Cardiologist Jeffrey F Caren, who has a monument of over 1,200 pens gifted to him by drug companies

The links between the pharmaceutical industry and doctors are many and tangled. Drug companies are keen to schmooze doctors and, directly or not, persuade clinicians to prescribe their drug instead of a similar one by a competitor. One way that drug companies try to influence doctors is by sponsoring events, such as conferences or lectures.

Despite legislation, the exact extent to which the pharmaceutical industy sways doctors via this approach is not really known. To try to unravel exactly how much is being spent on sponsoring events for doctors, Robertson and colleagues investigated pharmaceutical industry funding of events in Australia, which has laws stating that details of every sponsored “do”, including the costs of any hospitality, are posted on the Medicines Australia website.

The authors found that during a six month period, the drug industry spent AUD$1 million (about £555,000 or US$900,000) a week in Australia on sponsored “educational events” for health professionals. This equates to about 600 sponsored events a week and an average annual spending of around AUD$1,000 (£555 or US$930) on each doctor.

More than a third (35%) of events were held in plush spots like restaurants, hotels or function centres, which increased the spend on the event by five-fold compared with if the event was held in a hospital (AUD$71.35 vs AUD$12.11).

Bristol-Myers Squibb was the most generous company, with an average spend per head of AUD$95.26 (£53 or US$88), although Astra Zeneca held the most events (1,310 0ver six months).

Professionals specialising in psychology or oncology were the most likely to attend sponsored events, although the biggest spend was on endocrinologists, oncologists and cardiologists.  Tellingly, specialists in these particular disciplines tend to prescribe the highest cost drugs.

Companies had some control over what was discussed at the event in 91% of cases. Where provided, topic descriptions often matched the products made by the sponsor, although there were few mentions of specific drug names.

Evidence suggests that attending a drug company sponsored event can indeed change the prescribing practices of a doctor, making the figures in this report quite disturbing.  For example, judging by the numbers in this study, as many as 13,000 Australian doctors could be under the thumb of the pharmaceutical industry.  As the authors point out, “from a company perspective, it is cheap and easy to sponsor meetings in hospitals and health centres, and the return on this ‘investment’ is likely to be high.”

In the UK, the Association of the British Pharmaceutical Industry code of conduct states that pharmaceutical companies sponsoring meetings and seminars can only provide “subsistence” for events and can only offer economy air travel to delegates sponsored to attend meetings. The code also states that lavish venues must not be used and that the costs covered “must not exceed the level which the recipients would normally adopt when paying for themselves”.

In the US, several states have mandatory disclosure laws for physician payments so that it is a bit clearer to everybody who is cosying up with drug companies and who isn’t, but these data aren’t foolproof.  For example, laws on physician reporting of industry gifts in Vermont and Minnesota exempt payments of less than US$100.

It’s worth mentioning that the system in Australia is actually more transparent than that in either the UK or the US, given that since mid-2007, there has been mandatory reporting of details of every industry-sponsored event in Oz.  On that note, the situation is probably worse in the northern hemisphere, as noted by an article last year in British newspaper The Guardian.

And although there is legislation in place these days, as the authors point out, “lavish gifts and generous travel support … have been progressively discouraged by industry and professional guidelines. It is likely that the frequent, more modest, sponsored educational events will become increasingly important and influential, and the principal form of contact between industry and health professionals.”

This research clearly outlines how endemic industry courting of doctors really is.

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Robertson J, Moynihan R, Walkom E, Bero L, & Henry D. (2009) Mandatory Disclosure of Pharmaceutical Industry-Funded Events for Health Professionals. PLoS Medicine 6 (11). DOI: 10.1371/journal.pmed.1000128

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…

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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”

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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.

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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.”

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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

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.

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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

Metal, according to the Daily Mail, causes cancer, but nobody panic, iron and zinc prevent it.

Nuts prevent cancer, but peanuts cause it.  Cod liver oil can give you cancer, but fish oils will protect you.  Are you still with me?!

Absolutely hilarious.

See also: the Daily Mail Oncological Ontology Project

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.

The aim of this shiny new wing is to show visitors “the hidden world of museum science”.

The Natural History Museum is rightly most famous for it’s natural history collection, which comprises more than 70 million specimens amassed over the past 400 years. However, the museum is also an active research centre that covers biodiversity, disease, climate change and environmental science.

The striking Cocoon building at the Darwin Centre combines these two arms of the museum’s mission, housing over 200 working scientific experts and also a significant proportion of the museum’s specimens.

The specimens are in storerooms on the lower five floors in a controlled environment behind 4cm glass windows.  And the scientists?  They’re also on display behind glass windows, allowing guests to get a glimpse of science in action; for example, the preparation of specimens for cataloging or the extraction of DNA for sequencing.

Given my geeky tendencies, I particularly enjoyed the Decoding DNA area. This spot explained how and why scientists unravel DNA, and included a funky animation of PCR. One of the things I really liked about the whole Darwin Centre was that it explained the practicalities of what scientists do, and the clear explanation the rather complicated process of DNA sequencing was a great example.

The Decoding DNA area also had a cool game about sequencing the DNA of various disease carrying mosquitoes.  You first had to catch enough mosquitoes to fill your quota of PCR tubes, then run them on your virtual electrophoresis gel to get a look at the variation among different types of mosquitoes.  Once you knew what the different types were, you were given a list of their characteristics and asked how you think they should be controlled.

We suggested that our drug resistant Anopheles species of mosquito should be controlled with nets rather than drugs, and totally won the game.  Curing malaria isn’t bad for a morning’s work!

The Cocoon has more than 40 high-tech installations and hands-on interactive activities like this.  Some of my other favourites included a video about peer review and publishing research (predictable? me?!) and a collection of videos of scientists on field expeditions.  More great info on the day to day lives of Britain’s scientists.

Dotted around the exhibition are various barcode scanners for the museum’s NaturePlus scheme.  Each visitor is given a card with a unique barcode that they can scan at exhibits they find particularly interesting and save content to view later online.

I imagine this service is really helpful for school children who are working on a project about taxonomy, for example.  The kids can find out the basics about classification of organisms on their trip to the museum, then do further research about Linnaeus and co when they get home.

Overall I think the Darwin Centre is a great resource for teaching the general public, especially kids, about what it means to be a scientist.  Certainly when I was at school we learnt about DNA, photosynthesis, and so on, but were taught little about how this information was acquired bar the stories of big names like Darwin and Mendel.  The great “how to do biology” exhibition in the Darwin Centre would have no doubt filled the gaps in my schoolgirl knowledge and given me a clear idea of what further studies in science might eventually lead to.

However, I’m hoping to get a new perspective on the nuts and bolts of how clinical research is conducted as my Dad is currently taking part in a huge rheumatoid arthritis trial – the TRACE RA trial.  This study is investigating whether heart drugs – statins – reduce the risk of heart attack and stroke in people with rheumatoid arthritis.

People with rheumatoid arthritis are at higher risk of cardiovascular disease than the general population and are thus are more likely to have a fatal heart attack or stroke.  This increased risk is thought to be due to a higher incidence of atherosclerosis in patients with rheumatoid arthritis – the inflammation that attacks the joints in such people is though to also affect the lining of their blood vessels.

Statins reduce “cardiovascular disease events” and mortality in high risk populations, largely through lowering cholesterol but also possibly through reducing inflammation.  We don’t know whether statins are beneficial in rheumatoid arthritis though, as people with this highly inflammatory condition are usually excluded from statin trials.

The TRACE RA trial is a prospective, 5-year, multicentre, randomised, double blind, placebo-controlled study that will assess the hypothesis that a statin is more effective than a placebo in the primary prevention of cardiovascular events in patients with rheumatoid arthritis.

Up to 4,000 people over the age of 50 who have had rheumatoid arthritis for at least 10 years are being randomised to receive either the statin atorvastatin or placebo daily. The patients in the trial will be followed up for up to 7 years to see if those on the statin are less likely to have a cardiovascular event than those on the placebo.

My Dad joined the trial quite recently and is currently going through his initial follow-up visits, which take place at 3, 6 and 12 months. At each visit he gives a blood sample and also fills in a questionnaire, which he showed me last time I visited. Dad was a bit concerned about the questionnaire, as he was being asked quite dramatic things like whether he was able to dress himself or cut up his own food. Thankfully his arthritis is well controlled and he doesn’t have any mobility problems, so he can answer “no” to most the questions; I’m guessing other trial participants aren’t so lucky.

The questionnaire he has to fill in is a validated tool for assessing functional disability called the Health Assessment Questionnaire (HAQ).  I’ve come across the questionnaire when reading rheumatology papers – it’s used in patients with a wide variety of rheumatic diseases including rheumatoid arthritis, osteoarthritis, lupus, and ankylosing spondylitis – so I was intrigued to get a proper look at it.

Given how much I go on about clinical research, Dad was keen to be involved in a trial himself and hopefully contribute a small part to improving treatment for rheumatoid arthritis.  There’s also a history of heart disease in my family, so (potentially) receiving a statin when he otherwise wouldn’t be on the list to do so could prove doubly beneficial for Dad.

I’m looking forward to following my Dad’s progress in the trial and reading the first published paper.  The design of the trial seems pretty solid so any positive findings could have considerable implications for how patients with rheumatoid arthritis are treated.  And my Dad – subject number whatever out of n=4000 or so – is playing his own little part.

The prizes are awarded to “the creators of the most informative, striking and technically excellent images” on the basis of “the ability of the picture to communicate the wonder and fascination of science.”

Dr Alice M Roberts, who presented the awards, emphasised not only the utility of images in science, but also their value as beautiful work of art.  “Imaging and imagery can help scientists in many ways: to understand structures that are too small to be seen by the naked eye, or perhaps to elucidate the relationship between structure and function,” she said. “But as well as deepening understanding, the art of science can also be – in its own right – beautiful and awe-inspiring.”

My favourite images are those created using microscope techniques like electron microscopy and multiphoton microscopy, which provide an extraordinary insight into the detail of human anatomy.

This first picture is of villi in the small intestine – finger-like structures that absorb nutrients from the food passing through the gut.  Paul Appleton, who produced this image using fluorescent imaging techniques, hopes that it might help researchers identify cancerous change in colon tissue, pointing out that “Scientists have to characterise normal tissue before they can look for changes in abnormal tissue.”

Another of my favourites is this vivid picture of capillaries from a structure in the eye known as the ciliary body, which sits either side of the lens.  Capillaries measure 5-10 micrometres in diameter and are only one cell thick, so getting such a clear and informative image of these tiny vessels is quite an achievement.  The bright red colour is the result of a dye – likely to be carmine dye - that was injected into the artery that supplied the capillaries.

Number three is this picture of compact bone – the dense stuff that surrounds the bone marrow.  The structures that look like rings in a tree stump are called osteons, in which lamellae of bone tissue form around canals that house the blood and nerve vessels supplying the bone.  The black specks show osteocytes, the living cells that produce bone tissue.  The cells are lost during processing, however, leaving the holes within the bone that they once occupied.  Unlike the previous images, no false colour was added to this picture.  Your intestines aren’t blue and red like the image of villi above, but your bone definitely looks like this.

Last is this image of in vitro fertilization.  The “blazing sun” object is the egg, the “rays” produced by cumulus cells that protect the egg.  This image shows the moment of conception, with a sperm wiggling its way in on one side.

These images and more are available to view on the Wellcome Trust Image Awards website.  They’re also on display until Spring 2010 in a free exhibition at the Wellcome Collection.

However, a study published recently in the Journal of Nutrition has found that the diet consumed by the majority of French adults doesn’t meet nutrition recommendations.  Only 22% of adults could meet dietary requirements by fine tuning what they already ate, whereas the remaining 78% of French adults would need to expand their diet.

The authors of this study used modelling techniques to create diet plans based on an individual’s “habitual food repertoire” – i.e. the kinds of foods they regularly consumed.  The idea of this approach was to calculate a diet plan that met nutritional recommendations without deviating much from the foods the individual already liked to eat.

More than a thousand French adults who were participating in the French national food consumption study provided seven day food diaries. The authors then tried to design for each individual a diet plan that met 30 different food recommendations by using the foods in their weekly food repertoire.  The designed diets varied according to the individual’s gender, age and observed nutrient intake levels.

The authors found that they could only put together diets that met all 30 recommendations for 22% of adults – i.e. only a fifth of the sample had diets that could be tweaked to be nutritionally sound on the basis of how foods were combined or how big portion sizes were.  These individuals consumed more energy and more fruit and vegetables than those whose food repertoire couldn’t be juggled to meet requirements.

On the other hand, it was mathematically impossible to design a nutritionally adequate diet for the remaining 78% without extending the range of foods they ate.  The main problem among participants with unsatisfactory diets was that their favourite foods didn’t contain enough vitamin D, although their diet plans also couldn’t be manipulated to within maximum sodium levels or minimum magnesium recommendations.

Unsurprisingly, feasible diets could be put together for every participant when the food options were not limited to the individual’s food repertoire.

This study suggests not only that the diets of most French adults aren’t anywhere near meeting nutrition requirements, but also that considerable changes will need to be made to the foods eaten in order to meet a healthy diet.  Maybe French food isn’t all it’s cracked up to be after all…

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Maillot M et al. (2009) To Meet Nutrient Recommendations, Most French Adults Need to Expand Their Habitual Food Repertoire. Journal of Nutrition 139 (9): 1721-1727. DOI: 10.3945/jn.109.107318

The idea of trial registries is that researchers provide all the details of their study – such as the number of patients they need to recruit and the primary outcome (e.g. death or heart attack) – before they start the study. Then once the study has been completed and published, other people can refer to the record in the registry to see whether the pre-specified protocol has been followed and if the researchers have really done what they said they were going to do and how they said they were going to do it.

The JAMA study compared published articles with their entries in clinical trial databases and found that less than half of the 323 published articles in their sample were adequately registered and nearly a third weren’t registered at all.  Shockingly, 31% of adequately registered trials published different outcomes from the outcomes registered on the clinical trial databases – that is, the authors “changed their mind” about what they were researching at some point in the process.

The authors of the PLoS paper did their research the other way around and looked at whether trials in ClinicalTrials.gov, the registry set up by the US National Institutes of Health and the Food and Drug Administration, went on to be published.  Less than half of the 677 trials they studied were eventually published.  Trials sponsored by industry and, interestingly, trials funded by the government were less likely to be published than those funded by nonindustry or nongovernmental sources.

Why is this important? Imagine a group of researchers are looking into whether an new drug reduces the incidence of heart attack (the primary outcome). They spend thousands of pounds recruiting patients and studying them for years and years, then find out that their drug doesn’t prevent heart attack at all but is very helpful in patients with migraine. The researchers could then decide to change the primary outcome of their study from “incidence of heart attack” to “incidence of migraine”, even though the trial had been intricately designed to look at the former not the latter. Their statistics and results will be all out of whack and frankly unreliable, but they could still go ahead and market their blockbuster drug. Researchers could get away with this if they don’t put their trial details in a registry before they started.

Imagine that the wonder cardiovascular drug our shady researchers are investigating has no effect whatsoever on heart attack, so the researchers just decide not to publish their results. Other researchers looking at very similar drugs could plod on for ages with their own experiments to no avail because they had no idea that someone else had already shown the drug was useless. A more disconcerting possibility is that a drugs company could find out their key money spinner has a nasty side effect but decide to bury the research showing this and never publish it.  This is known as publication bias. Researchers, funding bodies and editors are all more interested in publishing studies that find something interesting rather than ones that show nothing at all – where’s the headline in “candidate drug doesn’t do much”? When it comes to drugs that are already on the market though, knowing the situations in which the drug doesn’t work is just as important as knowing when it does work.

And from a patient perspective? Imagine your doctor has been prescribing you a drug that should help your stomach ulcers. What he doesn’t know is that an unpublished trial somewhere says the drug will also dangerously thin your blood. If the doctor has no idea this trial ever existed – it wasn’t registered when the trial kicked off and was never published – or the negative results were masked by the paper reporting a different primary outcome to that in a registry, he or she will continue prescribing you a drug with risky side effects.  The example of arthritis drug Vioxx springs to mind…

These are all quite dramatic examples but illustrate why we need to know about trials at their inception rather than once they’re published and, therefore, why full use of clinical trial registries is important.