프라그마틱 무료 슬롯 is an open data platform that enables research into pragmatic trials. It gathers and distributes clean trial data, ratings and evaluations using PRECIS-2. This permits a variety of meta-epidemiological analyses to compare treatment effect estimates across trials of different levels of pragmatism.
Background
Pragmatic trials are increasingly recognized as providing real-world evidence for clinical decision-making. However, the use of the term "pragmatic" is inconsistent and its definition and evaluation requires further clarification. Pragmatic trials are intended to guide the practice of clinical medicine and policy decisions rather than prove a physiological or clinical hypothesis. A pragmatic study should aim to be as similar to real-world clinical practice as possible, such as its recruitment of participants, setting and design, the delivery and implementation of the intervention, as well as the determination and analysis of outcomes as well as primary analyses. This is a major distinction from explanation trials (as described by Schwartz and Lellouch1), which are intended to provide a more complete confirmation of a hypothesis.
Truly pragmatic trials should not conceal participants or the clinicians. This can lead to a bias in the estimates of the effects of treatment. The trials that are pragmatic should also try to enroll patients from a wide range of health care settings, to ensure that their findings can be compared to the real world.
Furthermore studies that are pragmatic should focus on outcomes that are vital for patients, such as quality of life or functional recovery. This is particularly relevant for trials that involve surgical procedures that are invasive or may have serious adverse effects. The CRASH trial29 compared a 2-page report with an electronic monitoring system for hospitalized patients with chronic cardiac failure. The catheter trial28 on the other hand utilized symptomatic catheter-related urinary tract infection as its primary outcome.
In addition to these aspects, pragmatic trials should minimize the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Finally pragmatic trials should try to make their findings as applicable to real-world clinical practice as they can by making sure that their primary method of analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs which do not meet the requirements for pragmatism but have features that are in opposition to pragmatism, have been published in journals of varying kinds and incorrectly labeled pragmatic. This can lead to false claims of pragmatism, and the term's use should be made more uniform. The development of the PRECIS-2 tool, which provides an objective and standard assessment of practical features is a great first step.
Methods
In a pragmatic study it is the intention to inform clinical or policy decisions by demonstrating how an intervention can be integrated into routine care in real-world contexts. This differs from explanation trials, which test hypotheses about the cause-effect connection in idealized conditions. In this way, pragmatic trials could have a lower internal validity than explanatory studies and be more susceptible to biases in their design, 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 degree of pragmatism in an RCT by scoring it across 9 domains, ranging from 1 (very explicative) to 5 (very pragmatic). In this study, the areas of recruitment, organisation, flexibility in delivery, flexible adherence, and follow-up scored high. However, the primary outcome and the method of missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial with excellent pragmatic features without compromising the quality of its results.
However, it is difficult to determine how practical a particular trial really is because pragmaticity is not a definite quality; certain aspects of a study can be more pragmatic than others. Moreover, protocol or logistic modifications made during the trial may alter its score in pragmatism. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to the licensing. The majority of them were single-center. Therefore, they aren't very close to usual practice and can only be described as pragmatic if their sponsors are tolerant of the lack of blinding in these trials.
Furthermore, a common feature of pragmatic trials is that researchers try to make their results more valuable by studying subgroups of the sample. This can lead to unbalanced comparisons and lower statistical power, which increases the risk of either not detecting or incorrectly detecting differences in the primary outcome. In the case of the pragmatic studies included in this meta-analysis this was a major issue since the secondary outcomes weren't adjusted for differences in baseline covariates.
In addition, pragmatic studies may pose challenges to gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported, and are prone to delays, inaccuracies or coding errors. Therefore, it is crucial to enhance the quality of outcomes for these trials, and ideally by using national registries instead of relying on participants to report adverse events in the trial's own database.
Results
Although the definition of pragmatism may not require that all trials be 100 100% pragmatic, there are some advantages to including pragmatic components in clinical trials. These include:
Increased sensitivity to real-world issues, reducing the size of studies and their costs, and enabling the trial results to be more quickly transferred into real-world clinical practice (by including routine patients). However, pragmatic trials can also have disadvantages. For instance, the right kind of heterogeneity can allow a trial to generalise its results to different settings and patients. However, the wrong type of heterogeneity can reduce assay sensitivity, and thus decrease the ability of a study to detect small treatment effects.
Several studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 developed a framework to distinguish between explanatory studies that confirm a physiological or clinical hypothesis, and pragmatic studies that inform the selection of appropriate therapies in real world clinical practice. The framework was composed of nine domains that were scored on a 1-5 scale with 1 being more informative and 5 being more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flexible compliance and primary analysis.
The original PRECIS tool3 was built on the same scale and domains. Koppenaal et al10 devised an adaptation to this assessment dubbed the Pragmascope that was easier to use in systematic reviews. They found that pragmatic reviews scored higher on average across all domains, however they scored lower in the primary analysis domain.
This distinction in the analysis domain that is primary could be explained by the fact that the majority of pragmatic trials analyse their data in an intention to treat manner however some explanation trials do not. The overall score for pragmatic systematic reviews was lower when the domains of organization, flexible delivery, and follow-up were merged.
It is crucial to keep in mind that a pragmatic study does not mean a low-quality trial. In fact, there is increasing numbers of clinical trials which use the word 'pragmatic,' either in their abstracts or titles (as defined by MEDLINE, but that is neither precise nor sensitive). These terms could indicate that there is a greater awareness of pragmatism within abstracts and titles, but it's not clear whether this is reflected in content.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the value of real-world evidence is becoming increasingly acknowledged. They are clinical trials randomized that compare real-world care alternatives instead of experimental treatments under development, they involve patients that more closely mirror the ones who are treated in routine medical care, they utilize comparators which exist in routine practice (e.g. existing drugs), and they depend on the self-reporting of participants about outcomes. This method is able to overcome the limitations of observational research for example, the biases associated with the reliance on volunteers and the lack of the coding differences in national registry.
Other advantages of pragmatic trials are the ability to utilize existing data sources, as well as a higher probability of detecting significant changes than traditional trials. However, these tests could still have limitations which undermine their validity and generalizability. For instance, participation rates in some trials might be lower than anticipated due to the healthy-volunteer effect and financial incentives or competition for participants from other research studies (e.g. industry trials). Many pragmatic trials are also restricted by the necessity to enroll participants in a timely manner. Additionally, 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 RCTs published from 2022 to 2022 that self-described as pragmatism. The PRECIS-2 tool was used to evaluate the pragmatism of these trials. It covers domains such as eligibility criteria as well as recruitment flexibility as well as adherence to interventions and follow-up. They found that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
Trials with high pragmatism scores tend to have broader criteria for eligibility than conventional RCTs. They also include patients from a variety of hospitals. The authors argue that these characteristics could make pragmatic trials more meaningful and applicable to daily practice, but they don't necessarily mean that a pragmatic trial is free from bias. In addition, the pragmatism that is present in a trial is not a predetermined characteristic and a pragmatic trial that does not contain all the characteristics of a explanatory trial may yield valuable and reliable results.