Constructing better multivariate biomarker composites

The earliest biomarkers, such a body temperature or blood pressure, were single measurements that reflected multiple physiological processes.  Today, though, our reductionist approach to biology has turned up the resolution of our lens: we can measure levels of individual proteins, metabolites and nucleic acid species, opening the biomarker floodgates. But this increased resolution has not necessarily translated into increased power to predict.  The principal use of biomarkers after all is to use things that are easy to measure to predict more

The HDL myth: how misuse of biomarker data cost Roche and its investors $5billion

On May 7th 2012, Roche terminated the entire dal-HEART phase III programme looking at the effects of their CETP inhibitor dalcetrapib in patients with acute coronary syndrome.  The immediate cause was the report from the data management committee of the dal-OUTCOMES trial in 15,000 patients that there was now no chance of reporting a 15% benefit with the drug. The market reacted in surprise and disappointment and immediately trimmed $5billion of the market capitalization of Roche.  After all, here was a

The interleukin lottery: playing the odds on numbers 9 and 16

The interleukins are an odd family.  One name encompasses dozens of secreted proteins that are linked by function rather than by structure.  And even that common function is very broadly defined: cytokines that communicate between cells of the immune system. Defined in such a way, its perhaps not surprising that the interleukins have yielded some of the best biomarkers of inflammatory disease conditions, and even more importantly are the target for a growing range of antibody therapeutics.  Interfering with interleukins is

Environmental Pollutants: Opening a Soup-Can of Worms

They are everywhere: so called ‘present organic pollutants’, or POPs for short.   Since almost all the everyday items that make modern life so much easier emerged from a chemical factory, its not surprising that environmental contamination with organic chemicals is increasing all the time – even ‘environmentally aware’ Western countries.  But maybe it will surprise you to learn they are in your food as well. New data, published in the Journal of the American Medical Association last week,

Smoke Screen: The intensifying debate about population screening generates more heat than light

If a test with prognostic value exists, should it be used for population screening? On the face of it, it’s a simple question, but it doesn’t have a simple answer.  Like most things in life, it depends on the context: how prevalent and how dangerous is the disease?  How invasive and how expensive is the test? So if we are dealing with cancer, which can be fatal if not diagnosed early, and a screening test such as a mammogram or a

Personalized Medicine Demands Investment in Innovative Diagnostics: Will the Returns be High Enough?

Several very senior pharma executives were recently overhead by a journalist discussing what each of them viewed as the most important changes in the way healthcare will be delivered over the coming decade.  Each of them listed several such factors, including increased payor pressure on prices, the mounting regulatory burden and the shift toward orphan indications, but there was unanimity on just one factor: the importance of personalized medicine. Personalized medicine is the great white hope for the pharmaceutical industry: by

Ultra-sensitive NMR-based diagnosis for infectious diseases: the tortoise races the hare again

Obtaining rapid and reliable diagnosis of infectious diseases is usually limited by the sensitivity of the detection technology.   Even in severe sepsis, accompanied by organ failure and admission to an intensive care unit, the causative organism is often present at a level of less than one bacterium per milliliter of blood.  Similarly, in candidiasis the yeast cells are present at vanishingly low levels in body fluids, while in chlamydia infections the pathogen is located intracellularly as is entirely absent from

Chemokines as biomarkers for cancer: Time to revisit an old friend?

A wide-ranging study pre-published on-line in Nature last month points the finger at the chemokine CCL2 (also known as MCP-1, or JE in mice) as a key regulator of tumour metastasis.  Intriguingly, CCL2 seems to participate in the generation of clinically-relevant metastatic disease on multiple levels: it promotes seeding of the shed metastatic cells, but it also promotes establishment and growth of the micrometastases, a process that is dependent on VEGF production from a tissue macrophage subset that

The final frontier – post-genomic biomarkers

Some biomarkers are easier to find than others.  Once a class of molecules has been noticed, and the assay methodology to measure their levels has been optimized, data rapidly accumulates.  Related molecules frequently pop up (often as a result of artifacts appearing in the assays under certain conditions or when particular samples are analysed).  Its rather like unearthing an ancient pyramid – if the first dig identifies the tip of the pyramid, the rest follows quite quickly. But imagine what it

Finding exogenous biomarkers of heart disease: humans are ecosystems too!

It is ten years this week (20th May 2011) since the Total Scientific team, together with our collaborators at Imperial College in London submitted the first large-scale clinical metabolomics study for publication in Nature Medicine.  We applied proton NMR spectroscopy to serum samples collected from patients with coronary heart disease (defined by angiography), as well as control subjects with normal coronary arteries.  The results were dramatic: we could completely separate the groups of subjects based on the