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Contains fulltext : 152302.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. STUDY DESIGN AND SETTING: Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. RESULTS: We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. CONCLUSIONS: IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials.

Rocuronium bromide, a nondepolarizing muscle relaxant has been shown to have a short onset and intermediate duration of action in adults and young children. We evaluated onset time, intubating conditions, as well as duration of action of rocuronium in children ages four to 12 years during nitrous oxide-halothane anaesthesia. Following a stable recording of train-of-four (TOF) impulses at the ulnar nerve, patients were given rocuronium 600 micrograms.kg-1 intravenously. We found that the time to 90% and 100% neuromuscular (N-M) block of the (TOF) was 51 +/- 18 s and 66 +/- 32 s respectively. Intubation was achieved at 94 +/- 31 s and rated as good or excellent in all cases. Time to recovery of N-M transmission to 25%, 75% and 90% of control was 29 +/- 8 min, 42 +/- 14 min and 46 +/- 16 min respectively. Heart rate increased approximately 12 BPM after drug injection, while the blood pressure remained unchanged. From our data we conclude that, as in other age groups, rocuronium has a rapid onset, intermediate duration of action in children 4-12 years of age, and appears devoid of significant side effects.

Summary Background Many randomised controlled trials have investigated the effect of adjuvant chemotherapy in operable non-small-cell lung cancer. We undertook two comprehensive systematic reviews and meta-analyses to establish the effects of adding adjuvant chemotherapy to surgery, or to surgery plus radiotherapy. Methods We included randomised trials, not confounded by additional therapeutic differences between the two groups and that started randomisation on or after Jan 1, 1965, which compared surgery plus adjuvant chemotherapy versus surgery alone, or surgery plus adjuvant radiotherapy and chemotherapy versus surgery plus adjuvant radiotherapy. Updated individual patient data were collected, checked, and included in meta-analyses stratified by trial. The primary endpoint was overall survival, defined as time from randomisation until death by any cause. All analyses were by intention to treat. Findings The first meta-analysis of surgery plus chemotherapy versus surgery alone was based on 34 trial comparisons and 8447 patients (3323 deaths). We recorded a benefit of adding chemotherapy after surgery (hazard ratio [HR] 0·86, 95% CI 0·81–0·92, p

In seven patients anaesthesia was induced by injection of a single dose of Innovar and maintained with nitrous oxide and oxygen. Marked respiratory depression persisted for longer than one hour. Tidal volume, respiratory rate and minute volume measurements were inadequate indicators of this effect which is well shown by measurement of end-tidal carbon dioxide tension. The best quantitation is the slope of the ventilatory response to elevated carbon dioxide tension, determined in l./min/mm Hg. Displacement of the response curve was very variable after loss of consciousness. The data indicate that spontaneous respiration with this anaesthetic technique, as with the majority of other general anaesthetics, is accompanied by respiratory acidosis.

Minute volume, tidal volume, respiratory frequency, end-tidal carbon dioxide, and ventilatory response to carbon dioxide inhalation were studied during anesthesia at three different concentrations of end-tidal methoxyflurane, 0.19, 0.37, and 0.82 per cent, in 12 unpremedicated patients prior to surgery. Minute volume rose during light anesthesia and fell with increasing concentrations. Tidal volume decreased progressively from 0.49 liters awake, to 0.22 liters at the highest concentration, while respiratory rate rose from 11 to 22 per minute. End-tidal carbon dioxide rose progressively from 38.6 torr while awake, to 43.4 torr during deep anesthesia. More striking was the change in slope of the carbon dioxide response curve, which decreased progressively with increasing depth of anesthesia from 56 per cent of the control response in light anesthesia, through 28 to 9 per cent during deep anesthesia. An estimate of MAC for methoxyflurane in this study was 0.17 per cent, which agrees with previous reports despite employment of different criteria.

ObjectivesTo demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer.Study Design and SettingPotential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses.ResultsWe identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials.ConclusionsIPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials.