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Press releases Saturday 15 September 2007

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(1) Taking anti-obesity drugs results in only 'modest’ weight loss
(2) Should the UK lower the age for prostate cancer detection?
(3) Low standards of child well-being linked to greater income inequality
(4) Some drug studies more likely to have favourable conclusions

(1) Taking anti-obesity drugs results in only 'modest’ weight loss
(Long term pharmacotherapy for obesity and overweight: updated meta-analysis)
BMJ Online First

(Editorial: Orlistat over the counter)
BMJ Online First

Children could have their cholesterol levels tested at about 15 months of age to prevent heart disease later in life, say doctors in a study published on bmj.com today.

Patients taking anti-obesity drugs will only see "modest" weight loss and many will remain significantly obese or overweight, according to a study published on bmj.com today.

The study, which looked at the long-term effectiveness of anti-obesity medications, found that three drugs recommended for long-term use - orlistat, sibutramine and rimonabant, reduced weight by less than 5kg (11 pounds). This equated to a loss of less than 5% of total body weight. Guidelines from the National Institute for Clinical Excellence recommend stopping the use of anti-obesity drugs if 5% of total body weight is not lost after three months.

While making changes to lifestyle and diet are recommended as the initial treatment for obesity, the use of anti-obesity drugs is common. It’s estimated that in 2005 global sales of anti-obesity drugs reached $1.2billion. Current UK guidelines recommend using drug therapy in addition to making lifestyle changes if a patient has a body mass index of greater than 30.

The Canadian researchers reviewed the evidence from thirty placebo-controlled trials where adults took anti-obesity drugs for a year or longer. The mean weight of the volunteers in all of the trials was 100kg (15.7 stone). The mean body mass index levels were 35 - 36.

Professor Raj Padwal and colleagues found orlistat reduced weight by 2.9kg, sibutramine by 4.2kg and rimonabant by 4.7kg. They also found that patients taking the weight loss pills were significantly more likely to achieve 5 - 10% weight loss, compared to those who took the placebo.

The health benefits associated with taking the drugs varied. For example, orlistat reduced the incidence of diabetes in one trial and all three drugs lowered patients’ levels of certain types of cholesterol. Adverse effects were recorded with all three drugs, in particular, rimonabant increased the risk of mood disorders such as depression or anxiety. The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills. They recommend that trials looking at this should be carried out in the future.

The authors also noted that there were high drop-out levels in all the trials. On average 30 - 40% of patients failed to complete the trial. They say this suggests that a failure to properly adhere to the treatment could be a major factor limiting the effectiveness of anti-obesity drug therapy.

In an accompanying editorial, Professor Gareth Williams warns of the potential damage to society if anti-obesity drugs are licensed to be sold without prescription. This already happens in the United States, and as Glaxo Smith Kline (GSK) has applied to sell orlistat over the counter throughout Europe, it could happen here. He warns:

"Selling anti-obesity drugs over the counter will perpetuate the myth that obesity can be fixed simply by popping a pill and could further undermine the efforts to promote healthy living, which is the only long term escape from obesity."

Contact:
Assistant Professor, Raj Padwal, University of Alberta, Canada
Email: rpadwal@ualberta.ca  
Editorial: Professor Gareth Williams, University of Bristol, UK
Email: gareth.williams@bristol.ac.uk  

(2) Should the UK lower the age for prostate cancer detection?
(Prostate cancer detection in an unselected young population: experience of the ProtecT study)
BMJ Online First

(Editorial: Screening for prostate cancer in younger men)
BMJ Online First

Should the UK lower the age for prostate cancer detection in line with the USA?

Prostate cancer screening occurs in many countries ahead of evidence from ongoing trials. In many countries, early detection (including the UK, when practised), and opportunistic screening commences at 50 years, but a lower age limit has recently been adopted in the USA based on two studies that found elevated prostate specific antigen (PSA) levels in men in their 40s was associated with subsequent prostate cancer.

So a team of UK researchers set out to investigate the feasibility of prostate cancer testing, disease prevalence and characteristics in a random group of younger men. Their findings are published on bmj.com today.

The study involved 473 men aged 45-49 years randomly selected from eight general practices in one UK city.

Of 442 men (34%) who agreed to PSA testing, 54 (12%) had an elevated PSA result. These men were invited for further testing (an ultrasound-guided prostate biopsy, a repeat PSA test, and a digital rectal examination).

Ten prostate cancers were detected (a 2.3% detection rate, similar to that in older men). The five men whose tumours were potentially risky to health agreed to have one of three treatment options (radiotherapy, surgery, or active monitoring).

This study shows that men younger than 50 years will accept prostate cancer testing, but at a much lower rate than older men, say the authors, so if screening were introduced, greater efforts would be needed to maximize uptake in this age group.

If the UK male population aged 45-49 years (2,236,000) were to undergo PSA screening they estimate that 272,905 men would have a raised PSA and of these 51,449 would have prostate cancer.

Some of these cancers may benefit from treatment, they say, but this has to be set against the likely distress caused to the 221,456 men with negative biopsy results and the risks of over-treatment and associated side-effects to those diagnosed with cancer.

This study will inform the debate about PSA thresholds and age limits only if prostate cancer screening is proven to be effective in ongoing trials, they conclude.

Until the results from ongoing trials are available, policy should advocate informed discussion between clinicians and patients about the benefits, potential harms, and limitations of prostate cancer screening, says an accompanying editorial.

Contacts:
Professor Freddie Hamdy, Head of Urology and Oncology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, UK  
Email: f.c.hamdy@sheffield.ac.uk 

(3) Low standards of child well-being linked to greater income inequality
(Child Well-Being and Income Inequality: An Ecological Study of Rich Societies)
BMJ Online First

(Editorial: Child Wellbeing and inequalities in rich countries)
BMJ Online First

Improvements in child wellbeing in rich countries might depend more on reductions in income inequality rather than further economic growth, according to a study published today on bmj.com.

Poorer children fare less well than richer ones in each society. But a recent UNICEF report detailing 40 indicators of child wellbeing, said children in the UK and the USA fared worse than in any of the other rich countries. The new research examines whether the damage is done by being poor, or by being poorer than others.

To answer this question, the authors examined whether measures of child wellbeing were most closely related to average income (material living standards) or to the scale of income differences (inequality) in each society.

The authors studied these relationships in two different settings: among 23 rich countries, and then, independently, among the 50 states of the USA (and District of Columbia).

Among the 23 rich countries, the UNICEF index of child wellbeing (covering material wellbeing, health and safety, educational wellbeing, family and peer relationships, unhealthy and risky behaviours, and subjective wellbeing) was unrelated to average income, but was strongly related to the size of the income differences between rich and poor within each country.

Findings were similar among the 50 states of the USA. Data were analysed for teenage births, juvenile homicides, infant mortality, low birth weight, educational performance, high school drop-out rate, the proportion of children overweight, and mental health problems. All were more strongly related to the scale of income inequality in each state than to its average income.

The authors used data from various sources, including the United Nations, Organisation for Economic Co-Operation and Development (OECD), UNICEF, World Bank, US Census Bureau, and US National Centre for Health Statistics.

Among the 50 states of the USA and among affluent countries, the results suggest that children’s wellbeing is not higher, either among the richest of the 50 US states, or among the richest of the affluent countries. It is instead, significantly better in those countries and states in which income differences are smaller.

Commenting in an accompanying BMJ editorial, other researchers state that "We know enough to say that inequalities affect child wellbeing and that relative poverty kills as effectively as any disease," They believe that we need to get better at identifying the programmes that work and much better at getting governments to invest in the wellbeing of children.

Contacts:
Dr Kate Pickett, Senior Lecturer, Department of Health Sciences, University of York, UK  
Email: KP6@York.ac.uk 
or
Richard Wilkinson, Professor of Social Epidemiology, Division of Epidemiology and Public Health, University of Nottingham Medical School, QMC, Nottingham, UK 
Email: Richard.Wilkinson@nottingham.ac.uk 

(4) Some drug studies more likely to have favourable conclusions
(Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort)
BMJ Online First

(Editorial: Influence of pharmaceutical funding on the conclusions of meta-analyses)
BMJ Online First

Previous work has shown that, when a drug study was funded by the company that made that drug, the results might be biased in favour of that drug because the methods or analyses were manipulated.

New research published on bmj.com today shows that, for blood pressure drugs, studies are now much less likely to have biased results but still tend to have overly positive conclusions favouring the company's products.

The authors call on editors and peer reviewers to scrutinise the conclusions of these studies to ensure that they contain an unbiased interpretation of the results.

Meta-analyses represent the highest level of research evidence in the hierarchy of study types. They pool data from multiple studies to provide summary statistics on the effectiveness of a given treatment. They have a great deal of influence on patient care and healthcare policy and drug companies have started to reference meta-analyses in their advertisements.

Previous studies have shown that randomised controlled trials with financial ties to single drug companies are more likely to have results and conclusions that favour the sponsor’s products, and a recent study suggests that the same holds true for meta-analyses.

So researchers in the US set out to determine whether financial ties with single drug companies are associated with favourable results or conclusions in meta-analyses on blood pressure lowering (antihypertensive) therapies.

A total of 124 meta-analyses were included in the study, 49 (40%) of which had single drug company financial ties. Differences in study design and quality were measured.

Meta-analyses with single drug company financial ties were not associated with favourable results but were significantly more likely to have favourable conclusions, even when differences in study quality were taken into account.

In fact, the data show that studies funded by a single drug company have a 55% rate of favourable results that is transformed into a 92% rate for favourable conclusions, representing a 37% gap. The gap shrinks to 21% (57% to 79%) when two or more drug companies provide support. Yet the gap vanishes entirely for studies done by non-profit institutions alone or even in conjunction with drug companies.

These findings suggest a disconnect between the data that underlie the results and the interpretation or "spin" of these data that constitutes the conclusions, say the authors.

The findings also expose a failure of peer review, add the authors, and should act as a wake-up call to editors and peer reviewers, as well as to policy-makers, meta-analysts, and readers. All of these groups should closely scrutinise the conclusions of meta-analyses to ensure that they contain an unbiased interpretation of results, they conclude.

The clear inference from this study is that impartial studies are more reliable, say researchers in an accompanying editorial. However, rather than imposing legal restrictions on drug company funding or participation in these studies, they suggest that doctors should be warned to be cautious in interpreting the conclusions of studies.

Contacts:
Veronica Yank, Clinical Instructor, Stanford University, California, USA 
Email: veronica.yank@gmail.com 

Editorial: Richard Epstein, Professor of Law, University of Chicago Law School, Chicago, USA  
Email: repstein@uchicago.edu 

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