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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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 .
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ConsumerIndexis availableon
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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 '
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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 .