The challenges faced in the design, conduct and analysis of surgical randomised trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessment of surgical interventions and enable the conduct of appropriate and well-designed trials

Making a decision about trial participation : the feasibility of measuring deliberation during the informed consent process for clinical trials

Peer reviewedPublisher PD

The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?

Acknowledgements The authors would like to acknowledge helpful discussions on this topic held with various colleagues in connection with a variety of projects. Funding No funding was received for this work.Peer reviewedPublisher PD

Using the literature to quantify the learning curve: a case study

Objective: To assess whether a literature review of a technology can allow a learning curve to be quantified. Methods: The literature for fibreoptic intubation was searched for studies reporting information relevant to the learning curve. The Cochrane Librar y, Medline, Embase and Science Citation index were searched. Studies that reported a procedure time were included. Data were abstracted on the three features of learning: initial level, rate of learning and asymptote level. Random effect meta-analysis was performed. Results: Only 21 studies gave explicit information concerning the previous experience of the operator(s). There were 32 different definitions of procedure time. From 4 studies of fibreoptic nasotracheal intubation, the mean starting level and time for the 10th procedure (95% confidence interval) was estimated to be 133s (113, 153) and 71s (62, 79) respectively. Conclusions: The review approach allowed learning to be quantified for our example technology. Poor and insufficient reporting constrained formal statistical estimation. Standardised reporting of non-drug techniques with adequate learning curve details is needed to inform trial design and costeffectiveness analysis

Non-compliance with randomised allocation and missing outcome data in randomised controlled trials evaluating surgical interventions : a systematic review

Acknowledgements JAC held MRC training (reference number: G0601938) and methodology (reference number: G1002292) fellowships while this research was undertaken. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors accept full responsibility for this manuscript.Peer reviewedPublisher PD

Interplay between finite resources and local defect in an asymmetric simple exclusion process

When particle flux is regulated by multiple factors such as particle supply and varying transport rate, it is important to identify the respective dominant regimes. We extend the well-studied totally asymmetric simple exclusion model to investigate the interplay between a controlled entrance and a local defect site. The model mimics cellular transport phenomena where there is typically a finite particle pool and non-uniform moving rates due to biochemical kinetics. Our simulations reveal regions where, despite an increasing particle supply, the current remains constant while particles redistribute in the system. Exploiting a domain wall approach with mean-field approximation, we provide a theoretical ground for our findings. The results in steady state current and density profiles provide quantitative insights into the regulation of the transcription and translation process in bacterial protein synthesis. We investigate the totally asymmetric simple exclusion model with controlled entrance and a defect site in the bulk to mimic the finite particle pool and non-uniform moving rates in particle transport processes.Comment: 9 pages, 12 figures; v2: minor format changes; v3: major revision, additional references; v4: minor format change to figures, additional reference

Association Analysis of Fetal Alcohol Syndrome and Hypertension Status in Children, Adolescents, and Young Adults

Abstract: Background: Fetal Alcohol Syndrome (FAS), located on the severe end of a spectrum of disorders known as Fetal Alcohol Spectrum Disorders (FASDs), is one of the most detrimental, and publicized, teratogenic outcome of alcohol consumption during pregnancy within the United States. During pregnancy, alcohol that is consumed by the mother passes through the placenta and transfers to the baby via the umbilical cord. The same prenatal transference of alcohol that leads to FAS and FASDs might also be contributing to an increased likelihood of hypertension in youth. Additionally, factors such as stress influenced by familial instability, an increased likelihood of developing congenital and conotruncal heart defects, and a reduction in nephron count might be leading to an increased likelihood of hypertension in FAS-affected youth. The purpose of this study is to examine the relationship between prenatal exposure to alcohol, manifested through FAS, and hypertension in children, adolescents, and young adults. Methods: A case-control study design was incorporated to analyze the association between FAS status and hypertensions status; cases (n=165) were collected from a FAS clinical database in Atlanta, Georgia. Controls (n=177) were taken from the National Health and Nutrition Examination Survey (NHANES). Chi-square analyses were used to examine the extent to which FAS status, sex, race/ethnicity, medication use, and obesity status each relate to hypertension status. A logistic regression was performed analyzing the relationship between FAS status (y/n: independent) and hypertension status (y/n: dependent) whilst controlling for sex, race/ethnicity, medication use, and obesity status. Results: The univariate relationships between FAS status and hypertension status (OR=4.491, p\u3c.001) as well as medication use and hypertension status (OR= 2.951, p=.002) proved to be statistically significant (p\u3c.05). Through the regression, FAS status significantly predicted hypertension status (β = 1.646, OR = 5.184, p\u3c .001) after accounting for sex, race/ethnicity, medication use, and obesity status. Those with a race/ethnicity categorized as either Non-Hispanic African American (β =1.259, OR = 3.523, p = .049) or Hispanic (β = 1.192, OR = 3.294, p = .061) were significantly more likely to have hypertensions than those categorized as non-Hispanic Caucasian. Conclusion: The major findings of this study suggest a significant relationship between FAS and hypertension in youth. Race/ethnicity also proved important in predicting hypertensive blood pressure readings independent of FAS diagnosis. The most obvious biological mechanism catalyzing the relationship between FAS and hypertension is prenatal alcohol exposure. Because prenatal alcohol exposure is the primary definitional and diagnostic factor of FAS, associative connectivity may exist independently between prenatal alcohol exposure and blood pressure at various levels of severity along an alcohol exposure dose-response spectrum. Further research is needed to isolate and measure the effect that prenatal alcohol exposure has on blood pressure independently of FAS as well as to assess the extent to which the risk for hypertension in alcohol-affected individuals increases with age and through the life course