in clinical trials, or for use in clinical practice, perhaps to allow an intervention intended to reverse, or at least slow, clinical progression. A good example of a biomarker that has proven value as an early indicator of the need for clinical action is the rate of change in serum creatinine as a biomarker for incipient renal failure [12, 13] . Surrogate endpoints have a chequered history. In the statistical literature, the widely cited criteria" for surrogacy [7] are very difficult to establish “Prentice in practice. In particular, establishing a correlation between a health outcome and a biomarker is far from sufficient to establish surrogacy [14] . In the medical literature, Psaty et al [15] discuss how treatments that appear beneficial on the basis of a surrogate end-point can later prove to have a harmful effect on the relevant clinical end-point. Modern technological developments are increasingly opening up new possibilities for biomarker discovery. Traditionally, the term trial refer to a direct biophysical “biomarker” or biochemical measurement. Nowadays, however, the term can include summary descriptors of an intrinsically high-dimensional object, such as a digital image, a time series, or a chemical spectrum, termed Our work to explore acoustic “biosignals”. emission (AE) as a biomarker for knee OA [16-19] illustrates some of the challenges which are being raised by the ever-broadening scope of technologies being explored as potential biosignals. As described below, the raw data from an AE time series consist of a record of levels recorded from knees throughout a person's sit-stand-sit movement. Low of AE are potentially contaminated by background noise. For this reason, the recording equipment stores only AE levels that exceed a pre-specified threshold. Each such exceedance is termed a Potential biomarkers include the frequency and positions of “hit”.
in clinical trials, or for use in clinical practice, perhaps to allow an intervention intended to reverse, or at least slow, clinical progression. A good example of a biomarker that has proven value as an early indicator of the need for clinical action is the rate of change in serum creatinine as a biomarker for incipient renal failure [12, 13] . Surrogate endpoints have a chequered history. In the statistical literature, the widely cited “Prentice criteria" for surrogacy [7] are very difficult to establish in practice. In particular, establishing a correlation between a health outcome and a biomarker is far from sufficient to establish surrogacy [14] . In the medical literature, Psaty et al [15] discuss how treatments that appear beneficial on the basis of a surrogate end-point can later prove to have a harmful effect on the relevant clinical end-point. Modern technological developments are increasingly opening up new possibilities for biomarker discovery. Traditionally, the term “biomarker” refer to a direct biophysical or biochemical measurement. Nowadays, however, the term can include summary descriptors of an intrinsically high-dimensional object, such as a digital image, a time series, or a chemical spectrum, termed “biosignals”. Our work to explore acoustic emission (AE) as a biomarker for knee OA [16-19] illustrates some of the challenges which are being raised by the ever-broadening scope of technologies being explored as potential biosignals. As described below, the raw data from an AE time series consist of a record of recorded from knees throughout a person's sit-stand-sit movement. Low levels of AE are potentially contaminated by background noise. For this reason, the recording equipment stores only AE levels that exceed a pre-specified threshold. Each such exceedance is termed a “hit”. Potential biomarkers include the frequency and positions of trial
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