Continual Reassessment and Related Dose-Finding Designs

During the last twenty years there have been considerable methodological developments in the design and analysis of Phase 1, Phase 2 and Phase 1/2 dose-finding studies. Many of these developments are related to the continual reassessment method (CRM), first introduced by O'Quigley, Pepe and Fisher (\citeyearQPF1990). CRM models have proven themselves to be of practical use and, in this discussion, we investigate the basic approach, some connections to other methods, some generalizations, as well as further applications of the model. We obtain some new results which can provide guidance in practice.Comment: Published in at http://dx.doi.org/10.1214/10-STS332 the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Non invasive detection of biological fluids: a new perspective in monitoring pH in saliva and sodium in sweat

The chemical composition of body fluids contains crucial information about the state of health of an individual. While many efforts have been already directed toward real time analysis of blood and urine, there is still a pressing need for new solutions to non-invasively monitor other fluids like saliva and sweat1. Towards this aim, the main technological challenge is the development of devices that are at the same time low-cost, minimally invasive and wearable, so that they could be used for in situ and real-time monitoring of physiological conditions2. For example, continuous recording of sodium levels in sweat could be an informative tool to assist clinicians in prescribing a more personalised treatment of diseases such as Cystic Fibrosis3 and in assessing athletes’ performances4. Similarly, the monitoring of pH levels in saliva provides valuable information for the treatment of pathologies where physiological mouth conditions are compromised, like in Gastroesophageal Reflux Disease (GERD)5. Ion Selective Electrodes (ISEs) are potentiometric sensors designed to detect specific ions in blood and saliva. Using dual-screen printed electrodes as substrates, we were able to reduce their production cost, improve reproducibility, and combine pH5 and sodium ISEs with solid contact reference electrodes. In our design, the sensors will be interfaced to two miniaturized potentiometric platforms (WIXEL for pH and Tyndall Mote for sodium detection) that were wirelessly connected to a base station. For pH measurements, the device will be accommodated into a gum shield. For sodium detection instead, we will use a microfluidic channel to convey sweat to the electrodes. The mote communication platform was adapted so that it could be worn on the upper shoulder through a fiber strip

Screen printed electrochemical sensors for real-time sodium monitoring in sweat

We report on the preparation of disposable potentiometric sensor strips for monitoring sodium in sweat. We also present their integration in a microfluidic chip used to harvest sweat in-situ during exercise. The sensor-chip is integrated with a miniaturized electronic platform able to transmit data wirelessly in real time during a stationary cycling session in a controlled environment

Wearable chemical sensing – sensor design and sampling techniques for real-time sweat analysis

Wearable chemical sensors have the potential to provide new methods of non-invasive physiological measurement. The nature of chemical sensors involves an active surface where a chemical reaction must occur to elicit a response. This adds complexity to a wearable system which creates challenges in the design of a reliable long-term working system. This work presents the design of a real-time sweat sensing platform to analyse sweat loss and composition. Sampling methods have an impact on composition therefore skin encapsulation needs to be avoided so as not to disrupt normal sweating patterns. Sensors ideally need to be placed close to the sampling site which may be subject to motion artefacts [1]. The design of this device takes into account sample collection and delivery, sensor placement and associated electronics. The overall design is ergonomic to interface with the contours of the body. Results of lab-based simulations and real-time exercise trials are presented. This device can offer valuable information regarding hydration status and electrolyte balance which may be especially important for optimised rehydration during or after sports activities. [1] Curto, V. F. S. Coyle, R. Byrne, N. Angelov, D. Diamond, F. Benito-Lopez., Sens. Actuators, B, 2012, 175, 263-270

Personal sensing wear: the role of textile sensors

Wearable sensors for fitness tracking are becoming increasingly popular and are set to increase as smartwatches begin to dominate the wearable technology market. Wearable technology provides the capacity to track long-term trends in the wearer’s health. In order for this to be adopted the technology must be easy to use and comfortable to wear. Textile based sensors are ideal as they conform to the body and can be integrated into the wearer’s everyday wardrobe. This work discusses fabric stretch sensors that can measure body movements. An application using a sensor glove for home assessment of Rheumatoid Arthritis is presented. This work is the result of a multidisciplinary effort, involving expertise in material science and functional design, computer science, human health and performance and influenced by the end user needs

A Hierarchical Bayesian Design for Phase I Trials of Novel Combinations of Cancer Therapeutic Agents

We propose a hierarchical model for the probability of dose-limiting toxicity (DLT) for combinations of doses of two therapeutic agents. We apply this model to an adaptive Bayesian trial algorithm whose goal is to identify combinations with DLT rates close to a prespecified target rate. We describe methods for generating prior distributions for the parameters in our model from a basic set of information elicited from clinical investigators. We survey the performance of our algorithm in a series of simulations of a hypothetical trial that examines combinations of four doses of two agents. We also compare the performance of our approach to two existing methods and assess the sensitivity of our approach to the chosen prior distribution.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78700/1/j.1541-0420.2009.01363.x.pd

Parametric non-mixture cure models for schedule finding of therapeutic agents

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75664/1/j.1467-9876.2008.00660.x.pd