Pragmatic Free Trail Meta is an open data platform that facilitates research into 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 various levels of pragmatism.
Background
Pragmatic studies are increasingly recognized as providing real-world evidence for clinical decision making. The term "pragmatic" however, is not used in a consistent manner and its definition and assessment require clarification. The purpose of pragmatic trials is to guide clinical practice and policy decisions, rather than confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should also aim to be as similar to the real-world clinical environment as is possible, including the selection of participants, setting up and design as well as the implementation of the intervention, determination and analysis of outcomes as well as primary analyses. This is a key distinction from explanatory trials (as described by Schwartz and Lellouch1) which are designed to provide more thorough confirmation of the hypothesis.
Trials that are truly pragmatic should not attempt to blind participants or 프라그마틱 정품 clinicians, as this may cause distortions in estimates of the effect of treatment. The trials that are pragmatic should also try to recruit patients from a variety of health care settings, to ensure that the results can be applied to the real world.
Finally the focus of pragmatic trials should be on outcomes that are vital for patients, such as quality of life or functional recovery. This is especially important when it comes to trials that involve the use of invasive procedures or potential for serious adverse events. The CRASH trial29, for instance was focused on functional outcomes to compare a two-page report with an electronic system for the monitoring of patients in hospitals suffering from chronic heart failure, and the catheter trial28 utilized symptomatic catheter-associated urinary tract infections as the primary outcome.
In addition to these features pragmatic trials should reduce the requirements for data collection and trial procedures to cut costs and time commitments. Additionally these trials should strive to make their findings as applicable to current clinical practice as is possible. This can be accomplished by ensuring that their analysis is based on the intention to treat approach (as described within CONSORT extensions).
Despite these guidelines however, a large number of 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 made more uniform. The creation of the PRECIS-2 tool, which offers a standard objective assessment of pragmatic characteristics is a good initial step.
Methods
In a practical study the aim is to inform clinical or policy decisions by showing how an intervention could be integrated into routine treatment in real-world settings. Explanatory trials test hypotheses regarding the cause-effect relationship within idealised conditions. In this way, pragmatic trials could have lower internal validity than explanatory studies and be more prone to biases in their design as well as analysis and conduct. Despite their limitations, pragmatic studies can be a valuable source of data for making decisions within the healthcare context.
The PRECIS-2 tool measures the degree of pragmatism in an RCT by scoring it across 9 domains, ranging from 1 (very explicative) to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery and follow-up domains scored high scores, however, the primary outcome and the method of missing data were not at the practical limit. This suggests that it is possible to design a trial that has excellent pragmatic features without compromising the quality of its results.
It is hard to determine the amount of pragmatism in a particular trial because pragmatism does not have a binary characteristic. Some aspects of a research study can be more pragmatic than others. Moreover, protocol or logistic changes during a trial can change its score on pragmatism. Additionally 36% of 89 pragmatic trials identified by Koppenaal and co. were placebo-controlled or conducted prior to licensing, and the majority were single-center. This means that they are not very close to usual practice and can only be called pragmatic when their sponsors are accepting of the lack of blinding in such trials.
A common feature of pragmatic studies is that researchers try to make their findings more meaningful by studying subgroups within the trial sample. However, this can lead to unbalanced comparisons and lower statistical power, increasing the chance of not or misinterpreting the results of the primary outcome. In the instance of the pragmatic trials included in this meta-analysis, this was a serious issue because the secondary outcomes were not adjusted for variations in the baseline covariates.Furthermore the pragmatic trials may have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events are typically reported by participants themselves and are susceptible to reporting errors, delays or coding errors. It is essential to improve the accuracy and quality of the outcomes in these trials.
Results
While the definition of pragmatism does not require that all trials are 100 percent pragmatic, there are benefits of including pragmatic elements in clinical trials. These include:
By including routine patients, the results of trials are more easily translated into clinical practice. But pragmatic trials can be a challenge. For example, the right kind of heterogeneity can allow the trial to apply its findings to a variety of settings and patients. However, the wrong type of heterogeneity may reduce the assay's sensitiveness and consequently lessen the ability of a trial to detect even minor effects of treatment.
A number of studies have attempted to categorize pragmatic trials using various definitions and scoring systems. Schwartz and Lellouch1 created a framework to distinguish between explanatory studies that support the physiological hypothesis or clinical hypothesis and pragmatic studies that help inform the selection of appropriate treatments in the real-world clinical practice. The framework was comprised of nine domains assessed on a scale of 1-5, with 1 being more informative and 5 was more practical. The domains included recruitment, setting, intervention delivery, flexible adherence, follow-up and primary analysis.
The initial PRECIS tool3 included similar domains and a scale of 1 to 5. Koppenaal and colleagues10 created an adaptation of the assessment, known as the Pragmascope that was simpler to use for systematic reviews. They found that pragmatic systematic reviews had higher average score in most domains, with lower scores in the primary analysis domain.
The difference in the primary analysis domain could be explained by the fact that the majority of pragmatic trials analyze their data in an intention to treat manner while some explanation trials do not. The overall score for systematic reviews that were pragmatic was lower when the domains of organisation, flexible delivery and follow-up were merged.
It is crucial to keep in mind that a study that is pragmatic does not mean a low-quality trial. In fact, there are increasing numbers of clinical trials which use the term "pragmatic" either in their abstract or title (as defined by MEDLINE however it is neither precise nor sensitive). The use of these terms in titles and abstracts could suggest a greater awareness of the importance of pragmatism, but it is unclear whether this is evident in the contents of the articles.
Conclusions
In recent years, pragmatic trials are gaining popularity in research as the value of real-world evidence is increasingly recognized. They are randomized clinical trials that compare real-world care alternatives rather than experimental treatments under development. They have populations of patients that are more similar to the patients who receive routine medical care, they utilize comparators which exist in routine practice (e.g., existing drugs) and depend on participants' self-reports of outcomes. This approach could help overcome limitations of observational studies that are prone to biases that arise from relying on volunteers and the lack of availability and coding variability in national registries.
Other advantages of pragmatic trials include the ability to utilize existing data sources, and a higher chance of detecting meaningful changes than traditional trials. However, they may be prone to limitations that undermine their effectiveness and generalizability. Participation rates in some trials could be lower than expected due to the healthy-volunteering effect, financial incentives or competition from other research studies. Many pragmatic trials are also limited by the need to enroll participants in a timely manner. Additionally certain pragmatic trials don't have controls to ensure that the observed differences aren't due to biases in trial conduct.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-described themselves as pragmatic and were published from 2022. The PRECIS-2 tool was employed to assess the degree of pragmatism. It includes domains such as eligibility criteria and flexibility in recruitment as well as adherence to interventions and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or above) in at least one of these domains.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs which have very specific criteria that aren't likely to be used in the clinical environment, and they include populations from a wide range of hospitals. The authors claim that these characteristics can help make pragmatic trials more effective and useful for everyday practice, but they do not necessarily guarantee that a pragmatic trial is free of bias. The pragmatism is not a fixed characteristic; a pragmatic test that doesn't have all the characteristics of an explicative study may still yield valuable and valid results. 
