Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that facilitates research on pragmatic trials. It collects and shares cleaned trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological research studies to compare treatment effects estimates across trials that have different levels of pragmatism as well as other design features.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. However, the usage of the term "pragmatic" is not consistent and its definition and evaluation requires clarification. The purpose of pragmatic trials is to inform clinical practice and policy decisions, rather than to prove an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should also aim to be as similar to actual clinical practice as is possible, including the selection of participants, setting and design of the intervention, its delivery and implementation of the intervention, and the determination and analysis of outcomes and primary analysis. This is a major difference between explanatory trials as defined by Schwartz & Lellouch1 which are designed to test a hypothesis in a more thorough manner.
The most pragmatic trials should not blind participants or clinicians. This could lead to an overestimation of the effects of treatment. The pragmatic trials also include patients from various healthcare settings to ensure that the results can be applied to the real world.
Additionally the focus of pragmatic trials should be on outcomes that are crucial to patients, like quality of life or functional recovery. This is especially important when it comes to trials that involve invasive procedures or those with potential for dangerous adverse events. 프라그마틱 슬롯 조작 trial29, for example focused on the functional outcome to compare a two-page report with an electronic system for the monitoring of hospitalized patients with chronic heart failure. Similarly, the catheter trial28 utilized urinary tract infections that are symptomatic of catheters as the primary outcome.
In addition to these characteristics pragmatic trials should also reduce the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Finally pragmatic trials should strive to make their findings as applicable to clinical practice as is possible 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 which do not meet the criteria for pragmatism, however, they have characteristics that are contrary to pragmatism have been published in journals of various kinds and incorrectly labeled pragmatic. This could lead to misleading claims of pragmaticity, and the usage of the term needs to be standardized. The development of a PRECIS-2 tool that can provide an objective, standardized evaluation of pragmatic aspects is a good start.
Methods
In a pragmatic research study the aim is to inform clinical or policy decisions by demonstrating how an intervention could be integrated into routine care in real-world situations. Explanatory trials test hypotheses concerning the cause-effect relation within idealized conditions. In this way, pragmatic trials may have lower internal validity than explanation studies and be more prone to biases in their design, analysis, and conduct. Despite these limitations, pragmatic trials can contribute valuable information to decision-making in the context of healthcare.
The PRECIS-2 tool evaluates an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatic). In this study, the recruit-ment organization, flexibility in delivery, flexible adherence and follow-up domains received high scores, however the primary outcome and the procedure for missing data fell below the practical limit. This indicates that a trial can be designed with effective pragmatic features, without harming the quality of the trial.
It is hard to determine the degree of pragmatism in a particular study because pragmatism is not a have a binary characteristic. Certain aspects of a research study can be more pragmatic than others. A trial's pragmatism could be affected by changes to the protocol or logistics during the trial. In addition, 36% of the 89 pragmatic trials discovered by Koppenaal et al were placebo-controlled or conducted prior to licensing and most were single-center. They are not close to the usual practice, and can only be considered pragmatic if their sponsors accept that the trials are not blinded.
A typical feature of pragmatic research is that researchers attempt to make their findings more meaningful by analyzing subgroups within the trial. This can lead to unbalanced results and lower statistical power, which increases the risk of either not detecting or incorrectly detecting differences in the primary outcome. In the case of the pragmatic trials included in this meta-analysis, this was a serious issue because the secondary outcomes weren't adjusted for variations in the baseline covariates.
Furthermore, pragmatic studies may pose challenges to gathering and interpretation of safety data. This is because adverse events are usually self-reported and prone to reporting errors, delays, or coding variations. It is crucial to improve the accuracy and quality of the results in these trials.
Results
While the definition of pragmatism does not mean that trials must be 100 100% pragmatic, there are advantages of including pragmatic elements in clinical trials. These include:
Incorporating routine patients, the trial results can be more quickly translated into clinical practice. However, pragmatic trials have their disadvantages. The right type of heterogeneity, like could help a study expand its findings to different patients or settings. However the wrong type of heterogeneity could reduce the sensitivity of an assay, and therefore reduce a trial's power to detect even minor effects of treatment.
Numerous studies have attempted to classify pragmatic trials with a variety of definitions and scoring systems. Schwartz and Lellouch1 created an approach to distinguish between explanation-based trials that support a physiological or clinical hypothesis, and pragmatic trials that help in the selection of appropriate treatments in real-world clinical practice. Their framework comprised nine domains, each scored on a scale ranging from 1 to 5, with 1 being more informative and 5 indicating more practical. The domains included recruitment and setting up, the delivery of intervention, flexible compliance and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal and colleagues10 created an adaptation of this assessment, dubbed the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic systematic reviews had higher average scores in the majority of domains, but lower scores in the primary analysis domain.
The difference in the analysis domain that is primary could be due to the fact that most pragmatic trials process their data in an intention to treat manner, whereas some explanatory trials do not. The overall score for pragmatic systematic reviews was lower when the areas of management, flexible delivery and follow-up were merged.
It is crucial to keep in mind that a pragmatic study does not mean that a trial is of poor quality. In fact, there is an increasing number of clinical trials that employ the term "pragmatic" either in their title or abstract (as defined by MEDLINE, but that is not precise nor sensitive). The use of these words in abstracts and titles could suggest a greater awareness of the importance of pragmatism however, it is not clear if this is reflected in the contents of the articles.
Conclusions
In recent years, pragmatic trials have been gaining popularity in research as the value of real world evidence is becoming increasingly acknowledged. They are randomized trials that evaluate real-world alternatives to experimental treatments in development. They involve patient populations closer to those treated in regular care. This method can help overcome the limitations of observational research like the biases that are associated with the use of volunteers as well as the insufficient availability and the coding differences in national registry.
Other benefits of pragmatic trials include the possibility of using existing data sources, and a greater chance of detecting meaningful changes than traditional trials. However, pragmatic tests may still have limitations which undermine their reliability and generalizability. For instance, participation rates in some trials might be lower than expected due to the healthy-volunteer effect and financial incentives or competition for participants from other research studies (e.g., industry trials). The need to recruit individuals in a timely fashion also reduces the size of the sample and the impact of many practical trials. Additionally certain 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 self-labeled as pragmatist and published up to 2022. The PRECIS-2 tool was employed to evaluate pragmatism. It covers areas such as eligibility criteria as well as recruitment flexibility, adherence to intervention, and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Studies with high pragmatism scores are likely to have broader criteria for eligibility than traditional RCTs. They also contain populations from various hospitals. The authors suggest that these characteristics could make the pragmatic trials more relevant and useful for daily practice, but they don't necessarily mean that a trial using a pragmatic approach is free from bias. Moreover, 프라그마틱 슬롯버프 of the trial is not a definite characteristic A pragmatic trial that does not have all the characteristics of an explanatory trial can produce valuable and reliable results.