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Correspondence
www.thelancet.com Vol 379 May 26, 2012
1947
As was made clear in the accom-
panying Comment by Grace Malenga
and Malcolm Molyneux,3 these interim
fi ndings should be judged with
appropriate caution. The comparison
between Millennium and matched
villages was not randomised, and so
no causal attribution of measured
changes can be conclusively ascribed
to the interventions. That said, the
results presented, in the words of
one of the original reviewers of the
paper, are “encouraging evidence—a
big intervention rapidly leading to
measurable results.” And, in fairness
to those attempting to evaluate
the eff ects of complex health pro-
grammes, non-randomised com-
pari sons do have the power to
illum inate—one example being
the retrospective non-randomised
assessment of UNICEF’s Accelerated
Child Survival and Development pro-
gramme in west Africa.4
The next phase of the Millennium
Villages project will involve the
monitoring of actual vital events
(instead of relying on recall). To ensure
that all future data from the project
are fully and fairly evaluated, Prof
Jeff rey Sachs, the Principal Investigator
of the Millennium Villages project, is
establishing new internal and external
oversight procedures, including the
creation of an International Scientifi c
Expert Advisory Group, chaired by
Prof Robert Black, Chairman of the
Department of International Health,
Johns Hopkins Bloomberg School
of Public Health, which will report
to the Principal Investigator and
also communicate its fi ndings to
The Lancet. The goal is to provide
a further independent means of
verifying the quality of the project’s
design and analysis. It is important
that this work, which is of considerable
signifi cance for understanding how
countries scale up multiple complex
interventions across sectors, receives
proper scientifi c evaluation before,
during, and after publication.
The Editors of The Lancet
editorial@lancet.com
32 Jamestown Road, London NW1 7BY, UK
1 Pronyk PM, Muniz M, Nemser B, et al, for the
Millennium Villages Study Group. The eff ect of
an integrated multisector model for achieving
the Millennium Development Goals and
improving child survival in rural sub-Saharan
Africa: a non-randomised controlled
assessment. Lancet 2012; published online
May 8. DOI:10.1016/S0140-6736(12)60207-4.
2 Editorial. With transparency comes trust.
Nature 2012; 485: 147.
3 Malenga G, Molyneux M. The Millennium
Villages project. Lancet 2012; published online
May 8. DOI:10.1016/S0140-6736(12)60369-9.
4 Bryce J, Gilroy K, Jones G. The Accelerated Child
Survival and Development programme in west
Africa: a retrospective evaluation. Lancet 2010;
375: 572–82.
Misleading report on
clinical trials in India
We are sorry to note that Amy Yee, in
her World Report (Feb 4, p 397),1 did
not consider it proper to seek comment
from the principal investigators whose
ethics she questions. Her report is
biased and portrays the clinical trial
scenario in India in general and at
Indore, Madhya Pradesh, in particular in
an unjust, negative matter. The report
falls into the type of partisan coverage
noted more often in the lay press.2
All trials in which we participated
were legal, ethical, and done as per
the norms of clinical practice and
guidelines set out by the Indian
Council of Medical Research (ICMR)
and the Medical Council of India.
The protocols for all trials, including
the Hindi version of the informed
consent form, were approved by
the Institutional Ethics Committee,
which had been constituted and was
working as per the ICMR guidelines. All
patients were insured by the sponsors
against trial-related adverse events
and outcomes. All the trials in which
we participated were multicentre
and multinational in nature, being
simultaneously conducted at many
prestigious institutions in India and
other countries (including in North
America, Europe, Australia). The same
protocol, same informed consent
form, and same insurance policies
were applicable at all centres.
Since none of the serious adverse
events or deaths were related to
invest igational products or the pro-
cess of participation in the trial, there
was no reason to off er compensation.
The 81 adverse events and a few
deaths out of 3300 patients over a
span of 4 years were due to the natural
history of the illness or unrelated
circumstances.
The money received by six doctors
over the same period refl ects the gross
receipt of the trial budget, most of
which is spent on doing the trial, and
a 10% share which is deposited in the
respective departments as per the
orders of the Dean of the college. The
residual income is duly audited and tax
is paid. The Government of Madhya
Pradesh and the Economic Off ence
Wing of the police have conceded
this money as being a legitimate
professional income. Similar practices
are prevalent in other parts of India
and the world over.
The Government of Madhya Pradesh
did ban initiation of new trials in
October, 2010, owing to reports in the
media, but permitted continuation of
ongoing trials, which are still ongoing
to date. No vulnerable patients were
exploited by us. The demographic
profi le of patients enrolled in our
studies refl ects that of the population
attending government clinics.
The “improper procedures” for
which a fi ne of Rs5000 was selectively
imposed on 12 doctors comprise a
trivial technicality of failing to provide
information to (another part of)
the health department about some
details of the clinical trials. However,
all information had already been
submitted on more than one occasion
to other more relevant departments
and agencies. The fi ne had nothing
do with the legality, ethics, or proper
conduct of the trials as per norms of
good clinical practice.
There is no restriction in the ICMR
guidelines on principal investigators
also being members of ethics com-
mittees. The ICMR guideline says
that members who also happen to be
Getty Images
Correspondence
1948
www.thelancet.com Vol 379 May 26, 2012
investigators should not be involved
in the process of decision making
about approval of the trial. This
guideline has always been followed.
We are proud in saying that we have
been associated with many important
clinical trials related to coronary
artery disease, stroke, Alzheimer’s
demen tia, parkinsonism, and asthma,
lead ing to many publications and
sub sequent approval of a few new
mole cules or formulation by licensing
authorities in India, the USA, and
other countries. A prime example was
pub lished in The Lancet,3 and WHO
and the Government of India have
acknowledged the role of this vaccine
in making India polio free for the past
year, for the fi rst time in the history of
the nation.
We declare that we have no confl icts of interest.
*Apoorva Pauranik, Anil Bharani,
Salil Bhargava, Ashok Bajpai,
Hemant Jain, Pushpa Verma
apauranik@gmail.com
MGM Medical College, Indore, Madhya Pradesh
452001, India
1 Yee A. Regulation failing to keep up with
India’s trials boom. Lancet 2012; 379: 397–98.
2 Yuji K, Narimatsu H, Tanimoto T, Komatsu T,
Kami M. Sharing information on adverse
events. Lancet 2011; 377: 1654.
3 Sutter RW, John TJJ, Jain H, et al.
Immunogenicity of bivalent types 1 and 3 oral
poliovirus vaccine: a randomised, double-blind,
controlled trial. Lancet 2020; 376: 1682–88.
fi ne is re garded as an improper
procedure; the World Report did not
directly link the penalty to ethical
violations. Activists claim that Hindi
translations of consent forms were far
shorter than the English versions and
were not exact.
Pauranik and colleagues state that
there is no restriction in the Indian
Council of Medical Research guidelines
on principal investigators also being
members of ethics committees. But
Clinical Trials Registry India (CTRI)
itself has raised concerns about
strength ening ethics committees
and called for investigators and
committee mem bers to declare
confl icts of interest.
I phoned and emailed CTRI and the
Ministry of Health multiple times, but
never received a reply. If The Lancet
does a follow-up story on clinical
trials, we will be sure to contact
Pauranik and colleagues.
I declare that I have no confl icts of interest.
Amy Yee
amyyee2006@gmail.com
A 9/8 Vasant Vihar, New Delhi 110057, India
Author’s reply
Apoorva Pauranik and colleagues’
points are well taken. However, it is a
fact that activists have made formal
allegations of ethical violations and
fi led com plaints with the Indian
Supreme Court and other agencies.
The Court will decide how to proceed,
and whether clinical trials were legal
and ethical.
My World Report acknowledged
that patients’ deaths were not
found to be linked to the trials. It
also acknow ledged that the money
received by six doctors was to run
clinical trials. But large amounts of
money are clearly involved. A “trivial
techn icality” relating to the Rs5000
Pregnancy should not
rule out FDG PET/CT
for women with cancer
In the excellent Series papers about
the management of pregnant
women with gynaecological and
haemato logical cancers (Feb 11,
pp 558 and 580)1,2 the authors
discourage the use of fl uorine-18-
labelled fl uorodeoxyglucose (FDG)
PET/CT during pregnancy, because
of the potential risks associated
with radiation exposure to the fetus.
These recommendations were partly
inspired by the fetal dosimetric
measurements in pregnant women
we previously published,3 and partly
by data from monkey models.
It is my contention that these
data do not justify such strong
recommendations.
First, the measured absorbed
doses we reported (3·3–4·0×10–
mGy/MBq)3 are actually higher
than current dosimetric standards
(about 2·0×10– mGy/MBq), but
our measurements were obtained
from women in the fi rst weeks
of pregnancy. The fi rst trimester
is characterised by rapid cellular
proliferation, which leads to a
higher glucose consumption and
consequently a high absorbed dose
of FDG. Indeed, more recent data
from women at a later stage of
pregnancy show much lower fetal
FDG uptake, and the absorbed dose
is about 1·0×10– mGy/MBq or less.4
Second, dosimetry extrapolations
from monkeys should be taken with
extreme caution. Data from monkeys
might not be a good dosimetric
model for man, since they often
signifi cantly and unpredictably
overestimate human values.5 Finally,
it should not be forgotten that, for
the range of doses delivered by a
PET/CT examination, especially when
appropriate measures are taken to
minimise the dose, there are no clearly
proven health eff ects on the fetus.
Therefore, when medically indicated,
FDG PET should not be avoided,
since the benefi t for the mother is
likely to outweigh the very small fetal
radiation risk.
I declare that I have no confl icts of interest.
Paolo Zanotti-Fregonara
fregonara@hotmail.com
CNRS UMR 5287, INCIA, Université de Bordeaux,
33076 Bordeaux, France
1 Morice P, Uzan C, Gouy S, Verschraegen C,
Haie-Meder C. Gynaecological cancers in
pregnancy. Lancet 2012; 379: 558–69.
2 Brenner B, Avivi I, Lishner M. Haematological
cancers in pregnancy. Lancet 2012;
379: 580–87.
3 Zanotti-Fregonara P, Jan S, Taieb D, et al.
Absorbed F-18-FDG dose to the fetus during
early pregnancy. J Nucl Med 2010; 51: 803–05.
4 Takalkar AM, Khandelwal A, Lokitz S, Lilien DL,
Stabin MG. (18)F-FDG PET in pregnancy and
fetal radiation dose estimates. J Nucl Med 2011;
52: 1035–40.
5 Zanotti-Fregonara P, Innis RB. Suggested
pathway to assess radiation safety of (11)
C-labeled PET tracers for fi rst-in-human
studies. Eur J Nucl Med Mol Imaging 2012;
39: 544–47.
