Medicine by numbers

时间：2015-10-01

发布：Theodora Bloom, Deputy Editor, The BMJ

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What’s the evidence that any of the 150 000 health apps available in Europe actually work? Not much, says Stephen Armstrong (doi:10.1136/bmj.h4597). Health professionals and lay people use them to monitor, manage, and even treat conditions. But apps are not heavily regulated. Compliance focuses on data protection and honest advertising, with few apps categorised as “medical devices” that need regulation by such organisations as the UK Medicines and Healthcare Products Regulatory Agency or the US Food and Drug Administration. The NHS Choices Health Apps Library lists apps found to be clinically safe and legally compliant. Meanwhile the Royal College of Physicians advises its members to use only apps that have a CE certificate. The UK government proposes a four stage assessment of apps, ranging from a crowdsourced initial stage to robust independent assessment, possibly involving the National Institute for Health and Care Excellence. But it’s unclear whether this assessment will have legal force; and it might process at most 10 000 apps a year.

Also without good evidence are calcium supplements or increased dietary calcium for reducing fracture risk in older people. Two research articles by Mark Bolland and colleagues published this week (doi:10.1136/bmj.h4580, doi:10.1136/bmj.h4183) make it plain that dozens of clinical trials with tens of thousands of participants have shown only a tiny effect on bone density in people who otherwise have a normal varied diet and no clinically relevant effect on fracture risk. Why then, asks Karl Michaëlsson in a linked editorial (doi:10.1136/bmj.h4825), do so many organisations continue to recommend intake of high levels of calcium and vitamin D that cannot be achieved by diet alone? The profitability of the global supplements industry might play a part, he speculates, noting how difficult it is to identify the influence of industry on people who write dietary recommendations.

Such interests are, of course, rife across healthcare. Timothy Anderson and colleagues (doi:10.1136/bmj.h4826) have quantified the links between academic leaders and US healthcare companies, including those producing medical equipment and biotechnology as well as drugs. In 446 publicly traded companies, they identified 279 directors affiliated with 85 non-profit academic institutions who collectively received nearly $55m (£36m; €50m) in individual payments (median individual compensation $193 000) alongside tens of thousands of company shares. Although some academic institutions place limits on the amounts their staff can receive from companies, David Rothman asks in a linked editorial (doi:10.1136/bmj.h5065), “Why is $5000 a day acceptable but not $50 000?” He recommends just saying no: non-profit medical leaders should be excluded from directorships of healthcare companies.

It may seem obvious that explosives and chemical weapons used in conflicts such as the current one in Syria affect civilian men, women, and children as well as combatants. Not so clear are how large the effects and how disproportionately they affect different populations. Debarati Guha-Sapir and colleagues (doi:10.1136/bmj.h4736) use the registries of violent deaths produced by human rights groups and non-governmental organisations to reveal the numbers behind the devastating effects of aerial bombardment and ground level explosives that have killed tens of thousands of Syrian civilians. As Hamit Dardagan notes in his linked editorial (doi:10.1136/bmj.h5041), these data underline the urgent need to ban the use of indiscriminate weapons in populated areas. We must hope these numbers prove persuasive.

BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h5228 (Published 01 October 2015)
Cite this as: BMJ 2015;351:h5228

The harmful haste of modern healthcare

时间：2015-09-24

发布：Kamran Abbasi, International Editor, The BMJ

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“Nature does not hurry,” said the Chinese philosopher Lao Tzu, “yet everything is accomplished.” In our rush to achieve targets, profits, success, and even happiness, it seems we have pitted ourselves against nature. We allow no time for reflection. Everything needs to be done now, sooner, faster—each journey completed, each meal consumed, each promotion obtained, each status updated. When we rush we surely accomplish less. Modern medicine and healthcare are in the business of haste, to provide rapid diagnoses and innovative treatments, to deliver immediate care at every second of every day. Therein lie problems, especially when an urgent political or commercial agenda is superimposed.

In England, the anger of junior doctors at the government’s plan to introduce a new contract in August 2016 is a result of the government’s political expediency (doi:10.1136/bmj.h5077, doi:10.1136/bmj.h5044). Extending working hours while holding firm on salaries, and possibly reducing them, is the behaviour of a bullying employer that cares little for its employees’ wellbeing. Demonising junior doctors (many of the affected doctors are advanced in their careers) is a political means to providing the truly seven day NHS that the government wishes to implement quickly without extra cost. The government’s plan for junior doctors and the health service has obvious benefits for a future political marketing campaign that is based on a 24/7 health service, but the consequences for patients are poorly understood. Junior doctors are considering strike action and announcing their intention to apply for jobs overseas. Our editorialists urge caution (doi:10.1136/bmj.h5077). This is an opportunity for advocacy and to channel public support for junior doctors, so as to achieve better working conditions and, ultimately, better patient care.

Other editorialists criticise the US Food and Drug Administration’s responsiveness to commercial expediency, namely industry’s profit drive (doi:10.1136/bmj.h4897). Patients and doctors, we are told, want newer drugs to be available sooner. Faster regulatory approval means that patients benefit more quickly, says the industry propaganda, and the revenue that companies generate can fund more research. Evidence is clear that the FDA is reviewing new drugs more rapidly and using quicker supplemental approval for existing products (doi:10.1136/bmj.h4633, doi:10.1136/bmj.h4679). Our editorialists Donald Light and Joel Lexchin argue against this approach. They believe that the FDA has learnt little from the Vioxx disaster in the early 2000s. Drugs are approved quickly with marginal evidence of real benefit, and Canadian data show that faster review increases the risk of serious harm. The FDA and other national drug and device regulators need an alternative model where “research focuses on better medicines for patients rather than for profits.”

In an issue that has authorities in its sights, Nina Teicholz’s investigation exposes questionable processes, evidence synthesis, and competing interests involved in the production of the next US Dietary Guidelines for Americans (doi:10.1136/bmj.h4962). A report underpinning the new guidelines reinforces the status quo: to eat less fat and fewer animal products and eat more plant foods, which fails to reflect much of the current science. For example, the report ignores evidence in favour of low carbohydrate diets. The concern about the report is such that the US Congress has intervened.

You may disagree with some of the strong editorial viewpoints expressed this week, but at The BMJ we are equally open to airing disagreement with what we publish, even with fashionable haste. The editorialists Nick Freemantle and Greta Rait (doi:10.1136/bmj.h4843) critique data presented a day earlier by Cole and colleagues (doi:10.1136/bmj.h4708) on the significance of errors in papers reporting clinical trials and question the researchers’ interpretation. The errors are not necessarily a marker of fraudulent or harmful research, as suggested by the researchers, but they do raise more fundamental questions about the rigour of journal editors and journal processes, which seems a good moment for editorial reflection.

BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h5083 (Published 24 September 2015)
Cite this as: BMJ 2015;351:h5083

Study 329

时间：2015-09-17

发布：Fiona Godlee, Editor in Chief, The BMJ

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This week we released our first “RIAT” reanalysis of a previously published randomised trial (doi:10.1136/bmj.h4320). Avid readers will remember that RIAT stands for “restoring invisible and abandoned trials.” As described by its originators in 2013 (doi:10.1136/bmj.f2865), it provides a mechanism for researchers unaffiliated with the original trial to publish unpublished (or to republish misreported) clinical trials when sponsors and original investigators fail to do so.

Last year in BMJ Open Tom Treasure and colleagues reported a trial whose data had remained unpublished for 20 years (doi:10.1136/bmjopen-2013-004385). In a narrative article in The BMJ the restorative authors said that the data cast doubt on the now common practice of carcinoembryonic antigen testing and metastasectomy in people with colorectal cancer (doi:10.1136/bmj.g2085).

We expect many other trials to fall within RIAT’s purview. However, when RIAT was first conceptualised, I and others had one specific trial in mind. Study 329 was a placebo controlled randomised trial of paroxetine and imipramine in adolescents with major depression. As originally reported in 2001, it concluded that paroxetine was “generally well tolerated and effective.”

Paroxetine has never been approved for use in children, but as Peter Doshi reports this week (doi:10.1136/bmj.h4629), millions of off-label prescriptions later Study 329 has become infamous. Funded by the manufacturer of paroxetine, SmithKline Beecham, now GSK, it was quickly dubbed by the US Food and Drug Administration a “failed trial,” as neither treatment was found to be better than placebo. We learnt that the paper was drafted not by any of the 22 listed authors but by a writer paid by the manufacturer. But most alarmingly, reports emerged of serious adverse effects of paroxetine in adolescents, including self harm and suicidal ideation. In 2012 the US Department of Justice, investigating a failure to report safety data and other misconduct by GSK, settled criminal and civil proceedings with a record $3bn fine. Efforts to get the authors, the journal that published the trial , the professional society that publishes the journal, and the authors’ institutions to act or even respond to criticism have failed.

Given this history, there was little doubt that the study needed restoration. That the original authors chose not to do this came as little surprise. The restorative authors set to work accessing and analysing the clinical study report and patient level data. From this immense task they concluded that there is no advantage of paroxetine or imipramine over placebo. They also uncovered “serious, severe, and suicide related adverse events” that had been overlooked or hidden.

The RIAT re-analysis marks a new chapter in the story of Study 329, showing the remarkable power of open data. But it also shows how much our current systems are failing patients and the public. It should not have taken 14 years to get to this point. It shows that we need regulation, and perhaps legislation, to ensure that the results of all clinical trials are made publicly available and that individual patient data are available for legitimate independent third party scrutiny.

BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4973 (Published 17 September 2015)
Cite this as: BMJ 2015;351:h4973