Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It collects and distributes cleaned trial data, ratings and evaluations using PRECIS-2. This allows for diverse meta-epidemiological analyses to evaluate the effects of treatment across trials with different levels of pragmatism.
Background
Pragmatic trials are becoming more widely recognized as providing real-world evidence for clinical decision making. However, the use of the term "pragmatic" is not uniform and its definition as well as assessment requires clarification. The purpose of pragmatic trials is to inform clinical practice and policy decisions, rather than confirm the validity of a clinical or physiological hypothesis. A pragmatic trial should try to be as similar to the real-world clinical environment as possible, including in its participation of participants, setting and design of the intervention, its delivery and implementation of the intervention, and the determination and analysis of the outcomes, and primary analysis. This is a significant distinction from explanatory trials (as described by Schwartz and Lellouch1) which are intended to provide a more complete confirmation of a hypothesis.
The trials that are truly pragmatic should not attempt to blind participants or healthcare professionals as this could cause bias in the estimation of treatment effects. The pragmatic trials also include patients from different healthcare settings to ensure that the results can be generalized to the real world.
Finally the focus of pragmatic trials should be on outcomes that are crucial to patients, like quality of life or functional recovery. This is particularly important for trials involving surgical procedures that are invasive or have potentially dangerous adverse events. The CRASH trial29, for instance was focused on functional outcomes to evaluate a two-page case report with an electronic system to monitor the health of patients in hospitals suffering from chronic heart failure. In addition, the catheter trial28 focused on symptomatic catheter-associated urinary tract infections as its primary outcome.
In addition to these characteristics pragmatic trials should reduce trial procedures and data-collection requirements to cut down on costs and time commitments. Finaly the aim of pragmatic trials is to make their results as applicable to current clinical practice as is possible. This can be accomplished by ensuring that their primary analysis is based on the intention-to treat method (as described within CONSORT extensions).
Despite these criteria however, a large number of RCTs with features that defy the concept of pragmatism have been mislabeled as pragmatic and published in journals of all types. This can lead to false claims about pragmatism, and the term's use should be standardized. The development of a PRECIS-2 tool that offers an objective, standardized assessment of pragmatic features is the first step.
Methods
In a practical study it is the intention to inform clinical or policy decisions by showing how an intervention could be integrated into routine care in real-world situations. This is distinct from explanation trials that test hypotheses about the cause-effect relationship in idealised conditions. In this way, pragmatic trials may have lower internal validity than studies that explain and be more susceptible to biases in their design as well as analysis and conduct. Despite these limitations, pragmatic trials may be a valuable source of information for decisions in the context of healthcare.
The PRECIS-2 tool assesses the degree of pragmatism in an RCT by assessing it on 9 domains ranging from 1 (very explanatory) to 5 (very pragmatic). In this study, the recruit-ment organization, flexibility in delivery and follow-up domains were awarded high scores, but the primary outcome and the method of missing data fell below the pragmatic limit. This suggests that it is possible to design a trial that has high-quality pragmatic features, without compromising the quality of its outcomes.
It is difficult to determine the degree of pragmatism within a specific study because pragmatism is not a have a binary characteristic. Some aspects of a study may be more pragmatic than other. Furthermore, logistical or protocol modifications made during the trial may alter its score on 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. They are not in line with the norm, and can only be called pragmatic if their sponsors agree that such trials aren't blinded.
Furthermore, a common feature of pragmatic trials is that researchers attempt to make their findings more meaningful by analysing subgroups of the trial sample. However, this often leads to unbalanced comparisons and lower statistical power, increasing the risk of either not detecting or incorrectly detecting differences in the primary outcome. This was a problem during the meta-analysis of pragmatic trials due to the fact that secondary outcomes were not corrected for differences in covariates at baseline.
Furthermore, pragmatic trials can also have challenges with respect to the collection and interpretation of safety data. This is because adverse events are typically reported by participants themselves and are susceptible to reporting errors, delays, or coding variations. 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 on a trial's own database.
Results
Although the definition of pragmatism does not require that all trials are 100% pragmatic, there are advantages to including pragmatic components in clinical trials. These include:
By including routine patients, the results of trials can be more quickly translated into clinical practice. But pragmatic trials can have their disadvantages. The right amount of heterogeneity, for example could allow a study to expand its findings to different patients or settings. However 프라그마틱 정품 확인법 of heterogeneity can reduce the sensitivity of an assay and, consequently, reduce a trial's power to detect even minor effects of treatment.
A variety of studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 created a framework for distinguishing between explanation-based trials that support a clinical or physiological hypothesis as well as pragmatic trials that aid in the selection of appropriate therapies in real-world clinical practice. Their framework comprised nine domains, each scored on a scale ranging from 1 to 5 with 1 indicating more explanatory and 5 indicating more pragmatic. The domains were recruitment setting, setting, intervention delivery and follow-up, as well as flexible adherence and primary analysis.
The original PRECIS tool3 was built on the same scale and domains. Koppenaal et al10 developed an adaptation of this assessment, called the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic reviews scored higher on average in most domains, but scored lower in the primary analysis domain.
This difference in the main analysis domain could be due to the fact that the majority of pragmatic trials analyse their data in an intention to treat manner, whereas some explanatory trials do not. The overall score was lower for pragmatic systematic reviews when the domains on organisation, flexible delivery and follow-up were merged.
It is important to remember that a pragmatic trial doesn't necessarily mean a poor quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, however it is neither sensitive nor specific) that use the term "pragmatic" in their abstracts or titles. These terms could indicate that there is a greater appreciation of pragmatism in abstracts and titles, but it's not clear whether this is reflected in the content.
Conclusions
In recent years, pragmatic trials have been gaining popularity in research as the value of real-world evidence is increasingly recognized. They are clinical trials randomized that evaluate real-world alternatives to care instead of experimental treatments under development. They include patient populations which are more closely resembling the ones who are treated in routine medical care, they utilize comparators which exist in routine practice (e.g., existing medications) and rely on participant self-report of outcomes. This method is able to overcome the limitations of observational research like the biases that come with the use of volunteers and the lack of coding variations in national registries.
Other advantages of pragmatic trials are the possibility of using existing data sources, as well as a higher likelihood of detecting meaningful changes than traditional trials. However, pragmatic trials may have some limitations that limit their reliability and generalizability. The participation rates in certain trials may be lower than anticipated because of the healthy-volunteering effect, financial incentives or competition from other research studies. The necessity to recruit people quickly restricts the sample size and the impact of many practical trials. Additionally certain pragmatic trials lack 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 published from 2022 to 2022 that self-described themselves as pragmatic. The PRECIS-2 tool was employed to evaluate the pragmatism of these trials. It includes domains such as eligibility criteria, recruitment flexibility, adherence to intervention, and follow-up. They discovered that 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 score tend to have higher eligibility criteria than traditional RCTs which have very specific criteria that are not likely to be present in clinical practice, and they contain patients from a broad variety of hospitals. These characteristics, according to the authors, may make pragmatic trials more relevant and applicable in the daily clinical. However they do not guarantee that a trial will be free of bias. Furthermore, the pragmatism of a trial is not a definite characteristic A pragmatic trial that doesn't possess all the characteristics of an explanatory trial may yield valid and useful results.