Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that facilitates research into pragmatic trials. It collects and distributes cleaned trial data, ratings and evaluations using PRECIS-2. This allows for 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 not used in a consistent manner and its definition and assessment need further clarification. Pragmatic trials are intended to guide clinical practices and policy decisions, not to verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should also strive to be as close to the real-world clinical environment as possible, such as its recruitment of participants, setting and design as well as the implementation of the intervention, and the determination and analysis of the outcomes, and primary analyses. This is a key distinction from explanation trials (as described by Schwartz and Lellouch1) that are designed to provide more thorough confirmation of a hypothesis.
Truely pragmatic trials should not be blind participants or the clinicians. This could lead to an overestimation of the effect of treatment. The pragmatic trials also include patients from various health care settings to ensure that the outcomes can be compared to the real world.
Furthermore, trials that are pragmatic must concentrate on outcomes that are important to patients, like the quality of life and functional recovery. This is particularly important in trials that require surgical procedures that are invasive or may have serious adverse effects. The CRASH trial29 compared a 2-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28, on the other hand was based on symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these characteristics pragmatic trials should also reduce the requirements for data collection and trial procedures to cut down on costs and time commitments. Additionally the aim of pragmatic trials is to make their results as relevant to real-world clinical practices as they can. This can be accomplished by ensuring that their analysis is based on an intention-to treat approach (as described in CONSORT extensions).
Despite these criteria, 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 the PRECIS-2 tool, which provides a standard objective assessment of practical features is a good initial step.
Methods
In a pragmatic research study it is the intention to inform policy or clinical decisions by demonstrating how an intervention can be integrated into routine care in real-world settings. This is distinct from explanation trials, which test hypotheses about the cause-effect connection in idealized settings. Therefore, pragmatic trials might have lower internal validity than explanatory trials and may be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials can provide valuable information to decision-making in healthcare.
The PRECIS-2 tool measures the degree of pragmatism in an RCT by assessing it on 9 domains, ranging from 1 (very explanatory) to 5 (very pragmatic). In this study, the areas of recruitment, organization as well as flexibility in delivery flexibility in adherence, and follow-up scored high. However, the main outcome and the method of missing data was scored below the pragmatic limit. This suggests that a trial can be designed with well-thought-out pragmatic features, without compromising its quality.
It is, however, difficult to assess how pragmatic a particular trial is since pragmatism is not a binary attribute; some aspects of a study can be more pragmatic than others. Additionally, logistical or protocol modifications during the course of a trial can change its score in pragmatism. In addition 36% of 89 pragmatic trials discovered by Koppenaal and colleagues 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 considered pragmatic if their sponsors agree that the trials aren't blinded.
Additionally, a typical feature of pragmatic trials is that researchers try to make their results more meaningful by analysing subgroups of the trial sample. This can result in unbalanced analyses that have lower statistical power. This increases the chance 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 major issue since the secondary outcomes weren't adjusted for the differences in the baseline covariates.
In addition, pragmatic trials can also present challenges in the gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported, and therefore are prone to delays, inaccuracies or coding errors. It is important to improve the quality and accuracy of the outcomes in these trials.
Results
While the definition of pragmatism does not require that all trials are 100% pragmatic, there are benefits to incorporating pragmatic components into clinical trials. These include:
By including routine patients, the results of the trial are more easily translated into clinical practice. However, pragmatic trials may also have drawbacks. For instance, the appropriate type of heterogeneity can help the trial to apply its results to many different settings and patients. However the wrong type of heterogeneity may reduce the assay's sensitiveness and consequently lessen the ability of a study to detect even minor effects of treatment.
Several studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed a framework for distinguishing between research studies that prove the clinical or physiological hypothesis, and pragmatic trials that aid in the selection of appropriate treatments in clinical practice. The framework consisted of nine domains that were assessed on a scale of 1-5, with 1 being more explanatory while 5 was more pragmatic. The domains included recruitment, setting up, delivery of intervention, flex compliance and primary analysis.
The original PRECIS tool3 featured similar domains and an assessment scale ranging from 1 to 5. 프라그마틱 무료체험 메타 pragmatickr and colleagues10 developed an adaptation of this assessment dubbed the Pragmascope that was easier to use in systematic reviews. They found that pragmatic reviews scored higher in most domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains could be due to the way in which most pragmatic trials analyse data. Some explanatory trials, however don't. The overall score for systematic reviews that were pragmatic was lower when the areas of organisation, flexible delivery and follow-up were merged.
It is important to remember that a pragmatic trial doesn't necessarily mean a poor quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is not specific nor sensitive) that employ the term "pragmatic" in their abstracts or titles. The use of these words in abstracts and titles could indicate a greater understanding of the importance of pragmatism, however, it is not clear if this is manifested in the content of the articles.
Conclusions
As the importance of real-world evidence grows widespread, pragmatic trials have gained momentum in research. They are randomized trials that compare real world treatment options with 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 limitations of observational studies, such as the biases associated with reliance on volunteers, and the limited availability and coding variability in national registries.
Other benefits of pragmatic trials include the possibility of using existing data sources, as well as a higher likelihood of detecting meaningful changes than traditional trials. However, they may still have limitations that undermine their reliability and generalizability. For example the rates of participation in some trials might be lower than anticipated due to the healthy-volunteer effect and financial incentives or competition for participants from other research studies (e.g. industry trials). Practical trials are often restricted by the need to recruit participants on time. In addition certain pragmatic trials do not 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-labeled themselves as pragmatist and published until 2022. They evaluated pragmatism using the PRECIS-2 tool that includes the eligibility criteria for domains and recruitment criteria, as well as flexibility in intervention adherence and follow-up. They discovered that 14 of the trials scored pragmatic or highly sensible (i.e., scoring 5 or higher) in any one or more of these domains and that the majority were single-center.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs that have specific criteria that are not likely to be used in the clinical environment, and they contain patients from a broad variety of hospitals. The authors argue that these characteristics can help make pragmatic trials more meaningful and relevant to daily practice, but they don't necessarily mean that a trial using a pragmatic approach is completely free of bias. Moreover, the pragmatism of a trial is not a predetermined characteristic; a pragmatic trial that doesn't contain all the characteristics of a explanatory trial can yield reliable and relevant results.