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 gathers and distributes clean trial data, ratings, and evaluations using PRECIS-2. This allows for diverse meta-epidemiological analyses to examine the effect 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 not used in a consistent manner and its definition and assessment require further clarification. The purpose of pragmatic trials is to inform clinical practices and policy decisions rather than prove a physiological or clinical hypothesis. A pragmatic study should strive to be as close to the real-world clinical environment as is possible, including the recruitment of participants, setting up and design as well as the implementation of the intervention, and the determination and analysis of outcomes as well as primary analyses. This is a major distinction from explanation trials (as described by Schwartz and Lellouch1) that are designed to provide more thorough confirmation of an idea.
Truly pragmatic trials should not blind participants or clinicians. This can lead to an overestimation of treatment effects. Practical trials also involve patients from different health care settings to ensure that their outcomes can be compared to the real world.
Finally studies that are pragmatic should focus on outcomes that are vital to patients, like quality of life or functional recovery. This is particularly important in trials that require the use of invasive procedures or could have dangerous adverse impacts. The CRASH trial29, for example was focused on functional outcomes to compare a two-page report with an electronic system for monitoring of patients admitted to hospitals 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 aspects, pragmatic trials should minimize the trial procedures and requirements for data collection to reduce costs. Finaly, pragmatic trials should aim to make their results as relevant to real-world clinical practices as they can. This can be accomplished by ensuring that their primary analysis is based on an intention-to treat method (as described in CONSORT extensions).
Despite these guidelines, many RCTs with features that defy pragmatism have been incorrectly self-labeled pragmatic and published in journals of all kinds. This can lead to false claims of pragmaticity, and the use of the term should be standardized. The creation of the PRECIS-2 tool, which provides an objective and standard assessment of practical features, is a good first step.
Methods
In a practical study it is the intention to inform policy or clinical decisions by showing how an intervention could be integrated into routine care in real-world contexts. 프라그마틱 이미지 test hypotheses regarding the cause-effect relation within idealized environments. In this way, pragmatic trials can have lower internal validity than explanation studies and be more prone to biases in their design as well as analysis and conduct. Despite their limitations, pragmatic studies can provide valuable data for making decisions within the healthcare context.
The PRECIS-2 tool measures the degree of pragmatism within an RCT by assessing it across 9 domains that range from 1 (very explicit) to 5 (very pragmatic). In this study the areas of recruitment, organization and flexibility in delivery, flexibility in adherence, and follow-up received high scores. However, the main outcome and the method for missing data were scored below the practical limit. This suggests that it is possible to design a trial using excellent pragmatic features without harming the quality of the results.
It is hard to determine the amount of pragmatism within a specific study because pragmatism is not a have a binary characteristic. Some aspects of a research study can be more pragmatic than other. Furthermore, logistical or protocol modifications during the course of an experiment can alter its score on pragmatism. In addition 36% of the 89 pragmatic trials identified by Koppenaal and co. were placebo-controlled, or conducted prior to approval and a majority of them were single-center. They are not close to the usual practice, and can only be called pragmatic if the sponsors agree that the trials are not blinded.
Additionally, a typical feature of pragmatic trials is that researchers attempt to make their findings more meaningful by analysing subgroups of the trial sample. This can lead to unbalanced analyses with less statistical power. This increases the possibility of missing or misdetecting differences in the primary outcomes. In the case of the pragmatic studies that were included in this meta-analysis this was a serious issue because the secondary outcomes were not adjusted to account for variations in the baseline covariates.
In addition practical trials can have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events are usually self-reported, and are prone to delays, inaccuracies or coding differences. Therefore, it is crucial to improve the quality of outcomes assessment in these trials, ideally by using national registries rather than relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism does not require that clinical trials be 100% pragmatist there are benefits to including pragmatic components in trials. These include:
Incorporating routine patients, the results of trials are more easily translated into clinical practice. However, pragmatic studies can also have disadvantages. For instance, the right kind of heterogeneity can allow a study to generalize its results to many different patients and settings; however, the wrong type of heterogeneity could reduce assay sensitivity and therefore reduce the power of a trial to detect small treatment effects.
A variety of studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed a framework that can discern between explanation-based studies that prove a physiological or clinical hypothesis and pragmatic studies 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 being more informative and 5 suggesting more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flexible adherence and primary analysis.
The original PRECIS tool3 was built on the same scale and domains. Koppenaal et. al10 devised an adaptation of this assessment, dubbed 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 distinction in the primary analysis domains can be due to the way in which most pragmatic trials approach data. Some explanatory trials, however don't. The overall score for pragmatic systematic reviews was lower when the domains of organization, flexible delivery, and following-up were combined.
It is important to understand that the term "pragmatic trial" does not necessarily mean a low quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but it is neither sensitive nor specific) that use the term 'pragmatic' in their abstract or title. The use 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 content of the articles.
Conclusions
As the value of real-world evidence grows commonplace, pragmatic trials have gained popularity in research. They are randomized studies that compare real-world alternatives to experimental treatments in development. They are conducted with populations of patients closer to those treated in regular medical care. This approach has the potential to overcome the limitations of observational studies which include the biases that arise from relying on volunteers and limited availability and the variability of coding in national registries.
Other benefits of pragmatic trials include the ability to use existing data sources, and a greater probability of detecting significant changes than traditional trials. However, they may be prone to limitations that undermine their effectiveness and generalizability. For 프라그마틱 이미지 of participation in some trials might be lower than expected due to the healthy-volunteer effect as well as incentives to pay or compete for participants from other research studies (e.g., industry trials). Many pragmatic trials are also limited by the need to enroll participants in a timely manner. Certain pragmatic trials lack controls to ensure that the observed differences aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatist and published from 2022. The PRECIS-2 tool was used to evaluate the degree of pragmatism. It includes domains such as eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered that 14 of the trials scored as highly or pragmatic pragmatic (i.e. scoring 5 or higher) in one or more of these domains and that the majority of these were single-center.
Trials with a high pragmatism rating tend to have higher eligibility criteria than traditional RCTs which have very specific criteria that aren't likely to be found in clinical practice, and they comprise patients from a wide range of hospitals. The authors claim that these characteristics could make the pragmatic trials more relevant and useful for everyday practice, but they don't necessarily mean that a trial using a pragmatic approach is free of bias. In addition, the pragmatism that is present in trials is not a predetermined characteristic; a pragmatic trial that doesn't have all the characteristics of an explanatory trial can produce valid and useful results.