How necessary are randomized controlled trials?

Randomized controlled trials (RCTs) are often deemed the gold standard for testing new treatments. This belief in turn justifies recruiting patients into such trials even when it is suspected that a new treatment is superior – although patients in the control group are thereby denied what might be the better treatment, we cannot know that the treatment actually is better, the thought runs, without conducting an RCT. But Robert Northcott argues that RCTs are not always the best choice after all. Rather, like any other method, they can go wrong sometimes, in several different ways. The main alternative to them is historical studies, which try to assess a treatment’s effectiveness from data not drawn from trials. These too can go wrong in several ways, and in the past have acquired a bad reputation. However, that prejudice has become outdated. The truer picture, Northcott argues, is that sometimes one method is preferable, sometimes the other. Things must be decided case by case. It follows that the ethical ramifications of conducting an RCT also must be examined case by case; there is no one-size-fits-all answer. An especially striking and emotional example concerns ECMO, a treatment for newborn babies with life-threatening lung problems. Historical studies indicated that ECMO was a major breakthrough, offering hugely increased survival rates. But it was still insisted that it also be tested in RCTs, in the course of which many babies receiving the conventional treatment died. A properly nuanced view of RCTs suggests that these deaths were tragically unnecessary

Randomized Controlled Trials

This paper covers the topic of randomized controlled trials in social, educational, criminological, health, and other human service sectors. It is studded with illustrations from developed and developing countries. We address the basic ideas that underlie trials in different ways, and cover contemporary definitions and vernacular, some history, and idea of cumulating evidence from such trials including recent work on replication and meta-analyses. Standards for evidence and reporting are considered. We attend to statistical matters and also recognize important non-statistical matters that must be taken into account in designing and executing such trials. Cluster randomized, place randomized, and other designs for such trials are covered on account of their increasing importance

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear

Fecal incontinence: the quality of reported randomized, controlled trials in the last ten years.

This study was designed to analyze the characteristics and the quality of reporting of randomized, controlled trials published during the last ten years on fecal incontinence

Stratification Trees for Adaptive Randomization in Randomized Controlled Trials

This paper proposes an adaptive randomization procedure for two-stage randomized controlled trials. The method uses data from a first-wave experiment in order to determine how to stratify in a second wave of the experiment, where the objective is to minimize the variance of an estimator for the average treatment effect (ATE). We consider selection from a class of stratified randomization procedures which we call stratification trees: these are procedures whose strata can be represented as decision trees, with differing treatment assignment probabilities across strata. By using the first wave to estimate a stratification tree, we simultaneously select which covariates to use for stratification, how to stratify over these covariates, as well as the assignment probabilities within these strata. Our main result shows that using this randomization procedure with an appropriate estimator results in an asymptotic variance which is minimal in the class of stratification trees. Moreover, the results we present are able to accommodate a large class of assignment mechanisms within strata, including stratified block randomization. In a simulation study, we find that our method, paired with an appropriate cross-validation procedure ,can improve on ad-hoc choices of stratification. We conclude by applying our method to the study in Karlan and Wood (2017), where we estimate stratification trees using the first wave of their experiment

Do antiarrhythmics prevent sudden death in patients with heart failure?

Beta-blockers (class II antiarrhythmics) reduce sudden death and total mortality in patients with heart failure (strength of recommendation [SOR]: A, based on systematic reviews of randomized controlled trials). Amiodarone (class III) may reduce sudden death in heart failure (SOR: B, extrapolation from randomized controlled trials), but evidence is weak that it reduces total mortality, and it has significant side effects. Class I and other class III antiarrhythmic agents appear cause an increase in mortality due to sudden death in heart failure (SOR: B, extrapolations from randomized controlled trials)

Randomized Controlled Trials in Neurosurgery

Background: Randomized controlled trials (RCTs) are the gold standard studies to evaluate the efficacy of therapeutic interventions. However, performing RCTs in surgical disciplines, including neurosurgery, faces several specific challenges such as recruitment difficulties, surgical selection bias, inclusion of an appropriate control group, definition of clinically relevant outcomes and perceived lack of equipoise. Therefore, little is known about the number of published RCTs in neurosurgery, how they are performed and reported and their scientific quality. This, in turn, raises questions regarding the sources of knowledge that currently support clinical decision-making by neurosurgeons. Therefore, the present investigation aims to explore the current scenario of RCTs in neurosurgery and sources of knowledge used for clinical decision-making. Hypothesis and significance: Given the previously reported difficulties inherent to design and perform RCTs in neurosurgery, it is hypothesized that RCTs in this field are low in number and of suboptimal quality, leading neurosurgeons to use other sources of knowledge for clinical decision-making. The current research aims to better understand the current scenario and ultimately contribute for better decision-making in this field. Aims and methodological approach: This research comprised four aims. Aim 1. To investigate the attitudes of Brazilian neurosurgeons in terms of access and use of different types of scientific information for clinical decision-making, by means of a cross-sectional survey that was sent to all members of the Sociedade Brasileira de Neurocirurgia. The answers were analyzed descriptively and comparisons were made among subgroups of practice place and time. Aim 2. To evaluate how easy it is to have access to published RCTs in neurosurgery using several electronic search strategies applied to commonly used databases. This was achieved by carrying out open searches on PubMed, the Cochrane Library and the Centre for Reviews and Dissemination, an advanced search on PubMed based on clinical entity-related keywords, and hand-searches on the reference list of the identified RCTs. The outcomes were the sensitivity and specificity calculated for the open keyword searches on PubMed, the Cochrane Library and the CRD database and for the Cochrane’s HSSS, based on the total number of the identified RCTs. Aim 3. To investigate the scientific quality of RCTs in neurosurgery through a systematic review performed in all identified randomized trials with two or more comparative groups and at least one neurosurgical intervention. Study design and other methodological aspects were analyzed. The quality of included RCTs was assessed using the Cochrane Risk of Bias tool. Aim 4. To investigate how feasible it is to use sham controls in neurosurgery RCTs by analyzing the frequency, type and indication of used sham interventions. Results: Aim 1: The survey’s response rate was 32%. Among the respondents, 53% had more than 10 years experience, 67% worked in public hospitals, 34% performed spine and 30% brain tumor surgeries. Therapeutic decisions were based mostly on internship learning (54%) and personal professional experience (52%). Most common information sources were scientific abstracts (53%) and the internet (47%). 89% believed Evidence-Based Medicine to be relevant, 93% believed protocols or guidelines were necessary and 74% subscribed to a medical journal. Nonetheless only 43% had protocols implemented in their services, 93% highly valued a surgeonś personal experience and 63% showed little familiarity with the interpretation of scientific concepts in the literature. 83% were willing to try an innovative treatment alternative if it showed improvement of the outcomes and reduction of severe complications. Aim 2: A total of 1102 RCTs identified through combined search strategies. PubMed open search yielded 4660 articles, among which 365 were RCTs (sensitivity: 33.1%; specificity: 7.8%). Cochrane open search yielded 621 among which 36 were RCTs (sensitivity: 3.2%; specificity:5.8%) and CRD open search returned 78 articles, among which 4 were RCTs (sensitivity: 0.4% sensitivity; specificity: 5.1%). The Cochrane HSSS retrieved 10702 results, among which 340 were RCTs (sensitivity: 30.9%; specificity: 3.2%). Aim 3: RCTs in neurosurgery were found to lack quality, as most lacked information on study design (93.6%), randomization method (59.9%), blinding (59.8%), and data analysis (76.3%). Although the overall risk of bias decreased over time, 25.5% of the RCTs published between 2010 and 2013 lacked a clear risk of bias classification due to insufficient critical information. The methodological aspects more frequently classified with high risk of bias were “blinding of participants and personnel” (21.2%) and “incomplete outcome information” (28.8%). Aim 4: From the 1102 identified RCTs, 82 (7,4%) used sham interventions. The most common indication was pain treatment (67,1%), followed by the treatment of movement disorders and other clinical problems (18,3%) and brain injuries (12,2%). The most used sham interventions were saline injections, both in the spine (31,7%) and peripheral nerves (10,9%), followed by cranial surgery (26,8%), spine surgery (15,8%) and insertion of probes or catheters for sham lesions (14,6%). Most RCTs using sham interventions were double-blinded (76,5%), whereas 9,9% were single-blinded, and 13,6% did not report the type of blinding. Discussion: Although RCTs constitute the highest level of evidence, in the field of neurosurgery they are currently not the main source of knowledge underlying therapeutic decision-making, as most neurosurgeons, particularly those with over 10 years of experience, prefer to rely on their own expertise. Additionally, RCTs in neurosurgery are not easily accessible through commonly used search strategies applied to electronic databases, which is mostly due to poor quality of reporting and indexing. Moreover, published RCTs in neurosurgery lack quality in terms of experimental methodology, and they are poorly reported, with missing information on several critical design aspects. Although the inclusion of sham procedures in neurosurgical RCTs is feasible, very few include such procedures, which limits the clinical relevance of the estimated effects. Our results highlight an urgent need to improve the methodological quality, reporting and indexing of RCTs in neurosurgery, which may be achieved through the implementation of reporting guidelines, adequate training and rigorous peer-review

OVERVIEW OF RANDOMIZED CONTROLLED TRIALS

Randomized controlled trials are considered to be the gold standard in clinical studies to establish level of evidence in medical research. But, they are not easy to conduct and various other aspects have to be looked into. Randomization offers each enrolled subject equal chance of being allocated to the intervention and the control groups. Randomized control trial (RCT) is most powerful tool in clinical research. In this, subjects  are assigned to different groups of interventions by chance for comparison. RCT is only study design which can help us evaluate a new treatment.  By assigning participants to different intervention groups by chance, comparison between the interventions groups is made. Purpose of randomization is to make the treatment groups comparable, eliminates the source of and it ensures that the difference in groups is only due to trial treatments. In this article, we review randomized control trial with special emphasis on various types of randomized controlled trials, their characteristics, the process of randomization, and advantages and drawbacks of randomized controlled trials.   Key words:Randmized controlled trials, study design, randomization, clinical researc

Osteoporosis Therapies: Evidence from Health-Care Databases and Observational Population Studies

Osteoporosis is a well-recognized disease with severe consequences if left untreated. Randomized controlled trials are the most rigorous method for determining the efficacy and safety of therapies. Nevertheless, randomized controlled trials underrepresent the real-world patient population and are costly in both time and money. Modern technology has enabled researchers to use information gathered from large health-care or medical-claims databases to assess the practical utilization of available therapies in appropriate patients. Observational database studies lack randomization but, if carefully designed and successfully completed, can provide valuable information that complements results obtained from randomized controlled trials and extends our knowledge to real-world clinical patients. Randomized controlled trials comparing fracture outcomes among osteoporosis therapies are difficult to perform. In this regard, large observational database studies could be useful in identifying clinically important differences among therapeutic options. Database studies can also provide important information with regard to osteoporosis prevalence, health economics, and compliance and persistence with treatment. This article describes the strengths and limitations of both randomized controlled trials and observational database studies, discusses considerations for observational study design, and reviews a wealth of information generated by database studies in the field of osteoporosis

Delivering successful randomized controlled trials in surgery:methods to optimize collaboration and study design

Randomized controlled trials in surgery are notoriously difficult to design and conduct due to numerous methodological and cultural challenges. Over the last 5 years, several UK-based surgical trial-related initiatives have been funded to address these issues. These include the development of Surgical Trials Centers and Surgical Specialty Leads (individual surgeons responsible for championing randomized controlled trials in their specialist fields), both funded by the Royal College of Surgeons of England; networks of research-active surgeons in training; and investment in methodological research relating to surgical randomized controlled trials (to address issues such as recruitment, blinding, and the selection and standardization of interventions). This article discusses these initiatives more in detail and provides exemplar cases to illustrate how the methodological challenges have been tackled. The initiatives have surpassed expectations, resulting in a renaissance in surgical research throughout the United Kingdom, such that the number of patients entering surgical randomized controlled trials has doubled