[e-drug] Compensation for diethylstilbestrol (DES) injury

["E-Drug" <e-drug@healthnet.org>]

E-DRUG: Compensation for diethylstilbestrol (DES) injury
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[Important Lancet comment on one of the biggest drug scandals of the last
century. www.thelancet.com Vol 369 January 20, 2007; copied as fair use. WB]

Society’s long struggle to compensate adequately the victims of drug injury
seems to have progressed a little further as a result of two recent
developments in the Netherlands and France about the long-running
controversy of diethylstilbestrol.

The story of diethylstilbestrol is well known.1,2 Developed in the UK in
1938 as an unpatented lowcost synthetic oestrogen,3 the drug was used widely
in pregnant women on the basis of an ill-founded theory that it could
prevent miscarriage by countering possible hormonal defi ciency.4 However,
the many companies that seized on its commercial potential sometimes claimed
much more: within a decade of diethylstilbestrol’s introduction, it was
promoted as a necessary adjunct to every pregnancy, and as capable of
developing “bigger and stronger babies”,5 despite a lack of evidence and in
the face of early warnings that the drug was carcinogenic.

Between the late 1940s and the mid 1970s, many expectant mothers routinely
received diethylstilbestrol. In the USA, about 5–10 million mothers and
their children were exposed to diethylstilbestrol; in the Netherlands, this
figure was about 440 000.

Only towards the end of this period did it become clear that the drug was
not only ineffective (as had long been suspected6), but also that it was
harmful. Cases of vaginal tumours, cervical tumours, and reproductive
difficulties accumulated in daughters of women who were given
diethylstilbestrol during pregnancy.

Moreover, treated mothers had a 30–40% increased excess risk of breast
cancer,7 and infertility and genital defects were recorded in sons of
mothers who received the drug. By the late 1970s, the use of
diethylstilbestrol in pregnancy had been abandoned worldwide; however, the
damage was done.

Of the countries involved most, the Netherlands initially seemed to address
the issue of compensation in the most practical way. Initial claims against
manufacturers by so-called diethylstilbestrol daughters stumbled on an
inability to prove which manufacturer’s product their mothers had taken.
However, the High Court of the Netherlands ruled that a claimant could sue
any firm known to have been supplying the drug at the relevant time. 

After this ruling, the manufacturers, their insurers, and a group
representing those exposed to diethylstilbestrol and their advisers formed a
settlement. In 2005, a new Law on Collective Settlements for Mass Injury
made such an agreement binding on all parties concerned, replacing
individual claims before the courts. 

Furthermore, on June 1, 2006, the Amsterdam Court validated the
diethylstilbestrol agreement.8 After 16 years of negotiations, claims can be
assessed and the first payments made. The diethylstilbestrol agreement is
based financially on Euro 38 million, made available by the pharmaceutical
firms and their insurers. Individuals are eligible for compensation if they
have a disorder that can be attributed reasonably to the effects of
diethylstilbestrol, provided that such treatment was given before 1977 to
their mother during pregnancy. The amount of compensation set for every type
of case is intended to reflect the severity of the disorder and the
probability of a causal association with diethylstilbestrol.9

However admirable the intentions, is the sum available adequate to provide
relief in a country where 440 000 people are thought to have been exposed to
diethylstilbestrol and where the overall incidence of injury remains
unknown? 

Nearly 35 years after the first effects of diethylstilbestrol exposure in
utero were reported, new side-effects of this drug continue to emerge. In
August, 2006, two studies10,11 reported that daughters exposed in utero have
a 2–3-times increased risk of developing breast cancer and are 50% more
likely to have natural menopause at an early age than are other women. 

What should we think of awards set at €550 for severe cervical or vaginal
dysplasia, €1450 for two or more miscarriages, and €4550 for metastatic
breast cancer? Such figures are less than the compensation reported from
France in October, 2006, where the court of Nanterre awarded €344 000 to the
family of a young woman who died of diethylstilbestrol-related cancer.12 Is
it not remarkable that when a woman in the Netherlands has died of
metastasised breast cancer, no compensation will be payable? 

The current agreement has no provisions to compensate daughters who were
exposed to diethylstilbestrol in utero and who developed breast cancer
(irrespective of survival) because such a risk of breast cancer was
suspected, but not scientifically established, when the agreement was
reached. Moreover, what happens if new scientific evidence confirms a causal
link between diethylstilbestrol and other types of second-generation or
third-generation injury that are not considered in the current compensation
agreement, thus spreading the funds more thinly? 

The Netherlands’ victims of diethylstilbestrol might have accepted an
inadequate financial settlement too readily.

*Ellen F M ‘t Hoen, M N Graham Dukes
Amsterdam School for Social Science Research, University of Amsterdam, 1012
CX Amsterdam, Netherlands (EFM‘tH); and University of Oslo, Norway (MNGD)

ellen.t.hoen@orange.fr

We declare that we have no conflict of interest.

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1 Buitendijk S. DES—the time bomb drug. Report of the 13th European
Symposium on Clinical Pharmacological Evaluation in Drug Control.
Copenhagen: World Health Organization, 1984.

2 Dukes MNG. The law and ethics of the pharmaceutical industry. Amsterdam:
Elsevier, 2005.

3 Dodds EC, Goldberg L, Lawson W, Robinson R. Estrogenic activity of certain
synthetic compounds. Nature 1938; 141: 247–48.

4 Smith OW. Diethylstilbestrol in the prevention and treatment of
complications of pregnancy. Am J Obstet Gynecol 1948; 56: 821–34.

5 Grant Chemical Company, Inc. Advertisement. Am J Obstet Gynecol 1957
(available from EFM‘tH).

6 Dieckman WJ, Davies ME, Rynkiewicz LM, Pottinger RE. Does the
administration of diethylstilbestrol during pregnancy have therapeutic
value? Am J Obstet Gynecol 1953; 66: 1062.

7 US National Cancer Institute. DES research update 1999: current knowledge,
future directions. http://women.cancer.gov/planning/
previous/DES/chapter3.html (accessed Nov 20, 2006).

8 Court of Amsterdam, Civil Division. LJN: AX6440, case number R05/1743,
judgement of June 1, 2006. http://www.rechtspraak.nl/
gerechten/gerechtshoven/amsterdam (accessed Nov 20, 2006).

9 DES-Rapport. Report on the rules governing compensation for injury
attributed to DES. July 5, 2005: http://www.desfonds.nl/fi les/
DESrapport.pdf (accessed Nov 20, 2006).

10 Palmer JR, Wise LA, Hatch EE, et al. Prenatal diethylstilbestrol exposure
and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2006; 15:
1509–14.

11 Hatch EE, Troisi R, Wise LA, et al. Age at natural menopause in women
exposed to diethylstilbestrol in utero. Am J Epidemiol 2006; 164: 682–88.

12 Agence France Presse. Distilbène: 344.000 euros pour la famille d’une
jeune femme morte du cancer. Oct 23, 2006: http://fr.news.yahoo.
com/13102006/202/distilbene-344-000-euros-pour-la-famille-d-unejeune. html
(accessed Nov 20, 2006).