Posts Tagged ‘FDA’

Anemia Drug Update

Posted by medconsumers on June 1, 2007

On May 10, 2007, the FDA held an emergency meeting of its Oncologic Drugs Advisory Committee to discuss the anemia drugs that supposedly help people cope with chemotherapy. But several recent studies were halted prematurely because these drugs—Epogen, Procrit, Aranesp—caused an increased death rate, cancer progression, deep-vein blood clots and heart damage (see last month’s newsletter). Ultimately, the FDA advisory committee asked for better studies and voted to put more stringent warnings on the labels for these drugs, known collectively as EPO. Unfortunately, few doctors ever read warning labels (one in ten, according to one survey), and the FDA has no authority over how they prescribe drugs.

As is often the case with drugs found to be risky long after they came on the market, the future of EPO comes down to money. There are huge financial incentives for oncologists to overprescribe EPO. Amgen and Johnson & Johnson, makers of EPO, sell their drugs directly to doctors and thanks to rebates (a.k.a. kickbacks) from the drug companies, many oncologists are making a fortune.

That was made clear the day before the FDA meeting in a front-page New York Times article entitled, “Doctors Reaping Millions for Use of Anemia Drugs.” A former business manager for a six-oncologist practice in the Pacific Northwest provided the Times with documentation showing that the six doctors received $2.7 million from Amgen for prescribing $9 million worth of its drugs last year. The rebates are available for cancer drugs other than those self-administered by the patient. The rebates are in addition to the reimbursements doctors get from Medicare and private insurers.

Normally, the FDA steers clear of drug costs, sticking solely to safety and efficacy issues, but the Times article loomed over the FDA meeting. When the advisory committee discussed how to inform patients of the adverse effects of EPO, one oncologist said it should be left to doctors. But another committee member Otis Brawley, MD, head of Atlanta’s Grady Hospital, objected. “The problem is at my hospital doctors get $1200 for every dose they give patients. And they don’t have to sign conflict-of-interest statements like we do,” he said, referring to the FDA requirement that each committee member reveal any financial ties to drug companies prior to participation.

Another oncologist on the committee expressed fury about the uncertainties regarding the safety of the doses currently in use. “Yes, we have a burning question: Are these drugs killing people?” asked Silvana Martino, MD. “What are the doses that are reasonable and appropriate?”
The misleading EPO advertising aimed at the public would never have come up at this meeting were it not for consumer advocates. Five advocates attacked Johnson & Johnson’s ads for Procrit, which fraudulently sold the drug as the cure for chemotherapy-induced fatigue in an ad campaign that ran from 1998 to 2005. They pushed the FDA to force Johnson & Johnson to mount a corrective ad campaign because there is no proof for its claim.

There is no proven quality-of-life benefit for EPO. The drugs were initially approved as a safer alternative to blood transfusions for a chemotherapy-induced drop in red blood cells. But transfusions are not as risky as they were 15 years ago when the first EPO was approved. One basic question lingered: What is the purpose of this drug?

Answers will take years, but Wall Street reacted immediately. Within days of the FDA meeting, Amgen shares dropped more than 15%.

Maryann Napoli, Center for Medical Consumers© June 2007

Posted in Advocacy, Cancer | Tagged: Advocacy, anemia drugs, Cancer, chemotherapy, FDA | Comments Off

Support for FDA Regulation of “Home Brew” Diagnostic Tests

Posted by medconsumers on February 8, 2007

Support for FDA Regulation of “Home Brew” Diagnostic Tests

On February 8, 2007, the FDA held a meeting to discuss the agency’s plan to regulate certain diagnostic laboratory tests for cancer and many other diseases. The central question of the day was: Should the FDA have regulatory power over “home brew” tests, which are multi-gene profiles? These tests will be used to diagnose cancer, determine the most effective treatment, as well as seeing who is at high risk of getting the disease. Traditionally, the FDA has not regulated tests, such as these, that are not done in one central lab. However, the agency has recently designated these tests, called in vitro diagnostic multivariate index assays, as devices. This opens the door to regulation.

At the public comment portion of the meeting breast cancer advocate, Helen Schiff, presented her position on behalf of the Center for Medical Consumers. Her testimony follows:

My name is Helen Schiff. I am a breast cancer survivor and a member of SHARE a breast and ovarian cancer organization in New York City. I am also a patient consultant for the FDA.

The potential for complex biomarkers known as IVDMIAs (In vitro diagnostic multivariate index assays) to change the face of breast cancer treatment is tremendous. For too long we have been plagued with a one size fits all approach to treatment. Even though many women are cured with surgery they have to suffer through radiation, chemotherapy, and 5 years of hormonal treatment because there is no way to know with certainty what treatment a woman really needs, IF ANY. While this treatment strategy has had a small impact onbreast cancer mortality, it has meant that many women have been exposed needlessly to the lethal and life altering effects of all these modalities. Just to name some of the worst ones: leukemia, cardiomyopathy, endometrial cancer, stroke, pulmonary embolism, infertility, lymphedema, “chemobrain,” and loss of libido.

So we welcome a new technology that has the potential to customize our treatments. To give us only what we need. To even tell us which chemotherapy, hormonal treatment, monoclonal antibodies, or small molecule will be optimal for our specific tumors. And we know that in the future IVDMIAs will also have the potential to find breast cancer earlier than is now possible and to do a better job than the Gail model at determining who is really at high risk for getting breast cancer.

Nevertheless, it is very important to be aware of the pitfalls that have plagued biomarker research over the years. In almost half a century of breast cancer biomarker research only TWO biomarkers have proved to be of clinical value: ER and Her2. The significance of what PR means is still disputed. We know for a fact that problems with assays have led to erroneous assessments, less than optimal treatment, and most importantly, premature loss of many lives. Unfortunately, recent studies indicate that there are still problems, for example, with accurate ER and Her2 assays. For example the cut point for ER positivity varies from 1 to 25% of cells with estrogen receptors. A recent study showed that 20% of Her2 tests were not accurate. As many have said, a treatment is only as good as its biomarker, and hence they too need to be rigorously regulated.

One of the most important recommendations of the National Breast Cancer Coalition’s Strategic Consensus Report on Breast Cancer Biomarkers is “to incorporate the best components of drug development to guide the development and validation of biomarker assays.” This new FDA Guidance for IVDMIAs is an important first step in that direction. It will assure that IVDMIAs are: 1) examined before they are marketed; 2) that their results are reproducible by an independent body; 3) that they are tested for accuracy; and 4) that they have clinical relevance. The writing of the IVDMIA label, as with new drugs, must be over seen by the FDA to ensure that there are no false claims and that the results of an INDMIA assays are understandable to both doctors and patients. It is clear to me that neither CLIA, the Federal Trade Commission, nor any other agency in HHS has the depth of the experience, the capabilities, or the resources to undertake such a job, nor do they have the regulatory power.

One need only look to the Ova Check experience to see why this kind of regulatory power is so important. Ova Check was developed as a blood test for the early detection of ovarian cancer in high risk women by Correlogic, a private company, in partnership with scientists from the FDA and the NCI. However, the FDA said that it would not allow Ova Check to be marketed until it published clinical evidence that it WORKED in patients. Keith Baggerly, a bioinformatics specialistat MD Anderson, when trying to replicate the study, found, among other problems, that test results were influenced by the order in which the assay was run. According to an article by David Ransohof in the Journal of the National Cancer Institute Ova Check had not been properly validated its finding in an independent data set and there was a possible problem with over-fitting and bias. Three years later, it has still not been approved to be marketed, confirming its problems were serious. If it were up to CLIA or the Federal Trade Commission, Ova Check would have been marketed-because they do not have the power to stop it. And we all know how hard it is to get something off the market once it is on. Not to mention the irreparable damage it would have done to women.

To me the arguments that FDA regulation of IVDMIAs will hinder development and commercialization, or that this new regulation is unfair, are non red herrings. Don’t we want to find out which IVDMIAs work and which ones don’t, regardless of when they were developed or by whom? If anything will hold up development in this field it will be the premature marketing of more Ova Checks. As we see this is not just a matter ofj “colorful characters” or fly by night companies as suggested in a recent GAO report. Reputable scientists can make honest mistakes.

As an advocate I think we need to introduce rigor and oversight into the biomarker field and I think the FDA Guidance on IVDMIAs is an important step in that regard. I certainly don’t follow the logic that when IVDMIAs are homebrews they should not be regulated by the FDA. My logic leads in the other direction. All biomarkers, including home brews, when used in the CLINIC should be regulated by the FDA. Otherwise we leave the successful commercialization of IVDMIAs to companies who write the best press release, do the most advertising or try and court advocacy groups.

Posted in Advocacy, Cancer | Tagged: Advocacy, Cancer, FDA, IVDMIAs, Screening | Comments Off

FDA Regulation of “Home Brew” Tests

Posted by medconsumers on February 8, 2007

Support for FDA Regulation of “Home Brew” Diagnostic Tests

At the public comment portion of the meeting breast cancer advocate, Helen Schiff, presented her position on behalf of the Center for Medical Consumers. Her testimony follows:

My name is Helen Schiff. I am a breast cancer survivor and a member of SHARE a breast and ovarian cancer organization in New York City. I am also a patient consultant for the FDA.

So we welcome a new technology that has the potential to customize our treatments. To give us only what we need. To even tell us which chemotherapy, hormonal treatment, monoclonal antibodies, or small molecule will be optimal for our specific tumors. And we know that in the future IVDMIAs will also have the potential tofind breast cancer earlier than is now possible and to do a better job than the Gail model at determining who is really at high risk for getting breast cancer.

Posted in Cancer, Screening, Women's Health | Tagged: breast cancer, FDA, Screening | Comments Off

New Cervical Cancer Vaccine Should Not Be Mandatory

Posted by medconsumers on December 1, 2006

The new cervical cancer vaccine raises concerns that did not show up in the news coverage about its approval last summer. Usually mass vaccinations are advised for diseases with a high rate of death and/or disability, but cervical cancer doesn’t come close to meeting those criteria. And most important: Is it safe to vaccinate all girls for a disease that afflicts only 9,710 American women yearly and causes 3,700 deaths? The answer might be yes, if the vaccine is risk-free. But the nation’s leading vaccine safety organization raises some serious reservations.

Those reservations were ignored last summer when the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices voted to recommend that all 11- to 12-year-old girls receive the human papillomavirus (HPV) vaccine called Gardasil. This is a major step toward making the vaccine mandatory—at an age well before girls are likely to become sexually active.

Only one company, Merck, makes the HPV vaccine, which is given in three injections over six months and will cost $360. Merck says its trials proved Gardasil is “100% effective in preventing HPV infection in those who do not already have HPV with strains 16 and 18, which together cause about 70% of all cases of cervical cancer.”

These Merck-sponsored trials were submitted to the FDA, and Gardasil was approved. But Barbara Loe Fisher, an advocate for vaccine-safety studies and the president of the National Vaccine Information Center, questions the need for a cervical cancer vaccine given the availability of the Pap test, which she believes has greatly reduced the incidence of the disease. She also sees methodological flaws and major deficiencies in what has been reported to the public about HPV disease and the vaccine.

“Most people who have sex will have experience with HPV, but the majority will clear it from the body and go on to have healthy lives. Only a tiny percentage will have persistent HPV infection and will experience changes over a long period of time that will lead to cancer. On the list of cancers that kill, this is at the bottom,” she said, referring to U.S. women, as opposed to those in developing countries where cervical cancer deaths are far more common.

As a former member of the FDA Vaccines and Related Biologic Products Advisory Committee, Fisher has considerable experience analyzing the lengthy documents submitted by the vaccine companies to the FDA, as well as the agency’s own review of company-sponsored trials. Fisher’s safety concerns center on the type of placebo Merck used in the Gardasil trials. “A true placebo would be a saline solution—something that is innocuous and has no potential to cause a reaction on its own,” she said, referring to the injection given study participants who were assigned to the control group against which Gardasil was compared.

Instead, Merck used a solution that contained aluminum, Fisher explained, and neither the company nor the FDA has publicly disclosed the amount used in the solution. “Aluminum is used as an adjuvant in many vaccines to boost the potency of the vaccine,” she continued, “and though it has been in vaccines for decades, it has never been tested in clinical trials to see whether it is safe.

“We know from animal and human biological mechanism research that aluminum can cause inflammation and brain cell death. Putting it in the placebo [in a clinical trial] violates the principle of the scientific method when trying to ascertain truth,” said Fisher. “To make matters worse, aluminum is also in the Gardasil vaccine which makes it difficult to tell whether the many adverse events reported in the trials were due to the aluminum-containing placebo or the Gardasil,” she explained, referring to the well-documented fact that adverse events will show up in all clinical trial participants, even those given an inactive placebo.

Why would the FDA overlook this potential for confounding trial results? “The FDA has become partners with the vaccine manufacturers in fast-tracking these vaccines and in the process, the precautionary principle has been thrown out,” Fisher responded, adding that most health problems occurring in vaccine trials are often dismissed. “The companies tend to write them off as unassociated with the vaccine.”

Maryann Napoli, Center for Medical Consumers ©
December 2006

Posted in Cancer, Conflict of Interest, Women's Health | Tagged: Cancer, FDA, prevention, vaccines | Comments Off

Center Director Calls for Sweeping FDA Safety Reform

Posted by medconsumers on October 9, 2006

The FDA and Drug Safety: A Proposal for Sweeping Changes
Curt D. Furberg, MD, PhD; Arthur A. Levin, MPH; Peter A. Gross, MD;
Robyn S. Shapiro, JD; Brian L. Strom, MD, MPH

Read the full report.

Posted in Advocacy | Tagged: FDA | Comments Off

FDA Credibility

Posted by medconsumers on June 1, 2006

FDA Credibility and New Information About Cox-2 Inhibitors

Public confidence in the FDA’s ability to protect users of prescription drugs from harm is slipping, according to a recent Wall Street Journal Online/Harris Interactive poll. When asked about how well the FDA is doing to ensure that new prescription drugs are safe, almost six out of every ten people polled said it was doing only a fair or poor job. When the same question was asked in a similar 2004 poll, a majority of respondents praised the FDA’s performance.

This should come as no surprise. Over the last few years FDA has been rocked by controversy over its handling of prescription drug safety. The most notable have been: FDA’s reluctance to acknowledge that antidepressants (Paxil, Effexor and Prozac among others) might increase the risk of suicide among children and adolescents; failing to respond quickly to emerging evidence that heart attacks and strokes were linked to the popular painkillers known as COX-2s (Vioxx, Bextra and Celebrex); and most recently, an almost begrudging acceptance of a duty to warn doctors and users about serious cardiac harm from attention deficit hyperactivity disorder drugs (ADHD) Ritalin, Adderal and others.

The latest information about COX-2 and ADHD drugs safety may further tarnish the FDA’s image. Recently, experts have reviewed new data and concluded that the risk of heart attack and stroke associated with COX-2 pain relievers starts earlier and lasts longer than previously thought. As a result, previous estimates of tens of thousands of users put in harm’s way by these drugs may have to be revised upwards. And a study by the Centers for Disease Control and Prevention estimates that 3,075 people visited hospital emergency rooms in 2004 because of adverse reactions to ADHD drugs.

Arguably, it’s the FDA’s safety lapses related to COX-2 drugs that may do the most damage. In May, Merck & Company announced results from a year-long followup of participants who had been in a study designed to test whether Vioxx prevents colon polyps. This study, which compared the painkiller to a placebo, had to be stopped ahead of schedule in 2004 because safety monitors observed that Vioxx users suffered twice the number of heart attacks and strokes as those not on the drug–a finding that led Merck to withdraw Vioxx.

After the study had been stopped, the participants continued to be followed for one year. The results were recently touted in Merck press releases as good news because the people who had stopped taking Vioxx purportedly showed no increased risk of a cardiac event. But several drug safety experts looked at the same study results and came to an entirely different conclusion, according to an article in The New York Times. “What it shows us is that you can stop taking Vioxx, and based on this study, for the next year you’re still at increased risk,” said cardiologist Steven E. Nissen, MD, of the Cleveland Clinic. Bruce M. Patsy, MD, of the University of Washington called on Merck to follow the colon polyp trial participants beyond one year—until it knew with certainty whether or not Vioxx caused long-term heart damage. “That would be an honorable thing to do.”

The news gets worse. National Public Radio recently asked clinical trial expert Curt Furberg, MD, of Wake Forest University to review a confidential report from Merck to the FDA which contained yet another analysis of data from the colon polyp study. In the NPR interview, Furberg said the original 2004 safety analysis that led Merck to withdraw Vioxx purportedly showed that “it takes about 18 months [of use] to see an increase in risk.” However, after reviewing the latest data, Furberg concluded, “The risk appears to be present from the beginning, and it increases gradually over time.” Amazingly, Merck admitted its error and confirmed Furberg’s analysis, according to a May 31 New York Times article.

Concern about COX-2 toxicity will likely lead to a new round of questions about the FDA’s competence to protect the public. What must not be lost in the finger pointing is that Congress has chronically underfunded the FDA and not given it adequate regulatory muscle to do its job. Legislation to bolster the agency’s drug safety programs remains stalled in Congress. With mid-term elections this November, what better time to demand that our elected representatives finally take action to fix FDA’s safety shortcomings.

Arthur A. Levin, MPH, Center for Medical Consumers ©
June 2006

Posted in Drug ads, Drugs | Tagged: Drugs, FDA | Comments Off

Protopic and Elidel: Eczema Drugs Have a Cancer Risk

Posted by medconsumers on May 1, 2006

Early this year, the Food and Drug Administration issued a warning about two prescription topical creams for the common skin disease, eczema. Both Elidel and Protopic must now include written material for professionals and patients that warns of a cancer risk based on “information from animal studies, case reports in a small number of patients, and knowledge of how drugs in this class work.”

Though the warning says, “a small number” of people who have used the products “have had cancer (for example, skin or lymphoma),” evidence from the FDA’s own reporting system indicates that this may be an understatement. Pretty alarming for drugs that are applied to the skin, primarily for young children. Doubly so, considering the fact that less than 10% of all serious adverse drug reactions are reported to the FDA.

People with eczema, also known as atopic dermatitis, and parents of children with this chronic skin disorder are often desperate for a treatment that alleviates the severe itchiness and inflammation. Eczema primarily afflicts babies and children, but can continue into adulthood in about 50% or show up (rarely) for the first time in adulthood. There is no cure. A drug might beat it back for a short time, but flare-ups are common.

Elidel (generic name: pimecrolimus) and Protopic (generic name: tacrolimus) control eczema by suppressing the immune system, and they can be extremely effective in producing improvements. Until they came along, corticosteroid cream was the standard treatment. Hopes for the newer drugs stem from fears about the side effects of corticosteroid cream like thinning of the skin and adrenal gland suppression. Novartis, the company that makes Elidel, and Astellas Pharma (formerly Fujisawa), maker of Protopic, fed these fears by promoting their products as “steroid-free.”

One example is Fujisawa’s fraudulent ad for Protopic that appeared six years ago in Prevention magazine stating, “Breakthrough research has finally uncovered a new kind of medicine for eczema. Made of a natural substance, this new treatment is steroid free.” The ad implies safety. But in reality both Elidel and Protopic are in the same drug class as Prograf, a powerful immunosuppressant drug that prevents liver or kidney transplant rejections. In fact, Protopic and Prograf (generic name: tacrolimus), which comes with a warning of “infection and development of lymphoma,” are the same drug!

FDA Explains Itself

Why hasn’t the FDA withdrawn the drugs, given their obvious dangers and the existence of a safer alternative? “FDA believes that the benefits of Elidel and Protopic outweigh the risks of these products,” responded Julie Beitz, MD, of the FDA’s Center for Drug Evaluation and Research, who would answer questions only by e-mail by way of a press officer. “The new warnings in the professional labels and in the Medication Guides* for these products convey what our concerns are, however, a causal link has not been established between the reports of cancer and use of these products.”

The FDA warning states that it may “take human studies of ten years or longer to determine whether Elidel or Protopic is linked to cancer.” Despite the lack of long-term data and what is surely an undercount of cancers associated with use of these drugs, Dr. Beitz defends the FDA position, “While there is under-reporting of adverse events to the FDA, we also know that use of these products is great, so relative to all users, the number of reports we have received is small.”

To some dermatologists, the question of whether Elidel and Protopic pose more than a rare cancer risk seems to hinge on how much is absorbed into the skin. In a January 19, 2006 press release that disagrees with the FDA’s decision to issue an warning, Clay J. Cockerell, MD, president of the American Academy of Dermatology, said, “Because these medications are applied to the skin, virtually none of it gets inside the body.”

That statement was quoted to Dr. Beitz, who commented, “We agree that very little of the drug is absorbed in general, however, we have data to show that some patients do absorb the drug to greater degrees. Additional factors to consider: 1) how long the patient is using the product; 2) how large an area of skin the product is being applied to; and 3) the fact that areas affected with atopic dermatitis are not normal and may allow for more absorption.” Babies under two should not be treated with either drug, according to the FDA warning.

“Infants have higher surface area to volume so they will have higher blood levels of the drug and their skin is more permeable,” said Peter M. Elias, MD, professor of dermatology, University of California, San Francisco, in a telephone interview. “The companies have over-marketed these drugs suggesting, for example that they are safe for infants by showing images of infants [in promotional materials].” The ads implying Elidel and Protopic are safer than corticosteroids are ridiculous, he continued, adding that neither drug has been shown to be safer or more effective than topical steroids in a head-to-head comparison as maintenance therapy for eczema. “Low- to mid-potency steroids are quite safe in eczema, although many clinicians prefer an even less potent agent, such as hydrocortisone, in infants,” said Dr. Elias.

When the FDA was deciding whether to approve these drugs in 2000, Dr. Elias wrote a letter to the agency expressing concerns, particularly about Protopic, which he described as “a powerful and potentially toxic immunosuppressive drug.” In the letter, which remains on the FDA Web site, Dr. Elias told the agency that he is “alarmed at what appears to be a potentially cavalier and uncritical attitude about the indications and long-term safety of topical tacrolimus [generic name for Protopic]. [This drug] is absorbed into the circulation through inflamed skin, and in low-body weight children it can produce transient therapeutic (transplant) drug levels.”

Dr. Elias sees a limited role for the drugs, “Protopic should be reserved for severe, recalcitrant flares of eczema in children and adults, and Elidel for similar bad flares in infants. Elidel might also be useful for periorbital dermatitis due to risk of glaucoma from steroids. But in all these examples, the use should be short term—days, weeks, but not months—and only in conjunction with sunscreens, which should always be used when these drugs are applied to sun-exposed skin. There is no rationale for long-term therapy with either drug.”

Pressure Not to Warn the Public

In the five to six years since the FDA approved each drug, Novartis and Astellas/Fujisawa mounted a massive, often misleading, advertising campaign aimed at doctors and the public. And in the last two years, both companies waged an aggressive campaign against the FDA’s planned warning. Under great pressure not to act, the FDA went ahead and called a meeting of its pediatric advisory committee in February 2005, which recommended a label change warning doctors and patients about the risk associated with both Elidel and Protopic.

The next month, a cancer warning appeared on the FDA Web site. (It is not known how many doctors or patients would think to look on the FDA’s Web site for new warnings.) As of January 2006, a Medication Guide for patients with the warning is supposed to be included with all prescriptions of Elidel and Protopic. The Guide does not spell out the safe duration (if there is one) of short-term use, though makes it clear that neither drug should be the first-choice treatment for eczema.

There are reasons to think that these efforts will go unheeded. Several studies show that only one in ten doctors read the drug label which is the most complete source of information about a drug’s use and harms. (Consumers are not much better.) A recent survey showed doctors are overwhelmed with drug warnings and have difficulty keeping them all straight. In the case of Protopic and Elidel, the dermatologists’ professional organizations were actively working against the FDA’s plan to issue a warning. The Society for Pediatric Dermatology, in a letter dated November 30, 2005, advised its members to write the FDA to tell the agency that warnings are not warranted because “abrupt discontinuation of these medications out of fear [will result] in disease flares in many children.” Furthermore, the letter claimed that an analysis of the clinical data presented to the FDA have not supported a malignancy risk.

“The great resistance in the dermatologic community to the FDA warning is based in part on the fact that many of the opinion leaders are in conflict of interest situations that too often go undisclosed,” said Dr. Elias, referring to funding from Novartis and Astellas that pays for the speakers bureau, conferences, and continuing education. And he doesn’t think much of the evidence cited to support objections to the FDA warning about Elidel and Protopic. “There are 55 articles about the safety of both drugs that claim to be long term,” Dr. Elias explained. “However, they are not, in fact, long term; the longest study lasted only six months; many are repeats—the same study published in multiple journals—and others are written by the drug company journal editor.” [Note: There are longer studies indicating the drugs are safe and effective, but they are funded by either Astellas or Novartis.]

It is quite possible that one day lawsuits will generate the publicity needed to adequately warn the public about inappropriate use of Elidel and Protopic. Several law firms now have Web sites specifically devoted to the drugs. One such firm headed by Larry M. Roth has a Web site (www.protopiclawyers.com) that features his detailed article on the history of FDA approval of topical immunosuppressants and reports of serious reactions, complete with extensive footnotes. It describes cancers, deaths, and other severe reactions reported to the FDA.

In a telephone interview, Laurilyn Cook-Arrington, a paralegal at Larry M. Roth, PA, said the law firm had retrieved this information from the FDA’s Adverse Events Reporting System with a Freedom of Information Act request. (Manufacturers are required “by regulation” to report serious drugs reactions to AERS.) Ms. Cook-Arrington said the firm has been gathering information on topical immunosuppressant drugs for three years. “Hundreds of potential claimants have contacted our firm in the last year. And many of these claims include deaths. Almost 50% of them are made on behalf of children. They involve skin cancers, as well as systemic malignancies like leukemia, Hodgkin’s disease, and multiple myeloma.”

What to do:

If you are using Elidel or Protopic, inform yourself about these medications. Start with the warnings at the FDA Web site (www.FDA.gov). Consumers and doctors can report serious adverse drug reactions to the FDA’s Medwatch Program 1(800) FDA-1088.
Ask your doctor about prescription emollients to reduce the amount of topical drugs needed to control eczema. According to Dr. Elias, “Topical prescription emollients alter biochemical abnormalities in the skin, lead to fewer flare ups, and fight off infection.” They can be used as the first treatment or as maintenance after short-term treatment with an immunomodulator, explained Dr. Elias, who is also chief science officer at Ceranix, makers of a yet-to-be-available emollient, EpiCeram.

Maryann Napoli, Center for Medical Consumers ©
May 2006

Posted in Cancer, Chronic Conditions | Tagged: Cancer, Drugs, FDA, pharmaceutical industry, product, side effects | Comments Off

Insomnia Treatments: What Works?

Posted by medconsumers on December 1, 2005

When the U.S. National Institutes of Health convened a State-of-the-Science Conference on insomnia last June, it came down hard on the drugs most people use for this common affliction. The independent panel of experts chosen months before the conference had been given the task of assessing the supporting scientific evidence for the full range of treatments. It concluded that the drugs most often used to treat insomnia—antihistamines and antidepressants—have never been proven effective for this purpose. And though insomnia can persist for decades, the panel found that most prescription drugs approved for this condition have not been carefully evaluated for long-term use. The panel advised greater use of one non-drug approach to sleeplessness, a technique called cognitive-behavioral therapy.

Still, most insomniacs continue to turn to drugs in greater numbers. And the ubiquitous drug advertising campaigns encourage them to do so.

Ambien CR and Lunesta

Eight prescription drugs are approved by the Food and Drug Administration (FDA) for insomnia. Two of them have dominated recently in terms of advertising to the public. Ambien CR is a new extended-release version of Ambien, which has been on the market for 12 years. Ambien is so well known that full-page ads for its new extended-release version are appearing in magazines without mention of what the drug is for. The manufacturer, Sanofi-Aventis, is aggressively selling this new version to hold on to its market share as Ambien is due to go off patent next year. (Ambien was the world’s most popular prescription sleep drug in 2004, accounting for $2.1 billion in sales.) The full-page ads announce a “Free 7-Day Trial Offer” for Ambien CR. An accompanying coupon falls out of the magazine that people are encouraged to bring to their doctors for a starter kit of free pills.

It’s good to keep in mind when reading such ads that omitting the purpose of the drug allows the manufacturer to avoid identifying the harms associated with the drug and the warning that it is only for short-term use. One would have to read the packet insert, or what the FDA calls the label (for access, see page 3) to learn about adverse effects that include abnormal thinking, behavior changes, anxiety, memory loss, and addiction. Companies that make sleeping pills assert that these reactions can occur in a small number of people who take any drug in this class known as sedative/hypnotics. All drugs in this class are also known to cause what the manufacturers prefer to call “dependency,” when taken for more than a few weeks.

Ambien CR purportedly has the advantage of keeping people asleep longer. Although short-term use is never spelled out, the packet insert indicates just how brief the FDA-required trials were. Only two trials were performed to demonstrate efficacy. Both were only three weeks in duration, and assessments were conducted after two weeks of treatment.

Lunesta, which came on the market last April, is the strongest rival to Ambien. So far, it is the only prescription sleep medication approved by the FDA for long-term use. Even so, its manufacturer, Sepracor, is explicit in the fine print of its magazine and newspaper ads, stating, “It [insomnia] usually requires treatment for only a short time, usually 7 to 10 days. If your insomnia does not improve after 7 to 10 days of treatment, see your doctor, because it may be a sign of an underlying condition.”

The packet insert for Lunesta has this summary of clinical trial findings without quantifying how much sleep improvement people can expect from this drug: “Lunestra significantly improved sleep latency and improved measures of sleep maintenance (objectively measured as wake time after sleep onset and subjectively measured a total sleep time).” And here’s a key warning that might be overlooked “Be aware that you may have more sleeping problems the first night or two after stopping any sleep medication.”

Lunesta and Ambien CR pose the risk of a form of memory loss known as “traveler’s amnesia.” This can occur during an airplane flight when the person wakes up before the effect of the medicine is gone. The drug should be avoided in such a circumstance when it is impossible to get a full night of sleep. Both Lunesta and Ambien CR carry the warning not to drink alcohol. And both drugs should be taken in the smallest effective dose by people over age 65 years.

Short-Term Use of Prescription Sleep Drugs

Suppose you are one of those rare older people who use sleep medicines appropriately—no more than ten days. What are the benefits and harms of short-term use? A team of Canadian researchers led by Jennifer Glass, PhD, University of Toronto, conducted an analysis of all studies in which people over the age of 60 years had been given one of the standard prescription drugs for insomnia, including Ativan, Xanax, Restoril, Dalmane, Ambien, and Sonata. Altogether, the analysis included 24 studies involving 2,417 participants who had taken either a placebo (sugar pill) or one of the above prescription drugs. To be included, the studies had to assess any of the above drugs taken for at least five consecutive nights for insomnia. Findings were published last month in the British medical journal, BMJ.

The drugs were associated with harms that are particularly detrimental to older people, such as cognitive effects, falls, and ataxia (inability to coordinate the muscles in voluntary movement);
adverse cognitive effects were five times more common in people on a drug than in those on the placebo;
daytime fatigue was nearly three times more common in people taking a drug;
and the drugs provided only marginal improvements.

Dr. Glass and colleagues concluded that the short-term benefits of these drugs may not justify the increased harm, especially to older people who are already at risk for adverse cognitive reactions.

Other Approaches to Sleeplessness

The panel of experts at the State-of-the-Science Conference identified antihistamines as the most commonly used over-the-counter treatment for insomnia. But there is no systematic evidence to demonstrate effectiveness and there are significant concerns about risks, according to the panel. The adverse effects include “residual daytime sedation, diminished cognitive function, and delirium, the latter being of particular concern to the elderly.”

Alcohol does reduce the time it takes to fall asleep, but large amounts will result in poorer quality sleep and awakening during the night. Melatonin, a natural hormone that can be purchased over the counter, is better for jet lag than insomnia. Furthermore, there is no information about the safety of long-term use.

The panel also assessed alternatives to drugs, such as tai chi, yoga, acupuncture, and light therapy. All were deemed potentially useful, but inadequately evaluated. Only one non-pharmacological approach to sleeplessness, called cognitive-behavioral therapy (CBT), was judged to have been proven effective in moderate to high-quality trials that compared it to drug therapy. This form of therapy was shown to be as effective as prescription drugs are for short-term treatment of insomnia minus the risks.

CBT was described by the panel as “cognitive restructuring in which anxiety-producing beliefs and erroneous beliefs about sleep and sleep loss are specifically targeted.” The treatment involves a series of visits to a therapist trained in this method, a prospect that might be out of reach for many people.

To explore a lower cost, self-help version of CBT that involves $35 and access to the Internet, go to www.myselfhelp.com, which describes itself as funded in part through a series of Small Business Innovative Research Grants from the National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services.

How to Obtain the Packet Insert, aka Drug Label

The packet insert, also known as the drug label, is produced by the drug’s manufacturer with FDA oversight. It is intended for the prescribing physician and is entirely different from the pharmacy-generated drug information. Only the packet insert has complete information on the drug, including what was proven in the FDA-required clinical trials. It is distinctive in its fine print and length (@20-40 pages), as opposed to the consumer friendly format of the usual pharmacy-generated drug information. The packet inserts of many drugs contain both a professional and a patient version. Read both.

There are several ways to obtain the packet insert. Ask the pharmacist for a copy when purchasing the drug; go to the public library and consult the Physicians’ Desk Reference; visit the FDA’s Web site (www.fda.gov) and click into the following sections: drugs, drugs@FDA, the drug’s name, and finally, drug label. And sometimes this works best: perform a google search with the drug’s name plus the word label.

Posted in Alternative Medicine, Men's Health, Women's Health | Tagged: Alternative Medicine, Drugs, FDA, pharmaceutical industry | Comments Off

Perils of Speedy Drug Approval

Posted by medconsumers on December 1, 2005

I was invited to speak at a November FDA meeting about the upcoming 2007 re-authorization of the Prescription Drug User Fee Act. Initially passed in 1992, PDUFA allows the FDA to collect a user fee from any drug company that submits a New Drug Application. In exchange, the FDA agrees to complete its review of the drug company’s clinical trials proving safety and efficacy within six months for priority drugs. And within a year for all others. What follows is a summary of my remarks.

In 2004, most of the money for new drug reviews came from industry. Its growing role as the major source of funds for FDA reviews creates a potential conflict of interest that is likely to erode, if it hasn’t already, the public’s trust in both the FDA’s independence and the safety of new drugs.
PDUFA has clearly enabled the FDA to complete the review of new drug applications more quickly. Almost all reviews are completed within the specified time limits. And the agency reports that more than 1,000 new drugs have been approved since PDUFA. But there is no evidence that either faster review times or access to the 1,000 new drugs, many of which offer no advantage over older drugs, have benefited the public.
There has been concern that faster review times may be causing harm by exposing millions of people to new products that are subsequently found unsafe. Vioxx and Bextra are perhaps the best known examples. And 14 other drugs, approved since 1992, have been withdrawn because of serious harm.
The FDA asked all the people who addressed the meeting to comment on the successes and failures of PDUFA since 1992 and what should be improved or changed in 2007. But since there is little or no research evidence on which to base such an assessment, that leaves only anecdotes, which is a poor substitute for science when making public policy.
Despite the paucity of evidence about the consequences of continuing the user fees, the realities of a strained federal budget and chronic underfunding of the FDA by Congress, mean that user fees are likely to be a necessary evil for the foreseeable future.
The FDA’s voluntary MedWatch program that collects reports of adverse drug reactions from doctors and the public is of limited value, even if it were provided with more resources. If PDUFA is reauthorized, it should fund the FDA’s ability to monitor drug safety using 21st century technologies. This includes proactive monitoring of data derived from such large electronic databases as those of the Veteran’s Administration and health plans like Kaiser-Permanente. This would allow the FDA staff to link prescription drug use with medical histories—a critical tool for both uncovering unexpected adverse drug reactions and having enough information to establish cause.
If PDUFA is reauthorized, user fees must be increased to a level permitting FDA to hire a sufficient number of trained staffers to monitor adverse reactions after the drugs become available. Money is also needed to beef up FDA’s computer capacity and to enable its top officials to share safety information with other federal health agencies, specifically the National Institutes of Health, Centers for Disease Control and Prevention, and the Agency for Healthcare Quality and Research.
Unfortunately, industry funding of drug safety surveillance creates a potential conflict of interest. For that reason, reliance on user fees to pay for enhanced FDA drug safety efforts must be contingent on erecting a firewall between industry and the agency so he who pays the piper cannot call the tune.
Congress should mandate the creation of a new Office of Drug Safety that operates independently of the FDA drug approval staff. The new office should be given the authority to order a drug off the market if safety concerns warrant. It must also have the power to take other actions to limit harm such as ordering a drug maker to put warnings about adverse reactions in the product information given to professionals and patients. At present FDA can only negotiate such critical changes in labeling with the maker. In the case of Vioxx, it took almost two years for Merck to agree to include even a mild caution about an increased risk of heart attack and stroke.

Posted in Drugs | Tagged: Advocacy, Drugs, FDA | Comments Off

Reliable Information on the Internet

Posted by medconsumers on November 1, 2005

Written by Maryann Napoli at the request of the New Zealand Guidelines Group in anticipation of her appearance at the National Consumer Summit in Auckland, October 31, 2005.

Much as I’d like to respond to this assigned topic with a list of sure-fire ways to identify trustworthy Web sites, I’m sorry to say that I cannot. From this USA-based consumer advocate’s point of view, there isn’t much I can wholeheartedly recommend out there. I wouldn’t think of relying on the standard sources like the American Heart Association and the National Cholesterol Education Program given their considerable pharmaceutical industry funding.

And the fact that a board of academic physicians oversees a Web site’s content is no guarantee of high-quality information. Case in point is the U.S. National Cancer Institute’s Physicians Data Query (PDQ) database www.cancer.gov I still see it as the best source of evidence-based cancer treatment information, despite the fact that I have found numerous gross errors in this Web site over the years. Lobular carcinoma in situ, for example, was described as a breast cancer (leading women to think immediate aggressive treatment is critical); whereas LCIS is merely a marker for cancer. In another instance, prostatectomy was described (in 1989) as the most common first choice treatment for prostate cancer—a misleading statement given the fact that there is no evidence that proves it superior to no treatment at all. Worse, the no-treatment option appeared in the “health professionals” section of the database but not in the material directed at “patients.” My critiques of the PDQ have always been taken seriously and often led to changes. “Watchful waiting”, for example, now heads the list of treatment options for men with early-stage prostate cancer…in both the “patient” and the “health professional” sections of the database.

The American Cancer Society, on the other hand, was unresponsive when I asked why it instructs doctors to tell their patients about the risks and benefits only where it concerns the PSA screening test for prostate cancer. After all, that’s not the only cancer screening test with risks as well as benefits.

Though the explosion of information available on the Internet is gratifying in many ways, it is still hard to find certain information crucial to informed decision-making. Just take a decision many of us will have to make: Should I take a prescription drug for the rest of my life? Millions of healthy adults around the world have accepted the idea that risk factors like bone loss and high cholesterol should be treated with lifelong drug therapy.

The woman with osteoporosis told to take the bone drug Fosamax will find lots of information about how the drug improves bone density. But how good is it at reducing the rate of hip fracture, the most serious consequence of osteoporosis? It’s not easy to ferret out the three-year trial which found 2% of women on the placebo experienced a hip fracture, compared to 1% of women on Fosamax. These results are enlightening, considering how heavily promoted this drug is. Only 1% of the women on Fosamax actually benefited from the drug; and only 2% had a hip fracture without the drug. You can find this information at the U.S. Food and Drug Administration’s Web site (www.fda.gov). but it takes some doing. First, you must find your way to the right section of the site and then slog through reams of fine print of the drug labeling information that the pharmaceutical company publishes with FDA oversight.

Even then, you wouldn’t know that this three-year trial provides the best long-term effectiveness information on Fosamax—and it applies only to elderly women with osteoporosis and at least one fracture. That doesn’t represent the primary Fosamax users in the USA, thanks to misleading drug advertising aimed at physicians. When Fosamax first came on the market ten years ago, its maker Merck mounted an advertising campaign featuring white women in early middle-age. No mention of prior fractures, but plenty of encouragement for bone-density testing (screening creates customers). As an antidote to this market-driven poison, osteoporosis researcher Susan M. Ott, MD, University of Washington, maintains an advertising-free Web site that helps women and doctors determine when drug therapy is and is not appropriate (http://courses.washington.edu/bonephys).

Anyone about to go on an open-ended drug regimen would want to weigh the benefit against the odds of having a serious adverse drug reaction. Three years ago, when writing about the popular cholesterol-lowering drugs called “statins” (Lipitor, Zocor, Pravachol, etc.), I was pursuing that question on behalf of my readers with high cholesterol but no heart disease. Fortunately, I found my way to a trustworthy source of drug information, Therapeutics Initiative in British Columbia, Canada (www.ti.ubc.ca Letter 48). It was the only place I found the odds of benefit compared to the odds of having a serious adverse drugs reaction. Five major trials have compared statins with placebos in people without heart disease. Only two trials, however, have released their serious adverse events (SAE) data! Working with what they had, the Canadian researchers combined the results of the two trials and found only one modest benefit to statins. These much-touted drugs reduced the odds of a non-fatal heart attack by 1.8% (in men only). But this modest benefit was canceled by a 1.4% increase in the rate of SAEs among the statin users! And if someone wants to check whether a particular statin—or any other drug—is so risky it should be taken off the market, there’s always the Washington, DC-based Health Research Group (www.citizen.org/hrg).

Consumer advocates willing to take the time can find some gems of hypocrisy at the most mainstream of Web sites. Every November the federal government in the form of the U.S. Centers for Disease Control and Prevention scares us (via the media) with influenza death statistics. This has the desired effect of making people think they’re going to die if they don’t get a flu shot. (The death stats, by the way, are deeply suspect.) One consumer advocacy organization, the National Vaccine Information Center (www.909shot.com), led the media to transcripts of the FDA’s Vaccines Advisory Committee meetings freely available at the FDA’s Web site (though, once again, difficult to find). There for all to read were the flu experts saying in early 2003 that they had screwed up. One key viral stain had been omitted from the flu shot that was promoted vigorously as the 2003-04 flu season approached. Federal health officials just couldn’t bring themselves to be honest with the American public until the time to get a flu shot had passed. After all, we might not line up for our shots, and then the vaccine companies would have to discard their unsold products. Go to flu vaccine reviews at the Web site of the Cochrane Collaboration (www.cochrane.org), and you’ll find that, worldwide, flu vaccines haven’t worked very well in the last 35 years.

I know people don’t want to hear this, but you practically have to become an investigative reporter to find what you want…or don’t yet know you want. One has to sift through a considerable amount of information on the Internet to learn how to determine what’s valid and what isn’t. My parting advice: No matter what the topic, start with a Google search (www.google.com). It produces a wealth of information—both good and bad—and often free access to entire articles.

Posted in Advocacy, Chronic Conditions, Conflict of Interest, Drugs, Heart | Tagged: FDA, marketing, pharmaceutical industry | Comments Off

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