Clinical biomarker innovation: when is it worthwhile?

Background Choosing which biomarker tests to select for further research and development is not only a matter of diagnostic accuracy, but also of the clinical and monetary benefits downstream. Early health economic modeling provides tools to assess the potential effects of biomarker innovation and support decision-making. Methods We applied early health economic modeling to the case of diagnosing primary aldosteronism in patients with resistant hypertension. We simulated a cohort of patients using a Markov cohort state-transition model. Using the headroom method, we compared the currently used aldosterone-to-renin ratio to a hypothetical new test with perfect diagnostic properties to determine the headroom based on quality-adjusted life-years (QALYs) and costs, followed by threshold analyses to determine the minimal diagnostic accuracy for a cost-effective product. Results Our model indicated that a perfect diagnostic test would yield 0.027 QALYs and increase costs by €43 per patient. At a cost-effectiveness threshold of €20,000 per QALY, the maximum price for this perfect test to be cost-effective is €498 (95% confidence interval [CI]: €275-€808). The value of the perfect test was most strongly influenced by the sensitivity of the current biomarker test. Threshold analysis showed the novel test needs a sensitivity of at least 0.9 and a specificity of at least 0.7 to be cost-effective. Conclusions Our model-based approach evaluated the added value of a clinical biomarker innovation, prior to extensive investment in development, clinical studies and implementation. We conclude that early health economic modeling can be a valuable tool when prioritizing biomarker innovations in the laboratory.

Daily oxytocin patterns in relation to psychopathy and childhood trauma in residential youth.

Inconsistent findings have been found on the relation between oxytocin levels and psychopathy or callous-unemotional (CU) traits in humans, potentially because the role of trauma in oxytocin secretion and the distinction between primary and secondary psychopathy have been overlooked so far. Primary psychopathy has a stronger biological background, whereas secondary psychopathy mainly develops due to environmental adversity, such as childhood trauma. This study investigated the interaction effects of CU traits and childhood trauma on daily salivary oxytocin levels in 57 males living in residential youth care facilities. Participants provided six saliva samples (morning, afternoon, and evening for two consecutive days) and completed self-report questionnaires on CU traits and childhood trauma. A mean daily oxytocin and an oxytocin pattern across the day were examined. A significant interaction between CU traits and one trauma category (emotional neglect) on mean daily oxytocin was observed, demonstrating that subjects with high CU traits and low levels of emotional neglect (primary psychopathy) exhibited lower daily oxytocin secretion compared to subjects with high CU traits and high levels of emotional neglect (secondary psychopathy). There were no significant interactions with the other trauma types or in daily oxytocin patterns. Our findings provided a first insight into the potentially distinct oxytocin concentrations in primary and secondary psychopathy, suggesting that primary psychopathy might be linked to lower daily oxytocin output. Future longitudinal studies are required to unravel the developmental patterns of oxytocin secretion and determine whether lower oxytocin output might be a biomarker of primary psychopathy.