Effects of study design and allocation on participant behaviour-ESDA: study protocol for a randomized controlled trial

Background: What study participants think about the nature of a study has been hypothesised to affect subsequent behaviour and to potentially bias study findings. In this trial we examine the impact of awareness of study design and allocation on participant drinking behaviour. Methods/Design: A three-arm parallel group randomised controlled trial design will be used. All recruitment, screening, randomisation, and follow-up will be conducted on-line among university students. Participants who indicate a hazardous level of alcohol consumption will be randomly assigned to one of three groups. Group A will be informed their drinking will be assessed at baseline and again in one month (as in a cohort study design). Group B will be told the study is an intervention trial and they are in the control group. Group C will be told the study is an intervention trial and they are in the intervention group. All will receive exactly the same brief educational material to read. After one month, alcohol intake for the past 4 weeks will be assessed. Discussion: The experimental manipulations address subtle and previously unexplored ways in which participant behaviour may be unwittingly influenced by standard practice in trials. Given the necessity of relying on self-reported outcome, it will not be possible to distinguish true behaviour change from reporting artefact. This does not matter in the present study, as any effects of awareness of study design or allocation involve bias that is not well understood. There has been little research on awareness effects, and our outcomes will provide an indication of the possible value of further studies of this type and inform hypothesis generation

The HIM (Health for Izhevsk Men) trial protocol

BACKGROUND: Russia is one of the very few industrialised countries in the world where life expectancy has been declining. Alcohol has been implicated as a major contributor to the rapid fluctuations observed in male life expectancy since 1985 that have been particularly marked among working-age men. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. There is limited understanding in Russia of the salience and applicability of Motivational Interviewing (MI), a well-defined brief intervention commonly used to target alcohol-related behaviour, but MI may have important potential for success within the Russian context. METHODS/DESIGN: The study will be an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous drinking at 3 months. The secondary hypothesis is that it will be effective in reducing self-reported past week beverage alcohol consumption, alcohol dependence and related problems at 3 months and at 12 months. MI will also be effective at 12 months in reducing self-reported hazardous drinking, alcohol dependence and related problems, proxy reported hazardous drinking, and recent alcohol use as indicated by bio-markers. Participants are drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous drinking in the past year. All participants undergo a health check, with MI subsequently delivered to those in the intervention arm. Signed consent is obtained from those in the intervention arm at this point. Both groups are then invited for 3 and 12 month follow ups. The control group will not receive any additional intervention. TRIAL REGISTRATION: ISRCTN82405938

Dealing with Missing Outcomes: Lessons from a Randomized Trial of a Prenatal Intervention to Prevent Early Childhood Caries

Severe early childhood caries (S-ECC) affects 17% of 2-3 year old children in South Australia impacting on their general health and well-being. S-ECC is largely preventable by providing mothers with anticipatory guidance. Randomised controlled trials (RCTs) are the most decisive way to test this, but that approach suffers from near inevitable loss to follow-up that occurs with preventative strategies and distant outcome assessment

Bayesian robustness for decision making problems: Applications in medical contexts

AbstractPractical implementation of Bayesian decision making is hindered by the fact that optimal decisions may be sensitive to the model inputs: the prior, the likelihood and/or the underlying utility function. Given the structure of a problem, the analyst has to decide which sensitivity measures are relevant and compute them efficiently. We address the issue of robustness of the optimal action in a decision making problem with respect to the prior model and the utility function. We discuss some general principles and apply novel computational strategies in the context of two relatively complex medical decision making problems

A New Family of Covariate-Adjusted Response Adaptive Designs and their Asymptotic Properties

It is often important to incorporating covariate information in the design of clinical trials. In literature, there are many designs of using stratification and covariate-adaptive randomization to balance on certain known covariate. Recently Zhang, Hu, Cheung and Chan (2007) have proposed a family of covariate-adjusted response-adaptive (CARA) designs and studied their asymptotic properties. However, these CARA designs often have high variabilities. In this paper, we propose a new family of covariate-adjusted response-adaptive (CARA) designs. We show that the new designs have smaller variabilities and therefore more efficient

Early efficacy of CABG care delivery in a low procedure-volume community hospital: operative and midterm results

BACKGROUND: The Leapfrog Group recommended that coronary artery bypass grafting (CABG) surgery should be done at high volume hospitals (>450 per year) without corresponding surgeon-volume criteria. The latter confounds procedure-volume effects substantially, and it is suggested that high surgeon-volume (>125 per year) rather than hospital-volume may be a more appropriate indicator of CABG quality. METHODS: We assessed 3-year isolated CABG morbidity and mortality outcomes at a low-volume hospital (LVH: 504 cases) and compared them to the corresponding Society of Thoracic Surgeons (STS) national data over the same period (2001–2003). All CABGs were performed by 5 high-volume surgeons (161–285 per year). "Best practice" care at LVH – including effective practice guidelines, protocols, data acquisition capabilities, case review process, dedicated facilities and support personnel – were closely modeled after a high-volume hospital served by the same surgeon-team. RESULTS: Operative mortality was similar for LVH and STS (OM: 2.38% vs. 2.53%), and the corresponding LVH observed-to-expected mortality (O/E = 0.81) indicated good quality relative to the STS risk model (O/E<1). Also, these results were consistent irrespective of risk category: O/E was 0, 0.9 and 1.03 for very-low risk (<1%), low risk (1–3%) and moderate-to-high risk category (>3%), respectively. Postoperative leg wound infections, ventilator hours, renal dysfunction (no dialysis), and atrial fibrillation were higher for LVH, but hospital stay was not. The unadjusted Kaplan-Meier survival for the LVH cohort was 96%, 94%, and 92% at one, two, and three years, respectively. CONCLUSION: Our results demonstrated that high quality CABG care can be achieved at LVH programs if 1) served by high volume surgeons and 2) patient care procedures similar to those of large programs are implemented. This approach may prove a useful paradigm to ensure high quality CABG care and early efficacy at low volume institutions that wish to comply with the Leapfrog standards

Predisposing factors for bacterial vaginosis, treatment efficacy and pregnancy outcome among term deliveries; results from a preterm delivery study

<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) during pregnancy is associated with an increased risk of preterm delivery but little is known about factors that could predict BV. We have analyzed if it is possible to identify a category of pregnant women that should be screened for BV, and if BV would alter the pregnancy outcome at term; we have also studied the treatment efficacy of clindamycin.</p> <p>Methods</p> <p>Prospective BV screening and treatment study of 9025 women in a geographically defined region in southeast Sweden. BV was defined as a modified Nugent score of 6 and above. Data was collected from the Swedish Medical Birth Register. Women allocated to treatment were supplied with vaginal clindamycin cream. The main outcome goals were to identify factors that could predict BV.</p> <p>Results</p> <p>Vaginal smears were consistent with BV criteria in 9.3%. Logistic regression indicates a significant correlation between smoking and BV (p < 0.001) and a greater prevalence of BV in the lower age groups (p < 0.001). We found no correlation between BV and history of preterm deliveries, previous miscarriages, extra-uterine pregnancies, infertility problems or reported history of urinary tract infections–factors that earlier have been associated with BV. Treatment with clindamycin cream showed a cure rate of 77%. Less than 1% of women with a normal vaginal smear in early pregnancy will develop BV during the pregnancy. There was no association between BV and the obstetric outcome among women who delivered at term. Women with BV, both treated patients and nontreated, had the same obstetric outcome at term as women with normal vaginal flora.</p> <p>Conclusion</p> <p>BV is more than twice as common among smokers, and there is a higher prevalence in the younger age group. However these two markers for BV do not suffice as a tool for screening, and considering the lack of other risk factors associated with BV, screening of all pregnant women might be a strategy to follow in a program intended to reduce the number of preterm births.</p

Estimation in a Competing Risks Proportional Hazards Model Under Length-biased Sampling With Censoring

International audienceWhat population does the sample represent? The answer to this question is of crucial importance when estimating a survivor function in duration studies. As is well-known, in a stationary population, survival data obtained from a cross-sectional sample taken from the population at time $t_0$ represents not the target density $f(t)$ but its length-biased version proportional to $tf(t)$, for $t>0$. The problem of estimating survivor function from such length-biased samples becomes more complex, and interesting, in presence of competing risks and censoring. This paper lays out a sampling scheme related to a mixed Poisson process and develops nonparametric estimators of the survivor function of the target population assuming that the two independent competing risks have proportional hazards. Two cases are considered: with and without independent consoring before length biased sampling. In each case, the weak convergence of the process generated by the proposed estimator is proved. A well-known study of the duration in power for political leaders is used to illustrate our results. Finally, a simulation study is carried out in order to assess the finite sample behaviour of our estimators

Efaproxiral red blood cell concentration predicts efficacy in patients with brain metastases

Efaproxiral (Efaproxyn™, RSR13), a synthetic allosteric modifier of haemoglobin (Hb), decreases Hb-oxygen (O2) binding affinity and enhances oxygenation of hypoxic tumours during radiation therapy. This analysis evaluated the Phase 3, Radiation Enhancing Allosteric Compound for Hypoxic Brain Metastases; RT-009 (REACH) study efficacy results in relation to efaproxiral exposure (efaproxiral red blood cell concentration (E-RBC) and number of doses). Recursive partitioning analysis Class I or II patients with brain metastases from solid tumours received standard whole-brain radiation therapy (3 Gy/fraction × 10 days), plus supplemental O2 (4 l/min), either with efaproxiral (75 or 100 mg/kg daily) or without (control). Efaproxiral red blood cell concentrations were linearly extrapolated to all efaproxiral doses received. Three patient populations were analysed: (1) all eligible, (2) non-small-cell lung cancer (NSCLC) as primary cancer, and (3) breast cancer primary. Efficacy endpoints were survival and response rate. Brain metastases patients achieving sufficient E-RBC (⩾483 μg/ml) and receiving at least seven of 10 efaproxiral doses were most likely to experience survival and response benefits. Patients with breast cancer primary tumours generally achieved the target efaproxiral exposure and therefore gained greater benefit from efaproxiral treatment than NSCLC patients. This analysis defined the efaproxiral concentration-dependence in survival and response rate improvement, and provided a clearer understanding of efaproxiral dosing requirements