TheFDA

Magazine

January

of the

-=

U=.S

February

.Food

2000

and

•=Vol.

Drug

34

ConsumerNo. 1

Administratio

Buying Drugs Online

Ve Olde Online Drugstore

[ 28066420.4010 :34 / 1

OK

.......

SA

Donna E. Shalala, Ph.D.SecretaryofHealth a

nd

HumanServices

FDA Consumer

SES

Jane E . Henney , M . D .

Commissionerof

Food and

Drugs The Magazine of the U . S .Food and Drug Administration

January -February 2000 • Vol . 34 No . 1LawrenceBachorik , Ph . D .

InterimAssociateCommissionerfor

PublicAffairs

Isadora Stehlin /Editor

Special Section : The Many Faces of Drug StudiesPatricia N . Edwards / Art

Director

Michael L . Herndon / ProductionManager

Carol L . Ballentine / CopyEditor

Experimental Treatments : Unapproved butNot Always UnavailableUnder a

n FDA program , patients with life-threatening diseases such as

AIDS or

cancer can receive promising " investigational " drugs before they are approved for

general use .Cover Design : RichardThompsonJr .

FDA on

the

Internet : www . fda.gov

14

FDA

Consumer( ISSN

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Drug

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The Healing Power of

Placebos

The mind is a powerful thing , as proven by

the number of patients whose condi

tions improve when given only a "dummy " pill

as

treatment .

EditorialMatters

Addressfor

editorialmattersis FDAConsumer,Food and

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FDA

ConsumerIndexis availableon

FDA' s Websiteat

www. fda. gov/ fdac/ index/ conindex. htm.

Are Bioengineered Foods Safe ?

Found in products ranging from spaghetti sauce to soft drinks , bioengineered foodingredients are becoming more and more prominent . In an interview with FDA

Consumer , the agency ' s commissioner says that products on themarket have

passed FDA review and are safe .

24

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Buying Drugs Online : It ' s Convenient and Private , but Beware of 'Rogue Sites '

Though the

Internet can bea good place to buy prescription drugs and other

health needs , consumers should watch out

for

illegal sites that sidestep traditional

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Inside Front Cover Photo :

While the number of

foods produced by

bioengineering continues to grow , someconsumers a

re concerned about the safety of these foods . FDA Commissioner Jane E .

Henney , M . D . , explains how FDA is addressing those concerns ,page 18 .

FDA Consumer / January -February 2000 / 1

UPDATESSNS

FDA Proposes Adding 'Trans Fats ' Info to Food LabelsUnder a rule recently proposed by FDA , the Nutrition Facts labels on vegetableshortenings and some cookies, crackers ,margarines , and other foods may soon carryinformation about an ingredient called “ trans fatty acids ,” or trans fats ,which studies indicate may increase the risk of coronary heart disease .Beyond requiring that some labels list the amountof trans fats in the food , the

rule, as proposed ,also defines the

term “ trans fat

free ” and limits the use of

certain

nutrient or

health claims related to fat

content ,such as “ lean ” and “ low saturatedfat . ”

Scientific studies show that trans fats can raise the level of

blood LDL (low -density lipoprotein , or “bad ” ) cholesterol ,which is associated with coronary heart disease and stroke . The American Heart Association estimates that about 500 ,000Americans die each year from coronary heart disease ,making it the number onecause o

f

death in theUnited States .

The proposed rule was published in the Nov . 17 , 1999 , Federal Register and is

available on

the Internet atwww .fda .gov /ohrms /dockets /98fr /111799c .txt . Commentsmay b

e

submitted until Feb . 15 , 2000 , by writing to FDA ’ s Dockets ManagementBranch ,HFA - 305 , 5630 Fishers Lane , Room 1061 , Rockville ,MD 20852 .

Study Suggests Folate Deficiency -Down Syndrome Link

Mothers of

children with Down syn - FDA ' s requirement , according to FDAdrome show biochemical and genetic Commissioner Jane Henney , M . D .

signs of

impaired metabolism of

the nu - Down syndrome is a leading genetic

trient folate , according to a study by cause of

mental retardation that affects 1

FDA ' s National Center for Toxicological out of 700 live births . Also called triResearch . somy 2

1 , it is caused byan extra copy of

In March 1996 , FDA began requiring chromosome 21

that is usually maternal

that folic acid be added to certain grain in origin .

products , such as flour , breakfast cere While the FDA study provides some

als , and pasta . The agency based the new insights into possible causes of

the

move on evidence that an insufficient disease , larger clinical studies are necesfolic acid level in early pregnancy in sary to confirm it

s findings and to deter

creases the risk of

birth defects in the mine definitively whether folic acid

brain and spinal cord . The new study , supplementation ( at least twomonthspublished in the American Journal o

f

before pregnancy )will reduce DownClinical Nutrition , further supports syndrome incidence .

Benefit of Soy Is Heartfelt

Certain foods containing soy protein

may now carry a health claim about the

role of soy in reducing the risk of

coro

nary heart disease (CHD ) .

FDA is allowing the claim based on

evidence that soy protein ,when compared with other proteins such as

those

from milk or

meat , can lower cholesterollevels when part o

fa diet low in saturated fat and cholesterol .

CHD , one of

the most serious formsof

cardiovascular disease , causesmoredeaths in the United States than any

other disease . CHD risk factors includehigh total cholesterol levels and elevated

amounts of

low -density lipoprotein

(LDL , or “ bad ” ) cholesterol .

Studies show that 25 grams of

soy

protein daily in the diet can lower both

total and LDL cholesterol levels . To

qualify for the approved health claim ,

foods must contain at least 6 . 25 grams

of

soy protein per serving .

Eligible foods include soy beverages ,tofu , tempeh , and soy -based meat alternatives . Foods carrying the claim alsomust b

e

low in fat , saturated fat , and

cholesterol . Foodsmade with wholesoybeans , however ,may carry the claim

if no other fat is present besides thatfound naturally in the whole bean .

FDA approved the claim last October

in response to a petition by

Protein

Technologies International .

“ E ” deficiencies found . . .Nearly a third of Americans have low levels of vitamin E ,

says a study published by

the

national Centers for Disease Control and Prevention .

Researchers found the low levels in 41 percent of

African - Americans , 28 percent of

Mexican -Americans , 26 percent of whites , and 32 percent of other groups . Datafrom a periodic federal government study focusing o

n

the health of

Americanswereused in the study . Researchers were most concerned about how the information re

lates to the relatively high death rate from cardiovascular disease and cancer in the

African -American population . Despite the important role vitamin E may play in pre -

venting or controlling chronic disease , few population -based studies of distributions

and correlates of

blood concentrations of

vitamin E have been performed . (American

Journal of

Epidemiology , August 1999 )

2 / January -February 2000 / FDA Consumer

New estimates on food -borne diseases ...Government data released last Septem

ber says food -borne diseases sickenmore people than previously thought butkill fewer . The national Centers for Disease Control and Prevention says that 76million people a

re sickened , 325 , 000 arehospitalized , and 5 ,000 d

ie each year

from food poisoning , a revision of

the

previously reported 33

million sick

nesses and 9 ,000 deaths . CDC says thedata were revised because better information is now available o

n which to

base the estimates ,which should helpguide food -borne illness prevention e

f-

forts and assess the effectiveness of

food

safety regulations .Eleven Programs Awarded FDA Food Safety Grants

The innovative food safety projects of11

state and local regulatory agencies will

geta boost in the

form of

FDA grants totaling almost $500 ,000 . The one -yeargrants , awarded a

s part of

President Clinton ' s food safety initiative , apply to fourkey areas : inspection , regulation and compliance , information systems , and education and health information .

The

following programs and agencies received grants :

• Minimize or

Eliminate Filth Organisms and Human Pathogens from SeedSprouts (Florida Department o

f Agriculture and Consumer Services )

• Web -Based Training for Inspection of

Apple Cider Processing Plants (WisconsinDepartment o

f

Agriculture )

• Food Safety for Festivals , Fairs , and Fundraisers — An Instructional Website andVideo (McDonough County , II . , Health Department )

• Multi -Language Audio Food Safety Education and Testing Program (SouthwestWashington County ,Wash . , Health District )

• Food Worker Certification Pilot Project for High School Students (Kentucky

Cabinet for Health Services )

• Training Program for Professional Sanitarians (Michigan Department ofAgricul

ture )

• Food Safety Standards for Residential and Other Meal Sites for

the Elderly

(Rhode Island Department of

Health )

• Risk -Based Assessment Program forOff -Site Food Service (Maricopa County ,

Ariz . , Environmental Services Department )

• User -Friendly Database of Facilities and Inspection Data (Jefferson County ,Mo . ,

Health Center )

• Integrated Food Safety Information Delivery System (Iowa Department of

Inspections and Appeals )

• Hands -On HACCP for the Ready - to -Eat Food Industry (Georgia Department of

Agriculture ) .

Eat less , live longer ? . . .Genes that play

a vital role in aging tend to stay healthier

in response to a low - calorie diet , says a

study by

researchers at

the University of

Wisconsin ,Madison . In mice fed a re

stricted diet , about 84 percent of the ge

netic alterations associated with aging

were completely or partially suppressed .

Scientists say this research may lead to

drugs that could help slow aging in humans ,although n

o studies have yetproven that a reduced -calorie diet willextend life in humans . (Science , August1999 )

Doctors fail to discuss concerns . . . Physicians counselingwomen on

the

use of

hormone therapy do not address patient fears , says a Harvard University study . Womenidentified a

n average of15 factors that were important to them as they decided to

use prescription hormones to ease menopause

symptoms ,but these were not addressed by

their

doctors . Nearly every woman said that her

doctor ' s opinion was critical to her decision . Theresearchers found that the guidelines for physi

cians on hormone replacement therapy that are is

sued by

the American College of Physicians , the

American College of

Obstetricians and Gynecologists , and the U . S . Preventive Services Task Forcemay not reflect patient concerns .New methods fo

r

promoting shared decision making with patients

are being considered . (Annals of InternalMedicine , August 1999 )

FDA Consumer / January -February 2000 / 3

UPDATES (continued )

Where Others Have Failed , New Antibiotic May HelpThough multiple other antibiotics have been ineffective , a new antibacterial drug

ious against a hardy infection that occurs most often in hospitalized

patients and those with weakened immune systems .Synercid (a combination of quinupristin and dalfopristin )was approved to treatinfections associated with the Enterococcus faecium bacterium when there is no

other effective treatment and an infection has even

resisted treatment with the drug vancomycin , previously viewed as the last -resort medication .Since 1989 , when the first case of vancomycin

resistant Enterococcus faecium was reported , theU .S . incidence of this potentially life -threatening

condition has increased rapidly .Because Synercid is for such a serious condition , the drug was granted early approval based on

its ability to clear the

bloodstream of

infection . A study is under way to verify the

drug ' s beneficial effect at the specific site of infection .

In clinical trials of

more than 2 ,000 patients , the overall effectiveness rate amongthose who could b

e fully evaluated was 52 percent . The drug ' smost common side

effects were muscle and joint pain , nausea , diarrhea , vomiting , rash , and ,when thedrug was injected through a peripheral vein , reactions around the injection site such

as

pain and inflammation .

FDA ' s approval of Synercid in September 1999made it the first drug in its

“ streptogramin ” class to be approved in the United States for human use . The

approval followed the recommendations of

the Anti - Infective Drugs Advisory Committee .

Also approved to treat complicated skin and soft tissue infections , Synercid is

marketed by

Rhône -Poulenc Rorer , a French company with U . S . headquarters in

Collegeville , Pa .

United States is nearly measles - free . . .

Only 100 cases of

measles were re

corded in the United States in 1998 , virtually stamping out what was once a

common childhood disease . The nationalCenters for Disease Control and Preven

tion said all

but 29 of

those cases involved people who were initially infected in other countries . The numbersuggests thatmeasles has joined the

ranks of

smallpox , polio , diphtheria , andother diseases essentially wiped out in

the

United States , due mainly to immunizations . Just 10 years ago , there wereover 27 ,000 domestic measles cases and64 deaths .

Breastmilk may help reduce allergies . . .

Breast -feeding babies for

their first four

months may protect against asthma andallergies . A study b

y

Australian re

searchers examined 2 ,187 newborns

from birth until 6 years , and those who

are exclusively breast -fed for

the

firstfour months of life were significantly

less likely to develop asthma and allergies a

t6 than children who began drink

ing other types of

milk before 4 months

of

age . The findings are consistent withother studies showing breast -feeding

benefits . Breast milk appears to containimportant nutritional , anti - inflammatory

or

other substances that may help guard

against asthma . (British Medical Journal , September 1999 )

Daily Capsule Bolsters Flu -Fighting Arsenal

Flu sufferers have onemore weapon in ported that symptoms improved a littletheir fight against the miseries o

f

influ - more than a day earlier than did those

enza . The new oral drug Tamiflu taking a placebo .

(oseltamivir phosphate ) can shorten the Themost common side effects of

the

flu ' s troublesome symptoms , such as drug were nausea , vomiting , bronchitis ,

sore throat , congestion , cough , chills and sleep disturbance , and dizziness . Tamiflufever ,headache , body aches , and fatigue . has not been shown to prevent flu infec

Tamiflu is approved for treatment of

tion or

decrease the chance of

transmitType A and B influenza , the twomost ting it to others . It is not approved forcommon types in the United States . Pa - use b

y

children under 18 and has nottients should start treatment with Tamiflu been shown to b

e

safe and effective for

within two days of

the first flu symp - patients with chronic heart or lung dis

toms . The recommended dose is one 75 - ease .

milligram capsule twice a day for

five Tamiflu was approved in October and

days ,with orwithout food . is marketed by Roche Laboratories Inc . ,

In clinical studies in more than 1 ,000 Nutley , N . J .

patients , those treated with Tamiflu re

4 / January -February 2000 / FDA Consumer

Blood pressure warning ... New findings fromthe long -term Framingham Heart Study show

ing the dangers of not treating peopletype of hypertension called elevated systolic

high blood pressure has prompted NIH to warn250,000 U .S. health professionals thatmillionsof Americans are at risk ofdangerous complications . Systolic blood pressure is produced as th

e

heart contracts and pumps blood to the body .

Until recent years , the systolic reading had often

not been considered a significant indicator

of

blood pressure problems . ButNIH ’ s advisoryurges more aggressive treatment o

f

the condition . An estimated 43million people in

the United States have high blood pressure , says the National Center for Health

Statistics , and the prevalence rises with age . Left uncontrolled , high blood pressuresignificantly increases the risk o

f

heart attack , stroke , and kidney disease , and is theleading cause o

f congestive heart failure .

Drug OK ' d to TreatBreast Cancer After Surgery

For early -stage breast cancer that hasspread to the lymph nodes under the

arm , FDA has approved a new drug totreat the cancer after surgery has removed a

ll

known tumor .

Epirubicin hydrochloride injection

(Ellence ) is a member of

the

anthracycline class of

anti -cancer medications . These a

re believed to work by

interfering with a number of

biochemi

cal and biological functions within cancer cells , though their precise mechanism o

f

action is not completely

understood . These drugs are commonly

used in combination with other medica -

tions to slow or halt the cancer ' s pro

gression and potentially prolong somepatients ' lives .

FDA based its September 1999 ap

proval on the results of

two long -term ,

clinical studies in about 1 ,200 patients .

The findings showed significant lengthening o

f

the time without a relapse of

the disease ( recurrence of

tumor ) and in -

creased five -year overall survival .

Adverse effects associated with the

drug include nausea , vomiting , diarrhea ,

sores in the mouth , and hair loss . In addition ,women have a slightly increased

risk for treatment -related leukemia whiletaking the drug . Epirubicin may harmthe fetus if given to a pregnant woman ,

and the drug may also cause premature

menopause in premenopausal women .

Also ,men undergoing treatment withepirubicin should use effective contraceptive methodsbecause therapy with

the drug can cause chromosomal damage in sperm . Patients should be in

formed that there is a risk of

irreversible

heart damage associated with the drug .

The drug is manufactured by

Pharmacia & Upjohn Company , N . J .

Cancer -shrinking protein found . . . Scientists have identified another humanprotein thatmight starve tumors o

ftheir blood supply and shrink cancers with fe

w

or

no

side effects . One more in a growing list of“ angiogenesis ” inhibitors , this new

protein halted the growth of blood vessels to human tumors inmice and caused them

to shrink into small nodules . This research further supports a promising area of

cancer research in the United States and Canada over the past two years . Twenty

angiogenesis inhibitors are under study in cancer patients in the United States alone .

(Science , September 1999 )

New Drug May Help Prevent Rejection of Transplanted Kidneys

Kidney transplant patients now have required treatment with cholesterolavailable to them a new drug that can lowering drugs . Suppressing the immunebolster the effects o

f

existing treatments system also increases the

risk of infec

in suppressing the immune system and tion and lymphoma .

helping to prevent rejection of

trans Only doctors experienced in immunoplanted kidneys . suppression and managing organ

The drug ,Rapamune (sirolimus ) , is transplant patients should prescribe

taken with two other immunosuppres Rapamune . Ifmeasures ofkidney funcsants used to prevent tissue rejection tion indicate impairment , doctors shouldcyclosporine and corticosteroids — but adjust the immunosuppression drugs as

works differently from other immuno necessary .

suppressants and has few overlapping Patients take Rapamune in liquid formtoxic effects . mixed with water o

r

orange juice . TheyTwo clinical studies supported the should not drink grapefruit juice withdrug ' s safety and effectiveness . Adverse Rapamune o

r

use grapefruit juice to

reactions seen in some of

the 1 , 300 dilute the drug .

study patients included increases in Rapamune , approved by

FDA lastserum cholesterol and triglycerides September , ismanufactured b

y

Wyeth

(another type of

fat found in the blood ) Ayerst Laboratories , Philadelphia .

as

well as high cholesterol levels that

FDA Consumer / January -February 2000 / 5

S

UPDATES (continued )ICO

Don 'tmix herbs and standard drugs ... Users of prescription drugs and alternativeremedies could place themselves at risk if they don 't tell their doctors they are combining these substances , say researchersfrom George Washington

University and the National Institutes of

Health . One in

every five pre

scription drug

users also takes

alternative medicines , setting the stagefor potentially serious drug interactions . Little is known to date about herb -drug, herb -herb , and nutrient -drug interactions . Consumers should discuss thesemedications and combinations with theirdoctors . (Psychosomatic Medicine , September 1999 )

Changes Proposed forRegulating Disposable DevicesFacilities that reprocess medical de

vices intended for single use would beregulated the same way as th

e originalequipment manufacturer , under a strategy FDA recently proposed .

Reprocessing and reuse of

these disposable devices — catheters , for example — have grown in recent years ,

heightening concern about patient safety ,

informed consent , and ethics of

the

practice .

FDA ' s proposal covers :

• registration and listing of reprocessing

firms

• premarket notification and approval

requirements for

certain devices

• submission of

adverse event reports

• development of

performance stan

dards

• labeling requirements

• research needs .

The agency also proposes categorizing

the reprocessed devices as“ low , ” “mod -

erate , ” or“ high ” risk based on potential

hazards to patients .Devices posing themost significant public health risks afterreprocessing would b

e

classified as high

risk and be required to comply with all

relevant regulatory requirements , such as

applying for

premarket approval .

Reprocessors of

moderate - risk devices

would have to assure FDA that the devices are a

s

safe and effective as

the

original product . Low -risk devices ,

which pose little or no public health risk ,

would be a low agency priority andwould be exempt from any premarket

submission requirements .

FDA also may require original equipment makers to label their single -use

products to alert users and reprocessors

to the potential risks associated with re

processing the devices .

Full details of

the

proposed policy are

available at

www .fda .gov /ohrms /dockets /

98fr /110399i .txt .

A shocking success . . . A device that delivers lifesaving shocks to victims of

car

diac arrest is the latest trend in airport safety , says the Airports Council International , a trade group . The effort is part of the Chicago HeartSave program that provides publicly accessible defibrillators within one minute o

f

any location in the

O 'Hare and Midway airport terminal buildings . Emergency defibrillators installed

in one airport saved four lives in less than five weeks . Now other airports are considering equipping their facilities with the easy - to -use devices . The latest

defibrillators automatically detect erratic heartbeats and decide when a shock is

needed , proving beneficial even in the hands of

people with little training .

Serious Product Problem ? Report It

Health professionals can report serious adverse reactions or

other prod

uct problems to FDA ’ sMedWatch program by:

• Mail : Use the postage -paid MedWatch form

• Phone : 1 -800 -FDA - 1088 ( 1 -800 -332 - 1088 )

• Fax: 1 - 800 -FDA -0178 ( 1 -800 -332 -0178 )

• Internet :www . fda.gov /medwatch /

Call the 800 number or

visit the Website for

forms or

for

further

assistance .

FDA encourages consumers to report through their doctors , but if they

prefer , theymay submit the

MedWatch form themselves .

6 / January -February 2000 / FDA Consumer

Free PublicationsTo order single copies of th

efollowing

publications , use the

contact information

listed after the title . To order 2 to 50

copies , write to FDA , HFI - 40 ,

Rockville ,MD 20857 .

Full -Length Feature Articles :

• New Vaccine Targets Lyme Disease

(FDA ) 99 -1304

Write to FDA (HFM - 40 ) , Rockville ,

MD 20852

• New Drug Label Spells ItOut Simply

(FDA ) 99 -3232

Write to FDA (HFD -210 ) , Rockville ,

MD 20857

Pet ChewsMay Cause Illness in People , Agency WarnsBased o

na number of re

ports of

human illnesses in

Canada . FDA recently warned

U . S . consumers about the po

tential risk from contact with

dog chew products made frompork o

r

beef .

According to FDA , dog

chew products , including pigears , beef jerky treats , smokedhooves , and p

igskins ,may

pose a risk of

bacterial infec

tion , such as Salmonella

infantis . In normally healthypeople , these infections cancause fl

u -like symptoms (nausea , vomiting , abdominal pain ,

and diarrhea , for

example ) , but

in those with weakened immune systems the infection can b

e

more serious — even life - threatening .

FDA is urging pet owners to wash their hands with hot water and soap after coming into contact with these pet chews . Elderly people , young children , and those withweakened immune systems should avoid contact with the treats altogether .

FDA is working with other U . S . and Canadian health officials and has issued an

import bulletin on products that have been directly linked to illnesses .Also , the

agency is examining the manufacturing processes for products containing pig ears to

determine how this product and similar ones can

be

made safely .

9

29

fda

2k

Preparingfor the

NewMillenniumani

Help For MenopauseCorrection

On page 11 of

the article “ FDA

& Y2K ” in the November -Decem

ber 1999 FDA Consumer , an incor

rectnumber was listed for the Food

Marketing Institute . The correctnumber is (202 ) 452 -8444 .• FDA & Y2K (FDA ) 00 -1307

Call 1 - 888 -INFO -FDA ( 1 -888 -463

6332 ) and select “ 1 ” for

the

FDA Y2K

Hotline

• Critical Controls for Juice Safety

( FDA ) 99-2324

Write to FDA (HFS -555 ) ,Washington ,

DC 20204

Easy Reader :

• Help for Menopause (FDA ) 99 - 1300

Write to FDA (HFD -210 ) ,Rockville ,

MD 20857

FDA Consumer / January - February 2000 / 7

GO

VAAZIITVI Tu IV.EXPERIMENTAL TREATMENTS

Unapproved ButNotAlways UnavailableLast Option Fo

r

The Desperately Ill

by Larry Thompson

The scalpel has failed . The IV tubing stands abandoned on

the side of

the room . Friends and nurses visit less often . The

doctors say the limits of

medical knowledge have been reached

and there is nothing left for

you to do but go

home and put“ The hope part ofit is that it

might work and keep them

alive a little longer . Even if it

is only twomonths , by

then

there mightbe a cure . It is a

wonderful survival instinct . ”

- Theresa Toigo , associate

your affairs in order .

This is a crushing moment . It ' s even more frightening than

the day the doctors announced that you had a serious and life

threatening disease , such as AIDS , cancer or Alzheimer ' s dis

ease . For many people , however , the limitations of

medical commissioner for the Office of Special

knowledge do not define the limits of human hope . As

long as Health Initiatives

life lingers ,many patients will fight on , refusing to give up

even when biology is against them . So , they set

out on a search

for

treatment options .

Andmany alternatives exist . In today ' smedical bazaar , options range from alternative and complementary

therapies like acupuncture and homeopathic and naturopathic medicine to nutritional supplements and macrobiotic

diets , home -brewed remedies ,and even outright frauds like laetrile . But greater promise resides in the drug devel

opment pipeline where tomorrow ' s therapeutics await proof that they work .Unlike alternative therapies , billions of

dollars and decades of

scientific study often have been invested in the research that leads to promising new thera

pies .Might there be , somewhere in that high -priced gauntlet , just the rightmolecule that cures a patient who is

running out of

time ?

FDA Consumer / January -February 2009 / 9

The answer is possibly ,but finding it

isn ' t easy . Short of randomly hearing

about a promising study through theme -

dia ,most people know relatively littleabout what drugs are in development .

Even if experimental drugs existed in a

database , “ it is hard to know which

drugs are truly promising , ” says DavidBanks o

f

the Food and Drug

Administration ' s Office of SpecialHealth Issues . But on average , about 80

percent of

the drugs in testing will ultimately b

e approved .

Getting your hands ona novelmedi

cine can be

even more difficult . Usually ,

policymakers to reconsider long -heldbeliefs .

Experimental treatments should be

available , The Washington Post quotedone activist at the time , “ so peoplewould b

e

able to choose for themselves ,

working with their doctors , whether they

want to risk taking a drug because of

the

tions .As a result , the agency has put in

place a number of

regulatory mecha -

nisms and worked with manufacturers to

ensure that seriously ill patients can getaccess to promising , but not fully evalu -

ated , products . At

the same time , FDAhas protected the critical scientific stud

ies thatmust be carried out so that pa

tients , physicians and the

agency can determine which drugs are truly safe and

effective , and how they can

best be used .

“We believe that the best means of

providing access to useful medical treat -

ments for all Americans is to continue to

shorten the

review times , ” Henney says ,

“ and to continue to work with the indus -

try to shorten development times fordrugs , biologics andmedical devices . ”

The Intervention ofAIDS

Before the 1980s , amore paternalistic

medical community argued that itwasthe government ' s jo

bto protect patients

from possible harm by

withholding experimental drugs until there is proof thatthey work and are safe .

AIDS helped alter that view .Not onlydid that lethal disease spread with terri -

fying speed ,but it struck a patient popu -lation capable o

fmounting a political re -sponse that grabbed the nation ' s

attention and galvanized public health

Critics accused FDA ofdenying dyingpatients access to possibly lifesavingdrugs . To drive home the point , in October 1988 ,more than 1 ,000 gay activistsstaged a protest outside FDA ' s

Rockville ,Md . , headquarters , trappingthe agency ' s staff inside .

“ FDA is the nexus between the gov

ernment , the private sector and the consumer , ” the spokeswoman for one o

f

the

protest organizers told the Post . “ That ' s

whywe ' re targeting [the agency ] . "

The protest had an effect . The agency ,

already focused on

the issue by

the ur

gency of AIDS ,accelerated its reexami

nation of

the way people with serious

and life -threatening diseases could gain

access to unproven remedies . Althoughthe treatment IND regulations were fi

nalized in 1987 , FDA put in place additional mechanisms to make experimental

drugs available to seriously ill patientsearlier in the drug development process .

new medicine , which is extremely limited to begin with , andmost o

f

what is

made will be used in clinical studies .

As if these hurdles are not enough ,

there is the long -held , but incorrect , pub -

lic perception that FDA erects regulatory

barriers that block patients from getting

investigationalnew drugs (INDs ) . Theseare drugs that pharmaceutical companies

have in clinical trials to demonstrate

their safety and effectiveness , butwhichhave yet to b

e approved by

FDA formarketing . For those with a serious ill -

ness , the agency rarely blocks access to

unproven medications . But FDA doesstrive to protect all patients , even thosewhomay be dying , from undue risks associated with investigational new drugs .

At

the same time , FDA believes that thebest way to benefit all patients is to

speed promising new therapies through

the

development and approval process

so safety , effectiveness and proper usecan be established .

“ FDA has worked diligently to balance two compelling , and sometimescompeting , factors , ” says FDA Commissioner Jane E . Henney , M . D . “On onehand , there is the need for the disciplined , systematic , scientifically controlled studies necessary to identify

treatments thatmay improve patient

health and that lead to the approval of

new drugs . At the same time , there is thedesire o

f seriously ill persons ,with no

effective options available , to have the

earliest access to unapproved products

that could be

the best therapy for them . ”

Over the last decade , FDA ' s institutional philosophy has evolved to be

more supportive of thoughtful risk -tak

ing

by

patients who have run

out of op

For many people , however , thelimitations ofmedical knowledge donot define the limits of

human hope .

10 / January -February 2000 / FDA Consumer

Finding Information About Investigational New Drugs

(laulTrukDalam

SPRE

While finding and getting into an appropriate clinical trial for your individual disease is something like a scavenger hunt , the Internet hasmade it

much easier to track down these studies.The following is a listing of major

Internet sites where you can search for a

clinical trial thatmay benefit you .• Information Program on ClinicalTrials , (www . lhncbc .nlm .nih .gov/ clin /)mandated by the FDA ModernizationAct of 1997 , is a joint FDA /National Institutes of Health resource .While initially containing only NIH studies , itwill eventually include all federally andprivately financed clinical studies .• CancerNet (cancernet .nci.nih .gov ) isrun by NIH 's National Cancer Institute(NCI). It provides information on clinical trials . Information is also availablethrough NCI's Cancer Information Service at 1-800 -4 -CANCER .• ACTIS (www .actis .org ), the AIDSClinical Trials Information Service , pro -vides a wide range of information oncurrent AIDS research , including drugtrials , vaccine trials , and other educational material. Sponsored by the U. S.Public Health Service , including FDA ,NIAID , Centers for Disease Control andPrevention ,and the National Library ofMedicine , ACTIS also can be reached at1- 800 - TRIALS - A .• Information regarding clinical trials

for

rare disease can be found at

rarediseases .info . nih. gov /ord /

research - ct .html , a database compiled by

NIH ' s Office of Rare Diseases .

• CenterWatch Clinical Trials Listing

Service (www .centerwatch .com ) is published o

n

the Internet by

Center Watch

Inc . , amultimedia publishing company

in Boston , Mass . It provides information

on

more than 5 ,000 active clinical trials

as well as other information .

When a clinical trial is not an option ,

FDA facilitates access to an investiga

tional new drug oran investigational

medical device through other programs .

For information on programs for , or ac

cess to , an unapproved investigationalnew drug , call FDA ' s Office of SpecialHealth Initiatives a

t

301 -827 -4460 . I

2 . T .

With the activism around AIDS andthe demands o

f

people with other seri -

ous illnesses for access to unproven

treatments , the medical community , in

cluding FDA , began to appreciate thatthe traditional risk /benefit models may

have been inappropriate for

people with

serious and life -threatening diseases .

Dying patients were willing to take big -

ger risks for even the slenderest hope of

benefit .

“ The hope part ofit is that itmight

work and keep them alive a littlelonger , ” says Theresa Toigo , associatecommissioner for the Office of Special

Health Issues . “ Even if it is only twomonths , b

y

then theremight be a cure . It

is a wonderful survival instinct . ”

Getting AccessFor patients in search ofa cutting edge

treatment , the possibilities have improved dramatically . First of all , thereare more clinical studies under way thanever before . FDA has on file more than

13 ,000 active drug and biologic studies .

These range from a few

dozen patients

to asmany as 50 ,000 participating in a

single investigational new drug trial .

More than 100 ,000 patients are enrolledeach year in National Institutes o

f

Health -sponsored studies conducted allover the United States .

Studies with investigational new drugs

can be

conducted by

the federal govern

ment ,primarily through the National In -

stitutes of

Health ; by

research universi -

ties , usually with federal funding ,though also through private foundations

or drug companies ; and by private , for

profit companies on behalf ofpharma

ceutical manufacturers .

Clinical trials are essential to the development and approval o

f

new drugs .

In these studies , a group of

human volunteers receiving the investigational

therapy are compared with another

group that receives either the standard

treatment ora placebo . Placebos , some

times called sugar pills , are any faketreatment that has n

o therapeutic benefit .

This allows the researchers to compare

the effect of

the treatment to no treat

ment in otherwise similar patients .

When the control group is given the

FDA Consumer / January -February 2000 / 11

Is The Risk Worth It ?

Nomatter how promising a clinicaltrial or investigational new drug seems,

there is no way to know about all therisksbefore the study begins .While thehope is that the study will produce acure , it's important to recognize thatrisks ca

n

prove significant . For example , in 1992 , tests for a promising

hepatitis B drug severely damaged the

liver in 10 patients . Some died andothers required liver transplants .

Because of

these inherent uncertain

ties the health -care professionals conducting the study must ensure that thepatient understands the risks as well as

the benefits beforehand and is willing to

proceed .

Here are some questions patients

might want to ask tomake sure they understand the consequences o

f entering a

study orusing an investigational new

drug :

1 .What are the potential benefitsfrom the treatment being studied ?

What have the animal or

other human studies shown about the effec

tiveness of the drug ?

2 .What are the potential dangers

from using this drug ? Again , what do

other animal and human studies show

about the side effects ?

3 . In what phase is this clinical trial ?

Clinical trials are generally performed

in three phases . A phase 1 trial is prima -

rily designed to assess the safety profile

in a small number of patients . Phase 2

tests the effectiveness ofthe

treatment

in a relatively small number of patients .

Many drugs never progress beyond

phase 2 because they are not

effective . In phase 3 , a largenumber o

f

patients receive the

drug to substantiate that the

effectiveness seen in phase 2

is real and to work out the details o

fits

use . Individual patients are most likely to benefit from drugs in the later

phases of development .

4 . Will there bea control

group ?For a clinical trial to produce

useful information , the group

of patients receiving the new

treatment needs to be com

pared with patients who receive something — o

rnoth

ing - else . Often , patients inthe control group receive

whatever is the current stan

dard therapy for the disease . Sometimes ,

the control group patients will receive aplacebo - so -called sugar pills that pro

duce no therapeutic benefit . In a clinicalstudy , patients are randomly assigned to

either the group treated with the experi

mental drug orto a group receiving the

standard therapy or placebo .

5 .How do I know if I am eligible to be

in the study ?

Every trial has a set of

criteria to select

the people thatwill be included in thestudy . These criteria generally relate to

general health , stage of disease , andprior treatments and are designed to produce useful scientific information .

6 .Do I have to pay to be in a clinicalstudy ?

Generally , studies funded by

the federal

government are free for the patient .

Many studies funded by drug companiesalso d

o not cost anything . Some costs ,

however ,may be paid bya patient ' s

health insurance ormanaged -care plan .

7 . So I ' m just a guinea pig , right ?

By the timemost studies reach the stage

where the new drug is being tested in

people , a great deal is known about how

it affects the body .While there is always

the chance that something could go

wrong , the safety ofmost drugs beingstudied is well understood . It is true ,

however , that researchers do notknow if

a treatment being studied works better

than current therapies or not . I

7 . 1 .

standard treatment , researchers are able

to determine whether the

experimental

treatment provides a better outcome than

what is already available .

The clinical trial setting helps ensurethat risks are minimized because the research protocol , the set o

f

rules by

which the clinical trial is conducted ,

have been scrutinized by

FDA and a lo

cal ethics committee called an institu

tional review board .

“Wewant to encourage people to participate in the clinical trial process be

cause that is where information is best

developed about the drug product , ” saysDavid Lepay , M . D . , director of the division o

f

scientific investigation in FDA ' s

Center for Drug Evaluation and Research .

The downside of

being in a clinicaltrial , indeed the downside o

f

using any

unproved medication , is that the newdrug may not work . Itmay even be dangerous and , sometimes , deadly .

Not everyone who wants to participate

in a clinical trial can do

so . Limits on the

number of participants and specific eli

gibility criteria keep some people out . In

addition , it is often inconvenient for thepatient to travel to the research center .

When individuals are unable to participate in a clinical study , FDA provides

alternative mechanisms for patients andtheir doctors to get their hands o

na

promising new drug .

Beyond Clinical Trials

in 1987 , FDA created a regulatorymechanism (first proposed in 1982 ) to

12 / January -February 2000 / FDA Consumersumer

What FDADoes Not Do

..

permit expanded access to investiga company must be willing to provide thetional drugs outside of controlled clini new drug to the patient . This can be excal trials . The “ treatment IND” allows pensive and time consuming for thepeople with serious and life -threatening company since , in addition to providingillnesses to take investigational drugs the drug , the company needs to track

while the products are being tested in a shipments of the drug , create special inclinical trial . Typically , however , drugs structions for it

s

use , and create a way of

allowed under treatment INDs already collecting safety data and a mechanismhave shown promise and proven safety . fo

r

tracking outcomes for each patient .

In addition to thebenefit to individual Second , the patient must give informedpatients , treatment INDs generate useful consent , understanding that the drug is

information about how the drug affects not approved and may cause side effects

larger segments of

the patient population from mild to fatal . Third , the patient ' s

thanmight otherwise receive it in a physician must be willing to take re

clinical study . sponsibility for treating the patient and

For example , the AIDS drug Videx agree to collect information about the ef

(ddI )wasmade available to people with fects of

the drug .

AIDS outside the clinical trial at a time Companies sometimes say that they

when the choices for AIDS therapy were cannot make the drug available to a pa

few and many people had already ex tient because FDA won ' t allow it , buthausted the then available options .Al that is rarely true . FDA only denies acthough patients seeking treatment with cess when there is evidence that the risk

ddl were told that it was still under study of

using the experimental drug clearly

and that there were risks ,more than outweighs any potential benefit to the

20 ,000 decided to take ddl anyway . This patient .

not only gave them a better chance to If a drug is frequently used in single

survive but also gave researchers more patient INDs , FDA streamlines the proinformation about the drug ' s safety than cess for obtaining permission . One exwould have been possible from the some ample is thalidomide , a drug initially

4 ,000 patients involved in the clinical associated with birth defects in the

studies . 1950sbut now being used experimen

Since the final treatment IND rule was tally to treat cancer . (FDA approved thapublished more than a decade ago , FDA lidomide in 1998 to treat leprosy . )

hasmademore than 40 drug or biologic FDA has similar rules that give painvestigational products available to p

a- tients access to investigational new

tients early and has approved 36 .Of medical devices .

these , nearly a dozen were for cancerand another dozen for AIDS or AIDS A Difficult Decisionrelated conditions . All things being equal , is itworth it

for a patient to get access to an experi

Single -Patient INDs mentalmedication ?

As with a clinical trial , theremay not For society the

additional safety infor

be

an appropriate treatment IND for

an mation about the new drug may prove

individual patient ' s condition , but there useful . And sometimes it does make a

may bea new drug still working its way difference for individual patients . For

through development . If enough is example , people with AIDS who partici

known about the drug ' s safety , and there pated in the clinical trials for a category

is some clinical evidence of

effective of drugs called protease inhibitors prob

ness , FDA may allow a patient to be ably benefited because this class of

come his or

her own study . This so drugs proved so dramatically effective .

called single -patient IND , or But formany other INDs , the successcompassionate use IND , virtually en rates aremuch less impressive , such a

s

sures that any patient can get access to tacrine (Cognex ) for the treatment of

any investigational new drug . Alzheimer ' s disease .

Although FDA ' s requirements fora Even if access does not change long

single -patient IND are relatively simple , term survival , it may provide for the pasetting up

this kind of

access for an indi - tient and the family a sense that they are

vidual patient is not . First of all, the doing something and are not simply vic -

Although FDA is responsible for overseeing th

e

field of

drug development ,

there are a number of

services the

agency cannot provide to individual pa

tients . For one thing , it cannot give out

the

name of

drugs in development , a

common request from patients who callthe agency . Unless the company publicly

releases information about the experi

mental treatment , FDA is currently

forbidden to even acknowledge that it

knows about the drug .

Along the same lines , FDA cannotmake the drug available to individual pa

tients or physicians . The agency simply

does not have the product ; only the company that is developing the drug has a

supply . And FDA has no authority to re

quire that the company make its drug

available outside of

the clinical trial .

FDA , itself , does not conduct anyclinical trials or drug studies . Theagency carries out its drug review andapproval responsibilities b

y

examining

clinical and other data generated by

thedrug company .

And lastly , FDA does not give advice .

While staff from the Office of Special

Health Issues and the Center for Drug

Evaluation and Research ' s drug information branch will often provide detailedinformation and explain the process forgetting access to a

n experimental medication , the agency does not steer patients

in one direction or

the other . Information

is provided so patients , in consultationwith their physicians , can make theirown informed decisions . I

L . T .

tims of

some serious disease . Biomedical research advances rapidly and breakthroughs come from unexpected places ,

all feeding the hope that the next experi

mental drug will be the one that curesour ills .

Larry Thompson is a member of

FDA ' s

public affairs staff .

FDA Consumer / January -February 2000 / 13

TheHealing PowerOf25

si22

SAS

PLACEBOSby Tamar Nordenberg One patient stands out in th

e

memory of

Stephen Straus , M . D . , for

her remarkable

recovery ,more than 10 years ago , from chronic fatigue syndrome . The woman , then

in her 30s ,was “ very significantly impaired , ” says Straus , chief of the Laboratory of

Clinical Investigation at

the National Institute of

Allergy and Infectious Diseases .

“ She had no energy , couldn ' t work , and spent most ofher time at home . ” But her

strength was restored during a study to test the

effectiveness ofan experimental

chronic fatigue drug .

“ She and her parents were so thrilled with her recovery that they were blessing me

andmy colleagues , ” recalls Straus , the principal investigator on

that study .

14 / January -February 2000 / FDA Consumer

Today ' s brain imagery techniques lend supportto the theory that thoughts and beliefs not only

affect one's psychological state , but also cause the

body to undergo actual biological changes .body

Like many drug studies , the chronicfatigue medication trial was a “placebo

controlled ” study ,meaning that a portion

of

the patients took the experimental

drug ,while others took look -alike pillswith n

o

active ingredient ,with neitherresearchers nor patients knowing whichpatients were getting which .

It ' s human nature , Straus explains , forpatients and investigators alike to tr

y

and guess in each case : Is it the realdrug or a dummy pill ? But people

shouldn ' t kid themselves , he says , thatthey can consistently tell the actual drug

from the sham by

seeking out tell -talesigns o

f

improvement .

Turns out , the woman ' s quick turnaround from chronic fatigue occurred a

f -

ter taking placebo pills , not the experi -

mental drug . Straus says , “ She wasamazed b

y

the revelation that she ' d gotten better on placebo . ”

Research has confirmed that a fake

treatment ,made from an

inactive sub

stance like sugar , distilled water , or sa

line solution , can have a “ placebo ef -

fect ” — that is , the

sham medication can

sometimes improve a patient ' s conditionsimply because the person has the expectation that itwill be helpful . For a

givenmedical condition , it ' s not unusualfor one -third of patients to feel better in

response to treatment with placebo .

“ Expectation is a powerful thing , ”

says Robert DeLap , M . D . , head of

one

of

the Food and Drug Administration ' s

Offices of Drug Evaluation . “ The moreyou believe you ' re going to benefit from

a treatment , themore likely it is that you

will experience a benefit . ”

To separate out this power of

positive

thinking and someother variables from

a drug ' s truemedical benefits , companies seeking FDA approval of a newtreatment often use placebo -controlleddrug studies . If patients o

n the new drug

fare significantly better than those takingplacebo , th

e

study helps support the con -

clusion that themedicine is effective .

searcher H . K . Beecher published hisgroundbreaking paper “ The PowerfulPlacebo , ” in which he concluded that ,

across the 26 studies he analyzed , an av

erage of32 percent of patients re

sponded to placebo . In the 1960s , break -

through studies showed the potential

physiological effects of dummy pills

they tended to speed up

pulse rate , in

crease blood pressure , and improve reaction speeds , for example , whenparticipants were told they had taken a

stimulant , and had the opposite physiological effects when participants weretold they had taken a sleep -producingdrug .

Yet , even after 40 years , big questionsremain about the interplay o

f psychological and physiological mechanismsthat contribute to the placebo effect .

Today ' s brain imagery techniques do

lend support , though , to the theory thatthoughts and beliefs not only affectone ' s psychological state , but also causethe body to undergo actual biological

changes .

the phenomenon needn ' t baffle us ,

saysMichael Jospe , a professor at

the

California School of Professional Psy

chology who has studied the placebo ef

fect for more than 20 years . He points

out that all people experience physi

ological reactions to anticipation and

stress — something like the fight - or- flightresponse — that help them to survive and

cope .When you step out of your officeand a spider jumps out a

t you , Jospeanalogizes , “ you ' ll get a frightand have

a physiological reaction . And the nexttime you g

o

out that way , the thoughtthat it could happen again can produce a

physiological reaction before you evenopen the door . ” So , he says , the relation -

ship between a thought and a negative

psychophysiological reaction like fear is

something we experience daily .

That goes for

positive associations ,

too , Jospe continues . “ The placebo ef

fect is part of

the human potential to re

act positively to a healer . You can

reduce

a patient ' s distress by

doing something

which might not bemedically effective . ”

It ' s like kids and Band -Aids , Jospe says .

“When you put a Band -Aid ona child and

it has stars or comics on it , it can actually

make the kid feel better by

its soothing ef

fect , though there ' s nomedical reason it

shouldmake the child feel better . ”

There is no medical reason , either ,

that look -alike placebo tablets used in a

1997 study of benign enlargement of

the

prostate gland should havemade thestudy participants feel better .But in thisCanadian study ,more than half o

f

the

men who got the placebo pills reportedsignificant relief from their symptoms ,

including faster urine flow . Researcher

J . Curtis Nickel theorized that the patients ' positive expectations of the experimental drug ' s benefits may havecaused therapeutic smooth muscle relaxation b

ydecreasing nerve activity affect

ing the bladder , prostate and urethra .

Study participants on placebo com

plained of

side effects , too ( sometimescalled the “nocebo ” effect ) , ranging fromimpotence and reduced sex drive to nausea , diarrhea and constipation .

It ' s this powerful placebo effect ,coupled with the fact that many medicalconditions involve a natural course ofbetter and worse periods (arthritis andmultiple sclerosis are examples o

f

diseaseswith flair - ups and lulls ) , that canmake it difficult to know if a health upswing should b

e

credited to a drug ef

fect .One way to account for such variables in a drug study : give one group o

f

patients placebo and another the experi

mental drug , and see if the drug group ' s

health improvements sufficiently surpass those from placebo . In Straus '

study , the chronic fatigue syndromedrug failed to adequately demonstrate it

s

superiority over dummy pills .

(Continued on page 17)

Benefiting from Belief

Researchers have been studying theplacebo effect for decades . In 1955 , re -

FDA Consumer / January -February 2000 / 15

Placebos In The Doctor'sOfficeOpposing Views

Today ,when 26 -year -old Jennifer Kennedy (not her real

name ) from Rockville ,Md.,has a panic attack , she simply

distracts herself with a book or crossword puzzle . But attheir height, several years ago , the attacks scared her somuch that she finally went to the emergency room . “ Ithought Iwas going to die from a heart attack ,” saysKennedy

She didn 't believe her doctor when he told her to “ justrelax ” and she would feel okay ,and he ended up prescribing pills. He didn 't tell her until two weeks later ,after herpanic attacks had subsided , that the pills were simply

placebos with no active medical ingredient .

Those who oppose the

use of

placebo pills in medical

practice say that such deceit can undermine the essential

trust between patient and doctor . Gastroenterologist

Michael Kirsch , M . D . ,has called doctors who prescribeplacebos outside medical research “ con artists . ” Kirschasks in a 1998 editorial in Priorities , th

e

magazine of

the

nonprofit American Council on Science and Health , “ If

using placebos therapeutically is ethical and reasonable ,

shouldn ' t we encourage judges to render extralegal activistrulings ,winegrowers to bottle ‘placebo ’ vintages , curators

to display masterpiece lookalikes mislead

ingly ,andjournalists and

newscasters to

sanitize news ? ”

He continues ,

“ In such a

world , all ofus

would be grop

ing for truth in

a hall of

mir

rors . "

But placebo

researcher

Michael Jospe

disagrees with

what he

calls

this “ strict , grumpy approach that concludes that any doc

tor

who uses placebos is acting unethically . ” Some circum

stances , he says , justify this kind ofbenevolent decep

tion — like when a patient insists on amedicine that is

unnecessary and carries needless risks .

“ You ' ve got to be there on

the oncology ward , ” Jospesays , “ and see how suffering people get so demanding of

drugs thatmight be extremely harmful to them . If you look

at sugar pills in the broader context ofa supportive doctor

patient relationship rather than just as ripping off the pa

tient , you may come to a different conclusion ” about theethics o

f placebos .

It ' s not uncommon fora patient to feel betrayed initially

upon hearing that they were given a placebo , Jospe says ,

but a sensitive doctor can

explain to the

patient , “No , thatthe placebo worked doesn ' tmean you ' re crazy . You werejust in distress and thus more prone to reacting to anything

with the

potential to help . ”

Kennedy admits to feeling deceived when she first

found out

the

pills her

doctor prescribed were fake ,butsays she now appreciates th

edoctor ' s decision to prescribe

the placebo . “ At

first , I felt stupid . But that day at the

hos

pital , the doctormust have real

ized Iwasn ' t going to accept

‘you ' re fine , it ' s

allin yourmind .

The placebo

helped me realize

that I ' m not unhealthy and I ' m

going to be okay .

Now , I think it ' s

really neat that

something that

didn ' t really af

fectme had such

a big effect on

my life . ”

_TN .

16 / January -February 2000 / FDA Consumer

It's not unusual for

one - third of patients controlplacebo controlcan provide the

to feel better in

clearest insight intoresponse to

treatmentwithplacebo .

what a treatment can

accomplish .

(Continued from page 15)

Proof in the Placebo

FDA doesn 't require that a drug studyinclude a placebo control group , DeLapsays , only that its design be capable of

establishing a drug ' s safety and effectiveness . Non -placebo types of drugstudies include “ head - to -head ” studies ,

which compare the experimental drug to

an existing treatment , and historically

controlled studies , which compare the

new drug ' s effects with informationgathered in the past about the expected

progression ofamedical condition .

Often , however , a placebo control canprovide the clearest insight into what a

treatment can accomplish ,according to

DeLap , especially with somepsychiatricand other drugs in which the placebo

effect is known to play a particularlyweighty role . In fact , DeLap says , in

some cases the placebo effect “makes it

almost hopeless , statistically ” to usestudies that test a new treatment side - b

y-

side against an existing one and determine whether the new treatment works .

The placebo controls that have traditionally been used to testmedications

have recently been used , too , to test the

effectiveness of surgical procedures . In

one well -publicized study sponsored bythe National Institutes of Health , half o

f

the Parkinson ' s disease patients enrolled

in the trial underwent a sham surgery in

which doctors drilled holes into their

skulls but didn ' t implant the

potentially

beneficial human fetal tissue in theirbrains .

While FDA doesn ' t evaluate the safety

or

effectiveness of

most surgical techniques , th

e

agency does regulate surgicalimplantation o

f

animal cells orre -engi

neered human tissues . The agency hasapproved a

t

least one sham surgery -controlled trial ,which will study the effectiveness o

f

implanted pig fetal cells for

Parkinson ' s .

Even with the powerful scientific advantages o

f including a placebo control ,

researchers and FDAmust look at eachtreatment individually to decide if theuse o

f

placebos is appropriate and ethical . In fact ,much medical research doesnot involve a placebo control because

“ it ' s just not an option , ethically , ” DeLapsays .

To determine whether a placebo -con

trolled trial is acceptable , drug companyand FDA experts ask : For what condition is this drug being tested ? What is

the natural progression of

the disease ?

How serious is the risk if a patient gets a

placebo rather than an active treatment ?

In DeLap ' s specialty , oncology , pla-

cebo -controlled studies are often unac -ceptable because o

f

the great risk to

cancer patients of

any treatment delays . For a headache , on the other

hand , patients in a study may be un

comfortable for a time , but are not at

risk ofa lasting health impact . So , for

those conditions in which the down

side ofbeing on placebo ismodest and

short -lived , DeLap says , it ' s an

individual ' s prerogative to say , “ I

know what I ' m getting into , and I want

to further this scientific research . ”

To help ensure that patients know

the pros and cons of enrolling in a

study , each participant must sign an

“ informed consent ” form , whichclearly explains :

• the purpose of

the study

• what enrollees will be asked to do

( take a pill twice a day for threemonths , for example , and visit the doctor once a week for blood and otherlaboratory tests )

the possible benefits and known adverse reactions associated with the experimental treatment

• other therapies that are available fortheir condition .

Even willing participants can ’ t sign

away their right to a well -designed

study , though ,DeLap points out . “Wecan ' t fall into the trap of thinking that ,

once someone says “ I ' m willing to participate , ' their consent covers u

s for deficiencies .Our responsibilities g

o way

beyond getting informed consent . ” Onesuch responsibility : As a studyprogresses , researchers monitor results

so ifmajor positive or negative drug ef

fects are seen , the study can be

stopped . The firstmajor clinical studyof

the AIDS drug AZT (zidovudine ) ,

for example , was halted early when re

searchers saw

that AZT patients wereliving significantly longer than others

in the

study .

Still , some critics say today ' s safeguards are not sufficient and oppose the

use of placebo - controlled studies in al

most all

drug research . Patients desperately seeking to end their suffering ,

some say ,may not be capable of givingtrue informed consent .

DeLap and other FDA experts viewany far -reaching ban o

n placebos in research a

s paternalistic . “We at FDAdon ' t have an ethical blind spot , as

some would suggest , ” DeLap says . “ A

patient ' s right to the best treatment is

always paramount . But the social hope

is that careful scientific research can

help us

learn beyond a shadow ofa

doubt what works and what doesn ' t , so

that these patients 'kids will have bettertreatments available to them . ”

Tamar Nordenberg is a staffwriter for

FDA Consumer .

FDA Consumer / January -February 2000 / 17

Are Bioengineered

FoodsSafe ?

by

Larry Thompson

18 / January -February 2000 / FDA Consumer

ince 1994 , a growing number of foods developed using protein toxic to certain caterpillars , eliminating the need for

the tools of the science of biotechnology have come onto both certain conventional pesticides .

the domestic and internationalmarkets .With these products has In 1992, the Food and Drug Administration published a

come controversy , primarily in Europe where some question policy explaining how existing legal requirements for food

whether these foods are as safe as foods that have been developed safety apply to products developed using the tools of biotech

using the

more conventional approach of hybridization . nology . It is the agency ' s responsibility to ensure the

safety of

Ever since the latter part of

the 19th century ,when Gregor all

foods on the

market that come from crops , including

Mendel discovered that characteristics in pea plants could be bioengineered plants , through a science -based decision -making

inherited , scientists have been improving plants by

changing process . This process often includes public comment from con

their genetic makeup . Typically , this was done through hybrid - sumers , outside experts and industry . FDA established , in 1994 ,

ization in which two related plants were cross -fertilized and the a consultation process that helps ensure that foods developed

resulting offspring had characteristics of

both parent plants . using biotechnology methodsmeet the applicable safety stan

Breeders then selected and reproduced the offspring that had dards . Over the last five years , companies have used the con

the

desired traits . sultation process more than 40 times as they moved to intro

Today , to change a plant ' s traits , scientists are able to use the

duce genetically altered plants into the U . S .market .

tools of

modern biotechnology to insert a single gene — or , Although the agency has no evidence that the policy and

often ,two or three genes - into the crop to give it new , advanta - procedure do not adequately protect the public health , there

geous characteristics .Most geneticmodifications make it easier have been concerns voiced regarding FDA ' s policy on

these

to grow the crop .About half of the American soybean crop foods . To understand the agency ' s role in ensuring the safety of

planted in 1999 , for

example ,carries a gene that makes it resis - these products , FDA Consumer sat

downwith Commissioner

tant to an herbicide used to controlweeds . About a quarter of Jane E .Henney , M . D . , to discuss the

issues raised by

U . S . corn planted in 1999 contains a gene that produces a bioengineered foods :

FDA Consumer : Dr . Henney , whatdoes itmean to say that a food crop is

bioengineered ?

Dr.Henney :Whenmost people talk

about bioengineered foods , they are re

ferring to crops produced by

utilizing

themodern techniques of

biotechnology .

But really , if you think about it , all

crops

have been genetically modified through

traditional plant breeding for

more than

a hundred years .

Since Mendel ,plant breeders havemodified the genetic material o

f crops

by

selecting plants that arise through

natural or , sometimes , induced changes .

Gardeners and farmers and , at times , in -

dustrial plant breeders have crossbred does what all genes do : It directs theplants with the intention of

creating a production ofa specific protein thatprettier flower , a hardier ormore pro makes the plant uniquely different .

ductive crop . These conventional tech - This technology provides much moreniques are often imprecise because they control over , and precision to , whatshuffle thousands o

f genes in the off characteristic breeders give to a new

spring , causing them to have some of

the plant . It also allows the changes to be

characteristics of

each parent plant .Gar - made much faster than ever before .

deners or

breeders then look for the No matter how a new crop is creplants with th

e

most desirable new trait . ated - using traditionalmethods or bioWith the tools developed from bio technology tools — breeders must contechnology , a gene can be inserted into a duct field testing fo

r

several seasons to

plant to give it a specific new character - make sure only desirable changes have

istic instead ofmixing allof

the genes been made . Theymust check to makefrom two plants and seeing what comes sure the plant looks right , grows right ,

out . Once in the plant , the new gene and produces food that tastes right . They

FDA Consumer / January -February 2000 / 19

also must perform analytical

tests to see whether the levels ofnutrients have changed and

whether the food is still safe toeat .

As we have evaluated the results of the seeds or crops created using biotechnology techniques ,we have seen noevidence that the bioengineered

foods now on themarket pose

any human health concerns or

that they are in any way less safethan crops produced through traditional breeding .FDA Consumer : What kindsof genes do plant breeders try to

put in crop plants ?

Dr.Henney : Plant researcherslook for genes that will benefitthe farmer , the food processor , orthe consumer . So far ,most of thechanges have helped the farmer .For example , scientists have inserted into corn a gene from the

bacterium Bacillus thurigiensis , FDA CommissionerJane E. Henney, M.D.

usually referred to as BT. Thegene makes a protein lethal to certaincaterpillars that destroy corn plants . This We have seen no evidenceform of insect control has two advantages : It reduces the need for chemical thipesticides , and the BT protein ,which ispresent in the plant in very low concen - n

trations , has no effect on humans .Another common strategy is inserting any human healtha gene thatmakes the plant resistant to aparticular herbicide. T

he

herbicide nor - concerns or

that they are in

mally poisons an enzyme essential for

plant survival . Other forms of

this normal plant enzyme have been identifiedthat are unaffected b

y

the herbicide . Putting the gene for this resistant form o

f

the enzyme into the plant protects it traditraditional breeding .

from the herbicide . That allows farmers

to treat a field with the herbicide to killthe weeds without harming the crop . working diligently to develop crops with

The new form of

the enzymeposes no enhanced nutritional properties .

food safety issues because it is virtually FDA Consumer : Do

the new genes ,

identical to nontoxic enzymes naturally or

the proteins they make , have any ef

present in the plant . In addition , the re fect on the people eating them ?

sistant enzyme is present at very low Dr.Henney : No , it doesn ' t appear so .

levels and it is as easily digested as the All of the proteins that have been placed

normal plant enzyme . into foods through the tools of

biotech -

Modifications have also been made to nology that are on themarket are non -

canola and soybean plants to produce toxic , rapidly digestible , and do

not have

oils with a different fatty acid composi the characteristics of proteins known

tion so they can be

used in new food to cause allergies .

processing systems . Researchers are As for the genes , the chemicalthat en -

codes genetic information is

called DNA . DNA is present in

all foods and its ingestion is not

associated with human illness .

Some have noted that sticking a

new piece ofDNA into the

plant ' s chromosome can disruptthe function o

f

other genes , crippling the plant ’ s growth or altering the level o

f

nutrients or

tox

ins . These kinds of

effects can

happen with any type of plant

breeding — traditional or

biotech .

That ' swhy breeders do extensive field -testing . If the plant

looks normal and grows normally , if the food tastes rightand has the expected levels o

f

nutrients and toxins , and if the

new protein put into food hasbeen shown to b

e

safe , then theycan be presumed to b

e

as

safe as

conventional foods .

FDA Consumer : You mentioned allergies . Certain pro

teins can cause allergies , andthe genes being put in these

plants may carry the code for new pro

teins not normally consumed in the diet .

Can these foods cause allergic reactions

because of

the genetic modifications ?

Dr.Henney : I understand why people

are concerned about food allergies . If

one is allergic to a food , it needs to be

rigorously avoided . Further , we don ' t

want to create new allergy problems

with food developed from either tradi

tional or biotech means . It is important

to know that bioengineering does not

make a food inherently different fromconventionally produced food . And thetechnology doesn ' tmake the food morelikely to cause allergies .

Fortunately , we know a lotaboutwhich foods trigger allergic reactions .

About 90 percent of

all

food allergies in

the United States are caused by

cow ' s

milk , eggs , fish and shellfish , tree nuts ,

wheat , and legumes , especially peanutsand soybeans .

To be

cautious , FDA has specifically

focused on allergy issues . Under the law

and FDA ' s biotech food policy , companies must tell consumers o

n the food label when a product includes a gene from

one of

the common allergy -causingfoods unless it can show that the proteinproduced b

y

the added gene does not

eed

for

chemical that the

bioengineered foods because of th

now on

the

market pose are concerned abou

anyway less

safe than crops to know

that

20 / January - February 2000 / FDA Consumer PHOTOGRAPHS BY

RHODA BAER

make the

food cause allergies .

We recommend that companies

analyze the proteins they intro

duce to see if these proteins pos

sess properties indicating that theproteins might b

e allergens . So

far , none of the new proteins in

foods evaluated through the FDAconsultation process have caused

allergies . Because proteins resulting from biotechnology and now

on

the market are sensitive to

heat , acid and enzymatic diges

tion , are present in very low levels in the food , and do not havestructural similarities to knownallergens ,we have no scientificevidence to indicate that any o

f

the new proteins introduced into

food by

biotechnology will causeallergies .

FDA Consumer : Letme askyou onemore scientific question .

I understand that it is commonfor scientists to use antibiotic resistance marker genes in the pro

cess of bioengineering .Are you

concerned that their use in food crops

will lead to an increase in antibiotic resistance in germs that infect people ?

Dr . Henney : Antibiotic resistance is a

serious public health issue , but thatproblem is currently and primarily

caused by

the

overuse ormisuse ofanti

biotics .We have carefully consideredwhether the use o

f

antibiotic resistance

marker genes in crops could pose a pub

lic health concern and have found no

evidence that it does .

I ' m confident of this for several reasons . First , there is little if any transfer

of

genes from plants to bacteria . Bacte

ria pick up

resistance genes from other

bacteria , and they doit easily and often .

The potential risk of

transfer from plants

to bacteria is substantially less than the

risk of

normal transfer between bacteria .

Nevertheless , to be on the safe side , FDA

has advised food developers to avoid using

marker genes that encode resistance to

clinically important antibiotics .

FDA Consumer : You ' vementionedFDA ' s consultative process a couple of

times . Could you explain how genetically engineered foods are regulated in

the United States ?

Dr . Henney : Bioengineered foods actually are regulated by

three federal

nle ? If a bioengineered food is

significantly different from

its conventional

counterpart — if the

nutritional value changes

orit causes allergies — it

must be

labeled to indicate

thatdifference .

Letme talk about FDA ' s role .

Under the federal Food , Drug ,

and Cosmetic Act , companieshave a legal obligation to ensure

that any food they sell meets the

safety standards of

the

law . This

applies equally to conventionalfood and bioengineered food . If

a food does notmeet the safety

standard , FDA has the authority

to take it off the market .

In the specific case of

foodsdeveloped utilizing the tools o

f

biotechnology , FDA set

upa

consultation process to help

companies meet the require

ments .While consultation is

voluntary , the legal requirements that the foods have to

meet are not . To the best of

ourknowledge , all bioengineered

foods on the market have gonethrough FDA ’ s process beforethey have been marketed .

Here ' s how itworks . Companies send us

documents summarizing the information and data

they have generated to demonstrate that

a bioengineered food is as safe as the

conventional food . The documents describe the genes they use :whether theyare from a commonly allergenic plant ,

the characteristics of

the proteins made

by

the

genes , their biological function ,

and how much of

them will be found in

the food . They tell uswhether the newfood contains the expected levels o

f

nutrients or

toxins and any other information about the safety and use o

f

the

product .

FDA scientists review the informationand generally raise questions . It takesseveral months to complete the consultation , which is why companies usually

start a dialog with the agency scientistsnearly a year o

rmore before they submit

the data . At

the conclusion of

the consul

t ation , if we are satisfied with what we

have learned about the food ,we providethe company with a letter stating thatthey have completed the consultation

process and we have no further ques

tions at

that time .

FDA Consumer : Since genes are being added to the plant , why doesn ' tFDAreview biotech products under the same

food additive regulations that it reviews

(Continued on page 23 )

agencies : FDA , the Environmental Pro -

tection Agency , and the U . S . Department

ofAgriculture . FDA is responsible for

the

safety and labeling ofall

foods and

animal feeds derived from crops , includ -

ing biotech plants . EPA regulates pesti -

cides , so the BT used to keep caterpillarsfrom eating the corn would fall under its

jurisdiction .USDA ' s Animal and PlantHealth Inspection Service oversees theagricultural environmental safety o

f

planting and field testing genetically

engineered plants .

FDA Consumer / January -February 2000 / 21

Methods forGenetically Engineering a Plant

DNA encoding

desired trait

FDO001

Two very different techniques exist for

giving a plant new genetic characteristics .

But both share several steps .

Introduce DNA

into

agrobacterium

DNA coating

of microscopic

metal particles

If the metal

particlesmetal

Xchromosome typical

plasmid

gene

transferplasmid ONADNA

Bacterial

transfer of

DNAGene transfer Accelerate

particles into

plant cells

DODO

O OStep 1 : The DNA that encodes the

genetic information for

the desirable trait

must be isolated .

At

step 2 , the different techniques

diverge into an“ a ” path and a “ b ” path :

In Step 2a , the new DNA is linked to a

circular ring of genetic material called a

transfer plasmid . Plasmids act likemolecular taxicabs that carry genes from

one place to another . The plasmid can be

absorbed bya bacterium that transfers it

to plant cells .

At

Step 3a , the bacterium attaches to

the plant cells , liberating the plasmid

inside . The new DNA migrates to the

plant ' s chromosomewhere the gene for

the new trait is permanently integrated

(Step 4 ) .

At

Step 5 , themodified plant cells are

identified and placed into a cell culture to

multiply . As the cells reproduce , the newgene is reproduced along with them .

The bioengineered plant cells are then

grown in a special culture (Step 6 ) that

causes the cells to differentiate into theunique types o

f

cells that make up

the

plant .

Finally , Step 7 , the plantlets aretransferred from the laboratory culture to

soil where they grow like normal plants ,

except now they carry a gene that can

give them a new , beneficial trait .

nucleus plant cellwall

DNA insertion

JL

Cell division

Cells regenerate

into plantlets

Plantswith

new traits

The alternative pathway uses a

completely different gene -delivery

technique . In Step 2b , naked DNA

encoding the desired trait is painted on

microscopic metal particles .

In Step 3b , themicroscopic particles are

then loaded into a so -called “ gene gun"

and fired as

projectiles at plant cells

growing in the laboratory . Theminiature ,

gene -carryingbullets penetrate the plant

cells where the fluids inside wash the

DNA off themetal particles .

As

before , in Step 4 , the DNAmigratesinto the cell ' s nucleus ,where the geneticmaterial is permanently integrated into the

chromosomes . The rest of the sequence

is the same .

Transfer

to soil

Source : Monsanto

22 / January -February 2000 / FDA Consumer

(Continued from page 21)

food colors and preservatives ?

Dr. Henney : The food additive provision of the law ensures that a substance with an

unknown safety profile is notadded to food without the

manufacturer proving to the

government that the additive is

safe . This intense review ,however , is not required under thelaw when a substance is generally recognized a

s

safe (GRAS )

by qualified experts . A

substance ' s safety can

be estab

lished by

long history of

use in

food orwhen the nature of

the

substance and the information

generally available to scientists

about it is such that it doesn ' t

raise significant safety issues .

In the

case of bioengineered

foods , we are talking about add

ing

some DNA to the plant thatdirects the production o

fa spe

cific protein .DNA already is

present in all

foods and is pre

sumed to be GRAS . As I described before , adding a

n extra bit of

DNAdoes not raise any food safetyissues .

As

for

the resulting proteins , they too

are generally digested andmetabolized

and don ' t raise the kinds of food safetyquestions a

s

are raised by

novel chemicals in the diet . The proteins introducedinto plants so far either have been pesti -

cides or enzymes . The pesticide pro

teins , such as BT , would actually be

regulated by EPA and go through its ap

proval process before going on

themar -

ket . The enzymes have been considered

to be GRAS , so they have not gone

through the food additive petition pro

cess . FDA ' s consultation process aidscompanies in determining whether the

protein they want to add to a food is

generally recognized as

safe . If FDA hasconcerns about the safety o

f

the food ,

the productwould have to go through

the full food additive premarket approvalprocess .

FDA Consumer : Why doesn ' t FDArequire companies to tell consumers o

n

the label that a food is bioengineered ?

Dr . Henney : Traditional andbioengineered foods are all subject to

the same labeling requirements . All

ference from conventional soy

and canola oils . If a food had a

new allergy -causing protein introduced into it , the label wouldhave to state that it contained the

allergen .

We are not aware of any infor

mation that foods developed

through genetic engineering differ as a class in quality , safety , or

any other attribute from foods developed through conventional

means . That ' s why there has been

no requirement to add a special

label saying that they are

bioengineered . Companies arefree to include in the labeling o

fa

bioengineered product any state

ment as long as the

labeling is

truthful and notmisleading .

Obviously , a label that implies

that a food is better than another

because itwas , or

was not ,

bioengineered , would bemisleading .

FDA Consumer : Overall , areyou satisfied thatFDA ' s current

system for regulating bioengineered

foods is protecting the public health ?

Dr . Henney : Yes , I am convinced thatthe health o

f

the American public is wellprotected by the current laws and proce

dures . I also recognize that this is a rapidly changing field , so FDAmust stay o

n

top of

the science as biotechnology

evolves and is used to make new kinds

of

modifications to foods . In addition ,

the agency is seeking public input about

our policies and will continue to reachout to the public to help consumers understand the scientific issues and the

agency ' s policies .

Not only must the food that Americanseat b

e

safe , but consumers must have

confidence in its safety , and confidence

in the government ' s role in ensuring thatsafety . Policies that are grounded in science , that are developed through openand transparent processes , and that areimplemented rigorously and communi

cated effectively are what have assured

the consumers ' confidence in an agency

that has served this nation for

nearly 100

years . I

Bioengineered foods

actually are regulated by

three federal agencies , FDA ,

the

Environmental

Protection Agency , and

the

U . S . Department of

Protec

Agriculture .

labeling for a food product must be

truthful and notmisleading . If a

bioengineered food is significantly different from it

s conventional counterpart — if the nutritional value changes or

it causes allergies — itmust be labeled to

indicate that difference . For example ,

genetic modifications in varieties of

soy -

beans and canola changed the fatty acid

composition in the oils of

those plants .

Foods using those oils must be

labeled ,

including using a new standard name

that indicates the bioengineered oil ' s dif

Larry Thompson is a member ofFDA ' s

public affairs staff .

FDA Consumer / January - February 2000 / 23

Goth parehe

Lbuying drugs online

It's Convenientand Private ,but Beware of 'Rogue Sites'

by John Henkel

The scene is becoming increasingly common in the United States :

Consumers are replacing a trip to the corner drugstore with a click onto the

Internet , where they find hundreds of Websites selling prescription drugs and other

health products .

Many of these are lawful enterprises that genuinely offer convenience , privacy ,

and the safeguards of traditional procedures for prescribing drugs . For the most

part , consumers can use these services with the same confidence they have in their

One way consumers can

ensure the quality of an online

pharmacy is to look for

the

VIPPS seal , which is proof that

the

site

has passed the rigid

criteria of

the Verified Internet

Pharmacy Practice Sites

program . Because VIPPS

certification is fairly new and

voluntary , only a few sites

have been certified so far.

neighborhood druggist . In fact ,while some are familiar large drugstore chains ,many of

these legitimate businesses are local “mom and pop ” pharmacies ,set up toserve their customers electronically .

But consumers must bewary of

others who are using the Internet as an outlet

for products or practices that are already illegal in the offline world . These so

called “ rogue sites ” either sell unapproved products , or if they deal in approved

ones , they often sidestep established procedures meant to protect consumers . For

example , some sites require customers only to fill out a questionnaire before

ILLUSTRATION BY

JACK PARDUE FDA Consumer / January - February 2000 / 25

Some sites require customers only to fill out a questionnaire before

ordering prescription drugs, bypassing the important face-to-face

interaction with a health professional .

ing the law and plans to take legal action

if appropriate . The agency hasmadeInternet surveillance an enforcement p

ri-

ority , targeting unapproved new drugs ,

health fraud , and prescription drugs soldwithout a valid prescription .

sources say that number is likely stillfairly small .

For some people , buying prescriptiondrugs online offers advantages notavailable from a local drugstore , including :

A Brave New WorldMore and more consumers are using

the Internet for health reasons . According to themarket research firm Cyber

Dialogue Inc . , health concerns are thesixth most common reason people g

o

online . Internet drugstores , however ,

won ' tmake “brick andmortar ” pharma -

cies obsolete anytime soon . Industry fig -

ures predicted that 2 . 97 billion prescrip -tions would b

e dispensed in 1999 , andthough n

o

reliable figures gauging total

online sales are yet available , industry

• greater availability of drugs for shut

in people or

those who live far

from the

pharmacy

• the ease of comparative shopping

among many sites to find the best prices

and products

• greater convenience and variety of

products

• easier access to written product information and references to other sources

than in traditional storefront pharmacies

the ability for consumers to orderproducts and consult with a pharmacist

in the privacy of

their homes .

ordering prescription drugs , bypassingany face - to -face interaction with a

health professional .

“ This practice undermines safeguards

of

direct medical supervision and a

physical evaluation performed bya li

censed health professional , ” says JeffreyShuren , M . D . ,medical officer in theFood and Drug Administration ' s Office

ofPolicy , Planning and Legislation .

“ The Internet makes it easy to bypassthis safety net . ”

Skirting the

system this way sets thestage for problems that include danger

ous drug interactions and harm from

contaminated , counterfeit or

outdated

drugs . “ Websites that prescribe based on

a questionnaire raise additional health

concerns , ” says Shuren . “ Patients riskobtaining a

n inappropriate medication

andmay sacrifice the opportunity for a

correct diagnosis or

the

identification of

a contraindication to the drug . "

To

date , FDA has received only a fewreports o

f

adverse events related to

Internet drug sales , but some of

these

cases point out the potential danger of

buying prescription drugs on

the basis

of

just a questionnaire . For example , a

52 -year -old Illinois man with episodes

of

chest pain and a family history of

heart disease died ofa heart attack last

March after buying the impotence drugViagra ( sildenafil citrate ) from a

n

online

source that required only answers to a

questionnaire to qualify for the

prescription . Though there is no prooflinking theman ' s death to the drug ,

FDA officials say that a traditionaldoctor -patient relationship , along with a

physical examination ,may haveuncovered any health problems such a

s

heart disease and could have ensured

that proper treatments were prescribed .

FDA is investigating numerous phar

maceuticalWebsites suspected of break

Pkusmaca

A consultation between

patient and pharmacist helps

ensure that the

patient is aware

ofa drug ' s side effects and its

possible harmful interactions with

other drugs . Some Websites may

put patients at

risk by

bypassing

this relationship .

26 / January -February 2000 / FDA Consumer

FDA hasmade surveillance of Internet pharmacies an enforcement

priority , targeting unapproved drugs , health fraud , and drugs sold

without a valid prescription .

Internet drug shopping also purports to any state or country having phone lines.save consumers money. In some cases Some feel new laws will be needed to

this is true . A survey last fall by Con - improve this situation . “ Currently , theresumer Reports showed that buyers could is nothing to require a drug -dispensingsave as much as 29 percent by obtaining Website to disclose anything to the pub

certain drugs online . But another study, lic , ” says Rep . Ron Klink ( D - Pa . ) ,whoconducted in 1999 b

y

the University of is sponsoring Internet pharmacy legisla

Pennsylvania and published in the An- tion . “ Buyers have no way ofknowing

nals of Internal Medicine , tracked whether a site is licensed or if the site

Internet sales of

Viagra and Propecia and uses licensed doctors or pharmacists or

found that the two drugs were an average even in what state they are located . ”

of10 percent more expensive online than Klink ' s billwould require Internet -based

at

local Philadelphia -area pharmacies . pharmacies to list the name , address and

In another part of

that study , research - phone number of

the principal place of

ers Bernard Bloom , Ph . D . , and Ronald business , the name of each pharmacistIannocone found that 37 of the 46 sites and health professional who providesthey examined required a prescription medical consultation , and the statesfrom a personal physician o

r

offered to where the

pharmacy , pharmacists ,andprescribe amedication based solely on a other health professionals a

re licensed .

questionnaire . But nine sites , all based Certain pharmacy industry representa -

outside the United States , did

not require tives oppose legislation or additional

a prescription . The researchers also powers for regulatory agencies on the

found that even when Websites offered a premise that current laws are sufficientquestionnaire with the promise that a to address the problem . “ There a

re [conphysician would review the form , noth - trols ] already in place for regulating

ing was generally known about the pharmaceutical sales , ” saysMary Anndoctor ' s qualifications , and itwas easy Wagner , vice president of pharmacyfor users to provide false information to regulatory affairs for the National Assoobtain a prescription . ciation o

f

Chain Drug Stores . “ ThatConsumers seeking health products hasn ' t changed . ”

online can find dozens of

sites that FDAofficials say are legally questionable . A Overseeing Online Sales

number of

them specialize in providing Whether new legislation will improvedrugs such a

s Viagra , the baldness oversight of

online pharmacies remainstherapy Propecia (finasteride ) , or the to b

e

seen . For themoment , regulators

weight -loss treatment Xenical (orlistat ) . have entered what FDA ' s Shuren calls “ a

Others , based in foreign countries , prom - whole new ball game ” that cuts acrossise to deliver prescription drugs at a the limited jurisdictions o

f

several fedmuch cheaper price than their domestic eral and state agencies . State medicalcost ,but the drugs may be different from boards regulate medical practice , whilethose approved in the United States o

r

state pharmacy boards oversee phar

may be past their expiration dates . Still macy practice . FDA and the Federal

other sites make fraudulent health claims Trade Commission ensure that drug selle

or blatantly advertise that a customer can ersmake legal claims for their products .

buy drugswith no prescription .Online Numerous other agencies such as

the

drug sites can now be located in nearly U . S . Customs Service and the U . S .

Postal Service enforce laws regarding

the shipment of drug products .

FDA regulates the

safety , effectivenessand manufacturing o

f

pharmaceutical

drugs , as well as a part of

the prescribing process . “ It is a violation o

f

the

Food , Drug , and Cosmetic Act to sell a

prescription drug without a valid prescription , ” says Shuren . “ Therefore ,

FDA can take action against sites thatbypass this requirement . ” He adds thatthe advantage o

f

FDA being involved is

that states have difficulty enforcing their

laws across state boundaries . If one statesuccessfully shuts down an illegal

Website within its borders , the site theo

retically still has 49 other potential lo

cales in which to sell . However , if thefederal government shuts down an illegalWebsite , that operation is out o

f

business .Last July , FDA announced that itwasjoining forces with state regulatory

agencies and law enforcement groups to

combat illegal domestic sales of prescription drugs . The agency signedagreements with the National Association o

f

Boards of

Pharmacy and the Federation o

f

State Medical Boards repre

senting the commitment of

these

organizations to help enforce federal and

state laws against unlawful Internet sell

ers and prescribers of drugs in the

United States .

Though regulating Internet sales of

health products is still fairly new , FDAhas successfully taken action in the past

against illegal sites . For example , a California company called Lei -Home AccessCare in 1996 and 1997 used the Internet

to sell a home kit

advertised asa blood

test for the AIDS virus .Not only was the

kit

unapproved , but the

maker also fabricated test results to users who submitted

a drop of

blood . After an extensive FDAinvestigation , the site was shut down ,

DA

Consumer / January -February 2000 / 27

How OnlineSales Work

Drugs obtained from foreign sites may be different

from those approved in the United States or may

be past their expiration dates.

and its operator , Lawrence Greene ,was

sentenced to more than five years in

prison .

Last July , the Federal Trade Commission announced a program called “Operation Cure .All , ” which aims to stopbogus Internet claims for products and

treatments touted as cures for various

diseases . Over two years , the program

identified about 800 sites and numerous

Usenet newsgroups containing question -

able promotions .

“Miracle cures , once thought to be

laughed out of existence ,have found a

new medium , ” says Jodie Bernstein , di

rector of FTC ' s Bureau of Consumer

Protection . “ Consumers now spendmil -

lions on unproven , deceptively marketedproducts o

n

the Web . ”

As part of the program , four companies settled FTC charges o

f deceptive

health claims . These included sites that

claimed to cure arthritis with a fatty acid

derived from beef tallow , to treat cancerand AIDS with a Peruvian plant derivative , and to treat cancer and high bloodpressure with magnetic devices . FDA is

working closely with FTC on Operation

Cure .All and has taken its own regulatory actions , such a

s sending warning

letters to help ensure that false and misleading statements are removed from the

Internet .

More than a dozen states also havetaken some kind o

f

action against

Internet pharmacies , including Kansas ,

which last year prohibited several phar

macies from operating illegalWeb -based

businesses within the state .

Industry Polices Itself

At

the same time that regulatory agen

cies are stepping up

enforcement efforts

against illegal online drug sales ,profes

In general , legitimate online pharma

cies operate this way :

• Users open an account with the phar

macy , submitting credit and insurance

information . The pharmacy is licensed

to sell prescription drugs by

the state in

which it operates and in those states to

which it sells , if an out - of -state license

is required .

• After establishing an

account , users

must submit a valid prescription . Doc

tors can

call it in , or users can deliver it

to the

pharmacy by

fax

or

mail .

• Some online pharmacies send prod

ucts from a central spot ,while others al

low users to pick the prescription up

ata

local drugstore . Prescriptions usually are

delivered within three days , often for no

shipping charge . For an extra fee ,many

sites will deliver overnight .

• Sites typically have a mechanism for

users to ask questions of

the pharmacist ,

either through e -mail or a toll -free

number .

- J . H .

A physical examination bya licensed health professional is a critical part of

the drug

prescribing process . Websites that sell prescription drugs based only on answers to a

questionnaire expose consumers to potentially dangerous drug interactions and harm

from contaminated or

outdated products .

What Consumers Can Do

With hundreds of drug -dispensing

Websites in business , how can consum

ers tell which sites are legitimate ones ,

especially when it is very easy to set up

a site that is very professional looking

and promises deep discounts oramini -

mum of

hassles ?

“ Consumers need to be

cautious , ” saysJeffrey Shuren , M . D . ,medical officer in

FDA ' s Office of Policy , Planning andLegislation . “ You should use the samekind o

f

common sense you use whenbuying from any business . You look for

a reputable dealer . You get recommenda -

tions from friends . You check the place

· Check with the National Association

of

Boards of

Pharmacy to determine if

the

site is a licensed pharmacy in good

standing (visit their website at

www .nabp .net , or call (847 )698 -6227 ) .

• Don ' tbuy from sites that offer to prescribe a prescription drug for the first

time without a physical exam , sell a preewithout a physical exam , sell a pre -

scription drug without a prescription , or

sell drugs not approved by

FDA .

• Don ' t do business with sites that do

not provide access to a registered phar

macist to answer questions .

. Avoid sites that donot identify withwhom you are dealing and d

o not provide a U . S . address and phone number to

contact if there ' s a problem .

• Beware of

sites that advertise a “ new

cure ” for a serious disorder ora quick

cure - all

for a wide range of

ailments .

• Be

careful of

sites that use impressive

sounding terminology to disguise a lack

of good science or those that claim the

government , the medical profession , or

research scientists have conspired to

suppress a product .

• Steer clear of

sites that include undocumented case histories claiming

“ amazing ” results .

• Talk to your health -care practitioner

before using any medication for the firsttime .

If you suspect a site is illegal , you canreport it to FDA b

y

sending ane -mail to

webcomplaints @ ora .fda .gov . Iout . ”

FDA offers these tips to consumers

who buy health products online : J . H .

sional organizations are launching programs with the goal o

f

cleaning house

from within . Late last year , the NationalAssociation o

f

Boards of Pharmacy

(NABP ) unveiled its Verified Internet

Pharmacy Practice Sites (VIPPS ) pro

gram ,which provides consumers valu -

able information about the credentials of

online pharmacies .

VIPPS is a voluntary certification pro -

gram . The fairly rigid conditions theonline pharmacy must agree to fo

r

acceptance into the program include :

• maintaining all state licenses in good

standing

• allowing information about the phar

macy to be posted and maintained on the

VIPPS Website (http : / /vipps .nabp .net /

verify .asp )

• allowing an NABP -sanctioned team to

inspect its operations , given reasonable

notice

• displaying and maintaining the VIPPS

seal with a link to the VIPPS Website .

VIPPS officials say the program is es -

pecially beneficial to seniors . “ There is

particular concern among the elderlypopulation ,which is often the target of

unscrupulousmarketing ploys , ” says

Kevin Kinkade ,NABP executive committee chairman . “ VIPPS will be of tre -

mendous benefit to consumers who need

to be

certain that the prescription medications they receive are from legitimate

online pharmacies . ” At

press time , threebusinesses had been awarded VIPPS ce

r-

tification : drugstore .com ,Merck -MedcoRx Services , and PlanetRx .com .

At its June 1999 annual meeting , theAmerican Medical Association draftedguidelines fo

r

doctors that specifically

address Internet prescriptions . Thoughthese voluntary principles weren ' t finalized at press time , AMA officials saythey are geared to ensure that doctors

who prescribe over the Internet follow

minimum standards of

care . This in

cludes actually examining patients to determine a diagnosis o

r

ensure that a

medical problem really exists .

Many in the pharmaceutical industry

back the AMA ’ s action . “ The relationship between physician and patient is

critically important , “ saysMartinHirsch , public affairs director for RocheLaboratories Inc . ,maker of Xenical .

“We support guidelines thatwill ensurethat this relationship continues . ”

With regulatory and voluntary actions

in full swing , it still will be hard to stayon top of illegal Internet drug sales .

“ Even if the state boards , FDA , and others do their jobs , consumers are going to

need to be

educated about the issue , ”

says Wagner of

the National Association

of

Chain Drug Stores .FDA plans to help increase public

awareness with an education campaign

that informs consumers about the health ,

economic and legal risks of

online sales

ofmedical products . The campaign also

will target health -care practitioners andindustry . Other federal and privategroups are conducting similar outreach .

“ Consumers need to know the

risks of

buying prescription drugs online so they

can remain vigilant , ” says FDA ' s

Shuren , “ The public also needs to

know , ” he adds , “ that there ' s a price to

pay for

operating an illegal Internet

pharmacy .Even bringing a few

highly

publicized cases into the public eye willsend a powerfulmessage that these illegal sites will not be tolerated . ”

John Henkel is a staffwriter for FDAConsumer .

FDA Consumer / January -February 2000 / 29

Joint Program Pools FoodResearch Resources by Paula Kurtzweil

Aside from the occasional opening

and closing of a refrigerator door andthe padding of footsteps to and from the

laboratory bench , it's a quietMaymorning in a Food and Drug Administrationlaboratory in suburban Washington ,

D . C. Six or so researchers workingalone or in a group of two or three prepare test tubes , calibrate instruments ,

and analyze chemical data .Though their conversation isminimal ,

their work is not: These researchers , employed by FDA’s Center fo

r

Veterinary

Medicine , are

addressing one of

today ' s

most pressing health concerns : antibi

otic resistance in humans . The researchers hope to answer such questions as

“ What causesmicrobial pathogens in

food animals to develop antibiotic resistance ? ” “ Can scientists overcome this

resistance ? ” “ How can this transfer of

resistant pathogens to humans bemini

mized ? ”At

other sites in the Washington area ,

research is focused on such important

health issues as lycopene , an antioxidant

found in tomatoes and some fruits that

may help lower the

risk for

certain diseases (such as cancer and heart disease ) ,

and " biofilms , ” groups of

bacteria often

encased in a protective -like layer that

cannot be penetrated by

standard cleaning solutions .

This research is being done under theauspices o

f

the Joint Institute for Food

DEL

A specialist in nuclear magnetic resonance

(NMR ) , FDA ' sGeneMazzola , Ph . D . , loadsthe agency ' s NMR instrument with a

n extract

from moldy food to learn what type of

mold

byproducts are present and whether they

pose a health risk .

(Photographs by

Edwin Remsburg for

the

University ofMaryland College ofAgriculture

and Natural Resources )

30 / January -February 2000 / FDA Consumer

Safety and Applied Nutrition ( JIFSAN ).Through research and education , the institute, a cooperative program betweenFDA and the University ofMaryland ,will help ensure the safety and nutritional quality of the U .S. food supply .By pooling their resources , th

e

university and FDA look to gain both profes

sional and public health benefits .

FDA hopes the studies will add to its

scientific knowledge and will contribute

to future regulatory decisions . This plan

is consistent with the agency ' s

longstanding policy of relying on

science as the basis of

all agency deci

sions . “ JIFSAN provides a uniqueapproach to increasing FDA ' s sciencebase , ” says David Lineback , Ph . D . ,

JIFSAN director .

The education portion will focus on

training various professional and regula -

tory groups — including those in foreign

countries — in key food safety and nutrition practices .

Created in 1996 , JIFSAN is one of

two such FDA food programs central

ized in institutions of higher education

with both government and industry in -

volvement . The other program is the Na -

tional Center for

Food Safety and Tech -

nology (NCFST ) in Summit -Argo , Ill .

Created in 1988 , this consortium of

gov -

ernment , industry , and academia is fi

nancially supported by

FDA and the Illinois Institute o

f

Technology , the IITResearch Institute , and the University o

f

Illinois . (See “ Food Safety ResearchCenter Offers Taste o

f

the Future ” in the

December 1991 FDA Consumer . )

“ Toa large extent , the future develop

ment of food regulatory science andpolicies fo

r

the

United States is depen

dentupon the success of

these programs , ” Lineback says .

Analysis and Critical Control Point

(HACCP ) food safety programs .

JIFSAN focuses ona range of

foodsafety and nutrition issues , including

risk analysis , food composition , toxinsandmicrobial pathogens , animal drugresidues , and animal health . “ JIFSANwill be amore al

l- encompassing pro

gram , ” Lineback says .

Also , JIFSAN serves as a WorldHealth Organization Food Safety Collaborating Center , focusing o

n risk as

sessment of

contaminants in food andmycotoxin analysis .Mycotoxins a

re poi -

sonous substances formed by

mold in

wheat , corn , peanuts , and othermajorfood crops .

According to Lineback , plans to relocate FDA ' s Center fo

r

Food Safety andApplied Nutrition from Washington ,

D . C . , to suburban College Park ,Md . ,

near the

University of Maryland campus ,

will allow for easier collaboration between the two institutions . SomeJIFSAN research also is done a

t

FDAlaboratories in Laurel ,Md . , about 10

miles from College ParkThe proximity o

f FDA headquartersand the University o

fMaryland was amajor reason FDA chose the universityfor the JIFSAN collaborative effort .

“ The proximity allows for

ease of col

laboration , ” says Norris Alderson , Ph . D . ,

director of

research for FDA ' s Center forVeterinary Medicine . “ And , the University o

fMaryland is one of

the premier

research universities in the Washington ,

D . C . , area . ”

JIFSAN officials say the close proximity will :

• widen FDA and the university ' s access

to a larger combined base of

experts in

such disciplines as regulatory science ,

behavioral science , economics , chemis

try , food science , and microbiology

• allow for shared use of

costly state -ofthe -art instrumentation , such a

sa

nuclear magnetic resonance spectrom

eter and electron microscopes and mass

spectrometers ,necessary in today ' s research world

• assist FDA with recruitment of top

notch scientists by allowing FDA scien

tists to seek teaching opportunities andprofessorships a

t

the University of

Maryland .

m

Investigations Under Way

JIFSAN is usingmore than $ 500 ,000

in research funds for various studies , including :

• Transfering antibiotic - resistantpathogens to humans . Part of the study

is aimed at identifying drug levels at

power

RE

JIFSAN FeaturesBoth JIFSAN and NCFST are set up

to allow researchers to remain affiliated

with their respective employers , al

though personnel may work in facilitiesbelonging to another group . Also , eachorganization has an internal review

board , aswell as an advisory committee

of

experts from industry , academia , gov -

ernment , and consumer organizations .

NCFST focuses on the safety of

food

processing and packaging technologies ,

applied microbiology , and Hazard

JIFSAN researchers (left to right ) Robert Hall , Ph . D . , an FDA microbiologist ; Jianghong

Meng , Ph . D . , a University ofMaryland assistant professor in nutrition and food science ;

and Edward Corrigan , Ph . D . , president of Diachemix Corp . , prepare bacterial cultures

for

testing a new rapid method to detect various Escherichia coli bacteria in food .

FDA Consumer / January -February 2000 / 31

For more information on antibiotic

resistance , see “Miracle Drugs vs .

Superbugs : Preserving the Usefulness of Antibiotics ” in the Novem

ber-December 1998 FDA Consumer

(available on FDA'sWebsite atwww . fd

a.gov /fdac /features /1998 /

698 _ bugs .html ) .

The researchers hope to answer such questions as

“What causes microbial pathogens in food animals

to develop antibiotic resistance ? " " Can scientists

overcome this resistance ? "

In addition , JIFSAN has sponsoredseveral international workshops andtraining programs . One dealtwith transmissible spongiform encephalopathies

( TSEs ) , progressively degenerative cen -

tral nervous system diseases of

humansand animals . One TSE that has beenwidely reported is bovine spongiformencephalopathy , often referred to in thepopular press a

s“mad cow disease . ”

Another training program was aimed at

educating foreign health officials whosecountries export foods to the United

States on how to detectmycotoxins in

foods .

grounded in science , and they must dealwith a regulatory food safety o

r

nutrition

issue . “We ' re looking for

creative re

search that reflects FDA ' s regulatoryprogram priorities , ” Page says .

The JIFSAN committee reviews theprogress o

f

research projects yearly to

determine which ones should continue to

be

funded . In many cases , Page says , theinitial funding is allocated with the hope

that the research will eventually qualify

for other grants from additional federal ,

university or

industry sources .

With this kind of

support , plus thebacking of a five -year formal agreement

between FDA and the University of

Maryland , JIFSAN hopes its research

will lead to sound solutions to one of

today ' smost perplexing questions :

“How can we keep America ' s food sup

ply

safe and nutritious ? ”

Creative ScienceDeciding what topics to focus o

n is

somewhat ofa collaborative effort itself .

Yearly , a JIFSAN committee of

Univer -

sity ofMaryland faculty and FDA staff

reviews and selects for funding researchproposals created and submitted by university researchers , working alone o

r

with FDA scientists .

To receive funding , proposals must

meet two criteria : They must be

Paula Kurtzweil wrote this article whilea member of FDA ' s public affairs staff .

She is now with the Federal Trade Commission .

which various bacteria become resistant

to the drugs ' effects . Scientists also are

trying to determine the

genetic makeup

of

antibiotic - resistant bacteria in thehopes o

f developing appropriate agents

that work against these bacteria . “Ourgoal is to provide the framework for determining how we can safely use antibi

otics in food -producing animals , ”

Alderson says .

• Identifying the form of the antioxi

dant lycopene that is best absorbed by

the body . According to the federalgovernment ' s Dietary Guidelines forAmericans , antioxidants are substances

in food that may have a role in reducingthe risk for cancer and other chronic d

is -

eases . Knowing which form of

lycopene

is most beneficial will enable FDA to

help determine the criteria under which

a health claim on lycopene ' s benefits

could be

used in the labeling of

foods and

dietary supplements . (See also “ Staking a

Claim to Good Health ” in the November

December 1998 FDA Consumer . )

• Identifying the best ways to get consumers to improve their food safetypractices .Results o

f

that study are expected in 2000 , says Sam Page , Ph . D . ,

FDA ' s scientific director for JIFSAN .

• Evaluating an interactive Website ,

the Food Safety Risk AssessmentClearinghouse , to see if it can be usedfor formatting risk information to assess

risk and formanaging and communicating food safety risk assessments .

• Identifying strategies for preventingSalmonella enteritidis contamination

in eggs . (See “ Safer Eggs Laying theGroundwork ” in the September -October

1998 FDA Consumer . )

• Discovering new analytical methodsfor detecting and identifying microbialpathogens .

Former University ofMaryland students Chris Larkin ( left ) and Susie Ahn prepare

bacterial cultures fora JIFSAN -sponsored study on developing rapid test

methods to

detect microbial pathogens .

32 / January -February 2000 / FDA Consumer

fda .govHot spots and cool links on FDA'sWebsite and beyond .

Keeping Cholesterol DownOne out ofevery two men and one out of every three women will develop heart disease ,whichclaims nearly a halfmillion lives yearly in this country .Whether you have heart disease orwant toprevent it, you can reduce your risk of having a heart attack by lowering your cholesterol level.

How ? The National Heart, Lung ,and Blood Institute tells you at www .nhlbi. nih.gov /chd / .On the

“Live Healthier , Live Longer ”Website , you can learn all

about coronary heart disease and its con

nection to high cholesterol levels , as well as risk factors and prevention tips .

Hey , Students ! SomeHot Tips for TermPapers

‘Micro 'ManagingYour Ovens

Stumped for ideas that ' ll helpyou ace your nextschool re

port ? Then check out the FDA

Center for Food Safety and

Applied Nutrition ' s “ StudentResources ” page . It containsvaluable research and writing

tips and links to good report topics , including : cosmetics ,

health fraud , losing weight ,nutrition , pesticides , how lawsaremade , and food labels . For a leg u

p

on your next research

paper , go to www .cfsan .fda .gov / ~ comm /students .html .

Ever wonder how safe microwave ovens are and

how best to use them ? Or how microwaves work

their magic in heating food ? FDA ' s Center forDevices and Radiological Health explains this and

more at

www . fda.gov /cdrh /consumer /

microwave .html . Learn about FDA ' s standard thatlimits th

e

quantity of

microwaves that can leak

from an oven throughout its

lifetime . The

site also

has other tips , such asa warning that commercial

microwave testing devices are generally inaccurate

and unreliable .

Curbing Racial Disparities in HealthDespite ongoing progress in the nation ' s overall health , disparities in illness and death continue to exist for

blacks , Hispanics , American Indians , and Alaskan natives compared with the U . S . population asa whole ,

according to the Department of Health and HumanServices . One of the ways the federal government is

combating these inconsistencies is by boosting out

reach in six

areas of

concern within racial and ethnic

communities : infantmortality , cancer , cardiovasculardisease , diabetes ,HIV /AIDS , and immunizations . At

www .raceandhealth .omhrc .gov , you can find background on the si

x

areas , as well as a description of

how to reach goals for curbing disparities and how to

get involved in the program .

FDA Consumer / January -February 2000 / 33

GOSNONINVESTIGATORS ' REPORTSSTEINE NE

- - -- -- -- - --

Unapproved Body Fat Tester

FetchesWeighty Fine

by Larry Thompson

The president and chairman of the

board of amedical device companybased in Gaithersburg ,Md., pleadedguilty early in 1999 to charges that hiscompany imported and sold to hospitals

and clinics a device formeasuring body

fatbefore FDA approved the device formarketing

Robert Rosenthal , head of Futrex Inc.,

was sentenced on April 29 , 1999 , byU . S. District Judge Deborah K .Chasanow to four months of home detention , 18months of probation , a$ 3,000 fine , and a $200 special assessment fee. In addition to the sentence imposed by Judge Chasanow , Rosenthalwas ordered to pay a $ 90 ,000 fine to theU . S. Customs Service and a $50 ,000

fine to the U . S. Securities and ExchangeCommission (SEC ) as a result of civilsettlements with those agencies .

Rosenthal's plea followed an investigation by FDA's Office of Criminal Investigations (OCI) initiated after an FBI to the SEC for permission to make ainquiry into possible investment fraud . public stock offering to raise researchFDA ended up looking into reports of funding for hi

s

device . The demonstra -

unverifiable clinical data and an interna tion showed the

device performing as

tional conspiracy to smuggle unap Rosenthal said itwould , but the SEC be -

proved medical devices into this country . came suspicious when a former Futrex

The FBIbrought its concerns about official -turned -whistle -blower allegedRosenthal and his company to FDA ' s at - that Rosenthal had rigged the demontention in March 1996 . The FBIhad stration . The SEC called in the FBI ,

learned about Rosenthal when the SEC which referred the problem to FDA .

reported that he

had demonstrated to that FDAwas not unaware of

Rosenthalagency ' s representatives a device h

e

and his company when the FBI apcalled The Dream Beam , which h

e proached the agency . FDA was alreadyhoped to develop into a noninvasive engaged in ongoing discussions with

method for measuring blood glucose . He Rosenthal over a medical device appli

claimed that the device used light to cation his company had submitted in

measure blood sugar levels without re - 1992 for the Model F -5000 and Modelquiring a drop of

blood . Rosenthal went F - 5000A fat testers . Both devices were

manufactured by

Kett Electric Laboratories in Tokyo , and Rosenthal wanted to

sell them in the United States .

The devices , which FDA has since

cleared for marketing , use near -infraredradiation to measure percentage body

fat , lean mass , and bodywater to give an

indication of

overall leanness or obesity .

The device is basically a wand that is

aimed at

the mid -point of the largest

bicep muscle in the arm . The wand thenemits wavelengths o

f

infrared light that

are selectively absorbed by

fat

and re

flected by

lean bodymass . The amount

of light absorbed correlates to the total

body fat .

In a letter acknowledging that it hadreceived the application for these de

34 / January -February 2000 / FDA Consumer

vices, FDA's Center for Devices and Ra-diological Health told the company thatit could not place the device into com -mercial distribution until FDA cleared it

for marketing

FDA 's approval was held up becausethe agency identified problems with

Futrex 's application . Richard Williams,the reviewer in CDRH 's Office of Device Evaluation, placed the applicationon hold because the submitted data did

not support the company 's claimsof thedevices ' accuracy and effectiveness . Thisfinding led to a series of correspondence

and meetings over three years as the

agency worked with the company to resolve the questions about the data .During its investigation ,OCI receivedinformation that the clinical data used to

validate the fat

tester had been allegedly

fabricated . FDA could not confirm thisbecause when FDA asked for the clinicaldata , the company said that the datawere stored o

n

an

old computer and

could not be retrieved .

Search warrants were executed jointly

by FDA ' s Office of Criminal Investigations , the FBI , and the U . S . CustomsService in March 1997 at Futrex ’ s facil

ity

in Maryland . In January 1998 , search

warrants were also executed atKett

Electric in Japan by

the Japanese National Police and the Tokyo Metropoli

tan Police at

the request of , and with as

sistance from , the agents ofOCI , the

FBI , and the U . S . Customs service . Evidence recovered in these searches

showed that Futrex began to import and

sell its fat tester in 1988 , even though

FDA did not clear it for marketing untilDecember 1995 . To keep FDA and U . S .

Customs officials from becoming suspi -

cious , Futrex arranged with Kett Electric

to ship the devices to the United Statesas animal and poultry fat testers .

The company adopted this ploy after

FDA held upa shipment of fat testers

that arrived at

the Baltimore -WashingtonInternational Airport .An FDA inspectorhad checked the agency ' s records to seewhether a device application for the fat

testerwas pending . When he learned

that an application was still under re

view , he held the cargo . FDA later re

leased it when the company said the de

vices were “ fitness instruments ” that

were not regulated by

FDA asmedical

devices .

In response to this temporary seizure ,

Rosenthal told Kett Electric to label the

machines , the packaging , and the mani -

fests so it appeared as though the de

vices were intended for use as animal fat

testers . In addition , Rosenthal instructed

Kett to remove the user manuals that

showed how to use the F - 5000s to make

measurements on

humans before shipping the testers to the United States .

Rosenthal had Kett Electric send thelabeling for th

e

devices as

human fat

testers separately .

A review of

Futrex ’ s records showedthat between July 1994 and December

1995 , the company imported more than

2 ,000 human body fat testers falsely described o

n

commercial invoices and import entry documents a

s animalandpoultry fat testers . The total declaredvalue o

f

these products was $678 ,602 .

Although the fat testers were labeled for

animal use , Futrex sold 11 percent of

them to doctors and othermedical per

sonnel , records show , amounting to a declared value o

f$ 74 ,646 . Evidence seized

during the

search of

Futrex ’ s headquarters in March 1997 included returned

warranty cards showing thatmany of thebuyers o

f

the devices intended to use

them in testing laboratories at hospitals

and clinics .

The search of

the company ' s officesalso turned u

pamarketingmemowrit

ten by a doctor that explained how to receive medical insurance reimbursementfor use of the unapproved device .

The device FDA cleared formarketing

is now sold as

the Futrex -5000 . Although CDRH reviewers were never satisfied with the company ' s data about accuracy and efficacy , the agencyapproved the device because , under thelaw , companies thatmarket a device

such as

the fat tester have to demonstrateonly that their device is substantially

similar to one already on

the U . S . market before 1976 . Futrex was able to dem

onstrate this . Also , FDA determined that

the fat tester did not pose any safety

risks .

FDA never pursued Rosenthal on thenoninvasive blood glucose monitor , the

so -called Dream Beam , because he

never attempted tomarket it in theUnited States .

Larry Thompson is a member of FDA ' S

public affairs staff .

Summaries ofCourt Actions

will not appear in this issue of

FDA Consumer , butwill re

turn in the March -April issue .

FDA Consumer / January -February 2000 / 35

Statement ofOwnership ,Management , and Circulation(Required by 39 U .S.C . 3685 )

FDA Consumer , ISSN 0362 - 1332 ; owner and publisher: Food and Drug Administration (HFI -40), 5600 Fishers Lane, Rockville ,MD 20857 ; editor : Isadora Stehlin .

Date of filing : October 1999 ; issued 6 times annually (bimonthly ); annual subscription price $12 ($ 15 foreign ).

Extent and Nature of Circulation : Average No.Copies Each

Issue DuringPreceding 12

Months

Actual No.Copies of SingleIssue Published

Nearest toFiling Date

A . Total number of copies

(net press run ) 25 ,220 25 , 377

22 , 346 22 ,500

B . Paid and /or requested circulation

1. Paid /requested outside -county mailsubscriptions

2. Paid in - county subscriptions

3. Sales through dealers and

carriers , street vendors , counter

sales , and other non -USPSpaid distribution

4. Other classes mailed through the USPS

C . Total paid and/or requested circulation( sum of B1, B2 , B3 and B4 ) 22,346 22 ,500

D. Free distribution bymail(samples , complimentary ,and other free ) 2,119 2,112

E . Free distribution outside themail(carriers or other means ) 600 600

F. Total free distribution

(sum of D and E ) 2,719 2,712

G . Total distribution(sum of C and F) 25 ,065 25,212

H . Copies not distributed 155 165

1. Total ( sum of G and H ) 25,220 25 , 377

89 % 89 %Percent paid and /or requested circulation(C / G x 100 )

I certify that the statements made byme above are correct and complete .

Isadora Stehlin , editor

36 / January -February 2000 / FDA Consumer

Soon , all

over - the-counter medicines

willhave one

thing in common .

Drug FactsActive ingredient

( in each tablet

)

Chlorpheniraminemaleate

2 mg . . . . . . . . . . . . . . . . . .

PurposeAntihistamine

Uses temporarilyrelievesthese

symptomsdue to hayfever or otherupper

respiratory

allergies: sneezingrunnynose

itchy,wateryeyesitchythroat

K

WarningsAsk a doctorbefore

use if youhave

glaucoma zabreathingproblemsuch

as emphysemaor chronicbronchitis

troubleurinatingdue t

o an enlargedprostate

gland

Ask a doctororpharmacistbefore

use if youaretakingtranquilizerso

r sedatives

Whenusingthisproduct

youmaygetdrowsyavoidalcoholic

drinks

alcohol, sedatives

, andtranquilizersmayincreasedrowsiness

becarefulwhendrivinga motorvehicle

or operatingmachinery

excitabilitymayoccur

, especiallyin children

Ifpregnant or breast-feeding

, ask a healthprofessionalbefore

use .

Keepoutof reachofchildren. I

n case ofoverdose

, getmedicalhelp or contacta Poison

ControlCenterrightaway.

Directionsadultsandchildren

12 yearsandover

children6

years to under 12 years

take 2 tabletsevery 4 to 6 hours

;

notmorethan 12 tablets in 24 hours

take 1 tabletevery4 to 6 hours

;

notmorethan 6

tablets in 24 hours

ask a doctor

childrenunder

6 years

&

I

DRUG

Other information

, store at 20 -25°C ( 68 -77°F ) protect

fromexcessivemoisture

FACIS

Inactiveingredients D & C

yellow no . 10 ,lactose,magnesium

stearate

,microcrystalline

cellulose

,pregelatinizedstarch

SimplicityZUILL

The easy - to -read format of thenew Drug Facts labelwill help

consumers choose the over - the - counter medicine that ' s rightfor them . Formore information , see the FDA Consumer article

" New Drug Label Spells It Out Simply " at

www .fda .gov /fdac /features /1999 /499 otc .html

or

call 1 -888 -INFO -FDA .