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Cdnc K Uaecines!Training the Immune Systemto Fight Cancer

Tommy G. ThompsonSecretary of Health and Human Services

Lester M. Crawford, D.U.M., Ph.D.

Acting Commissioner of Food and Drugs

Lawrence Bachorilr, Ph.D.Assistant Commissioner for Public Affairs

Raymond Formanek Jr. / Editor

Michael Ermarth / Art Director

Renee Gordon / Production Editor

Jan Eiicker/Copy Editor

Linda Bren, IVllcheiie Meadows, Carol Rados/Staff Writers

Lisa Latimer / Production Assistant

Cover: Phototake

FDA on the internet: www.fda.gov

FDA Consumer{\SSn 0362-1332) is publishedbimonthly by the Food and Drug Administration(HFI-40), 5600 Fishers Lane, Rockviiie, MD 20857,U.S. Public Health Service, Department of Health andHuman Services.

E d i t o r i a l M a t t e r s

Address for editorial matters is FDA Consumer, Foodand Drug Administration (HFi-40), 5600 FishersLane, Rockviiie, MD 20857. Text of articles in FDAConsumer may be republished without permission.Credit to FDA Consumer as the source is appreciated.Ail photos, illustrations, and other graphic materialsin FDA Consumer are covered under various copyrightand usage restrictions. FDA Consumerls indexed inthe Reader's Guide to Periodical Literature.

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U.S. Department Of Health And Human Services

YDkConsumerThe Magazine of the U.S. Food and Drug Administration

September-October 2004 • Vol. 38 No. 5

9 Beyond Bloodletting: FDA Gives Leeches a Medical MakeoverThe FDA approves the use of leeches as a medical device.

1 0 P s o r i a s i s : M o r e T h a n C o s m e t i cThere is no cure for this physically and emotionally painful disease, but new treatmentsare available.

17 FDA Reiterates Warning Against Online Drug BuyingThe risks of buying prescription drugs online.

18 lOM Report: No Link Between Vaccines and AutismNeither the measles-mumps-rubella (MMR) vaccine nor the vaccine preservativethimerosal is associated with autism, a new report says.

Cover Story20 Cancer Vaccines: Training the Immune System to Fight Cancer

Experimental vaccines teach the body's own defenses to attack cancer cells.

26 The Critical Path: Accelerating the Development of Medical ProductsThe FDA is working with researchers and medical product developers to modernizedevelopment tools and to speed the approval of new treatments.

29 Got Milk? Make Sure It's PasteurizedDrinking unpasteurized milk or eating products made from "raw milk" is a dangerouspractice, the FDA warns.

32 Making an Informed Decision About Breast ImplantsKnowing the risks is just as important as being aware of the benef its of breast implantsurge ry.

D e p a r t m e n t s

2 O b s e r v a t i o n s

2 L e t t e r s t o t h e E d i t o r

3 U p d a t e s

8 R e s e a r c h N o t e b o o k

38 FDA Consumer Quiz

3 9 f d a . g o v

4 0 T h e L a s t W o r d

< I ns i de Cove r :

P h o t o R e s e a r c h e r s I n c .

Psoriasis that is slowly healing. To find out more about this chronic skin disease, see page 10.

FDA Consumer / September-October 2004 /1

Observat ions

Surgery. Chemotherapy. Radiation. For decades, these have beenthe primary weapons used by physicians in the battle against cancer.And, while the battle is far frombeing won, there have been victor i es .

According to a recent reportreleased by the National CancerInstitute (NCI) and the Centers forDisease Control and Prevention, there are about 10 millioncancer survivors in the United States. The report defines asurvivor as someone who has been diagnosed with cancer,from the time of diagnosis through the balance of his orh e r l i f e t i m e .

Currently, researchers are working to develop new therapies that use the body's own defenses, called the immunesystem, to fight or prevent cancer. According to the NCI, theimmune system generally doesn't recognize cancer cells asdangerous or foreign. That's why tumors may not stimulatean immune response. Although as of August 2004 thereare no vaccines licensed by the FDA to treat cancer, there isone vaccine licensed to be used to protect against hepatitisB, an infectious agent associated with liver cancer.

Scientists continue to evaluate several different vaccinesin large human clinical trials to determine which may hean effective treatment for particular kinds of cancers. Inan effort to improve the review of potential cancer vaccines and imaging devices used in cancer diagnosis andtreatment, the FDA is creating a new Office of OncologyDrug Products to consolidate three existing areas withinthe agency.

For more on the development of cancer vaccines and thehope they hold, see our cover story titled "Cancer Vaccines:

Training the Immune System to Fight Cancer," beginningon page 20.

A chronic skin disease characterized by scaling andinflammation, psoriasis affects between 6 million and 7.5million Americans, according to the National Institute ofArthritis and Musculoskeletal and Skin Diseases. Psoriasisinvolves a type of white blood cell called a T cell, which ispart of the immune system. The disease occurs when skincells rise quickly from their origin below the surface of theskin and pile up before they have a chance to mature.

Typically, the result is patches of red, inflamed skin covered with silvery flakes that can appear virtually anywhereon the body. For more on this skin disease and the latesttreatments, see our feature story titled "Psoriasis: MoreThan Cosmetic," on page 10.

Earlier this year, the FDA released a draft of its new guidelines for manufacturers of breast implants, identifying thetype and amount of scientific data that will allow the agencyto evaluate whether these products are safe and effective.The new recommendations include guidance on testing,modes and causes of rupture, clinical study information,and labeling.

To find out more about the risks and potential benefitsof breast implants, read our feature story "Making anInformed Decision About Breast Implants," beginning onpage 32.

We also take a look at the dangers of unpasteurized milkand explain the results of a new Institute of Medicine reportthat found no link between childhood vaccines, the preservative thimerosal, and autism.

Raymond Formanek Jr.E d i t o r

To The Ed i t o r

Prescription Drug informationHave you ever tried to read the

patient information booklet enclosedwith your medication? The print type issmall, the letters are crammed in eachline, and the medical information islike reading another language.

Just recently, I had to sit downwith my mother to explain the dosing information regarding her heartmedications. She couldn't read thepatient information booklet or whatwas printed on the pill bottle. Not very

2 / September-October 2004 / FDA Consumer

comforting if English isn't your firstlanguage or if your eyesight isn't thesharpest.

Drug labeling should consist of largeletters, easy-to-read language (in different languages), comprehensive graphics, and simple layout and design. But isthat what we see? Have we really madesignificant changes to drug labels andpackages? And who exactly is policingthis? If it's the FDA, has there been arecent report on the progress of druglabeling? Has there been progress with

pharmacies and pharmaceutical agencies?

As an average consumer and a concerned daughter, it would give me greatcomfort to see my mother read fromher pill bottle, so that she knows howmany times a day she should take herheart medicat ion.

Linda ThrasybuleB r o n x , N . Y.

To The Ed i to r

The FDA's Office of Drug Safetyresponds:

Thank you for sharing your concernswith the FDA. Understanding why amedicine has been prescribed and howto use it is essential to gaining the greatest benefit f rom the medic ine whi le

keeping any harmful or annoying sideeffects to a minimum. Information onhow to use any medical product shouldbe written clearly and in a format thatis understandable to the consumer.

Recognizing the importance of useful written information for consumerswho receive prescription medicines,Congress passed a law in 1996 requir

ing that by 2006, 95 percent of allU.S. prescriptions be accompanied byinformation that is useful to the consumer. The FDA has the responsibilityof monitoring how well pharmacies areprogressing in meeting this goal.

A nationwide study done by the FDAin 2001 showed that, while 90 percentof all prescriptions are accompanied bysome form of wri t ten information forconsumers, the majority of this informat ion does no t mee t the "use fu l "criterion. In many cases, as you pointout, the letters are too small to readand the information is incomplete. Theresearch report is available on the FDA

Web site at www.fda.govlcderjreponslprescriptioninfo/. The FDA is currentlyworking with a broad coalition of pharmacy and consumer groups to improvethis situation and meet the 2006 goalspecified in the 1996 law.

However, the information that pharmacists put on the "amber bottle" thatcontains the medicine given to thepatient is not regulated by the FDA.

We encourage you and other consumers to tell your pharmacist: "Pleasegive me a label that I can read and written information about my medicinethat I can understand." ■

1 U p d a t e s

New Drug to Treat AlcoholismThe drug Campral (acamprosate) has

been approved by the FDA for treatingalcohol-dependent individuals whowant to cont inue to remain alcohol-free after they have stopped drinking.Campral is the first new drug approvedfor alcohol abuse in a decade.

Alcoholism, or alcohol dependence,is a disease. The consequences of alcohol misuse are serious and, in manycases, life threatening. Heavy drinkingcan increase the risk for certain cancers,especially those of the liver, esophagus,throat, and voice box (larynx). Heavydrinking can also cause liver cirrhosis,immune system problems, brain damage, and harm to the fetus during pregnancy. Chronic alcoholism continues tobe a widespread and debilitating disorder that places a tremendous burden onsociety in terms of health care costs, lostwages, and personal suffering.

How Campral works is not fully understood, but the drug is thought to act onthe brain pathways related to alcoholabuse. Campral was demonstrated tobe safe and effective by multiple clinical studies involving alcohol-dependentpeople who had already been withdrawnfrom alcohol (detoxified). Campralproved superior to an inactive substance

(placebo) in maintaining abstinence.This was indicated by a greater percentage of people who were treated withthe drug being assessed as continuously keeping off alcohol consumptionthroughout treatment.

T h e m o s t c o m m o n s i d e e f f e c t s

reported for patients taking Campral inclinical trials included headache, diarrhea, flatulence, and nausea. Campralis not addicting.

Campral may not be effective inpeople who are actively drinking atthe start of treatment, or in peoplewho abuse other substances in addition to alcohol. Treatment with Campral should be part of a comprehensivemanagement program that includespsychosocial support.

Campral is manufactured by MerckKGaA of Darmstadt, Germany, and willbe distributed in the United States by Forest Laboratories Inc. of New York City.

Botox Approved for SevereUnderarm Sweating

After being approved for severalother purposes since 1989, includingimproving the appearance of frownlines between the eyebrows, Botox nowcan treat severe underarm sweating(primary axillary hyperhidrosis) that

cannot be managed by topical agents.Botox (botulinum toxin type A) is

a protein produced by the bacteriumC l o s t r i d i u m b o t u l i n u m . W h e n u s e dto treat underarm sweating, smallinjected doses of the sterile purifiedbotulinum toxin stop release of thechemical messenger acetylcholine,temporarily blocking the nerves in theunderarm that stimulate sweating.

Before being treated for underarmsweating, patients should be evaluated for other potential causes of theproblem. The most common adverseevents associated with the new treatment included injection site pain andhemorrhage, sweating in other parts ofthe body, flu-like symptoms, headache,fever, itching, and anxiety.

Botox was first approved in December 1989 to treat the eye muscle disorders blepharospasm and strabismus.Since then, it has been approved totreat a neurological movement disorder causing severe neck and shouldermuscle contractions (cervical dystonia). In 2002, it was approved as BotoxCosmetic to improve frown lines.

The safety and effectiveness of Botoxfor sweating that occurs in other areasof the body have not been establ i s h e d .

FDA Consumer / September-October 2004 / 3

Updates

'Take a Loved OneDo you have a friend, neighbor, or family member

who hasn't seen a doctor, nurse, or other health careprofessional in quite a while?The U.S. Department of ffealthand Human Services suggeststhat you take charge and "Takea Loved One to the Doctor" on

Sept. 21, 2004.Americans are encouraged to

take charge of their health onthat day—or any day—by visitinga health care professional, mak-ing an appointment for a visit,attending a health event in the

community, or helping a friend, neighbor, or familymember do the same.

Launched by HHS Secretary Tommy G. Thompson andTom Joyner, a nationally syndicated radio personality andchairman of the event, the annual campaign is designedto reduce health disparities affecting racial and ethnicminorities by encouraging individuals to go to a doctoror health professional for a health screening.

Take a Loved One to the Doctor Day is part of "Closing the Health Gap," an ongoing campaign partner-

to the Doctor Day'ship that combines HHS' medical expertise with thebroadcast resources of ABG Radio Networks and theefforts of hundreds of national and community-basedorganizations. In 2003, 500 national and local organizations signed on as partners in the Take a Loved Oneto the Doctor Day campaign by organizing screening,health fairs, and other events promoting health andw e l l n e s s .

"Because of Doctor Day, thousands of Americans areshowing their family, friends and colleagues how muchthey care by taking someone to the doctor. This one preventive measure can help add years to your life," Thompson says. "Preventable diseases take a terrible toll onour nation, especially in minority communities. DoctorDay is about bringing people to health care early, whendiseases can be prevented or treated successfully. It isalso about creating awareness, providing informationand motivating Americans to make healthier lifestylec h o i c e s . "

For campaign information and materials on the Glos-ingthe Health Gap program orTake a Loved One to theDoctor Day, including a tool kit to help communitiesorganize local health events, call (800) 444-6472 orvisit www.healthgap.omhrc.gov.

Chinese Infant Formula Not SafeThe FDA is warning consumers against

using infant formula imported fromGhina because the safety and nutritional adequacy of the products areu n k n o w n .

Although no illnesses or injuriesassoc ia ted wi th Ghinese in fant fo rmula have been reported to date, ananalysis by the New York State Department of Agriculture and Markets foodlaboratory found that a Ghinese infantformula called Guan Wei Yuan contained less than 14 percent of the minimum amount of protein per servingrequired by federal regulations. Theanalysis also found the formulas contained only one-fourth of the requiredamount of fat per serving, and onlyminute amounts of the declared calcium and magnesium levels.

There is no guarantee that this product, as a potential sole source of nutrition, would provide adequate nutrientsfor an infant, FDA officials say. Infants

who are fed this formula according toinstructions provided with the productcould become severely ill or die.

Federal law requires that infant formula sold in the United States mustbe registered with the FDA at least 90days before marketing. Manufacturersare required to provide assurances thatthey are following good manufacturingpractices and quality control procedures and that the formula will allowinfants to thrive. Such assurances havenot been provided for any infant formulas from Ghina.

Gonsumers are advised to report anyadverse reactions related to infant formula immediately to health care providers as well as to the FDA and stateand local agencies.

Adverse Events Associated With'Permanent Makeup'

The FDA has alerted the public toa number of reported adverse eventsassociated with so-called "permanent

makeup," a form of tattooing calledmicropigmentation. The procedure isused to apply lip liner, eyeliner, or eyebrow color. The adverse events are associated with certain ink shades of thePremier Pigment brand of permanentmakeup inks, which are manufacturedby the American Institute of Intradermal Gosmetics, doing business as Premier Products of Arlington, Texas.

Reactions that have been reportedinclude swelling, cracking, peeling,blistering, and scarring as well as formation of chronically inflamed tissue massassociated with an infection (granulomas) in the areas of the eyes and lips. Insome cases, the effects reported causedserious disfigurement, resulting in difficulty in eating and talking.

In luly 2003, the manufacturerreported to the FDA its intent to removefive of its ink shades from the market.However, the agency has obtainedadditional reports of adverse eventsinvolving ink shades not included


Updates

in t he fi rm ' s r emova l e f f o r t . Wh i l ethe investigation continues, the FDAis alerting consumers to associatedadverse event reports received aboutPremier Products ink shades ident ified on its Web site at www.cfsan.fda.gov/r dms/cos-tat2.html.

The FDA considers tattoos, includingpermanent makeup, to be cosmetics.And the agency considers the pigmentsused in the inks to be color additivesrequiring premarket approval underthe Federal Food, Drug, and CosmeticAct. However, the agency traditionallyhas not regulated tattoo inks or pigments used in them. The actual practiceof tattooing is governed by state andlocal regulations.

The FDA urges people to reportadverse reactions from tattoos andpermanent makeup to state and localhealth authorities. Adverse events alsomay be reported to the FDA's Emergency Operations Center at (301) 443-1240 or the Center for Food Safetyand Applied Nutrition Adverse EventsReporting System (CAERS) at (301)436-2405. People also may send e-mailto [email protected].

New An th rax Tes tThe first test approved for detect

ing antibodies to anthrax will soonbe available in state and private labs.Before FDA approval of the AnthraxQuick ELISA test in June 2004, fewlaboratories other than those operated by the Centers for Disease Controland Prevention (CDC) and the U.S.Army could test blood for antibodiest o a n t h r a x .

The test helps confirm a diagnosis ofanthrax in people by showing that a person's immune system has responded toa protein produced by the anthrax-causing bacteria—BflciHiis anthracis. The testis quicker and easier to interpret thanprevious antibody testing methods. Itcan be completed in less than an hour,compared with about four hours forprevious testing methods. ImmuneticsInc. of Boston produced the test withfunding from the CDC.

Anthrax is a serious infectious disease that most commonly occurs inwild and domestic cattle, sheep, ando t h e r h e r b i v o r e s . H u m a n s c a n c o n t r a c t

anthrax by handling products frominfected animals or by breathing in orcoming in close contact with B. anthracis spores from infected animal products, such as unprocessed hides andbones. Anthrax also can be transmitted to humans when anthrax spores areused as a bioterrorist weapon. Twenty-two people became ill and five diedafter letters containing anthrax weresent through the mail in 2001.

Software System DetectsLung Nodules

In July 2004, the FDA approved anew image analysis system designedto help radiologists detect solid lungnodules. Such nodules can indicatelung cancer.

The ImageChecker CT CAD softwaresystem uses computer-aided detectionsoftware to analyze computed tomog

raphy (CT) images of the chest. Thesystem, which is the first of its kind foruse with CT chest exams, highlightsareas in the images that appear to bes o l i d n o d u l e s .

In a clinical study, 15 radiologistsindependently reviewed 90 cases from

lung CT scans andt h e n r e v i e w e dthe cases againusing the Image-Checker system.Radiologists wereable to identifym o r e n o d u l e sw i t h t h e n e w

system than theyc o u l d w i t h o u t i t ,

improving theirability to detect lung nodules thatrequire further evaluation.

The software system is manufacturedby R2 Technology Inc. of Sunnyvale,C a l i f .

Te c h P o o l S t u d i o s I n c .

Company Ordered to Halt Sales of Unapproved Drugs,Reimburse Buyers

A New Jersey judge has found that two products sold as dietary supplementsand another touted as a cosmetic are unapproved new drugs under federallaw because they were being marketed as treatments for cancer and HIVwithout FDA approval. The three products are BeneFin, a purported treatment for cancer, MGN-3, marketed as an HIV treatment, and SkinAnswer,promoted as a treatment for skin cancer. BeneFin is produced from sharkcartilage, MGN-3 is a rice bran extract, and SkinAnswer is a skin cream.

OnJuly9,2004, U.S. District Judge William G. Bassler permanently enjoinedthe defendants. Lane Labs-USA Inc. and its president, Andrew J. Lane, fromdistributing drug products unless they are first approved for marketing bythe FDA or are distributed under an Investigational New Drug application forpurposes of conducting a clinical trial. Bassler also ordered the defendants topay restitution to all purchasers of the products since Sept. 22, 1999.

"Today's action by Judge Bassler sends a strong signal that the promotionand sale of unapproved drug products, especially for the treatment of cancerand other serious diseases, will not be tolerated," said Dr. Lester M. Graw-ford. Acting FDA Commissioner.

The FDA issued a warning letter to the company and Lane in September1997. Nevertheless, the promotions of BeneFin, MGN-3, and SkinAnswercontinued through mass mailings, Internet sites, and employee statements.

The government's request for a permanent injunction was based on thedefendants' demonstrated unwillingness to comply with the law.


FDA Cautions Breast-Feeding MomsWomen who are breast-feeding

should not use the unapproved drugdomperidone to increase milk production due to safety concerns, the FDAsays. The drug is excreted in breastmilk and could expose a breast-feeding infant to unknown risks.

Published reports and case studieshave cited cardiac arrhythmias, cardiac arrest, and sudden death in peoplereceiving an intravenous form of domperidone, which has been withdrawnfrom the market in several countries. Inareas where the oral form of domperidone continues to be available, labelsfor the product contain specific warnings against its use by breast-feedingw o m e n .

Recognizing the immense healthbenefits that breast milk provides fora nursing infant, the FDA has issuedthe warning, not to discourage womenfrom breast-feeding, but rather toinform them of the potential harm

from using this particular drug whilebreast-feeding. In fact, the U.S. Department of Health and Human Services'Office on Women's Health and theAdvertising Council announced inJune 2004 the launch of a new nationalcampaign that encourages first-timemothers to breast-feed exclusively fors i x m o n t h s .

The FDA has issued six warning letters to pharmacies that compoundproducts containing domperidoneand firms that supply the drug foruse in compounding. Compounding,as it relates to pharmacies, includesthe preparation, mixing, assembling,packaging, or labeling of a drug inresponse to a prescription written bya licensed health care practitioner. Theletters state that all drug products containing domperidone, whether compounded or not, violate the FederalFood, Drug, and Cosmetic Act becausethey are unapproved new drugs andmisbranded. Further violations may

Robotic Device Cleared for Heart SurgeryA new use for a robotic device that assists surgeons in the operating

room was cleared by the FDA in July 2004.Now approved to assist in coronary bypass surgery, the da Vinci Endo

scopic Instrument Control System allows a surgeon to perform heartsurgery while seated at a console with a computer and video monitor. Afiber-optic instrument with a small video camera gives doctors a magnified internal view of the surgical site on a television screen.

The surgeon uses handgrips and foot pedals on the console to controlrobotic arms, which perform surgery with a variety of tools. A built-inwrist at the end of the tools helps the surgeon perform more exact and

U I 3 j v . ■ . m o t i o n s ._ s u r g i c a l s y s t e mis already cleared for generalabdominal laparoscopic surgeries such as gall bladderremova l and to t rea t seve reheartburn, for general chestsurgery using an endoscopethat doesn't involve the heart,and for thorascopically assistedheart procedures such as mitralvalve repair. The system is manufactured by Intuitive Surgical

W.Randolph Chitwood Jr., M.D. Suuuyvale, Calif.

result in enforcement actions, including seizure, according to the FDA lett e r s .

In addition, the agency has alertedfield personnel to watch for anyattempts to import domperidone sothat it can be detained and refusedentry into the United States. Importation of domperidone-containing products also is a violation of the law.

New Director at FDA's CDRHDaniel C. Schultz, M.D., has been

named director of the FDA's Centerfor Devices and Radiological Health(CDRH) by Dr. Lester M. Crawford,Acting FDA Commissioner.

Schultz leads the center that isresponsible for the review of medical devices, as well as radiation-emitting products such as magnetic resonance imaging equipment and X-raymachines. He also will oversee implementation of the Medical Device UserFee and Modernization Act of 2002,which authorizes the FDA to collectuser fees for its review of medicaldevice marketing applications and setsperformance goals for the reviews.

In April 1994, Schultz joined theFDA as a medical officer in the GeneralSurgery Branch of CDRH. He went onto become chief medical officer in theDivision of Reproductive, Abdominal, and Radiological Devices. Helater served as director of the Office ofDevice Evaluat ion.

Schultz received a medical degreefrom the University of Pittsburgh in1974. After entering the Commissioned Corps of the U.S. Public HealthService in July 1975, he worked as clinical director of the Tuba City IndianHospital on the Navajo reservation inArizona. He is board-certified in general surgery and family practice and isa Fellow of the American College ofSurgeons.

Schultz has been acting director atCDRH since April 1, 2004.


Updates

FDA, Alliance Work to improve Health Information AccessDid you know that among all Americans with high hlood pressure,

Mexican-Americans are less likely than whites or African-Americans toknow that they have it? Or that one-third of Hispanics with diabetes areundiagnosed?

Those statistics, prepared by the U.S. Department of Health andHuman Services Office of Minority Health, highlight the need to reinforce the commitment to improve consumer access to health information, especially to Hispanic communities, according to Dr. Lester M.Crawford, Acting FDA Commissioner.

Crawford and lane Delgado, Ph.D., president and CEO of the NationalAlliance for Hispanic Health, are working together to provide timely,accurate, and scientifically based health information to Hispanics tohelp them take active steps to prevent disease and stay healthy.

As part of that effort, the FDA and the Alliance are promoting NationalHispanic Heritage Month, Sept. 15 through Oct. 15, 2004. The outreacheffort promotes two sources of consumer health information:• The FDA web site at www.fda.govloclSpanishI provides a wealth of consumer-friendly health information in Spanish and English on topics ranging from medicine and children to mammograms and breast cancer.• Su Farnilia, a toll-free National Hispanic Family Health Helpline,offers free, reliable and confidential health information in Spanish andEnglish. The Helpline—(866) SU-FAMILIA (783-2645) operates Monday through Friday, 9 a.m. to 6 p.m. EST. Su Farnilia is a program of theNational Alliance for Hispanic Health and is made possible by supportf r o m H H S .

Safeguards Strengthened AgainstMad Cow Disease

The FDA and the U.S. Department ofAgriculture (USDA) have taken threeactions to strengthen existing safeguards that protect consumers againstthe agent that causes bovine spongiform encephalopathy (BSE), alsoknown as "mad cow disease."

In July 2004, the FDA published aninterim final rule (IFR) that prohibitsthe use of certain materials from cattle that could carry the BSE-infectiousagent in human food, dietary supplements, and cosmetics. These high-riskmaterials, known as "specified riskmaterials" (SRMs), include the brain,skull, eyes, and spinal cord of cattle 30months of age or older, and a portionof the small intestine and tonsils fromall cattle, regardless of their age. Alsoprohibited are materials from nonambulatory disabled cattle, materialfrom cattle not inspected and passed

for human consumption, and mechanically separated beef.

This IFR, in conjunction with IFRsissued by the USDA in January 2004,w i l l m i n i m i z e h u m a n e x p o s u r e t omaterials that may put people at riskfor a disease similar to BSE called variant Creutzfeldt-Jakob disease (vCJD).Scientific studies have demonstratedthat SRMs could contain the BSE agentwhen derived from cattle that are harboring the BSE agent. Consumption ofproducts contaminated with the agentthat causes BSE is the likely cause ofvCJD in people. This rule was effectiveimmediately, but the FDA is accepting comments until Oct. 12, 2004, forconsideration before publishing a finalr u l e .

In a second action, the FDA published a proposed rule requiring manufacturers and processors of humanfood, dietary supplements, and cosmetics derived from certain cattle

materials to maintain records showingthat prohibited materials are not usedin their products.

Finally, the USDA and the FDAjointly published an advance notice ofproposed rulemaking (ANPR) requesting comments and scientific information on additional measures to helpprevent the spread of BSE. In the ANPR,the FDA is requesting comments onpotential new controls on animal feed,including:• removing SRMs from all animal feed,including pet food, to control the risksof cross contamination throughoutfeed manufacture and distribution, aswell as on the farm• requiring dedicated equipment orfacilities for handling and storing feedand ingredients that may contain prohibited material during manufacturingand transportation, to prevent crossc o n t a m i n a t i o n• prohibiting the use of all mammalian and poultry protein in feed forruminants (such as cows, sheep, andgoats), to prevent cross contaminat i o n• prohibiting materials from nonambulatory disabled cattle and deadstock from use in all animal feed.

The FDA's current animal feed rule,which became effective in 1997, helpsprevent the establishment and spreadof BSE through feed in the UnitedStates. FDA and state investigatorsinspect animal feed firms to ensurecompliance with the rule. Accordingto the latest inspection results of July17, 2004, among companies handlingmaterial prohibited in feed for ruminants, compliance rates remain greaterthan 99 percent.

For more information, visit ivww.fda.gov/oc/opacom/hottopics/bse.html or www.fsis.usda.gov/oa/topics/bse.htm. ■


Research No tebook

Report: Number of Cancer Survivors IncreasingThere are 9.8 million cancer survi

vors in the United States, according toa recent report released by the Centersfor D isease Cont ro l and Prevent ion

(CDC) and the National Cancer Institute (NCI). A cancer survivor is definedas anyone who has been diagnosedwith cancer, from the time of diagnosisthrough the balance of his or her life.

The findings in the report are basedon incidence and follow-up data fromthe NCI's Surveillance, Epidemiologyand End Results (SEER) program toestimate annual cancer prevalence—the number of people living followinga diagnosis of cancer—and trends incancer survivorship.

The data show that:• 64 percent of adults whose cancer isdiagnosed today can expect to be living in five years.• Breast cancer survivors make up thelargest group of cancer survivors, 22percent, followed by prostate cancersurvivors, 17 percent, and colorectalcancer survivors, 11 percent.• The majority, 61 percent, of cancersurvivors are age 65 and older.• An estimated 1 of every 6 people over65 is a cancer survivor.• 79 percent of childhood cancer survivors will be living five years after diagnosis and nearly 75 percent will be living10 years following diagnosis.

"The findings in this report haveimportant implications for both the

public and health practitioners," saysLoria Pol lack, M.D., a CDC medicalofficer. "There is a growing need to promote health and ensure the social, psychological and economic well-being ofcancer survivors and their families."

Getty Images

In the past. Pollack says, publichealth programs concentrated on earlydetection and prevention of cancer.However, the focus has now expandedto include cancer survivorship, transforming survivorship research intopractice, and developing clinical guidelines to provide attentive follow-up andhealth promotion to survivors.

"Issues faced by cancer survivorsinclude maintaining optimal physicaland mental health, preventing disability and late-effects related to cancer andits treatment, and ensuring social and

economic well-being for themselvesand their family," says julia Rowland,M.D., director of the Office of CancerSurvivorship at the NCI. She adds,"NCI takes these factors into consideration when conducting research toidentify, examine and prevent or contro l adverse effects associated wi thcancer. We are working to enhancesurvivors' quality of life."

The CDC's Division of Cancer Prevention and Control is supportingstates, tribes, and tribal organizationsto develop and incorporate survivorship priorities into their comprehensivecancer control plans. The CDC is alsoworking with national organizationsto promote education, awareness, andcommunity programs that offer servicesand support for cancer survivors.

"Cancer is the second leading causeof death in the United States after heartdisease. The number of cancer survivorsin this country has increased steadilyover the past 30 years for all cancerscombined. We expect the number ofsurvivors to increase as improvementsare made in cancer detection, treatment,and care and as the population ages,"says Health and Human Services Secretary Tommy G. Thompson.

The report was published in the June25, 2004, issue of the CDC's Morbidityand Mortality Weekly Report.

To view the article, visit www.cdc.goulmmwr/PDF/wk/mm5324.pdf. ■

We're eager to hear what you like and what you don't like. We also want to know the subjects you'd like to seec o v e r e d .

To contact FDA Consumer:

Letters to the Editor should be 200 words or less. If you would like your comments to be considered for publication,please include your name, address, and telephone number during business hours. The editor reserves the right to editletters for space and appropriateness. E-mail your letters to [email protected] or send to the address below.Inquiries about the magazine: E-mail other questions to [email protected] or write to the address below.General FDA questions: E-mail [email protected].

Mailing address: Food and Drug Administration (HFI-40), 5600 Fishers Lane, Rockville, MD 20857


Beyond Bloodletting:FDA Gives Leeches a Medical MakeoverBy Carol Rados

For thousands of years, leeches have been worming their way in and out of medicine as a questionable cure for anything from headaches to gangrene,

reaching their height of medicinal use in the mid-1800s.Today, the slimy aquatic creatures are making a comebackas a legitimate treatment that can help heal skin graftsand restore blood circulation. Their primary function is todrain blood. Pooled blood around a wound can threatent issue surv iva l .

In June 2004, the Food and DrugAdministration cleared the first application for leeches {Hirudo medicinalis)to be used in modern medicine as medical devices. By definition, a medicaldevice is an article intended to diagnose, cure, treat, prevent, or mitigate adisease or condition, or to affect a function or structure of the body, that doesnot achieve its primary effect througha chemical action and is not metabol i z e d .

Surgeons who do plastic and reconstructive surgery find leeches especiallyvaluable when regrafting amputatedappendages, such as fingers or toes. Severed blood vessels in such cases oftenare so damaged that they lack the abilityto clear the area of blood. In these cases,it is difficult for the surgeon to make aroute for blood to leave the affected partand return to circulation.

"The i dea beh ind the l eeches i sto cause blood to ooze so that thebody's own blood supply will eventually take over and the limb can goon and survive," says Rod 1. Rohrich,M.D., president of the American Society of Plastic Surgeons and chairmanof the Department of Plastic Surgeryat the University of Texas Southwestern Medical Center. Leeches apply theperfect amount of suction to get theblood flowing. But Rohrich also sayshe uses the leeches only when there'sa compromised situation, such as fol

lowing surgery, "whenthe patient's own bloodsupply isn't adequate."

Packing a one-twochemical punch, thebenefit o f leech ther

apy comes not fromthe amount of blood that is extracted,but in the powerful anti-clotting agenthirudin, contained in the parasite'ssaliva, which keeps blood flowingfreely. At the same time, leeches emit anatural anesthetic that minimizes painduring their feast.

Having disk-shaped suckers oneach end of their bodies helps leechesfeed, as well as hang on. The number of leeches used varies with eachpatient—typically two or three leechesare applied to the body until they dropoff after about 40 minutes, and thenthe process is repeated with a newleech "team." At $7 to $10 apiece, theirexpense won't break budgets of physicians or hospitals.

The FDA considered safety data aspart of reviewing the marketing application for the leeches submitted byRicarimpex SAS of Lysines, France.In addition, the agency studied published literature on the use of leechesin medicine, how the leeches are fed,their environment, and the personnelw h o h a n d l e t h e m .

Leeches were already being usedin hospitals. A 1976 law has allowed

P h o t o R e s e a r c h e r s I n c .

The saliva of medicinal leeches contains hirudin, a substance that prevents blood from clotting.

companies that raised and sold medical leeches before that year to continuedoing so. Newcomers seeking to market leeches for medical purposes, however, were required by the 1976 law togain FDA approval.

You won't find the type of leechesapproved for medical use in a lake,river, or swamp. Rudy Rosenberg,owner and vice president of LeechesUSA Ltd., the initial importer and distributor for Ricarimpex in the UnitedStates, says the leeches are raised underoptimum conditions in controlledbasins and laboratories. The facilitiesare certified, and all lots are tracked.This, he says, protects patients frominfection. Leeches drop off after "feeding," and must be treated as infectiouswaste material. Rosenberg says that heknows of no case of leech-borne infection having been reported.

How do people react to being treatedwith these slimy parasites? "Initially,they're repulsed by the idea of leechesas a treatment," says Rohrich, "but eventually, they come to terms with the factthat it may be saving their lives." ■


Psoriasis:More Than Cosmetic

By Linda Bren

It's not easy living in Leah Bird's skin. "The worst thing is when people juststare," says Bird. "I almost like it better if someone comes up to me andasks me what i t is."

Then she'll tell them, "I have psoriasis. It's not contagious."Bird, 51, of suburban Boston, has had flare-ups of this chronic skin disease

since she was a teen-ager. The dry, red, scaly patches of skin that characterize

psoriasis have covered as much as 85 percent of her body, she says. "It alarmspeople. It looks very scary to people who don't know what it is."

But psoriasis is more than cosmetic. "This disease is common, chronic, and

costly, both in monetary terms and in quality of life," says lonathan Wilkin,M.D., director of the Food and Drug Administration's Division of Dermato-logic and Dental Drug Products.

More than 5 million Americans have psoriasis, and they spend between $1.6billion and $3.2 billion each year to treat the disease, according to the NationalPsoriasis Foundation (NPF). Between 150,000 and 260,000 new cases are diagnosed each year, including 20,000 in children younger than 10.

"Psoriasis can be painful and can be profoundly disruptive to a person'slife," says lill Lindstrom, M.D., an FDA dermatologist. "People who don't haveit don't understand how burdensome the disease can be. There is constant

shedding of scales. There can be functional impairment, itching, and pain."And health complications, such as arthritis, accompany some cases.

Leah Bird of suburban Boston has had psoriasis for more than30 years. She says it's important for people who have theskin condition to "work on their emotional well-being."

B l a c k S t a r / D a n a S m i t h

FDA Consumer / September-October 2004 /11

There is no cure for psoriasis, but abroad range of treatments is availableto reduce the symptoms, clear up theskin, and send the disease into remission. FDA-approved treatments rangefrom creams rubbed into the skin, tolasers that aim ultraviolet rays at theskin, to the newest treatments—injectable drugs made from living cells.

W h a t i s P s o r i a s i s ?

Psoriasis is an inflammatory skindisease in which skin cells replicateat an extremely rapid rate. New skincells are produced about eight timesf a s t e r t h a n n o r m a l — o v e r s e v e r a l

days instead of a month—but therate at which old cells slough off isunchanged. This causes cells to buildup on the skin's surface, formingthick patches, or plaques, of red sores(lesions) covered with flaky, silvery-white dead skin cells (scales).

Rarely life-threatening, at its mildest, psoriasis can be itchy and sore. At

Skin Diseases, about 15 percent ofpeople with psoriasis also get psoriaticarthritis, which can be progressivelydisabling if untreated.

Wayward White Blood CellsScientists believe that certain white

blood cells called T lymphocytes (Tcells) play an important role in psoriasis. "And the disease has a geneticcomponent," says Lindstrom. In aboutone-third of psoriasis cases, there is afamily history of the disease.

T cells circulate throughout the body,orchestrating the immune system'sresponse to foreign invaders like bacteria or viruses. In people with psoriasis, the defective T cells are overactiveand migrate to the skin as if to heal aw o u n d o r w a r d o f f a n i n f e c t i o n . T h i s

process leads to the rapid growth ofskin cells, triggering inflammation andthe development of lesions.

Both the environment and geneticsmay play a role in the development of

ers used to treat high blood pressure,and antimalarial drugs.

Diagnosis and TreatmentNo single test exists to diagnose pso

riasis, but a dermatologist can usuallydetermine it by the appearance of theskin and by looking at an individual'spersonal and family medical history.In some cases, a specialist will confirmthe diagnosis by examining a smallpiece of skin (biopsy) under a micros c o p e .

P s o r i a s i s t r e a t m e n t s f a l l i n t o t h r e e

categories: medications externallyapplied to the skin (topical), ultraviolet light applied to the skin (phototherapy) , and medications taken by mouthor injected (systemic).

Topical TreatmentsTopical lotions, ointments, creams,

gels, and shampoos for the skin andscalp are prescribed for mild-to-moderate cases of psoriasis or in combination

Both the environment and genetics may play a rolein the development of psoriasis.

its worst, it's painful, disfiguring, and psoriasis. "In genetically predisposed with other treatments for more severedebilitating. About two-thirds of the children, psoriasis can be triggered by cases. FDA-approved prescription topi-people with psoriasis have a mild form a strep or other infection," says Lind- cals to treat psoriasis include cortico-of the disease, says the NPF. About one- strom. That's what happened to author steroids, retinoids, calcipotriene, andthird have moderate or severe psoriasis. John Updike. After an attack of mea- coal tar products. These drugs slowPsoriasis can affect people at any age, sles at the age of 6, Updike developed down skin cell production and reducebut it most often strikes those between psoriasis "in all its flaming scabbiness inflammation.the ages of 15 and 35. from head to toe," as he later described Corticosteroids are synthetic drugs

There are five forms of psoriasis, it in his memoir. Self-Consciousness. that resemble naturally occurring hor-P laque pso r ias i s i s t he mos t common— mones . S ide e f fec ts may inc lude th in -affecting 4 out of 5 people who have Remission and Reactivation ning of the skin and stretch marks atpsoriasis, says the NPF. Plaque psoria- While the disease never goes away, the area where the topical is applied,sis may start with small red bumps and the symptoms of psoriasis subside for Corticosteroids may also suppress theprogress to larger lesions. a while (remission) and then return adrenal glands' production of natural

The plaques of psoriasis occur most (flare-up, or reactivation). Remission steroids, which could leave the bodyfrequently on the elbows, knees, other can last for years in some people; in susceptible to disease,parts of the legs, scalp, back, face, others, flare-ups occur every few weeks. Retinoids are derivatives of vitamin Apalms, and soles of the feet. Psoriasis Certain triggers, such as stress and sea- and calcipotriene is a synthetic form ofcan also affect the fingernails and toe- sonal changes, can reactivate psoriasis, vitamin D. Retinoids and calcipotrienenails, causing pitting, discoloration, "Certain drugs may also exacerbate it," are not the same as over-the-counteror tissue buildup around the nails, says Lindstrom, including lithium, pre- vitamin A and D supplements, whichAccording to the National Institute scribed for bipolar disorder (also called have no value for treating psoriasis,of Arthritis and Musculoskeletal and manic-depressive illness), beta-block- says Wilkin. "These topical creams on


Healthy Skin vs. Psoriasis

Healthy Skin Psor ias is

keratin layer

epidermis

sweat glandh a i r f o l l i c l e

d e r m i s

s u b c u t a n e o u s —

layer

sca les

plaques

inflamed skin H

In psoriasis, an activated immune system triggers the skin cells to reproduce every threeto four days, building up on the outer layers (epidermis and keratin). The epidermisthickens, blood flow increases and reddens the skin, and silver-gray scales cover it.

the sk in de l i ve r t he v i t am in - l i ke chemicals right to where you want them," hesays. Skin irritation where the topical isapplied may be a side effect. Retinoidsare also available by prescription asoral systemic drugs.

Coal tar products can help with scaling, itching, and inflammation butare not used as commonly as someother topicals, says Lindstrom. Theyare messy, can stain, and have a strongo d o r .

Carol Bentson of Washington, D.C.,has had plaque psoriasis for more than30 years, causing "major itching" allover and pain along the scalp line. Shehas treated it with topical corticosteroids, ultraviolet light, and cortisoneinjected into her scalp, elbows, toes,and legs. At times, "ointment wouldn'tpenetrate the areas of heavy plaquebuildup, no matter how much I puton," she says.

B e n t s o n h a s a c c u m u l a t e d " s a c k s o flotions" to treat psoriasis. She would

find a topical treatment that worked fora while but then quit working, forcingh e r t o s w i t c h t o a n o t h e r o n e .

"With a potent topical steroid, thereis a phenomenon called tachyphylaxis," says Craig Leonardi, M.D., associate clinical professor of dermatologyat the Saint Louis University Medical School. "Prolonged use can causedown-regulation [decrease] of steroidreceptors in cells. The net effect is thatthe skin becomes less responsive tos t e r o i d s o v e r t i m e . "

Wilkin adds that this unresponsiveness may be a temporary effect. "Apatient may need to be off the steroidfor a few days or a week and when putback on it, the responsiveness couldc o m e b a c k . "

Light TherapyExposing the skin to ultraviolet

(UV) light—either from the sun or anartificial source—sets off a biologicalprocess that kills T cells, which slows

Infographic: FDA/Renee Gordon

the buildup of skin cells and reducesi n fl a m m a t i o n .

Light boxes that emit UV light to treatmoderate-to-severe psoriasis and others k i n d i s e a s e s a r e m e d i c a l d e v i c e s t h a t

require licensing by the FDA. A personsteps into the light box, which is aboutthe size of a telephone booth, whilelamps direct the light onto the body.

" T r e a t m e n t w i t h t h e s e d e v i c e s i s

complex," says Richard Felten, an FDAc h e m i s t a n d s e n i o r m e d i c a l d e v i c ereviewer. The physician must determine an individual's sensitivity to UVand adjust the light emissions for them o s t e f f e c t i v e t r e a t m e n t w i t h t h e l e a s trisk of side effects, he says. Side effectsmay include burning, darkened skin,premature aging, and skin cancer. Threeto five treatments per week for severalweeks or months may be needed to getthe psoriasis under control, followed byweekly maintenance treatments.

Light therapy, or phototherapy, isusually done in the physician's office or


Types ofPsor iasis

Plaque psoriasis—Skin lesions are red atthe base and covered by silvery scales. Theycan appear on any skin surface, although theknees, elbows, scalp, trunk, and nails are themost common locations. About 80 percent ofpeople with psoriasis have this type.

P u s t u l a r p s o r i a s i s —Bl i s te rs o f non in fec t iouspus appear on the sk in,particularly the hands andfeet. Attacks of pustularpsoriasis may be triggeredby medications, infections,stress, or exposure to cert a i n c h e m i c a l s .

G u t t a t a p s o r i a s i s —Small, drop-shaped lesionsappear on the trunk, limbs,and scalp. Guttata psoriasis is most often triggeredby upper respiratory infections, such as a sore throatcaused by streptococcalbacteria (strep throat). f

J

Inverse psoriasis—Smooth, red patchesoccur in the folds of the skin near thegenitals, under the breasts, or in thearmpits. The symptoms may be worsenedby friction and sweating.

E r y t h r o d e r m i c p s o r i a s i s -Widespread fiery redness andscaling of the skin may be areaction to severe sunburn or totaking corticosteroids (cortisone)or other medications. It can alsobe caused by a prolonged periodof increased activity of psoriasisthat is poorly controlled.

Sources: National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nationai Psoriasis Foundation


a medical facility that has the devices,says Felten. "The FDA has clearedsome dev i ces f o r home use unde r ce rt a i n c o n d i t i o n s a n d w i t h a d o c t o r ' s

prescription," he says. Home devicesinclude handheld devices for scalppsoriasis and stand-alone light boxesfor other areas of the body.

Light therapy usually involves a shortwavelength of ultraviolet light, calledUVB. For people with resistant moderate-to-severe psoriasis, a combination ofan oral or topical drug called psoralenand a longer wavelength ultraviolet A

tin, methotrexate, cyclosporine, andbiologies, which are drugs made fromproteins of living cells. Methotrexate,cyclosporine, and the biologic drugsare immunosuppressants, meaningthey lower the body's normal immuneresponse. "These drugs suppress theimmune cells that cause psoriasis, butthey don't distinguish these cells fromthe immune cells that protect our bodyfrom infections," says Elektra Papado-poulos, M.D., an FDA dermatologist.

Acitretin, a retinoid that is givenorally for severe psoriasis, helps nor-

T-cell activation. Raptiva inhibits theactivation of T cells and the migrationof those ce l l s ac ross b lood vesse ls andinto tissues, including the skin.

E n b r e l i n h i b i t s t h e a c t i o n o f a ninflammatory chemical messenger inthe immune system called tumor necrosis factor-alpha (TNF-alpha), which isbelieved to play a role in both the skinand the joint symptoms of psoriasis.

All three biologies are injected. TheFDA has licensed Amevive to be givenin a physician's office, either injectedinto the muscle or into a vein (intrave-

'Biologies are an alternative treatment tosome of the traditional therapies/

(UVA) light is used. This treatment is malize the growth of skin cells. One nously). It's a once-a-week treatmentcalled "psoralen plus UVA" (PUVA). of the side effects is raised fat (lipid) for 12 weeks; further treatments may

"Psoralen makes the patient more levels in the blood, and people taking be given after a waiting period,sensitive to the UVA," says Lindstrom, this drug must get regular blood tests The FDA has licensed Raptiva and"so once they've taken a dose of pso- to monitor their cholesterol and tri- Enbrel for home treatment. People canralen, a smaller dose of UVA is needed glyceride levels. inject themselves with Raptiva underto treat them." Patients must be very Methotrexate and cyclosporine slow the skin once a week or with Enbrelcareful to protect both skin and eyes the growth of skin cells. Methotrexate, once or twice a week. Both drugs arefor 24 hours after psoralen use to pre- taken orally or by injection, is also a recommended for continuous use tovent damage, she says. chemotherapy drug for cancer patients, maintain results.

The FDA has also approved a spe- Cyclosporine, taken orally, was first Since biologic drugs are immunosup-cial type of laser, an excimer laser, as approved to prevent organ rejection pressants, they may carry an increaseda phototherapy device to treat mild-to- in transplant recipients. People using risk of infection and cancer. Rare butmoderate psoriasis. "These lasers can either of these drugs must be closely serious effects have also included blooddeliver a much more controlled beam monitored and should use them only abnormalities and autoimmune dis-of light to small areas of the affected for short periods of time because of eases such as lupus. Other side effectsskin," says Felten. serious, potentially fatal, side effects. are flu-like symptoms and pain and

Biologies are the newest systemic inflammation at the injection site.Systemic Treatments psoriasis treatments. Since 2003, the Some dermatologists prescribe bio-

The FDA has approved oral and FDA has licensed three biologies to logics alone for psoriasis or in combi-injected drugs that circulate through- treat moderate-to-severe plaque psoria- nation with topical treatments. Leon-out the body to treat psoriasis that is sis: Amevive (alefacept), manufactured ardi says when he prescribes biologies,moderate, severe, or disabling. These by Biogen Inc.; Raptiva (efalizumab), I don t have to resort to adding othersystemic drugs are very powerful, and made by Genentech Inc.; and Enbrel systemic therapies such as methotrex-while some may be used continuously, (etanercept), marketed by Amgen Inc. ate, cyclosporine, acitretin, or photo-others can only be used for a limited and Wyeth Pharmaceuticals. Enbrel therapy."time because of their severe side effects, was first licensed in 2002 to treat the "Biologies are an alternative treat-Once a drug is discontinued, the pso- arthritis associated with psoriasis, and ment to some of the traditional thera-riasis may reactivate. The risk of birth in 2004 to treat psoriasis itself. pies, says Papadopoulos.defects prevents many systemics from "All are immunosuppressive and have "Now we need to get the expensebeing taken by pregnant women or different proposed mechanisms," says down," says Leonardi, who has patientswomen planning to become pregnant. Papadopoulos. Amevive simultane- who pay $30,000 per year on drugs to

Systemic drugs that may be pre- ously reduces the number of immune treat psoriasis,scribed for psoriasis include acitre- cells, including T cells, and inhibits Bird feels fortunate that her insur-


ance company covers most of theexpense of Enbrel, which is prescribedfor both her psoriasis and psoriaticarthritis. Because of the arthritis pain,she has used a cane to help her walkand has had surgery on her wrist tocorrect some of the arthritis damage.Although Enbrel has been less effectiveover time for the psoriasis, she says, it sreduced her arthritic pain by about 95percent. "I can jog down to the cornerto chase after the dog," she says. "Andlast summer, I went hiking with mychildren in Colorado."

Reducing Treatment RisksBiologies, other systemic drugs, and

phototherapy are powerful treatmentswith increased risks, says Lindstrom.

Biologies may raise the risk for developing cancer and serious bacterial orfungal infections that spread throughout the body (sepsis).

Cyclosporine can damage the kidneys, methotrexate puts the liver andlungs at risk, and phototherapy cancause skin cancer. To reduce these risks,doctors often put patients on "rotationaltherapy." "The thought is by movingfrom one therapy to another therapyover time, the risk to any individualorgan is reduced," says Lindstrom.

"We also try to choose a drug with anappropriate benefit-risk ratio," she says.For mild psoriasis, a topical steroidmay be appropriate. For more severedisease, where it becomes impracticalto apply topicals over a large surfacearea several times a day, a patient mayneed a systemic treatment.

Most of the highly effective treatments for psoriasis affect the immune

system in some way. For steroid drugs,which have been around for more than50 years, the risks are well known. Butless is known about the long-term sideeffects of newer drugs, such as the bio-logics. The safety and side effects ofbiologies and other immune-suppressing drugs to treat psoriasis continue tobe monitored by drug manufacturersand t he FDA .

Emotional ImpactFor many people, dealing with the

emotional impact of psoriasis can beas challenging as treating the disease.

Bird says that mothers have pulledtheir children away from her on thesubway, and some people, horrified byher skin lesions, have asked her if shehas AIDS. As her disease has evolvedover 30 years, so has Bird's way of dealing with these reactions. In her teens,she'd tell people she had leprosy just forthe shock value, she says. Today, Bird isopen about the disease but still relies onher defiant attitude to "steel myself forthe experience" of going to the beach. "Ilove to swim," she says. But Bird knowsthat without covering herself up in apublic place, she "runs the risk of peoplejust rubbernecking."

"When I'm feeling forgiving, I try toignore them," she says, "but when I'mangry, 1 think 'didn't your mother teachyou not to stare?"'

Bird advises others with psoriasisto find out what works best for themto cope with the emotional effectsof the disease. Going to therapy hashelped her, she says. So has leading asupport group for psoriasis sufferers."It's important for people to work on

their emotional well-being," says Bird,"however they choose—whether it'smeditation, yoga, or putting on longpants and going out dancing."

The Fu tu re o f Psor ias is Trea tmentResearchers con t inue to look fo r

reasons why immune cells overreactand what genes may be responsible forpsoriasis, hoping to find better treatments, and eventually a cure. Psoriasisresearch is aided by the visibility of thesymptoms on the skin.

"You can see the disease," says Leon-ardi. "You don't have to do invasivetesting to see the effects of therapy."Psoriasis research has a "tremendous

spillover into other fields besides dermatology," he adds. "There is a hugeneed for drugs to suppress the immunesystem without the side effects."

Multiple sclerosis, Crohn's disease,rheumatoid arthritis, and type 1 diabetes are just a few of the diseasesthat may also benefit from psoriasisr e s e a r c h . ■

F o r M o r e I n f o r m a t i o nNational Institute of Arthritis and Musculoskeletal and Skin DiseasesInformation Clearinghouse(877) 226-4267TTY: (301) 565-2966www.niams.nih.gov/hi/

National Psoriasis Foundation(800) 723-9166www.psoriasis.org

American Academy of Dermatology(847) 330-0230www.aad.org

Sea, Salt, and SunSome psoriasis sufferers have tried salt water to relieve Epsom salts may have limited value. "It can help remove

their itchy or painful skin. Some have even made pilgrim- the scales of psoriasis and make people feel better," saysages to the world s saltiest lake, the Dead Sea. Parish, "but no one has shown these salts to have a thera-

"The Dead Sea is excellent for psoriatic treatment," says peutic effect."Lawrence C. Parish, M.D., clinical professor of dermatol- Whether at the Dead Sea or anywhere else, sunlightogy and cutaneous biology at Jefferson Medical College can have a positive effect on psoriasis. "But be reason-of Thomas Jefferson University in Philadelphia. "But no able about it," Parish says. "A little bit of sun is fine." Heone knows if the water itself has merit or whether the sun advises wearing a wide-brimmed hat and applying sun-is the important part." As the lowest point on the planet, screen several times a day. "Anyone who wears makeupthe Dead Sea region has unique weather and receives a knows if you put it on at 8 o'clock in the morning, itdistincdve spectrum of ultraviolet light from the sun. doesn't last until 8 at night," he says, and neither does

Soaking in bath water containing Dead Sea salts or sunscreen. ■


F D A R e i t e r a t e sWarning

Against OnlineDrug Buying

By Carol Rados

Buying prescriptiondrugs online fromu n k n o w n f o r e i g n

sources is risky business, andpeople are being advised bythe Food and Drug Administration once again to usecare when doing so. A recent

analysis of three commonlyprescribed drugs purchasedby the FDA from a Canad i a n - a d v e r t i s e d We b s i t e

showed that the "generics"were fake, substandard, and

potentially dangerous.

"Consumers who believe they aregetting equivalent products from reputable sources are being misled andputting their health at risk," says Dr.Lester M. Crawford, Acting FDA Commissioner. "This firm shipped drugsthat were the wrong strength, including some that were substantially super-potent and that pose real health risksas a result, drugs that didn't dissolveproperly, drugs that contained contaminants, and drugs that should not havebeen given because of potentially dangerous drug interactions," he says.

The FDA purchased so-called"generic" versions of Viagra (sildenafil), Lipitor (atorvastatin), andAmbien(Zolpidem). None of the drugs has aU.S.-approved generic version, so allof the purchased drugs were unapproved.

The "generic" Ambien, a controlledsubstance approved for short-terminsomnia, contained too much activeingredient, including one tablet that

was nearly double the labeled potency.Taking super-potent Ambien putspatients at risk for central nervous system depression, especially in elderly ordebilitated patients.

The "generic" Lipitor, a drug used forlowering cholesterol, was subpotentand failed to dissolve, providing onaverage only 57 percent of the activeingredient claimed on the label. It alsofailed the FDA's purity testing. Subpotent products could present a long-termrisk for the various complications ofhigh cholesterol, such as heart disease.Further, the Lipitor product was furnished to the FDA's online purchaser,even though the purchaser said that hewas taking the antibiotic erythromycin. Lipitor's label warns against takingthese two drugs at the same time.

The "generic" Viagra, normally soldto treat impotence, contained too littleof the active ingredient, failed to dissolve, and had an unacceptable level ofimpurities.

The FDA warns that, although aWeb site may appear to be reputableand may look similar to other retailpharmacy Web sites, many of theseare in fact operating from outside theUnited States and are providing unapproved drugs from unreliable sources.The National Association of Boards ofPharmacy (NABP) has established aprogram called Verified Internet Pharmacy Practice Sites (VIPPS), designedto certify Web sites that meet industrystandards. Consumers should lookfor the VIPPS certification seal on thesite or check with the NABP for a listofVIPPS-certified pharmacies at www.nabp.net/vipps/ to help minimize therisks of getting bad quality drugs fromdisreputable sources. ■


lOM Report: No LinkBetween Vacc ines andA u t i s mBy Michelle Meadows

The report, released in May 2004,was prepared by a committee of independent experts established by thelOM in 2001 at the request of the Centers for Disease Control and Prevention(CDC) and the National Institutes ofHealth (NIH) to evaluate evidence onpotential links between childhood vaccines and health problems. The agencies explored the issue because of growing controversy and questions from thepublic about vaccine safety.

Some parents have expressed concern because the symptoms of autismtypically emerge in a child's secondyear of life, around the same time children first receive the MMR vaccine.Autism is a complex set of severe developmental disorders characterized by

repetitive behavior and impaired socialinteract ion and communicat ion abi l ities. Other concerns the committeelooked at include the use of thimero-sal, a mercury-based compound usedas a vaccine preservative, because manyforms of mercury are known to damagethe nervous system in high doses.

R e v i e w o f t h e R e s e a r c hThis latest lOM report follows two

reports on vaccines and autism published in 2001. The committee determined then that the evidence did notshow an association between the MMRvaccine and autism, but that more evidence was needed regarding thimero-sal . "The commit tee conc luded thatthe evidence available at that time was

inadequate to accept or reject a causalrelationship between thimerosal andneurodevelopmental disorders," saysMarie McCormick, M.D., Sc.D., chairwoman of the immunization safetycommittee and a professor at the Harvard School of Public Health.

The committee revisited these issuesbecause several studies exploringpossible links between vaccines andautism have been published since2001. Committee members concludedthat the hypothesis about how theMMR vacc ine and th imerosa l cou ldtrigger autism lacks supporting evidence. Their conclusions were basedon a careful review of well-designedstud ies and o the r i n fo rmat ion f romresearchers and parents.


Five large studies in the United States,the United Kingdom, Denmark, andSweden done s ince 2001 found no ev id e n c e o f a l i n k b e t w e e n a u t i s m a n dvaccines containing thimerosal. And14 large studies consistently showedn o l i n k b e t w e e n t h e M M R v a c c i n e a n da u t i s m . T h e c o m m i t t e e a l s o r e v i e w e dseveral studies that did report associat ions be tween vacc ines and au t i sm andfound tha t these s tud ies had l im i ta t ionsand lacked supporting evidence.

The committee reviewed potentialbiological links between vaccines andautism and found them to be onlytheoretical. Examples of some of thehypothesized links include a suggestionthat the measles virus in the MMR vaccine might lodge in the intestines andtrigger the release of toxins that could

v a t i v e i n m u l t i - d o s e v i a l s o f v a c c i n e s

to prevent bacterial contamination.The active ingredient in thimerosal isethylmercury.

Even though the risk of thimerosalis hypothetical, thimerosal began tob e r e m o v e d f r o m c h i l d h o o d v a c c i n e sin 1999. The federal government, theAmerican Academy of Pediatrics, andothers agreed that thimerosal shouldb e r e d u c e d a n d e l i m i n a t e d i n v a ccines as a precautionary measure. TheFDA encouraged companies to complywith this recommendation. Currently,all routinely recommended vaccinesmanufactured for infants in the UnitedStates are either thimerosal-free or contain only trace amounts.

" W e m o v e d i n t h i s d i r e c t i o n t oaddress public concern and because it

preservative will increase as manufacturing capabilities expand. "To eliminate thimerosal as a preservative fromflu vaccines, manufacturers will have toswitch from multi-dose to single-dosepreparations, which requires greaterfilling and storage capacity," Midthunsays .

Based on federal guidelines onlevels of mercury exposure, a childwon't receive excessive mercury fromvaccines, regardless of whether theirinoculation against the flu containst h i m e r o s a l .

R e c o m m e n d a t i o n sThe lOM's immunization safety com

mittee did not recommend any changeswith the MMR vaccine or with the curr e n t s c h e d u l e o f r o u t i n e c h i l d h o o d

The lOfsA's immunization safety committee did not recommendany changes with the MMR vaccine or with the current

schedule of routine childhood immunizations.

lead to autism. Another hypothesis isthat the MMR vaccine might stimulate the release of immune factors that

damage the central nervous system. Yetanother hypothesis is that thimerosalmay interfere with biochemical systemsin the brain, thereby causing autism.But according to the lOM report, noevidence has shown that the immunesystem or its activation play a direct rolein causing autism, and autism has notbeen documented as being a result ofexposure to high doses of mercury.

"There is no convincing evidenceof serious harm from the low dosesof thimerosal in vaccines," says KarenMidthun, M.D., deputy director formedicine in the FDA's Center forBiologies Evaluation and Research(CBER). CBER regulates vaccines inthe United States and works with theCDC and the NIH to study and monitor vaccine safety and effectiveness.

Limiting Thimerosal UseSince the 1930s, small amounts of

thimerosal have been used as a preser-

was feasible to eliminate mercury fromvaccines," Midthun says. "We couldeliminate thimerosal in vaccines as away to reduce a child's total exposureto mercury, whereas other environmental sources of exposure are moredi fficul t to e l iminate."

In its latest report, the lOM's immunization committee reported that itdoes not dispute that mercury-containing compounds, including thimerosal,can be damaging to the nervous system. But the committee did not findthat these damaging effects are relatedto the development of autism.

For the 2004-2005 flu season, theCDC is recommending that childrenages 6 months to 23 months get vaccinated annually against the flu (influenza) with the inactivated flu shot."The influenza vacc ine i s ava i lab leboth with thimerosal as a preservativeand without it," Midthun says. "But thebenefits of flu vaccination outweighany theoretical risk from thimerosal."

According to the CDC, the amountof flu vaccine without thimerosal as a

i m m u n i z a t i o n s ."While the committee strongly sup

ports research that focuses on achieving a better understanding of autism,we recommend that future research bedirected toward other lines of inquirythat are supported by current knowledge and evidence, and that offermore promise for finding an answer,"McCormick said at a media briefing. "Given the current evidence, thevaccine hypothesis doesn't offer thatpromise."

The lOM is part of the National Academy of Sciences. ■

F o r M o r e I n f o r m a t i o nImmunization Safety Review: Vaccinesa n d A u t i s mImmunization Safety Review Committee, Institute of Medicinehttp:llbooks.nap.edu/catalogll0997.html

Thimerosal in Vaccines

www.fda.govjcberjvaccinelthimerosal.h t m


Training the Immune Systemto Fight CancerBy Michelle Meadows

Vaccines traditionallyhave been used to prev e n t i n f e c t i o u s d i s

eases such as measles and the

flu. But vdth cancer vaccines,the emphasis is on treatment,at least for now. The idea is to

inject a preparation of inactivated cancer cells or proteinsthat are unique to cancer cellsinto a person who has cancer.The goal: to train the person'simmune system to recognizethe living cancer cells andattack them.

"The best settings are for treatingpeople who have minimal disease ora high risk of recurrence," says JeffreySchlom, Ph.D., chief of the Laboratoryof Tumor Immunology and Biology atthe National Cancer Institute (NCI)."But at this time, most therapeutic cancer vaccines are being studied in peoplewho have failed other therapies."

Cancer vaccines are experimental;none have been licensed by the Foodand Drug Administration. But thereare about a dozen cancer vaccinesin advanced clinical trials, says Steven Hirschfeld, M.D., a medical offi

cer in the FDA's Center for BiologiesEvaluat ion and Research. "Researchhas shown us that the fundamenta l

approach to cancer vaccines is right;we are moving in the right direction,"he says.

The three standard cancer therapiesare surgery to remove tumors; chemotherapy, which modifies or destroyscancer cells with drugs; and radiation,which destroys cancer cells with high-energy X-rays. Immunotherapy, whichincludes cancer vaccines, is considereda fourth, and still investigational, typeof therapy. Cancer vaccines are sometimes used alone, but are often combined with a standard therapy.

W h i l e s t a n d a r d t r e a t m e n t s a l o n ehave proven effective, they also havelimitations. Radiation and chemotherapy can wipe out a person's cancer cells,but they also damage normal cells. "Wewant to find t rea tment tha t i s more ta r

geted and less toxic," says Mirschfeld."Cancer vaccines are designed to bespecific, targeting only the cancer cellswithout harming the healthy ones."

The approach has made cancer vaccines generally well tolerated, allowingthem to be used in outpatient settings.And they can be added to standardtherapy with a low likelihood of causing further serious side effects.

How Cancer Vacc ines WorkCancer is a term for more than 100

diseases characterized by the uncon-

A photograph taken througha microscope shows a cancercell (red) being attacked by Tlymphocytes (yellow).

trolled, abnormal growth of cells. Tothe immune system—the body's natural defense system against disease—cancer cells and normal cells look thesame. The immune system tends totolerate the cancer cells, just as it tolerates the normal cells. That's becausethe immune system doesn't recognizecancer cells as something foreign,Hirschfeld says. Rather, cancer cells areonce-normal cells that have gone awry.Cancer vaccines try to get the immunesystem to overcome its tolerance of cancer cells so that it can recognize themand attack them.

All cells have unique proteins or

Gary Montgomery, a retired engineer from Redmond, Wash., flies toGeorgetown University's LombardiCancer Center in Washington, D.C.,every month. There, he receives a cancervaccine to treat a rare form of abdominal cancer as part of a clinical trial.

Black Star/Doug Wilson FDA Consumer / September-October 2004/21

bits of proteins on their surface calledantigens. Many cancer cells makecancer-specific antigens. The goal ofusing cancer antigens as a vaccine isto teach the immune system to recognize the cancer-specific antigens andto reject any cells with those antigens.The antigens activate white blood cellscalled B lymphocytes (B cells) and Tlymphocytes (T cells). B cells produceantibodies that recognize a particularantigen and bind to it to help destroythe cancer cells. T cells that recognizea particular antigen can attack and killcancer cells. In 1991, the first humancancer antigen was found in cells of aperson with melanoma, a discoverythat encouraged researchers to searchfor antigens on other types of cancer,according to the NCI.

The two main approaches for cancer

/


vaccines are whole-cell vaccines and

antigen vaccines. Whole-cell vaccinesmay take whole cancer cells from apatient or sometimes several patients,or use human tumor cell lines derivedin a laboratory. "Some cell-based vaccines use tumor cells from the patient,some contain something that looks likea tumor cell but was created in a lab,and others are personalized vaccinesthat use some cells from the patientand some f rom the lab," Hi rschfe ld

says. Cells that are taken from peoplewith cancer are altered in a lab to inactivate them so that they are safe to reinject.

Regardless of the exact source of thecells, whole cell vaccines potentiallyuse all the antigens found on the tumorcells. Antigen vaccines try to trigger animmune response by using only certain

antigens from cancer cells. Hirschfeldsays antigens may be particular to anindividual, to a certain type of cancer,or to several types of cancers.

Boosting the Immune ResponseIn the early 1990s, Steven Rosenberg,

M.D., one of the pioneers of immunotherapy and chief of surgery at the NCI,wrote that trying to use the immunesystem to fight cancer is so difficult thatit made him feel "like a dog trying tobite a basketball." Among Rosenberg'scontributions was identifying the antigens that trigger an immune response,and cloning genes that look for, or"code for," those antigens.

Researchers have been working todevelop cancer vaccines for more than100 years in one form or another, andthe main mission has always been to

The Immune System and How It Works

^ t o n s i l s

b o n em a r r o w

spleen

r- lymphn o d e s

Your immune system includes yourspleen, lymph nodes, tonsils, bonemarrow, and white blood cel ls. Theseall help protect you from gettinginfections and diseases. When yourimmune system works the way itshould, it can tell the differencebetween "good" cells that keep youhealthy and "bad" cells that makeyou sick. But sometimes this doesn'thappen. Doctors are doing researchto learn why some immune systemsdon't fight off diseases like cancer.

White blood cells are an importantpart of your immune system. Whenyour doctor or nurse talks about yourwhite blood cells, he or she may usew o r d s l i k e :

• Monocytes (MON-o-cites) are typesof white blood cel ls.

• Lymphocytes (LYM-fo-cites) aretypes of white blood cells.

• 8 cells, T cells, and "natural killercells" are kinds of lymphocytes.

N a t i o n a l C a n c e r I n s t i t u t e

make the immune system's responseto the cancer antigens as strong as possible.

One major strategy involves combining vaccines with additional substancescalled adjuvants, which act as chemical messengers that help T cells workbetter. An example of one type of adjuvant, called a cytokine, is interleukin-2. This protein is made by the body'simmune system and can also be madein a lab.

There have also been improvementsin vaccine delivery. For example,Schlom developed a vaccine in whichgenes for tumor antigens are put intoa weakened virus called a "vector" thatdelivers genetic materials to cells. Thismakes the tumor antigen more visibleto the immune system. The CEA-TRICOM vaccine was developed at theNCI through a cooperative researchand development agreement withTherion Biologies in Cambridge, Mass.Researchers use the vaccinia virus, thesame virus in the smallpox vaccine,as the vector. The carcinoembryonicantigen (CEA), which is found on mostbreast, lung, colon, and pancreatict u m o r s , i s a d d e d t o t h e v i r u s .Researchers also add three molecules,called "costimulatory molecules,"which serve as signals that make thevaccine more potent than it wouldbe if the antigen were used alone. Asimilar vaccine developed under theNCI agreement with Therion is thePA N VA C v a c c i n e , w h i c h h a s n o wentered advanced study as a treatmentfor pancreatic cancer.

In addition to studying this type ofvirus-based technique, researchers atDuke University's Cancer Center inDurham, N.C., have been studying vaccines that mix white blood cells calleddendritic cells with genetic materialfrom a person's tumor.

Dendritic cells, which can activateT cells, work by looking around, finding antigens, and showing them tothe fighter T cells. Researchers havefound ways to increase the number ofdendritic cells in a vaccine. "Employing millions of'pumped up' dendriticcells can help elicit a strong immuneresponse," says H. Kim Lyerly, M.D.,d i rec to r o f the Duke cancer cen te r.

Recent work by Lyerly and Duke

investigators Michael Morse, M.D., andTimothy Clay, Ph.D., has focused onmodifying dendritic cells with virusesso that they activate even stronger T cellresponses against cancer antigens.

"This is an evolving area, and it'sexciting to be able to make progress," says Lyerly. "For decades, peoplethought it wasn't even fundamentallypossible to develop cancer vaccines,and here we are. The science behindcancer vaccines is leading us to believethat we will find the answers."

Promising, But Still EarlyAs with any new treatment, cancer

v a c c i n e s m u s t b e fi r s t s t u d i e d i n l a b

animals and then tested for safety and

NCI's Cancer Therapy Evaluation Program, it's too soon to say which cancerswill be treated with vaccine therapy.The types of tumors that have provenmost susceptible to vaccines so far,he says, are: skin cancer (melanoma);kidney cancer (renal cell); a group ofcancers that affect the lymphatic system (lymphoma); a malignant tumorof the bone marrow (myeloma); andsolid tumors, such as lung cancer. Themost work has been done in the areaof melanoma, a type of skin cancerin which treatment options are limi t e d w h e n t h e d i s e a s e i s i n a d v a n c e d

stages."After having a tumor removed,

about half of patients with stage 111

C a n c e r Va c c i n e F a c t s• Cancer vaccines are intended either to treat existing cancers (therapeutic vaccines) or to prevent the development of cancer (prophylactic vaccines).• Therapeutic vaccines, which are administered to cancer patients, aredesigned to treat cancer by stimulating the immune system to recognizeand attack human cancer cells without harming normal cells. Prophylactic vaccines, on the other hand, are given to healthy individuals to stimulate the immune system to attack cancer-causing viruses and prevent virali n f e c t i o n .• The only cancer vaccine licensed by the Food and Drug Administrationis a prophylactic vaccine against hepatitis B virus, an infectious agent assoc i a t e d w i t h l i v e r c a n c e r.• Scientists are currently evaluating several different vaccines in largehuman trials to determine which approaches are most effective for particular kinds of cancers.S o u r c e : N a t i o n a l C a n c e r I n s t i t u t e

effectiveness in three phases of humanstudies, called "clinical trials," beforethey can be approved by the FDA. InPhase 1 clinical trials, cancer vaccinesare used alone and studied for safetyand to determine the proper dose. InPhase 2 trials, they are tested for effectiveness and may be used alone or incombination with another therapy.Phase 3 trials are large-scale studiestesting effectiveness and usually comparing a vaccine with some standardtherapy. Researchers are testing vaccines using various adjuvants, deliverymethods, and types of antigens.

Cancer vaccines have shown promise in clinical trials with many types ofcancer. According to Howard Streicher,M.D., a senior investigator with the

melanoma may have a recurrence, andwe want to prevent that," Streicher says."Chemotherapy doesn't work in thisarea, so our hope is that this could bejust the right place for a vaccine."

James Mule, M.D., Ph.D., associated i rec to r o f the H . Lee Moffi t t Cancer Center and Research Institute inTampa, Fla., says, though some earlystudies have shown that some people'stumors shrank or even disappeared inresponse to a cancer vaccine, it's stillearly. Mule was an investigator on thefirst study that tested dendritic cells inchildren. In the Phase 1 study, one 16-year-old with cancer that had spread toher lungs and spine showed significantshrinkage of tumors.

"There is promise in the sense that


With a cancer vaccine, there may be fewer signs oftumor shrinkage, but a person might live longer.

some of these vaccines can i l l ici t apowerful immune response in somepatients, but 1 think we have to be careful about getting too excited over earlystudies that can't be reproduced," Mulesays.

Jeffrey Weber, M.D., Ph.D., directorof the Norris Melanoma Center at theUniversity of Southern California, saysthere is also still a lot of work to bedone in discovering new antigens andadjuvants and more sophisticated strategies to overcome the immune system'sto le rance o f cancer ce l l s . "We a re s t i l l

discovering molecules that regulate theimmune system such as CTLA-4, sowe're still in the dark in some areas,"Weber says. Recent research has foundthat inhibiting CTLA-4 can help theimmune system attack some tumors.

Experts say that no therapeuticcancer vaccine has been licensed yetbecause few Phase 3 studies have been

completed, and those that have beencompleted did not meet their goals ofdemonstrating safety and effectivenessof the vaccine. "We are still workingwith industry to define the characteristics, including potency," says the FDA's

Hirschfeld. "So a trial may look promising early on, but our job is to makesure it can be reproduced. We have toask: 'Will this treatment work in thelarger population?"'

One of the challenges is that cancer vaccines may produce differenteffects than those caused by cancerdrugs. With cancer drugs, experts askwhether there is an objective, measurable response, such as tumor shrinkage. A cancer drug may cause tumorsto shrink, but a person still may notlive longer. With a cancer vaccine, theremay be fewer signs of tumor shrinkage,but a person might live longer.

There aren ' t the same landmarks that

you would see with traditional therapies, says Natalie Sacks, M.D., medic a l d i r e c t o r i n t h e c l i n i c a l r e s e a r c hd i v i s i o n a t S a n F r a n c i s c o - b a s e d C e l l

Genesys, which is studying its vaccines,called GVAX, in people with prostatecancer, pancreatic cancer, leukemia,and myeloma. These whole-cell vaccines all use a hormone that stimulatesimmune response, called granulocytemacrophage colony stimulating factor(GM-GSF).

The Role of FDA and NCIAfter conducting preclinical research in lab animals, drug companies or

clinical investigators submit an investigational new drug application to theFood and Drug Administration, requesting permission to move forwardwith testing in humans called clinical trials. The agency and the sponsorscontinue to communicate throughout the three phases of clinical trials,and the FDA ensures that treatments are safe and effective before they canb e m a r k e t e d .

The National Gancer Institute (NGI) is the main federal agency thatsupports and conducts cancer research. The NGI funds studies conductedby hospitals, universities, and businesses. The institute also supports anetwork of cancer centers across the country.

Both agencies are part of the U.S. Department of Health and HumanServices, and they share responsibility and oversight for clinical trials.In 2003, the FDA and the NGI entered an agreement to enhance the efficiency of clinical research and the evaluation of new cancer medications.An NGI-FDA Oncology Task Force involves senior staff from both agencies and oversees the agreement. The agencies collaborate on developingthe markers that show whether a treatment is effective, such as survivaltime, tumor shrinkage, and time to relapse. ■

"As sponsors, we want to developtreatments and get them out to themarket and help patients," Sacks says."In the case of cytotoxic chemotherapies, the traditional endpoints usedin drug development are shorter-termoutcomes, such as tumor responseand progression-free survival. Where1 expect immunotherapy to be successful is in longer-term outcomesand increased survival. Because of themechanism of action, the patient maynot show an immediate response as isgenerally observed with standard chemotherapies, and the trial may take

Finding a Clinical TrialGancer researchers say their work

won't mean much if more people don'tenroll in clinical trials. According tothe NGI, less than 3 percent of U.S.adults with cancer participate in clinica l t r i a l s .

If there is a standard treatment available for a type of cancer, the NGI recommends choosing it over an experimental therapy. Gancer vaccines showthe most promise at preventing a recurrence of cancer after surgery, radiation,or chemotherapy because the immunesystem will need to recognize andattack a smaller number of cancer cells.Gancer vaccines are also being tested asa treatment for advanced cancer.

Gary Montgomery, 66, of Redmond,Wash., enrolled in a cancer vaccine trialin 2002 to treat a rare form of abdominal cancer called pseudomyxomaperitonei. According to the NationalOrganization for Rare Disorders, thedisease is characterized by the accumulation of mucus-secreting tumor cellsin the abdomen and pelvis. As the massof tumor cells grows, the abdomenswells and digestive function becomesimpaired.

Montgomery first had the standard therapy of surgery to remove thetumors in 2000. "They opened me uplike a sardine can—from the sternumt o t h e a b d o m e n — a n d t o o k o u t a s

24 / September-Octc er 2004 / FDA Consumer


A researcher prepares the carcinoembryonic antigen (CEA) vaccinia vaccine.

many tumors as possible," Montgomery says. Then they inserted a tube intothe abdomen, which delivered chemotherapy for six months. He experiencedno tumor growth for about a year,but then the tumors came back. "It'sknown as a relentless form of cancerthat wears you down," he says. "Thedoctor said that with the exception ofanother surgery, there was really nothing else they could do."

So Montgomery started with theInternet and found one NCI studythat involved surgery and chemotherapy with an agent different from theone he had before. But the trial wasclosed. Taking advice from a friend, hechecked at the Lombard i Cancer Centerat Georgetown University in Washington, D.C. "1 was feeling pretty low atthis point," he says. He found out theone vaccine study he was interested inhad just ended. But a nurse told himt h a t a n o t h e r t r i a l w i t h n e w e r v e r s i o n sof cancer vaccines developed at theN C I w a s a b o u t t o s t a r t . " T h e r e w e r etwo slots left," he says. "Luckily, I mett h e c r i t e r i a . "

Montgomery received a "prime-boost regimen" of Therion Biologies'T R I C O M v a c c i n e . H e fi r s t r e c e i v e d a n

injection in the upper leg of a modified version of the smallpox vaccineto prime the immune system. Then hereceived monthly boosters of a vaccinecalled fowlpox CEA [carcinoembryonicantigen), an antigen found on mostcolorectal and pancreatic cancers. Healso received a shot of the hormoneGM-CSF, which helps stimulate thecells of the immune system. He had togive some of the injections to himselfwhen he arrived back home in Washington state.

He says he experienced minimal sideeffects, such as soreness at the site ofinjection and mild flu-like symptoms.Though most cancer vaccines havebeen we l l - t o le ra ted , i n o the r t r i a l ssome people have experienced autoimmune problems such as inflammationof the thyroid gland, skin disorders,a n d c o l i t i s . A u t o i m m u n e c o n d i t i o n sare those in which the immune systemmistakenly attacks the body's tissuesand organs. Before he began the trial,Montgomery signed an informed consent form acknowledging that he was

aware of a l l the r isks.

Montgomery continues to participatein the trial and flies to the nation's capital every month to receive treatmentbecause it's been working. "It hasn'tcured the cancer," Montgomery says,"but it seems to be keeping it in check.

And that's good enough for me."Those interested in finding out about

c l in ica l t r ia ls to t reat cancer should ta lkw i t h t h e i r d o c t o r s a n d c o n t a c t t h e N C Iat (800) 4-CANCER (422-6237) or onthe Web at www.clinicaltrials.gov. ■

New Cancer Office and ProgramIn July 2004 the FDA announced plans to create the Office of Oncology

Drug Products, which will be housed in the agency's Center for Drug Evaluation and Research (CDER). The new office will consolidate three existingareas within CDER that are responsible for reviewing drugs and biologiesused to prevent, diagnose, and treat cancer. The creation of this office willimprove the consistency of review and policy toward oncology drugs andbring together oncologists who will help develop new therapies.

"Biomedical research in the United States is second to none, and it isour responsibility to see that patients reap the fruits of that research," saysHealth and Human Services Secretary Tommy G. Thompson. "We are committed to creating the most effective and efficient review process possibleto ensure life-saving treatments are made available to cancer patients."

The FDA also is creating a new oncology program within the office, whichwill coordinate cancer-related work performed throughout the FDA. Theprogram will promote cross-agency consultation and discussion and thedevelopment of regulatory policy and standards, and will serve as a focalpoint for agency interactions with the National Cancer Institute and others t a k e h o l d e r s . ■


The Critical Path:Accelerating the Developmentof Medica l Products

By Carol Rados

Drugs recently approvedby the Food and DrugAdministration help chil

d r e n w i t h r h e u m a t o i d a r t h r i t i s

walk, prevent or halt heart disease,slow the progression of multiple

sclerosis, and cure infectious dis

eases. New medical devices improvethe heart's blood-pumping ability in

patients with heart failure, and the latestvaccines protect against the threat of bioter-r o r i s m .

Advances in medical products ultimately cashorten hospital stays, lengthen life expectanciesreduce overall health care costs. New classes of drugs—a few

pills, for example—have virtually replaced major surgery fortreating ulcers.

Illustration: Jack Hornady


B u t t h e r e c e n t s l o w d o w n — i n s t e a dof the expected acceleration—of newmedical treatments actually reaching patients concerns the FDA. Products fail before they reach the marketbecause they could not be proved safeor effective, or they could not be manufactured commercially at a coirsistentlyhigh quality.

Despite recent innovations, manyserious and life-threatening diseasess t i l l l a c k e f f e c t i v e t r e a t m e n t s . I n t h e

agency's view, the scientific tools neededto develop medical products have notkept pace with the rapid advances inproduct discovery. As a result, fewero f t h e s o u n d i d e a s

spawned inm e d i c a l

l a b o r a

t o r i e s a r e

b e c o m i n gsafe and effec

t i v e t r e a t m e n t s ,in the interest of public health,

the FDA says that action is needed tomodernize the product developmentprocess.

In March 2004, the agency issued amajor report that identifies both theproblems and the potential solutionsfor bringing more breakthroughs inmedical science to patients as quicklyand efficiently as possible. The report,"Innovation or Stagnation? Challengeand Opportunity on the Critical Patht o N e w M e d i c a l P r o d u c t s , " e x a mines the crucial steps that determine

whether and how quickly a discovery leads to a reliable treatment forpatients.

The report, which looks at the development processes for drugs, biologies,and medical devices, calls for a jointeffort of industry, academic researchers, product developers, patient groups,and the FDA to identify key problemsand to develop solutions.

T h e P r o b l e m s

Despite notable advances in basicbiomedical research, such as the studies of gene structure (genomics), proteins in living cells (proteomics), andof miniaturized equipment (nanotech-

nology), there has been a downw a r d t r e n d i n t h e n u m b e r o f

new drug and biologic marketing applications being

s u b m i t t e d t o t h e F D Af o r r e v i e w. T h i s m e a n s

t h a t t h e n e w s c i e n c e sare not yet having asubstantial impact onpatient care.

" W e c a n s e e f r o mo u r r e v i e w s t h a t

t h e s e p r o d u c t saren't being movedalong," says KathyCarbone, M.D., acting associate direc

t o r f o r r e s e a r c h i n t h eFDA's Center for Biologies

Evaluation and Research.She adds, "Sometimes can

didate medical products get presented to us where we simply lack thetools to easily determine the safety andeffectiveness of these products that arebased on exciting, but edge-of-the-wedge, technologies."

As a result, many of the investigational products that enter clinical trialsfail. And sometimes product development programs must be abandonedafter extensive investment of time andresources. This high rate of failure candrive up costs, and the critical pathto market—even for successful product candidates—is costly, timely, andunpredictable. And researchers areforced to rely on cumbersome, oftenimprecise assessment methods.

For example, product developers usescientific tools, such as laboratory tests.

computer models based on past experiences, and animal studies, to predict ahigh probability of safety and effectiveness. Other tools for making these predictions include knowledge of bloodmarkers that accurately predict diseaseremission or the benefits of devices, orthat can be used in early human trialsto indicate effect and guide dose andregimen decisions. Developers also uses c i e n t i fi c t e s t s t o d e m o n s t r a t e t h e b i o -

compatibility of implanted devices.But in many cases, product develop

ers have no choice but to use the tools

and concepts of the last century to assessthis century's potential products.

"We are dealing routinely with novelproducts—novel technology," says Car-bone, and part of the difficulty is predicting ultimate success with a novelcandidate. If industry and the FDAcould make these predictions moreaccurately, fewer products would failon the critical path from laboratory toconsumer. Similarly, new tools to measure product quality in process wouldmean more efficient, higher qualitymanufacturing.

"We think we have a way to fix it,"says Carbone, "and we're asking industry, academia and others to help usfocus on the gaps."

T h e S o l u t i o n sTo meet the challenge, the FDA is

calling for a new focus on modernizing the tools that researchers andproduct developers use to assess thesafety and effectiveness of potentialnew products and to mass-producehigh-quality therapies. New scientificand technical tools—including assays(tests), standards, computer modelingtechniques, biomarkers, and clinicalevaluation techniques—will improvepredictability and efficiency of products along the development path, morelikely resulting in safe products thatbenefit patients.

For example, the FDA rapidly developed standards and calibration toolsthat enabled product developers todesign and produce test kits to screendonated blood for the presence ofWest Ni le v i rus. Th is work invo lvedextensive collaboration with publichealth laboratories, industry, and U.S.blood banks, as well as using applied


research. During 2003, roughly 8.6m i l l i o n b l o o d d o n a t i o n s w e r e t e s t e d .Of these, more than 1,000 donationsconfirmed positive for West Nile virusw e r e i d e n t i fi e d a n d r e m o v e d f r o m t h eblood supply.

The FDA also developed and implem e n t e d a m o r e fl e x i b l e a n d i n n o v a t i v e

approach to the clinical trials neededto evaluate medical screening devices.This new trial design allows small companies, which often cannot afford thelarge trials needed to evaluate screening devices, to use common protocolsso that their data can be pooled for

to maximize patient benefits with am i n i m u m o f r i s k .

The Opportunit iesThe FDA is uniquely suited to take

a major role in these efforts becauseof its experience overseeing medicalproduct development, its vast clinicaland animal databases, and its closeinteractions with all the major playersin the critical path process. The agencysees the product development problems industry-wide.

Building on the agency's proven "bestpractices" for expediting the availabil-

by smart, articulate AIDS activists inthe late 1980s." Much work, however,s t i l l n e e d s t o b e d o n e o n c l i n i c a l t r i a l

design and patient response measuresto ensure that new therapies accuratelyreflect patient needs and values.

Binita Ashar, M.D., acting clinicaldeputy director for the FDA's Center forDevices and Radiological Health, saysthat, while medical devices don't seemto be experiencing the product development delay to the degree that drugsand other products have, the concernsabout improving product developmenttools still apply.

The FDA believes that patientshave an important role to play in this effort.

analysis. The design currently allows ityofpromising medical technologies, "There doesn't necessarily have to bemanufacturers to test the effectiveness there is an urgent need, for example, a problem to support the innovationofdigital mammography for screening to develop tools to accurately assess process that critical path promotes,"use. the r isk that a new drug wi l l cause she says. Ashar sees the cr i t ica l path

Such success stories can only be heart rhythm abnormalities. Ongoing initiative working together with theaccomplished through a concerted international efforts include develop- goal of providing the "least burden-and joint effort by industry, academia, ing, testing, and validating nonclinical some" path to market—a provision ofpatient groups, and the FDA. Key to tools such as computer models that FDAMA (the Food and Drug Admin-this effort will be the development of may be useful in predicting human istration Modernization Act of 1997)a Critical Path Opportunities List" risk. Examples of tools that the FDA that applies only to devices,that will identify and prioritize the says are urgently needed include bet- For example, scientists involved inmost pressing development problems ter predictors of human immune reviewing medical devices at the FDAand the areas that provide the greatest responses to foreign substances, meth- report an urgent need for predictiveopportunities for rapid improvement ods to further enhance the safety of software to model the human effectsand public health benefits. transplanted human tissues, and new of design changes for rapidly evolving

To create this list, the FDA is con- techniques for assessing drug-induced devices. Ashar adds, "There's a learningsuiting and soliciting suggestions from liver toxicity. curve with devices, and we have to tryall interested parties to identify and The FDA believes that patients to anticipate the problems users mightaddress specific defined critical path have an important role to play in this encounter."opportunities to make product devel- effort. Thanks to the enormous growth inopment more efficient and predictable. "The FDA's critical path initiative now research, the FDA is dealing with moreThe agency will publicize the list and encourages patients and their advocates complex and innovative products strug-encourage collaborations to address to join us as we roll up our sleeves to gling in development. As discover-the problems and create new product identify the difficult problems in drug ies made in the laboratory begin thedevelopment tools. development," says Theresa Toigo, transformation toward effective medi-

In addition, the FDA intends to the FDA's assistant commissioner for cal products consumers can safely use,refocus its own activities and take on special health issues. This, she says, both the FDA and industry seek a newnew partnerships, as needed, to ful- "may uncover a promising treatment and better set of tools to accelerate thatfill these priority opportunities. These or technology that otherwise might development and better predict the per-actions promise not only to bring med- not be developed." The critical path to formance of these new products. ■ical breakthroughs to patients more the development of effective therapiesquickly, but also to do so in ways that for HIV and AIDS, Toigo adds, "wasensure greater understanding of how cleared of overgrowth and underbrush


Got Mi l k?Make Sure It'sP a s t e u r i z e dBy Linda Bren

Ppasteurization, since its adoption'in the early 1900s, has beencred i t ed w i t h d rama t i ca l l y

reducing illness and death caused bycontaminated milk. But today,some people are pass

ing up pasteurized milkfor what they claim istas t ie r and hea l th ie r

" r a w m i l k . "

Public health offi

c ia ls cou ldn ' t d is

a g r e e m o r e .

Drinking raw (untreated) milk or eatingraw milk products is"like playing Russian roulette with your health,"says John Sheehan, director of the Food andDrug Administration's Division of Dairy and Egg Safety."We see a number of cases of foodborne illness every yearrelated to the consumption of raw milk."

J a c k L e f k o w i t z


More than 300 people in the United killing disease-causing bacteria, pas- is barely perceptible.States got sick from drinking raw milk teurization destroys bacteria that cause "Milk is a good source of the vita-or eating cheese made from raw milk in spoilage, extending the shelf life of mins thiamine, folate, B-12, and ribo-2 0 0 1 , a n d n e a r l y 2 0 0 b e c a m e i l l f r o m m i l k . fl a v i n , " a d d s S h e e h a n , " a n d p a s t e u r i z a -these products in 2002, according to Milk can become contaminated on tion results in losses of anywhere fromthe Centers for Disease Control and the farm when animals shed bacteria zero to 10 percent for each of these.Prevention. into the milk. Cows, goats, and sheep which most would consider only a mar-

Raw milk may harbor a host of dis- carry bacteria in their intestines that ginal reduction."ease-causing organisms (pathogens), do not make them sick but can cause While the major nutrients are leftsuch as the bacteria Campylobacter, illness in people who consume their unchanged by pasteurization, vitaminescherichia, listeria, salmonella, yer- untreated milk or milk products. D, which enhances the body's absorp-sinia, and brucella. Common symp- But pathogens that are shed from tion of calcium, is added to processedtoms of foodborne illness from many animals aren't the only means of con- milk. Vitamin D is not found in signifi-

Research has shown that there is no

significant difference in the nutritional valueof pasteurized and unpasteurized milk.

of these types of bacteria include diarrhea, stomach cramps, fever, headache,vomiting, and exhaustion.

Most healthy people recover fromfoodborne illness within a short periodof time, but others may have symptomsthat are chronic, severe, or life-threatening.

People with weakened immune systems, such as elderly people, children,and those with certain diseases orconditions, are most at risk for severeinfections from pathogens that maybe present in raw milk. In pregnantwomen. Listeria monocytogenes-causedillness can result in miscarriage, fetaldeath, or illness or death of a newborninfant. And Escherichia coli infectionhas been linked to hemolytic uremicsyndrome, a condition that can causekidney failure and death.

Some of the diseases that pasteurization can prevent are tuberculosis, diphtheria, polio, salmonellosis,strep throat, scarlet fever, and typhoidf e v e r.

Pasteurization and ContaminationThe pasteurization process uses heat

to destroy harmful bacteria withoutsignificantly changing milk's nutritional value or flavor. In addition to

tamination, says Tom Szalkucki, assistant director of the Wisconsin Centerfor Dairy Research at the University ofWisconsin-Madison. Cows can pickup pathogens from the environmentjust by lying down—giving germs theopportunity to collect on the udder,the organ from which milk is secreted."Think about how many times a cowlays down in a field or the barn,"says Szalkucki. "Even if the barn iscleaned thoroughly and regularly, it'snot steamed. Contamination can takeplace because it's not a sterile environm e n t . "

The Health HypeRaw milk advocates claim that

unprocessed milk is healthier becausepasteurization destroys nutrients andthe enzymes necessary to absorb calcium. It also kills beneficial bacteriaand is associated with allergies, arthritis, and other diseases, they say.

This is simply not the case, says Sheehan. Research has shown that there isno significant difference in the nutritional value of pasteurized and unpasteurized milk, he says. The caseins,the major family of milk proteins, arelargely unaffected, and any modification in whey protein that might occur

cant levels in raw milk."Pasteurization will destroy some

enzymes," says Barbara Ingham, Ph.D.,associate professor and extension foodscientist at the University of Wisconsin-Madison. "But the enzymes thatare naturally present in milk are bovineenzymes. Our bodies don't use animalenzymes to help metabolize calciumand other nutrients."

"Enzymes in the food that we eat anddrink are broken down in the humangastrointestinal tract," adds Ingham."Human bodies rely on our own nativeenzymes to digest and metabolizef o o d . "

"Most of the native enzymes ofmilk survive pasteurization largelyintact," says Sheehan, "including thosethought to have natural antimicrobialproperties and those that contributeto prolonging milk's shelf life." Otherenzymes that survive are thought toplay a role in cheese ripening.

Ingham says that pasteurization willdestroy some bacteria that may be helpful in the fermentation of milk intoproducts such as cheese and yogurt,but the benefit of destroying the

harmful bacteria vastly outweighs thesupposed benefits of retaining thosehelpful microorganisms. Plus, by add-

30 / September-October 2004 / FDA Consume

A Sampling of Raw Milk Incidents• July 2004—^The Indiana Public Health Department advised consumers to check their refrigerators and freezers for raw milk cheese that maybe contaminated with salmonella. Routine product sampling foundthe bacteria in lot number 139 of "Natural Raw Milk Cheese" made byMeadow Valley Farm after the cheese was distributed to farmers' markets and specialty food stores in parts of Indiana and Wisconsin.• 2002-2003—Two children were hospitalized in Ohio for infectionwith Salmonella enterica serotype Typhimurium. These children and 60other people in Illinois, Indiana, Ohio, and Tennessee developed bloodydiarrhea, cramps, fever, chills, and vomiting from S. Typhimuriumtracked to consuming raw milk. The milk producer voluntarily relinquished its license for selling raw milk upon recommendation of theOhio Department of Agriculture.• 2000-2001—In North Carolina, 12 adults were infected with Listeria monocYtogenes linked to homemade, Mexican-style fresh soft cheeseproduced from contaminated raw milk sold by a local dairy farm. Tenof the 12 victims were pregnant women, and infection with the bacterium resulted in five stillbirths, three premature deliveries, and twoi n f e c t e d n e w b o r n s .• 1998—In Massachusetts, 66 people received injections to protectagainst potential exposure to rabies after drinking unpasteurized milkfrom a local dairy. A cow that died at the dairy was found to be infectedwith rabies. Transmission of the rabies virus through unpasteurizedmilk, although not the common route of infection, is theoretically possible, according to the Centers for Disease Control and Prevention. ■Sources: CDC, Indiana State Board of Animal Health

ing the microorganisms that we needfor fermentation, we can assure a consistently high quality product."

Sc ience has no t shown a connec t i onbetween drinking raw milk and disease prevention. "The small quantitieso f an t i bod ies i n m i l k a re no t abso rbedin the human intestinal tract," saysIngham. "And there is no scientifice v i d e n c e t h a t r a w m i l k c o n t a i n s a n

an t i - a r t h r i t i s f ac to r o r t ha t i t enhancesres is tance to o ther d iseases . "

Fans of raw milk often cite its creamyrich taste, says Szalkucki, who addsthat it may be creamier because it isnot made according to the standardsfor processed milk. "If you go to a grocery store and buy fluid milk, it's beenstandardized for a certain percentageof fat, such as 2 percent," he says. "Rawmilk is potentially creamier because ith a s n o t b e e n s t a n d a r d i z e d a n d i t h a sa higher fat content."

T h e L a wIt is a violation of federal law enforced

by the FDA to sell raw milk packagedfor consumer use across state l ines

(interstate commerce). But each stateregulates the sale of raw milk withinthe state (intrastate), and some statesallow it to be sold. This means that insome states dairy operations may sellit to local retail food stores, or to consumers directly from the farm or atagricultural fairs or other communityevents, depending on the state law.

In states that prohibit intrastate salesof raw milk, some people have tried tocircumvent the law by "cow sharing,"or "cow leasing." They pay a fee to afarmer to lease or purchase part of acow in exchange for raw milk, claiming that they are not actually buyingthe milk since they are part-owners ofthe cow. Wisconsin banned cow-leasing programs after 75 people becameinfected with Campylobacter jejuni bacteria in 2001 from drinking unpasteurized milk obtained through sucha p r o g r a m .

R a w M i l k C h e e s e sThe FDA a l l ows the manu fac tu re

and interstate sale of raw milk cheesesthat are aged for at least 60 days at atemperature not less than 35 degreesFahrenheit. "However, recent research

calls into question the effectiveness of60-day aging as a means of pathogenreduction," says Sheehan.

The FDA's Center for Food Safetyand Applied Nutrition (CFSAN) is currently examining the safety of raw milkcheeses and plans to develop a riskprofile for these cheeses. This information will help FDA risk managers makefuture decisions regarding the regulation of these products to protect publich e a l t h .

Ensuring Milk SafetyThe FDA provides oversight for the

processing of raw milk into pasteurizedmilk, cottage cheese, yogurt, and sourcream under the National Conferenceon Interstate Milk Shipments "GradeA" milk program. This cooperativeprogram between the FDA and the 50states and Puerto Rico helps to ensurethe uniformity of milk regulations andthe safety of milk and milk products.The program is based on standardsdescr ibed in the FDA's Pasteur izedMilk Ordinance (PMO), a model code

of regulations that can be adopted bythe states in their own regulations.

Under the Grade A program, statepersonnel conduct inspections andassign ratings and FDA regional milkspecialists audit these ratings, saysRichard Eubanks, M.P.H., a senior milks a n i t a t i o n o f fi c e r o n C F S A N ' s M i l kSafety Team. "It's a rigorous process ofinspection and auditing," he says, and"it covers from cow to carton," startingwith the dairy farm and continuingthrough the processing and packagingof products at milk plants. Productsthat pass inspection may be labeled"Grade A."

The FDA Grade A milk programincludes pasteurized milk from cows,goats, sheep, and horses. Raw milk andraw mi lk cheeses cannot be labeledGrade A, since they are not pasteurizedand not covered under the program. ■


M a k i n g a n 'I N F O R M E D D E C I S I O N

By Carol Rados

Despite more than a decade of controversy over their safety, breastimplants are more popular than ever among women who want to buildupon what nature gave them or who want to restore what disease has

taken away. Whatever the reason, opting for breast implants is a personal decision that should be made only after a woman fully understands and acceptsthe potential risks of the devices and the importance of follow-up evaluationswith her physician.

Some people see an enormous benefit to getting implants and are willingto accept associated risks. They say thatusing breast implants to rebuild thebreast (reconstruction), or change itssize and shape (augmentation), significantly improves the quality of lifefor many women. Advocates of breastimplants also say that a woman's consent to the surgery should he considered valid as long as she weighs therisks and benefits of the procedure.

implant surgeries in 2003, nearly twicet h e n u m b e r d o n e i n 1 9 9 8 . A n o t h e r

68,000 women received breast implantsfor reconstruction following mastectomy due to cancer or other disease.

But also in 2003, 45,000 augmentation patients and 17,000 reconstruction patients had their breast implantsremoved. The medical community andothers, including the Food and DrugAdmin is t ra t ion , wou ld l i ke to be t te runderstand why.

vary in shape, size, and shell texture.At this t ime, there are two manu

facturers with approved saline-filledbreast implants. No manufacturer hasyet received FDA approval to market asilicone gel-filled breast implant.

The Silicone ControversyBreast implants were first marketed

in the early 1960s, before the 1976Med ica l Dev ice Amendments to theFederal Food, Drug, and Cosmetic

While every surgical procedure has potential risks,such as infection, bleeding, and scarring, there are risks

that are specific to breast implants.

While every surgical procedure haspotential risks, such as infection,bleeding, and scarring, there are risksthat are specific to breast implants.Learning about them is key to beingproperly informed about the proced u r e .

A Primer on Breast ImplantsAccording to the American Society

of Plastic Surgeons (ASPS), there werenearly 255,000 breast enhancement

Breast implants are designed foraugmentation, a cosmetic procedure;reconstruction; and replacement ofexisting implants, called revision.There are two primary types: saline-filled and silicone gel-filled. Depending on the type of implant, the shell iseither pre-filled with a fixed volumeof solution or filled through a valveduring the surgery to the desired size.Some allow for adjustments of the fillervolume after surgery. Breast implants

Act required a reasonable assurance ofsafety and effectiveness to he shownfor certain medical devices. The 1976law gave the FDA authority over suchdevices, hut breast implants were"grandfathered" into the regulatoryscheme, meaning that manufacturerswere not required to provide the agencywith scientific evidence of productsafety unless questions arose aboutthe safety and effectiveness of thesealready-marketed devices. Silicone was

P h o t o t a k e


initially assumed by manufacturers tobe biologically inactive and, therefore,to have no harmful effects.

But over the years, questions didarise about the effects of silicone onthe body. In 1991, the FDA publisheda regulation that required manufacturers of silicone gel-filled breast implantsto submit premarket approval applications (PMAs). This requirementmeant that the FDA needed to agreethat the manufacturer has presenteddata showing a reasonable assuranceof safety and effectiveness in order forthe devices to remain on the market.

In January 1992, the FDA called

cone gel-filled implants, claiming thedevices had caused serious ailments,such as connective tissue diseases,neurological diseases, and cancer. Consumer groups repeatedly filed petitionsurging more studies on the implants.But many women said they werepleased with their implants, including cancer patients who had pleadedfor the opportunity to choose siliconegel-filled implants for reconstruction.

A T u r n o f E v e n t s

In October 2003, the FDA held a two-day advisory panel meeting to discussa manufacturer's PMA for a silicone

Questions to Ask a Surgeon AboutBreast Augmentation

• What are the risks and complications associated with having breastimplants?• How many additional implant-related operations can 1 expect over myl i f e t i m e ?• How will my breasts look if 1 choose to have the implants removedwithout replacement?• What shape, size, surface texturing, incision site, and placement site isrecommended for me?• How will my ability to breast-feed be affected?• How can 1 expect my implanted breasts to look over time?• How can I expect my implanted breasts to look after pregnancy? Afterbreast-feeding?• What are my options if I am dissatisfied with the cosmetic outcome ofmy implanted breasts?• What alternate procedures or products are available if 1 choose not tohave breast implants?• Do you have before-and-after photos I can look at for each procedureand what resu l t s a re reasonab le fo r me? ■

for a voluntary moratorium—a delayon the use of these implants—untilnew safety information could be thoroughly reviewed. The moratorium wasnot intended to "ban" the implants, butinstead to a l low t ime to rev iew the new

safety information.In April 1992, the agency decided

that no PMA yet submitted containedsufficient safety and effectiveness datato support approval. However, access tothese silicone gel-filled breast implantsw o u l d c o n t i n u e f o r w o m e n e n r o l l e d i nc e r t a i n c l i n i c a l s t u d i e s .

In the years that followed that decision, thousands of women filed lawsuits against the manufacturers of sili-

gel-filled breast implant. Some peoplecomplained that the meeting was premature in light of the fact that long-term studies had not been completed,but the FDA proceeded because theagency was required by law to considerthe pending PMA within a specifiedtime frame. The meeting also providedpatients and others with timely accessto information and expert analyses onthe issue. The issues before the panelreflected much of the decades-longdebate over the implants. Moreover,the meeting provided a valuable public forum for discussing the issue frommany diverse perspectives and for raising important additional questions.

As a panel member, Benjamin O.Anderson, M.D., voted with the majority to recommend that the FDA approvethe new PMA, but only with specificconditions. Anderson says he wantsto avoid getting into the business ofdetermining how a woman defines thevalue of breast reconstruction or augm e n t a t i o n .

"The use of implants and augmentation conjures up some social judgmentsthat may well be unfair," says Anderson, a professor of surgery and directorof the University of Washington s BreastHealth Center. Rather than decidingthat no woman can have access tosilicone gel-filled implants because asmall number may be at risk for certain illnesses, he says, "I believe thebetter approach is to make the devicesavailable and inform all women of the

degree of risk involved."That, according to Anderson, "is rea

sonable informed consent."In January 2004—contrary to the

recommendation of the agency's advisory panel—the FDA determinedthat the new silicone gel-filled breastimplant PMA was "not approvable" atthat time. This meant that the implantswere not approved for marketing pending additional information, but thatw o m e n w o u l d c o n t i n u e t o h a v e l i m i t e daccess to them by enrolling in clinicals t u d i e s .

"The public scientific process that hasbeen used to cons ider these dev ices i s

fully consistent with the FDA's miss ion—to use the bes t ava i l ab le sc ienceto protect and promote the publichealth interests of the American people," says Linda Kahan, deputy director of the FDA's Center for Devices and

Radiological Health (CDRH).Also in January 2004, the agency

released a draft of its new guidelinesfor companies submit t ing breastimplant PMAs, explaining the scient i fi c i s s u e s t h a t t h e F D A r e c o m m e n d sbe addressed as part of their applications. The guidance document reflectsthe FDA's current thinking about newscientific information that the agency,manufacturers, and the cl inical community have gained over the last 10years, including information learnedat the October 2003 advisory panelmeeting. Consistent with the FDA's


pod ppance practices, the agency ing silicone gel-filled implants remain of whether it is saline-filled or siliconehas asked for public comments on the controversial. Women sense a change gel-filledbreast implant guidance. The guidance more easily when saline-filled breast Another potential complicationIS not intended for implementation implants rupture. But the silicone of implant surgery is nerve damage,until It IS finalized. gel-filled implants are more likely to which can cause some women to expe-

urrent testmg doesn t reflect maintain their shape after they rup- rience a loss or increase in sensation inreality, says Michael A. Choti, M.D., ture, which can make it more difficult their nipples and breast tissue Thesean associate profespr of surgery and to detect a break. symptoms may disappear eventually,oncology at the phns Hopkins Uni- Called "silent ruptures," these breaks but can be permanent in some cases. Itversity Spool of Medicine in Balti- involving silicone gel implants may is unclear at this time whether insuffi-more, and also an FDA advisory panel occur without a visible change. And cient milk production to breast-feed-member. The implants, he says, are a woman may not feel any sensation, another reported problem—is due toepremely durable when tested outside says Sahar M. Dawisha, M.D., a medi- damaged nerves or to other reasonsthe body. 'You can virtually run a truck cal officer in CDRH who has reviewed Women should know that regardlessover them and they'll hold up. Butthe question is, what happens whenimplanted long-term in a woman's Questions to Ask a Surgeon About""rhe FDA's draft guidance docunren, Reconstructionsays that two to three years of follow-up * What are all my options for breast reconstruction?data may not be enough to allow the * What are the risks and complications of each type of breast reconstruc-agency to evaluate the safety and effec- surgery and how common are they?tiveness of breast implants. The agency * at if my cancer recurs or occurs in the other breast?recommends the use of tests that can * reconstruction interfere with my cancer treatment?predict clinical outcomes, such as how * How many steps are there in each procedure? What are they?long breast implants will last before * much experience do you have with each procedure?rupturing in the body, as well as tests * What is the estimated total cost of each procedure?that explain how and why the breast * complete my reconstruct ion?implants rupture. In addition, the * have before-and-after photos I can look at for each procedureagency recommends that more data be what results are reasonable for me?gathered regarding the rate of rupture * What will my scars look like?over time, as well as the health conse- * What kind of changes in my reconstructed breast can I expect overq u e n c e s o f r u p t u r e . t i m e ?• What kind of changes in my implanted breast can I expect with preg-B r e a s t I m p l a n t R i s k s n a n c y ?

In 1999, the Institute of Medicine * options if I am dissatisfied with the cosmetic outcome of(lOM) issued a report on a review implanted breast?of information related to health * rnuch pain or discomfort will I feel and for how long?effects associated with silicone breast * hospital? Will I need blood transfusions, andimplants, both gel-filled and saline- ^n I donate my own blood?filled, in humans. An important goal ' ^ble to resume my normal activities? ■of the lOM was to provide women with source; fdadetailed information about the potential risks of silicone breast implants. data submitted by implant manufac- of the type of implant, it is likely they

One risk is capsular contracture, turers. Magnetic resonance imaging will need to have one or more addi-which is a tightening and squeezing (MRI) with equipment specifically tional surgeries (reoperations) over theof the scar tissue that naturally forms designed for imaging the breast may course of their lives, because of compli-around the implant. This contracture be used for evaluating women with cations from breast implants. Reasonsmay result in hardening of the breast suspected rupture of their silicone for reoperations include any of thetissue, rippling of the skin, and changes gel-filled implant. The FDA considers potential complications, such as capsu-in breast shape. It also may cause pain, MRI to be the best method at this time, lar contracture, wrinkling, asymmetry,which, if severe, can require surgery to There are no standards on how often rupture, or implant malposition,remove the scar tissue or replace the to screen for silent rupture with MRI, The lOM committee also found thatimplant. and the costs of this procedure must be women with silicone breast implants

In addition, a rupture can occur at considered when choosing a silicone are no more likely than women with-any time. While saline-filled breast gel-filled breast implant. Physicians out implants to develop the life-threat-implants leak only salt water when usually recommend removal of the ening systemic illnesses that somethey rupture, the health effects of leak- implant if it has ruptured, regardless people have claimed might be related


to the implants.But many women disagree. They

have reported health problems relatedto their immune systems or neurological symptoms that they believe arecaused by ruptured or intact breastimplants. And some women who havereceived breast implants claim theyweren't fully informed of the risks.

Lynda Roth, who wasdiagnosed with breastcancer in 1990, says shewas forced to make a quickdecision, based on veryl i t t l e i n fo rmat ion , abou t

getting breast implantsfollowing a mastectomy.

"1 t rus ted what myhighly respected doctorswere telling me was true,"says the 63-year-old socialw o r k e r i n c e n t r a l C o l orado. "You're in shock, youthink you're going to die,s o w h a t k i n d o f i n f o r m e ddecision can you possibly make about what youwant your breasts to looklike if you're lucky enought o s u r v i v e ? "

R o t h d i d s u r v i v e — b o t hbreast cancer and two si l icone breast implants gonebad. But the rupturedd e v i c e s , s h e b e l i e v e s ,c a u s e d h e r t o l o s e h e r

good health, her job, andeventua l ly her hea l thi n s u r a n c e o v e r t h e n e x t11 years. "I found outthe hard way," she says."There were many riskswith the implants that Id i d n ' t k n o w a b o u t . "

O t h e r w o m e n a r e

p l e a s e d w i t h t h e i rimplants. Clara Fi l ionu n d e r w e n t r e c o n s t r u c t i o n i n 1 9 9 3 a f t e r

having a breast removal that includedthe lymph nodes under the arm (modified radical mastectomy) due to cancer.The 67-year-old Bedias, Texas, residentsays she's thrilled with the outcomeof her saline-filled implant, as wellas with her surgeon, even though heroriginal implant will need replacings o o n d u e t o s c a r t i s s u e — a l o c a l c o m

plication that Filion says she always

knew could occur. Filion has experienced no other complications relatedto the implant in 11 years.

O t h e r C o n s i d e r a t i o n s

"My doctor told me that theseimplants would go with me to mygrave," says 44-year-old Patty Faussettof Henderson, Nev., who chose to aug-

Patty Faussett of Henderson, Nev., says she regained her goodhealth after she had her saline breast implants removed.

ment her breasts with sal ine breastimplants in 1997, after years of breastfeeding distorted their shape.

Faussett had her implants removeda year after implantation because shebelieves they caused a mixed bag ofhealth problems, including disturbedvision, heart palpitations, muscletwitching, and an autoimmune thyroid disease. She says, "The risks weremuch greater than my surgeon led me

t o b e l i e v e . "

Experts caution that breast implantsd o n o t l a s t a l i f e t i m e . W o m e n s h o u l dbe prepared for long-term follow-upand additional surgeries to treat complications. They also should be prepared for the accompanying additionalcosts. One of the biggest problemsFaussett says she hears from women

in her breast implant support group is that "mostdon't plan for the moneyit takes to fix what goeswrong."

I n a d d i t i o n , w o m e nshou ld be aware tha t hard

pressure on the breast(compression) duringmammography may causeimplant rupture. Breastimplants also can interferewith finding breast cancerduring mammography.Doctors say the implantcan hide breast tissue and,as a result, hide lesionsa s w e l l . E x t e n s i v e s c a r

ring and calcium deposits in tissue surroundingan implant can mimicthe appearance of cancer, making the depositsdifficult to distinguishf r o m t u m o r s o n a m a m

m o g r a m .A n o t h e r c o n s i d e r a t i o n

is the choice of a surgeon.Patient advocates, professional groups, and others agree that it's important to choose a plasticsurgeon who has beentrained in breast implantsurgery and who has performed it successfully onm a n y w o m e n .

After switching to anew, firmer silicone gel-filled implantthrough a clinical study only a yearafter experiencing rippling with hersaline implants, Kathy Bracy says it'simportant that women who are considering breast implants do their homew o r k .

"I love my breast implants, but Ialso spent six months researching thedevices, which included picking thebest doctor for me," says Bracy, a 38-

B l a c k S t a r / L e e M c D o n a l d


year-old self-employed bookkeeperfrom Tampa, Fla. "It's not necessarilythe product, but who is doing the surgery." The key to breast implant satisfaction, she says, is to "find a doctorwho is willing to answer all your questions and take all your concerns seriously. And the relationship with yourdoctor doesn't end after the surgery."

Experts also advise women to haverealistic expectations about breastimplants. There is no guarantee thatt h e r e s u l t s w i l l m a t c h t h o s e o f o t h e r

women. Overall health, age, cheststructure, the shape and position ofthe breast and nipple, skin texture, the

A laboratory worker at a silicone breast implantmanufacturing plant does a product check.

tendency to bleed, prior breast surgeries, and the surgical team's skill andexperience all figure into the outcomeof breast implant surgeries.

T h e Te e n S c e n e

In addition to safety issues, thereis concern about the growing use ofbreast implants among teen-agers.Health officials worry that teen-agersand their parents may not realize therelative permanence of the changescaused by the devices. They also wantto be sure that teens are physicallyready—that is, they're finished developing—and that they are psychologically mature enough to handle theoutcome of surgery.

"I didn't know my breasts were stillgrowing when I signed up for the surgery," admits Kacey Long, who gotsaline-filled breast implants in July2001, when she was 19. Prior to her

surgery, the college student from Ennis,Texas, was a 34B—a breast size shethought would be with her for life.

Teen-agers who are dissatisfied withtheir bodies see breast implants as aharmless—and, according to Long,"fun"—thing to do to improve theirself-image. Long says she felt that herbody was too "bottom heavy" for herb r e a s t s a n d w a n t e d t o " e v e n o u t " h e r

figure. "But I never thought about myimplants being dangerous," she says.A friend's mother worked for a plastic surgeon for 12 years and told Longshe knew of no problems with patientswho had gotten the implants. "I really

thought that I had insidei n f o r m a t i o n , a n d t h a tt h e s e d e v i c e s w e r e c o m

pletely safe and mainten a n c e - f r e e . "

Fo l l ow ing imp lan tation, Long went to a 34D.But complications conv i n c e d h e r t o h a v e t h e

implants removed a shorttime later. "I had shootingpains in my arms, excruciating pain in every joint,bone, and muscle of mybody, I was exhausted allthe time, had no energy,lost my hair, and hadpains in my chest, heart,a n d r i b s . I h a d t r o u b l e

remembering things and thinkingclearly, and the list goes on," she says."Before the implants, all I had wasallergies."

Many of the changes to the breastthat occur with an implant cannot beundone. If a teen chooses to have herimplants removed, she may experience dimpling, puckering, wrinkling,or other cosmetic changes.

Three years later. Long's breastsmeasure 36C—one size larger thanbefore she was implanted—suggesting that her own breasts continued todevelop even after the implants wereremoved. "When you're making a decision that can impact your life at 19,"Long advises other young women, "youneed to research the subject like you're50 years old."

Ongoing clinical studies for unapproved saline-filled and silicone gel-filled breast implants do not allow for

those younger than 18 to receive theimplants for augmentation purposes.S o m e o f t h e s e c l i n i c a l s t u d i e s e v e nl i m i t r e c o n s t r u c t i o n a n d r e v i s i o n u s e st o w o m e n 1 8 a n d o v e r .

Consumers can get a copy of the"FDA Breast Implant Consumer Handbook 2004," which provides in-depthi n f o r m a t i o n o n b o t h s a l i n e a n d s i l icone breast implants, by visiting www.fda.gov/cdrh/breastimplants/, or by writing to: FDA, Office of Device Evaluation, Division of General, Restorative,and Neurological Devices, 9200 Corporate Blvd., HFZ-410, Rockville, MD2 0 8 5 0 . ■

F o r M o r e I n f o r m a t i o nFood and Drug Administrationwww.fda.gov/cdrh/breastimplants/

F D A C e n t e r f o r D e v i c e s a n d

Radiological HealthC o n s u m e r A f f a i r s S t a f f

(800) 638-2041

N a t i o n a l W o m e n ' s L l e a l t hI n f o r m a t i o n C e n t e r

www.4woman.gov(800)994-9662

I n s t i t u t e o f M e d i c i n ew w w. i o m . e d u


www.nci.nih.gov(800) 422-6237

Office of Research on Women'sH e a l t h

www4.od.nih.gov/orwh/

American Society of Plastic Surgeonswww.plasticsurgerY.org(888) 475-2784

American Society for AestheticPlastic Surgeryw w w. s u r g e r y. o r g(888) 272-7711


Take theFDA ConstirDer

Are breast implants a safe and effective way to enhance yourappearance? Will cancer vaccines someday replace chemotherapyand other treatments in the war against cancer? How prevalentis the skin disease psoriasis, and is it fatal? To find oothow mtich yod know abodt these and other health-related topics, take odr qyiz.Hint: The answers to all of these questions can be fodndin the September-October 200f issde of FDA Consumerand at the bottom of this page. Good luck/1. What percentage of U.S. adults with cancer participates inc l i n i c a l t r i a l s ?a. less than 3 percentb. 25 percentc. 10 percentd. 50 percent

2. About how many cancer vaccines are being studied ina d v a n c e d c l i n i c a l t r i a l s ?a . n o n e

b . 5c . 1 2

d . 2 5

Q0I2

3. How long have researchers been working to develop a cancerv a c c i n e ?a. for the last 5 yearsb. for the last 10 yearsc. for the last 50 yearsd. for more than 100 years

4. Psoriasis most often strikes people between the ages of;a. 6 and 10b . 15 and 35

c . 35 and 55d . 5 5 a n d 7 0

5. How many new cases of psoriasis are diagnosed each yearin the Un i ted S ta tes?a. nearly 10 millionb. between 150,000 and 260,000c . 1 m i l l i o nd. 500,000

6. A health complication that occurs in about 15 percent ofpeople with psoriasis is:a . a r t h r i t i s

b . a s t h m ac. glaucomad. lupus

7. How many people in the United Statesgot sick from drinking unpasteurized milk oreating cheese from unpasteurized milk in the years 2001a n d 2 0 0 2 ?a. nearly 70b . a b o u t 1 0 0c . 3 0 0

d. nearly 500

8. Symptoms of foodborne i l lness f rom dr ink ingunpasteurized milk may include:a. diarrhea, stomach cramps, feverb. headache, vomiting, exhaustionc. kidney failured. miscarriagee. a l l o f t he above

9 . M e d i c i n a l l e e c h e s a r e r a i s e d i n :a . s w a m p sb . c o n t r o l l e d b a s i n s a n d l a b o r a t o r i e s i n c e r t i fi e d f a c i l i t i e sc . l a kes and r i ve r s

d. special mud

10. Buying prescription drugs online from unknown foreignsources is:a. safe in some casesb. risky businessc. safe in al l casesd. a good way to save money on prescription drugs

A n s w e r s

38 / September-October 2004 / FDA Consumerq '01 'q '6 '3 '8 'P -L 'E "9 'q "S 'q k 'P '£ P 'Z 'l

By John Henkel

Magnets Attracting You? Read ThisFor centuries, magnets have been used in attempts to treat

pain. And though scientific evidence so far doesn't support aconclusion that magnets can ease pain, some patients usingthem do experience relief.

So what's the story on magnets?To help sort out fact from hype, the National Center for

Complementary and Alternative Medicine has posted questions and answers that should give consumers the tools tomake informed choices about using magnets. View the listat http:llnccam.nih.govlhealthlmagnetlmagnet.htm.

Note: The FDA has not approved the marketing of magnetswith claims of benefits to health (such as "relieves arthritispain"), and the agency, along with the Federal Trade Commission, has taken action against unscrupulous magnetm a r k e t e r s .

S o m e G r e a t A d v i c e f o r G i r l sToday is a great time to be a girl ... You have many possi

bilities and choices ... You can make goals for yourself anddevelop your talents ... All these choices are exciting, butthey can be a little confusing.

So reads a page about self esteem found on Girl Power, aWeb site created by the Department of Health and HumanServices to promote positive values in girls ages 9 to 13 bytargeting health messages to their unique needs and intere s t s .

The site, at wtvw.girlpower.gov, is colorful and interactive,with loads of fun ideas for wholesome activities. Lookingfor a neat outdoor activity? Try one of more than 30 of GirlPoiver's ideas. Like to surf the Net? Check out Girls Allowedor White House Kids or any of the site's other suggestions.The site also has a guest page with upbeat messages fromfolks such as singer Brandy, astronaut Ellen Ochoa, authorJudy Blume, and even cartoon character Lisa Simpson.

Mom and Dad can get in on the act, too, with a special section containing advice on better sleeping, keeping childrendrug-free, and getting involved with your community.

An Easy Way to 'Get the Facts'Did you know that about 12 percent of women in the

United States suffer from depression, but that 80 percent ofthem get better with treatment? Or that most health planswon't cover the cost of LASIK eye surgery? Are you awarethat dietary supplements such as vitamin pills should notbe used as a substitute for eating a variety of foods?

These are a few of dozens of useful health tidbits thatyou'll find in a series of fact sheets called "Get the Facts,"available online in graphical (PDF) form or in a printer-

friendly text format. Produced by the FDA Office ofWomen'sHealth, the series offers reliable background on nearly 30topics, some of interest just to women, but many of valueto all consumers. Among them:• d i a b e t e s• allergies• tattoos and permanent makeup• inferti l i ty• h e a r t d i s e a s e

The fact sheets are brief and written in an easy-to-under-stand style. To "Get the Facts," go to www.fda.govjivomenslgetthefacts/.

Our World is Dangerous Now—AreYou Ready?

There was a time not long ago when disaster preparednessin the Linked States focused on natural calamities: bracingfor a predicted tornado or creating structures to withstandearthquakes. But events in recent years have put Americaon notice that disaster preparation now must include dealing with catastrophes created by human actions ratherthan nature. The Department of Homeland Security (DLIS)points out that terrorists are working to obtain biological,chemical, nuclear, and radiological weapons and that thethreat of an attack is real.

On its Web site Ready.gov (wtvw.ready.gov), the DHS offersmuch helpful advice on how to prepare yourself and yourloved ones for natural and man-made emergencies. Tacticssuch as assembling a kit of basic survival items and developing a family communications plan can give an edge shoulda disaster occur. The site contains detailed instructions andsupply checklists.

Also on Ready.gov are tips on what to do in the event of anattack if you are in a moving vehicle, a high-rise building,or at work or school. Though the DHS cautions that there'sno way to predict what will happen in an attack, it says that"with a little planning and common sense, you can be better prepared for the unexpected."

The FDA also has an online gateway to other helpfulinformation on its counterterrorism Web site: www.fda.gov/oc/opacom/holtopics/bioterroristn.html. ■

John J-Jenkel is a member of the FDA'sWebsite Management Staff.


I The Last Word : ^ .

Living with PsoriasisBy Michael Paranzino

When that very first patch ofpsoriasis appeared on my elbowduring 10th grade, I was actuallyhappy. It gave me a sense of solidarity with one of my older brothers, who had been living with substantial psoriasis as long as I couldremember. It was not until eightyears later, sitting in the hospitalcovered head to toe in psoriasis,that I realized the absurdity ofwelcoming that first patch. Now,

not wisn It on my worst enemy.Psoriasis is a disease driven by the immune system that

typically manifests itself as patches of incredibly dry, flakyskin. For many people with psoriasis, it never moves beyondsome annoying patches on places like the elbows, knees,or scalp, but I am not so lucky. I am part of that one-thirdof patients with what the experts call "moderate-to-severe"psoriasis.

Psoriasis, because it is so unsightly, can be emotionallytaxing—I have psoriasis on my hands and face, for example,so hiding it is not an option. Everyone who sees me seesit, and everyone who shakes my hand feels it. But psoriasiscan also be physically draining—walking, bending, evensitting can be painful because of psoriasis on the feet, legs,arms, or on the folds of the skin. I am one of those psoriasis patients whose skin bleeds—somewhere—almost everysingle day, and it itches constantly and ferociously.

In short, psoriasis is dreadful. And the kicker is that thetreatments for moderate-to-severe psoriasis offer a choiceamong unpalatable potential side effects, including risks ofliver damage, kidney damage, cancer, and serious infections.And this is just to minimize, not eliminate, my psoriasis.

But many new options are now becoming available. Threenew psoriasis drugs have recently hit the market, and others are on the way.

And not a moment too soon. You see, I now have a 3-year-old son. So while I have grown more or less accustomed tobleeding, and itching, and looking strange, every day of mylife, I do not want my child to face that same fate. I poreover the statistics suggesting that I have given him a 1 in 4chance of developing psoriasis. I have met several psoriasispatients who elected not to have children for this reason. Iworry every time he gets a scrape, which, for a 3-year-old,

means every day, because skin trauma can trigger psoriasisin those susceptible to it. I stare at the computer printoutshowing that the federal government spends one dollarper patient per year researching psoriasis, and I fret that hedeserves more. I read that the pharmaceutical industry nowconsiders the psoriasis market promising, and I am thrilled.It sure beats being ignored.

Comparing myself to other psoriasis patients, I considermyself lucky. While I have a more severe case than most, atleast I have never been thrown out of a pool by a misguidedlifeguard, like some other psoriasis patients I have met. 1have not yet had the arthritis symptoms that make activityso painful for many others. And I did not have psoriasis inelementary school, when the teasing might have been horrible. But every day, some 50 American kids under age 10are diagnosed with psoriasis. What about them?

While seeing psoriasis on my 8-year-oId niece, or justimagining it on my son, can bring tears to my eyes, Iremain optimistic, because the treatment options are rapidly improving beyond what I was offered during my firsthospitalization in 1990. We're not out of the woods yet, byany means—my leg psoriasis bled, in fact, as 1 wrote thispiece—but scientific ingenuity is bringing us closer to thatscenario we are all looking for: better treatments with fewers ide e f fec ts .

In the end, those of us with incurable diseases draw bopefrom scientists. Perhaps that's why I married a neurobiolo-gist. She won't cure psoriasis, but someday, maybe somebody else's spouse will. ■

Michael Paranzino is a government affairs consultant in Bethesda,Md. His clients include the National Psoriasis Foundation.


www. heal thgap. omhrc. gov

1 . 8 0 0 * 4 4 4 * 6 4 7 2 ( j IC L O S I N G ,

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