Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a free and non-commercial open data platform and infrastructure that supports research on pragmatic trials. 프라그마틱 정품확인방법 is a platform that collects and shares clean trial data and ratings using PRECIS-2, which allows for multiple and varied meta-epidemiological research studies to compare treatment effects estimates across trials that employ different levels of pragmatism, as well as other design features.
Background
Pragmatic trials provide real-world evidence that can be used to make clinical decisions. However, the usage of the term "pragmatic" is not uniform and its definition and assessment requires clarification. The purpose of pragmatic trials is to inform clinical practices and policy decisions rather than confirm a physiological hypothesis or clinical hypothesis. A pragmatic study should strive to be as close as it is to the real-world clinical practice which include the recruitment of participants, setting, designing, delivery and implementation of interventions, determining and analysis results, as well as primary analysis. This is a major distinction between explanation-based trials, as defined by Schwartz and Lellouch1 which are designed to prove a hypothesis in a more thorough way.
The most pragmatic trials should not be blind participants or the clinicians. This can lead to an overestimation of treatment effects. Practical trials also involve patients from different healthcare settings to ensure that the results can be generalized to the real world.
Finally, pragmatic trials must be focused on outcomes that matter to patients, like the quality of life and functional recovery. This is particularly relevant in trials that require invasive procedures or have potentially dangerous adverse consequences. The CRASH trial29, for instance, focused on functional outcomes to compare a 2-page case-report with an electronic system for monitoring of patients admitted to hospitals with chronic heart failure, and the catheter trial28 utilized urinary tract infections caused by catheters as its primary outcome.
In addition to these features pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to cut down on costs and time commitments. Finaly the aim of pragmatic trials is to make their findings as relevant to real-world clinical practices as they can. This can be accomplished by ensuring that their primary analysis is based on an intention-to treat approach (as described within CONSORT extensions).
Many RCTs which do not meet the criteria for pragmatism, but have features that are in opposition to pragmatism, have been published in journals of different types and incorrectly labeled pragmatic. This can lead to false claims about pragmatism, and the use of the term should be standardised. The creation of the PRECIS-2 tool, which provides an objective standard for assessing practical features is a good initial step.
Methods
In a practical trial it is the intention to inform clinical or policy decisions by demonstrating how an intervention would be implemented into routine care. Explanatory trials test hypotheses regarding the cause-effect relationship within idealised environments. Therefore, pragmatic trials might have lower internal validity than explanatory trials and may be more susceptible to bias in their design, conduct, and analysis. Despite these limitations, pragmatic trials can be a valuable source of information for decisions in the context of healthcare.
The PRECIS-2 tool measures the degree of pragmatism in an RCT by scoring it across 9 domains that range from 1 (very explicative) to 5 (very pragmatic). In this study, the domains of recruitment, organisation as well as flexibility in delivery flexible adherence, and follow-up were awarded high scores. However, the principal outcome and the method of missing data were scored below the practical limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without harming the quality of the outcomes.
It is hard to determine the degree of pragmatism within a specific study because pragmatism is not a have a binary attribute. Some aspects of a study can be more pragmatic than others. Additionally, logistical or protocol modifications during the course of a trial can change its score in pragmatism. Additionally 36% of 89 pragmatic trials identified by Koppenaal and colleagues were placebo-controlled, or conducted prior to approval and a majority of them were single-center. They are not in line with the usual practice and can only be considered pragmatic if their sponsors agree that the trials aren't blinded.
Another common aspect of pragmatic trials is that the researchers attempt to make their findings more meaningful by analysing subgroups of the sample. This can lead to imbalanced analyses and less statistical power. This increases the chance of omitting or ignoring differences in the primary outcomes. In the case of the pragmatic trials included in this meta-analysis, this was a serious issue since the secondary outcomes were not adjusted for variations in the baseline covariates.
In addition practical trials can have challenges with respect to the collection and interpretation of safety data. It is because adverse events tend to be self-reported and are susceptible to delays, inaccuracies or coding differences. It is important to improve the accuracy and quality of outcomes in these trials.
Results
While the definition of pragmatism may not mean that trials must be 100 percent pragmatic, there are advantages of including pragmatic elements in clinical trials. These include:
Enhancing sensitivity to issues in the real world, reducing cost and size of the study and allowing the study results to be faster implemented into clinical practice (by including patients from routine care). However, pragmatic trials may also have drawbacks. The right kind of heterogeneity, for example could allow a study to extend its findings to different settings or patients. However, the wrong type can decrease the sensitivity of the test and, consequently, reduce a trial's power to detect minor treatment effects.
A variety of studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 developed a framework to differentiate between explanation studies that support a physiological hypothesis or clinical hypothesis, and pragmatic studies that inform the choice for appropriate therapies in the real-world clinical practice. Their framework included nine domains that were scored on a scale of 1 to 5 with 1 indicating more lucid and 5 suggesting more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flex adhering to the program and primary analysis.
The initial PRECIS tool3 included similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 developed an adaptation of this assessment, known as the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
This difference in the main analysis domain could be explained by the fact that most pragmatic trials analyse their data in an intention to treat way however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery, and follow-up were combined.
It is important to remember that a pragmatic study should not mean a low-quality trial. In fact, there is a growing number of clinical trials that employ the term 'pragmatic' either in their abstracts or titles (as defined by MEDLINE but which is neither sensitive nor precise). These terms may signal that there is a greater understanding of pragmatism in abstracts and titles, however it's unclear if this is reflected in the content.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the importance of real-world evidence is increasingly recognized. They are randomized trials that evaluate real-world care alternatives to experimental treatments in development. They involve patient populations closer to those treated in regular care. This method is able to overcome the limitations of observational research, such as the biases that are associated with the use of volunteers and the limited availability and codes that vary in national registers.
Pragmatic trials offer other advantages, including the ability to use existing data sources and a higher likelihood of detecting meaningful differences from traditional trials. However, these trials could have some limitations that limit their validity and generalizability. For instance the rates of participation in some trials might be lower than expected due to the healthy-volunteer effect as well as financial incentives or competition for participants from other research studies (e.g., industry trials). The need to recruit individuals quickly limits the sample size and the impact of many pragmatic trials. In addition some pragmatic trials do not have controls to ensure that the observed differences aren't due to biases in the conduct of trials.
The authors of the Pragmatic Free Trial Meta identified RCTs that were published between 2022 and 2022 that self-described as pragmatism. The PRECIS-2 tool was employed to determine the pragmatism of these trials. It covers areas such as eligibility criteria and flexibility in recruitment, adherence to intervention, and follow-up. They discovered that 14 of the trials scored pragmatic or highly practical (i.e., scoring 5 or more) in one or more of these domains, and that the majority of them were single-center.
Trials with a high pragmatism score tend to have higher eligibility criteria than traditional RCTs which have very specific criteria that are not likely to be found in clinical practice, and they contain patients from a broad range of hospitals. The authors argue that these traits can make pragmatic trials more effective and useful for daily practice, but they do not guarantee that a trial conducted in a pragmatic manner is free of bias. The pragmatism principle is not a definite characteristic and a test that doesn't have all the characteristics of an explicative study may still yield valid and useful outcomes.