Montori, Víctor M.

Abstract: Randomized controlled trials in orthopaedics are often underpowered to detect important differences in outcomes. Composite end points (CEPs) hold promise as a strategy to address this issue by combining multiple end points into one summary measure, thus increasing the observed event rate. The use of CEPs by trialists, however, can be problematic when they include components that vary greatly in importance to patients and when differences in apparent effect between components are large. We present an overview of CEPs with a focus on appropriate design and interpretation of results.

In this paper, we explore the relative value that different methods offer in answering some stereotypical comparative effectiveness research questions with the goal of informing development of a ‘translation table’ – a selection tool for choosing appropriate methods for specific comparative effectiveness research questions. This paper was written as a parallel effort to Greenfield and Kaplan (also in this volume) to support the endeavor described in the manuscript by Tunis et al. (also in this volume). Originally based on four cases, the current article has been shortened to two cases for the current discussion. These cases represent research priorities proposed to orient the work of the Patient-Centered Outcomes Research Institute, comparative clinical effectiveness and comparative health services.

Amiodarone therapy in adults with congenital heart disease (CHD) is associated with a significant risk of amiodarone-induced thyrotoxicosis (AIT). We developed a risk index to identify those patients being considered for amiodarone treatment who are at high risk for AIT. We reviewed the health records of adults with CHD and assessed the association between potential clinical predictors and AIT. Significant predictors were included in multivariate analyses. The parameter estimates from multivariate analysis were subsequently used to develop a risk index. 169 adults met eligibility criteria and 23 developed AIT. The final model included age, cyanotic heart disease and BMI. The risk index developed identified 3 categories of risk. Their AIT likelihood ratios were: 0.37 for low risk (95% CI 0.15–0.92); 1.12 for medium risk (95% CI 0.65–1.91); and 3.47 for high risk (95% CI 1.7–7.11). The AIT predicted risk in our population was 5% for the low risk group, 15% for the medium risk group and 47% for the high risk group. Conclusions . We derived the first model to quantify the risk for developing AIT among adults with CHD. Before using it clinically to help selecting among alternative antiarrhythmic options, it needs validation in an independent population.

We review controversies associated with randomized controlled trials (RCTs) stopped early for apparent benefit (truncated RCTs or tRCTs) and present our groups’ perspective. Long-established theory, simulations and recent empirical evidence demonstrate that tRCTs will on average overestimate treatment effects, and this overestimation may be large, particularly when tRCTs have small number of events. Theoretical considerations and simulations demonstrate that on average, meta-analyses of RCTs with appropriate stopping rules will lead to only trivial overestimation of treatment effects. However, tRCTs will disproportionally contribute to meta-analytic estimates when tRCTs occur early in the sequence of trials with few subsequent studies, publication of nontruncated RCTs is delayed, there is publication bias, or tRCTs result in a ‘freezing’ effect in which ‘correcting’ trials are never undertaken. To avoid applying overestimates of effect to clinical decision-making, clinicians should view the results of individual tRCTs with small sample sizes and small number of events with skepticism. Pooled effects from meta-analyses including tRCTs are likely to overestimate effect when there is a substantial difference in effect estimates between the tRCTs and the nontruncated RCTs, and in which the tRCTs have a substantial weight in the meta-analysis despite themselves having a relatively small number of events. Such circumstances call for sensitivity analyses omitting tRCTs.

OBJECTIVE Patients with diabetes may experience high burden of treatment (BOT), including treatment-related effects and self-care demands. We examined whether patients with type 2 diabetes and their clinicians discuss BOT, the characteristics of their discussions, and their attempts to address BOT during visits. RESEARCH DESIGN AND METHODS Two coders independently reviewed videos of 46 primary care visits obtained during a practice-based trial and identified utterances concerning BOT, classifying them by topic and by whether BOT was addressed (i.e., whether statements emerged aimed at alleviating BOT). RESULTS Of the 46 visits, 43 (93.5%) contained BOT discussions. Both coders identified 83 discussions: 12 involving monitoring, 28 treatment administration, 19 access, and 24 treatment effects. BOT was unambiguously addressed only 30% of the time. CONCLUSIONS BOT discussions usually arise during visits but rarely beget problem-solving efforts. These discussions represent missed opportunities for reducing treatment-related disruptions in the lives of patients with diabetes, which may affect adherence and well-being.

Adherence to recommended preventive services and immunizations in adults is suboptimal and often associated with socioeconomic status, race, and access to care. The aim of this study is to evaluate adherence in a cohort without these barriers to ascertain realistically optimal adherence rates and to examine remaining barriers among relatively advantaged individuals. Specifically, it employed a sample of 6889 patients presenting for executive health care from 2005 to 2009. Adherence varied across colorectal cancer screening (79%), mammography (89%), cervical cancer screening (91%), tetanus immunization (82%), and pneumococcal vaccination (62%). Multivariate logistic regressions revealed that age, education, alcohol use concerns, and being married were positively associated with adherence to certain services. Individuals without the usual barriers to care have variable, less-than-ideal rates of adherence to preventive services, which correlate with some health behaviors and demographics. Understanding the predictors of adherence may inform quality improvement processes aimed at optimizing disease prevention. ( Population Health Management 2012;15:65–70)