Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that enables research into pragmatic trials. It collects and distributes clean trial data, ratings, and evaluations using PRECIS-2. 프라그마틱 공식홈페이지 allows for diverse meta-epidemiological analyses to compare treatment effect estimates across trials of different levels of pragmatism.
Background
Pragmatic trials are becoming more widely recognized as providing real-world evidence for clinical decision-making. However, the usage of the term "pragmatic" is inconsistent and its definition and assessment requires clarification. Pragmatic trials are intended to inform clinical practices and policy choices, rather than verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should aim to be as close as possible to actual clinical practices which include the recruitment of participants, setting, design, delivery and implementation of interventions, determination and analysis outcomes, and primary analysis. This is a significant difference between explanatory trials as defined by Schwartz and Lellouch1, which are designed to test a hypothesis in a more thorough way.
Truely pragmatic trials should not conceal participants or clinicians. This can lead to bias in the estimations of the effects of treatment. The trials that are pragmatic should also try to recruit patients from a variety of health care settings, to ensure that their findings are generalizable to the real world.
Additionally, clinical trials should concentrate on outcomes that are important to patients, like the quality of life and functional recovery. This is particularly important in trials that involve surgical procedures that are invasive or have potentially dangerous adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients with chronic heart failure. The catheter trial28 on the other hand, used symptomatic catheter associated urinary tract infections as its primary outcome.
In addition to these features, pragmatic trials should minimize the trial's procedures and data collection requirements to reduce costs. In the end these trials should strive to make their results as relevant to actual clinical practices as possible. This can be accomplished by ensuring that their primary analysis is based on an intention-to treat approach (as defined in CONSORT extensions).
Despite these guidelines, many RCTs with features that challenge the concept of pragmatism have been mislabeled as pragmatic and published in journals of all kinds. This can lead to false claims of pragmatism, and the usage of the term must be standardized. The development of a PRECIS-2 tool that provides an objective, standardized evaluation of pragmatic aspects is a first step.
Methods
In a pragmatic research study, the goal is to inform policy or clinical decisions by demonstrating how an intervention could be integrated into routine care in real-world contexts. This is different from explanatory trials that test hypotheses about the cause-effect connection in idealized settings. Therefore, pragmatic trials could have lower internal validity than explanatory trials and may be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic research can provide valuable information to make decisions in the context of healthcare.
The PRECIS-2 tool measures the degree of pragmatism within an RCT by scoring it across 9 domains ranging from 1 (very explicative) to 5 (very pragmatic). In this study, the domains of recruitment, organisation as well as flexibility in delivery flexibility in adherence, and follow-up received high scores. However, the principal outcome and the method of missing data was scored below the pragmatic limit. This suggests that a trial could be designed with effective pragmatic features, without compromising its quality.
It is hard to determine the level of pragmatism in a particular trial since pragmatism doesn't have a binary characteristic. Certain aspects of a study can be more pragmatic than other. Additionally, logistical or protocol modifications made during an experiment can alter its score in pragmatism. Koppenaal and colleagues found that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to the licensing. They also found that the majority were single-center. They aren't in line with the standard practice, and can only be considered pragmatic if the sponsors agree that these trials aren't blinded.
Another common aspect of pragmatic trials is that researchers attempt to make their findings more meaningful by analysing subgroups of the trial. This can lead to unbalanced analyses that have less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. This was the case in the meta-analysis of pragmatic trials because secondary outcomes were not corrected for covariates' differences at baseline.
In addition, pragmatic studies can present challenges in the gathering and interpretation of safety data. This is due to the fact that adverse events are generally reported by the participants themselves and are susceptible to delays in reporting, inaccuracies, or coding variations. It is essential to increase the accuracy and quality of the outcomes in these trials.
Results
Although the definition of pragmatism doesn't require that all clinical trials are 100% pragmatic, there are benefits to including pragmatic components in trials. These include:
Increasing sensitivity to real-world issues, reducing the size of studies and their costs as well as allowing trial results to be more quickly implemented into clinical practice (by including patients from routine care). However, pragmatic trials can also have disadvantages. For example, the right type of heterogeneity can help a trial to generalise its results to different patients and settings; however the wrong kind of heterogeneity could reduce assay sensitiveness and consequently reduce the power of a study to detect even minor effects of treatment.
A variety of studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed a framework that can differentiate between explanation studies that support a physiological or clinical hypothesis and pragmatic studies that help inform the choice for appropriate therapies in clinical practice. The framework was comprised of nine domains evaluated on a scale of 1-5 with 1 being more explanatory while 5 being more pragmatic. The domains were recruitment, setting, intervention delivery with flexibility, follow-up and primary analysis.
The original PRECIS tool3 included similar domains and scales from 1 to 5. Koppenaal and colleagues10 developed 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 higher average scores across all domains, but lower scores in the primary analysis domain.
This distinction in the main analysis domain could be explained by the fact that most pragmatic trials analyze their data in an intention to treat manner, whereas some explanatory trials do not. The overall score for pragmatic systematic reviews was lower when the areas of management, flexible delivery and following-up were combined.
It is crucial to keep in mind that a study that is pragmatic does not mean that a trial is of poor quality. In fact, there are increasing numbers of clinical trials that use the term 'pragmatic' either in their abstract or title (as defined by MEDLINE however it is neither sensitive nor precise). These terms may indicate that there is a greater understanding of pragmatism in abstracts and titles, however it's unclear whether this is reflected in content.
Conclusions
In recent years, pragmatic trials are becoming more popular in research as the importance of real-world evidence is becoming increasingly acknowledged. They are randomized trials that evaluate real-world alternatives to clinical trials in development. They include patient populations closer to those treated in regular medical care. This approach can overcome the limitations of observational research, for example, the biases associated with the reliance on volunteers and the limited availability and coding variations in national registries.
Pragmatic trials offer other advantages, such as the ability to draw on existing data sources and a greater likelihood of detecting meaningful differences from traditional trials. However, pragmatic tests may be prone to limitations that undermine their effectiveness and generalizability. For instance, participation rates in some trials may be lower than expected due to the healthy-volunteer effect and incentives to pay or compete for participants from other research studies (e.g., industry trials). Practical trials are often limited by the need to enroll participants on time. Additionally, some pragmatic trials don't 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 48 RCTs that self-labeled themselves as pragmatic and were published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which includes the eligibility criteria for domains, recruitment, flexibility in intervention adherence, and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Trials with a high pragmatism rating tend to have more expansive eligibility criteria than traditional RCTs, which include very specific criteria that are not likely to be present in clinical practice, and they comprise patients from a wide range of hospitals. According to the authors, can make pragmatic trials more useful and applicable in everyday practice. However they do not ensure that a study is free of bias. The pragmatism is not a fixed characteristic; a pragmatic test that doesn't have all the characteristics of an explicative study can still produce valid and useful outcomes.