Category Archives: Policy

Comment for Proposed Rulemaking, Menthol in Cigarettes, Tobacco Products; Docket No. FDA-2013-N-0521

Testimony & Briefings, , , , , ,
November 2013

We write today to urge the FDA to remove menthol cigarettes from the market as quickly as possible.

Tobacco use is responsible for more than 400,000 deaths each year in the United States and is the leading preventable cause of death. A quarter of all cigarettes sold are menthol cigarettes, which studies show are preferred by younger smokers and new smokers. Since almost 9 out of 10 (88%) adult smokers began smoking before age 18, it will save lives to make smoking as unappealing as possible for teenagers and young adults. Menthol’s “cooling effect” does the opposite: it makes smoking as palatable (perhaps more palatable) to young people and nonsmokers as candy flavoring, which was banned in 2009 under the Family Smoking Prevention and Tobacco Control Act. According to the FDA’s Preliminary Scientific Evaluation of the Possible Public Health Effects of Menthol Versus Nonmenthol Cigarettes, “the weight of the evidence supports the conclusion that menthol in cigarettes is likely associated with increased initiation and progression to regular cigarette smoking.”

Not only are menthol cigarettes a starter product for youth, they are harder to quit because they are likely associated with: 1) “increased dependence,” and 2) “reduced success in smoking cessation, especially among African American menthol smokers.”  For these reasons, we strongly agree with the FDA conclusions that “menthol cigarettes pose a public health risk above that seen with nonmenthol cigarettes.”

The Tobacco Products Scientific Advisory Committee (TPSAC), before which we testified, concluded over two years ago that “removal of menthol cigarettes from the marketplace would benefit public health in the United States.” A conservative modeling scenario published in a peer-reviewed medical journal estimated that over 320,000 deaths—most of them among African Americans—could be averted by 2050 had menthol been banned in 2011 as recommended.1 The FDA must not drag its feet any longer. The decision to extend the comment period an additional two months itself cost thousands of lives.

The Cancer Prevention and Treatment Fund represents the millions of American families whose lives have been touched by cancer, and our mission is to gather and scrutinize research to determine how programs and policies can reduce the incidence of cancer and improve treatment options for cancer patients.  Our scientific analysis indicates that hundreds of thousands of lives will be saved when the FDA removes menthol cigarettes from the market, and we strongly urge the FDA to protect the public health by implementing a final rule to do so.

Sincerely,

Cancer Prevention and Treatment Fund

Testimony of Brandel France de Bravo, MPH, at the Gastroenterology-Urology Devices Panel on Computed Tomography Colonography (Virtual Colonoscopy)

Policy, Testimony & Briefings,
September 9, 2013

I am Brandel France de Bravo, and I am speaking on behalf of the Cancer Prevention and Treatment Fund of the National Research Center for Women & Families. Our non-profit research center scrutinizes medical data, evaluating scientific evidence of benefits and risks for patients.  We analyze and review research and provide objective and understandable health information to patients, health care providers, and policy makers.  Our organization does not accept funding from companies that make medical products, and therefore I have no conflict of interest.

The research presented in the FDA summary makes clear five points that are essential in considering the benefits and safety of Computed Tomography Colonography or CTC:

1)      There is NO ONE method of screening asymptomatic patients for colon cancer that meets the three necessary criteria for increasing compliance with screening guidelines: that the method be highly accurate; very low risk; and involve little to no discomfort—either physical or psychological – including the “yuck”  factor. Optical colonoscopy has not been as widely embraced as many health experts would have liked, except perhaps by unscrupulous surgical centers, which The New York Times reports are charging insurance companies as much as $6,000.   The Times noted that colonoscopies “are the most expensive screening test that healthy Americans routinely undergo — and often cost more than childbirth or an appendectomy in most other developed countries.” While traditional colonoscopy has downsides, it at least offers a “two-for”: it screens patients for colon cancer and removes potentially pre-cancerous polyps all in the same procedure.

2)      Virtual colonoscopies don’t screen and treat; they just screen, which is why the term “virtual colonoscopy” is a misnomer. It is, however, a great marketing tool as it implies a clean, no-muss-no-fuss approach. In fact, patients still have to go through the grueling process of bowel preparation.

3)      CTC is not as good as optical colonoscopy at detecting polyps or lesions of 10 mm or smaller. This, however, may not be so important given that polyps under 10mm are less likely to be suspicious and in need of removal. Smaller polyps grow slowly, and some will even shrink and disappear on their own.

4)      While CTC is less sensitive for smaller lesions and exposes patients to relatively high doses of radiation, it does offer one major benefit over colonoscopy: it reduces the risk of major bleeding and disease transmission—both of which are of particular concern in older patients.

5)      Besides exposing patients to radiation and missing smaller polyps, CTC opens a Pandora’s box of “extra-colonic findings”—suspicious findings in nearby organs. These findings can lead to more diagnostic tests, some of which may be invasive or harmful, but they also sometimes save lives.

While radiologists often dismiss worries about excessive exposure to radiation, our Center continues to be concerned because so many patients are being exposed to radiation from so many different medical tests, as discussed today by Dr. Berrington de González. Two pieces of information or safeguards that would help make the decision about CTC easier are missing:

  • We need to know if patients in the U.S. are more likely to undergo regular screening with so-called virtual colonoscopies than regular ones. This is the purpose of patient-centered outcomes research—how do real patients in the real world respond to these two options, and what are the benefits of each in attracting patients who should get screened?Dr. Summers shared data on patient acceptance, showing a preference for CTC, but that data was based on answers to questionnaires—given either after the procedure or about a hypothetical screening.  To date there are no studies in the U.S. where asymptomatic patients who have never before been screened are given a choice between CTC and regular colonoscopy and then actually undergo their preferred screening.
  • When is a professional society or government agency going to address the health threat of increased lifelong exposure to radiation from medical tests and treatments? The advent of electronic medical records provides the opportunity to implement a plan to reduce patients’ total exposure to radiation. It wouldn’t cap exposure but rather allow providers to make informed decisions: by enabling them to review a patient’s previous radiation exposure before choosing what kind of screening to recommend.  For example, a heavy smoker undergoing regular CT scans for her lungs should probably be screened with colonoscopy rather than CTC, since the latter also exposes part of the lungs to radiation.

There are no easy answers, but we trust the US Preventive Services Task Force to stay on top of this important issue, providing unbiased information on the risks and benefits as new data become available.  We agree with the Task Force that at this point, there is no reason to recommend virtual colonoscopies for most patients who need screening.  We would add, however, that if specific patients are unwilling to undergo regular colonoscopies, then a virtual colonoscopy is a reasonable alternative.

 

Comments of the Patient, Consumer, and Public Health Coalition on Proposed Order “General and Plastic Surgery Devices: Reclassification of Ultraviolet Lamps for Tanning, Henceforth To Be Known as Sunlamp Products”

Testimony & Briefings, ,
August 7, 2013
[Docket No. FDA-2013-N-0461]

As members of the Patient, Consumer, and Public Health Coalition, we urge you to finally follow the recommendations made by FDA classification panels[end The General and Plastic Surgery Device Classification Panel and the Physical Medicine Device Classification Panel.] in 1977 and upclassify sunlamp products. All sunlamps should be reclassified as Class III devices because of their known risks, especially the increased likelihood of developing the most serious type of skin cancer.

By law, high-risk devices that can cause substantial harm or even death are Class III.  Clearly, sunlamps satisfy those criteria.

Over 30 million Americans, including 2 million adolescents between age 11 and 18, use tanning devices each year. Those who began using tanning beds before age 30 are 75 percent more likely to develop cutaneous melanoma, a potentially fatal cancer. There are virtually no medical benefits to using sunlamp products.  Despite claims, there is no clear evidence that sunlamp products are safe and effective for treating depression, seasonal affective disorder, or vitamin D deficiency. A device that has only minor cosmetic benefits and that the World Health Organization’s International Agency for Research on Cancer has called “carcinogenic to humans” is a threat to public health and should be more strictly regulated.

While we agree with the FDA that sunlamp products should be reclassified, we do not agree that the proposed special controls will adequately protect consumers from the harms associated with indoor tanning. We strongly urge the FDA to require the following safeguards:

  1. Sunlamp products currently are allowed to use a mix of UVA and UVB rays. FDA should set a standard for the UVA/UVB mix that is based on scientific research. Performance testing should disclose the percent of UVA and UVB rays used and this information should be included in labeling.
  2. Because of how sunlamps are used, even the best labeling would not be sufficient to inform consumers of the risks of using sunlamp products. Patients should have to read and sign a patient disclosure form prior to a tanning session. This disclosure form, written at a 6th grade reading level,  should briefly describe the risks of indoor tanning, skin cancer warning signs, and recommended limits on using sunlamps for tanning. Copies of the disclosure form should be given to consumers to take home.
  3. Tanning facilities should be required to post very visible warning information about cancer risks in waiting/reception areas and also on or near the machine itself.
  4. The American Academy of Pediatrics and American Academy of Dermatology both recommend banning minors from tanning salons. We strongly agree.  If no ban is imposed, parents should be required to sign informed consent forms in person at the time a minor is using the tanning facility.
  5. The FDA should consult with scientific advisors to create a recommended limit on sunlamp use for tanning. The limits should include time per exposure, amount of UV radiation per exposure, and number of exposures per year. Customers should be limited to a number of minutes per year that the FDA advisors consider safe. Recommended limits should be included on labels, posted warnings, and patient disclosure forms. Safety and performance testing of sunlamp products should meet the limits.

The classification of sunlamp products should reflect the known safety risks and lack of medical benefits of these devices. Skin cancer is preventable, and requiring higher safety standards for unsafe devices will reduce healthcare costs and save millions of Americans from developing this disease.

 

American Medical Women’s Association
American Public Health Association
Cancer Prevention and Treatment Fund
Connecticut Center for Patient Safety
National Consumers League
National Physicians Alliance
National Women’s Health Network
Our Bodies Ourselves
Center for Science and Democracy, Union of Concerned Scientists
WoodyMatters

 

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

Testimony of Dr. Jennifer Yttri at FDA Advisory Committee on Tivozanib

Other Cancers, Other Cancers, Policy, Testimony & Briefings
May 2013

I am Dr. Jennifer Yttri and I am speaking on behalf of the Cancer Prevention and Treatment Fund of the National Research Center for Women & Families. Our non-profit research center scrutinizes medical data, evaluating scientific evidence of benefits and risks for patients.  We analyze and review research and provide objective and understandable health information to patients, health care providers, and policy makers.  Our organization does not accept funding from pharmaceutical companies and therefore I have no conflict of interest.

Today’s fundamental question is whether the one completed Phase 3 clinical trial is enough to approve the new drug tivozanib as a treatment for patients with renal cell carcinoma.

FDA guidelines recommend two trials that support efficacy of a drug. In some cases, FDA will approve a new drug based on only one trial if that trial shows a significant improvement over existing therapy. In the FDA’s own words: “A conclusion based on two persuasive studies will always be more secure than a conclusion based on a single, comparably persuasive study. Reliance on only a single study will generally be limited to situations in which a trial has demonstrated a clinically meaningful effect on mortality, irreversible morbidity… and [when] confirmation of the result in a second trial would be practically or ethically impossible.”

The NDA submitted for tivozanib relies on one phase 3 study comparing tivozanib to sorafenib. While tivozanib was shown to increase progression free survival by 3 months in patients with renal cell carcinoma, it did not improve overall survival. In fact, there was a non-significant lower overall survival for tivozanib, suggesting the drug may actually harm patients more than it helps them. This one study alone is not enough to meet the FDA’s guidelines for drug approval.

In addition, the study results have inconsistencies that raise red flags about the research and about the drug itself.

1.       Patients receiving tivozanib had increased progression free survival, so why were they more likely to die in the first 30 days due to disease progression, compared to sorafenib. This does not make sense. The deaths in the first 30 days could be due to chance, but the disease free survival could also be due to chance.  More research is needed to clarify the risks as well as the long-term benefits.

2.       FDA noted that 70% of sorafenib patients stopped taking the drug at least temporarily and 44% ended up with a reduced dose. This is much higher than other studies – for example one study highlighted by the FDA had only 14% interruption and 10% reduction.  There is no logical explanation for this, but these unusual problems could make sorafenib seem inferior to tivozanib, when in fact it might be superior.

These inconsistencies may be due to chance or to irregularities in how the studies were conducted in other countries.  Standard of care and assessment of disease varies in the US and other countries, and fewer than 10% of patients enrolled in the trial were in the US.  We agree with the FDA reviewer that it is preferable to enroll US patients, so that the study reflects the disease burden and treatment in the US and can provide better insight into treatment outcomes for US patients.

Regardless of the reason for the inconsistencies in the study, a second, independent, phase 3 study would help determine the safety and efficacy of this drug for treatment of renal cancer.

We urge you to recommend that the FDA require the sponsor to complete a second trial to confirm the positive effect of tivozanib on PFS; address the concern over lower OS; and provide better information on how generalizable the results are in the US population. Based on the data provided, there are no ethical concerns with requiring another trial. With the additional information, the FDA can make an informed decision as to whether tivozanib meets their standards of safety and efficacy.  That is not possible based on this one study with such inconsistent results.

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

Statement of Dr. Jennifer Yttri at the Public Hearing on Creating an Alternative Approval Pathway for Certain Drugs Intended to Address Unmet Medical Need

Testimony & Briefings
Dr. Jennifer Yttri, Cancer Prevention and Treatment Fund, February 4, 2013

My name is Dr. Jennifer Yttri and I speak today on behalf of the National Research Center for Women & Families.

Our nonprofit research center includes scientists and medical and public health experts who analyze and review research to provide objective and understandable health information to patients, health care providers, and policy makers.  My PhD is in immunology from Washington University.

My statement today also reflects the written remarks of numerous members of the Patient, Consumer, and Public Health Coalition. The Coalition is comprised of nonprofit organizations united to ensure that medical treatments are safe and effective, and to enhance the scientific and public health focus of the FDA.

Thank you for the chance to speak today.  Like everyone here, we recognize the need for new drugs to reach patients with serious or life-threatening diseases but we have grave concerns about how this vaguely defined pathway will improve development of safe and effective drugs.

The FDA already has 6 pathways to quickly get drugs to patients with unmet needs. Where is the evidence that this new pathway is needed? How will it promote development of drugs that help patients live longer or have a better quality of life? Almost 50% of the drugs approved in 2009 and 2011 were through a priority pathway2  so there are many ways to get these drugs to patients.

In the President’s Council of Advisors on Science and Technology recommendations, from which the FDA’s proposal was derived, the council said such a pathway would be ineffective without changes in the FDA’s approval and regulatory processes to protect patients.  PCAST said that the FDA would need to establish clear guidelines for clinical trials of drugs to prove benefit given serious and unknown risks. They emphasized the harm that this pathway would cause to ALL patients without a change in the FDA’s authority to regulate distribution after drug approval for one indication. Without first addressing these major changes, designing this new approval pathway is premature.

FDA currently requires adequate and well-controlled trials for drug approval.  As you know, there are inherent dangers when drugs are approved based on smaller and shorter clinical trials. The quality of the research is even more important when the study is done on a narrow population.  Small, short-term studies provide limited information about drug toxicity and safety. Small studies can also overestimate the benefits to patients.

Surrogate endpoints have become common in clinical trials, but they still need to be APPROPRIATE. A surrogate endpoint is valid only if it correlates with the outcomes patients care about which are their health, quality of life, and how long they live. The therapeutic must affect the surrogate endpoint in the same way it affects mortality and morbidity. Clarithromycin was great at killing mycobacterium, with a higher mortality in patients with AIDS. Benlysta helps some patients with lupus get rid of their rash but in exchange will leave them susceptible to severe infection or death.  Avastin slowed breast cancer progression but did not extend or improve patientss’ quality of life – in fact, it did the opposite. These are all cases where surrogate endpoints showed promise but later studies proved the opposite.

The proposed pathway can’t promise improved health, quality of life, or lifespan.  It can try to make a drug available sooner, but shorter trials will have LESS information about whether the drug accomplishes ANY of those 3 patient-centered outcomes.

Waiting for data from post-market studies to identify the safety risks means that patients will meanwhile pay for unproven treatments while serve as unwitting guinea pigs.  Patients may die or be harmed for years before post-market studies are completed.

There is an added complication for approving drugs for very small groups of patients. For many of these serious and life-threatening conditions, specific target populations cannot be readily identified prior to clinical trials. A limited population pathway provides an incentive to create smaller trials but NOT ones that use APPROPRIATE studies with the right PATIENTS.

This brings up the problem of off-label use.  If these drugs are to be used in a limited population, physicians need to prescribe these drugs only in patients who clearly fit the limited population AND have no better options.

This is unlikely to happen.  Currently, 21% of all prescriptions, and 62% of pediatric prescriptions are for unapproved use.  Once a product is approved, it is likely to be taken by many patients who are not in the targeted patient group.  Doctors will be tempted to use these drugs on any patient who might benefit, without evidence of its efficacy or risks in a broader population. In the case of antibiotics, a class of drugs likely to seek approval through this pathway, inappropriate use, even one dose, will add to the problem of antibiotic resistance, the very condition we’re trying to fight.

The goal of the proposed pathway is that, at best, only a small number of patients will be harmed by unknown risks since the approval will be for a limited population. With widespread off-label use, thousands of patients will be exposed to unnecessary harm before we understand under what conditions these drugs work and what the safety risks are.

Since 2004, there have been 28 settlements with companies that promoted drugs for unapproved use, often targeting patient populations in whom these drugs have never been tested.   Just last year, major lawsuits were settled against GlaxoSmithKlein, Johnson & Johnson, and Amgen.  This could change, but not for the better. The FDA has so far done nothing to overturn the recent case of United States versus Caronia, which decided that pharmaceutical representatives can promote off-label use under the First Amendment.

The FDA has not developed effective strategies to stop off-label promotion, and therefore will not be able to restrict the use of drugs to the approved limited populations. A study by Chen et al found that physicians were barely above chance in knowing if their prescription was off-label or for an FDA approved use – even though many of these doctors had prescribed the very same drugs for years.

Worse yet, in another study, only 15% of medical providers stated that they provided safety information to patients if it was indicated on a drug label.  A formal designation and logo will not help much at all. Even with some extended educational plan for clinicians and patients, or medical guide inserts, most patients will not fully understand to what extent the drug is proven safe or effective for their needs.

In conclusion, this poorly defined pathway would promote unproven drugs to high-risk patients. We know that there are desperate patients who are willing to take risks, but with smaller, shorter trials, you won’t be able to tell either the patients or the doctors what the risks are.  If approved based on such limited information, there is no doubt that some of these drugs would harm more patients than they help.  Patients, some of whom would never benefit from these drugs, will die or be irreparably harmed.

There are already 6 expedited pathways used in the approval of almost half of all new drugs.  I share the FDA’s desire to help patients with unmet needs to get access to drugs that could possibly help them.  I wish there were a way to do so without jeopardizing patients who have other treatment alternatives or whom we know are unlikely to benefit.  But, wishing isn’t science.  The FDA is a scientific agency, and it has not provided the science to support this proposal.

Statement by Dr. Diana Zuckerman, Capitol Hill Press Conference

In the News, Testimony & Briefings
Diana Zuckerman, PhD, Cancer Prevention and Treatment Fund, November 14, 2012

The FDA law is supposed to make sure that all medical products sold in the U.S. are safe and effective.  Unfortunately, it doesn’t.

There are several giant loopholes in the law, including loopholes for compounding pharmacies, as well as companies that call themselves compounding pharmacies but aren’t.  That loophole is enormous, and that’s why hundreds of people are now sick with fungal meningitis and so many have died.

And that’s just the tip of the iceberg, because thousands of people got medications that are not proven safe and not proven effective.   And I’m not just talking about the injections that harmed Jerry, which we heard about today.  There have been many other examples of unsafe medical drugs sold through compounding pharmacies, including cancer drugs that were either weaker or stronger than they should have been.

There’s enough blame to go around, but I don’t want to play the blame game today.  Obviously, a major part of the blame is on the compounding pharmacies that didn’t care enough about patients to make sure the products they were making were safe.  This includes the specific pharmacies in Massachusetts that have been identified, but also includes many other compounding pharmacies.  We also have to wonder about the state and FDA inspectors and officials who knew that there were serious, life-threatening problems but didn’t do enough to fix them, and the doctors who ordered products from compounding pharmacies without considering safety issues.

The innocent victims are the patients who trusted their doctors and the FDA to make sure their medications are safe.  The costs to them are enormous, but the human costs and the financial costs.

This VALID Compounding Act is designed to close the loopholes that are so harmful to patients.  It is a well thought out, comprehensive, and balanced bill, and I congratulate Rep. Markey and his staff on the bill and on their excellent report.

The FDA will do a much better job of enforcement if the law is improved.  The FDA’s hands have been tied — they haven’t been able to get the information they needed to fully investigate.  FDA’s resources are very limited, so the agency tends to focus on the slam dunks, not the efforts that are less likely to be successful.

This law will save lives.  It will save a lot of lives if it isn’t watered down by those who care more about protecting companies than protecting people.  We heard a lot of opposition to safety regulations this past year in the House of Representatives, based on claims that safety regulations kill jobs.  Let’s remember that having more inspectors and requiring research evidence of safety will create jobs.  Personally, I’d rather make new jobs for inspectors and researchers, than jobs for people making unsafe medical products.  This law will make new jobs and it will save lives and healthcare dollars, a great combination.

In closing, I want to point out that the history of the FDA is a history of disasters followed by improvements in the law.  The Food, Drug, and Cosmetic Act passed in 1938 after 107 people died, mostly women and children, from taking an elixir made with an antifreeze that was added to improve the color.  That law was greatly strengthened in 1962, after the Thalidomide tragedy caused thousands of babies to be born without terribly deformed arms, legs, fingers, and toes, and in some cases no arms or legs. And, medical devices – even implanted ones – were not regulated until 1976, after many women died or became infertile from the Dalkon Shield IUD.

This is the latest tragedy, and it is an important opportunity to prevent similar tragedies in the future.  That’s why it is essential to act now.  It is not a partisan issue, and we look forward to working with Congress to act quickly.

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

Testimony of Brandel France de Bravo, MPH, at the Medical Devices Advisory Committee to the FDA on MarginProbe

Testimony & Briefings
Brandel France de Bravo, Cancer Prevention and Treatment Fund, June 21, 2012

I am pleased to have the opportunity to testify on behalf of the Cancer Prevention and Treatment Fund.  We are dedicated to improving the health and safety of adults and children, and we do that by scrutinizing medical and scientific research to determine what is known and not known about specific treatments and prevention strategies.

According to a recent study in JAMA, 1 in 4 women who undergo a lumpectomy will have to have a second surgery because the pathology report found that the margins were not clear. For Ductal Carcinoma In Situ (DCIS), re-surgery rates are even higher, ranging from 21% to 50% -something we heard first hand last year when we conducted in-depth interviews with women treated for DCIS.  Most patients were thoroughly unprepared for the possibility of a second surgery and all that it entailed; and several got fed up with the surgeon not being able to “get all the cancer out,” and opted for a mastectomy that was absolutely not medically necessary. In addition to the high re-lumpectomy rates, prophylactic mastectomies among DCIS patients are on the rise. Not surprisingly, we would welcome a device that reduces the likelihood of re-lumpectomy and makes breast conserving surgery a one-time solution, as mastectomy already is. Our organization has worked on DCIS for a decade so we were very heartened to learn that in a post market study carried out in Germany MarginProbe cut the re-operation rate for women with DCIS by half.  Unfortunately, the re-operation rates in the Pivotal Study were not nearly so impressive: 20.8% in the device arm vs. 25.8% in the control arm.

In addition, we share some of the FDA’s concerns about the device, namely:

  • Did the device perform better in Israel due to more extensive training prior to use, or because the design dataset was generated by an Israeli population that is not reflective of the U.S. one? Either way, what are the implications for women in the U.S.?
  • Did the device perform better in the Pivotal Study because of design bias giving surgeons an additional opportunity to shave compared to the standard-of-care control arm?
  • Also, why was the mastectomy conversion rate higher in the device arm? Was the slightly higher tissue volume causing women faced with re-operation to opt for mastectomy because they were dissatisfied with their appearance following the primary lumpectomy? Any future study would need to include qualitative data from patients after their primary lumpectomy and any subsequent lumpectomies regarding satisfaction with their appearance.

The FDA asks whether the device’s sensitivity is worth its poor specificity. We are somewhat less concerned than the FDA about the false positives and excessive tissue removal because that occurs with or without this device and patients can be informed about this choice.  Patients should be asked: Is it more important to you to avoid repeat surgeries or to preserve as much breast tissue as possible?

Given that routine or complete shaving of the lumpectomy cavity is just as effective at converting to negative final margins, with only slightly more tissue removed, is the device worthwhile? The FDA worries that the extra 5 minutes of intraoperative time in the device arm muddied the results, favoring the device. We believe that this is a positive aspect of the device: it forced surgeons to spend more time assessing the margins.

While many of the FDA’s concerns could be effectively addressed in a post-market study, we know from long experience that post-market studies are rarely implemented with the rigor of pre-market studies, in part because the incentives to retain patients simply are not there: why eat your veggies after you’ve already been given dessert?  Has the FDA ever withdrawn approval of a device because post-market studies weren’t carried out or because of poor results?  I don’t think so, but certainly that is rare if it happens. Given Dune’s track record of responding “too little and too late” to FDA requests, there is no reason to believe that the company will follow FDA requirements better post-market than it did pre-market.

In summary, the benefits of this device are important, and the manufacturers have provided adequate proof of safety, but that is not the only issue here. While the POTENTIAL benefits of the device clearly outweigh the risks-the main risk being the possible removal of noncancerous tissue-the device’s actual benefits have not yet been fully established for the intended use in the U.S.  At the very least, the large number of confusing outcome measures should be reduced and clarified prior to the FDA’s decision, so that patients and physicians can make an informed choice.