A recent study in the journal Pediatrics reported that only 29% of clinical studies in children have been published. This finding reinforces previous studies that there is significant publication bias in paediatric studies. These findings are a cause for serious concern.

What is publication bias? Essentially, it is the selected publication of studies based on the results, such as only publishing studies that demonstrate a drug works while not publishing studies that demonstrate harms.

Publication bias is a serious problem in healthcare and can have a large influence on treatment decisions by only providing limited information. Researchers have demonstrated substantial publication bias in certain areas such as the antidepressant medication reboxetine.

Several initiatives have been spearheaded to help reduce publication bias. The creation of open-access journals have shifted the focus from the importance of the results (as judged by a journal editorial committee) to the methodological rigour by which the study was completed.

But more importantly has been the creation of online trial registries, such as ClinicalTrials.gov launched in 2000. These registries serve as central databases of all the current and on-going clinical studies. Registration is optional, however in 2005 the ICMJE made registration of clinical trials as a pre-requisite of publication. Although this does not represent all journals, it sent a strong message of the importance of registration.

However despite the creation of trial registries, less than half of US based National Institute of Health (i.e. government) funded trials in children were registered on ClinicalTrials.gov. Another important finding was the lack of information included on the registries. One-third of all clinical studies terminated early did not provide any information about why they were stopped. The situation was similar for suspended studies with one quarter not providing information.

Were these studies stopped because of harms? Were the investigators no longer able to recruit children to enroll? Whatever the reason the studies were stopped, this information must be made public.

Registration of all clinical studies involving children must be made mandatory. This is the only way to minimise publication bias and increase the reporting of research. This would create massive industry uproar, but is it ethical to enroll children in a clinical study without having it publicly registered? At a minimum any trial that receives government funded must be registered.

However registration of studies is only one element of the formula. What about the dissemination of the results? Less than 10% of completed studies in children had results posted and publicly available. With the low publication rates of registered studies, and the even lower rate of posting results, how much information is still missing?

Indeed progress has been made to increase the quality and transparency of clinical studies in children but more is needed. We cannot assume that because trial registries exist that they are being used. Complacency must be replaced with compliance. It seems that more often than not, the little ones have the biggest problems.

A recent letter to the editor in the Canadian Medical Association Journal (CMAJ) highlighted a potential opportunity to increase access to subscription-based journals for individuals in low and middle-income countries. It turns out that a few journals give their peer reviewers’ free journal access or a free subscription as a thank you gift for their effort.

How widespread is this policy in the medical publishing world?

Unfortunately not very. Of the 21 journal editors contacted (including CMAJ, Lancet, BMJ, JAMA, etc.), only three actually provide reviewers with free journal access. The gift ranges from a 3-month (Lancet) to a 12-month subscription (BMJ and the Journal of Intellectual & Developmental Disability).

On the positive side, 20 out of the 21 journals were members of the Health InterNetwork Access to Research Initiative (HINARI), the World Health Organisation’s programme to provide free or low cost online access in the developing world to scientific research. This is encouraging, but HINARI is not perfect and many are still left without access.

For example, a BMJ Rapid Response highlighted that health care workers in middle-income countries such as Malaysia are often caught in the middle. Too rich for aid but not wealthy enough to afford the high cost of journal subscriptions.

However, despite the fact that most original research relevant to low and middle-income countries is open-access, the majority of the education articles, clinical reviews, news pieces and commentaries are still often behind firewalls that require payment.

The move for more open-access journals is encouraging. For example, the Howard Hughes Medical Institute, the Max Planck Society and the Wellcome Trust will be launching eLife, a new open access journal later this year.

Why don’t more journals provide peer reviewers with free subscriptions? Not only is it a symbol of appreciation for the hours of gratuitous time altruistically invested but it could be used to help others. Likely there is no pressure or demand for it. The majority of peer reviewers are already at academic institutions with subscriptions.

Has this happened to you before? What have you done with this free gift? Although few journals seem to be endorsing this policy, it may serve as a small way to increase access to those who otherwise do not have it.

In the future, if you review an article for the BMJ, the Lancet or the Journal of Intellectual & Developmental Disability (or other journals that provide free subscriptions after peer reviewing), rather than deleting the email consider who might benefit.

If you review for a journal that does not, ask the editor why not?

As the UK descends into hysteria around petrol and pasties, I have been reflecting for the last week on Peter Rothwell’s recent Lancet papers about cancer prevention and the role of aspirin. Basically, daily low-dose aspirin not only prevents development of new cancer, but also the spread of cancer. Aspirin is one of the oldest drugs in the drug cabinet of hospital wards and GP surgeries, but we continue to discover more about its roles in medicine. As new evidence appears on the horizon, the information and guidelines for practising doctors and their patients still continues to change. There are inevitably time delays in how quickly new information filters through healthcare settings and broader society, and how it is interpreted by both the patient and the doctor.

Aspirin has several different uses which are proven by large bodies of evidence, including as a painkiller, prevention of cardiovascular disease in people at risk (primary prevention) and people with known cardiovascular disease (secondary prevention) and now for prevention of cancer. I always love to refer back to the Hippocratic Oath, and so we have to weigh aspirin’s harms with these many benefits. The main harm with aspirin is bleeding, particularly people who have a tendency towards bleeding anyway, e.g. individuals with history of gastric ulcers.

Interestingly, as the new data is emerging about the long-term preventive effects on cancer, the use of aspirin for two other indications is in decline due to evidence of not that much good when weighed against the risk of bleeding. First, most doctors do not recommend low-dose aspirin for primary prevention of cardiovascular disease, largely due to available data from meta-analyses showing that it does not change mortality in diabetics or non-diabetics. Second, in patients with atrial fibrillation, a heart rhythm problem which increases risk of stroke, aspirin is no longer recommended, yet most guidelinesaround the world still include it. So while we can recommend aspirin for long-term cancer prevention, we may not be able to recommend it in healthy individuals for long-term stroke prevention.

Evidence-based medicine is following a moving target of diseases and treatments and so the evidence is also always changing, even for drugs as old as aspirin. So for newer drugs, you can begin to imagine how little we know. The challenge is to keep all people, both doctors and patients up-to-date with all available evidence and guidelines. However, we know that this is difficult, given that both doctors do not always follow guidelines and people do not generally like to take tablets. Notably, most news reports covering the “aspirin and cancer” story advised people to go and see their doctor before starting the drug. Fergus Walsh, of the BBC, quoted a notable academic, “Doctors were good at treating disease, but when it came to preventing ill-health then people had to make their own judgements”. I agree. I wonder whether people have as much chance of making the “right decision” themselves. And before you ask, I do not take an aspirin a day yet, but I did start cycling to work again this week. One preventive step at a time.