Controlled clinical trials最新文献

Methods

The prevalence of asthma in adults in the United States is approximately 7%, and 9% of asthma patients will require hospitalization each year. Many patients do not seek care, as they do not recognize overuse of beta-agonists as a risk factor for poorly controlled asthma. However, pharmacists are able to identify these patients through refill information on reliever medication prescriptions and potentially initiate community-management opportunities for these patients.

Design

The study is a randomized, controlled trial. Patients are randomized to intervention or usual care.

Study population

Patients are high-risk asthma patients (defined as having an ER visit or hospitalization in the previous year, or using >2 canisters of short-acting beta-agonist in the previous 6 months). They are identified through community pharmacies.

Objectives

The primary objective is to determine the effect of an education and referral intervention program initiated by community pharmacists, working with high-risk asthma patients, family physicians and respiratory therapists, on asthma control, as measured by the Asthma Control Questionnaire (ACQ). Secondary objectives include determining the effect of this program on ER visits/hospitalizations, inhaled corticosteroid use, courses of oral steroids and FEV₁.

Intervention

The intervention includes patient education, assessment and optimization of drug therapy, and physician referral as needed. Patients are referred to a respiratory therapist within 1 week of randomization for measurement of FEV₁ and reinforcement of education. Patients assigned to usual care receive written asthma information, referral to a respiratory therapist and usual pharmacy and physician care.

Unique aspects

The design of the Better Respiratory Education and Asthma Treatment in Hinton and Edson (BREATHE) study is unique, given the multidisciplinary involvement, rural and community based, pharmacist initiated and targets specifically high risk patients. We believe that this study will show that management of asthma patients, involving the major role-players in their asthma care, will improve their asthma control.

Background

It is widely believed that baseline imbalances in randomized trials must necessarily be random. In fact, there is a type of selection bias that can cause substantial, systematic and reproducible baseline imbalances of prognostic covariates even in properly randomized trials. It is possible, given complete data, to quantify both the susceptibility of a given trial to this type of selection bias and the extent to which selection bias appears to have caused either observable or unobservable baseline imbalances. Yet, in articles reporting on randomized trials, it is uncommon to find either these assessments or the information that would enable a reader to conduct them. Nevertheless, there have been a few published reports that contain descriptions of either this type of selection bias or indicators that it may have occurred.

Objective

To document that the same type of selection bias has been described in numerous randomized trials and therefore that it represents a problem deserving of greater attention.

Study selection

Computerized searches were not useful in locating trials with one or more elements that contribute to or are indicative of selection bias in randomized trials. We limit our treatment to trials that were previously questioned for susceptibility to selection bias or for large baseline imbalances.

Results

We found 14 randomized trials that appear to be suspicious for selection bias. This may represent only the tip of the iceberg, because the status of other trials is inconclusive.

Conclusions

Authors of clinical trial reports should be required to disclose sufficient details to allow for an assessment of both allocation concealment and selection bias. The extent to which a randomized study was susceptible to selection bias should be considered in determining the relative contribution it makes to any subsequent meta-analysis, policy or decision.

The allocation of sufficient time for participant recruitment is one of the fundamental aspects in planning a clinical trial. This paper illustrates how a Poisson process can be used to determine an optimal period of time for participant recruitment by simulating Poisson arrival into a clinical trial. The simulation study provides the means to generate of an empirical probability density function for the recruitment time based on time-dependent changes in the accrual rate. From this empirical distribution, a clinical trial recruitment period can be planned to provide a high level of confidence (e.g., 90% probability) of enrolling the sample size within the planned amount of time given the simulation assumptions.

The clinical trials industry relies heavily on paper-based source documents as the foundation for the collection of its clinical research data from human subjects and medical records. This focus on paper documents has been prevalent throughout the history of clinical trials conduct, even as computing solutions advanced throughout the past 20 years. With the advent of additional electronic capabilities recently with the growth of Internet-based products to enhance business operations in many fields, the clinical trials industry remains uniquely behind most other industries in electronic technology adoptions. Valid reasons exist for the slow growth of technology adoptions in clinical trial activities, but there are now discussions about how to use technology more effectively in clinical trial conduct. One area of enhanced clinical trial conduct is believed to be available by moving from paper-based source documents to electronic source documents, that is, eliminating paper from clinical data capture, and collecting the information initially in a computer system. An important concern in moving to electronic source data is the validation of such data. This paper summarizes the history of clinical data capture through paper and electronic advancements to date and identifies three reasons for the slow movement to more electronic source data. The paper then illustrates two methods for the validation of electronic source data.

Adherence is a complex phenomenon involving interactions among the individual, the environment and the community. In an adherence workshop, a small group of investigators discussed their experiences with challenges and innovations regarding adherence gleaned from clinical research. This article summarizes the information and outcomes of that meeting. Guided by theoretical frameworks for understanding and promoting adherence, challenges in the areas of measurement, community-based research, and interventions were explored and innovations for meeting these challenges suggested. The article concludes with recommendations for enhancing the adherence agenda: (1) adherence research must have a well-defined conceptual and theoretical basis; (2) individual perceptions and social context of behavior must be incorporated; (3) research must be undertaken as a collaborative process involving participants and the community. Looking ahead, it is clear that if we hope to develop a new and integrated model of adherence, we must continue to advance theory through theory testing, with particular attention given to mediators and diverse samples. Moreover, an interdisciplinary agenda is necessary to set the stage for bringing together researchers from various disciplines and backgrounds with both participants and community representatives.

The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was designed to determine whether maintenance interferon therapy could slow disease progression in patients who had failed to eradicate hepatitis C virus (HCV) during prior interferon treatment (nonresponders). Ten clinical sites, a virological testing center, and a data coordinating center (DCC) were selected to collaborate in the design and implementation of the final protocol. Eligible patients had been treated previously with interferon for at least 12 weeks, with or without another antiviral, ribavirin, but still had persistent viremia. Because patients had received a variety of prior treatments, and as a perceived benefit of enrollment, we incorporated a Lead-in period of treatment with long-acting pegylated interferon alfa-2a plus ribavirin into the study design, a combination believed to be more effective but not approved by the Food and Drug Administration at the Trial's inception. If patients failed to achieve clearance of virus from the blood after 20 weeks of this Lead-in therapy, they were entered into the main trial at week 24 and randomized to receive either a lower dose of pegylated interferon weekly alone or no further therapy for an additional 3 1/2 years. The original protocol was amended later in three respects to improve enrollment and to adapt to Food and Drug Administration approval of the Lead-in therapy, including allowing patients to proceed directly to the randomized part of the study if treatment resembling the Lead-in had been completed. The protocol changes enhanced enrollment while upholding the original goals of the study and its integrity.

In this note, we outline the benefits of a partial cross-over design for a class of experiments where the interest is the cumulative effect of dose versus placebo. The goal of our design strategy is to answer several complex question efficiently in a phase II setting with a minimal number of assumptions with an eye towards planning a phase III study.