Public Library of Science

To screen or not to screen?

Gavin Yamey — Tue, 5 Aug 2008 16:08:55 -0700

To screen or not to screen? One of the more “interesting” experiences of my journalistic career was co-authoring an Op-Ed for the San Francisco Chronicle in 2002 on the lack of evidence for prostate cancer screening using the PSA test.

The piece caused quite a reaction, which we later discussed in the BMJ:

“Within hours of our piece being published, prostate cancer charities, support groups, and urologists around the country had circulated a "Special Alert" by e-mail. This community has huge faith in PSA tests, and it did not care for our opinion. The e-mail, under the header "ATTENTION MEN!!" urged the community to take action. By the end of the day, accusations, abuse, and personal threats jammed our e-mail inboxes. We were compared to Josef Mengele, and accused of having the future deaths of hundreds of thousands of men on our hands.”

I suspect that this same community will now be up in arms about the latest guidance from the US Preventive Services Task Force (USPSTF), one of the best respected independent health agencies in the country.

As the New York Times reports in a huge cover story today, headlined Panel Urges End to Prostate Screening at Age 75, the task force has systematically reviewed the best evidence on the value of such screening and concludes:

“The USPSTF recommends against screening for prostate cancer in men age 75 years or older.”

It also concludes that “the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years.”

The New York Times notes that the new guidance, which now clearly advises against screening men aged 75 and older, represents "an abrupt policy change by an influential panel," a panel that had previously withheld giving specific advice regarding screening for prostate cancer.

In a terrific NPR commentary today on the new guidance, Doug Kamerow says:

“There just aren't any good studies to show that men who get screened and treated for prostate cancer live longer than those who don't. So the benefits are unknown. But the harms of screening and treatment are real and well documented. They include not just the costs and pain of treatment, but also the incontinence and impotence that some men get after surgery. The problem is that some prostate cancer grows quickly and is lethal. Some, especially in older men, is slow-growing and never causes a problem. That is why people say that more older men die with prostate cancer than of prostate cancer.”

I suspect that despite the new USPSTF guidance, the “great prostate debate” is far from over. It is merely, says NBC news’ chief science correspondent Robert Bazell, “the latest shot in an ongoing war among many factions who hold various positions on this disease.”

Hopefully the war will be settled when we have the results of two ongoing clinical trials of prostate cancer screening, one in the U.S. and one in Europe.

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ONE journal, two birthdays

Liz Allen — Fri, 1 Aug 2008 10:32:43 -0700

The English Monarch has two birthdays – their real date of birth is celebrated in private with family and friends and the official date (which could historically be moved should their real birthday fall at a time of year when the weather was inclement) which is celebrated in public through the Trooping of the Colour Ceremony and a fly-past over Buckingham Palace in London.

PLoS ONE also celebrates twice (but far less grandly) – first there’s the date we opened our doors for submissions, 4 August 2006 (the date of our conception) and then there’s the date we launched (our birth), 20th December 2006.

Within less than 3 weeks of opening our doors we had received 70 manuscripts which represented far more papers flowing far faster than we’d ever experienced before. Now, two years later, we receive approximately 350 submissions per month. Not surprisingly, the PLoS team has grown since then to cope with the increased workload.

Two folks who deserve special mention for being there at the start and still being on board now - they are Bex Walton and Lindsay King.

Two years on, the person who still sums up our publishing philosophy well is the author of the first paper accepted for PLoS ONE, Andrej Romanovsky of St. Joseph's Hospital, Phoenix, Arizona, USA. He said "A traditional publisher uses complex rules to determine who, when, how, and at what price will be allowed to see your results. You can continue supporting this system ... or you can submit your next paper to PLoS”.

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Happy, er, conception-day?

from A Blog Around The Clock on Mon, 2008-08-04 04:55

Two years ago on this day, PLoS ONE opened for submissions (and surprisingly many manuscripts - 70 - got submitted immediatelly)....

Tyrannosaurus Re-examined

Rebecca Walton — Fri, 1 Aug 2008 08:38:54 -0700

This week saw the publication of another dinosaur study in PLoS ONE. In the article, entitled, Dinosaurian Soft Tissues Interpreted as Bacterial Biofilms, Thomas Kaye, at the Burke Museum of Natural History, and colleagues reported that material recovered from dissolved dinosaur bones by palaeontologists in 2005 (and believed to be dinosaurian soft tissue) may actually have been slimy biofilm created by bacteria that coated the voids once occupied by blood vessels and cells.

This study has already generated a large number of news articles and blog posts, including the following: New Scientist (T. rex 'tissue' may just be bacterial scum), Scientific American (Presumed dinosaur flesh may just be bacterial sludge), National Geographic (Dinosaur Slime Sparks Debate Over Soft-Tissue Finds), USA Today (New study has a bone to pick about dinosaur soft tissue), Aetiology (Dinosaur soft tissue--just bacterial biofilm?) and Pharyngula (Tyrannosaur morsels).

Several comments have already been posted on the published article and you can join in the discussion once you have created an account on the PLoS ONE publication website.

On the topic of biofilm, Carsten Matz’s paper, Marine Biofilm Bacteria Evade Eukaryotic Predation by Targeted Chemical Defense, published last week also picked up some coverage in the Washington Post (Social Lives of Bacteria May Yield Benefits for Humans) and Chemistry World (Biofilms deploy chemical weapons).

Also on a watery theme was Natalia Ospina-Álvarez and Francesc Piferrer’s paper on the potential effects of climate change on sex determination in fish. In vertebrates with separate sexes, sex determination can be genotypic (GSD) or temperature-dependent (TSD). The Spanish researchers used field and laboratory data to critically analyze the presence of TSD in the 59 species of fish where this type of sex determining mechanism had been postulated and found that increasing temperatures invariably resulted in highly male-biased sex ratios and that even small changes of just 1-2°C can significantly alter the sex ratio from 1:1 (males:females) up to 3:1 in both freshwater and marine species. Time Magazine covered the article (Global Warming's Fish-Sex Effect) and the story has also been Dugg several times.

Danish palaeontologist Per Christiansen compared the evolution of skull and mandible shape both in modern cats and in (the now extinct) sabercats; Greg Laden has posted a nice write-up of the study on his blog and there also posts on The Dragon’s Tales and on Counter Minds.

Finally, here is a quick round-up of some of coverage of several papers published in PLoS ONE on July 23^rd: Does Pathogen Spillover from Commercially Reared Bumble Bees Threaten Wild Pollinators? (New Scientist, Reuters, Greg Laden’s blog); Sample Size and Precision in NIH Peer Review (The Scientist, Mike the Mad Biologist); and Changes in Gray Matter Induced by Learning—Revisited (Mind Hacks).

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To IRB or not to IRB?

Emma Veitch — Tue, 29 Jul 2008 09:46:58 -0700

The Committee on Publication Ethics (COPE), of which PLoS Medicine, and other PLoS journals, are members, has recently released guidance for editors on the thorny topic of "research, audit and service evaluations". This guidance aims to help editors decide how to handle their journal's requirement for ethical review in relation to these types of studies. As outlined by COPE, most journals require that for any research involving human subjects, the study has been approved by a properly constituted ethics committee.

However, for some types of studies and in some countries, ethical approval is not required (or, may not even be possible). For example, the
US Department of Health and Human Services exempts research from review if it involves studying existing data or specimens, providing data is anonymised and delinked from the participant it originated from; exemptions also apply for five other major categories of research. In the UK, the National Research Ethics Service issues its own guidelines to help people to work out whether what they are planning to do is research (which requires ethical review) versus audit or service evaluation (which don't).

The PLoS Medicine editors recently discussed the COPE guidance. That guidance suggests that editors think about four key components, quite apart from the "box-ticking" exercise of checking that ethical review and informed consent have been obtained. Those four areas are: 1) scientific validity; 2) minimisation of harm; 3) whether benefits outweigh harms; and to 4) the need to seek clarification from authors or ethics committees regarding local laws and regulations, as necessary.

At PLoS Medicine, our journal policy is that "All research involving humans and animals must have been approved by the authors’ institutional review board or equivalent committee...". We do however recognise that many studies may be exempt from ethical review, and therefore our overriding approach is that authors describe clearly in their paper how ethical oversight for the study was obtained, and how the informed consent of participants was handled. This means that reviewers, and readers, will be able to judge for themselves whether the protection of human participants in the study was appropriate.

At the same time, we recognise that "journals should not automatically defer to ethics committees", as Kamran Abbasi and Iona Heath have pointed out in a BMJ editorial, and we consider the key areas outlined by COPE as part of our editorial review process. If we do have concerns regarding the protection of human participants in a study, irrespective of whether that study was approved by an ethics committee (or exempt from ethical review), the editors reserve the right to follow up, under the guidance of our advisory group on publication ethics, as necessary.

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Natural and Synthetic Vision - call for papers

Liz Allen — Mon, 28 Jul 2008 12:53:08 -0700

We're seeking more articles in the field of Natural and Synthetic Vision (an area in which we have already published 40+ papers, you can see them listed below).

We would like to expand our coverage of this area by announcing the publication of a Special Collection that emphasizes electronic and computational image processing, including machine learning in vision. We look forward to publishing your research.

Special Collection—submit by September 1st

PLoS ONE would like to receive your work so that we may consider it for inclusion in the collection. Since we pride ourselves on fast publication, for all articles submitted by September 1, 2008, we will strive to get a first decision back to the authors by October 1, 2008. Allowing a month for any revisions and resubmissions, we will then aim to publish the Special Collection in late autumn 2008.

The Academic Editors leading this call for papers include Andreas G. Andreou (Johns Hopkins University), Eugenio Culurciello (Yale University), Yann Lecun (New York University), and Teresa Serrano-Gotarredona (Microelectronics Institute of Seville). The following three articles have been chosen by these Academic Editors to showcase the quality and breadth of our coverage in this area:
* Visual Coding in Locust Photoreceptors by Olivier Faivre and Mikko Juusola.
* Neural Decision Boundaries for Maximal Information Transmission by Tatyana Sharpee and William Bialek.
* Integration across Time Determines Path Deviation Discrimination for Moving Objects by David Whitaker, Dennis M. Levi, and Graeme J. Kennedy.

I interviewed the corresponding author of the paper entitled Visual Coding in Locust Photoreceptors listed above about why he and his co-author chose PLoS ONE, their experiences publishing with us and where their work is heading now.

Q. Why did you choose PLoS ONE to publish your work?
A. We chose to publish in PLoS ONE because the publication process is fast and authors are given great freedom for deciding the layout of the article and choosing the way they present they data. The fact that there was no size restriction, for the text or the number of (colour) figures was an appreciable bonus. Furthermore, we strongly support the open-source policy of PLoS ONE.
Q. What was your publishing experience like and would you do it again? A. The publication process went well, and was overall pretty fast. We especially appreciated that 2 out of 3 referees decided to reveal their identities. We would certainly do it again and recommend our colleagues to publish in PLoS ONE.

Why are Natural and Synthetic Vision researchers like these already publishing in PLoS ONE? Because it is:
* Open Access—freely and immediately available to everyone online. * Fast—papers that pass peer review are rapidly published.
* Peer-Reviewed—for technical soundness and scientific rigor.
* Interactive—tools for rating, commenting on, and discussing research with an online scientific community.
* Funder-Compliant—everything we publish is automatically deposited in PubMed Central.

Here are the papers that we've already published in this field categorized for your convenience.
Neuronal Mechanisms for Vision
Visual Coding in Locust Photoreceptors Olivier Faivre, Mikko Jussola (2008)
Ganglion Cell Adaptability: Does the Coupling of Horizontal Cells Play a Role? Dedek K, Pandarinath C, Alam NM, Wellershaus K, Schubert T, Willecke K, Prusky GT, Weller R, Nirenberg S (2008)
High-Pass Filtering of Input Signals by the Ih Current in a Non-Spiking Neuron, the Retinal Rod Bipolar Cell Cangiano L, Gargini C, Della Santina L, Demontis GC, Cervetto L (2007)
A Novel Interhemispheric Interaction: Modulation of Neuronal Cooperativity in the Visual Areas Carmeli C, Lopez-Aguado L, Schmidt, KE, De Feo O, Innocenti GM (2007)
A Functional Architecture of Optic Flow in the Inferior Parietal Lobule of the Behaving Monkey Raffi M, Siegel RM (2007)

Network Properties and Modeling
Effects of Active Conductance Distribution over Dendrites on the Synaptic Integration in an Identified Nonspiking Interneuron Takashima A, Takahata M (2008)
On How Network Architecture Determines the Dominant Patterns of Spontaneous Neural Activity Galen RF (2008)
Long-Term Activity-Dependent Plasticity of Action Potential Propagation Delay and Amplitude in Cortical Networks Bakkum DJ, Chao ZC, Potter SM (2008)
Network ‘Small-World-Ness’: A Quantitative Method for Determining Canonical Network Equivalence Humphries MD, Gurney K (2008)
Calmodulin Activation by Calcium Transients in the Postsynaptic Density of Dendritic Spines Keller DX, Franks KM, Bartol TM, Sejnowski TJ (2008)
Spike Timing Dependent Plasticity Finds the Start of Repeating Patterns in Continuous Spike Trains Masquelier T, Guyonneau R, Thorpe SJ (2008)
Information and Discriminability as Measures of Reliability of Sensory Coding Grewe J, Weckstrom M, Egelhaaf M & Warzecha A-K (2007) Cellular and Network Contributions to Excitability of Layer 5 Neocortical Pyramidal Neurons in the Rat Bar-Yehuda D, Korngreen A (2007)
Identification and Classification of Hubs in Brain Networks Sporns O, Honey CJ, Kotter R (2007)
Development of Neural Circuitry for Precise Temporal Sequences through Spontaneous Activity, Axon Remodeling, and Synaptic Plasticity Jun JK, Jin DZ (2007)
Synaptic Transmission and Plasticity in an Active Cortical Network Reig R, Sanchez-vives MV (2007)
Neural Decision Boundaries for Maximal Information Transmission Sharpee T, Bialek W (2007)
On the Dynamics of the Spontaneous Activity in Neuronal Networks Mazzoni A, Broccard FD, Garcia-Perez E, Bonifazi P, Ruaro ME, Torre V (2007)
Subspace Projection Approaches to Classification and Visualization of Neural Network-Level Encoding Patterns Osan R, Zhu L, Shoham S, Tsien JZ (2007)
Spike Timing and Reliability in Cortical Pyramidal Neurons: Effects of EPSC Kinetics, Input Synchronization and Background Noise on Spike Timing Rodroguez-Molina VM, Aertsen A, Heck DH (2007)

Visual Psychophysics and Perception
Visual Learning in Multiple-Object Tracking Makovski T, Vázquez GA, Jiang YV (2008)
Spatial and Temporal Dynamics of Attentional Guidance during Inefficient Visual Search Zenon A, Ben Hamed S, Duhamel J-R, Olivier E (2008)
Saccadic Eye Movements Minimize the Consequences of Motor Noise van Beers RJ (2008)
Integration across Time Determines Path Deviation Discrimination for Moving Objects Whitaker D, Levi DM, Kennedy GJ (2008)
Are There Multiple Visual Short-Term Memory Stores? Sligte IG, Scholte HS, Lamme, VAF (2008)
Crayfish Recognize the Faces of Fight Opponents Van der Velden J, Zheng Y, Patullo BW, Macmillan DL (2008)
Self-Consistent Estimation of Mislocated Fixations during Reading Engbert R, Nuthmann A (2008)
Benefits of Stimulus Congruency for Multisensory Facilitation of Visual Learning Sandkuhler S, Bhattacharya J (2008)
Multi-Timescale Perceptual History Resolves Visual Ambiguity Brascamp JW, Knapen THJ, Kanai R, Noest AJ, van Ee R, van den Berg AV (2008)
The Role of Temporally Coarse Form Processing during Binocular Rivalry van Boxtel JJA, Alais D, Erkelens CJ, van Ee R (2008)
Visual Feedback Is Not Necessary for the Learning of Novel Dynamics Franklin DW, So U, Burdet E, Kawato M (2007)
The Effect of Real-World Personal Familiarity on the Speed of Face Information Processing Balas B, Cox D, Conwell E (2007)
Illusory Stimuli Can Be Used to Identify Retinal Blind Spots Crossland MD, Dakin SC, Bex PJ (2007)
Cross-Modal Object Recognition Is Viewpoint-Independent Lacey S, Peters A, Sathian K (2007)
Retinal Encoding of Ultrabrief Shape Recognition Cues Greene E (2007)
Stimulus Motion Propels Traveling Waves in Binocular Rivalry Knapen T, van Ee R, Blake R (2007)
Parts, Wholes, and Context in Reading: A Triple Dissociation Pelli DG, Tillman KA (2007)
Changing Human Visual Field Organization from Early Visual to Extra-Occipital Cortex Jack AI, Patel GH, Astafiev SV, Snyder AZ, Akbudak E, Shulman GL, Corbetta M (2007)
Onset Rivalry: Brief Presentation Isolates an Early Independent Phase of Perceptual Competition Carter O, Cavanaugh P (2007)
Spatio-Temporal Interpolation Is Accomplished by Binocular Form and Motion Mechanisms Kandil FI, Lappe M (2007)
High-Throughput Sequencing of Arabidopsis microRNAs: Evidence for Frequent Birth and Death of MIRNA Genes Fahlgren N, Howell M, Kasschau K, Chapman E, Sullivan C, Cumbie J, Givan S, Law T, Grant S, Dang J, Carrington J (2007)
Perceptual Learning of Motion Leads to Faster Flicker Perception Seitz AR, Nanez JE Sr, Holloway SR, Watanabe T (2006)

We look forward to publishing your research.

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Natural and Synthetic Vision - call for papers

from 2007 on Mon, 2008-07-28 19:11

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Is the NIH open access policy regressive?

Jocalyn Clark — Fri, 25 Jul 2008 13:31:04 -0700

I was thrilled that several PLoS colleagues attended the ISMB conference this past week in Toronto, where I live. The massive event is the official conference of the International Society for Computational Biology, and PLoS Computational Biology is the official journal of the Society.

My friends asked me: “What is computational biology?”

I said: “Good question!”

Wikipedia tells me it’s an intoxicating mix of computer science, applied mathematics, and statistics applied to biology. (ok, I added the intoxicating bit).

My PLoS Biology colleague Robert Shields tells me it’s “the biology that counts.” (ba dum dum).

Definitions aside, I took two things away from the conference that matter to PLoS Medicine.

First, Mark Gerstein from Yale University gave an outstanding talk in a session called The Future of Scientific Publication, remarking that it was unusual (but inspiring) for a computational biology conference to include a session on publishing.

He emphasised the use of text mining to study the “structure of science.” He says this is Science 2.0 (or, the science of science), which uses network theory and technologies to discover new scientific relationships. Whereas conventional challenges have us struggling to keep up with the volume and growth of scientific papers (this reminds me of Muir Gray’s information paradox in medicine - overwhelmed with information but unable to find the knowledge when we need it), new technologies to structure and text mine scientific publications can help scientists share information and foster collaboration. (Including using publications as the annotation for the genome).

Gerstein and colleagues' fascinating maps of publication patterns, gene names, topic clusters within whole research areas, and the emergence of new scientific fields are reminiscent of the recent PLoS Medicine editorial in which we argue that everything in medicine is connected through networks. (When I chatted with Gerstein after his session he agreed that network guru Albert-Lásló Barabási is a genius.)

But none of this is possible without open access, countered Matt Cockerill from BioMed Central. He said that we absolutely need the raw material (whether it be biological data or bibliometric information) freely and openly available to apply the network algorithms so we can visualise the structure of science. Currently, much information is behind access controls thus disrupting the whole vision of an interconnected and collaborative scientific world.

The second issue of note was raised during the session’s Publishers’ Panel, populated by Catherine Nancarrow (PLoS), Claire Bird (Oxford University Press), and Matt Cockerill (BioMed Central). Panellists noted that the recent NIH public access policy emphasises free not open access. That is, the policy may lead to freely accessible publications (for which publishers or organisations may reap profits from charging authors a fee to deposit their manuscripts), but these will remain under restrictive licenses (thus limiting text-mining).

This, Cockerill argued, makes the NIH policy regressive.

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In(s) and Out(s) of Academia

from A Blog Around The Clock on Fri, 2008-07-25 18:52

Bjoern Brembs is on a roll! Check all of these out: Incentivizing open scientific discussion: Apart from the question of whether the perfect scientist is the one who only spends his time writing papers and doing experiments, what incentives can...

Open Access to Health and Human Rights

Gavin Yamey — Wed, 23 Jul 2008 01:37:23 -0700

Here’s another important step forward in the open access movement. Under its new editor Paul Farmer (who is often talked about as a future Nobel laureate), the international journal Health and Human Rights (HHR) has become fully open access.

The entire contents are freely available and are published under a progressive copyright license that allows readers to reuse the materials for any legal non-commercial purpose.

Farmer and colleagues, in a message from the editors in the “new look” HHR, explain why they are abandoning the previous subscription-based model:

“In embracing the open-access model, HHR aligns itself with a global movement for the democratization of scientific knowledge production and a more equitable distribution of the benefits of science, particularly in health. HHR’s distinctive contribution to this movement will come through the journal’s systematic linking of conceptual and legal human rights analysis with documentation of concrete, front-line experiences translating rights principles into social change and health progress on the ground.”

Online interactivity, which is a natural complement to open access, will be a key feature of the new HHR. In addition to the core articles in the journal, the HHR website also showcases a section of “Perspectives.” The editors describe these as “web-only features, including policy analyses, issue briefs, and advocacy documents, as well as invited opinion pieces and short essays aimed to stimulate debate on health and rights.”

“Over time,” they say, “the website will also provide links, not only to other online journals and information resources, but to emergent spaces in which communities of practice are organizing to strengthen peer-to-peer learning among practitioners in rights-based health program design and service delivery (for example, the Global Health Delivery Project at Harvard University).”

In the interests of full disclosure, I ought to declare two things.

First, I’m on the editorial board of HHR and have advised the editors on transitioning the journal to open access. They used the terrific Open Journal Systems platform.

Second, the journal has just published a peer-reviewed paper of mine, called “Excluding the poor from accessing biomedical literature: A rights violation that impedes global health.” Here’s an excerpt:

“Through its transition from a subscription-based to an open access journal that publishes materials under the Creative Commons Attribution License, Health and Human Rights joins the knowledge commons movement. The journal now has the opportunity to help catalyze the creation of an online “health and human rights commons” that would be an extremely powerful tool in the worldwide promotion and protection of health as a human right. This commons could, among other things, provide researchers, clinicians, and activists with unfettered access to the data that they need to support their human rights work. It could become a rich public venue for sharing research and policy data, global analysis, discussion and debate, case reports, and experiences from the field.”

HHR has so far posted two responses to my piece, one from Maurice Long of HINARI, who seems deeply upset that I didn’t heap more praise upon the HINARI project (I stated that “HINARI is a step in the right direction,” which is true, but also that it is “a very long way from providing universal open access,” true again). I’ll respond to Maurice’s critique shortly.

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Open Access to Health and Human Rights

from rights on Wed, 2008-07-23 18:30

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New in: Open Access and Science 2.0

from A Blog Around The Clock on Wed, 2008-07-23 11:22

The complexity of sharing scientific databases: Under US law, pretty much anything you write down is copyrighted. Scrawl an original note on a napkin and it's protected until 70 years after your death. Facts, however, are another matter - they...

Prying into protocols

Emma Veitch — Tue, 22 Jul 2008 09:00:47 -0700

Just spotted an interesting letter in last week's Lancet discussing selective reporting of clinical trials. This may sound like something you've heard many times before (eg here) but in the Lancet letter the authors describe what happenned to trials for which the original protocols were posted on Lancet's own website.

Evidence regarding selective reporting has been around for a while (eg the 2004 study mentioned above pulled out a set of protocols approved by Danish ethics committees, and matched them up with corresponding results publications. The authors showed that 62% of trials had "at least 1 primary outcome that was changed, introduced, or omitted"). However, at the moment very few trial protocols are ever published; the decision to publish or not is entirely voluntary, and very few journals offer the service. The Lancet offers protocol review - although the page is a bit hard to find), as do many of the BioMed Central journals.

In their letter to the Lancet, Al-Marzouki and colleagues describe how, for the set of trials they examined, unreported or switched primary and secondary outcomes were common, with no explanation for why outcomes were included, left out, or changed between the original plan and final report. What's amazing here is that this phenomenon occurs despite the fact that the protocol has been made public at an early stage, entirely voluntarily, and that triallists are presumably aware that as a result their eventual papers might be compared against the original analysis plans.

PLoS Medicine doesn't offer protocol review, but we do require authors to send us copies of the trial protocol when they submit their papers. We, our reviewers and academic editors find it's an incredibly tough job to compare submitted trial reports against protocols, but do occasionally find discrepancies. Al-Marzouki and colleagues suggest that a universal standard for protocols might simplify the process - but we're not there yet. The Good Clinical Practice guidelines provide a format - but only for trials done by drug or device companies to gain regulatory approval. Sadly it seems that in order to carry out a thorough scientific evaluation of a submitted trial, someone -- either an editor, reviewer, or careful reader -- has to .... actually read through the entire protocol... plus the report of course. Surely technology can give us something better than this?

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Harms of promoting off-label uses to doctors

Gavin Yamey — Fri, 18 Jul 2008 02:39:33 -0700

The FDA’s recent proposal to allow drug companies to send doctors journal articles about off-label drug use has come under major fire over the last few months.

Back in April, The New York Times, in a news feature in its business section (F.D.A. Plan on Medical Articles Takes More Heat), highlighted the widespread opposition to the proposal. This opposition came from, among others, Public Citizen, New York State’s health commissioner, Representative Henry Waxman (who sent a letter to the FDA outlining his concerns), and the Blue Cross Blue Shield Association, a trade association of 39 major health insurance plans. Needless to say, the pharmaceutical industry supports the proposal.

The proposal includes a set of principles that drug companies are supposed to follow, such as only sending doctors articles that have been peer-reviewed. As Randall Stafford (Stanford University) points out, there are two particularly striking things about the proposal:

“First, manufacturers need no longer limit their promotion of off-label uses to drugs and indications for which they are working toward FDA evaluation; and second, there is no requirement for advance FDA review of the journal articles to be distributed.”

But given that off-label prescribing is widespread in the US, what could be the harm of simply allowing drug companies to promote more of it? That’s a question answered by Andy Gass (University of California Berkeley) and Jennifer Wilson (University of California San Francisco) in a recent editorial in the American Journal of Bioethics (Disclosure: Andy used to work at PLoS as our outreach coordinator).

The authors lay out four potential harms.

First, they say, the selection of articles distributed to physicians by industry is likely to be biased.

Second, “the requirement that information passed on by industry be limited to peer reviewed journal articles may do little, in practice, to ensure the scientific quality of the evidence contained therein.” Or, as Joseph Ross (Mt Sinai School of Medicine), author of a JAMA study on ghostwriting in trial reports on rofecoxib, told the New York Times: “What does it mean to be peer-reviewed… if the company has essentially conceived the article, composed the draft and written the paper?”

Third, say Gass and Wilson, a rapid proliferation of off-label prescriptions, which might plausibly follow from a rapid proliferation of off-label marketing to physicians, could make it more difficult to track drug safety.

Finally, they say, the omission of a requirement that companies pursue approval for the off-label uses they promote “eliminates any incentive for industry to invest in studies beyond those necessary to earn preliminary approval.” The effect of this policy change, they say, could be quite radical. “The FDA might be left out of the regulatory loop for many of the indications for which companies market drugs to physicians.”

Although the American Journal of Bioethics is a subscription based journal, Andy’s time at PLoS naturally made him an open access advocate—so he has retained copyright on the piece (using the Creative Commons Attribution License) and deposited a copy into the freely available eScholarship repository at UC Berkeley.

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Journal Websites - Topaz 0.9 rc1 Upgrade

Richard Cave — Thu, 17 Jul 2008 17:03:14 -0700

Last night, we upgraded the journal websites to Topaz 0.9 rc1 (rc1 because this is a “beta” 0.9 release). The development for this release focused on performance and stability - specifically to alleviate the sluggish speed of the websites and the pain of ingests.

The development included a major re-architecture of the publishing application and weeks of performance testing. There are a few minor issues but the sites are quite zippy and the new ingest times have, to quote James "exceeded expectations." We’ll probably have a few more quick restarts over the next few days as we shift through the logs/bugs but we won’t have to rebuild the article cache ever again (another pain point).

Thanks to Russ for the heroic migration day, Josh for the speedy drive rebuilds of the Mulgara server last night, and to the Topaz/PLoS developers that got this "beta" release out the door. We still have some cleanup after the dust settles, but I feel confident that the site performance/stability has greatly improved.

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Journal Websites - Topaz 0.9 rc1 Upgrade

from journal on Fri, 2008-07-18 01:21

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TOPAZ upgrade

from A Blog Around The Clock on Thu, 2008-07-17 17:09

TOPAZ software, the one that hosts five out of six PLoS journals (ONE, Pathogens, Neglected Tropical Diseases, Genetics and Computational Biology) has just been upgraded. There is not much new in the terms of functionality visible to readers, but the...