Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a free and non-commercial open data platform and infrastructure that facilitates research on pragmatic trials. It shares clean trial data and ratings using PRECIS-2 allowing for multiple and diverse meta-epidemiological studies that examine the effects of treatment across trials that employ different levels of pragmatism, as well as other design features.
Background
Pragmatic trials provide evidence from the real world that can be used to make clinical decisions. The term "pragmatic", however, is a word that is often used in contradiction and its definition and assessment require further clarification. 프라그마틱 이미지 of pragmatic trials is to guide clinical practices and policy choices, rather than prove a physiological or clinical hypothesis. A pragmatic study should try to be as similar to real-world clinical practice as possible, such as the recruitment of participants, setting and design, the delivery and execution of the intervention, as well as the determination and analysis of outcomes and primary analyses. This is a major distinction between explanatory trials, as described by Schwartz and Lellouch1 which are designed to confirm a hypothesis in a more thorough way.
Truely pragmatic trials should not be blind participants or clinicians. This could lead to bias in the estimations of treatment effects. The trials that are pragmatic should also try to recruit patients from a variety of health care settings to ensure that their findings can be compared to the real world.
Finally, pragmatic trials must focus on outcomes that matter to patients, like the quality of life and functional recovery. This is particularly relevant in trials that involve surgical procedures that are invasive or have potentially serious adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28 on the other hand was based on symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these characteristics pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to reduce costs. Additionally these trials should strive to make their results as relevant to real-world clinical practice as is possible. This can be accomplished by ensuring that their primary analysis is based on the intention to treat approach (as described in CONSORT extensions).
Many RCTs that don't meet the requirements for pragmatism however, they have characteristics that are in opposition to pragmatism, have been published in journals of various types and incorrectly labeled pragmatic. This could lead to false claims of pragmatism and the usage of the term should be made more uniform. The creation of the PRECIS-2 tool, which offers a standard objective assessment of pragmatic features is a good initial step.
Methods
In a pragmatic study, the aim is to inform clinical or policy decisions by showing how an intervention could be implemented into routine care. Explanatory trials test hypotheses concerning the cause-effect relation within idealized environments. In this way, pragmatic trials may have lower internal validity than explanation studies and are more susceptible to biases in their design as well as analysis and conduct. Despite their limitations, pragmatic research can be a valuable source of information to make decisions in the context of healthcare.
The PRECIS-2 tool assesses the degree of pragmatism within an RCT by assessing it on 9 domains that range from 1 (very explicit) to 5 (very pragmatic). In this study, the domains of recruitment, organisation and flexibility in delivery, flexibility in adherence, and follow-up were awarded high scores. However, the main outcome and the method for missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial using high-quality pragmatic features, without damaging the quality of its results.
It is, however, difficult to assess how pragmatic a particular trial is, since pragmatism is not a binary attribute; some aspects of a trial can be more pragmatic than others. Moreover, protocol or logistic changes during the trial may alter its score on pragmatism. Koppenaal and colleagues found that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to licensing. The majority of them were single-center. Thus, they are not very close to usual practice and can only be described as pragmatic in the event that their sponsors are supportive of the lack of blinding in such trials.
Another common aspect of pragmatic trials is that the researchers attempt to make their findings more valuable by studying subgroups of the trial. However, this often leads to unbalanced results and lower statistical power, thereby increasing the chance of not or misinterpreting the results of the primary outcome. In the case of the pragmatic trials included in this meta-analysis, this was a serious issue since the secondary outcomes weren't adjusted for differences in baseline covariates.
Additionally the pragmatic trials may have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events are usually self-reported and are susceptible to reporting delays, inaccuracies or coding deviations. It is therefore important to improve the quality of outcome for these trials, ideally by using national registries instead of relying on participants to report adverse events on the trial's own database.
Results
Although the definition of pragmatism may not require that all clinical trials be 100% pragmatic there are benefits to including pragmatic components in trials. These include:
By incorporating routine patients, the results of the trial can be more quickly translated into clinical practice. However, pragmatic trials may have their disadvantages. For instance, the right kind of heterogeneity can allow a trial to generalise its results to different patients and settings; however the wrong kind of heterogeneity may reduce the assay's sensitiveness and consequently reduce the power of a study to detect small treatment effects.
Many studies have attempted classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 created a framework for distinguishing between explanatory trials that confirm a clinical or physiological hypothesis as well as pragmatic trials that aid in the selection of appropriate treatments in real-world clinical practice. The framework was comprised of nine domains that were scored on a scale of 1 to 5, with 1 indicating more lucid and 5 indicating more practical. The domains included recruitment of intervention, 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 systematic reviews had a higher average scores in the majority of domains, with lower scores in the primary analysis domain.
The difference in the main analysis domain could be explained by the fact that most pragmatic trials process their data in an intention to treat way, whereas some explanatory trials do not. The overall score for pragmatic systematic reviews was lower when the areas of organisation, flexible delivery and following-up were combined.
It is important to remember that the term "pragmatic trial" does not necessarily mean a low-quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, however this is not specific nor sensitive) which use the word 'pragmatic' in their title or abstract. These terms may indicate that there is a greater appreciation of pragmatism in titles and abstracts, but it's unclear if this is reflected in content.
Conclusions
As appreciation for the value of real-world evidence grows commonplace the pragmatic trial has gained momentum in research. They are randomized clinical trials which compare real-world treatment options instead of experimental treatments under development. 프라그마틱 불법 have patients which are more closely resembling those treated in routine care, they use comparators that are used in routine practice (e.g., existing drugs) and rely on participant self-report of outcomes. This approach can help overcome limitations of observational studies which include the biases associated with reliance on volunteers and limited availability and the variability of coding in national registry systems.
Other advantages of pragmatic trials are the ability to use existing data sources, and a greater likelihood of detecting meaningful changes than traditional trials. However, these trials could still have limitations that undermine their validity and generalizability. For example, participation rates in some trials may be lower than anticipated due to the healthy-volunteer effect as well as incentives to pay or compete for participants from other research studies (e.g. industry trials). Many pragmatic trials are also restricted by the necessity to recruit participants in a timely manner. In addition some pragmatic trials lack controls to ensure that the observed differences aren't due to biases in trial conduct.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and that were published up to 2022. They assessed pragmatism using the PRECIS-2 tool, which includes the domains eligibility criteria as well as recruitment, flexibility in intervention adherence, and follow-up. They discovered that 14 of the trials scored pragmatic or highly practical (i.e. scoring 5 or higher) in any one or more of these domains, and that the majority of them were single-center.
Studies that have high pragmatism scores tend to have more criteria for eligibility than conventional RCTs. They also contain populations from many different hospitals. According to the authors, can make pragmatic trials more useful and applicable in everyday clinical. However, they don't ensure that a study is free of bias. In addition, the pragmatism that is present in a trial is not a predetermined characteristic and a pragmatic trial that doesn't contain all the characteristics of an explanatory trial can produce reliable and relevant results.