August 11, 2014

The Honorable Bill Nelson
United States Senate
Washington, DC 20510

Dear Senator Nelson:

On behalf of organizations dedicated to improving the health and safety of children, we write to express our support for the Child Nicotine Poisoning Prevention Act of 2014. This legislation recognizes the danger that liquid nicotine used to refill electronic cigarettes poses to small children and gives the U.S. Consumer Product Safety Commission (CPSC) the authority to require the use of child-proof packaging on liquid nicotine containers sold to consumers.

Recent data from the Centers for Disease Control and Prevention (CDC) indicate that there were 215 calls to poison control centers related to e-cigarettes in February 2014 alone, up from only one call per month in 2010. Liquid nicotine is highly toxic and sold in a highly concentrated form. It is common to find liquid nicotine containing upwards of 36 mg of nicotine per milliliter of liquid. At this concentration, a small 15 mL dropper bottle of liquid nicotine would contain over 500 mg of nicotine. Given that the estimated lethal dose of nicotine is 1 to 13 mg per kilogram of body weight, even at the high end of this range a bottle of liquid nicotine at this size and concentration would be enough to kill four toddlers.

In addition, these products come in bright colors and candy flavors that make these substances likely candidates for ingestion by young children. Alarmingly, these products are often sold in containers without any child-proofing, and there are currently no federal requirements for child-proof packaging for liquid nicotine despite the highly toxic nature of these products. Given that liquid nicotine may also be absorbed quickly through the skin as well as ingested, children are in extreme danger of being poisoned without simple safeguards to ensure that these liquids stay sealed in their containers.

CPSC has the expertise to quickly require child-proof packaging for liquid nicotine if given the authority by Congress. The Commission currently requires such packaging on toxic household substances like bleach, as well as Food and Drug Administration (FDA)-regulated products like prescription drugs. Parents have come to expect that household products that can cause serious harm to children come in child-resistant packaging. Liquid nicotine should be no different.

The FDA is in the process of extending its regulatory authority to include additional types of tobacco products, including e-cigarettes and liquid nicotine. S. 2581 preserves FDA’s authority to regulate the manufacture, marketing, sale, and distribution of tobacco products and the packages and containers in which they are sold. We also encourage action by the FDA to protect children from child poisoning and other dangers posed by tobacco products and their containers.

This is an urgent public health danger and quick action is needed to ensure that child poisoning from liquid nicotine is addressed as soon as possible. We look forward to working with you to pass this important legislation.

Sincerely,
American Academy of Otolaryngology – Head and Neck Surgery
American Academy of Pediatrics
American Association of Poison Control Centers
American Association for Respiratory Care
American College of Cardiology
American College of Physicians
American College of Preventive Medicine
American Public Health Association
Arizona Consumers Council
Association of Maternal and Child Health Programs
Association of State and Territorial Health Officials
Boston Public Health Commission
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Chicago Consumer Coalition
Consumer Federation of America
Consumer Federation of California
Consumer Federation of the Southeast
Consumers Union
EverThrive Illinois
First Focus Campaign for Children
Kids in Danger
March of Dimes
Minnesota Department of Health
National Association of County and City Health Officials
Ohio Public Health Association
Partnership for Prevention
Public Citizen
U.S. PIRG
Virginia Citizens Consumer Council

To view as a PDF, click here.

May 27, 2014

The Honorable Harold Rogers
Chairman
Committee on Appropriations
United States House of Representatives
Washington, DC 20515

The Honorable Nita Lowey
Ranking Member
Committee on Appropriations
United States House of Representatives
Washington, DC 20515

Dear Chairman Rogers and Ranking Member Lowey:

We are writing to express our strong opposition to any amendment that would exempt any type of cigar from regulation under the Family Smoking Prevention and Tobacco Control Act, P.L. 111-31, or would impede the current rulemaking process the Food and Drug Administration (FDA) has initiated to determine the appropriate level of oversight for tobacco products not currently regulated by the agency. We believe the FDA should retain the authority to regulate all tobacco products, including cigars, and should be permitted to use a science-based process for determining those regulations. Products containing tobacco cause disease and should not be exempted from oversight by the agency.

While the health risks of cigar smoking are not the same as cigarette smoking, cigar smoke is composed of the same toxic and carcinogenic constituents found in cigarette smoke. According to the National Cancer Institute, cigar smoking causes cancer of the oral cavity, larynx, esophagus and lung, and cigar smokers are at increased risk for an aortic aneurysm. Daily cigar smokers, particularly those who inhale, have an increased risk of heart disease and chronic obstructive pulmonary disease (COPD). Cigar smoking is not limited to adults; it is the second most common form of tobacco use among youth. According to national surveys, 17.8 percent of high school boys currently smoke cigars (i.e., large cigars, cigarillos, and small cigars),¹ and each day more than 2,700 youth under 18 years old try cigar smoking for the first time. ² Young adults (e.g., 15.9 percent of 18 to 24 year olds) are also much more likely to be cigar smokers than older adults (e.g., 4.9 percent of 45 to 64 year olds). ³ FDA has just issued a proposed rule to regulate cigars and other unregulated tobacco products. FDA is seeking public comment about whether all cigars should be regulated by FDA or whether “premium cigars” should be exempted from FDA oversight. During this rulemaking process, FDA will need to assess the available science concerning the health risks of smoking cigars and who smokes different kinds of cigars.

We oppose any amendment that would interfere with the current rulemaking process, prevent a science-based decision-making process, and place a broad category of cigars beyond the reach of FDA. An amendment to exclude certain types of cigars would prevent FDA from implementing even basic common-sense rules such as requiring manufacturers to report what ingredients are contained in their products.

With strong bipartisan support, in 2009 Congress gave FDA authority over the manufacture, sale and marketing of all tobacco products. Congress gave the FDA the flexibility to determine the type of regulation that is appropriate for different tobacco products. While the Act immediately applied all of FDA’s new authorities to cigarettes, cigarette tobacco, roll-your-own tobacco, and smokeless tobacco, it established a process for the Secretary of Health and Human Services to assert jurisdiction over other tobacco products, including cigars, and determine which requirements are appropriate for the protection of public health. Maintaining FDA’s current authority will ensure that any proposal about cigars is based on science and will be open to participation by all interested parties through Notice and Comment rulemaking.

Our organizations strongly urge you to oppose any amendment to exempt a type of cigar from regulation or impede the current rulemaking process for establishing oversight of currently unregulated tobacco products.

Sincerely,

American Academy of Family Physicians
American Academy of Pediatrics
American Association for Cancer Research
American Association for Respiratory Care
American Academy of Otolaryngology—Head and Neck Surgery
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Physicians
American College of Preventive Medicine
American Congress of Obstetricians and Gynecologists
American Dental Association
American Heart Association
American Lung Association
American Medical Association
American Psychological Association
American Public Health Association
American Society of Clinical Oncology
American Thoracic Society
Association of State and Territorial Health Officials
Association of Women’s Health, Obstetric and Neonatal Nurses
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Lung Cancer Alliance
National African American Tobacco Prevention Network
National Association of City and County Health Officials
National Hispanic Medical Association
National Latino Alliance for Health Equity
National Physicians Alliance
Partnership for Prevention
Society for Public Health Education
Society for Research on Nicotine and Tobacco
United Methodist Church, General Board of Church and Society

April 11, 2014

Margaret A. Hamburg, M.D.
Commissioner
Food and Drug Administration
10903 New Hampshire Ave
Silver Spring, MD 20993-0002

Re: Microbiology Medical Devices Panel on Cobas HPV Test Premarket Approval Application

Dear Commissioner Hamburg,

We are writing as members of the Patient, Consumer, and Public Health Coalition and other interested experts to express our grave concerns about the March 12, 2014 FDA meeting of the Microbiology Medical Devices Panel of the Medical Devices Advisory Committee.  Under consideration was the premarket approval of a new indication for the Cobas HPV test, as a first-line primary screening tool for cervical cancer in women aged 25 and older.

This is a radical change to current U.S. Preventive Services Task Force (USPSTF) guidelines, which recommend Pap smears every 3 years starting at age 21, with the option of replacing that regimen starting at age 30 with a combination of a Pap smear and HPV test.  As the American College of Obstetricians and Gynecologists (ACOG) stated in its comments to FDA regarding the lack of evidence for this proposal, “There is little comparative effectiveness data comparing primary HPV screening with co-testing, the preferred method in the ACS-ASCCP-ASCP guideline…providers will not be able to adequately counsel patients regarding the relative benefits and potential harms of primary HPV screening compared with currently accepted methods, particularly co-testing.”

Although FDA scientists and several members of the advisory committee expressed safety concerns about this radical shift, they voted in favor of approval.

The new indication is radical in several ways:

1)      It replaces a safe and effective well-established screening tool and regimen that has prevented cervical cancer successfully in the U.S. with a new tool and regimen not proven to work in a large U.S. population, and is not supported by any evidence-based U.S. guidelines.

2)      It interferes with the practice of medicine, by encouraging physicians to follow a positive result on the HPV test, which can identify a virus but cannot identify abnormal cells, with a colposcopy, an expensive and invasive procedure that could result in much lower compliance.  For no apparent reason, the Pap smear is not used to follow-up on the HPV test to determine if cellular abnormalities have occurred.

3)      The Pap smear is effective in detecting cellular signs of pre-malignancy that can be caused by HPV or other causes.  The new indication would replace the Pap smear with the HPV test, which can only detect the virus (which usually will not cause cervical cancer) but will not detect cancers that are not caused by HPV.

We have numerous concerns about both the implications of this decision and the quality of the pivotal trial used to support it:

No U.S. guidelines currently sanction HPV testing as a first-line screening test for cancer

Current guidelines sanction HPV testing in conjunction with cytology and restricted to patients 30 and older, due to evidence of unacceptable risks among younger patients, i.e. increases in invasive follow-up procedures such as colposcopy and cervical biopsy.  The latter, in cases of cone biopsy and further excisional procedures, can be associated with adverse events in pregnancy such as pre-term labor, perinatal death, low birth weight, and also subfertility, which would disproportionately affect the younger patient population being proposed in the new indication.

For these reasons, sister federal agencies and other medical associations such as the Centers for Disease Control and Prevention, USPSTF, ACOG, American Cancer Society, and American Association of Family Practitioners have not recommended HPV testing as a first-line screening tool in any patient population.  The USPSTF currently gives a “D” rating for HPV testing in women under age 30 in any clinical context, citing harms which outweigh benefits among younger women as seen in previous clinical trials, and also citing concerns regarding over-treatment of CIN2 in this patient population, where it is most likely to regress.

Interference with the practice of medicine

As was noted by the advisory committee, the new proposed indication would result in specific triage protocols for patient management following use of the Cobas HPV test.  The FDA briefing materials prepared for the advisory committee explicitly stated that the advisory committee cannot “establish or recommend guidelines for medical practice.” Approval of this indication would encroach on clinical practice guidelines which are outside the purview of the advisory committee and the FDA.

Significant design problems with the pivotal clinical trial

The basis for approval of this indication is a flawed clinical trial.  Flaws include the design of  the comparator arm, participant age and HPV vaccination status, trial duration, and testing interval.

The comparator arms were based on outdated clinical guidelines.  Specifically, the main comparator arm triaged all abnormal cytology ASC-US or higher to immediate colposcopy, which is no longer current practice.  As the FDA stated in its report, “this comparator was selected prior to the 2012 update of the 2006 Guidelines (2012 Guidelines), in which immediate colposcopy is no longer performed on women with ASC-US cytology and unknown HPV status.”  This triage design significantly increased colposcopy rates in the comparator arms, making the candidate arm colposcopy rate appear more favorable than if it had been compared to current clinical practice.   In order to accurately weigh risks and benefits, the comparator arm must represent current clinical practice and guidelines.

Furthermore, given the wording of the proposed indication, this test could be used repeatedly for the majority of women’s lives.  Yet the pivotal trial lasted only three years with annual clinical exams, which is not consistent with current guidelines.  The FDA also expressed this same concern in their questions for the panel, stating that “this study population does not have a history of screening using the newer, longer screening intervals.  Disease prevalence may differ in a population that has been screened under the new intervals.”

Lastly, the median trial participant age was 41, one-third were post-menopausal, and only 1% had been vaccinated against HPV, which the FDA also noted in its briefing materials.  As the proposed indication poses the greatest risk of unnecessary harm to a younger age group, it is not scientifically sound to make treatment decisions for young women based on research that lacks sufficient and relevant data for this critical population.

Minimal gains in detection

Minimal gains in detection must be weighed against jeopardized patient compliance and increased harms.  Most cervical cancers occur in women who have never been screened, were not screened in the last five years, or did not have appropriate follow-up treatment.  The sponsor does not provide any evidence that HPV testing will increase patient compliance.  On the contrary, the sponsor’s plan, based on the trial population, would result in 7% of women ages 25 to 29 being advised to undergo immediate colposcopy.  Are they likely to comply?

Several studies document numerous social, economic and cultural factors which contribute to reduced patient compliance with colposcopy and other longer, more invasive follow-up procedures, especially among younger, underserved populations who already suffer from disparities in cervical cancer survival.  Many studies have highlighted the critical importance of screening participation in these populations in order to make any meaningful gains in cervical cancer survival.  It should also be noted that HPV testing is significantly more expensive than cytology, and colposcopy is more expensive, more inconvenient, and more painful as well.  This proposed indication threatens to accomplish the very opposite of its intended purpose, which should be to reduce barriers to screening and to save lives.

Clinically important information thrown away

In 2013, the Cobas test received FDA approval to use the same sample vial as the Pap test, producing a streamlined co-testing platform.  The FDA stated in its questions for the panel that cytology “includes other diagnostic categories such as infectious organisms (candida sp., Trichomonas, Herpes viral changes, atypical repair, abnormal endometrial cells, etc.),” all of which the HPV test cannot identify.  The Pap test can identify non-HPV cancers of the cervix, such as choriocarcinoma, melanoma, metastatic carcinoma, and some adenocarcinomas from other primary sites, which the HPV test also cannot identify.  How can loss of this information be justified when it can be acquired from the same sample at little added expense?

Conclusion

This proposed indication for the HPV test would represent an unprecedented and significant shift in clinical practice that would affect millions of women for the majority of their adult lives.  With the health of so many at stake, we strongly urge the FDA to reject the application for this expanded indication, until evidence clearly indicates that this will not reduce the effectiveness of screening for cervical cancer.

Sincerely,

American Medical Student Association
American Medical Women’s Association
American Public Health Association
Annie Appleseed Project
Cancer Prevention and Treatment Fund
Community Catalyst
Connecticut Center for Patient Safety
Consumers Union
Jacobs Institute of Women’s Health
National Alliance of Hispanic Health
National Consumers League
National Organization for Women
National Physicians Alliance
Our Bodies Ourselves
The TMJ Association
Women Advocating Reproductive Safety
WoodyMatters
Individuals:

Benjamin A. Gitterman, M.D.
Nancy S. Hardt, M.D.
Vivian W. Pinn, M.D., F.C.A.P.
John H. Powers, M.D.
Alexandra Stewart, J.D.
Duchy Trachtenberg, MSW

Contact Information: Anna Mazzucco, PhD at (202) 223-4000 or am@center4research.org

cc: Jeffrey Shuren, M.D., J.D., Director, Center for Devices and Radiological Health

On April 24, the FDA wrote a letter in response to our letter and announced they had approved the HPV test as a replacement for the Pap smear. 

To view as PDF, click here.

March 27, 2014

Mitchell Zeller
Director, Center for Tobacco Products Food and Drug Administration
9200 Corporate Dr. Rockville, MD 20850

Dear Director Zeller:

The recently-issued report of the Surgeon General, The Health Consequences of Smoking – 50 Year of Progress (the SG Report), provides a comprehensive review of the progress our nation has made against the tobacco epidemic. Disturbingly, although the SG Report documents a sharp decline in the incidence of adult smoking in the decades since the historic 1964 Surgeon General’s Report, it also finds that smokers are at a far greater risk of developing lung cancer than they were 50 years ago. Moreover, the Report concludes that this outcome is the result of changes made during that time in the design and composition of U.S. cigarettes. For the first time in history, the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) gives the Food and Drug Administration (FDA) the authority to require changes in the content and design of cigarettes “appropriate for the protection of public health.”

The SG Report makes clear that FDA needs to act and act quickly to use this broad authority to require the tobacco companies to reverse the changes that have actually made their products even more dangerous. No manufacturer of any other product would have been allowed to make product changes that increased the risk of fatal disease to its users. In light of the Surgeon General’s unequivocal finding that today’s cigarettes do just that, we write to urge FDA to respond decisively by requiring whatever changes are needed in the design and composition of cigarettes to eliminate the increased risk of disease and death identified by the Surgeon General. The SG Report provides compelling evidence of the increased risk to smokers: “Although the prevalence of smoking has declined significantly over the past one-half century, the risks for smoking-related disease and mortality have not. In fact, today’s cigarette smokers – both men and women – have a much higher risk for lung cancer and chronic obstructive pulmonary disease (COPD) than smokers in 1964, despite smoking fewer cigarettes.” (emphasis added).

The Surgeon General found that, during the period 1959-2010, the risk of lung cancer to smokers increased 10-fold for women and more than doubled for men, whereas the risk of lung cancer for those who had never smoked remained the same. Thus, the Report concludes: “The evidence is sufficient to infer that the relative risk of dying from cigarette smoking has increased over the last 50 years in men and women in the United States.”

The SG Report also establishes that the increased risk of lung cancer to smokers is due to the tobacco industry’s changes in the design and composition of cigarettes. Specifically, the Report finds that the increase in lung cancer risk is driven largely by a dramatic increase in the risk of adenocarcinoma of the lung, which has become an increasing proportion of all lung cancers. In turn, the Report finds that “the increased risk of adenocarcinoma of the lung in smokers results from changes in the design and composition of cigarettes since the 1950s.” (emphasis added).The Report notes two specific changes in design and composition that may be responsible for the increased risk of adenocarcinoma of the lung: an increase in highly carcinogenic tobacco-specific nitrosamines in U.S. cigarettes and the use of ventilation holes in filters that enable smokers to inhale more vigorously, thereby drawing carcinogens in the smoke more deeply into the lungs. 

The Surgeon General’s conclusion that the increased risk of lung cancer to smokers is due to changes in cigarette design and composition has critical implications for FDA’s regulation of tobacco products. As the SG Report observes, “[a]bove all, if the risk of lung cancer has increased with changes in the design and composition of cigarettes, then the potential exists to reverse that increase in risk through changes in design and composition.” Under § 907 of the Tobacco Control Act, FDA has the authority to adopt standards for tobacco products “appropriate for the protection of the public health.” In short, FDA has the authority to require cigarette manufacturers to change the design and composition of cigarettes to reduce the risk of disease and death. The need for exercising this authority is particularly compelling when the scientific evidence demonstrates that changes in the design and composition of cigarettes unilaterally made by manufacturers have increased that risk. 

It should also be noted that the SG Report incorporates the findings of U.S. District Judge Gladys Kessler in United States v. Philip Morris, 449 F.Supp. 2d 1 (D.D.C. 2006), and of the U.S. Congress in enacting the Tobacco Control Act, that the cigarette companies “have designed their cigarettes to precisely control nicotine delivery levels and provide doses of nicotine sufficient to create and sustain addiction.”  Indeed, in the Consumer Guide to the SG Report, issued by the Department of Health and Human Services, it is noted that “[s]ome of today’s cigarettes are more addictive than those from earlier decades.” The Surgeon General observes that “[c]igarettes are highly engineered products.” It would appear that the cigarette companies have engineered products that are both more lethal and more addictive.

The Surgeon General calls for “effective implementation of FDA’s authority for tobacco product regulation in order to reduce tobacco product addictiveness and harmfulness.” It is imperative that FDA respond to the SG Report by moving decisively to exercise its statutory authority to require cigarette manufacturers to make necessary life-saving changes in the design and composition of their products. 

Over the past 50 years, smoking has killed more than 20 million Americans. We cannot afford to give the tobacco industry another 50 years to make cigarettes even more dangerous and addictive than they are  today.

Respectfully,

American Academy of Family Physicians
American Academy of Oral Medicine
American Academy of Otolaryngology – Head and Neck Surgery
American Academy of Pediatrics
American Association for Cancer Research
American Association for Respiratory Care
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Preventive Medicine American Congress of Obstetricians and Gynecologists
American Heart Association
American Lung Association
American Medical Association
American Psychological Association
American Public Health Association
American Society of Addiction Medicine
American Society of Clinical Oncology
American Thoracic Society Association of State and Territorial Health Officials
Association of Women’s Health, Obstetric and Neonatal Nurses Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
Community Anti-Drug Coalitions of America
Legacy
Lung Cancer Alliance
National African American Tobacco Prevention Network
National Association of County & City Health Officials
National Latino Alliance for Health Equity
North American Quitline Consortium
Oncology Nursing Society
Partnership for Prevention
Society for Cardiovascular Angiography and Interventions
Society for Research on Nicotine and Tobacco
cc: The Honorable Kathleen Sebelius The Honorable Margaret Hamburg