Competing interests at medical journals: industry sponsored trials boost impact factors

These days medical journals are rigorous when it comes to getting researchers to declare any associations with industry that might influence how a trial is reported. Before agreeing to publish a paper, many of the top medical journals require authors to sign a comprehensive conflicts of interest form that outlines any financial or personal relationships that could be perceived as inappropriately influencing the authors’ actions with regard to the research.

But what about the journals themselves, how do they fare when subjected to the same rigorous transparency they impose on their authors? Not too well according to a study published recently in PLoS Medicine. Industry supported trials published in six major medical journals were cited more often than trials not sponsored by industry, and had a considerable bolstering effect on the journals’ impact factors – a measure of the “importance” of a journal.

The authors of this study looked at 1,353 randomised controlled trials published in six general medical journals in 1996-7 and 2005-6: Annals of Internal Medicine, Archives of Internal Medicine, BMJ, Journal of the American Medical Association, Lancet, and New England Journal of Medicine. When they categorised these trials they found that a third (32%) of trials published in NEJM in 1996-7 were industry sponsored, compared with roughly one in 10 (13%) published in BMJ. These proportions dropped for all journals by 2005-6 except for NEJM, so the same proportions nine years later were 32% and 7%.

They then looked at citations for these trials, in 1998 for the 651 published 1996-7 and in 2007 for the 702 from 2005-6. For all journals, there was a significant association between the degree of industry support among the studies published in 2005-6 and the number of citations. This was most pronounced for Annals, Archives, and Lancet, where industry sponsored trials were cited more than twice as often as trials not supported by industry.
Citations are important because they indicate how much a paper has affected a field – the more it has been cited by other authors, the more it has influenced research in the field. Having a high number of citations thus reflects well on the journal that published the study, suggesting that it is featuring the most important research.

The authors then calculated approximate impact factors for the journals by dividing the number of citations by the number of trials published in order to figure out how often the “average” article would be cited. When they removed industry sponsored trials from these equations, the impact factors dropped notably, in particular for NEJM (13-15%) and Lancet (6-11%).

Lastly, editors in chief were contacted and asked to provide information on what proportion of the journal’s total income was from sales of advertisements, reprints, and industry supported supplements. Only BMJ and Lancet provided this data.

Almost half (41%) of Lancet‘s income was from article reprints, which are often bought up by drug companies that sponsored a particular trial to promote the efficacy of their product. A further 1% of the journal’s total income was from display adverts. On the other hand, only 3% of the BMJ‘s income was from reprints and 16% was from display adverts. Neither made much money from industry supported supplements.

Then the authors got cunning. To get financial data for the three American journals – Annals, Archives, and NEJM – they dug up publicly available tax information for the journals’ parent companies. The Massachusetts Medical Society, owner of NEJM, earned 23% of its income from adverts, whereas no data was available on reprints and supplements.

For the American Medical Association, publisher of JAMA, 53% of its income was from adverts and 12% from reprints (no data on supplements). Richard Smith, former editor of the BMJ, reported that reprint sales from a single trial may lead to an income of US$1 million for a journal, so the 12% figure for JAMA is quite noteworthy. The Internal Revenue Service data did not specify the income for the American College of Physicians, publisher of Annals.

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So what do all these findings mean? It seems that publishing industry sponsored trials boosts the reputation of journals, some more than others. Of course, it is important that industry data does get published rather than sit in a drawer somewhere, and it seems a bit misplaced to criticise journals for benefiting from this process. Instead perhaps journals should make clear to what degree they benefit from publishing industry supported trials – financially and status wise.


Lundh A et al. (2010) Conflicts of Interest at Medical Journals: The Influence of Industry-Supported Randomised Trials on Journal Impact Factors and Revenue – Cohort Study. PLoS Medicine 7 (10). DOI: 10.1371/journal.pmed.1000354.

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Half the top US academic medical centers have no policy on ghostwriting

Half of the top 50 academic medical centres in the United States have no policies on their staff ghostwriting research on the behalf of pharmaceutical companies – including UCLA and Mayo Medical School.

Medical ghostwriting is “the practice of pharmaceutical companies secretly authoring journal articles published under the byline of academic researchers.” By getting academics at top universities to put their names to papers, often for financial reward, pharmaceutical companies aim to improve the authority of their research or even sneak dodgy methodology or fabricated findings past journal editors and readers.

Only 10 (20%) of the top 50 US academic medical centres explicitly ban their staff from ghostwriting, according to the survey published in PLoS Medicine, although three of these institutions don’t specifically use the term “ghostwriting” in their policies.

A further three (6%) have authorship policies that prohibit medical ghostwriting in practice by insisting both that staff make a substantive contribution to the paper to qualify for authorship and that all who qualify for authorship be listed.

Although all the top 10 academic research centres in the US have authorship policies, only six ban ghostwriting and the remaining four – including Duke University and Yale – don’t have policies in place.

Ghostwritten articles can be used by pharmaceutical companies to influence the prescribing – and the sales – of their top products. The authors of the study explain this practise by describing how a pharmaceutical sales representative might use such an article to influence the prescribing of a practicing clinician. “When a pharmaceutical salesperson hands a clinician an article reprint, the name of the institution on the front page of the reprint serves as a stamp of approval,” they write. “The article is not viewed as an advertisement, but as scientific research; the reprint is an effective marketing tool because peer-reviewed journal articles generated in academia are perceived to be the result of unbiased scientific inquiry.”

For example, pharmaceutical companies have used ghostwritten articles to promote sertraline – the most prescribed antidepressant in the US in 2007 – methylphenidate – also known as ritalin, the widely used, and abused, ADHD drug – and rofecoxib – otherwise known as Vioxx, the arthritis drug withdrawn in 2004 because it caused heart attacks.

Given how ghostwritten articles can be used to influence drug approval or prescribing, the authors describe the practise as “a serious threat to public health.” To try to combat ghostwriting, they recommend that participating in medical ghostwriting is defined as academic misconduct akin to plagiarism or falsifying data.

Lacasse J & Leo J (2010) Ghostwriting at Elite Academic Medical Centers in the United States. PLoS Medicine 7 (2) DOI: 10.1371/journal.pmed.1000230

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Arch Intern Med roundup: diets, delays and disclosure

Arch intern MedThe journal Archives of Internal Medicine has a several cracking research papers this week.

Low carb dieters are grumpier than those on low fat diets

First up is Brinkworth et al.‘s research on the long-term psychological effects of low carbohydrate diets compared with low fat diets.

In this study, 106 overweight and obese individuals were randomly assigned to receive a low carbohydrate, high fat diet or a high carbohydrate, low fat plan. After one year, those participants on the low carbohydrate diet were more likely to be anxious, depressed, angry or confused than were those on the low fat diet. Both diets had the same number of calories and produced a similar amount of weight loss (13.7kg).

The authors suggest that the social difficulty of adhering to a low carbohydrate plan, which is counter to the typical Western diet full of pasta and bread, may be in part responsible for the mood deterioration in the low carb group. Alternatively, protein and fat intake may differently affect brain levels of serotonin, the so-called “happy hormone” (NB: its a neurotransmitter, not a hormone).

The Daily Telegraph points out that the infamous meat-heavy Atkins diet is essentially a low carb, high fat plan – bad news for all the celebrity fans.  Suddenly the term “hangry” makes more sense…

Brinkworth GD, Buckley JD, Noakes M, Clifton PM, & Wilson CJ (2009) Long-term Effects of a Very Low-Carbohydrate Diet and a Low-Fat Diet on Mood and Cognitive Function. Arch Intern Med 169 (20): 1873-1880. URL: Here

Fewer than ever emergency department patients are being seen on time

Next is Horwitz and Bradley’s paper on wait times to see a doctor in US emergency departments. The authors assessed more than 150,000 visits and found that only one in four patients were seen within the target triage time in 2006, compared with one in five in 2007.  By 2006, the odds of being seen on time were 30% lower than in 1997.

Interestingly, the proportion of patients seen on time did not differ on the basis of insurance status or race/ethnicity.  As the LA Times put it, “The conventional wisdom that throngs of low-income, uninsured people who use the ER as a substitute for primary care visits are to blame is wrong.”

Instead, the change in wait times was driven by delays in attending to emergency cases, who were 87% less likely to be seen within the target time than nonurgent cases.

As the authors says, “The percentage of patients in the emergency department who are seen by a physician within the time recommended … is at its lowest point in at least 10 years”

Horwitz LI & Bradley EH (2009) Percentage of US Emergency Department Patients Seen Within the Recommended Triage Time: 1997 to 2006. Arch Intern Med 169 (20): 1857-1865. URL: Here

GP visits are getting longer and better

Timings are also increasing in primary care, but rather than waiting times the time patients spend with their doctor is growing, according to Chen and colleagues.

Visits by adults to primary care physicians in the US between 1997 and 2005 increased by 10%, from 273 million to 338 million annually.  During this period, the mean duration of visit increased from 18.0 minutes to 20.8 minutes. Visit duration increased the most for people with any form of arthritis – by 5.9 minutes.

The increase in time spent with physicians seemed to be down to doctors spending longer counselling their patients. Visits for counselling or screening generally took 2.6-4.2 minutes longer than visits in which patients did not receive these services, whereas there was no change in the duration of visits in which doctors simply provided medication.

“Although it is possible that physicians have become less efficient over time, it is far more likely that visit duration has increased because it takes more resources or time to care for an older and sicker population,” the authors conclude. These findings thus contradict the belief that doctors are shaving time off consultations to meet efficiency goals, says the Wall Street Journal.

Chen LM, Farwell WR, & Jha AK (2009) Primary Care Visit Duration and Quality: Does Good Care Take Longer? Arch Intern Med 169 (20): 1866-1872. URL: Here

Patients rate care better if doctors disclose mistakes

Finally, López et al. looked at how health professional disclosure of adverse events – an injury caused by some aspect of medical care and not by the underlying medical condition – affects patient perceptions of care.  They found that in patients who experienced an adverse event in hospital, those whose doctor told them about the event were likely to rate their care more highly than patients whose caregivers did not address the problem.

A total of 845 adverse events were reported in this sample of almost 2,600 acute care adult patients, but only 40% of these were disclosed. However, disclosure of preventable and nonpreventable events was associated with high ratings of quality of care. In addition, patients who felt that they were able to protect themselves from adverse events were likely to rate their care favourably.

On the other hand, patients who experienced medical accidents that were preventable, caused increased discomfort, or continued to negatively affect the patient for some time after the event tended to rate their care poorly.

“Although rates of disclosure remain disappointingly low, our findings should encourage more disclosure and allay fears of malpractice lawsuits,” say the authors. “Patients want to be told the truth, and they perceive disclosure as integral to high-quality medical care.”

López L, Weissman JS, Schneider EC, Weingart SN, Cohen AP, & Epstein AM (2009) Disclosure of Hospital Adverse Events and Its Association With Patients’ Ratings of the Quality of Care. Arch Intern Med 169 (20): 1888-1894. URL: Here

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Nearly a third of clinical trials don’t adequately report adverse events

Medical libraryA study published in Archives of Internal Medicine has found that almost a third of clinical trials reported in top medical journals don’t adequately report the side effects of the intervention being tested.

Pitrou et al. assessed the reporting of safety data in 133 randomised controlled trials published between January 2006 and January 2007 in five high impact factor medical journals: New England Journal of Medicine, Lancet, Journal of the American Medical Association, British Medical Journal and Annals of Internal Medicine. PLoS Medicine was included in the search for relevant papers, but no trials from this journal were assessed.

Although 88.7% of published trials mentioned at some point the adverse effects of the study intervention – that is, the drug or non-pharmacological treatment being investigated – 32.6% of all trials didn’t properly report the adverse events data. For example, 17 articles only provided a description of the most common adverse events, whereas 16 reported just severe adverse events.

Thirty-six articles (27.1%) did not give any information the severity of the adverse events reported.  In addition, 63 reports (47.4%) did not give any data on the number of patients who withdrew from the trial owing to adverse events.

So why is this research important?  As the authors say, “the reporting of harm is as important as the reporting of efficacy in publications of clinical trials.”  Insufficient reporting of side effects affects the interpretation of the trial results and distorts the picture of the drug for both clinicians and patients – the drug seems effective but without full adverse effect data no-one can properly assess the risks and benefits of using it.

Writing in an Editorial in the same issue of Arch Intern Med, John PA Ioannidis discusses this issue further. “Accurate information on harms of medical interventions is essential for evidence-based practice”, he says. “Most newly introduced treatments usually have small, incremental benefits, if any, against already available interventions, and differences in the profile of harms should play a key role on treatment choice.”

In addition, this research raises the issue of reported research focusing on the benefits of the intervention being investigated and playing down the negative aspects – the dreaded publication bias.

Guidelines like the Consolidated Standards of Reporting Trials (CONSORT) statement have been put together to try to make sure that researchers report their trials in a complete and transparent way. The CONSORT Statement is a set of 22 recommendations for reporting randomised controlled trials that provides a standard way for authors to prepare reports of trial findings, thus aiding critical appraisal and interpretation of the results.

Granted, the CONSORT statement was only published in 2001 and thus it’s not entirely suprising that trial reporting wasn’t completely up to scratch in the 2006 papers analysed by Pitrou et al.

However, several journals, including BMJ, currently insist that authors fill in the CONSORT checklist and provide a flow chart before the paper can be accepted.  Let’s hope that researchers and publishers are now taking seriously the issue of thoroughly reporting adverse effects.

Pitrou I, Boutron I, Ahmad N & Ravaud P (2009) Reporting of safety results in published reports of randomized controlled trials. Archives of Internal Medicine 169 (19): 1756-61. PMID: 19858432

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So what happened to the AIDs vaccine?

HIVYou might remember all the hullabaloo last month about the HIV vaccine developed by the US military and tested on 16,000 people in Thailand.  Hailed as an “HIV breakthrough” and a “historic milestone“, the initial press release of the study certainly had the media convinced that a prevention for AIDs was just around the corner.

Now the research has been presented in full at the AIDS Vaccine 2009 Conference in Paris and in the New England Journal of Medicine, and reactions are far more circumspect.

Granted, the vaccine in question is the first ever to provide any kind of protection against HIV, but it only prevented HIV-1 infection in 31.2% of participants. 74 of the 8198 volunteer who received the placebo vaccine became infected with HIV-1, but 51 of the 8197 people who were given the vaccine still managed to get infected – a difference of only 23 people.

I’m not really sure what happened with this story.  Did it get press released before publication and before anyone had a good look at all the data?  To be fair the initial news stories were pretty good in their reporting of the research, but why is the story doing the rounds again?

New Scientist is on the ball with this.  In September they published an article “What to make of the HIV vaccine ‘triumph’“, in which they point out that “the victory was won by the slenderest of numerical margins.”

In addition, New Scientist provides some sort of answer to my previous question.  Says the article: “The result was disclosed at the earliest available opportunity at the request of the Thai collaborators, says Merlin Robb, deputy director for clinical research at the MHRP.  “The Thai Ministry of Public Health was very anxious to let the volunteers in Thailand know the result as soon as possible, instead of waiting for a scientific conference,” says Robb. “This reflects our commitment to the volunteers and transparency in all aspects of this trial,” he said.”

So what’s with this jumping of the gun and presenting research before it’s been published in a peer review journal?  But researchers live in a “publish or perish” environment and are in constant fear of being “pipped to the post”.

The BMJ says “We do not want material that is published in the BMJ appearing beforehand, in detail, in the mass media” and “The BMJ does not want to publish material that has already appeared in full elsewhere“. And the New England Journal of Medicine cites their “Ingelfinger rule“, which “requires that author-researchers not release the details of their findings to the mass media before their work undergoes peer review and is published.”

I don’t think this research would have subsequently been published in the NEJM if the authors had in fact broken the embargo, so there must have ben some intense behind the scenes bargaining to get the paper released early – but only a month early.

I’m not really sure what point I’m trying to make here, but I think it’s certainly interesting that this paper made a bug splash a month before the full data was published then did the rounds again.

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Nature Clinical Practice journals relaunch as Nature Reviews

Out with the old (L), in with the new (R)The eight specialty-based Nature Clinical Practice journals, which form part of the medical publishing arm of Nature Publishing Group, are to relaunch in April 2009 as Nature Reviews.

As well as joining the hugely successful Nature Reviews portfolio, which will increase in size from seven to fifteen titles in one fell swoop, the Nature Clinical Practice journals will be given a ‘facelift’ in print and online.  The previously rather austere journals are soon going to be printed in full colour, and the layout of the content has been shaken up to make the journals more eye catching and easier to navigate.

Nature Clinical Practice is a series of monthly review journals targeted at doctors and physicians. The peer-reviewed publications aim to deliver timely interpretations of key research developments, thus facilitating the translation of the latest findings into clinical practice.  Doctors often don’t have time to keep abreast of developments in their field, so Nature Clinical Practice does the reading for the clinician, filtering original research published in primary journals and highlighting the most important and relevant findings.


Launched in 2004 and 2005, the Nature Clinical Practice journals cover the fields of cardiology, clinical oncology, endocrinology, gastroenterology & hepatology, nephrology, neurology, rheumatology and urology. Articles are written by experts in the field and include editorial and opinion pieces, short highlights of research from the current literature, commentaries on the application of recent research to practical patient care, comprehensive reviews, and in-depth case studies.

“Including the eight clinical journals as part of the Nature Reviews series will enable us to bring to the clinical sciences the qualities that have made the life science Nature Reviews journals so successful,” says Dr James Butcher, Publisher of the clinical Nature Reviews titles. “No other publishing company is able to offer high quality monthly review journals covering advances in medical research from bench to bedside.”

“The clinical Nature Reviews journals will retain the high quality content that practicing clinicians rely on from the Nature Clinical Practice titles,” continues Dr Butcher. “We hope that the journals will now also become indispensable resources for clinical academics working in research settings who are familiar with the look and feel of the life science Nature Reviews titles.”

I actually used to work for Nature Clinical Practice and had the chance to check out samples of the relaunch journals before I left the company.  I thought the new full-colour Nature Reviews journals looked infinitely better than their somewhat dry and serious predessors, the vivid new layout really enhancing the high quality and rigorously edited content. I’m really looking forward to browsing the real thing once the first clinical Nature Reviews journals are published in April.

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Pharmaceutical industry promotion of off-label prescribing – responsible or reckless?

fda-logoLast week the US Food and Drug Administration ruled that the pharmaceutical industry could promote drugs for uses that haven’t been cleared by the regulatory body.  The new FDA guidelines permit the “dissemination of medical journal articles and medical or scientific reference publications on unapproved uses of drugs and medical devices.”

In order to be prescribed to treat a certain disease, a drug needs to be formally assessed and approved for this use by the FDA. The practice of ‘off-label prescribing’ entails doctors using a drug to treat a particular disease regardless of whether the FDA has confirmed that the drug is a safe and effective treatment for the disease in question.  As the FDA puts it, “Once a drug or medical device has been approved or cleared by FDA, generally, healthcare professionals may lawfully use or prescribe that product for uses or treatment regimens that are not included in the product’s approved labeling”.

Off-label prescribing is reasonably common, even though you may not have heard it described this way.  An article published in Archives of Internal Medicine in 2006 reported that more than 20% of prescriptions in the US during 2001 were for off-label uses of a drug. One example of off-label prescribing is the use of the drug Avastin – approved by the FDA for the treatment of metastatic colorectal cancer and breast cancer – to treat the condition wet macular degeneration, an age-related eye disease that can lead to vision loss.

The FDA highlight the importance of off-label prescribing, stating that “These off-label uses or treatment regimens may be important and may even constitute a medically recognized standard of care”.  Such practices permit innovation and allow physicians to use their own judgment on the basis of their personal experience prescribing a drug.

The new FDA guidelines sound like good news for the pharmaceutical industry. By promoting off-label uses of already approved drugs, companies can squeeze more profit out of ‘old’ drugs and can ease off the lengthy and expensive process of investigating novel drugs.  But what’s to stop such companies ruthlessly promoting dubious off-label uses for established drugs and risking the health of patients by encouraging doctors to use drugs when there’s not adequate evidence of their efficacy for a certain disease?

Well, the new FDA guidelines include a lot of restrictions as to exactly how off-label uses can be promoted to doctors.  For starters, the guidelines discuss the use of journal articles or medical publications to promote off-label prescribing, meaning that pharmaceutical sales reps will be handing out genuine research that has been conducted by independent groups, not self-penned marketing material.

The guidelines also include lots of important limitations on what type of journal articles, or reprints, can be handed out, including that the articles must:

  • Be published in a peer-reviewed journal that has experts on the subject on the editorial board
  • Not be part of a publication or supplement that is funded in whole or in part by the company that wishes to use the article
  • Be in the form of an unabridged reprint, copy of an article, or reference publication
  • Not be marked, highlighted, summarized, or characterized by the manufacturer in any way
  • Be disseminated with a representative publication, when such information exists, that reaches contrary or different conclusions regarding the unapproved use
  • Be distributed separately from information that is promotional in nature. For example, if a sales representative delivers a reprint to a physician in his office, the reprint should not be physically attached to any promotional material the sales representative uses or delivers during the office visit and should not be the subject of discussion between the sales representative and the physician during the sales visit

So the FDA have done their best to tie up pharmaceutical companies in such a way as to ensure that doctors receive the most accurate and unbiased information possible on off-label drug uses.

Having said that, bias and conflict of interest is an important problem here – of course sales representatives are going to do their best to only hand out journal articles that show the off-label use of their drug in a positive light.  You can bet that pharmaceutical companies won’t be providing doctors with the full body of evidence when it comes to use of their drug for a particular disease, as cumulatively such research could be more ambivalent about the benefits of an off-label use.

Also, in many cases even the total body of evidence doesn’t show that an off-label use is effective.  Indeed, the aforementioned Archives of Internal Medicine paper showed that three-quarters of off-label uses were not backed up by scientific evidence.  There is an argument that the clinical trials process and the publication procedure lags behind real life, and that although there are no trials showing that an off-label use is effective, many doctors will have prescribed a drug this way and seen the beneficial results for themselves.  Fair enough, to a degree, but this undermines the whole issue of the pharmaceutical industry giving out published research on off-label uses anyway, so will be of little interest to such companies.

Finally, how on earth is the FDA going to police their restrictions?  They can insist that the pharmaceutical industry follows their rules, but there is plenty of evidence that such regulations are regularly flouted.  For example, despite the new guidelines, the straightforward marketing of a drug for uses not cleared by the FDA is still illegal.  Global pharmaceutical company Eli Lilly used catchy slogans to persuade doctors to prescribe the antipsychotic agent Zyprexa for unauthorized use in elderly patients and has this month been fined $1.5 billion for doing so.

I’m not the only one with misgivings about these well-intentioned but ultimately flawed guidelines.  California senator Henry Waxman told Medscape that the new FDA decision “fundamentally undermines the requirement that companies prove to the FDA that each new use is safe and effective” and makes it easier for drugmakers to promote potentially risky medical practices.  Over on Nature Network, research scientist Craig Rowell proclaimed that “Alarm bells should be ringing” – despite his support of off-label prescribing, Craig is still deeply skeptical that pharmaceutical companies will stick faithfully to the restrictions.

What’s the bottom line for patients here?  Many will benefit from by off-label prescribing, or at least not be harmed, and doctors will be better able to prescribe off label if they are thoroughly informed about such practices.  The sticking point is whether the pharmaceutical industry can be relied on to accurately and fairly disseminate information about off-label uses; experience suggests probably not.  Whether the FDA has made a shrewd move in getting pharmaceutical companies to do this promotion for them, or a big mistake, remains to be seen.

  • The Pharma Marketing blog has an interesting post on this issue, which discusses policing of the new guidelines and the efficacy – or not – of off-label prescribing.
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Festive funnies in the BMJ Christmas issue

Christmas treeEvery year the British Medical Journal team get in the festive spirit with their Christmas issue, publishing zany or amusing research.  This year is no exception, with a host of genuine research papers and rigorous scientific analyses guaranteed to make you giggle.

Research articles in this week’s issue of BMJ include:

  • Head bangers: stuck between rock and a hard bass
  • Head banging to heavy metal is a popular dance form, but it increases the risk of head and neck injury. The effects may be lessened with reduced head and neck motion, head banging to lower tempo songs or to every second beat, and using protective equipment such as neck braces, say Australian researchers Declan Patton and Andrew McIntosh.

  • Rugby (the religion of Wales) and its influence on the Catholic church: should Pope Benedict XVI be worried?
  • Researcher Gareth Payne and his two colleagues from Cardiff investigate whether there is any substance to the intriguing urban legend that has arisen in Wales in recent times: “Every time Wales win the rugby grand slam, a Pope dies, except for 1978 when Wales were really good, and two Popes died.” Wales won the Grand Slam in 2008 – so should Pope Benedict XVI be worried?

  • Frankincense: systematic review
  • Edzard Ernst, the UK’s only professor of complementary medicine, systematically reviews the evidence on frankincense – a tree resin that was one of the first ever Christmas presents and is now a popular complementary remedy. He concludes that, although frankincense does not bestow supernatural instant youth or eternal life as many claims would have it, it has encouraging anti-inflammatory properties.

In the comment section, Deborah J Anderson, an author of the IgNobel-winning research on the use of coca cola as a spermicide, advises against this approach to contraception, while MA Buchanan and colleagues discuss whether modern golf clubs can cause hearing damage.

The Christmas issue also traditionally subjects prevalent medical myths to critical appraisal.  Last year Rachel Vreeman and Aaron Carroll showed that reading in low light does not damage eyesight and that turkey is not to blame for drowsiness after Christmas dinner.  This year they turn their attention to whether sugar causes hyperactivity in children and if wearing a hat reduces heat loss in cold weather, thoroughly debunking these popular beliefs.

The whole BMJ Christmas issue can be found online at  I hope you enjoy it as much as I did!

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Are researchers fudging clinical trial statistics?

Before a clinical trial can commence a protocol – a plan of exactly how a trial will be conducted – will be formulated.  As part of the planning, the individuals undertaking the trial will calculate approximately how many patients need to take part for the results to be meaningful (the ‘sample size’) and prespecify which statistical tests they will perform on the data once the trial is complete.

A new study of published clinical trials, however, has found that many do not report these crucial sample-size calculations and that authors often do not mention if they have changed their mind as to which statistical test they are going to use.  About half of the trials studied by Chan et al. did not include sample-size calculations or mention whether the statistical tests actually used on the data differed from those provided in the trial protocol.

It is important that people conducting clinical trials stick to the statistical methods outlined in their protocol, as different types of statistical test can produce different outcomes for the same set of raw data.  If trial authors plan to use a particular test then change their mind and use a different test once they have seen the data, the results can be inadvertently biased – or directly manipulated – so they appear much more positive.

In the recent BMJ study, Chan et al. compared the published papers of 70 Danish randomized clinical trials with the corresponding protocols, which had been submitted to the local ethics committees for approval before the trials commenced.

Only 11 trials fully and consistently described sample-size calculations in both the protocol and the published paper. There were unacknowledged discrepancies between the calculations in the protocol and those in the published paper in 53% of cases.

Most protocols and publications specified which statistical tests would be used on the trial data; however, in 60-100% of cases the tests listed in the published paper differed from those in the protocol.

So it seems that in many cases sample size calculations and statistical methods are not prespecified in trial protocols or are poorly reported.  If they are prespecified, authors don’t tend to acknowledge instances when the statistical methods used differ from those in the protocol.  These two practices can easily introduce bias into the analysis of clinical trials and, ultimately, lead to misinterpretation of study results.

All this is bad news for everyone – if trial results aren’t reported honestly and transparently then it will be impossible to tell which trials, and therefore treatments, will genuinely help patients.  Hopefully initiatives such as SPIRIT (Standard Protocol Items for Randomised Trials), launched by Chan et al., and CONSORT (Consolidated Standards of Reporting Trials) will improve the accuracy of clinical trial reporting, but always remember: “There are three kinds of lies: lies, damned lies, and statistics”.

Chan AW et al. (2008) Discrepancies in sample size calculations and data analyses reported in randomised trials: comparison of publications with protocols BMJ 337 (4 Dec 2008) DOI: 10.1136/bmj.a2299

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The Lancet website relaunch

Today medical journal The Lancet relaunched a sleek and efficient new version of their website

The team at The Lancet consulted 100 authors, readers, doctors and clinicians – or ‘development partners’ – to find out what users wanted, and the result is a much cleaner and easier to use website. In the new design, The Lancet journals The Lancet, The Lancet Infectious Diseases, The Lancet Oncology, and The Lancet Neurology are now all accessible and searchable from a single website.

In a special podcast to accompany the launch, the Editor-in-Chief Richard Horton outlines his favourite features:

“The most exciting things about The Lancet’s new site for me are first, we have the possibility for internet television … in the YouTube would that we live in I think that’s immensely important for communication, especially in health when you’ve got some pretty difficult concepts sometimes. And secondly, I think we’re also able to convey the personality of The Lancet in ways that we’ve never been able to before: the idea that we’re publishing research, educational material, and also opinion.”

The new video functionality is showcast Story, a very flashy and professional-looking production in which members of the journal staff and Dr Anne Szarewski, clinical consultant at Cancer Research UK and one of the development partners, discuss what the new website means to them. The Lancet hopes that in the future users will be able to submit their own medical videos to the site.

Richard Horton boasts that the website has “the best search engine in medicine”, and certainly it’s an awful lot faster than the search on the previous incarnation. Importantly, the search results include not only results from The Lancet family of journals, but also all relevant results in Medline, a life sciences and biomedical publication database run by the US National Library of Medicine.

Articles now include links to related material as well as social bookmarking tools, including parent company Elsevier’s 2Collab social networking tool. In addition, online community features are planned, including social networking, debates, wikis and discussion boards.

On the editorial side of things, original research articles now include drop-down Editors’ Notes within the table of contents – 2 or 3 sentences that summarize what is important about the research – while journal homepages feature three articles that represent the Editor’s choice. The news aspect of the website has been expanded with the inclusion of ‘This Week in Medicine’, short paragraph-long summaries of what has been going on in medicine worldwide. Specialty-based online collections comprising content from across The Lancet family of journals will launch in the near future, one mooted project being a cardiology portal.

I think the new version of is a vast improvement on the previous website, not least because it is so much easier to navigate and doesn’t trip you up with sign-ins every 5 minutes. The site also looks far crisper, in stark contrast to it’s cluttered forebear. I’m more into text than multimedia so I’m not fussed about using the new video content, but it’s certainly very impressive and a new direction for The Lancet.

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