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… Continue reading The Literature Isn’t Just Biased, It’s Also Late to the Party
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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… Continue reading Search, Bias, Flotsam and False Positives in Preclinical Research
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… Continue reading The Cost of Missing Information
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… Continue reading In Memorium for Kathy Glass
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… Continue reading The Ethics of Unequal Allocation
Pharmacodynamic Studies in Drug Development: What you don’t know can hurt you
Research biopsies involve the collection of tissues for scientific endpoints. In the early phase cancer trials, research biopsies are often used to assess the biological activity of a drug on a molecular level. This is called pharmacodynamics – the study of what a drug does to the body at the molecular or cellular level. Because… Continue reading Pharmacodynamic Studies in Drug Development: What you don’t know can hurt you
Uncaging Validity in Preclinical Research
High attrition rates in drug development bedevil drug developers, ethicists, health care professionals, and patients alike. Increasingly, many commentators are suggesting the attrition problem partly relates to prevalent methodological flaws in the conduct and reporting of preclinical studies. Preclinical efficacy studies involve administering a putative drug to animals (usually mice or rats) that model the… Continue reading Uncaging Validity in Preclinical Research
No trial stands alone
“The result of this trial speaks for itself!” This often heard phrase contains a troubling assumption: That an experiment can stand entirely on in its own. That it can be interpreted without reference to other trials and other results. In a couple of articles published over the last two weeks, my co-authors and I deliver… Continue reading No trial stands alone
When is it legitimate to stop a clinical trial early?
Inspired by a paper that I’m working on with a few of my colleagues from the STREAM research group on the subject of the accrual of subjects in human research, I’ve been reading through a number of articles related to the question, When is it legitimate to stop a clinical trial that is already in progress?… Continue reading When is it legitimate to stop a clinical trial early?
How Many Negative Trials Do We Need?
There is a growing concern in the clinical research community about the number of negative phase 3 trials. Given that phase 3 trials are incredibly expensive to run, and involve hundreds or sometimes thousands of patient-subjects, many researchers are now calling for more rigorous phase 2 trials, which are more predictive of a phase 3… Continue reading How Many Negative Trials Do We Need?