Category Archives: Uncategorized

Diversity in clinical trials

News Stories & Editorials, Uncategorized

We Need Better Clinical Trials

Our president explained to reporters why drugs have to be tested on all kinds of people to know who they work for and who can be harmed by them. Cancer patients deserve studies that include women and men, people under and over 65, and all major racial/ethnic groups.

 

FDA is Chastised Over its ‘Action Plan’ to Diversify Clinical Trial Participation

By Ed Silverman, The Wall Street Journal
August 28, 2014

In response to a law passed two years ago, the FDA was directed to assess the extent to which women and minorities are represented in clinical trials and also devise a plan to bolster their participation. The requirement was made in response to concerns that drugs and devices may often be used by subsets of the population on whom the products were not actually tested.

Well, the FDA released its plan the other day and it was met with what could best be described as faint praise. In particular, a pair of consumer advocacy groups says the biggest issue is that the so-called Action Plan lacks the sort of teeth needed to generate real change. They also complain the plan fails to require drug and device makers to contain specific demographic information in product labeling.

They acknowledged the plan does contain several constructive steps, such as working with drug and device makers to revise product applications with enhanced information on “demographic subgroups;” strengthening FDA reviewer training so the need for demographic data is communicated; improving FDA systems for collecting and analyzing such data; and updating or finalizing guidance for industry.

“The action plan has a lot of good things,” Diana Zuckerman, the president of the National Center for Health Research, tells us. “The problem is there is no incentive for industry to recruit more diverse groups of patients. As long as they continue to test mostly on white men under 65 [years old] and get drugs and devices approved, then they have no incentives” to diversify the pool of trial participants.

What does she suggest? The FDA ought to consider not approving drugs and devices for use in people on whom these products were not tested. As an example, if a drug is tested predominantly on men, then the agency should not endorse widespread use for women. “They need to put some muscle behind their actions. I think if FDA did this,” she says, “then the companies would find they’re able to miraculously find they can recruit all those groups.”

Read the original article here.

Surgery Studies Rarely Use Females

An analysis of papers published in several surgical journals reveals an overwhelming reliance on male subjects and male-derived cells.

By Kerry Grens, The Scientist

August 28, 2014

Sex biases are evidenced in many areas of science—from clinical trials in humans to basic neuroscience studies on animals. Often, male subjects are overrepresented, compromising the generalizability of findings. In a study published in the September issue of Surgery, researchers from Northwestern University analyzed more than 2,300 papers from five surgical journals, finding an overwhelming skew toward investigations involving male-only subjects and cells derived from males.

“Women make up half the population, but in surgical literature, 80 percent of the studies only use males,” Northwestern Medicine vascular surgeon Melina Kibbe, who led the study, said in a press release.

The studies Kibbe and her colleagues reviewed were published in the Annals of Surgery, the American Journal of Surgery, JAMA Surgery, the Journal of Surgical Research, and Surgery from 2011 to 2012. About a quarter of the studies involved animals or cells. Just 3 percent of the total reported using both male and female subjects or cells, while another 22 percent did not state the sex.

According to the release, “editors of the five major surgical journals reviewed in this study have responded to this finding and will now require authors to state the sex of animals and cells used in their studies. If they use only one sex in their studies, they will be asked to justify why.”

Although sex disparities in clinical trials have received considerable attention, such human studies still suffer from unsatisfactory diversity. Last week, for instance, the US Food and Drug Administration (FDA) released an action plan to address the need for more women and minorities in clinical trials. The Wall Street Journal’s Pharmalot blog pointed out that the plan was met with “faint praise,” lacking “the sort of teeth needed to generate real change.”

Speaking with MedPage Today, Diana Zuckerman, the president of the National Center for Health Research, said: “As long as the FDA is going to approve these products for everyone, when they haven’t been studied on everyone, then the [pharmaceutical] companies really have no incentive to improve.”

Read the original article here.

Free patient booklet on ductal carcinoma in situ (DCIS)

Breast Cancer, In the News, news-you-can-use, Uncategorized

To view, download, or print a free copy of our patient booklet, here is a PDF of DCIS: What You Need to Know.

The Cancer Prevention and Treatment Fund has developed a free, easy-to-read 32-page color booklet for women diagnosed with ductal carcinoma in situ (DCIS). It explains DCIS and commonly used medical terms in plain language and helps women make informed decisions about their treatment.

If a woman has a particularly low-risk type of DCIS, she may choose “active surveillance” instead of surgery and other treatment. Active surveillance consists of closely watching the patient’s DCIS to make sure it does not develop into breast cancer. The patient can choose surgery and other treatments if the DCIS develops into breast cancer, or if she decides she wants surgery for any other reason. Another option for women with particularly low-risk types of DCIS is to take the hormone pills tamoxifen to prevent breast cancer, rather than surgery.

Experts estimate that at least half of all women diagnosed with DCIS would never develop breast cancer even if they never received any treatment for their DCIS. Since no one knows for sure which women with DCIS will develop breast cancer and which won’t, most women with DCIS choose to get some form of surgery. This booklet focuses on helping women decide what kind of surgery to get and what other kinds of treatment they might want or need.  Patients should keep in mind that if their physician tells them that they have a particularly low-risk type of DCIS, they may want to consider active surveillance or tamoxifen only, rather than surgery in addition to other treatments.

The current booklet was approved and funded by a grant from the D.C. Cancer Consortium through the Department of Health, Government of the District of Columbia, and a grant from the Jacob and Hilda Blaustein Foundation.  To request copies of the free patient booklet, write  info@stopcancerfund.org   or call    202-223-4000.

We are currently updating the booklet to include information about active surveillance. 

Testimony of Dr. Anna E. Mazzucco to FDA advisory committee on olaparib

Testimony & Briefings, Uncategorized
June 25, 2014

Thank you for the opportunity to speak today on behalf of the Cancer Prevention and Treatment Fund. My name is Dr. Anna Mazzucco, and after completing my Ph.D. in Cell and Developmental Biology from Harvard Medical School I conducted research at the National Cancer Institute. I speak from those perspectives today.

Our nonprofit organization conducts research, scrutinizes data in the research literature, and then explains the evidence of risks and benefits to patients and providers.  Our president is on the Board of Directors of the Alliance for a Stronger FDA, which is a nonprofit dedicated to increasing the resources that the FDA needs to do its job.  Our organization does not accept funding from pharmaceutical companies, and therefore I have no conflicts of interest.

Maintenance therapy for ovarian cancer patients is vital to extending the recovery time between chemotherapeutic regimens and preserving the efficacy of those agents.  Under consideration today is whether there is sufficient evidence at this time to approve olaparib for a maintenance therapy indication for platinum-sensitive high-grade relapsed serous ovarian cancer.

The goal of maintenance therapy is to extend the time between therapeutic intervals with an optimal risk-benefit ratio.  Otherwise, these patients would not be taking any medication during this time and need this period to recover before additional chemotherapy is needed.  Therefore safety, efficacy, and quality-of-life measures are defining features of maintenance therapy.

Afterreviewing the study evidence, we have three major concerns about olaparib, which were also raised by the FDA.

Firstly, we are concerned about the reliability of the progression-free survival benefit of olaparib, especially since there was no improvement in overall survival during Study 19.

Secondly, we are concerned about the safety profile of olaparib in the context of maintenance therapy. Olaparib-treated patients were almost twice as likely to experience a serious adverse event, in addition to the potentially elevated occurrence of myelodysplastic syndrome orAML.

Lastly, we are concerned that there is not enough evidence of efficacy and low toxicity to ensure that use of olaparib will not compromise patient response to subsequent therapy, which is critical to successful maintenance therapy.

Previous studies of first-line therapy for ovarian cancer suggested that progression-free survival can be predictive of overall survival.  However, a recent paper by the Society of Gynecologic Oncology cautioned against extrapolation of progression-free survival to presumed overall survival benefit in the context of prolonged post-progression survival and multiple lines of treatment.

I’m sure we all agree with the FDA that overall survival is clearly the most significant efficacy measure.  Progression-free survival may only be an acceptable efficacy endpoint when certain criteria are met.  These criteria include low toxicity and efficacy which is both truly predictive of clinically significant benefit and is of robust magnitude, in this particular case, an extension of progression-free survival by six months or more.

Given these stipulations, the seven month extension of progression-free survival in gBRCAm patients may meet a minimal efficacy threshold, but there are strong concerns about the reliability of this observed effect.  In the exploratory analysis conducted by the FDA within the placebo arm, the gBRCAwt/vus population unexpectedly had a superior progression-free survival outcome when compared to the gBRCAm population.  This suggests that the placebo-treated gBRCAm population may have “underperformed”, meaning that the progression-free survival improvement observed in the gBRCAm population may be overestimated.  The SOLO-2 trial currently underway is powered to precisely detect changes in the hazard ratio.  That data is critical to clarifying the potential progression-free survival benefit of olaparib due to this uncertainty.

While the patient-reported FACT-O quality-of-life measures did not indicate detriment, there were significantly increased adverse events with olaparib treatment, including a 2-fold increase in nausea, a 4-fold increase in anemia, a 2-fold increased incidence of various infections, and a near 2-fold increase in gastrointestinal disorders.

As the FDA stated, the patient-reported measures may not capture all possible negative effects of olaparib treatment, and any reported improvements could also reflect cessation of previous platinum treatments.

In addition, approximately four times as many patients in the olaparib-treated arm versus the placebo-treated arm underwent dose reductions, and about six times as many underwent dose interruptions due to adverse events.  Many adverse events also lasted longer in the olaparib-treated arm. There were ten adverse event categories which lasted more than a month longer for olaparib-treated patients, including abdominal, joint, musculoskeletal pain and nausea.  For these reasons, we are concerned that olaparib does not meet the low toxicity and quality-of-life parameters that are essential in the maintenance therapy setting.

The ongoing phase III SOLO-2 trial has the potential to clarify the potential progression-free survival benefit of olaparib, in addition to providing an additional analysis of overall survival and quality-of-life measures.

The results of SOLO-2 are needed In order to be able to guarantee patients an effective maintenance therapy that is not likely to jeopardize their quality-of-life and overall prognosis.  Therefore, we urge the committee to delay approval of olaparib until sufficient evidence has been provided.

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

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.

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

news-you-can-use, Uncategorized

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. 

harvard_medical

AAAS logo

Rosa
Keynote speaker Congresswoman Rosa DeLauro delivers her welcoming address.

 

Fast Facts: Should you get screened for Lung Cancer?

Uncategorized, ,

For our in-depth article on lung cancer screening, click here.

By Tiffanie L. Hammond, Amrita Ford, MA, and Anna E. Mazzucco, Ph.D.
January 2014

Lung cancer is the second most commonly diagnosed cancer in both men and women in the U.S., but it is the #1 cancer killer. In 2013, approximately 228,000 men and women were diagnosed with lung cancer and close to 160,000 men and women died from it.  One of the reasons lung cancer is so deadly is that symptoms usually appear during the later stages, when treatment is least effective. General symptoms include:

  • a persistent cough that may worsen over time, including coughing up blood
  • breathing trouble, such as shortness of breath
  • chest pain
  • raspy or hoarse voice
  • frequent lung infections, such as pneumonia
  • extreme and constant fatigue
  • unintentional weight loss

If you experience any of these symptoms, call your doctor.

The purpose of screening for cancer is to diagnose it before symptoms appear, when it can be treated more effectively.  In July 2013, the U.S. Preventative Task Force (USPTF) released a draft recommendation for screening those at highest risk for lung cancer using low-dose computerized tomography scans (low-dose CT), which was finalized in December.  CT scans provide very detailed pictures of your lungs, much more detailed than x-rays. Researchers found that using low-dose CT scans could reduce lung cancer deaths by 20%.  People who should be screened include:

  • Current smokers between 55 and 79 years-old who have a smoking history of “30 pack-years” (20 cigarettes a day for 30 years, 40 cigarettes a day for 15 years, and so on)
  • Former smokers (who quit in the last 15 years) who are between 55 and 79 years-old and had a “30 pack-year history of smoking.

 

To calculate your pack years, visit http://smokingpackyears.com/.

This draft recommendation was finalized at the end of 2013. Already insurance companies are covering the cost of the screening, as long as the person meets the screening criteria.

As with any screening, there are risks as well as benefits. Some of the risks include radiation exposure and a high rate of false positive test results—test results indicating that a person has something worrisome in their lung that turns out to be nothing serious. Some experts call this “over-diagnosis.” In the largest study done so far, about 1 in 4 people had a false positive finding if they had three years of annual screening.  A false positive finding can lead to invasive procedures, such as needle biopsies, which can puncture the lung and cause it to collapse.  Although very serious complications are rare (less than one in 1,000), they can occur.  Even low-dose CT scans of the lungs expose patients to much more radiation than a chest x-ray. There is almost no short-term risk from this radiation, but having many x-rays or several CT scans can increase a person’s risk of cancer. A 2012 law increased funding for lung cancer research to promote better detection and treatments in the future.   Research is also being done to find ways to reduce the number of false-positives and unnecessary follow-up procedures.

For more detailed information about lung cancer risk factors, symptoms, detection, and CT screening, including the risks of radiation and over-diagnosis, see this article.

Comments of the Cancer Prevention and Treatment Fund on FDA draft guidance to industry on Acrylamide in foods

Testimony & Briefings, Uncategorized, , ,
January 14, 2014

The Cancer Prevention and Treatment Fund strongly supports the Food and Drug Administration in its efforts to advise industry on reduction of acrylamide in food products.  The Grocery Manufacturers Association estimates that acrylamide is present in approximately 40% of the total caloric intake in a typical American diet.1 Given this near-ubiquity, and the fact that the chemical reaction which produces acrylamide also produces commercially desirable color, taste and texture characteristics, reduction of acrylamide represents a challenge.  However, the evidence of possible human harm necessitates its treatment as a significant public health issue. While this report represents an important step in FDA regulation of acrylamide and suggests many possible acrylamide reduction methods, we are concerned that this guidance is not specific enough in providing clear and concrete recommendations that can be implemented.  Although FDA guidance does not have the force of law or regulation, the addition of terms such as “when feasible” implies that the FDA is not serious in its efforts to persuade companies to substantially reduce acrylamide.  FDA monitoring of acrylamide in 2002 indicated wide variation even among products from the same food category –as much as 5 or 10 fold differences in several categories.  This is clear evidence that significant acrylamide reduction can be accomplished without losing desirable product qualities. Thus, although there is clearly much room for improvement, this report contains few immediately implementable guidelines for industry. Since 2002, it has been known that acrylamide is created in food products as the result of a reaction between carbohydrates and the amino acid asparagine at high temperatures during browning (i.e., the Maillard reaction).2  In addition to its known neurotoxic properties, both animal toxicology and human epidemiological studies suggest that acrylamide may be cancer-promoting, which has led to its carcinogen classifications by EPA, NTP and IARC.3,4,5,6 Higher dietary acrylamide consumption has been associated with increased risk of endometrial, ovarian, pancreatic, renal and possibly breast cancer.7,8,9,10.  Acrylamide is already regulated in drinking water and was classified by EPA as “likely to be a carcinogen to humans” and was classified by the National Toxicology Program as “reasonably anticipated to be a human carcinogen,” both more than a decade ago.  The European Food Safety Authority has been overseeing acrylamide monitoring within the European Union since 2007, and the European Commission has set recommended indicative values for acrylamide in food products, providing a quantitative framework for both assessment of reduction efforts and investigative action.  This is a very important health issue and we strongly urge the FDA to intensify its efforts and assert leadership of both the national and international efforts to regulate acrylamide and ensure public safety. Our areas of specific concern are the following:

  • While encouraging manufacturers to conduct their own testing, FDA should update and expand its own monitoring efforts.  Monitoring of acrylamide in food products over time is needed for any reduction efforts to be assessed and successfully implemented.  The current FDA monitoring strategy tested only several hundred foods in four geographic regions annually between 2002 and 2006, and the last publicly available information is from 2006.11  Given the wide range of acrylamide levels even within a single food category, more extensive and up-to-date monitoring is needed to adequately evaluate acrylamide levels and the success of reduction methods.
  • While this report encourages manufacturers to monitor acrylamide levels, it does not give any specific values which should prompt corrective efforts.  Without such guideposts, monitoring alone is unlikely to result in significant reductions.  Recommended target values or action levels, together with active monitoring, will allow FDA and manufacturers to directly access efficacy of reduction efforts and trigger investigation when needed.  The European Commission has set indicative values for acrylamide in food products, including separate values for products intended for infants and young children, and these values are intended to be gradually reduced.12  Indeed, these indicative values have been broadened to include more specific categories and some have already been lowered since their release in 2011, and the European Food Safety Authority is currently conducting a risk assessment at the request of the European Commission to determine if current recommendations are sufficiently protective.  Such a system provides a quantitative framework for reduction efforts and allows increased surveillance of items of special health importance.  Values at least as low as the 2013 European Commission indicative values should be adopted, with the shared intent of gradual lowering of these values as reduction efforts improve.
  • Without accurate and affordable detection techniques, manufacturers are unlikely to measure acrylamide in their products, especially when participation is voluntary.  This guidance encourages manufacturers to be aware of acrylamide levels in their food products.  This is a crucial step towards evaluating reduction efforts.  However, this vital imperative is followed by a discussion of both the technical limitations and expense associated with current methods of acrylamide detection.  While FDA has committed to improving these techniques, they remain costly and fraught with technical limitations, making widespread voluntary use, especially by small manufacturers, unlikely.  FDA should continue to investigate means to improve acrylamide detection and make specific recommendations to industry regarding best possible techniques in order to facilitate participation in monitoring.  As an example, the European Commission has recently set measurement uncertainty (MU) values and tasked the European Committee for Standardisation (CEN) with analytical standardization of LC-MS and GC-MS for acrylamide detection.  Such efforts, in addition to adoption of standard references, will increase consistency and improve confidence in acrylamide detection efforts.
  • In this guidance, the FDA specifically states that it does not intend to recommend one method over another.  This is unfortunate because it leaves both guesswork and legwork to industry.  FDA states that “this guidance is intended to suggest a range of possible approaches to acrylamide reduction and not to identify specific recommended approaches.”  The role of federal agencies should include evaluating reduction approaches to determine which are more efficacious and feasible than others, and providing that potentially useful information to industry, even if only to help identify and encourage prioritization of those approaches first, in addition to continuing research in this area.  Clear communication of superior and cost-effective approaches to acrylamide reduction may result in higher industry participation and more successful reduction efforts.
  • FDA monitoring since 2002 has shown that many foods contain higher levels of acrylamide than the level considered safe by the EPA for drinking water.  Some of the highest acrylamide levels are found in potato and cereal products which are common in the American diet.  These surveys also show that a healthy diet which includes whole grains can have significant acrylamide levels, potentially even higher than a diet which includes less healthful choices such as potato chips and French fries.  The FDA has maintained its message to consumers that a balanced, healthy diet is a way to manage concern over acrylamide consumption, when the evidence shows that this advice is not accurate. 
  • The effects of acrylamide reduction on overall product nutrition should be considered in the context of all health risks and benefits.  For example, lower temperature frying reduces acrylamide, but also requires longer cooking time, resulting in higher fat content in fried foods.  While we commend thorough consideration of all possible health implications of acrylamide reduction methods, FDA should also consider which outcomes can be more easily mitigated by other dietary or lifestyle interventions in order to fully assess risks and benefits.

Lastly, as acrylamide accumulates in food as a result of the handling and cooking process, rather than in the raw food itself, and is a serious human health concern, it could be viewed as source of food adulteration and regulated as such under Section 402(a) of the Federal Food, Drug and Cosmetic Act with action levels.  We ask that FDA consider these improvements to this draft guidance, and use its full authority to ensure that the public is sufficiently protected.

The Cancer Prevention and Treatment Fund

 For additional information, contact Anna Mazzucco at am@center4research.org or (202) 223-4000.

Statement of Dr. Diana Zuckerman before the FDA Advisory Committee Regarding Dapagliflozin (Farxiga)

Testimony & Briefings, Uncategorized
By Diana Zuckerman, Ph.D.
December 12, 2013

Thank you for the opportunity to speak today.  I’m Dr. Diana Zuckerman. I’m president of the Cancer Prevention and Treatment Fund.

Our center is dedicated to improving the health and safety of adults and children, and we do that by conducting and scrutinizing research and explaining the findings to health professionals, patients, and the general public.   Our non-profit center does not accept funding from pharmaceutical companies, so I have no conflicts of interest.

Today I am speaking from my perspective as someone trained in epidemiology at YaleMedicalSchool. I also was on the faculty at Yale and at Vassar and conducted research at Harvard, and was a fellow at the Center for Bioethics at the University of Pennsylvania.  I’ve also discussed the data with an expert on our staff who previously worked at NCI, Dr. Anna Mazzucco.  I’m putting together all of those perspectives, as well as having worked for the U.S. Department of Health and Human Services, as a consultant to the Institute of Medicine., and as someone with several close family members with diabetes, one of whom died from the disease..

My concern about this drug is that there are just too many unanswered questions – and those unanswered questions are frightening ones.  That was true when the FDA rejected this application for approval 2 years ago, and it is still true today.

Question #1: How well does it work?

The results indicate that DAPA is NOT effective for patients with moderate to severe renal impairment.  As the FDA has noted, 20-40% of diabetes patients have compromised renal function.

DAPA is better than placebo but does not provide a significant improvement over currently available drugs.  Specifically, glipizide was superior in the short-term and comparable to DAPA at week 52.

So, in the context of these limited benefits what are the risks?

FDA stated that the animal studies conducted could not rule out the possibility that dapagliflozin contributes to bladder cancer.   We completely agree.  Experiments done using cell lines and tumor models which are not implanted in the bladder cannot answer questions about the risks to humans.  Because in humans, changes in the bladder microenvironment or urine flow may be most relevant to carcinogenesis.  FDA has already suggested use of an appropriate animal model which could address these concerns, specifically a “a (BBN) chemically-induced rodent bladder cancer model (4-hydroxybutyl(butyl)nitrosamine).

Why didn’t the company do the right kind of animal study?  That’s an important question to keep in mind.  But, until the correct type of animal studies are done, DAPA must be considered a possible cause of bladder cancer.  Since other effective diabetes drugs are already on the market, and those drugs are more effective for more patients, bladder cancer is an unacceptable risk.

But bladder cancer isn’t the only concern.  What about breast cancer?  The FDA consultant gave several reasons why DAPA is unlikely to have caused the breast cancers that were observed.

These reasons included:

  • short treatment time prior to onset,
  • the decline in incidence risk ratio over time, and
  • the fact that the breast cancers were estrogen receptor positive.

 

Let’s start with the short treatment time before onset.  We all know that cancer usually takes years to develop.  So, it would be easy to assume – or perhaps hope – that the increase in cancer happened by chance.  But wishful thinking isn’t enough.  We need to know.

When the percentage of women taking hormone replacement therapy for menopause dropped dramatically, the rate of new cancers in the U.S. went down for the first time ever.  Experts in the field agree that this unexpected quick effect was because of the drop in use of hormone therapy.  So, we know from that experience that even a slow growing cancer can be stimulated by a drug.

We challenge the other 2 assumptions as well.  Hormone receptor status is irrelevant because the potential mechanism for this drug to cause breast cancer is unknown.  It is entirely possible that dapagliflozin could act in multiple biological pathways, including hormone receptor signaling, or in a biological pathway that is common to breast cancers regardless of hormone receptor status.

Similarly, long-term biological responses to dapagliflozin and potential feedback mechanisms in breast tissue are also unknown.  Thus, the decline in incidence risk ratio over time doesn’t mean the drug is safe — because the body could respond differently to dapagliflozin over time.

Diabetes and the prior use of hypoglycemic medications were also listed as reasons to doubt potential breast cancer risk, but these factors are common among all patient groups in these trials.

In summary, these arguments cannot rule out the possibility that dapagliflozin causes breast cancer.  The only way to answer this question is with appropriately designed animal models of mammary tumors, or human patients.

Other Safety Issues:

Renal impairment/failure adverse events were associated with dapagliflozin treatment in data based on 13 short-term studies (3.2% in dapagliflozin-treated patients vs. 1.8% with placebo) and the 9-short-term plus long-term studies (6.7% vs. 4.2%) studies.  As many diabetes patients already have compromised renal function, this risk represents a significant health hazard primarily for the patients most likely to receive this drug.

At two different doses, the DAPA patients had elevated LDL levels, while placebo patients did not.  This increase raises concerns that any potential cardiovascular benefits – which are questionable — cannot justify the additional risks.

Lack of Diversity in the Studies

In the entire clinical program, less than 4% of the patient s were African American.  And yet 13% of African Americans have type II diabetes.  They should have been tested if the intent was to approve the drug for all Americans, not just white Americans.

But, given the risks, it would be difficult to justify recruiting African Americans or whites for more research at this time.

When I speak at FDA advisory committee meetings it is always as a scientist, but today I also want to speak on behalf of patients.  My Dad developed diabetes at the age of 90, probably because he took lupron for prostate cancer.   In retrospect, that was probably not a good treatment decision, since prostate cancer is rarely fatal.   It would certainly be ironic if a diabetes patient developed bladder cancer, which is often fatal, or breast cancer, which can be fatal, as a result of taking a diabetes medication that is no more effective, and often less effective, than other diabetes treatments on the market.

It’s hard to imagine a well- informed patient choosing DAPA, but unfortunately, patients are rarely well-informed.   I assume that the physicians on this panel would clearly and carefully inform their patients of the risks of this drug, but in the real world, many doctors won’t be well-informed because the company that makes DAPA is telling doctors very clearly that DAPA is safe and does NOT cause cancer, when the truth is we don’t know, but it might.

We can’t solve this with a black box warning on a label, because many doctors and patients don’t read the labels.  We can’t ethically rely on post-market studies, because it would not be ethical to prescribe this medication with all these unanswered questions.

I sympathize with the companies’ repeated efforts to get this drug approved, but I wonder why they didn’t do the animal study that the FDA recommended.   And I would not want anyone I care about to take a drug with such serious potential risks when so many alternatives are on the market that do not cause cancer.

Have colon cancer? Skip the hot dogs, deli, and burgers

Colon Cancer, Colon Cancer, Diet, Habits, & Other Behaviors, Uncategorized
Caitlin Kennedy, Ph.D.

New research shows that eating red meat and processed meat increases the risk of colon cancer or of dying from colon cancer. The 2013 Cancer Prevention study by the American Cancer Society has been studying the impact of diet on cancer by following 184,000 patients for 18 years.13

Among the men and women diagnosed with colon cancer, those who ate more than 4 servings per week of red or processed meat before and after they were diagnosed with colon cancer were significantly more likely to die from colon cancer than those who ate fewer than 4 servings per week. Processed meats include deli foods such as hot dogs, sausage, bacon, and bologna, ham and other lunch meats, and bacon. Those who ate more than 4 servings per week had a 79% higher risk of dying from colon cancer compared to those who ate these foods less often. Those who had a family history of colon cancer and ate these foods frequently were especially likely to die from colon cancer.

Remember that “portion” sizes are smaller than what many people typically eat in a meal. For example, 2 hot dogs are considered 2 portions, and one double quarter pound hamburger is considered 3 portions. A large steak could be counted as 3 portions or even more.

Previous research has found connections between eating red meat frequently and an increased likelihood of being diagnosed with colon cancer and other health problems. However, this study is the first to show an increased risk of death from colon cancer.

Bottom line

These very popular foods are more harmful than any of us would like to think. The best way to prevent a variety of health problems, including colon cancer, is to limit red and processed meats in your diet. While the chicken or turkey you make in your oven is fine, the processed chicken and turkey sold at the deli counter or packaged in the supermarket are processed foods. Unfortunately, grilled foods including grilled chicken have also been associated with colon cancer.14 Fish and beans are other healthier sources of protein. If you have a family history of colon cancer, you should be especially careful to eat red and processed meats less frequently. Keep in mind that the American Cancer Society study found an increased chance of dying from colon cancer for men and women who ate these foods either before or after they were diagnosed with colon cancer.

The good news is that it’s never too late to start eating healthy and cutting back on your red and processed meat consumption! Even if someone is already diagnosed with colon cancer, eating less red meat and less processed meat can increase the chances of cancer survival.