From BMJ. See letter at end. B'adant
RISKS OF HRT COULD HAVE BEEN REVEALED MUCH EARLIER
(Synthesising licensing data to assess drug safety) bmj.com518Open ↗
The risks of hormone replacement therapy would have been revealed much earlier if better use had
been made of existing evidence. As such, women have been needlessly exposed to an INCREASED RISK OF
HEART DISEASE argue researchers in this week's BMJ.
The large US Women's Health Initiative trial was stopped prematurely in 2002 after showing an
increased risk of cardiovascular events from combined hormone replacement therapy.
However, well before the Women's Health Initiative trial was published, the authors analysed 23
small trials of hormone replacement therapies and found that they were not as protective as the
observational data had shown. Many of these trials were done by pharmaceutical companies to obtain
drug licences and were not publicly available.
When they published their findings in 1997, they were ridiculed. But extra data from six further
studies confirmed their concerns. High Court dispensation was required to access these trials.
If trials done by pharmaceutical companies for licensing purposes had to include adequate data on
harms and ineffectiveness, we could learn much more quickly what we need to know about new drugs,
say the authors.
Regulators should require drug manufacturers to record adverse events and make the results public,
they conclude.
Contact:
Klim McPherson, Visiting Professor in Public Health Epidemiology, Nuffield Department of Obstetrics
and Gynaecology, Churchill Hospital, Oxford, UK Email: klim.mcpherson@obstetrics-
gynaecology.oxford.ac.uk
AND
The following BMJ Rapid Response from Hazel Thornton, Honorary Visiting Fellow, Department of Health
Sciences, University of Leicester "Saionara", 31 Regent Street, Rowhedge, Colchester.
"Many excellent notions or experiments, by sober and honest men, are suppressed." Robert Boyle. 1661
Little has changed, it seems.[1] This report of hidden, unpublished drug company data about HRT is
depressingly similar to the SEROXAT anti- depressant drug scandal, where GlaxoSmithKline "managed"
(i.e. held back) data from clinical trials internally within the company "in order to minimise any
potential negative commercial impact." [2]
Public exposure of this scandal on the BBCC "Panorama" programme was made possible by researchers
working closely together with patients and public. The researchers` report [3] also compared adverse
drug reaction reports from professionals with those of users. Analysis of professional reports was
made possible through negotiated access to `Yellow Card` reports from the Medicine and Healthcare
Products Agency and Committee on Safety of Medicines: probably the first such analysis of the
scheme. The users` analysis was from 1374 e-mails sent in response to the "Panorama" programme. The
programme also received 67,000 calls.
This successful exposure demonstrated the important active role that public and patients can play in
partnership with professional researchers in producing evidence about a treatment`s harms and
benefits. Evidence is incomplete unless effects on quality of life are included. It is time clinician-
researchers became equally alert to the motivations of drug companies and the pernicious effects of
conflicting interests.
Over a decade ago we were told that under-reporting of research is unethical and constitutes
scientific misconduct. [4] For too long, obtaining evidence in randomised controlled trials about
side-effects was deemed an optional extra. Even when included in a trial protocol, data are not
always comprehensively gathered or reported. [5] This raises questions about the degree of open-ness
in clinician/pharmaceutical research partnerships.
[1] Klim McPherson, Elina Hemminki. Synthesising licensing data to assess drug safety. BMJ 2004;
328:518-20
[2] bmj.com UK Health News. Company `held back` data on Seroxat for children. 3rd February 2004.
Source: The Guardian.
[3] Charles Medawar, Andrew Herxheimer. A comparison of adverse drug reaction reports from
professionals and users, relating to risk of dependence and suicidal behaviour. International
Journal of Risk and Safety of Medicine. 2003/4; 16:5-19
[4] Chalmers I. Under-reporting research is scientific misconduct. JAMA 1990; 263:1405-1408
[5] Hazel Thornton. Questions about anastrozole for early breast cancer. Lancet 2002;360:1890
Competing interests: None declared