Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It collects and shares cleaned trial data and ratings using PRECIS-2, which allows for multiple and varied meta-epidemiological studies to compare treatment effects estimates across trials that have different levels of pragmatism, as well as other design features.
Background
Pragmatic trials are becoming more widely acknowledged as providing evidence from the real world for clinical decision-making. The term "pragmatic", however, is used inconsistently and its definition and measurement require clarification. Pragmatic trials should be designed to inform clinical practice and policy decisions, rather than to prove an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should aim to be as close as possible to actual clinical practices, including recruitment of participants, setting, design, implementation and delivery of interventions, determining and analysis outcomes, and primary analysis. This is a significant difference between explanation-based trials, as defined by Schwartz and Lellouch1, which are designed to test the hypothesis in a more thorough manner.
Truly pragmatic trials should not be blind participants or clinicians. This can lead to bias in the estimations of the effect of treatment. Practical trials should also aim to enroll patients from a wide range of health care settings to ensure that the results can be applied to the real world.
Finally, pragmatic trials must concentrate on outcomes that are important to patients, like quality of life and functional recovery. This is particularly relevant in trials that require invasive procedures or have potentially serious adverse impacts. The CRASH trial29 compared a 2 page report with an electronic monitoring system for hospitalized patients with chronic heart failure. The catheter trial28 however was based on symptomatic catheter-related urinary tract infection as its primary outcome.
In addition to these aspects pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to reduce costs. Additionally the aim of pragmatic trials is to make their findings as relevant to real-world clinical practice as is possible. This can be achieved by ensuring their primary analysis is based on the intention to treat approach (as described in CONSORT extensions).
Many RCTs which do not meet the criteria for pragmatism but contain features contrary to pragmatism, have been published in journals of various types and incorrectly labeled as pragmatic. This can result in misleading claims of pragmatism, and the use of the term needs to be standardized. The development of a PRECIS-2 tool that provides a standardized objective evaluation of the pragmatic characteristics is a first step.
Methods
In a pragmatic trial the goal is to inform policy or clinical decisions by demonstrating how an intervention would be integrated into everyday routine care. Explanatory trials test hypotheses regarding the cause-effect relationship within idealised conditions. In 프라그마틱 무료 , pragmatic trials may have a lower internal validity than explanatory studies and be more susceptible to biases in their design as well as analysis and conduct. Despite these limitations, pragmatic trials can contribute valuable information to decisions in the context of healthcare.
The PRECIS-2 tool evaluates the level of pragmatism that is present in an RCT by assessing it on 9 domains that range from 1 (very explicative) to 5 (very pragmatic). In this study, the recruit-ment, organization, flexibility in delivery, flexible adherence and follow-up domains were awarded high scores, however, the primary outcome and the method for missing data were not at the pragmatic limit. This suggests that a trial can be designed with good practical features, yet not compromising its quality.
It is difficult to determine the degree of pragmatism that is present in a study because pragmatism is not a possess a specific characteristic. Certain aspects of a research study can be more pragmatic than other. The pragmatism of a trial can be affected by changes to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. They also found that the majority were single-center. They are not close to the norm and can only be considered pragmatic if the sponsors agree that such trials aren't blinded.
A common feature of pragmatic research is that researchers attempt to make their findings more relevant by studying subgroups of the trial sample. This can lead to unbalanced comparisons and lower statistical power, thereby increasing the likelihood of missing or misinterpreting the results of the primary outcome. This was the case in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for covariates' differences at the time of baseline.
Furthermore practical trials can have challenges with respect to the collection and interpretation of safety data. This is because adverse events are usually self-reported and prone to reporting errors, delays, or coding variations. It is therefore important to improve the quality of outcomes assessment in these trials, ideally by using national registry databases instead of relying on participants to report adverse events on the trial's database.
Results
While the definition of pragmatism may not require that all trials are 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
By including routine patients, the trial results can be more quickly translated into clinical practice. However, pragmatic trials may also have drawbacks. For instance, the right kind of heterogeneity can allow a study to generalize its findings to a variety of settings and patients. However the wrong type of heterogeneity may reduce the assay's sensitivity, and thus reduce the power of a study to detect even minor effects of treatment.
Numerous studies have attempted to classify pragmatic trials with a variety of definitions and scoring systems. Schwartz and Lellouch1 developed a framework to distinguish between explanation-based trials that support a clinical or physiological hypothesis as well as pragmatic trials that help in the choice of appropriate therapies in real-world clinical practice. The framework was composed of nine domains that were evaluated on a scale of 1-5 with 1 being more lucid while 5 was more pragmatic. The domains included recruitment, setting, intervention delivery and follow-up, as well as flexible adherence and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et al10 created an adaptation to this assessment, dubbed the Pragmascope which was more user-friendly to use in systematic reviews. They found that pragmatic systematic reviews had a higher average scores across all domains, but lower scores in the primary analysis domain.
This difference in the main analysis domain could be explained by the fact that the majority of pragmatic trials analyze their data in an intention to treat method however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains of the organization, flexibility of delivery and follow-up were merged.
It is crucial to keep in mind that a study that is pragmatic does not necessarily mean a low-quality study. In fact, there are increasing numbers of clinical trials which use the word 'pragmatic,' either in their abstract or title (as defined by MEDLINE however it is neither precise nor sensitive). The use of these terms in abstracts and titles could indicate a greater understanding of the importance of pragmatism, however, it is not clear if this is evident in the contents of the articles.
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 clinical trials which compare real-world treatment options instead of experimental treatments in development, they have patients which are more closely resembling those treated in routine care, they employ comparators that are used in routine practice (e.g., existing medications), and they depend on the self-reporting of participants about outcomes. This method has the potential to overcome limitations of observational studies that are prone to biases that arise from relying on volunteers and limited availability and coding variability in national registries.
Other advantages of pragmatic trials include the possibility of using existing data sources, and a higher probability of detecting significant changes than traditional trials. However, pragmatic trials may have some limitations that limit their reliability and generalizability. For instance the participation rates in certain trials might be lower than expected due to the healthy-volunteer effect as well as incentives to pay or compete for participants from other research studies (e.g. industry trials). Practical trials are often restricted by the necessity to recruit participants on time. In addition, some pragmatic trials lack controls to ensure that the observed differences are not due to biases in the conduct of trials.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatist and published up to 2022. The PRECIS-2 tool was used to evaluate the degree of pragmatism. It covers areas like eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered that 14 of the trials scored highly or pragmatic pragmatic (i.e. scores of 5 or higher) in any one or more of these domains, and that the majority of these were single-center.
Trials with a high pragmatism rating tend to have more expansive eligibility criteria than traditional RCTs, which include very specific criteria that are unlikely to be used in the clinical environment, and they comprise patients from a wide range of hospitals. The authors argue that these characteristics could make pragmatic trials more effective and applicable to daily practice, but they don't necessarily mean that a trial conducted in a pragmatic manner is free of bias. The pragmatism is not a fixed characteristic and a test that does not have all the characteristics of an explanation study can still produce valid and useful outcomes.