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 collects and shares cleaned trial data and ratings using PRECIS-2 allowing for multiple and diverse meta-epidemiological studies that compare treatment effects estimates across trials that have different levels of pragmatism as well as other design features.
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 evaluation require clarification. Pragmatic trials must be designed to inform policy and clinical practice decisions, rather than to prove an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should strive to be as close to real-world clinical practice as is possible, including the recruitment of participants, setting and design of the intervention, its delivery and implementation of the intervention, and the determination and analysis of the outcomes, and primary analysis. This is a significant distinction from explanatory trials (as described by Schwartz and Lellouch1) which are designed to provide more thorough proof of a hypothesis.
The trials that are truly practical should be careful not to blind patients or healthcare professionals, as this may result in bias in the estimation of the effect of treatment. Pragmatic trials will also recruit patients from various healthcare settings to ensure that their results can be generalized to the real world.
Finally, pragmatic trials must focus on outcomes that matter to patients, like quality of life and functional recovery. This is especially important for trials that involve the use of invasive procedures or could have serious adverse impacts. The CRASH trial29, for instance was focused on functional outcomes to compare a two-page report with an electronic system for monitoring of hospitalized patients with chronic heart failure, and the catheter trial28 focused on symptomatic catheter-associated urinary tract infections as the primary outcome.
In addition to these aspects pragmatic trials should also reduce the procedures for conducting trials and requirements for data collection to reduce costs and time commitments. Furthermore, pragmatic trials should seek to make their findings as applicable to clinical practice as possible by making sure that their primary analysis is based on the intention-to-treat method (as described in CONSORT extensions for pragmatic trials).
Despite these requirements however, a large number of RCTs with features that challenge the concept of pragmatism have been mislabeled as pragmatic and published in journals of all types. This can lead to false claims of pragmatism and the use of the term must 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, the goal is to inform clinical or policy decisions by demonstrating how an intervention can be integrated into routine treatment in real-world settings. This is different from explanatory trials, which test hypotheses about the causal-effect relationship in idealized settings. In this way, pragmatic trials can have lower internal validity than explanation studies and are more susceptible to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging between 1 and 5 (very pragmatist). In this study, the recruit-ment, organisation, flexibility: delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the procedure for missing data were not at the practical limit. This suggests that it is possible to design a trial that has high-quality pragmatic features, without compromising the quality of its results.
However, it's difficult to assess how pragmatic a particular trial is, since pragmaticity is not a definite quality; certain aspects of a study can be more pragmatic than others. Additionally, logistical or protocol modifications made during a trial can change its score on pragmatism. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. The majority of them were single-center. This means that they are not quite as typical and are only pragmatic in the event that their sponsors are supportive of the lack of blinding in these trials.
Furthermore, a common feature of pragmatic trials is that researchers try to make their results more valuable by studying subgroups of the sample. This can result in unbalanced analyses with less statistical power. This increases the possibility of missing or misdetecting differences in the primary outcomes. In the instance of the pragmatic trials included in this meta-analysis, this was a significant problem since the secondary outcomes were not adjusted for differences in the 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 prone to delays, errors or coding differences. It is therefore important to enhance the quality of outcomes assessment in these trials, and ideally by using national registries instead of relying on participants to report adverse events in the trial's database.
Results
Although the definition of pragmatism may not require that all clinical trials be 100% pragmatist there are benefits of including pragmatic elements in trials. These include:
By incorporating routine patients, the results of the trial can be more quickly translated into clinical practice. However, pragmatic trials have disadvantages. For instance, the appropriate kind of heterogeneity can allow the trial to apply its findings to a variety of settings and patients. However the wrong type of heterogeneity can reduce assay sensitivity and therefore decrease the ability of a trial to detect minor treatment effects.
Numerous studies have attempted to classify pragmatic trials with various definitions and scoring systems. Schwartz and Lellouch1 developed an approach to distinguish between explanation-based trials that support a physiological or clinical hypothesis and pragmatic trials that aid in the selection of appropriate therapies in clinical practice. The framework consisted of nine domains scored on a 1-5 scale which indicated that 1 was more informative and 5 was more practical. The domains included recruitment and setting up, the delivery of intervention, flex adhering to the program and primary analysis.
The original PRECIS tool3 included similar domains and a scale of 1 to 5. Koppenaal et al10 developed an adaptation of this assessment, dubbed the Pragmascope, that was easier to use for systematic reviews. They found that pragmatic reviews scored higher on average in all domains, but scored lower in the primary analysis domain.
This 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 method while some explanation trials do not. The overall score was lower for pragmatic systematic reviews when the domains on the organization, flexibility of delivery and follow-up were merged.
It is important to remember that a study that is pragmatic does not mean that a trial is of poor quality. In fact, there is a growing number of clinical trials that employ the term "pragmatic" either in their abstract or title (as defined by MEDLINE but which is neither sensitive nor precise). The use of these terms in abstracts and titles may suggest a greater awareness of the importance of pragmatism but it isn't clear if this is evident in the contents of the articles.
Conclusions
As the value of real-world evidence grows commonplace the pragmatic trial has gained momentum in research. They are randomized clinical trials that evaluate real-world alternatives to care instead of experimental treatments in development, they include patient populations that are more similar to those treated in routine medical care, they utilize comparators which exist in routine practice (e.g., existing medications) and depend on participants' self-reports of outcomes. This method is able to overcome the limitations of observational research for example, the biases associated with the use of volunteers and the limited availability and coding variations in national registries.
Other advantages of pragmatic trials are the ability to use existing data sources, and a higher likelihood of detecting meaningful changes than traditional trials. However, they may have some limitations that limit their validity and generalizability. For example the participation rates in certain trials might be lower than anticipated due to the healthy-volunteer effect as well as financial incentives or competition for participants from other research studies (e.g., industry trials). 프라그마틱 슬롯 체험 to recruit individuals quickly limits the sample size and the impact of many pragmatic trials. In addition 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-labeled themselves as pragmatist and published up to 2022. They evaluated pragmatism using the PRECIS-2 tool, which consists of the domains eligibility criteria, recruitment, flexibility in adherence to interventions, and follow-up. They discovered that 14 of these trials scored highly or pragmatic pragmatic (i.e. scoring 5 or higher) in one or more of these domains, and that the majority of them 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 aren't likely to be found in the clinical setting, and contain patients from a broad variety of hospitals. The authors claim that these characteristics can help make pragmatic trials more meaningful and relevant to everyday practice, but they do not necessarily guarantee that a trial conducted in a pragmatic manner is free of bias. Moreover, the pragmatism of the trial is not a predetermined characteristic and a pragmatic trial that doesn't contain all the characteristics of an explanatory trial can yield valid and useful results.