무료슬롯 is an open data platform that allows research into pragmatic trials. It gathers and distributes clean trial data, ratings, and evaluations using PRECIS-2. This permits a variety of meta-epidemiological studies to evaluate the effects of treatment across trials of various levels of pragmatism.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic" however, is used inconsistently and its definition and measurement need further clarification. Pragmatic trials are intended to guide the practice of clinical medicine and policy decisions, not to confirm a physiological hypothesis or clinical hypothesis. A pragmatic trial should try to be as close as is possible to the real-world clinical practice, including recruitment of participants, setting, design, delivery and implementation of interventions, determining and analysis outcomes, and primary analysis. This is a major distinction from explanatory trials (as described by Schwartz and Lellouch1) which are intended to provide a more thorough confirmation of the hypothesis.
Truly pragmatic trials should not be blind participants or the clinicians. This can result in bias in the estimations of the effect of treatment. Pragmatic trials will also recruit patients from different health care settings to ensure that their results can be generalized to the real world.
Additionally, clinical trials should focus on outcomes that matter to patients, such as quality of life and functional recovery. This is particularly important for trials that involve invasive procedures or have potentially dangerous adverse impacts. The CRASH trial29, for instance focused on the functional outcome to compare a 2-page case-report with an electronic system for monitoring of patients in hospitals suffering from chronic heart failure. In addition, the catheter trial28 utilized symptomatic catheter-associated urinary tract infections as the primary outcome.
In addition to these aspects pragmatic trials should reduce the trial's procedures and data collection requirements to reduce costs. In the end, pragmatic trials should aim to make their results as relevant to actual clinical practice as is possible. This can be achieved by ensuring their primary analysis is based on the intention-to treat method (as described in CONSORT extensions).
Despite these requirements, a number of RCTs with features that challenge the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all kinds. This could lead to misleading claims of pragmaticity, and the use of the term should be standardized. The creation of a PRECIS-2 tool that provides an objective and standardized evaluation of the pragmatic characteristics is the 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 everyday routine care. This is distinct from explanation trials, which test hypotheses about the causal-effect relationship in idealized conditions. In this way, pragmatic trials can have less internal validity than explanation studies and be more prone to biases in their design analysis, conduct, and design. Despite these limitations, pragmatic trials can be a valuable source of information for decisions in 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 areas of recruitment, organization as well as flexibility in delivery flexible adherence and follow-up were awarded high scores. However, the primary outcome and the method of missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial with good pragmatic features without compromising the quality of its results.
It is, however, difficult to determine how pragmatic a particular trial really is because pragmaticity is not a definite quality; certain aspects of a study can be more pragmatic than others. Moreover, protocol or logistic modifications made during the trial may alter its pragmatism score. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. The majority of them were single-center. Therefore, they aren't quite as typical and can only be called pragmatic when their sponsors are accepting of the absence of blinding in these trials.
A typical feature of pragmatic studies is that researchers attempt to make their findings more meaningful by analyzing subgroups of the trial sample. However, this often leads to unbalanced comparisons and lower statistical power, which increases the risk of either not detecting or misinterpreting differences in the primary outcome. In the case of the pragmatic trials that were included in this meta-analysis this was a major issue because the secondary outcomes weren't adjusted for the differences in baseline covariates.
In addition, pragmatic studies may pose challenges to collection and interpretation safety data. This is due to the fact that adverse events are typically self-reported and are susceptible to delays, errors or coding variations. It is crucial to increase the accuracy and quality of outcomes in these trials.
Results
While the definition of pragmatism does not require that all trials are 100 100% pragmatic, there are advantages to incorporating pragmatic components into clinical trials. These include:
Increasing sensitivity to real-world issues as well as reducing cost and size of the study, and enabling the trial results to be more quickly implemented into clinical practice (by including routine patients). However, pragmatic trials be a challenge. The right type of heterogeneity, for example, can help a study expand its findings to different patients or settings. However the wrong type of heterogeneity could reduce the assay sensitivity and thus reduce a trial's power to detect small treatment effects.
A variety of studies have attempted to classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 created a framework to distinguish between explanation-based trials that support a clinical or physiological hypothesis, and pragmatic trials that inform 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 pragmatic. The domains covered recruitment of intervention, 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 to this assessment, dubbed the Pragmascope which was more user-friendly to use in systematic reviews. They found that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
This difference in primary analysis domain can be explained by the way most pragmatic trials analyze data. Some explanatory trials, however, do not. The overall score for pragmatic systematic reviews was lower when the domains of organisation, flexible delivery and following-up were combined.
It is important to remember that a pragmatic study should not mean that a trial is of poor quality. In fact, there are a growing number of clinical trials that use the term 'pragmatic' either in their abstract or title (as defined by MEDLINE, but that is not precise nor sensitive). These terms could indicate a greater appreciation of pragmatism in abstracts and titles, however it isn't clear whether this is reflected in the content.
Conclusions
As the value of real-world evidence grows widespread the pragmatic trial has gained popularity in research. They are randomized clinical trials that evaluate real-world alternatives to care rather than experimental treatments under development, they include patients which are more closely resembling those 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 approach can help overcome limitations of observational studies which include the biases that arise from relying on volunteers and the lack of availability and coding variability in national registries.
Pragmatic trials have other advantages, like the ability to draw on existing data sources and a greater likelihood of detecting meaningful differences from traditional trials. However, they may still have limitations which undermine their validity and generalizability. Participation rates in some trials could be lower than expected due to the health-promoting effect, financial incentives, or competition from other research studies. Many pragmatic trials are also restricted by the necessity to enroll participants quickly. Additionally, some pragmatic trials do not have controls to ensure that the observed differences are not due to biases in the conduct of trials.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-described themselves as pragmatist and published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which includes the eligibility criteria for domains, recruitment, flexibility in adherence to interventions, and follow-up. They discovered that 14 of the trials scored highly or pragmatic pragmatic (i.e. scores of 5 or more) in one or more of these domains, and that the majority of them were single-center.
Trials with high pragmatism scores tend to have broader criteria for eligibility than conventional RCTs. They also contain populations from many different hospitals. These characteristics, according to the authors, may make pragmatic trials more useful and applicable in the daily practice. However they do not guarantee that a trial will be free of bias. Moreover, the pragmatism of trials is not a definite characteristic; a pragmatic trial that does not contain all the characteristics of an explanatory trial may yield valid and useful results.