Clinical trials are becoming more complex: a machine learning analysis of data from over 16,000 trials.

The past decade has seen substantial innovation in clinical trials, including new trial formats, endpoints, and others. Also there have been regulatory changes, increasing competitive pressures and other external factors which impact clinical trials. In parallel, trial timelines have increased and success rates remain stubbornly low. This has led many observers to question whether clinical trials have become overly complex and if this complexity is always needed. Here we present a large-scale analysis of protocols and other data from over 16,000 trials. Using a machine learning algorithm, we automatically assessed key features of these trials, such as number of endpoints, number of inclusion-exclusion criteria and others. Using a regression analysis we combined these features into a new metric, the Trial Complexity Score, which correlates with overall clinical trial duration. Looking at this score across different clinical phases and therapeutic areas we see substantial increases over time, suggesting that clinical trials are indeed becoming more complex. We discuss drivers of increasing trial complexity, necessary or helpful ('good') complexity versus unnecessary ('bad') complexity, and we explore mechanisms of how sponsors of clinical trials can reduce trial complexity where appropriate.

Corrosion Behavior and Susceptibility to Stress Corrosion Cracking of Leaded and Lead-Free Brasses in Simulated Drinking Water.

Duplex α + ß' brasses are widely used in drinking water distribution systems for tube fittings, valves, and ancillaries because they are low cost, easy to fabricate, and exhibit high mechanical strength. However, depending on application conditions and alloy composition, they may undergo dealloying and stress corrosion cracking. In this research, three different brass types, two leaded (CW617N and CW602N) alloys and one lead-free brass (CW724R), were investigated to assess their corrosion behavior and susceptibility to stress corrosion cracking (SCC) in simulated drinking water (SDW) solutions containing different chloride concentrations, compatible with drinking water composition requirements according to Moroccan standard NM 03.7.001. The corrosion behavior was assessed by electrochemical tests such as polarization curve recording and electrochemical impedance spectroscopy (EIS) monitoring, coupled to SEM-EDS surface observations. The susceptibility to SCC was investigated by slow strain rate tests (SSRT). The tests showed that corrosion was mainly under diffusion control and chlorides slightly accelerated corrosion rates. All alloys, and particularly CW617N, were affected by SCC under the testing conditions adopted and in general the SCC susceptibility increased at increasing chloride concentration.