desire for innovative new sunscreen products but this must not come at the expense of safety or effectiveness. We urge you to finalize this draft guidance without delay.

 

Advocating Safety in Healthcare E-Sisters (ASHES)
Annie Appleseed Project
Breast Cancer Action
Cancer Prevention and Treatment Fund
Iowa Breast Cancer Edu-Action (IBCE)
Medication-Induced Suicide Prevention and Education Foundation (MISSD)
MedShadow Foundation
National Organization for Women
National Physicians Alliance
National Women’s Health Network
Our Bodies Ourselves
Washington Advocates for Patient Safety
Woodymatters
The Patient, Consumer, and Public Health Coalition is an informal coalition of nonprofit organizations representing the interests of millions of patients, consumers, health-care professionals, scientists, and public health experts. The Coalition can be reached through Tracy Rupp at (202) 223-4000 or at tr@center4research.org.

 

Comments in Support of FDA’s Proposed Updated Performance Standards for Tanning Devices

March 21, 2016

Comments on Proposed Rule
Proposed Amendment to Performance Standard
[Docket No. FDA-1998-N-0880]

Since there are virtually no medical benefits to using commercial sunlamp products (tanning beds) and the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC) classified indoor tanning devices as carcinogenic to humans, 36 we are writing as members of the Patient, Consumer, and Public Health Coalition to recommend that the Food and Drug Administration (FDA)  ban the devices entirely (see our comments on the proposed rule regarding Restricted Sale, Distribution, and Use of Sunlamp Products, Docket No. FDA-2015-N-1765).

In the meantime, however, we support the proposed rule to update the performance standard for sunlamp products to “improve consumer safety.”37

We agree with the FDA that the adverse effects of ultraviolet radiation are well known and that sunlamp products emit UV radiation. In addition to long-term exposure causing skin cancer (including squamous cell carcinoma, basal cell carcinoma, and melanoma), the adverse effects from UV radiation include sunburns and ocular melanoma.2

FDA’s performance standards for sunlamp products have not been updated in more than 30 years.  Since then, there have been changes in the FDA’s understanding of how UV radiation interacts with human skin, and there have been many changes in indoor tanning equipment.2

Below are our specific comments on the proposed updated standards:

We strongly support the requirement that the emergency stop button (sometimes referred to as the ‘panic button) “be easily accessible and readily identifiable to the user.”2

We strongly support FDA’s proposal to modify the warning statements on sunlamp products to make them shorter and more user-friendly so that they “more effectively communicate the risks of indoor tanning to users.”2  We support retaining the requirement that label information must be “legible and readily accessible to view by a sunlamp product user immediately prior to use” (emphasis added).2  We also support the added requirement that the warning statement be in all catalogs, specification sheets, brochures, and websites.

We strongly support FDA’s efforts to require that manufacturers of protective eyewear maintain test records that show their products comply with UV requirements.

We strongly support the proposed rule to use the International Electrotechnical Commission’s (IEC) “equivalency code” system to make sure that the correct replacement UV lamp bulbs are used. Currently, there is confusion over the compatibility requirement for lamp replacements, which could lead to a lamp being used that puts out more UV radiation than it is supposed to.

Conclusion

An estimated 77.000 new cases of melanoma are diagnosed in the United States every year, resulting in approximately 9,500 deaths.38  And, every year in the U.S. approximately 400,000 cases of skin cancer (including melanoma) are caused by indoor tanning, according to the American Academy of Dermatology.39

We strongly support the FDA’s proposed rule to update the performance standards for sunlamp products because much stronger standards are necessary to reduce “sunburn, photokeratitis, skin cancer, cataracts, and ocular melanoma” by limiting exposure to UV radiation.2  However, those standards should be merely a first step.  The FDA should go even further to protect the public health by banning commercial sunlamp products entirely.

American Medical Women’s Association
Cancer Prevention and Treatment Fund
MISSD
MRSA Survivors Network
National Physicians Alliance
Our Bodies Ourselves
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

Comments in Support of FDA’s Proposed Age Restrictions on Tanning Beds

March 21, 2016

Comments on Proposed Rule
Restricted Sale, Distribution, and Use of Sunlamp Products
[Docket No. FDA-2015-N-1765]
As members of the Patient, Consumer, and Public Health Coalition, we strongly support the proposed rule that bans minors (individuals under the age of 18) from using commercial tanning beds (sunlamp products).  However, we think the age limit should be 21, as it is for alcohol, and as it is for cigarettes in more than 100 U.S. cities.[i]

In 2013, our coalition submitted comments to the FDA recommending that the agency up-classify sunlamp devices from Class I (low risk devices) to Class III (high risk devices).[ii] Unfortunately, the agency only up-classified the device to Class II (moderate risk devices).  Now, in its proposed rule, the FDA cites studies that the devices are directly correlated to skin cancer including the most deadly form, melanoma.  Since there are virtually no medical benefits to using commercial tanning beds and the World Health Organization’s (WHO) International Agency for Research on Cancer (IARC) classified indoor tanning devices as carcinogenic to humans,[iii] we recommend that FDA ban the devices entirely (not just for users under age 18).  At the very least the FDA should ban the devices for users under 21 and reclassify sunlamp products as Class III (high risk devices). High-risk devices are ones that can cause substantial harm or even death, and clearly, sunlamps satisfy those criteria.

In the meantime, however, we support the requirement that adult users of indoor tanning salons sign a risk acknowledgment certificate, and the proposed rule’s requirement that user manuals be provided by salon staff to other staff and any customer who asks for one.

Below are our specific comments on the proposed rule.

Age Restrictions on Tanning Devices

Young people, especially women (who use the devices more often than young men), are extremely vulnerable to the health risks of tanning devices.  Using indoor tanning beds before age 35 can increase the risk of melanoma—the deadliest form of skin cancer—by 59%.[iv] The risk increases with the number of sunbed sessions and is higher if the person begins using tanning devices at a younger age.3  Medical evidence points to a “direct correlation between sunlamp product use among youths and their developing melanoma skin cancer.”[v] Melanoma is a leading cause of cancer death in women ages 15 to 29 years.5  In 2013, the American Cancer Society (ACS) estimated 76,690 new cases of melanoma in the United States and 9,480 deaths from the disease during the year.[vi]  Each year, approximately 400,000 cases of skin cancer (including melanoma) in the U.S. are caused by indoor tanning, according to the American Academy of Dermatology.4

A recent study showed that restrictions on access to tanning beds will reduce the number of young people using them.  Female high school students in states with indoor tanning laws were less likely to engage in indoor tanning compared to students in states without any laws, according to the Centers for Disease Control and Prevention.[vii]

The FDA’s proposed rule banning use by minors under 18 will reinforce regulatory actions already taken by more than 40 states.  Minors are banned from using commercial tanning beds in 11 states (California, Delaware, Illinois, Louisiana, Minnesota, Nevada, New Hampshire, North Carolina, Oregon, Texas, and Vermont) and the District of Columbia.6  Just this month, Kansas House lawmakers overwhelmingly passed a bill to ban minors from indoor tanning salons and the legislation has been sent to the state Senate.[viii]

The FDA’s proposed rule will protect minors in all states, but only under the age of 18. The cancer damage associated with sun tanning devices is substantial and could be avoided by stricter regulations.3  The FDA’s proposed rule dovetails with recommendations from the IARC, which stated: “Policymakers should consider enacting measures, such as prohibiting minors and discouraging young adults from using indoor tanning facilities, to protect the general population from possible additional risk for melanoma.”[ix]

We strongly support the proposed rule that would ban minors from using the devices and agree with the FDA that “by restricting sunlamp product use to individuals 18 and older, we would be protecting a subpopulation that generally tends to discount risk information and favor risk taking.”5  Unfortunately, however, young adults over 18 also tend to ignore risk information.  There is no logical reason to have an age limit of 18 for sunlamps, when the age limit is 21 for alcohol and tobacco products in more than 100 U.S. cities.

Prospective Users Signing Risk Acknowledgement Certificates    

The proposed rule does not go far enough in protecting those 18 and older when it requires the owners of tanning salons to have those users sign a risk acknowledgement statement, which is supposed to counteract any false or misleading information about the devices.  However, without an effective enforcement or monitoring policy established, it is unlikely tanning salon owners will comply with this part of the proposed rule. Congress found in 2012 that tanning salons were providing “false and misleading Information” to customers.  Congress also found that 90 percent of operators stated to customer inquiries “that indoor tanning presented no risks.”5

Providing Sunlamp Product User Manuals

Until sunlamps are either tested as PMA devices or banned entirely, we support requiring that  the user manuals for the devices be provided to anyone who requests them. However, this protection is too weak.  The manuals should be provided by salon staff within 5 minutes of a request and the FDA should not allow the salon operator to merely provide the address of the manufacturer/distributor or the address of the 510(k) holder).   The reason is simple: those two options greatly delay the availability of the information that clients need to make an informed choice.  In addition, it puts a burden on clients who request information that could save their lives, rather than putting the onus on the tanning salon to provide information needed for informed consent regarding the use of dangerous devices.

Getting information from the manufacturer or distributor will inevitably take days, weeks, or months to receive.  Getting the information from a 510(k) holder is completely ludicrous even assuming that person’s name and address can be accurately provided.  The National Center for Health Research conducted a study on publicly available information regarding 510(k) medical devices and the Center found that the addresses provided were frequently out of date.  Moreover, although the companies were required by law to provide information upon request, only 20% of the 510(k) holders provided the requested information in unredacted form.[x]

Conclusion

We strongly support the FDA’s proposed rule to ban the use of commercial tanning devices by minors. This would reduce the risk of skin cancer for many Americans. However, since the FDA has not required that sunlamps be carefully studied through the PMA process, we recommend that the FDA go even further to protect the public health by banning commercial sunlamp products entirely.

American Medical Women’s Association
Cancer Prevention and Treatment Fund
MISSD
MRSA Survivors Network
National Physicians Alliance
Our Bodies Ourselves
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

[i] Sandrick, B (December 8, 2015). More than 100 U.S. Cities Raise Smoking Age to 21. Cleveland.com  http://www.cleveland.com/metro/index.ssf/2015/12/cleveland_follows_growing_nati.html

[ii] Patient, Consumer, and Public Health Coalition (August 7, 2013).  Comments on Proposed Order on “Reclassificaiton of Ultraviolet Lamps for Tanning, Henceforth To Be Known as Sunlamp Products.  Docket No. FDA-2013-N-0461.

[iii] BMJ (2012).  Boniol M, et al. Cutaneous melanoma attributable to sunbed use: systematic review and meta-analysis.  http://www.bmj.com/content/345/bmj.e4757

[iv] American Academy of Dermatology web page. https://www.aad.org/advocacy/skin-cancer-and-indoor-tanning/stop-skin-cancer

[v] Federal Register (Tuesday, December 22, 2015).  Proposed rule: General and Plastic Surgery Devices: Restricted Sale, Distribution, and Use of Sunlamp Products.

[vi] National Conference of State Legislatures. Web page: Indoor Tanning Restrictions For Minors – A State-By-State Comparison. http://www.ncsl.org/research/health/indoor-tanning-restrictions.aspx

[vii] Centers for Disease Control and Prevention (2014). Press Release: Rates of indoor tanning among female high school students lowest in states with multiple restrictions on youth access. http://www.cdc.gov/media/releases/2014/p0213-indoor-tanning.html

[viii] Associated Press (March 10, 2016). Lawmakers vote to ban Kansas minors from indoor tanning. Reported in the Kansas City Star. http://www.kansascity.com/news/state/kansas/article65208207.html

[ix] World Health Organization(WHO), International Agency for Research on Cancer (2006). Exposure to Artificial UV Radiation and Skin Cancer.

[x] Zuckerman, D, Brown, P, and Das A (2014) Lack of Publicly Available Scientific Evidence on the Safety and Effectiveness of Implanted Medical Devices. JAMA Intern Med.