Press releases Monday 10 January to Friday 14 January 2011

Please remember to credit the BMJ as source when publicising an article and to tell your readers that they can read its full text on the journal's website (http://www.bmj.com).

• (1) Revealed: Secret businesses which aimed to exploit vaccine fears
• (2) Common painkillers linked to increased risk of heart problems
• (3) DNA blood test can cut invasive testing for Down's syndrome by 98%
• (4) Call for full access to Tamiflu trial data to allow for independent scrutiny
• (5) Is 'breast only' for first six months best?
• (6) Taking more steps every day can help ward off diabetes

(1) Revealed: Secret businesses which aimed to exploit vaccine fears - "MMR doctor" planned scheme to make millions from his health scare

(Secrets of the MMR scare: How the vaccine crisis was meant to make money)
http://www.bmj.com/cgi/doi/10.1136/bmj.c5258

Andrew Wakefield, the disgraced doctor who claimed a link between MMR and autism, planned secret businesses intended to make huge sums of money, in Britain and America, from his now-discredited allegations.

The Wakefield scheme is exposed today in the second part of a BMJ series of special reports, "Secrets of the MMR scare", by investigative journalist Brian Deer. Last week we revealed the scientific fraud behind the appearance of a link between the vaccine and autism. Now Deer follows the money.

Drawing on investigations and documents obtained under the Freedom of Information Act, the report shows how Wakefield's institution, the Royal Free Medical School in London, supported him as he sought to exploit the MMR scare for financial gain.

It reveals how Wakefield met with medical school managers to discuss a joint business even while the first child to be fully investigated in his research was still in the hospital, and how just days after publication of that research, which triggered the health crisis in 1998, he brought business associates to the Royal Free to continue negotiations.

One business, named after Wakefield's wife, intended to develop Wakefield's own "replacement" vaccines, diagnostic testing kits and other products which only stood any real chance of success if public confidence in MMR was damaged.

Documents reveal the planned shareholdings of Wakefield and his collaborators, and how much Wakefield expected to receive personally. Financial forecasts made available for the first time today show Wakefield and his associates predicting they could make up to £28 million ($43,367,082; €33,290,350) a year from the diagnostic kits alone.

"It is estimated that the initial market for the diagnostic will be litigation driven testing of patients with AE [autistic enterocolitis] from both the UK and the USA," said a 35 page "private and confidential" prospectus obtained by Deer, aimed at raising an initial £700,000 from investors. "It is estimated that by year 3, income from this testing could be about £3,300,000 rising to about £28,000,000 as diagnostic testing in support of therapeutic regimes come on stream."

Deer's investigation also reveals today that Wakefield was offered support to try to replicate his results, gained from just 12 children, with a larger validated study of up to 150 patients, but that he refused to carry out the work, claiming that his academic freedom would be jeopardised. His research claims have never been replicated.

Contacts:
Fiona Godlee, Editor in Chief, BMJ, London, UK
Email: edickinson@bmjgroup.com
Brian Deer, Journalist, London, UK
Email: mail61@briandeer.com

(2) Common painkillers linked to increased risk of heart problems

(Research: Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis)
http://www.bmj.com/cgi/doi/10.1136/bmj.c7086
(Editorial: Cardiovascular safety of NSAIDs)
http://www.bmj.com/cgi/doi/10.1136/bmj.c6618

Commonly used painkillers for treating inflammation can increase the risk of heart attacks and strokes, according to an analysis of the evidence published on bmj.com today.

The drugs include traditional non-steroidal anti-inflammatory drugs (NSAIDS) as well as new generation anti-inflammatory drugs, known as COX-2 inhibitors.

The researchers say that doctors and patients need to be aware that prescription of any anti-inflammatory drug needs to take cardiovascular risk into account.

NSAIDs have been the cornerstone of managing pain in patients with osteoarthritis and other painful conditions. In 2004, the COX-2 inhibitor rofecoxib was withdrawn from the market after a trial found that the drug increased the risk of cardiovascular disease. Since then, there has been much debate about the cardiovascular safety of COX-2 inhibitors and traditional NSAIDs, which several studies have not been able to resolve.

So researchers in Switzerland performed a comprehensive analysis of all randomised controlled trials comparing any NSAID with other NSAIDs or placebo.

They included 31 trials and 116,429 patients taking seven different drugs (naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, rofecoxib, lumiracoxib) or placebo to provide a more reliable estimate of the cardiovascular risks of these drugs than previous studies.

Overall, the number of harmful outcomes that could be compared for placebo versus treatment was low. In 29 trials there was a total of 554 heart attacks; in 26 trials there were 377 strokes, and in 28 trials there were 676 deaths. So the absolute risk of cardiovascular problems among people taking painkillers was low, but the researchers did find that, relative to placebo, the drugs carried important risks.

For instance, compared with placebo, rofecoxib and lumiracoxib were associated with twice the risk of heart attack, while ibuprofen was associated with more than three times the risk of stroke. Etoricoxib and diclofenac were associated with the highest (around four times) risk of cardiovascular death.

Naproxen appeared least harmful in terms of cardiovascular safety among the seven analysed preparations.

Although the number of cardiovascular events in the trials was low, the authors say "our study provides the best available evidence on the safety of this class of drugs." They conclude: "Although uncertainty remains, little evidence exists to suggest that any of the investigated drugs are safe in cardiovascular terms. Cardiovascular risk needs to be taken into account when prescribing any non-steroidal anti-inflammatory drug."

An accompanying editorial says these cardiovascular risks are worrying because many patients have both cardiovascular disease and musculoskeletal disease, and suggests that it is time for an evaluation of a broader range of alternatives.

Contacts:
Research: Professor Peter Juni, Head of Division, Institute of Social and Preventive Medicine, University of Bern, Switzerland
Email: juni@ispm.unibe.ch
Editorial: Wayne Ray, Professor and Director, Department of Preventive Medicine, Nashville, TN, USA
Email: wayne.ray@vanderbilt.edu

(3) DNA blood test can cut invasive testing for Down's syndrome by 98%

(Research: Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study)
http://www.bmj.com/cgi/doi/10.1136/bmj.c7401

Women in high risk pregnancies for Down's syndrome could have a DNA blood test to detect the disorder and avoid invasive procedures such as amniocentesis or chorionic villus sampling, finds a large scale study published on BMJ.com today.

The blood test could mean that 98% of invasive procedures could be avoided, say the authors. The test uses the latest DNA technology to analyse genetic components in the mother's blood that indicate whether the foetus has Down's.

Down's syndrome or trisomy 21 occurs in around 1 in 800 births and older women are at higher risk.

Women in high risk groups tend to undergo a combination of scans and hormone level tests in order to determine if they need to have an invasive test such as amniocentesis or chorionic villus sampling. The latter tests take samples of genetic material from the foetus but they carry a 1% risk of miscarriage and are therefore reserved for high risk pregnancies. Invasive testing still takes place in 3 to 5% of pregnant women in the UK.

The research team, led by Professor Dennis Lo from The Chinese University of Hong Kong, used the most up-to-date DNA technology to test the blood samples from 753 pregnant women (all were at high risk of having a baby with Down's) based in Hong Kong, the UK and the Netherlands. Eighty-six of the women were found to be carrying a foetus with Down's syndrome.

The results show that the test is highly accurate in detecting Down's syndrome in unborn babies and does not give false negative results.

The authors conclude that the blood test could be used to accurately rule out Down's syndrome among high risk pregnancies before amniocentesis or chorionic villus sampling is considered. In this way the number of women requiring invasive procedures can be reduced.

Contact:
Rossa Chiu, Li Ka Shing Institute of Health Sciences and Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong, China
Email: rossachiu@cuhk.edu.hk

(4) Call for full access to Tamiflu trial data to allow for independent scrutiny

(Analysis: Ensuring safe and effective drugs: who can do what it takes?)
http://www.bmj.com/cgi/doi/10.1136/bmj.c7258

Leading researchers today call for access to all clinical trial data (published and unpublished) to allow drugs to be independently assessed by the scientific community.

Tom Jefferson and colleagues from the Cochrane Group argue that the current system for assessing the safety and effectiveness of drugs, based on published trial data only, is "wholly inadequate" and "ethically dubious."

They propose a new approach that would allow in-depth scrutiny of the complete set of trial data for a new drug.

Their call comes after they reviewed the evidence for the antiviral drug oseltamivir (Tamiflu), and were unable to find sufficient published data to support the conclusion that oseltamivir reduces complications in healthy adults.

As a result, Roche (oseltamivir's manufacturer) publicly pledged to make full results for ten unpublished clinical trials available for scrutiny. Yet, to date, they have failed to fulfil this promise.

The Cochrane team's concern deepened after finding reports of ten serious adverse events in patients enrolled in two key manufacturer-funded trials that were not reported in journal publications arising from those trials.

Other recent cases, where the "true" effects of drugs have emerged only after all the evidence (including unpublished data) has been analysed, have further highlighted the importance of independent evaluation.

"The answer is to make the data freely available: we should accept nothing less than a full dataset," say the authors. "Before licensing a drug - and certainly before large purchase decisions are made - our governments and policy makers should ensure that all researchers can access data in sufficient detail to allow for the independent exploration and re-analysis of trials," they add.

Their proposed new approach involves compiling a complete list of drug trials (published and unpublished) and requesting full clinical study reports. It is available at http://www.editorial-unit.cochrane.org/neuraminidase-inhibitors-influenza-hta-project

They urge researchers, the public, and the media to work together to put pressure on industry to embrace the ethical responsibility to release data in the public interest. They also call on medical journals to require submission of the most detailed report available.

They conclude: "It is time the media, the Cochrane Collaboration, and any reader interested in knowing what they are prescribing or are being prescribed increase the pressure on policy makers. If you swallow a medication, you need to know how it works - for real."

Contact:
Peter Doshi, Graduate Student, Massachusetts Institute of Technology, Cambridge, MA, USA
Email: pnd@mit.edu

(5) Is 'breast only' for first six months best?

(Analysis: Six months of exclusive breast feeding: how good is the evidence?)
http://www.bmj.com/cgi/doi/10.1136/bmj.c5955

Current guidance advising mothers in the UK to exclusively breast feed for the first six months of their baby's life is being questioned by child health experts on bmj.com today.

The authors, led by Dr Mary Fewtrell, a consultant paediatrician at the UCL Institute of Child Health in London, have reviewed the evidence behind the current guidance and say the time is right to reappraise this recommendation.

The researchers stress that while they fully back exclusive breast feeding early in life, they are concerned that exclusively doing so for six months and not introducing other foods may not always be in the child's best interests.

In 2001 the World Health Organisation (WHO) made its global recommendation that infants should be exclusively breast fed for the first six months. Many western countries did not follow this recommendation but in 2003 the UK health minister announced that the UK would comply.

Fewtrell and colleagues support six months exclusive breast feeding in less developed countries where access to clean water and safe weaning foods is limited and there is a high risk of infant death and illness. However they have reservations about whether the WHO's guidance about when to introduce other foods is right for the UK.

The WHO's recommendation that mothers should breast feed exclusively for six months is largely based on a systematic review undertaken in 2000 that considered existing research in this area, say the authors. This review concluded that exclusively breast fed babies have fewer infections and that the babies experience no growth problems.

Dr Fewtrell argues that the evidence that breast milk alone provides sufficient nutrition for six months is questionable. She says there is a higher risk of iron deficiency anaemia if babies are exclusively breast fed and that there could also be a higher incidence of celiac disease and food allergies if children are not introduced to certain solid foods before six months.

The authors also fear that prolonged exclusive breast feeding may reduce the window for introducing new tastes, particularly bitter taste which may be important in the later acceptance of green leafy vegetables. This could encourage unhealthy eating in later life and lead to obesity, they say. Fewtrell and colleagues conclude that it is time to review the UK's guidance in the light of the evidence that has built up on this issue over the last ten years.

Contact:
UCL Institute of Child Health and Great Ormond Street Hospital (GOSH) press office
Email: dodmah@gosh.nhs.uk

(6) Taking more steps every day can help ward off diabetes

(Research: Association of change in daily step count over five years with insulin sensitivity and adiposity: population based cohort study)
http://www.bmj.com/cgi/doi/10.1136/bmj.c7249

Simply taking more steps every day not only helps ward off obesity but also reduces the risk of diabetes, finds a study published on bmj.com today.

While several studies have shown that physical activity reduces body mass index and insulin resistance - an early stage in the development of diabetes - this is the first study to estimate the effects of long-term changes in daily step count on insulin sensitivity.

A popular guideline is to do 10,000 steps every day, though a more recent recommendation is 3,000 steps, five days a week.

The research, by the Murdoch Childrens Research Institute, Melbourne, involved 592 middle aged adults who took part in a national study to map diabetes levels across Australia between 2000 and 2005.

At the start of the study, participants completed a detailed diet and lifestyle questionnaire and underwent a thorough health examination. They were also given a pedometer and instructed how to use it. Participants were monitored again five years later.

Other lifestyle factors, such as diet, alcohol and smoking were taken into account.

A higher daily step count over five years was associated with a lower body mass index, lower waist to hip ratio, and better insulin sensitivity.

These associations were independent of dietary energy intake and appeared to be largely due to a change in adiposity (fatness) over the five years, say the authors.

The authors estimate that, in their setting, a sedentary person who takes a very low number of daily steps but who was able to change behaviour over five years to meet the popular 10,000 daily step guideline would have a threefold improvement in insulin sensitivity compared with a similar person who increased his or her steps to meet the more recent recommendation of 3,000 steps for five days a week.

They conclude: "These findings, confirming an independent beneficial role of higher daily step count on body mass index, waist to hip ratio, and insulin sensitivity, provide further support to promote higher physical activity levels among middle aged adults."

Contact:
Eszter Vasenszky, Media and Communications Officer, Murdoch Childrens Research Institute, Melbourne, Australia
Email: eszter.vasenszky@mcri.edu.au

Emma Dickinson
Tel: +44 (0)20 7383 6529
Email: edickinson@bma.org.uk

Press Office telephone : 020 7383 6254 (Weekdays : 0900hrs - 1800hrs)
British Medical Association
BMA House, Tavistock Square, London WC1H 9JR

and from:

the EurekAlert website, run by the American Association for the Advancement of Science (http://www.eurekalert.org)
http://intranet.bmj.com/departments/dept-bmj/bmj-team-resources/web-team-resources/General_blogging_principles.doc