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 is a platform that collects and shares clean trial data and ratings using PRECIS-2 permitting multiple and varied meta-epidemiological studies to evaluate the effect of treatment on trials with different levels of pragmatism and other design features.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world for clinical decision making. The term "pragmatic" however, is not used in a consistent manner and its definition and assessment require clarification. Pragmatic trials should be designed to inform policy and clinical practice decisions, rather than confirm a physiological or clinical hypothesis. A pragmatic study should strive to be as close as possible to real-world clinical practices that include recruiting participants, setting, design, delivery and implementation of interventions, determination and analysis results, as well as primary analysis. This is a major difference between explanatory trials, as described by Schwartz & Lellouch1, which are designed to confirm a hypothesis in a more thorough manner.
Studies that are truly practical should not attempt to blind participants or the clinicians, as this may lead to distortions in estimates of the effects of treatment. Practical trials also involve patients from various healthcare settings to ensure that the results can be generalized to the real world.
Additionally studies that are pragmatic should focus on outcomes that are vital for patients, such as quality of life or functional recovery. This is particularly important in trials that involve surgical procedures that are invasive or have potential for serious adverse events. The CRASH trial29, for instance, focused on functional outcomes to compare a 2-page case-report with an electronic system to monitor the health of patients in hospitals suffering from chronic heart failure. Similarly, the catheter trial28 utilized urinary tract infections that are symptomatic of catheters as the primary outcome.
In addition to these features, pragmatic trials should minimize the requirements for data collection and trial procedures to reduce costs and time commitments. In the end these trials should strive to make their results as applicable to current clinical practice as is possible. This can be achieved by ensuring that their analysis is based on the intention-to treat approach (as defined in CONSORT extensions).
Despite these requirements, many RCTs with features that challenge the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all kinds. This can lead to misleading claims of pragmatism and the term's use should be standardized. The development of the PRECIS-2 tool, which provides a standard objective assessment of pragmatic characteristics is a great first step.
Methods
In a pragmatic study, the aim is to inform clinical or policy decisions by showing how an intervention could be integrated into everyday routine care. This is distinct from explanation trials, which test hypotheses about the causal-effect relationship in idealized conditions. Therefore, pragmatic trials could be less reliable than explanatory trials and might be more susceptible to bias in their design, conduct, and analysis. Despite their limitations, pragmatic research can be a valuable source of information to make decisions in the healthcare context.
The PRECIS-2 tool evaluates an RCT on 9 domains, ranging between 1 and 5 (very pragmatic). In this study, the areas of recruitment, organisation as well as flexibility in delivery flexibility in adherence, and follow-up received high scores. However, the main outcome and method of missing data scored below the pragmatic limit. This suggests that a trial could be designed with effective practical features, but without harming the quality of the trial.
It is difficult to determine the degree of pragmatism within a specific trial because pragmatism does not possess a specific characteristic. Certain aspects of a study can be more pragmatic than others. 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 the 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. Most were also single-center. They aren't in line with the usual practice and can only be considered pragmatic if the sponsors agree that such trials aren't blinded.
A typical feature of pragmatic research is that researchers try to make their findings more meaningful by analyzing subgroups within the trial. However, this often leads to unbalanced comparisons with a lower statistical power, which increases the likelihood of missing or misinterpreting the results of the primary outcome. 프라그마틱 게임 was the case in the meta-analysis of pragmatic trials as secondary outcomes were not corrected for covariates' differences at the time of baseline.
Additionally, studies that are pragmatic may pose challenges to collection and interpretation safety data. This is because adverse events are usually self-reported and are prone to reporting errors, delays or coding deviations. Therefore, it is crucial to enhance the quality of outcomes ascertainment in these trials, in particular 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 incorporating pragmatic components into clinical trials. These include:
Incorporating routine patients, the results of the trial are more easily translated into clinical practice. However, pragmatic studies can also have disadvantages. For example, the right type of heterogeneity could help the trial to apply its results to different patients and settings; however, the wrong type of heterogeneity could reduce assay sensitivity, and thus lessen the ability of a trial to detect small treatment effects.
Numerous studies have attempted to categorize pragmatic trials with various definitions and scoring systems. Schwartz and Lellouch1 created a framework to discern between explanation-based studies that confirm the physiological hypothesis or clinical hypothesis, and pragmatic studies that inform the selection of appropriate therapies in clinical practice. The framework was comprised of nine domains, each scoring on a scale of 1-5, with 1 being more informative and 5 indicating more pragmatic. The domains included recruitment and setting, delivery of intervention and follow-up, as well as flexible adherence and primary analysis.
The initial PRECIS tool3 featured similar domains and scales from 1 to 5. Koppenaal and colleagues10 created an adaptation of the assessment, called the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic systematic reviews had 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 the intention to treat manner, whereas some explanatory 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 pragmatic study should not mean a low-quality trial. In fact, there are an increasing number of clinical trials which use the word 'pragmatic,' either in their abstracts or titles (as defined by MEDLINE but which is neither sensitive nor precise). These terms could indicate an increased understanding of pragmatism in titles and abstracts, but it's not clear whether this is reflected in content.
Conclusions
As the importance of evidence from the real world becomes more popular, pragmatic trials have gained popularity in research. They are randomized clinical trials that evaluate real-world alternatives to care instead of experimental treatments under development, they have patients that more closely mirror the ones who are treated in routine care, they employ comparisons that are commonplace in practice (e.g., existing drugs), and they depend on participants' self-reports of outcomes. This method can help overcome the limitations of observational research, like the biases that are associated with the use of volunteers and the limited availability and coding variations in national registries.
Pragmatic trials have other advantages, including the ability to leverage existing data sources and a greater chance of detecting significant differences from traditional trials. However, these trials could still have limitations that undermine their reliability and generalizability. For instance the participation rates in certain trials could be lower than anticipated due to the healthy-volunteer effect and incentives to pay or compete for participants from other research studies (e.g. industry trials). The requirement to recruit participants in a timely fashion also reduces the size of the sample and the impact of many practical trials. 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 RCTs published from 2022 to 2022 that self-described as pragmatic. The PRECIS-2 tool was employed to assess pragmatism. It includes domains such as eligibility criteria and flexibility in recruitment and adherence to intervention and follow-up. They discovered that 14 of the trials scored pragmatic or highly practical (i.e. scoring 5 or more) in any one or more of these domains and that the majority were single-center.
Trials with a high pragmatism score tend to have broader eligibility criteria than traditional RCTs which have very specific criteria that are unlikely to be found in clinical practice, and they contain patients from a broad range of hospitals. The authors claim that these traits can make the pragmatic trials more relevant and useful for everyday clinical practice, however they do not guarantee that a trial conducted in a pragmatic manner is completely free of bias. The pragmatism is not a definite characteristic the test that does not possess all the characteristics of an explanatory study could still yield valuable and valid results.