Introduction Intravaginal ejaculation latency time (IELT), defined as the time between the start of vaginal intromission and the start of intravaginal ejaculation, is increasingly used in clinical trials to assess the amount of selective serotonin reuptake inhibitor-induced ejaculation delay in men with premature ejaculation. Prospectively, stopwatch assessment of IELTs has superior accuracy compared with retrospective questionnaire and spontaneous reported latency. However, the IELT distribution in the general male population has not been previously assessed. Aim To determine the stopwatch assessed-IELT distribution in large random male cohorts of different countries. Methods A total of 500 couples were recruited from five countries: the Netherlands, United Kingdom, Spain, Turkey, and the United States. Enrolled men were aged 18 years or older, had a stable heterosexual relationship for at least 6 months, with regular sexual intercourse. The surveyed population were not included or excluded by their ejaculatory status and comorbidities. This survey was performed on a “normal” general population. Sexual events and stopwatch-timed IELTs during a 4-week period were recorded, as well as circumcision status and condom use. Main Outcome Measures The IELT, circumcision status, and condom use. Results The distribution of the IELT in all the five countries was positively skewed, with a median IELT of 5.4 minutes (range, 0.55–44.1 minutes). The median IELT decreased significantly with age, from 6.5 minutes in the 18–30 years group, to 4.3 minutes in the group older than 51 years (P < 0.0001). The median IELT varied between countries, with the median value for Turkey being the lowest, i.e., 3.7 minutes (0.9–30.4 minutes), which was significantly different from each of the other countries. Comparison of circumcised (N = 98) and not-circumcised (N = 261) men in countries excluding Turkey resulted in median IELT values of 6.7 minutes (0.7–44.1 minutes) in circumcised compared with 6.0 minutes (0.5–37.4 minutes) in not-circumcised men (not significant). The median IELT value was not affected by condom use. Conclusion The IELT distribution is positively skewed. The overall median value was 5.4 minutes but with differences between countries. For all five countries, median IELT values were independent of condom usage. In countries excluding Turkey, the median IELT values were independent of circumcision status.

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BackgroundGreater transparency and, in particular, sharing of patient-level data for further scientific research is an increasingly important topic for the pharmaceutical industry and other organisations who sponsor and conduct clinical trials as well as generally in the interests of patients participating in studies. A concern remains, however, over how to appropriately prepare and share clinical trial data with third party researchers, whilst maintaining patient confidentiality. Clinical trial datasets contain very detailed information on each participant. Risk to patient privacy can be mitigated by data reduction techniques. However, retention of data utility is important in order to allow meaningful scientific research. In addition, for clinical trial data, an excessive application of such techniques may pose a public health risk if misleading results are produced. After considering existing guidance, this article makes recommendations with the aim of promoting an approach that balances data utility and privacy risk and is applicable across clinical trial data holders.DiscussionOur key recommendations are as follows:Data anonymisation/de-identification: Data holders are responsible for generating de-identified datasets which are intended to offer increased protection for patient privacy through masking or generalisation of direct and some indirect identifiers.Controlled access to data, including use of a data sharing agreement: A legally binding data sharing agreement should be in place, including agreements not to download or further share data and not to attempt to seek to identify patients. Appropriate levels of security should be used for transferring data or providing access; one solution is use of a secure ‘locked box’ system which provides additional safeguards.SummaryThis article provides recommendations on best practices to de-identify/anonymise clinical trial data for sharing with third-party researchers, as well as controlled access to data and data sharing agreements. The recommendations are applicable to all clinical trial data holders. Further work will be needed to identify and evaluate competing possibilities as regulations, attitudes to risk and technologies evolve.

PurposeTo evaluate the efficacy and safety of intravenous sildenafil for immediate postoperative pulmonary hypertension (PH) in pediatric patients undergoing congenital heart surgery.MethodsA double-blind, multicenter, placebo-controlled, dose-ranging, parallel-group trial was conducted. Patients were randomized to one of three doses of intravenous sildenafil, or placebo, for a minimum of 24 h.ResultsThe study was heavily underpowered. Whereas enrollment of 228 patients (57 per treatment arm) was required to achieve the sample size estimate to detect difference between arms, the sponsor terminated the study after 15 months owing to slow patient accrual. Seventeen patients (median age 5 months) experiencing postoperative PH were randomized and treated, five with placebo and four each with low-, medium-, and high-dose sildenafil. In the first 24 h, 40% of placebo and 17% of sildenafil patients required additional therapy (p = 0.330). Median time to extubation (3 versus 8 days, p = 0.023) and intensive care unit stay (6 versus 15 days, p = 0.008) were shorter for sildenafil patients. Mean ± standard deviation systolic pulmonary artery pressure was reduced with sildenafil (46 ± 11 to 35 ± 6 mmHg, p = 0.027 versus placebo). No adverse events or systemic hypotension were attributed to sildenafil.ConclusionIntravenous sildenafil reduced pulmonary artery pressure and shortened time to extubation and intensive care unit stay in children with postoperative PH.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-010-2065-4) contains supplementary material, which is available to authorized users.

In this paper we consider study designs which include a placebo and an active control group as well as several dose groups of a new drug. A monotonically increasing dose-response function is assumed, and the objective is to estimate a dose with equivalent response to the active control group, including a confidence interval for this dose. We present different non-parametric methods to estimate the monotonic dose-response curve. These are derived from the isotonic regression estimator, a non-negative least squares estimator, and a bias adjusted non-negative least squares estimator using linear interpolation. The different confidence intervals are based upon an approach described by Korn, and upon two different bootstrap approaches. One of these bootstrap approaches is standard, and the second ensures that resampling is done from empiric distributions which comply with the order restrictions imposed. In our simulations we did not find any differences between the two bootstrap methods, and both clearly outperform Korn's confidence intervals. The non-negative least squares estimator yields biased results for moderate sample sizes. The bias adjustment for this estimator works well, even for small and moderate sample sizes, and surprisingly outperforms the isotonic regression method in certain situations.