[Ip-health] Drug Devt for Maternal Health Cannot be Left to the Whims of the Market

[Sarah Rimmington]

http://medicine.plosjournals.org/perlserv/?request=3Dget-document&doi=3D10.=
1371/journal.pmed.0050140
EDITORIAL

Drug Development for Maternal Health Cannot Be Left to the Whims of the
Market
The PLoS Medicine Editors
S Med 5(6): e140 doi:10.1371/journal.pmed.0050140
Published: June 24, 2008
The PLoS Medicine Editors are Virginia Barbour, Jocalyn Clark, Larry
Peiperl, Emma Veitch, Mai Wong, and Gavin Yamey.
E-mail: medicine_editors@plos.org

In an essay published in this month's PLoS Medicine, Nicholas White and
colleagues [1] lament that an insufficient understanding of even
well-established drugs has led to a lack of effective treatments in
pregnancy. They conclude that =93we do not know how best to treat most
tropical infectious diseases in pregnancy=94=97an alarming and shameful
situation=97and lay out causes of this ignorance. For example, concern
about teratogenicity has led to the exclusion of pregnant women from
clinical trials regardless of their stage of pregnancy, resulting in a
crucial lack of evidence even in late pregnancy, when teratogenicity is
not a concern. Gaps in the evidence on pharmacokinetics of some
antimalarial drugs have often led to under-dosing of pregnant women, and
in some cases the erroneous conclusion that such drugs are not effective
in pregnancy. The authors note that =93=91better safe than sorry=92 is the
mantra of our risk-averse age.=94 But since severe malaria has a mortality
approaching 50% in late pregnancy, we concur with the authors that this
mantra has actually produced harm.

But if the situation is bad for tropical diseases in pregnancy, the lack
of new therapies can only be considered dire for diseases that result
from pregnancy itself. In a policy paper published in January of this
year, Nicholas Fisk and Rifat Atun [2] concluded that =93the market has
failed pregnant women.=94 Their analysis of the drug pipeline for
obstetric disease between 1980 and 2007 found just 17 new drugs
undergoing evaluation between the preclinical and preregistration
phases. This number compares with 660 new drugs for cardiovascular
diseases and 34 for amyotrophic lateral sclerosis=97a rare disease
affecting two to five per 100,000 people. Even worse, of these 17
obstetric drugs, only one represents a new class of drug.

Further, many maternal deaths are due to potentially avoidable
non-obstetric causes, as highlighted by Clara Men=E9ndez and colleagues,
who analyzed deaths from a tertiary hospital in Mozambique [3] and found
that infectious diseases accounted for at least half of all maternal
deaths, =93even though effective treatment is available for the four
leading causes, HIV/AIDS, pyogenic bronchopneumonia, severe malaria, and
pyogenic meningitis.=94 For surgical treatments that are known to be
effective for obstetric complications, another PLoS Medicine article
this month [4] argues that =93the lack of basic surgical supplies and
equipment limits the delivery of surgical services=94 in sub-Saharan
Africa, for obstetrics as well as for other surgical conditions.

In developed countries, with low rates of maternal and perinatal deaths,
it is perhaps easy to be complacent about the lack of new drugs for
pregnancy and the perinatal period, but globally the situation is
urgent. According to the World Health Organization, there were more than
half a million maternal deaths in 2005 and over 6 million child deaths
in the perinatal and neonatal periods [5]. Most of these deaths are in
low-income countries=97a huge, and potentially avoidable, loss of life.
Appropriately, therefore, maternal and child health are part of the
United Nations Millennium Development Goals, with specific goals between
1990 and 2015 to reduce the under-five mortality rate by two-thirds and
the maternal mortality ratio [6] by three-quarters. Unfortunately, 18
years into the program, it seems unlikely that these goals will be met.

No one would suggest that improving the health of pregnant women and
their infants is easy. For millions of women, even the most basic
determinants of maternal and child health are still lacking: access to
basic health care and nutrition, autonomy over reproductive choices, and
freedom from violence and poverty. When it comes to drug development,
however, innovations that work for other areas of health care simply do
not suffice for maternal and infant health, and new ways of thinking are
needed. As Fisk and Atun argue, the current business model of the
pharmaceutical industry provides no real incentive but rather, because
of potential litigation in developed countries, confers strong
disincentives to produce novel drugs for pregnant women.

For pregnancy-related disorders, the development of drugs is perhaps
further hindered by issues that rarely arise in other conditions.
Although childbirth remains hazardous in all countries, there is an
increasing expectation in developed countries that nowadays birth should
be a =93natural=94 event for both mother and child and that medical
interventions are to be discouraged. Such expectations make doing
clinical trials uniquely difficult when any suggestion of risk appears
unacceptable. A qualitative study [7] of participants in the ORACLE
trial of antibiotics in women presenting with preterm rupture of
membranes, for example, concluded that =93the main motivation for trial
participation was the possibility of an improved outcome for the baby.
The second and less prominent motivation was the opportunity to help
others, but this was conditional on there being no risks associated with
trial participation.=94 This expectation of no risks is unrealistic and
was surely not what was explained to the participants; nevertheless, it
was what the women themselves believed and expected. So while women in
less developed countries urgently need more effective interventions in
pregnancy, it may be increasingly difficult to test such drugs in ways
that are acceptable to pregnant women, at least in the developed world.
The market-driven pharmaceutical model has little incentive to resolve
the conflict of providing the safety that women expect from trials,
while at the same time accepting liability and providing compensation in
cases when testing does, as it inevitably will, cause harm.

What's the answer then? The issue of the market failing to develop
necessary drugs is of course not a new one. In 2004, Tim Hubbard and
James Love [8] argued that reliance on intellectual property rights to
finance research and development in the pharmaceutical industry was both
driving up drug prices and hindering essential drug development.
Recognizing this hindrance, in 2003 five public sector organizations
teamed up with M=E9decins Sans Fronti=E8res and the Special Programme for
Research and Training in Tropical Diseases to launch the Drugs for
Neglected Diseases Initiative (DNDI; http://www.dndi.org/). This drug
development project does not prioritize maximum profitability over
medical need. Instead it adopts a =93needs-driven=94 portfolio-based
approach that facilitates basic science, preclinical, and clinical
research on targeted diseases. Fisk and Atun present ways in which such
=93push=94 and =93pull=94 mechanisms can provide solutions. An example of a=
 push
mechanism is DNDI's dedicated financial support to research networks for
developing drugs for specific indications; pull mechanisms include an
advanced market commitment aimed at creating a market for a future drug.
These mechanisms have been successfully applied thus far for malaria,
AIDS, tuberculosis, and neglected tropical diseases and might be applied
to maternal health.

Fisk and Atun go on to urge that not-for-profit options be carefully
explored and suggest that new initiatives be put in place to encourage
the testing and collection of data on old and new drugs, especially for
the most life-threatening conditions in pregnancy. One such mechanism is
noted by White and colleagues and involves the systematic collection of
data via pregnancy registries; an essential but expensive long-term
investment that would, like other long-term initiatives, be unlikely to
find support in the current business environment of the pharmaceutical
industry. A key part of any mechanism would be the need to specifically
accept liability when harm occurs. And, as an aside, the publishing
industry has a part to play too. It is essential that the results,
especially harms, generated by these initiatives be made widely
available. Open access to all such data is not a luxury, and should be
ensured by publishers.

The time has come to accept that the development of drugs for maternal
health cannot be constrained by market-driven needs. There is no lack of
ideas for addressing this issue; what's needed is political will.
References

1. White NJ, McGready RM, Nosten FH (2008) New medicines for tropical
diseases in pregnancy: Catch-22. PLoS Med 5: e133.
doi:10.1371/journal.pmed.0050133. Find this article online
2. Fisk NM, Atun R (2008) Market failure and the poverty of new drugs in
maternal health. PLoS Med 5: e22. doi:10.1371/journal.pmed.0050022. Find
this article online
3. Men=E9ndez C, Romagosa C, Ismail MR, Carrilho C, Saute F, et al. (2008)
An autopsy study of maternal mortality in Mozambique: The contribution
of infectious diseases. PLoS Med 5: e44.
doi:10.1371/journal.pmed.0050044. Find this article online
4. Ozgediz D, Riviello R (2008) The =93other=94 neglected diseases in globa=
l
public health: Surgical conditions in sub-Saharan Africa. PLoS Med 5:
e121. doi:10.1371/journal.pmed.0050121. Find this article online
5. World Health Organization (2007) Maternal mortality in 2005:
Estimates developed by WHO, UNICEF, UNFPA and The World Bank. Available:
http://www.who.int/reproductivehealth/publications/maternal_mortality_2005/=
mme_2005.pdf.
Accessed 22 May 2008.
6. United Nations (2008) The UN Millennium Development Goals. Available:
http://www.un.org/millenniumgoals/. Accessed 22 May 2008.
7. Kenyon S, Dixon-Woods M, Jackson CJ, Windridge K, Pitchforth E (2006)
Participating in a trial in a critical situation: A qualitative study in
pregnancy. Qual Saf Health Care 15: 98=96101 doi:10.1136/qshc.2005.015636.
Find this article online
8. Hubbard T, Love J (2004) A new trade framework for global healthcare
R&D. PLoS Biol 2: e52. doi:10.1371/journal.pbio.0020052. Find this
article online


Citation: The PLoS Medicine Editors (2008) Drug Development for Maternal
Health Cannot Be Left to the Whims of the Market. PLo

Copyright: =A9 2008 The PLoS Medicine Editors. This is an open-access
article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction
in any medium, provided the original author and source are credited.

--
Sarah Rimmington
Attorney
Essential Action, Access to Medicines Project
Washington, DC
Tel: (202) 387-8030
Cell: (202) 422-2687
www.essentialaction.org/access/