Because she was less socially invisible than impeccable in her refinement, the trial testimony about her friendship with an ambitious political comer struck a weirdly dissonant note.
Such values may require further refinement using trial-and-error procedures upon implementation.
Over time, incremental refinement in trial design will likely aid robust examination of treatment effects in client-owned dogs with arthritis.
The future success of targeted therapy will involve initiatives to identify the most promising targets, closer integration of preclinical and clinical data, a greater use of genomic and proteomic techniques, and further refinement of trial design.
Evaluation of these agents will therefore require refinements in trial design to robustly detect 'soft' end points such as stable disease, coupled with the development and validation of improved markers for assessing biological activity.
However, the preclinical data and the absence of a peak in circulating caspase-cleaved CK18 in trial patients suggest suboptimal timing of blood sampling, which will need refinement in future trials incorporating obatoclax.
With the refinement of clinical trial designs over the past 40 years, the randomized controlled trial (RCT) has assumed the role of gold standard, providing the highest level of evidence for therapeutic efficacy.
The trial encompasses a multimodal approach combining structural and functional outcomes with clinical measures enabling the refinement of future trial designs.
We discuss issues implicated in inadequate efficacy, variability of responsiveness, and poor retention of benefit, while recommending design and conceptual refinements for future trials of cerebral neuromodulation in management of chronic neuropathic pain.
Finally, Malcolm Ranson and Gordon Jayson consider the future of targeted therapy, highlighting the need for closer integration of preclinical and clinical data, a greater use of genomic and proteomic techniques, and further refinement of clinical trial design.
