The contentious history of pregnancy test drugs: will science find its own path to the truth?
Jesse Olszynko-Gryn |
Last week in the House of Commons, MPs debated a government inquiry set up in 2014 “to investigate and assess evidence on children born with serious deformities due to hormone pregnancy test drugs [HPTs] taken by expectant mothers between 1953 and 1975”.
The inquiry’s Expert Working Group (EWG) of fourteen scientists chaired by a consultant gynaecologist is meeting today for the fifth time; their report is planned for next spring. The Group’s terms of reference are to focus on the scientific evidence of a possible association between the use of HPTs (the most common of which was Schering’s Primodos, also marketed in West Germany as Duogynon), and congenital anomalies, as well as what lessons “may be learned for improving existing regulatory systems”.
MPs at last week’s debate voiced concerns that the inquiry was becoming a “whitewash” and David Mowat, the Parliamentary Under-Secretary of State for Health, acknowledged that campaigners had lost confidence in the process. He accepted that this was “unsatisfactory”, but added: “in the end, science will play a big part in getting to where we need to be. The science will find its own path”.
But will it? And does the scientist-led inquiry have the right approach? MPs particularly called into question the EWG’s remit to examine “the science”, construed as uncontentious, in isolation and ahead of any investigation of the regulatory chronology. As Mowat put it:
It would be quite wrong if we conflated the possible eventual need to look at the regulatory actions that were taken, the legal liabilities and everything that goes with that, with the first step of the process, which is to establish whether the science leads us to that link.
In contrast, for Yasmin Qureshi MP, the inquiry “is not so much about the medical evidence.” Rather, the “crux” for her “is that a lot of evidence was available at the time and the regulator failed to do anything.” In both scenarios there are several ways in which historical context and expertise will be vital to the EWG’s understanding of the issue.
Alternatives at the time
There was a crucial historical dimension missing from the debate, namely, the widespread albeit unevenly distributed availability of alternatives throughout the period under consideration (1953-75). The information pack for the debate states:
At the time hormone pregnancy tests were introduced, pregnancy was usually medically diagnosed later than it is today, without chemical tests, once it was obvious that there had been two or more missed periods and a pregnant uterus could be felt. Hormone pregnancy tests were thought to allow a relatively confident diagnosis of pregnancy.
But relative to what? While it is true that modern home tests like Clearblue were not introduced until the 1980s, reliable laboratory tests for pregnancy had been available since 1929. By 1953, when HPTs were first introduced, a single lab in Edinburgh was capable of performing more than 20,000 “toad tests” on women’s urine every year and could claim a reliability of 98%. By 1967, when a short letter in Nature first alerted regulators to the possible risks of Primodos, toads had been supplanted by more convenient immunological test kits. The first home pregnancy tests, which resembled small chemistry sets, hit pharmacy shelves in 1971, earlier than most people realise and a full seven years before Schering (now Bayer) voluntarily withdrew Primodos for “commercial reasons”. Between the early 1950s and late 1970s, doctors repeatedly questioned the reliability and safety of Primodos and other HPTs, whereas non-invasive alternatives were generally regarded as harmless and approached the reliability of today’s home tests.
Crucially, however, these alternatives were more expensive (a “toad test” cost around four times as much as Primodos in 1960) and distributed unevenly outside major cities. Access also depended on an individual doctor’s willingness to go to the trouble of posting a urine specimen, ordering a lab report and communicating the result to the patient; sending her home with tablets was often easier and always cheaper. Hence, geographic variation in income levels and uneven availability of alternatives could help explain why a Sunday Times survey found that 10 out of 12 doctors in South Wales still used HPTs in 1975. The inquiry needs to reckon with this broader historical context alongside the scientific evidence and regulatory chronology.
All the available evidence?
Mowat responded to the question of whether “all the available evidence will be reviewed by the expert group” with an unqualified, emphatic “yes.” The recently unearthed masses of German evidence in the Berlin State Archive (Landesarchiv Berlin) would be, Mowat assured the House, “translated, and all the translations will be put before the group.” This is a monumental task in itself and campaigners should take heart that the inquiry is willing to marshal the resources to undertake it. But the records in question, however important they may turn out to be, are not the whole story and a somewhat different picture might take shape if the evidence base were expanded to include reports published in languages other than English and German.
For example, a 2014 government review of the evidence includes a Paris study reported in the Lancet in 1977 that shows “no definitive evidence for the teratogenicity of hormonal pregnancy tests”, but not the follow-up report – in French, from 1979 – that contrastingly shows “an excessive number of newborn babies with malformation when the mothers took certain products”, including Duogynon.
Most of all, it seems essential at this critical juncture in the inquiry for the EWG to obtain, translate and examine the scientific evidence from Sweden, Norway and Finland, the first countries to take regulatory action in 1970-71. Until that is done, the inquiry will be working with evidence mainly from the UK and Germany, where regulators dragged their heels. Reports in the medical and general press in Scandinavia seem to suggest particular concerns involving dozens of cases of hypospadias, a defect of the urethra that was also noted in the UK.
As Mowat stated of the the possible link between HPTs and adverse effects in pregnancy:
this is an international issue that has been around for 40 to 50 years. We are the only country to have set up such an inquiry, and the only one to have attempted to find a scientific route to the truth in this way.
If he is right and the inquiry is serious about finding a "scientific route to the truth", then surely the EWG should examine all the available evidence, particularly that which led to early regulatory actions in Scandinavia. The science will not, contrary to Mowat’s assertion, “find its own path”. It needs help—not only from medical and scientific experts, but also from archivists, historians, journalists, MPs, translators, and, most of all, the campaigners themselves, for whom the inquiry was set up in the first place, and who have to date done the most work in bringing new evidence to light.
Acknowledgements: My thanks go to Susanne Berghofer, Eira Bjørvik, Petter Hellström, Cyrille Jean, Solveig Jülich, Hanna Östholm and the Medical Products Agency of Sweden (Läkemdelsverket) for much assistance in locating and translating archival records and other documents in France, Norway and Sweden.Please note: Views expressed are those of the author.
The House of Commons debate referred to can be found here.