Category Archives: Legislation

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

Comments of the Patient, Consumer, and Public Health Coalition on HELP Committee’s Draft Proposal on Pharmaceutical Compounding

Legislation, Policy
May 2013

Chairman Tom Harkin
731 Hart Senate Office Building
Washington, DC 20510

Dear Chairman Harkin:

As members of the Patient, Consumer, and Public Health Coalition, we welcome the opportunity to provide our views on the HELP Committee’s draft proposal on pharmaceutical compounding.

We are very concerned that the draft does not adequately address the public health threats posed by compounding pharmacies and will not do enough to prevent future health care crises.  Although it might reduce the likelihood of the deaths from products made by companies such as NECC, it will do little to protect the health and safety of thousands of patients who are unwitting customers of large compounding pharmacies that sell defective oral drugs to treat cancer or other life-threatening diseases, or that sell large quantities of sterile products within a state.

An example of the types of patients that would not be protected by the draft legislation are the cancer patients who received diluted cancer drugs from a Kansas City compounding pharmacy in 2000.  We are also concerned about compounders that will avoid FDA oversight by limiting their high-volume sales of sterile products to a single state. The risk posed by sterile compounded products, or any other high-risk medical products, does not change based on whether or not the product crosses a state line.

We are concerned that the draft proposal too narrowly defines compounding manufacturers and does not give the FDA adequate authority to regulate compounding manufacturers.

In addition, the draft proposal does not give the FDA access to records of companies that define themselves as traditional compounders, making it next to impossible for the FDA to identify compounding manufacturers that have misrepresented themselves as traditional compounders. This is particularly worrisome because the FDA now attempts to obtain the records and inspect any pharmacy which has been the subject of complaints.  Pharmacies have challenged the FDA in court, but the agency has been able to prevail in some cases.  This legislation could potentially reduce the agency’s current authority.

We strongly urge you to ensure that the final legislation clarifies and enhances the FDA’s authority to regulate compounding pharmacies that have the potential to harm thousands of patients, even if they do not meet all three criteria for non-traditional compounding manufacturers set forth in the current draft version of the bill.

Below are our comments on specific sections of the draft proposal:

Compounding Manufacturer (page 2)

We agree that compounding manufacturers should be regulated by the FDA. However, the definition of compounding manufacturer is too narrow. It requires that entities meet all three of the following criteria: 1. Compounds at least one sterile drug. 2. Compounds before receiving a prescription. 3. Ships (sells) those drugs interstate.

In order to protect the public, the definition of compounding manufacturers should be broader, such as any entity that meets either the 2nd or 3rd criteria.  Sterile drugs are not the only high-risk drugs made by compounders.  Incorrect dosage for non-sterile cancer or other life-safe-giving drugs can be just as deadly, and are almost impossible to detect since drugs for seriously ill patients are not always effective.  Therefore, when a cancer patient or heart patient dies after taking a compounded medication, it is unlikely that anyone will question the medication, and would instead assume that the drug just didn’t work on that patient.

In addition, a compounded antimicrobial drug that is not as potent as it should be will be ineffective and also add to our growing antibiotics resistance problem. By making the definition of manufacturing compounders too narrow, we are setting the stage for future public health disasters.

To protect patients across the country, we strongly believe that compounders who sell across state lines or sell “in anticipation” of prescriptions should be regulated as compounding manufacturers.  This protection is especially essential when compounders sell drugs with the potential to save lives, where defective drugs could result in death or serious injury.

Traditional Compounder (page 3)

The phrase “compounds a drug in limited quantities” needs to be defined.  What does “limited quantities” mean?  A dozen, one hundred, or more?

Drugs That May Not Be Compounded (page 6)

The Secretary needs more flexibility to amend the list as needed.  The bill should specify that the Secretary has administrative authority to update the Do Not Compound List (drugs added or taken off the list) and should not have to seek regulatory authority from Congress whenever a change is needed.

Licensed Pharmacist Oversight (page 18)

What does the term “direct supervision over the operations of the compounding manufacturer” mean?  If a compounding manufacturer produces products 24 hours a day, does that mean a licensed pharmacist will be there at all times, directly supervising?  Or could a licensed pharmacist just set up the operations and rarely be present? We urge you to clarify this definition to ensure robust oversight.

Listing of Drugs (page 18)

We support the six-month look-back on drugs that are made by compounding manufacturers. This allows the FDA to scrutinize them for products that should not be compounded such as commercially available products.

Adverse Event Reporting and Maintenance of Records (page 19)

We support Adverse Event Reporting and Maintenance of Records for compounding manufacturers. However, to truly protect public health, traditional compounders should also be required to report adverse events in a timely manner and maintain records of all serious adverse drug events for 10 years.

Labeling of Drugs (page 20)

The goal of the labeling is to make sure health care professionals and patients know that the drug is a compounded product.  We support the label stating: “This is a compounded drug.” However, the draft proposal adds “or a reasonable comparable alternative statement that identifies the drugs as a compounded drug.” That sentence opens the door for vaguely worded compounded drug labels, which may be misunderstood by patients and healthcare providers.  The alternative statement should either be deleted from the final draft or changed to “a statement that uses language suitable for an 8th grade reading level that clearly identifies the drug as a compounded drug that has not been evaluated by the FDA for safety and effectiveness or compliance with manufacturing and sterility standards.”  In addition, we support the proposed labeling “not for resale” on compounded drugs sold to health care entities (page 17).

Amount of Establishment Fee (page 22)

The establishment fee for compounding manufacturers is designed to cover inspection costs. How was the $15,000 fee ($5,000 for small firms) per drug establishment determined?  Did the FDA suggest this amount?  What is the average cost for the FDA to inspect manufacturing compounders?   Will the FDA have sufficient resources to do their job?

Applications of Inspection Requirements to Compounding Manufacturers (page 32)

The FDA should have access to the records of compounding manufacturers and traditional compounders.  If the FDA cannot review traditional compounders’ records, then it does not have the means to independently verify that the companies are actually traditional compounders.  This lack of access creates a Catch-22.  Unless the FDA can prove the pharmacy meets its compounding definition, it cannot exert oversight.  But it cannot prove the definition without access to records.

This lack of access also will make it difficult for the FDA to respond to complaints it receives about pharmacies, particularly in states where oversight may be lax.

What if the company meets all criteria of a compounding manufacturer but has not registered with the FDA?  At the very least, the FDA should have, upon the receipt of a complaint or evidence that the pharmacy is violating federal law, access to all records and the right to inspect.

Language Missing in the Proposed Draft 

There is no mention of penalties for compounding manufacturers who fail to follow the new regulations. FDA should have the authority to issue substantial civil penalties to serve as a disincentive for any compounding manufacturers that fail to register and pay an establishment fee to the FDA, or that fail to report adverse events within 15 days, and fail to retain records for ten years.  Those penalties must be stringent enough to discourage compounders from considering penalties part of the cost of doing business.

Other suggested revisions to the draft

The draft should make clear that states that wish to ban the sale of certain compounded pharmaceutical products will not be pre-empted from doing so.

The draft should also require a GAO study of the impact of the bill on the FDA’s ability to effectively oversee compounding pharmacies, and address problems swiftly to prevent patient harm.

The draft should require the FDA to warn the public and the compounding pharmacy’s customers of any violations that threaten public health within 24 hours of discovering such violations.

Thank you for the opportunity to comment on this important draft legislation.  It is our goal to work with you to make the improvements necessary so that this bill will provide the protections from unsafe medical products that the American public expects and deserves.

 

American Medical Student Association

Annie Appleseed Project

Consumers Union

Community Catalyst

Jacobs Institute of Women’s Health

National Consumers League

National Research Center for Women & Families

National Women’s Health Network

Center for Science and Democracy, Union of Concerned Scientists

U.S. PIRG

WoodyMatters

 

 

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

Letter to Representative Markey in Support of Legislation that would give FDA Authority to Oversee Compounding Pharmacies, October 31, 2012

Environmental Exposures, Legislation
October 31, 2012

The Honorable Edward J. Markey
Energy and Commerce Committee
U.S. House of Representatives
2108 Rayburn
Washington, DC 20515

Dear Congressman Markey,

As members of the Patient, Consumer, and Public Health Coalition, we thank you for your commitment to the health of patients and consumers by introducing the Verifying Authority and Legality in Drug (VALID) Compounding Act of 2012. This bill would strengthen FDA oversight of compounding pharmacies in several essential ways, and is clearly needed to prevent tragedies such as the contaminated steroid injections that have already resulted in 356 cases of fungal meningitis and 28 deaths.

The current laws and regulations regarding compounding pharmacies have resulted in giant loopholes that allow medical products that are neither safe nor effective to be sold throughout the country, putting patients’ lives at risk. We are very grateful to you for your leadership on this very important, life-saving bill.

The VALID Act would protect the activities of traditional small compounding pharmacies while ensuring that compounding pharmacies that are essentially operating as drug manufacturers are regulated by the FDA the same way as other drug manufacturers. It would require pharmacies that engage in interstate commerce to register with the FDA and comply with minimum safety standards. The bill would require compounding pharmacies to report deaths and other serious adverse events to the FDA in a timely manner, so that other patients would not be harmed. It would authorize the FDA to inspect pharmacy facilities, which is absolutely essential. It would also require a warning to patients that compounded drugs have not been approved safe and effective by the FDA.

We look forward to working with you on the VALID Act, and share your desire to make sure that waivers are available when the public health is at stake, but are not used to undermine the integrity of the legislation.

The scandal around the lack of oversight of compounding pharmacies has alarmed lawmakers on both sides of the aisle. We will make every effort to secure bipartisan support for this bill.

Cancer Prevention and Treatment Fund
Jacobs Institute for Women’s Health
National Consumers League
National Research Center for Women & Families
Our Bodies Ourselves
Union of Concerned Scientists

The original letter can be found here.

Press release from Representative Markey.

November 1, 2012
Washington, D.C.

VALID Compounding Act will give FDA authority it needs to ensure the safety of the compounding pharmacy sector nationwide

Today, Congressman Edward J. Markey (D-Mass.) announced legislation he plans to introduce tomorrow that will strengthen federal regulations for compounding pharmacies. The New England Compounding Center (NECC), a compounding pharmacy located in Rep. Markey’s Congressional District, has been found to be the source of contaminated injectable steroids that have led to 28 deaths and 377 illnesses in 19 states. The Verifying Authority and Legality in Drug (VALID) Compounding Act will give the Food and Drug Administration (FDA) clear, new authority to oversee compounding pharmacy practices throughout the country.

“Compounding pharmacies have been governed by fragmented regulations for too long, leading to the worst public health disaster in recent memory,” said Rep. Markey, senior member of the Energy and Commerce Committee. “The VALID Compounding Act ends this regulatory black hole by giving the FDA new, clear authority to protect patients and oversee these companies. I look forward to working with my colleagues in Congress on a bipartisan basis to move this legislation forward.”

A copy of the VALID Compounding Act can be found HERE. A one-page description of the legislation can be found HERE.

The VALID Compounding Act will:

  • Preserve state regulatory authority for traditional small compounding pharmacy activities;
  • Ensure that compounding pharmacies that are operating as drug manufacturers are regulated by the FDA as drug manufacturers;
  • Allow compounding pharmacies with a legitimate reason to compound drugs before the receipt of a valid prescription to request a waiver to enable them to do so;
  • Allow the FDA to waive the requirement to compound drugs solely for individual patients with valid prescriptions in the event of a drug shortage or to protect public health;
  • Allow the FDA to waive the requirement to compound drugs only if they are not copies of commercially-available drugs if doing so is necessary to protect public health or well- being; and
  • Increases transparency to the public by mandating that compounded drugs be labeled to ensure that recipients know that the drugs have not been tested for safety or effectiveness, publishing a “Do Not Compound” list of unsafe or ineffective drugs, and reporting of bad reactions to compounded drugs or any drug that poses a safety risk.

“This bill will save lives by ensuring that compounding pharmacies play by the rules that are essential to protect patients,” said Diana Zuckerman, PhD, president of the Cancer Prevention and Treatment Fund. “This month’s tragic meningitis outbreak from contaminated steroid injections was absolutely preventable. We call on Congress to work in a bipartisan manner to pass Congressman Markey’s legislation, which is necessary to protect our families from these predictable, preventable tragedies.”

The legislation has been endorsed by Cancer Prevention and Treatment Fund, Jacobs Institute for Women’s Health, National Consumers League, National Research Center for Women & Families, Our Bodies Ourselves, and Union of Concerned Scientists. A copy of the endorsement letter can be found HERE.

Earlier this week, Rep. Markey released the report “Compounding Pharmacies, Compounding Risk”, which revealed that even before the current outbreak, problems at compounding pharmacies led to at least 23 deaths and 86 illnesses in 34 states, and that state regulatory bodies typically focus on more non-safety related traditional pharmacy licensing activities. A timeline of Rep. Markey’s work on compounding pharmacies can be found HERE.

Letter to Senator Patrick Leahy, in support of the Camp Lejeune Historic Drinking Water Consolidated Document, August 31, 2012

Legislation
August 31, 2012

The Honorable Patrick J. Leahy

Chairman, Senate Judiciary Committee
437 Russell Senate Bldg.
United States Senate
Washington, DC  20510

Dear Senator Leahy:

The Cancer Prevention and Treatment Fund thanks you for your leadership regarding the Camp Lejeune Historic Drinking Water Consolidated Document Repository. The contamination of drinking water at Camp Lejeune Marine Corps Base, an unprecedented environmental disaster affecting the courageous men and women of our military, is of great concern to our organization.

We are especially concerned about the alarming number of breast cancer cases that have been documented in men who lived or worked at Camp Lejeune from the mid 1950’s until 1987. As you know, 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. One study of over 160 men with breast cancer reported that almost 25% of the men were experiencing “traumatic stress,” with some having clinical levels of depression and anxiety as a result of their diagnosis and related treatment. Because breast cancer support groups and other resources typically target women, men may feel isolated and become reluctant to seek help.

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 hope that the release of these documents will encourage better research investigating the link between exposure to trichloroethylene (TCE) and other known contaminants in the Camp Lejeune drinking water, and an increased risk for male breast cancer as well as other diseases.  It is likely that the exposures could cause other types of cancer as well, but those other cancers may not be as noticeable as male breast cancer, which is usually rare.

Again, thank you for your tireless efforts to shed light on this tragic problem, and to support increased­­­­­ access to vital information, health care and services for these veterans and their families.  Please let us know if we can be helpful to you or your staff on this or other important health/environmental justice issues.

Sincerely,

 

Diana Zuckerman, PhD
President
Cancer Prevention and Treatment Fund

Letter to Dr. Margaret Hamburg, FDA Commissioner, about Maintaining and Strengthening Conflict of Interest Policies for Advisory Committees

Legislation
August 3, 2011

August 3, 2011

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

Dear Commissioner Hamburg:

We are writing to make very clear that there is a significant element of the public health community that includes patient, consumer and scientific integrity advocates that strongly oppose any efforts by the FDA to loosen the current conflict of interest rules for members of FDA advisory committees. In fact, it has been our position that the agency’s management of such potential conflicts of interest needs to be made stronger.

Over the past several years, organizations that are members of the Patient, Consumer, and Public Health Coalition have consistently raised concerns that advisory committee member conflicts of interest, both disclosed and undisclosed, continue to raise the specter of bias in the advice that advisory committees provide the agency. The perception and reality of conflicts of interest seriously undermines the public’s faith in the integrity of recommendations made by advisory panels to the agency.

Earlier this year, in the context of our public comments on proposals regarding renewal of Prescription Drug User Fees, we once again brought up the issue of conflicts of interest and our belief that FDA must do more to manage potential conflicts in order to keep the public trust. We understand that there are differences of opinion on this issue.  However, your suggestion that most patient and consumer stakeholders want to loosen the rules is truly disappointing and puzzling to us.

We respectfully request an opportunity to discuss our concerns with you as soon as it is possible to schedule a face-to-face meeting.

Annie Appleseed Project

Breast Cancer Action

Center for Medical Consumers

Community Catalyst

Consumer Federation of America

Consumers Union

Jacobs Institute for Women’s Health

National Consumers League

National Research Center for Women & Families / Cancer Prevention and Treatment Fund

National Women’s Health Network

THE TMJ Association

Union of Concerned Scientists

U.S. PIRG

Woody Matters

For more information, contact Paul Brown at (202) 223-4000 or pb@center4research.org

Report: Medical Devices Lack Evidence of Safety and Effectiveness

Legislation, Policy
July 29, 2011

FDA Should Scrap Current Fast-Track Approval Process

The prestigious Institute of Medicine (IOM) recently released a report on the Food and Drug Administration’s 510(k) medical device clearance process, which is the short-cut used to review more than 90% of all medical devices.

Medical Devices and the Public’s Health, released in late July 2011, concludes that:

  • “The current 510(k) process is flawed” and should be scrapped. The FDA needs to develop a new system “that provides a reasonable assurance of safety and effectiveness.”
  • Information that the 510(k) clearance process promotes or hinders innovation “does not exist.”

In 2010, an FDA task force recommended numerous changes to strengthen the 510(k) process, but device companies strongly opposed the changes and enlisted the opposition of numerous Members of Congress.  As a result, the FDA delayed implementing the changes intended to protect the public health, with officials explaining that they would wait until the IOM reported on their findings.  Agency officials did not expect the IOM to come out so strongly against the current system.

The IOM report points out that the 510(k) process can’t ensure that devices are safe or effective because it bases FDA approval on a new device’s similarities to devices that are already on the market.  The IOM report determined that the system needs to require evidence of safety and effectiveness in order to protect the public health.  The report recommended that rather than spend scarce resources trying to improve the 5010(k) system, the FDA needs to create a new system that focuses on safety and effectiveness, although it can differ from the Premarket Approval (PMA) standards that are used for the highest risk devices.

“Too many patients have been injured or killed by medical devices cleared through this very flawed short-cut known as the 510(k) process,” said Dr. Diana Zuckerman, president of the National Research Center for Women & Families and the Cancer Prevention and Treatment Fund.  “Patients have been harmed by millions of devices, including defective hips, heart devices, diagnostic tests, and implanted mesh products that haven’t been tested on people. All devices that are implanted and life-sustaining should be held to a much higher standard.”  Dr. Zuckerman has advocated for stronger medical device safety regulations for years, testifying about this in the House of Representatives in 2006 and at a Senate hearing in 2011.

The IOM report is a major setback to the powerful medical device industry, which has spent a king’s ransom lobbying Senators and Congressmen to weaken medical device clearance regulations under the guise of promoting device innovation.

The report echoes the National Research Center for Women & Families’ concerns about the lack of evidence that these devices actually work and are safe. We found that millions of unsafe medical devices are recalled every year that were originally cleared through the 510(k) process.  See our study in the prestigious peer-reviewed journal, Archives of Internal Medicine,”Medical Device Recalls and the FDA Approval Process.”

NRC for Women & Families urges the FDA to immediately strengthen the device approval process by incorporating safety and efficacy standards into the current 510(k) review.  And it calls on the Congress to prioritize public health safety over industry demands to support the status quo.

Letter to Maine House of Representatives on the Children’s Wireless Protection Act

Legislation
February 26, 2010

The Honorable
State Representative
Maine House of Representatives
2 State House Station
Augusta, ME 04333

Dear Representative:

As nonprofit organizations dedicated to improving public health, we strongly support the “Children’s Wireless Protection Act.”  This legislation would require cell phones sold in Maine to include a prominent warning label on the phone and its packaging stating that the device may cause brain cancer, that children and pregnant women should be particularly cautious, and that people should keep the phones away from their heads and bodies.

The frequent, heavy use of cell phones is a relatively recent phenomenon, and since cancers usually take at least 10-20 years to develop, it will be years before research is likely to conclude whether cell phones cause cancer or not.  A good analogy is smoking: smoking causes lung cancer and most smokers start in their teens, but smokers don’t develop lung cancer for at least 25-35 years.

If we wait 20 years to determine the exact cancer risks of cell phones, it will be too late to protect ourselves or our family members.  The evidence of risk is growing.  A review of 18 studies of cell phones and brain tumors, published in Occupational and Environmental Medicine in 2007, concluded that studies of individuals using cell phones for more than 10 years “give a consistent pattern of an increased risk for acoustic neuroma and glioma,” with the risk being highest for a tumor on the same side of the head that the phone is used.1

A 2009 meta-analysis of 11 studies published in peer-reviewed journals on long-term cell phone use and the risk of developing brain tumors concluded that using a cell phone for ten or more years “approximately doubles the risk of being diagnosed with a brain tumor” on the side of the head where the cell phone user holds the phone.2 We are very concerned about the possible long-term risks associated with the use of cell phones for adults and children.  The brains of children under 8 absorb twice as much radiation from cell phones as adult brains, according to a 2008 study published in Physics in Medicine and Biology.3 A Swedish researcher found that people who begin using cell phones (and cordless landline phones) before the age of 20 are at an even higher risk of developing brain tumors than people who begin using them as adults.4, 5

Research also indicates that cell phone radiation harms sperm and may reduce male fertility.6 The solution: men of reproductive age who would like to have children should shut off their phones before putting it in their pants pockets or anywhere below the waist.  Of course, the radiation is much lower when a phone is on but not in use than when a person is speaking on the phone, but since a cell phone can sit in a man’s pocket for most of the day, the cumulative exposure while the phone is on is still substantial.

The cell phone industry insists that its phones are safe, but the industry tends to focus on studies they fund themselves and that draw conclusions favorable to their business.  Flaws in industry-funded studies include not evaluating on which side of the head the phone was used, rarely including business customers with corporate accounts (who tend to be the heaviest cell phone users), defining “regular cell phone users” as those who use cell phones at least one call per week, and publishing studies of adults who have used cell phones for less than 9 years.7 It is not surprising that such poorly designed studies have not found a significant increase in brain cancers linked to cell phones.

Meanwhile, prominent cancer researchers are urging people to reduce cell phone radiation exposures for themselves and their children.   Dr. Ronald Herberman, the director of the University of Pittsburgh Cancer Institute, warned his staff in July 2008 that the risks from cell phone radiation justified precautions, such as using ear pieces and minimizing cell phone usage by children.8

We strongly support this pioneering legislation, which would make Maine the first state to require warning labels that radiation from cell phones may cause brain cancer.  The “Children’s Wireless Protection Act” would provide Maine citizens with the information they need to decide whether they want to take precautions regarding cell phones.

Sincerely,

Annie Appleseed Project
Cancer Prevention and Treatment Fund of the National Research Center for Women & Families
Environmental Health Trust
Grassroots Environmental Education
Healthy Child Healthy World
HEAR (Health, Education and Resources, Inc.)
IHE (Institute for Health and the Environment of the University at Albany
Our Bodies Ourselves

For more information, contact Paul Brown at the Cancer Prevention and Treatment Fund of the National Research Center for Women & Families at pb@cente4research.org or (202) 223-4000.

PDF: Chlildren’s Wireless Wireless Protection Act

References:

1 Hardell L, Carlberg M, Soderqvist F, Hansson Mild K, Morgan LL (2007). Long-term use of cellular phones and brain tumours: increased risk associated with use for = 10 years. Occupational and Environmental Medicine 64(9):626-632.

2 Khurana VG, Teo C, Kundi M, Hardell L, Carlberg M (2009) Cell phones and brain tumors: A review including the long-term epidemiologic data. Surgical Neurology 72(3): 205-214.

3 Wiart J, Hadjem A, Wong MF, Bloch I. (2008) Analysis of RF exposure in the head tissues of children and adults. Physics in Medicine and Biology 53(13): 3681-3695 (15).

4 Hardell L, Carlberg M, Hansson Mild K. (2009) Epidemiological evidence for an association between use of wireless phones and tumor diseases. Pathophysiology 16 (2-3): 113-122.

5 Hardell L, Hansson Mild K, Carlberg M, Hallquist A. (2004) Cellular and cordless telephones and the association with brain tumours in different age group. Archives of Environmental Health 59 (3): 132-137.

6 De Iuliis GN, Newey RJ, King BV, Aitken RJ (2009) Mobile Phone Radiation Induces Reactive Oxygen Species Production and DNA Damage in Human Spermatozoa In Vitro. PLoS One 4(7):e6446.doi:10.1371/journal.pone.0006446. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0006446 (Accessed August 17, 2009).

7 Schuz J, Jacobsen R, Olsen JH, et al. (2006) Cellular telephone use and cancer risk: Update of a nationwide Danish cohort. Journal of the National Cancer Institute 98: 1707-1713.

8 “Researcher warns of brain cancer risk from cell phones. July 24, 2008. The New York Times. http://www.nytimes.com/2008/07/24/technology/24iht-cellphone.4.14767955.html Complete warning from Herberman can be read at: http://www.upci.upmc.edu/news/pdf/The-Case-for-Precaution-in-Cell-Phone-Use.pdf