Early phase clinical trials in oncology: Realising the potential of seamless designs.

BACKGROUND: The pharmaceutical industry's productivity has been declining over the last two decades and high attrition rates and reduced regulatory approvals are being seen. The development of oncology drugs is particularly challenging with low rates of approval for novel treatments when compared with other therapeutic areas. Reliably establishing the potential of novel treatment and the corresponding optimal dosage is a key component to ensure efficient overall development. A growing interest lies in terminating developments of poor treatments quickly while enabling accelerated development for highly promising interventions. METHODS: One approach to reliably establish the optimal dosage and the potential of a novel treatment and thereby improve efficiency in the drug development pathway is the use of novel statistical designs that make efficient use of the data collected. RESULTS: In this paper, we discuss different (seamless) strategies for early oncology development and illustrate their strengths and weaknesses through real trial examples. We provide some directions for good practices in early oncology development, discuss frequently seen missed opportunities for improved efficiency and some future opportunities that have yet to fully develop their potential in early oncology treatment development. DISCUSSION: Modern methods for dose-finding have the potential to shorten and improve dose-finding and only small changes to current approaches are required to realise this potential.

Augmented screwdrivers can increase the performance of orthopaedic surgeons compared with use of normal screwdrivers.

Orthopaedic screws insertion can be trivialised as a simple procedure, however it is frequently performed poorly. Limited work exists defining how well surgeons insert screws or whether augmented screwdrivers can aid surgeons to reduce stripping rates and optimise tightness. We aimed to establish the performance of surgeons inserting screws and whether this be improved with screwdriver augmentation. 302 orthopaedic surgeons tightened 10 non-locking screws to what they determined to be optimum tightness into artificial bone sheets. The confidence in the screw purchase was given (1-10). A further 10 screws were tightened, using an augmented screwdriver that indicated when a predetermined optimum tightness was reached. The tightness for unstripped insertions under normal conditions and with the augmented screwdriver were 81% (95% CI 79-82%)(n = 1275) and 70% (95% CI 69-72%)(n = 2577) (p < 0.001). The stripping rates were 58% (95% CI 54-61%) and 15% (95% CI 12-17%) respectively (p < 0.001). The confidences when using the normal and augmented screwdrivers respectively were 7.2 and 7.1 in unstripped insertions and 6.2 and 6.5 in stripped insertions. Performance improved with an augmented screwdriver, both in reduced stripping rates and greater accuracy in detecting stripping. Augmenting screwdrivers to indicate optimum tightness offer potentially enormous clinical benefits by improving screw fixation.