Cost-effectiveness studies are widely used to guide prescribing
policy in many countries, as part of health technology assessment
programmes. However, a new study published this week in /PLoS//
Medicine/ by Tjeerd-Pieter van Staa and colleagues suggests that
cost-effectiveness analyses based on data from randomized controlled
trials may not be realistic enough to accurately inform policy.

In the study the researchers (affiliated with the General Practice
Research Database, and London School of Hygiene & Tropical Medicine
in the UK, and Utrecht University in the Netherlands) specifically
examine the relative cost-effectiveness of two commonly used groups
of painkillers: selective cyclooxygenase-2 inhibitors (cox-2
inhibitors), versus conventional nonsteroidal anti-inflammatory drugs
(NSAIDs). One type of cox-2 inhibitor has now been withdrawn from use,
and recommendations regarding the use of others have changed as a
result of data on cardiovascular harms associated with these drugs.
The researchers collected data on the risk of upper gastrointestinal
effects associated with use of either type of drug, and calculated
the cost-effectiveness of the drugs in relation to these events using
either data from large randomized controlled trials or from routine
clinical practice using the UK General Practice Research Database.

These analyses showed that the average cost of preventing an upper
gastrointestinal effect by switching NSAIDs for a cox-2 inhibitor was
calculated at roughly US$104K, using the data from routine clinical
practice. However, the cost effectiveness was calculated as around
US$20K using randomized trial data.

The researchers suggest that in the specific scenario evaluated here,
patients in the randomized trials experienced more gastrointestinal
events than patients in routine practice, and that they used drugs
differently commonly involving higher daily doses leading to a
different estimate of cost-effectiveness. A more realistic assessment
might have led to differences in prescribing guidelines, according to
the authors. Tjeerd-Pieter van Staa says:

Real-world questions on what to prescribe to whom should consider
the varied group of patients in actual clinical practice rather than
just using data from highly selective randomized trials that have
narrow inclusion criteria.

However, one limitation of the study is that it involves an
assessment of cost-effectiveness of two specific types of
painkillers, and it isn t clear whether the observations will apply
to cost-effectiveness for other drug classes.

Funding: The authors received no specific funding for the paper. LS
is funded by a Wellcome Trust Senior Research Fellowship in Clinical
Science.

Competing Interests: TPvS and BZ: The General Practice Research
Database receives funding from the Medicines and Healthcare products
Regulatory Agency, pharmaceutical companies, universities, and
contract research organizations. TPvS and HGML: The Utrecht Institute
for Pharmaceutical Sciences at Utrecht University has received
unrestricted funding for pharmacoepidemiological research from
GlaxoSmithKline , Novo Nordisk, the private-public funded Top
Institute Pharma (http://www.tipharma.nl; includes co-funding from
universities, government, and industry), the Dutch Medicines
Evaluation Board, and the Dutch Ministry of Health. LS is funded by a
Wellcome Trust Senior Research Fellowship in Clinical Science.

Citation: van Staa T-P, Leufkens HG, Zhang B, Smeeth L (2009)
“A Comparison of Cost Effectiveness Using Data from Randomized Trials or
Actual Clinical Practice:
Selective Cox-2 Inhibitors as an Example. “
PLoS Med 6(12): e1000194.
doi:10.1371/journal.pmed.1000194

Heart disease and stroke are the leading causes of death for women worldwide, killing more than 8.6 million, more than the total number who die from malaria combined.

However, the risk for women is largely under-estimated, by both the general population and often by the medical profession itself. This is due to the fact that women usually suffer from CVD 10 years later in their life than men: the risk increases after menopause, partly because of ovarian hormone deficiency that favours hypertension, obesity and the metabolic syndrome.

In the report presented at the conference (2), Professor Stramba Badiale, MD, PhD at the Department of Rehabilitation Medicine, IRCCS Istituto Auxologico Italiano, finds that women are underrepresented in cardiovascular research in Europe. “In the 62 randomized clinical trials published between 2006 and July 2009, only 33.5% of enrolled participants were women,” he says.

This underrepresentation is particularly noticeable in the fields of cholesterol-lowering therapy, ischaemic heart disease and heart failure.

Professor Roberto Ferrari, President of the ESC says: “With regard to cardiovascular health, we do lack data for women simply because the majority of clinical trials are conducted on men. It is important to have special clinical trials conducted only on women because their cardiovascular pathology is, at least at some point during their lives, different from that of men and it is incorrect to apply data derived from studies on men to women.”

Another finding of the report that supports the conference programme is that only 50% of the clinical trials conducted in the last three years which enrolled both men and women reported the analysis of the results by gender.

Susanne Logstrup, director of the EHN, regrets that, as a result, “safety and efficacy of several drugs have been evaluated predominantly in male populations.”

Professor Stramba-Badiale is hopeful that the report and the conference will encourage new practice amongst the research community, with a systematic enrolment of women in clinical trials. “New data should improve the clinical management of CVD and, in the future, develop possible gender specific diagnostic and therapeutic strategies,” he says.

The research is part of the EuroHeart project, which aims at defining areas of policies and public health interventions which can contribute to prevent avoidable deaths and disability across Europe. It is led by the European Society of Cardiology, in partnership with the European Heart Network, and is co-funded by the European Commission Public Health Programme 2003-2008.

The ‘Red alert for women’s hearts’ conference will systematically review the place of women in all aspects of scientific literature, whether clinical trials, guidelines, medical curriculum or regulatory processes.

More than 60 awareness campaigns addressing the particular issue of women and cardiovascular diseases have been organised in the last 20 years in the 19 countries participating in WP 6 of the EuroHeart project. This is evidence that national Heart Foundations and Cardiac Societies have long been aware of the urgent need to promote the issue amongst the female population and health professionals. The results of campaigns showed an increased awareness that cardiovascular diseases are the leading cause of death for women. Despite this, gender-specific training for cardiologists is still lacking in the majority of European countries.

The objective of this conference is to create a series of recommendations for policy makers, research funding agencies and regulatory entities, at both national and EU level.

Red Alert for Women’s Hearts is also the opportunity to look at how countries address the lack of information of the population and of health professionals, by giving an overview of past campaigns and their impact, country by country.

Notes:

1. EuroHeart involves partners in 21 countries in the EU and the EEA receives co-funding from the European Commission Public Health Programme 2003-2008.

2. Research published by the ESC and the EHN in the report: Red Alert for Women’s Hearts, Women and Cardiovascular Research in Europe (November 2009).

References: The European Society of Cardiology (ESC) represents more than 62,000 cardiology professionals across Europe and the Mediterranean. Its mission is to reduce the burden of cardiovascular disease in Europe.

Source: ESC Press Office

European Society of Cardiology