Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial open data platform and infrastructure that supports research on pragmatic trials. It collects and distributes clean trial data, ratings and evaluations using PRECIS-2. This permits a variety of meta-epidemiological analyses that evaluate the effects of treatment across trials of different levels of pragmatism.
Background
Pragmatic trials provide real-world evidence that can be used to make clinical decisions. The term "pragmatic" however, is used inconsistently and its definition and evaluation need further clarification. Pragmatic trials are intended to guide clinical practices and policy decisions rather than confirm a physiological hypothesis or clinical hypothesis. A pragmatic study should strive to be as close as is possible to real-world clinical practices, including recruiting participants, setting, designing, delivery and execution of interventions, determining and analysis outcomes, and primary analyses. This is a major distinction from explanatory trials (as described by Schwartz and Lellouch1) that are designed to provide more thorough proof of an idea.
Studies that are truly pragmatic must not attempt to blind participants or healthcare professionals in order to lead to distortions in estimates of the effects of treatment. The pragmatic trials also include patients from different health care settings to ensure that their outcomes can be compared to the real world.
Additionally, clinical trials should focus on outcomes that matter to patients, like 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 2-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The trial with a catheter, however utilized symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these characteristics pragmatic trials should reduce the requirements for data collection and trial procedures to cut costs and time commitments. Finally, pragmatic trials should seek to make their results 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 that do not meet the requirements for pragmatism but have features that are in opposition to pragmatism, have been published in journals of various kinds and incorrectly labeled pragmatic. This can lead to misleading claims about pragmatism, and the usage of the term should be standardised. The development of a PRECIS-2 tool that provides an objective, standardized assessment of pragmatic features is a first step.
Methods
In a pragmatic study, the goal is to inform clinical or policy decisions by showing how an intervention could be integrated into routine treatment in real-world settings. This is different from explanatory trials that test hypotheses about the causal-effect relationship in idealized conditions. Therefore, pragmatic trials might be less reliable than explanatory trials and might be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool evaluates an RCT on 9 domains, ranging from 1 to 5 (very pragmatist). In this study the domains of recruitment, organisation, flexibility in delivery, flexible adherence, and follow-up scored high. However, the primary outcome and method of missing data were scored below the practical limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without damaging the quality of its results.
It is, however, difficult to determine how pragmatic a particular trial really is because the pragmatism score is not a binary quality; certain aspects of a trial can be more pragmatic than others. Furthermore, logistical or protocol changes during the trial may alter its pragmatism score. Additionally, 36% of the 89 pragmatic trials discovered by Koppenaal and colleagues were placebo-controlled, or conducted prior to licensing, and the majority were single-center. Thus, they are not as common and can only be called pragmatic if their sponsors are tolerant of the absence of blinding in these trials.
Another common aspect of pragmatic trials is that the researchers try to make their results more relevant by analyzing subgroups of the sample. This can lead to imbalanced analyses and less statistical power. This increases the risk of missing or misdetecting differences in the primary outcomes. In the case of the pragmatic studies included in this meta-analysis, this was a major issue since the secondary outcomes were not adjusted for variations in baseline covariates.
In addition practical trials can have challenges with respect to the gathering and interpretation of safety data. This is due to the fact that adverse events are typically reported by participants themselves and prone to delays in reporting, inaccuracies, or coding variations. It is therefore important to enhance the quality of outcomes for these trials, ideally by using national registry databases instead of relying on participants to report adverse events on the trial's database.
Results
While the definition of pragmatism doesn't require that all clinical trials are 100% pragmatist There are advantages when incorporating pragmatic components into trials. These include:
By incorporating routine patients, the trial results are more easily translated into clinical practice. However, pragmatic trials may also have drawbacks. For instance, the right type of heterogeneity can help the trial to apply its findings to a variety of patients and settings; however, the wrong type of heterogeneity can reduce assay sensitivity and therefore reduce the power of a trial to detect small treatment effects.
Numerous studies have attempted to categorize pragmatic trials, with a variety of definitions and scoring systems. Schwartz and Lellouch1 created a framework to distinguish between explanatory studies that prove a physiological hypothesis or clinical hypothesis and pragmatic studies that guide the selection of appropriate treatments in the real-world clinical practice. Their framework included nine domains, each scored on a scale of 1 to 5, with 1 indicating more lucid and 5 indicating more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flexible adhering to the program and primary analysis.
The initial PRECIS tool3 featured similar domains and scales from 1 to 5. Koppenaal and colleagues10 developed an adaptation of 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 in the majority of domains, with lower scores in the primary analysis domain.
The difference in the primary analysis domain could be explained by the fact that most pragmatic trials process their data in an intention to treat manner however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery, and follow-up were merged.
It is crucial to keep in mind that a pragmatic study should not necessarily mean a low-quality study. In fact, there are a growing number of clinical trials which use the term "pragmatic" either in their abstract or title (as defined by MEDLINE, but that is not precise nor sensitive). 프라그마틱 공식홈페이지 of these terms in abstracts and titles may suggest a greater awareness of the importance of pragmatism but it is unclear whether this is reflected in the contents of the articles.
Conclusions
As appreciation for the value of real-world evidence grows widespread, pragmatic trials have gained popularity in research. They are clinical trials that are randomized which compare real-world treatment options instead of experimental treatments in development, they have populations of patients that more closely mirror the patients who receive routine medical care, they utilize comparisons that are commonplace in practice (e.g. existing drugs) and depend on participants' self-reports of outcomes. This approach could help overcome the limitations of observational studies which include the biases associated with reliance on volunteers and the lack of accessibility and coding flexibility in national registry systems.
Other advantages of pragmatic trials are the possibility of using existing data sources, and a greater chance of detecting meaningful changes than traditional trials. However, they may still have limitations which undermine their validity and generalizability. Participation rates in some trials could be lower than anticipated due to the health-promoting effect, financial incentives or competition from other research studies. Practical trials are often restricted by the need to recruit participants on time. Additionally certain 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 self-labeled as pragmatist and published up to 2022. The PRECIS-2 tool was employed to determine pragmatism. It covers domains such as eligibility criteria, recruitment flexibility and adherence to intervention and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
프라그마틱 추천 with high pragmatism scores tend to have broader criteria for eligibility than conventional RCTs. They also have patients from a variety of hospitals. The authors argue that these characteristics could make the pragmatic trials more relevant and applicable to everyday clinical practice, however they don't necessarily mean that a pragmatic trial is free from bias. The pragmatism characteristic is not a fixed attribute; a pragmatic test that does not have all the characteristics of an explanation study could still yield valuable and valid results.