PE R S PE C T IV E
ies may be detected during this
The Perils of Trumping Science in Global Health
The Perils of Trumping Science in Global Health
The Mexico City Policy and Beyond
NathanC. Lo, B.S., and Michele Barry, M.D.
cent outbreak in Brazil highlights This article was published on March 8, 2017,
stage; however, viremia has usu-
ally resolved. Case-fatality rates
range from 20 to 60% in patients
in whom severe disease develops,
and treatment is supportive, since
no antiviral therapies are current-
ly available.3,4
Yellow fever is the most severe
arbovirus ever to circulate in the
Americas, and al-
An audio interview
with Dr. Fauci is
though vaccination
campaigns and vec-
available at NEJM.org
tor-control efforts
have eliminated it from many
areas, sylvatic transmission cycles
continue to occur in endemic
tropical regions. The most re-
D uring his first week in office,
President Donald Trump re-
instated an executive order ban-
ning U.S. aid to any international
organization that supports abor-
tion-related activities, including
counseling or referrals. The so-
called Mexico City Policy collo-
quially referred to as the global
gag rule on womens reproduc-
tive health is allegedly intended
to reduce the number of abor-
tions around the world, in accor-
dance with an antiabortion agen-
da. Scientific evidence suggests,
however, that the policy achieves
the opposite: it significantly in-
creases abortion rates.1 The policy
defunds and in so doing, in-
capacitates organizations that
would otherwise provide educa-
tion and contraceptive services to
reduce the frequency of unintend-
ed pregnancies and the need for
abortions.1 The reinstatement of
n engl j med 376;15 nejm.org April 13, 2017
The New England Journal of Medicine
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Copyright 2017 Massachusetts Medical Society. All rights reserved.
this phenomenon. If the current
outbreak leads to urban spread
through A. aegypti mosquitoes,
clinicians should adopt a high
index of suspicion for yellow fe-
ver, particularly in travelers re-
turning from affected regions.
As with all potentially reemerg-
ing infectious diseases, public
health awareness and prepared-
ness are essential to prevent a re-
surgence of this historical threat.
Disclosure forms provided by the authors
are available at NEJM.org.
From the Office of the Director, National
Institute of Allergy and Infectious Diseases,
National Institutes of Health, Bethesda, MD.
the Mexico City Policy is a stark
example of evidence-free policy-
making that ignores the best sci-
entific data, resulting in a policy
that harms global health and,
ultimately, the American people.
In policymaking, the devil is in
the details, and ignoring scien-
tific data on the effectiveness of
particular policies results in faulty
decision making. In addition to
increasing abortion rates, the re-
instatement of the Mexico City
Policy is likely to result in increases
in maternal deaths and will en-
danger childrens health around
the world.1-3 By restricting access
to modern contraception, the pol-
icy will lead to preventable deaths
from pregnancy-related complica-
tions, increased reliance on unsafe
abortions, and higher rates of un-
safe sex (permitting HIV transmis-
sion, for example).2
In these ways, the policy is ac-
Yellow Fever in the Americas
at NEJM.org.
1. Fauci AS, Morens DM. Zika virus in the
Americas yet another arbovirus threat.
N Engl J Med 2016;374:601-4.
2. Brazilian Ministry of Health. Surveillance
update. February 2017 (http://portalsaude
.saude.gov.br/index.php/o-ministerio/principal/
secretarias/svs/noticias-svs/27602-ministerio
-da-saude-atualiza-casos-notificados-de-febre
-amarela-no-pais-2).
3. Gardner CL, Ryman KD. Yellow fever:
a reemerging threat. Clin Lab Med 2010;30:
237-60.
4. Monath TP, Vasconcelos PF. Yellow fever.
J Clin Virol 2015;64:160-73.
5. Wu JT, Peak CM, Leung GM, Lipsitch M.
Fractional dosing of yellow fever vaccine to
extend supply: a modelling study. Lancet
2016;388:2904-11.
DOI: 10.1056/NEJMp1702172
Copyright 2017 Massachusetts Medical Society.
Yellow Fever in the Americas
tually at odds with both the pro-
life agenda and a prochoice
approach that promotes compre-
hensive access to womens repro-
ductive health education. Rescind-
ing the policy should therefore
be a winwin for antiabortion
and prochoice groups. Moreover,
the consequences of reinstating
this funding ban are farther-
reaching than family planning.
Trumps aggressive extension of
the policy will damage other hall-
mark U.S. programs by defund-
ing integrated health programs
that promote global maternal and
child health and HIV-prevention
efforts, including provision of ac-
cess to condoms, HIV clinics, and
family-planning counseling.1,2
First announced by the Reagan
administration in 1984 at the
Second International Conference
on Population (held in Mexico
City), the global gag rule has been
1399
PERS PE C T IV E
implemented primarily through
executive action. The policy has
been restored and rescinded re-
peatedly as administrations enter
and exit the White House and has
been in effect for approximately
17 of the past 32 years. Even when
U.S. aid has been provided to or-
ganizations that support abortion-
related activities, as it has for the
past 8 years, this funding has
never been used to directly finance
abortion services. That limit is re-
quired by the Helms Amendment,
passed after the Supreme Courts
1973 decision in Roe v. Wade, which
legally prohibits any U.S. funds
from being used to support abor-
tion as a method of family plan-
ning. Instead, U.S. foreign aid for
family planning has been restrict-
ed to organizations that offer re-
productive counseling, education,
and contraceptives preventive
services that often preempt the
need for abortion.
The scientific evidence suggests
that the Mexico City Policy has
historically led to an increase in
the number of abortions. A senti-
nel study by Bendavid and col-
leagues estimated the differential
changes in the number of induced
abortions by comparing women
in 20 countries in sub-Saharan
Africa who had high or low expo-
sure to the effects of the policy
(owing to variation in the levels
of relevant U.S. funding to each
country before the policy was
implemented).1 The investigators
analyzed abortions over a 15-year
period and found that women liv-
ing in the countries most affect-
ed by the Mexico City Policy had
2.6 times the odds (95% confi-
dence interval, 1.8 to 3.7) of hav-
ing an induced abortion after the
policy was implemented as women
living in countries less affected
by the policy. This analysis was
1400
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Copyright 2017 Massachusetts Medical Society. All rights reserved.
The Perils of Trumping Science in Global Health
corroborated by a study specific
to Ghana that revealed a relation-
ship between the Mexico City
Policy and an increase in abor-
tions in rural settings, as well as
reduced nutritional status (as in-
dicated by weight and height) in
children when the Mexico City
Policy was in place.3
U.S. foreign-aid strategy aims
to promote global economic and
geopolitical security, which bene-
fits the American people as well
as many others around the world.
Better health care systems in oth-
er countries can protect against
global spread of infectious dis-
eases, from Ebola to pandemic in-
fluenza. Economic development in
poor countries reduces the chances
of civil conflict. The U.S. foreign-
aid philosophy has operated on
the premise that a flourishing
global economy will benefit U.S.
markets. These considerations
may provide a foundation for our
foreign-aid strategy, but only when
our efforts are implemented effec-
tively with support from scientif-
ic data.
An illustration of the perils
of allowing ideology to trump
scientific evidence can be found
in the landmark U.S. Presidents
Emergency Plan for AIDS Relief
(PEPFAR), which provides two
contrasting examples of the role of
scientific data in policymaking.4,5
Since 2004, PEPFAR has provided
aid for prevention, treatment, and
care of HIV infection in many
low-income countries in an effort
to control the global epidemic.
A principal focus of PEPFAR has
been the scaling up of the provi-
sion of antiretroviral therapy, an
evidence-based and effective strat-
egy for reducing transmission of
HIV and related mortality. That
investment has resulted in mea-
surable reductions in global mor-
n engl j med 376;15 nejm.org April 13, 2017
The New England Journal of Medicine
tality, averting more than 700,000
deaths of adults within the pro-
grams first 4 years alone, with
related economic and employ-
ment gains.4
By contrast, PEPFAR includes
a prevention program focused on
sexual abstinence and being faith-
ful, whose goal is to change sex-
ual behaviors that confer a high
risk of transmission or acquisition
of HIV. Even though support for
the abstinence, be faithful pro-
gram was highly contentious be-
cause the approach had not been
demonstrated to be effective, this
strategy originally received one
third of the entire PEPFAR preven-
tion budget. After more than a
decade and a cumulative invest-
ment of more than $1.4 billion,
the first study evaluating the strat-
egys effectiveness was published.5
It showed no measurable relation-
ship between the substantial fi-
nancial investment in abstinence,
be faithful programs and chang-
es in high-risk sexual behaviors.5
Clearly, creating policies that are
not based on rigorous scientific
evidence can have substantial costs
a particular concern when
there is a limited budget with
which to achieve effective global
development.
The decision to ignore data
when crafting foreign-aid strate-
gies can jeopardize the mission
of U.S. foreign policy to help en-
sure economic and geopolitical
security. The Mexico City Policy
is but one of many foreign-aid
decisions that the Trump admin-
istration will have to make to
guide our country and the world.
Ineffective foreign-aid policies that
ignore basic scientific analysis
will undermine our ability to sup-
port global development, waste
valuable resources, and ultimately
hurt the American people.
PE R S PE C T IV E
Disclosure forms provided by the authors
are available at NEJM.org.
From the Division of Epidemiology (N.C.L.)
and the Department of Medicine (M.B.),
Stanford University School of Medicine,
and the Center for Innovation in Global
Health, Stanford University (M.B.) both
in Stanford, CA.
This article was published on February 22,
2017, at NEJM.org.
Ensuring Access to Injectable Generic Drugs
Ensuring Access to Injectable Generic Drugs
The Case of Intravesical BCG for Bladder Cancer
BenjaminJ. Davies, M.D., ThomasJ. Hwang, A.B., and AaronS. Kesselheim, M.D., J.D., M.P.H.
I n November 2016, one of the
two manufacturers of bacille
CalmetteGurin (BCG) informed
health care providers that it
planned to exit the market in
mid-2017.1 Intravesical immuno-
therapy with BCG is the standard
of treatment for preventing re-
currence and disease progression
in high-risk patients with non
muscle-invasive bladder cancer,
who account for a substantial
minority of patients with newly
diagnosed bladder cancer.2 Yet the
past few years have seen inter-
mittent disruptions of the BCG
supply. The most recent disrup-
tion occurred in 2014, after a
plant was temporarily closed be-
cause of manufacturing quality
issues. The November announce-
ment raises the prospect of a
sustained shortage or substantial
price increase, even as National
Comprehensive Cancer Network
treatment guidelines recommend
intravesical BCG over chemother-
apy for these patients.
Limits on access to BCG mean
that providers must use poten-
tially less efficacious alternatives,
current patients may have to dis-
continue or temporarily halt ther-
n engl j med 376;15 nejm.org April 13, 2017
The New England Journal of Medicine
Downloaded from nejm.org on April 23, 2017. For personal use only. No other uses without permission.
Copyright 2017 Massachusetts Medical Society. All rights reserved.
The Perils of Trumping Science in Global Health
1. Bendavid E, Avila P, Miller G. United
States aid policy and induced abortion in sub-
Saharan Africa. Bull World Health Organ
2011;89:873-880C.
2. Glasier A, Glmezoglu AM, Schmid GP,
Moreno CG, Van Look PF. Sexual and repro-
ductive health: a matter of life and death.
Lancet 2006;368:1595-607.
3. Jones KM. Evaluating the Mexico City
policy: how US foreign policy affects fertility
outcomes and child health in Ghana. Wash-
ington, DC:International Food Policy Re-
apy, and new patients may need
to undergo cystectomy. Similar
concerns about potential harms
to patients during shortages have
arisen in other areas of oncology.
One study revealed that drug sub-
stitutions due to shortages were
associated with higher relapse
rates among pediatric patients
whose lymphoma might other-
wise have been cured.2
Beyond leading to inferior out-
comes, alternative treatment agents
can be expensive, adding to the
substantial financial burden of
cancer care. Recent media cover-
age has focused on rapid price in-
creases for certain generic drugs,
but little is known about drug-
price changes during supply dis-
ruptions. To assess the effect of a
BCG shortage on treatment costs,
we compared the listed average
wholesale prices (AWPs) for mito-
mycin, the primary alternative
to BCG for high-grade bladder
cancer, and for the third-line
treatment agents valrubicin and
thiotepa, before and after the BCG
shortages that began in 2012
and 2014.
We found that the list prices
for mitomycin increased dramat-
search Institute, 2011 (http://www.ifpri.org/
publication/evaluating-mexico-city-policy).
4. Bendavid E, Holmes CB, Bhattacharya J,
Miller G. HIV development assistance and
adult mortality in Africa. JAMA 2012;307:
2060-7.
5. Lo NC, Lowe A, Bendavid E. Abstinence
funding was not associated with reductions
in HIV risk behavior in sub-Saharan Africa.
Health Aff (Millwood) 2016;35:856-63.
DOI: 10.1056/NEJMp1701294
Copyright 2017 Massachusetts Medical Society.
The Perils of Trumping Science in Global Health
ically during the BCG shortage
beginning in 2014, and prices for
third-line agents increased mod-
estly (see graphs). After BCG sup-
ply disruptions were reported in
August 2014, the listed AWP for
mitomycin increased on August 26,
2014, from $436.80 to $869.59 for
the 40-mg dose and from $67.20
to $165.60 for the 5-mg dose
increases of 99% and 146%, re-
spectively. Although actual drug
costs can differ from the AWP,
Medicare data show that these
price changes were passed on to
patients and were likely to trans-
late into higher costs for payers
and taxpayers. Between 2012 and
2015, annual spending by Medi-
care Part B on mitomycin in-
creased from $4.3 million to
$15.8 million. Since beneficiaries
are responsible for 20% of Part B
drug payments in coinsurance,
out-of-pocket costs for mitomy-
cin (substituted for BCG) for a
patient covered by Medicare would
have increased from approximate-
ly $49 per year in 2012 to $155
in 2015.3
Yet even with price increases,
the number of manufacturers pro-
ducing these second- and third-
1401