US Food and Drug Administration (FDA)‐approved diagnostic assays play an increasingly common role in managing patients to prolong lifespan while also enhancing quality of life. Diagnostic assays can be essential for the safe and effective use of therapeutics (companion diagnostic), or may inform on improving the benefit/risk ratio without restricting drug access (complementary diagnostic). This tutorial reviews strategic considerations for drug and assay development resulting in FDA‐approved companion or complementary diagnostic status.

The use of ASCT in adults with lymphoblastic lymphoma in first remission produced a trend for improved relapse-free survival but did not improve overall survival compared with conventional-dose therapy in this small randomized trial.

In vivo, two effects of beta-adrenergic stimulation in cardiac muscle are phosphorylation of troponin I and an increase in relaxation rate. In vitro, cardiac TnI can be phosphorylated by protein kinase A (PKA). We have used the technique of laser flash photolysis of the calcium chelator diazo-2 to investigate the effect of phosphorylation of TnI on the relaxation rate of skinned trabeculae from the guinea-pig at 12 degrees C. The fibres were phosphorylated by PKA, and double exponential curve fits of the average relaxation transients showed no significant difference between the rate constants of the phosphorylated and control cases. We conclude that TnI phosphorylation has no effect on the rate of relaxation in skinned trabeculae from the guinea-pig following diazo-2 photolysis.

The aim of this study was to examine the effect of the metabolites H+, ADP, and Pi on the rate of cardiac relaxation. We used guinea pig right ventricular trabeculae that had been chemically skinned, allowing the myofilaments to be studied in isolation. Laser-flash photolysis of the caged Ca2+ chelator diazo 2, causing a rapid fall in intracellular Ca2+, enabled investigation of relaxation independently of the rate of Ca2+ diffusion. On the photolysis of diazo 2, the trabeculae relaxed biphasically with exponential rate constants ( k 1 and k 2) of 10.07 and 4.23 s−1, respectively, at 12°C and 18.35 and 2.52 s−1, respectively, at a nominal 20°C. Increasing the concentration of both protons (pH 7.2–6.8) and MgADP (0.5–3.4 mM) slowed the two phases of the relaxation transients. Raising the concentration of Pi from the control level of 1.36 mM to 15.2 mM increased the rate of both phases, with relaxation becoming monoexponential at 19.4 mM Pi (with a k of 20.31 s−1 at 12°C). Cardiac muscle was compared with skeletal muscle under identical conditions; in cardiac muscle 19.4 mM Piincreased the rate of relaxation, whereas in skeletal muscle this concentration of Pi slowed relaxation. We conclude that the mechanism of relaxation differs between cardiac and skeletal muscle. This study is a direct demonstration of the effects of ATP metabolites on cardiac myofilament processes during relaxation.