Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a free and non-commercial open data platform and infrastructure that supports research on pragmatic trials. It shares clean trial data and ratings using PRECIS-2 permitting multiple and varied meta-epidemiological studies to examine the effects of treatment across trials that employ different levels of pragmatism as well as other design features.
Background
Pragmatic trials are becoming more widely recognized as providing real-world evidence to support clinical decision-making. However, the use of the term "pragmatic" is inconsistent and its definition as well as assessment requires further clarification. Pragmatic trials are intended to guide clinical practices and policy choices, rather than prove a physiological or clinical hypothesis. A pragmatic study should aim to be as similar to real-world clinical practice as possible, such as the participation of participants, setting up and design of the intervention, its delivery and implementation of the intervention, determination and analysis of outcomes as well as primary analyses. This is a major distinction from explanatory trials (as described by Schwartz and Lellouch1) that are designed to provide more thorough proof of an idea.
Truely pragmatic trials should not blind participants or the clinicians. This can lead to a bias in the estimates of the effect of treatment. Pragmatic trials will also recruit patients from various health care settings to ensure that their outcomes can be compared to the real world.
Additionally the focus of pragmatic trials should be on outcomes that are important to patients, like quality of life or functional recovery. This is especially important when it comes to trials that involve surgical procedures that are invasive or have potential for dangerous adverse events. The CRASH trial29 compared a 2 page report with an electronic monitoring system for patients in hospitals with chronic heart failure. The catheter trial28 however utilized symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these characteristics, pragmatic trials should minimize the requirements for data collection and trial procedures to reduce costs and time commitments. Additionally, pragmatic trials should seek to make their findings as applicable to clinical practice as possible by making sure that their primary method of analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Despite these requirements, many RCTs with features that defy the concept of pragmatism have been mislabeled as pragmatic and published in journals of all kinds. This could lead to false claims of pragmatism, and the use of the term should be made more uniform. The creation of the PRECIS-2 tool, which offers an objective standard for assessing pragmatic features is a good initial step.
Methods
In a practical trial, the aim is to inform clinical or policy decisions by demonstrating how the intervention can be implemented into routine care. This is distinct from explanation trials that test hypotheses about the cause-effect relationship in idealised situations. Consequently, pragmatic trials may be less reliable than explanatory trials and may be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials may be a valuable source of information for decision-making in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging from 1 to 5 (very pragmatic). In this study, the recruit-ment organisation, flexibility: delivery, flexible adherence and follow-up domains scored high scores, however, the primary outcome and the method of missing data were below the practical limit. This suggests that a trial can be designed with effective practical features, yet not compromising its quality.
It is difficult to determine the amount of pragmatism within a specific trial since pragmatism doesn't possess a specific characteristic. Certain aspects of a study can be more pragmatic than other. A trial's pragmatism could be affected by changes to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled or conducted prior to the licensing. The majority of them were single-center. Therefore, they aren't as common and can only be called pragmatic if their sponsors are tolerant of the lack of blinding in such 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 that have lower statistical power. This increases the risk of omitting or misinterpreting differences in the primary outcomes. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for covariates that differed at the time of baseline.
Additionally, studies that are pragmatic may pose challenges to collection and interpretation of safety data. This is due to the fact that adverse events are usually self-reported and are susceptible to reporting errors, delays or coding deviations. It is therefore important to improve the quality of outcome ascertainment in these trials, in particular by using national registry databases instead of relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism does not require that all clinical trials are 100% pragmatist there are benefits when incorporating pragmatic components into trials. These include:
Enhancing sensitivity to issues in the real world which reduces cost and size of the study, and enabling the trial results to be more quickly implemented into clinical practice (by including patients who are routinely treated). However, pragmatic trials may have disadvantages. For instance, the right type of heterogeneity could help the trial to apply its findings to a variety of patients and settings; however, the wrong type of heterogeneity could reduce assay sensitivity, and thus decrease the ability of a trial to detect minor treatment effects.
Several studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 developed a framework to differentiate between explanation studies that prove a physiological hypothesis or clinical hypothesis, and pragmatic studies that inform the selection of appropriate therapies in the real-world clinical practice. The framework was composed of nine domains scored on a 1-5 scale which indicated that 1 was more explanatory while 5 was more practical. The domains covered recruitment, setting up, delivery of intervention, flex adherence and primary analysis.
The original PRECIS tool3 had similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 created an adaptation of this assessment called the Pragmascope which was more user-friendly to use in systematic reviews. They discovered that pragmatic reviews scored higher on average across all domains, however they scored lower in the primary analysis domain.
This difference in the main analysis domain could be explained by the fact that most pragmatic trials analyze their data in the intention to treat manner however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery and follow-up were combined.
It is important to remember that a study that is pragmatic does not mean a low-quality trial. In fact, there are increasing numbers of clinical trials that employ the term 'pragmatic' either in their abstract or title (as defined by MEDLINE, but that is neither sensitive nor precise). These terms could indicate that there is a greater understanding of pragmatism in abstracts and titles, however it's unclear if this is reflected in content.
Conclusions
As the importance of real-world evidence becomes increasingly commonplace and pragmatic trials have gained traction in research. They are clinical trials randomized which compare real-world treatment options rather than experimental treatments under development, they include populations of patients which are more closely resembling the ones who are treated in routine medical care, they utilize comparisons that are commonplace in practice (e.g. existing medications), and they depend on the self-reporting of participants about outcomes. This method is able to overcome the limitations of observational research for example, the biases associated with the use of volunteers as well as the insufficient availability and coding variations in national registries.
Other advantages of pragmatic trials include the possibility of using existing data sources, and a higher probability of detecting significant changes than traditional trials. However, pragmatic tests may still have limitations which undermine their effectiveness and generalizability. Participation rates in some trials may be lower than expected due to the healthy-volunteering effect, financial incentives or competition from other research studies. The need to recruit individuals quickly restricts the sample size and the impact of many pragmatic trials. Additionally some 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 RCTs published from 2022 to 2022 that self-described as pragmatic. 프라그마틱 정품 확인법 -2 tool was used to determine the pragmatism of these trials. It includes domains such as eligibility criteria, recruitment flexibility and adherence to intervention and follow-up. They discovered that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
Trials with a high pragmatism score tend to have broader eligibility criteria than traditional RCTs that have specific criteria that are unlikely to be used in the clinical environment, and they comprise patients from a wide variety of hospitals. According to the authors, could make pragmatic trials more useful and useful in the daily clinical. However they do not guarantee that a trial is free of bias. The pragmatism principle is not a fixed attribute and a test that does not have all the characteristics of an explicative study may still yield reliable and beneficial results.