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Semantic natural language processing and philosophy of science
On 2015 February 18, James Overton visited the STREAM research group in Montreal, where he presented his research into what scientists are doing when give an explanation for something. Many accounts of scientific explanation have been offered by philosophers of science over the years, but Overton’s offering differs in that he set out to establish…
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Nope– It’s Still Not Ethical
Last year, Jonathan and I published a critique of unequal allocation ratios in late-phase trials. In these trials, patient-subjects are randomly allocated among the treatment arms in unequal proportions, such as 2:1 or 3:1, rather than the traditional equal (1:1) proportion. Strangely, despite introducing an additional burden (i.e., requiring larger sample sizes) the practice of unequal allocation…
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Charting the Unpredictable: Using fMRI patterns to determine outcome in acutely comatose patients
Every year in Canada around 50,000 people suffer brain injuries, with those experiencing severe traumas often becoming comatose for days or weeks post-incident. While there exists a battery of physiological prognostic indicators, such as pupillary light reflex (or lack thereof), and patterns of EEG activity, there remains a significant subset of patients who retain an…
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Unsuccessful trial accrual and human subjects protections: An empirical analysis of recently closed trials
The moral acceptability of a clinical trial is rooted in the risk and benefit for patients, as well as the ability of the trial to produce generalisable and useful scientific knowledge. The ability of a clinical trial to justify its claims to producing new knowledge depends in part on its ability to recruit patients to…
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The Landscape of Early Phase Research
As Jonathan is fond of saying: Drugs are poisons. It is only through an arduous process of testing and refinement that a drug is eventually transformed into a therapy. Much of this transformative work falls to the early phases of clinical testing. In early phase studies, researchers are looking to identify the optimal values for the various…
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The Literature Isn’t Just Biased, It’s Also Late to the Party
Animal studies of drug efficacy are an important resource for designing and performing clinical trials. They provide evidence of a drug’s potential clinical utility, inform the design of trials, and establish the ethical basis for testing drugs in human. Several recent studies suggest that many preclinical investigations are withheld from publication. Such nonreporting likely reflects…
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Search, Bias, Flotsam and False Positives in Preclinical Research
If you could change one thing- and only one thing- in preclinical proof of principle research to improve its clinical generalizability, what would it be? Require larger sample sizes? Randomization? Total data transparency? In the May 2014 issue of PLoS Biology, my co-authors Uli Dirnagl and Jeff Mogil offer the following answer: clearly label preclinical…
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The Cost of Missing Information
The medical research enterprise produces a massive amount of information that is critical for effective medical care, public health, innovation, and sound public policy. Yet only a fraction of this information is actually captured. Thus, for example, recent studies show that 17% of healthy volunteer phase 1 trials are published in scientific journals, whereas only 43% of…
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In Memorium for Kathy Glass
I first met Kathy in August 2001 when, newly arrived in Montreal with a totally useless PhD in molecular genetics, I approached her, hat in hand, looking for a postdoctoral position in Biomedical Ethics. Actually, my hat wasn’t in hand- it was on my head- I had a week earlier accidentally carved a canyon in…
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The Ethics of Unequal Allocation
In the standard model for randomized clinical trials, patients are allocated on an equal, or 1:1, basis between two treatment arms. This means that at the conclusion of patient enrollment, there should be roughly equal numbers of patients receiving the new experimental treatment as those receiving the standard treatment or placebo. This 1:1 allocation ratio…
