All posts by CPTFeditor

Coalition letter to FDA Commissioner about approving Cobas HPV test alone (without pap smear) and FDA response

Legislation
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. 

Letter to Director, Center for Tobacco Products FDA Michell Zeller on tobacco product regulation

Legislation

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

Letter to The Honorable Kathleen Sebelius on comprehensive cessation benefit

Legislation, Policy, Uncategorized

To view letter, click here.

February 19, 2014

The Honorable Kathleen Sebelius
U.S. Department of Health and Human Services
Hubert H. Humphrey Building
200 Independence Avenue, SW, Room 120F
Washington, DC 20201

Dear Secretary Sebelius:

We are writing to ask your Department to clearly define a comprehensive tobacco cessation benefit in the Affordable Care Act regulations or, at the very least, in corresponding guidance documents.

Recently, your Department released the 50th anniversary Surgeon General’s report, The Health Consequences of Smoking – 50 Years of Progress, which found that smoking is even more hazardous and takes an even greater toll on the nation’s health than previously reported. We appreciate the work that went into producing this historic report and applaud your commitment to reducing tobacco use.

Noting that the “current rate of progress in tobacco control is not fast enough. More needs to be done,” the report calls for a number of specific actions, including: “Fulfilling the opportunity of the Affordable Care Act to provide access to barrier-free proven tobacco use cessation treatment including counseling and medication to all smokers”. As you noted during the release of the report, and on previous occasions, the Affordable Care Act (ACA) “requires insurance companies to provide tobacco cessation services to their customers.” But we are concerned that tobacco users who are ready to quit do not have access to free cessation services under the ACA.

The Surgeon General report notes that the implementation of tobacco cessation treatment coverage mandated by the ACA varies significantly across private health insurance contracts. In fact, evidence indicates that many health plans are not covering services that have been proven to help tobacco users to quit. A 2012 study by Georgetown University’s Health Policy Institute found that many health insurance plans are failing to provide the coverage mandated by the ACA for treatments to help smokers and other tobacco users quit. Specifically, researchers found that only four of the 39 private plans analyzed clearly covered a full-range of evidence-based tobacco cessation services (i.e., individual, group and phone counseling and both prescription and over-the-counter tobacco cessation medications). Contract language for these plans often contained vague or conflicting language that made it impossible to determine which, if any, tobacco cessation services were covered. When the extent of coverage could be determined, many of these plans excluded coverage of prescription and/or OTC medications for tobacco cessation and excluded certain types of counseling. Also troubling, some of the plans analyzed impose cost-sharing requirements for tobacco cessation treatments.

We believe that this study makes clear that many insurance issuers are not in compliance with the ACA. As a result, many tobacco users’ access to tobacco cessation treatment may be limited. This information has been shared with your Department, yet HHS has not taken any action to make clear to insurers what is required under the ACA.

Tobacco cessation treatments have received an ‘A’ rating by the United States Preventive Services Task Force (USPSTF), which means there is a high certainty that tobacco users will benefit substantially from receiving these services. As an ‘A’ rated service non-grandfathered group plans and insurance issuers must cover these evidence-based tobacco cessation services with no cost-sharing.

The Interim Final Rule implementing Section 2713 of the PHS Act did not attempt to translate the clinical recommendations of the USPSTF into an insurance coverage benefit. The only description in the Interim Final Rule of the tobacco cessation services that must be covered is the following: “The USPSTF recommends that clinicians ask all adults about tobacco use and provide tobacco cessation interventions for those who use tobacco products.” This statement is only the summary of the USPSTF recommendation. The full USPSTF recommendation clearly indicates that counseling and medications are both effective and a combination of counseling and medications “is more effective at increasing cessation rates than either component alone.” USPSTF references the United States Public Health Service Clinical Practice Guideline, Treating Tobacco Use and Dependence: A 2008 Update (the “PHS Guideline”), as the source for a detailed description of effective evidence-based tobacco dependence treatments. Without further guidance from HHS, group plans and health insurance issuers have been able to decide for themselves how to translate the USPSTF clinical recommendation for tobacco cessation services into a covered benefit. Based on the results of the Georgetown University study, many insurers are interpreting the coverage requirement too narrowly, failing to cover tobacco cessation services that the USPSTF has specifically found to be effective.

We are aware that the implementing regulations for section 2713 of the PHS Act permit issuers to “use reasonable medical management techniques to determine the frequency, method, treatment, or setting for an item or service to the extent such frequency, method, treatment or setting are not specified in the recommendation or guideline.” We do not believe that reasonable medical management should allow plans and issuers to ignore the full USPSTF recommendation that specifically lists both the types of medications and counseling that have proven to be effective. All tobacco cessation services that the USPSTF has found to be effective should be covered, not merely some of them. HHS has been provided evidence that many insurance issuers are ignoring the USPSTF recommendations, and without guidance from the Department, group plans and issuers will continue to not provide tobacco users with the effective set of cessation services that Congress intended.

We strongly recommend that the Department of Health and Human Services, Department of Labor, and Department of the Treasury issue guidance to industry clarifying that “tobacco cessation interventions” include coverage of both counseling sessions and FDA-approved medications and that these interventions will be covered whether or not they are delivered during an office visit. As you know, tobacco users need to be encouraged to use cessation services, and lack of clarity about cessation coverage will result in confusion among both health care providers and consumers, leading to fewer successful quit attempts.

Evidence suggests that providing comprehensive tobacco cessation benefits is cost-effective. In 2006, Massachusetts’ Medicaid program (MassHealth) initiated a program to provide tobacco cessation treatments (tobacco cessation medications and counseling) to smokers. A 2012 study published in PloS One shows that Massachusetts saved more than $3 for every $1 it spent on services to help beneficiaries in the state’s Medicaid program quit smoking. These savings are conservative as they do not include long-term savings, savings that may occur outside the Medicaid program, or savings beyond cardiovascular-related hospital admissions. An earlier study found that after Massachusetts implemented this program for all Medicaid beneficiaries, the smoking rate among beneficiaries declined by 26 percent in the first 2.5 years.

There is precedent for HHS to provide guidance beyond the Interim Final Rule on how plans and issuers should comply with the required coverage of USPSTF-recommended services, such as through the FAQs released by the Departments of Labor and Health and Human Services. The failure to clearly define a comprehensive tobacco cessation benefit in regulations or in supplemental information will allow insurers to continue to provide inadequate coverage and impose cost-sharing requirements, contrary to the ACA.

As noted in the recent Surgeon General report, the tobacco cessation benefits contained in the ACA hold great promise but in order to ensure access to cessation services and coverage that reflects the full USPSTF recommendation, we urge you to provide additional guidance on the requirement for coverage of tobacco cessation treatment. With additional guidance, we believe you can make tremendous progress toward accomplishing the specific recommendation laid out in the Surgeon General report and fully maximize the public health benefit of CDC’s Tips from Former Smokers media campaign and other HHS efforts to reduce tobacco use.

The following groups stand ready to help in any way in these efforts, which will save lives and money.

Sincerely,

American Academy of Family Physicians
American Academy of Otolaryngology-Head and Neck Surgery
American Association for Cancer Research
American Association for Respiratory Care
American Cancer Society Cancer Action Network
American College of Cardiology
American College of Chest Physicians
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 Psychological Association
American Public Health Association
American Society of Clinical Oncology
American Thoracic Society
Association of Maternal and Child Health Programs
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
Legacy
Lung Cancer Alliance
National Association of City and County Health Officials
National Physicians Alliance
North American Quitline Consortium
Oncology Nursing Society
Society for Cardiovascular Angiography and Interventions
Society for Research on Nicotine and Tobacco

cc:
Marilyn Tavenner, Administrator, Centers for Medicare and Medicaid Services

Gary Cohen, Deputy Administrator and Director, Center for Consumer Information and Insurance
Oversight, Centers for Medicare and Medicaid Services

Open letter to America’s retailers, especially those with pharmacies from leading public health and medical organizations

Legislation, Policy

To view as PDF click here. 

Open Letter to America’s Retailers, Especially Those with Pharmacies

From Leading Public Health and Medical Organizations

February 26, 2014

As organizations committed to ending the tobacco epidemic in the United States, we applaud the bold decision by CVS Caremark to eliminate the sale of cigarettes and other tobacco products in all its stores. We urge other retailers, especially those with pharmacies, to move quickly to end tobacco sales in their stores. CVS Caremark is absolutely right: The sale of tobacco products – the number one cause of preventable death and disease – is fundamentally inconsistent with a commitment to improving health.

As we observe the 50th Anniversary of the landmark 1964 U.S. Surgeon General’s Report on Smoking and Health, the science on tobacco is unequivocal and inescapable. Tobacco products are uniquely lethal and addictive. They rob us of 480,000 American lives each year, sicken millions more and cost the nation at least $289 billion annually in healthcare expenses and other economic losses.

The latest Surgeon General’s report also underscored that tobacco use is a pediatric epidemic – 90 percent of adult smokers start by age 18 or earlier, and 5.6 million children alive today will die prematurely of smoking-caused disease unless all segments of our society join together to take strong action. 

No corporation truly devoted to saving lives – like the nation’s pharmacies are – can continue to simultaneously reap billions in profits from products that kill nearly half of the people who use them. Neither can any corporation committed to the well-being of our nation’s children. 

CVS Caremark’s decision was met with cheers from their customers and the public at large because it is simply the right thing to do. We urge other retailers, especially those with pharmacies, to put our nation’s children and health before tobacco profits and move quickly to end tobacco sales. Such action would reduce the availability and marketing of tobacco products, accelerate progress in reducing tobacco use and ultimately help end the tobacco epidemic for good. 

Respectfully,


American Association for Respiratory Care
American Association for Cancer Research
American Academy of Otolaryngology—Head and Neck Surgery
American Academy of Pediatrics
American College of Cardiology
American Congress of Obstetricians and Gynecologists
American Lung Association
American Public Health Association
American Society of Clinical Oncology
American Thoracic Society
Americans for Nonsmokers’ Rights
Action on Smoking & Health
Campaign for Tobacco-Free Kids
Cancer Prevention and Treatment Fund
CASA Columbia
Legacy
LIVESTRONG
Lung Cancer Alliance
National Consumers League
National African American Tobacco Prevention Network
National Association of City and County Health Officials
National Latino Alliance for Health Equity
National Physicians Alliance
North American Quitline Consortium
Oncology Nursing Society
Partnership for Prevention
Smoking Cessation Leadership Center
Trust for American’s Health

Statement of Laurén Doamekpor on the importance of including women, minorities, and the elderly in studies of the safety and effectiveness of new drugs and devices (FDASIA section 907 hearing)

Policy, Testimony & Briefings,
April 1st, 2014

My name is Laurén Doamekpor, a senior fellow speaking on behalf of the National Research Center for Women & Families and our Cancer Prevention and Treatment Fund. Thank you for the chance to speak today.

Ourresearch center evaluates data and provides objective health information to patients, providers and policy makers. We strongly support the inclusion of women, racial and ethnic minorities, and the elderly in clinical trials for drugs and devices.

The Section 907 report reveals that there is more work to be done to achieve greater diversity in clinical trials.  We believe that the key question today should be: what can the FDA do to ensure:

  1. greater diversity in clinical trials submitted to FDA,
  2. subgroup analyses submitted to the FDA
  3. Information from subgroup analyses are used as a basis of approval and labeling decisions, and made widely available in a user-friendly format to providers, patients, and other stakeholders.

The responsibility of collecting sufficiently representative demographic subgroup data sits solely on the shoulders of device and drug companies. The companies know how to persuade – they do it everyday in commercials.  Similarly, if they identify persuasive incentives for patients to participate in studies, and minimize disincentives, patients will participate and be available for follow-up.

The FDA’s crucial role is to hold companies accountable. The FDA guidance regarding diversity and subgroup analyses is regularly ignored by companies, and unfortunately FDA then approves their drugs and devices anyway.  If the FDA’s actions clearly showed that sponsor applications will be rejected — or perhaps approved for White men under 60 only — if companies do not include the relevant demographic data and conduct the necessary subgroup analyses – we are confident that companies will find a way to comply.

To successfully persuade companies to conduct subgroup analyses for the major subpopulations that will use their products, the FDA must consistently demonstrate that they believe those data are essential for proving safety and efficacy.

This is essential because research tells us that naturally occurring genetic variations may influence the way certain drugs are metabolized and work in women compared to men, older patients compared to younger, and certain racial and ethnic groups. Currently, the main challenges in conducting subgroup analyses is that the sample sizes are too small, and get miniscule when age and race and sex are all considered.  We understand that not every ethnic group or age group can be separately analyzed. However, we disagree with the assumption that it is not feasible to power studies to detect subgroup differences. It can be done, and should be done for major subgroups. If the FDA required this practice and held companies accountable, companies will find a way to achieve this.

Our Center participates in many FDA Advisory Committee meetings, and rarely is the lack of diversity in clinical trial data mentioned for more than one second by anyone other than us.  When the FDA’s clinical summaries provided to Advisory Committee members and the public, do not criticize the lack of diversity or lack of subgroup analyses, the FDA sends the message that safety and efficacy for all subgroups are not important.

In the last week, for example, we spoke at one FDA Advisory Committee meetings for a drug for heart failure and 2 for drugs forMRSA. Heart failure is the #1 killer of men and women of all races in the U.S. and MRSA disproportionately harms minority patients.  However, African American patients comprised less than 5% of the cardiac drug trial and less than 6% for one of the MRSA drugs.  NONE of the companies did subgroup analyses for all the primary and secondary endpoints. The lack of data was similar for Hispanic patients.

And, although many of these drugs are used primarily on elderly patients, few patients over 65 were included.  For one of the MRSA drugs, only one analysis of efficacy for patients over 65 was conducted and it clearly showed that the new drug was less effective than the comparison drug.  But, the FDA didn’t even mention that in their summary and the Advisory Committee recommended approval of the drug for all adults over 18 anyway.

On the rare occasion when our concerns about diversity inspires Advisory Committee members to speak up, the result is usually a recommendation to achieve better diversity in the post-market study.  Unfortunately, companies rarely do better in post-market studies, because the incentives to please FDA weaken greatly once their drug or device has already been approved for the general population.

In addition to showing companies that they must achieve diversity and conduct subgroup analyses, there is another action that the FDA should take.  FDA should gather information comparing recruitment and retention strategies from companies that are achieving greater and lesser diversity in their trials to determine which strategies are successful, and share that information with companies that need to improve.

Ultimately, patients and providers need to know whether subgroup data were collected, what the findings are, and how scientifically solid those results are. This information is essential for providers and patients to make well-informed medical decisions. The FDA should require that subgroup data be provided on labels and promotional efforts, using wording that is easy to understand by patients and providers.

Again, thank you for the opportunity to speak at this meeting. We hope that you will incorporate our comments and recommendations into the Action Plan.

 

2014 Foremother and Health Policy Hero Awards Luncheon

Uncategorized

To view invitation as PDF, click here.

flowers

 

The National Research Center for Women & Families

Cordially Invites You to Our

2014 Foremother Awards and Health Policy Hero Luncheon 

Friday, May 9, 2014 at Noon 

The Mayflower Hotel

1127 Connecticut Avenue, NW, Washington, D.C. 

Join ABC7/WJLA’s Maureen Bunyan, our Mistress of Ceremonies, on May 9th, the Friday before Mother’s Day, at the elegant Mayflower Hotel in Washington, D.C. as we celebrate our 15th anniversary as a national charity and honor our 2014 Foremothers.

  •  Irene Pollin has dedicated her life to improving the lives of others, as a psychiatric social worker, writer advocate, and philanthropist. She is the founder and chairperson of Sister to Sister: The Women’s Heart Health Foundation, the first organization to address the public health crisis that heart disease is the #1 killer of women. Sister to Sister has provided more than 100,000 free heart health screenings and counseling nationwide.  With her late husband, Abe, the Pollins co-owned the Washington Wizards and the Washington Capitals, and together helped revitalize Washington, DC through philanthropy, public service, and an unwavering commitment to the community.
  • Phyllis Reynolds Naylor is one of our nation’s most beloved authors of children’s and young adult fiction, best known for her trilogy Shiloh (a 1992 Newbery Medal book about a young boy and an abused dog) and for her Alice books, about a motherless girl looking for a role model while fumbling through adolescence, with the final book highlighting her life from ages 18-60. The Alice books have been praised and criticized for their realistic portrayal of the life of a teenage girl.  Naylor has written more than 135 books, many receiving awards as well as special recognition by the American Library Association and the International Reading Association, and as selections for the Junior Literary Guild.
  •  The Honorable Louise Slaughter is a powerful and unique Member of the U.S. House of Representatives. Serving her 14th term, Rep. Slaughter takes on the fights no one else will.  She co-authored the historic Violence Against Women Act and is now on the forefront of fighting sexual assault in the military.   As the only Member of Congress with a degree in microbiology, she has played a central role in the major health and science issues of our time, achieving landmark legislation such as federal funding for research on DES, the inclusion of women and minorities in clinical trials, and increased federal funding for breast cancer.  She is the original author of the Genetic Information and Non-Discrimination Act (GINA), which became law in 2008, and the  Preservation of Antibiotics for Medical Treatment Act, which would drastically reduce the epidemic of antibiotic resistance.

Our two health policy heroes are ProPublica’s Charles Ornstein and Tracy Weber, whose investigative series of articles delineating Medicare’s reimbursement for doctors prescribing massive quantities of inappropriate medications, and wasting billions on needlessly expensive drugs has resulted in Medicare broadening its powers to reduce fraud, waste abuse, and harmful prescriptions.

We hope you will take advantage of this great opportunity to meet these inspiring individuals, previous Foremother and health policy here honorees, and many of D.C.’s other movers and shakers.   Lunch is from noon to 1:30, preceded by a champagne reception for honorees and patron guests.

Seats are limited and tickets are not available at the door.

Regular lunch tickets are available for a donation of $100 each. Patron Tickets ($175 per ticket) include a champagne reception with honorees at 11:30, priority seating, and a listing in the program.  A table for 10 is $1600. Sponsorships are available, from $1,000-$5,000.

The National Research Center for Women & Families is the leading national organization dedicated to improving the health and safety of all adults and children. Donations for this event support our Cancer Prevention and Treatment Fund hotline.

To reserve a ticket, you may donate online at center4research.org and click “Make a Donation” (write “Awards Luncheon” in the comments box and be sure to provide contact information). Or, send a check payable to “NRC,” to 1001 Connecticut Ave, Suite 1100, Washington, DC 20036. For more info, contact Maura Duffy at md@center4research.org or (202) 223-4000.

 

For photos and information about previous Foremother and Health Policy Hero Awards Luncheons, click here.

The Cancer Prevention and Treatment Fund Responds to CDC study on Camp Lejeune Drinking Water Health Hazards

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By Anna E. Mazzucco, PhD and Diana Zuckerman, PhD, President of the Cancer Prevention and Treatment Fund
Updated March 24, 2014

The contaminated water at the Camp Lejeune Marine Corps base is a national disgrace that has jeopardized the health of many adults and children. Now the government’s focus needs to be on assisting all those who have been harmed – and that should include preventing cancer and other diseases in those who are not currently sick but at risk because of their exposure years ago. Righting the wrong that was done to our armed service families requires more than research and passing the buck – it requires a plan of action based on solid scientific information.

The Cancer Prevention and Treatment Fund expresses its strong support for the adults and children who have been harmed by contaminated drinking water at Camp Lejeune Marine Corps Base.  This unprecedented environmental disaster has been a tragic disservice to the courageous men and women of our military.

The new analysis by the Centers for Disease Control and Prevention indicates that pregnant women who were more exposed to contaminated drinking water at Camp Lejeune were 4 times as likely to give birth to children with serious birth defects such as spina bifida, compared to women who were less exposed.  There was also a slight increase in childhood cancers such as leukemia among these children.  A study published (reported) in 2014 found increased risk of death among Camp Lejeune residents from several cancers including kidney, liver, cervical, esophageal, multiple myeloma and Hodgkin lymphoma, in comparison to residents of another military base which did not have contaminated water.  Previous reports have indicated that men living or working on the base from the mid-1950s until 1987 were much more likely to develop breast cancer than men in the general population, but that study has not yet been completed.  Breast cancer is a rare occurrence among men, and is especially dangerous because men often do not recognize the symptoms or seek treatment in a timely manner. In addition, men with breast cancer often experience unique and significant physical, social and psychological issues.

The Cancer Prevention and Treatment Fund is dedicated to helping children and adults reduce their risks of getting all types of cancer, and assists them in choosing the safest and most effective treatments. We use research-based information to encourage more effective programs, policies and medical treatments. We strongly urge the federal government to continue investigating the link between exposure to trichloroethylene (TCE) and other known contaminants in the Camp Lejeune drinking water, and an increased risk for diseases among children and adults.  It is likely that the exposures could cause several different types of cancer, but those other cancers would not be as noticeable as male breast cancer, since that is so rare.

Testimony of Dr. Anna E. Mazzucco on HPV test

Testimony & Briefings
March 12, 2014
by Dr. Anna E. Mazzucco

My name is Dr. Anna Mazzucco, and I thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund.   After completing my Ph.D. in Cell Biology at HarvardMedicalSchool, I conducted research at the National Cancer Institute.  Those are the perspectives I bring today.  Our organization does not accept funding from medical device companies, and therefore I have no conflicts of interest.

The question today is whether HPV tests should be the first-line screening tool for cervical cancer.  This would be a significant departure from current recommendations of the CDC and US Preventive Services Task Force as well as ACOG, ACS and AAFP.

Currently, HPV tests are recommended ONLY for co-testing with a Pap smear and only for  patients 30 and older.  Those recommendations are based on clear evidence as well as common sense because we all know that HPV usually goes away by itself, and encouraging colposcopies for young women based on HPV tests, if those women are sexually active with multiple partners, would result in a lot of unnecessary, invasive treatment with no real benefit.

What is the sponsor’s proposal based on?   In their study, the comparator arm triaged ALL abnormal cytology ASC-US or higher with immediate colposcopy.  That does NOT reflect current practice.  6% of all women in the trial had abnormal cytology at baseline, so this strange clinical trial design resulted in an artificially high colposcopy rate in the comparator arms.

Manipulating the control arms in that way made it seem that the proposed indication didn’t increase the percentage of colposcopies.  But, we can’t trust that result because of the FLAW in the research design.

We have other concerns as well:

  • Current, the Roche cobas test is approved to use the same sample vial as the Pap test.  As FDA points out, this cytology is also used to diagnose candida and trichomonas infections, herpes viral changes, atypical repair, and abnormal endometrial cells.  The HPV test can’t identify ANY of those.  Therefore, eliminating the Pap smear every 3 years would result in losing that important information which is currently easily obtained from the same Pap smear sample at little additional cost.  This will put women at risk.
  • Most cervical cancers occur in women who have never been screened or were not screened in the last five years.   What is needed is to increase patient compliance with screening.  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 undergoing immediate colposcopy, which is more expensive AND more unpleasant than a Pap smear.  This is likely to reduce the chances of patients undergoing screening.   In this trial, for example, 14% of the patients were lost from the baseline colposcopy.
  • Colposcopy often results in biopsy, which can result in subfertility, pre-term labor, and perinatal death.  These are risks that are unnecessary but directly result from the sponsor’s plan.
  • The sponsor states that “Current U.S. screening guidelines already consider both cytology and HPV 16/18 genotyping to be established approaches to determining which HPV positive women require colposcopy”.   That is very misleading.  In fact, the US Preventive Services Task Force gives a “D” rating for HPV testing in women under age 30 because the risks outweigh the benefits, as shown in previous clinical trials.
  • The sponsor compares their proposed indication to other algorithms, but only relative to detection of CIN2 orCIN3.  Per10,000 women, the Candidate arm only detected 15 more cases >= CIN3, and 3 more cases of CIN2.  The vast majority of women will never develop CIN2 or CIN3, and CIN2 usually spontaneously goes away within 2 years.  These small benefits do not outweigh the risks of less screening compliance, pre-term labor, compromised fertility, and perinatal death.
  • The Comparator arm triages all cytology of ASC-US or greater with immediate colposcopy.  As the FDA noted, this is no longer current clinical practice.  The 2012 ASCCP guidelines recommend either repeat cytology in one year, or HPV testing, with only a positive result leading to colposcopy.  Similar observations can be made about the alternative comparator arms.  2012 ASCCP guidelines support a 1 year repeat of co-testing ONLY for women 30 or older who are cytology negative but HPV positive before recommending colposcopy.  USPSTF currently only sanctions co-testing for women over 30 who wish to lengthen the screening interval from 3 to 5 years, it does not explicitly prefer co-testing.  In order to accurately weight risks and benefits, we must have a comparator arm which represents current clinical practice and guidelines.
  • Of the patients in this clinical trial, 99% had not received the HPV vaccine, and the median age was 41, with one-third post-menopausal.  Only 6,654 women were between the ages of 25 and 29.  The proposed new indication would pose the greatest risks to young women who hope to have children, so they would need to be studied MUCH more carefully than the sponsor has done.

One last point: the sponsors identify economic and clinical complexities of performing two tests instead of one to justify elimination of cytology.  Economic considerations are outside of today’s considerations, but even if they were, HPV tests cost much more than cytology.  The clinical challenge of dealing with more information, rather than less, is also irrelevant, since the sponsor’s proposal would still often rely in colposcopy and cytology results as well as HPV results for clinical decision-making.

Moreover, to prevent cervical cancer while preserving young women’s ability to have children,  we should not be seeking less information, we should be seeking more information.

The data presented today are too discordant with current clinical practice and cannot be used to justify such sweeping change.  This proposed indication represents a radical shift in clinical practice which would affect millions of women for most of their adult lives.  These proposed indications also encroach on clinical practice, and FDA cannot “establish or recommend guidelines for medical practice.”

We urge the committee to consider the risks to young women and reject the proposed indication.

 

F.D.A. panel recommends replacement for the Pap test

In the News, News Stories & Editorials
BY ANDREW POLLACK, THE NEW YORK TIMES
MARCH 12, 2014

The Pap test, a ritual for women that has been the mainstay of cervical cancer prevention for 60 years, may be about to play a less crucial role.

A federal advisory committee recommended unanimously on Wednesday that a DNA test developed by Roche be approved for use as a primary screening tool.

“Has our Pap, as we know it, outlived its time?” Dr. Dorothy Rosenthal, a professor at Johns Hopkins University, testified to the committee, which advises the Food and Drug Administration. She said deaths from cervical cancer in the United States had stopped declining and that there would be “a tremendous gain” by moving to the new test.

The Roche test detects the DNA of human papillomavirus, or HPV, which causes almost all cases of cervical cancer. Pap testing involves examining a cervical sample under the microscope looking for abnormalities.

Until now HPV testing has been used mainly as a follow-up test when the Pap results were ambiguous, or used jointly with Pap testing.

Wednesday’s 13-to-0 vote — by a committee mainly of academic pathologists, microbiologists and gynecologists — would allow Roche’s test to be used alone as the initial test for women 25 and older.

The Roche test is seen as better than Pap tests in finding precancerous lesions.

The Pap test, which is well entrenched and has been highly successful, will not go away quickly, if at all, however.

Assuming the F.D.A. itself agrees with its advisory committee and approves the new use of Roche’s test, it would become just another option, not a replacement for the older testing regimens. And many doctors will not adopt the new test unless professional societies recommend it in guidelines, which could take years.

Use as a primary screening tool could mean much wider sales of HPV tests. The United States market for such tests is more than $200 million, according to DeciBio, a market research firm.

Qiagen is the leading seller of such tests, with Roche and Hologic and BD also participating. Various laboratories also offer their own tests. But the approval as a primary screening tool would be only for Roche’s Cobas test, which could help it gain market share.

Current United States guidelines recommend that women 30 to 65 undergo either co-testing with both HPV and Pap every five years, or Pap testing alone every three years. Women 21 to 30 are supposed to have Pap testing every three years.

The American Cancer Society estimates that about 12,360 new cases of invasive cervical cancer will be diagnosed in 2014 and about 4,020 women will die from the disease. Between 1955 and 1992, the cervical cancer death rate declined by almost 70 percent, mainly because of Pap testing. The death rate has remained stable in recent years.

HPV testing has advantages over the Pap test. Studies have shown it is much more sensitive in detecting precancerous lesions. Proponents say it is more objective, its results varying less from lab to lab than those of the Pap tests, which rely on the judgments of people viewing slides under a microscope.

The main drawback of HPV testing is that most people get infected with the virus after they become sexually active, although in most cases their immune systems can clear the virus. So many women, particularly young women, would be sent for additional examinations or biopsies that might not be necessary. That is why co-testing with both HPV and Pap is recommended only for women 30 and over.

Roche says it sidesteps that problem because its test specifically detects two subtypes of the virus, known as genotypes 16 and 18, that account for 70 percent of the cancer cases.

In its study, Roche showed that its test outperformed Pap testing alone in various measures, like the ability to detect precancerous lesions. A negative result on the HPV test was also a better predictor than a negative Pap test that a woman would remain free of lesions for the next three years.

Most people who testified to the committee, which met in College Park, Md., urged approval, some saying it was time to move to modern molecular science.

“George Papanicolaou did not know about HPV,” said Lee Shulman, a professor at Northwestern University, referring to the initial developer of the Pap test. He compared replacing Pap smears with HPV testing to the transition from the horse to the automobile.

But there were objectors who said the data was not sufficient to justify such a change.

“The proposed indication represents a radical shift in clinical practice which would affect millions of women for most of their adult lives,” said Anna E. Mazzucco of the Cancer Prevention and Treatment Fund, a patient support and advocacy group.

She said that most cases of cervical cancer were in women who did not undergo screening, not in those whose disease was missed by screening.

While the committee vote was unanimous, some members had reservations about using HPV testing for women under 30. Some said that HPV testing may not be much better, if at all, than the currently recommended use of both tests.

“I think women are going to be well served by having more choices, but it’s going to be very interesting to watch over the next several years as this rolls out,” said Dr. Alan G. Waxman, a professor of obstetrics and gynecology at the University of New Mexico.

June 13th, 2014 Conference "Evidence for New Medical Products: Implications for Patients and Health Policy"

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Co-hosted with Harvard Medical School and the American Association for the Advancement of Science, our conference “Evidence for New Medical Products: Implications for Patients and Health Policy” broke new ground in understanding the public health implications of FDA criteria for approval.  A video is available here. 

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Keynote speaker Congresswoman Rosa DeLauro delivers her welcoming address.