We also determined whether or not there were prior proof-of-principle RCTs relevant to each RCT and whether the same group did the POP and pivotal RCTs.
Ironically these large, pivotal RCTs moved forward because prior proof-of-principle (POP /Phase II RCTs showed significant results for a surrogate marker chosen to predict success in pivotal Phase III RCTs.
All but one of the RCTs was preceded by prior proof-of-principle (Phase II) RCTs, and one RCT [8] was preceded by a similar RCT of intensive insulin in the critically ill [19].
All but one of the RCTs was preceded by prior proof-of-principle Phase II RCTs, and another prior pivotal Phase III [8] RCT by the same group preceded the pivotal RCT.
We recorded source of sponsorship, sample sizes, types of interventions, mortality rates, ARI (as well as odds ratios, relative risks and number needed to harm), whether there were pre-specified interim analyses and early stopping rules, and whether or not there were prior proof-of-principle (also known as Phase II) RCTs.
We found wide ranges in sponsorship (industry or not), type(s) of intervention(s), use of DSMBs, presence of interim analyses and early stopping rules, absolute risk increase (ARI), and whether or not adequate prior proof-of-principle Phase II studies were done of RCTs that found increased mortality rates of the intervention compared to control groups.
Our hypothesis was that there would be wide ranges in sponsorship (industry or not), type(s) of intervention(s), use of DSMBs, presence of interim analyses and early stopping rules, absolute risk increase (ARI), and whether or not adequate prior proof-of-principle Phase II studies were done of RCTs that found increased mortality rates of the intervention compared to control groups.
The authors have described our prior proof-of-concept study on early posttransplant insulin administration (3), which has become the basis for currently ongoing NODAT prevention trials exploring strategies of insulin administration (clinical trial reg. nos. NCT01683331 and NCT01680185).
Coverage is a fundamental QoS of topology control in WSNs, we studied coverage provision based on a prior proof that if the radio range of sensor is equal to or greater than twice the sensing range, then complete coverage implies connectivity, as a result, the network connectivity is provided as well.
Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis.
