Pragmatic Free Trial Meta

Pragmatic Free Trail Meta is an open data platform that allows 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 to examine the effect of treatment across trials with different levels of pragmatism.

Background

Pragmatic trials are becoming more widely recognized as providing real-world evidence to support clinical decision-making. However, the usage of the term "pragmatic" is not consistent and its definition and assessment requires clarification. The purpose of pragmatic trials is to guide the practice of clinical medicine and policy choices, rather than confirm a physiological hypothesis or clinical hypothesis. A pragmatic trial should try to be as similar to the real-world clinical environment as possible, such as the recruitment of participants, setting up and design of the intervention, its delivery and execution of the intervention, and the determination and analysis of outcomes as well as primary analyses. This is a key distinction from explanation trials (as described by Schwartz and Lellouch1) which are designed to provide more thorough confirmation of a hypothesis.

Trials that are truly practical should avoid attempting to blind participants or clinicians as this could cause distortions in estimates of the effect of treatment. Practical trials should also aim to attract patients from a wide range of health care settings, to ensure that the results can be applied to the real world.

Additionally studies that are pragmatic should focus on outcomes that are important to patients, such as quality of life or functional recovery. This is particularly relevant when trials involve surgical procedures that are invasive or may have dangerous adverse consequences. The CRASH trial29, for instance focused on the functional outcome to evaluate a two-page case report with an electronic system for the monitoring of patients admitted to hospitals with chronic heart failure. In addition, the catheter trial28 focused on urinary tract infections caused by catheters as its primary outcome.

In addition to these characteristics, pragmatic trials should minimize trial procedures and data-collection requirements to cut down on costs and time commitments. Furthermore pragmatic trials should try to make their findings as applicable to clinical practice as they can by making sure that their primary analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).

Many RCTs that do not meet the criteria for pragmatism, but have features that are contrary to pragmatism have been published in journals of different types and incorrectly labeled pragmatic. This can result in misleading claims of pragmatism, and the use of the term should be standardized. The development of the PRECIS-2 tool, which provides an objective standard for assessing pragmatic features is a great first step.

Methods

In a pragmatic trial, the aim is to inform policy or clinical decisions by demonstrating how an intervention would be incorporated into real-world routine care. Explanatory trials test hypotheses about the causal-effect relationship in idealized conditions. Consequently, pragmatic trials may have less internal validity than explanatory trials and may be more susceptible to bias in their design, conduct, and analysis. Despite their limitations, pragmatic research can provide valuable data for making decisions within the context of healthcare.

The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatist). In this study the areas of recruitment, organization as well as flexibility in delivery flexible adherence and follow-up received high scores. However, the principal outcome and method of missing data were scored below the practical limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without compromising the quality of its results.

It is hard to determine the amount of pragmatism within a specific trial because pragmatism does not possess a specific characteristic. Some aspects of a research study can be more pragmatic than other. The pragmatism of a trial can be affected by modifications to the protocol or logistics during the trial. Additionally 36% of the 89 pragmatic trials discovered by Koppenaal and colleagues were placebo-controlled or conducted prior to licensing and most 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 these trials.

A common aspect of pragmatic research is that researchers try to make their findings more meaningful by studying subgroups within the trial. This can lead to imbalanced analyses and less statistical power. This increases the risk of omitting or ignoring differences in the primary outcomes. In the case of the pragmatic studies included in this meta-analysis, this was a major issue since the secondary outcomes were not adjusted to account for variations in baseline covariates.

In addition, pragmatic studies can pose difficulties in the collection and interpretation of safety data. It is because adverse events are typically self-reported, and therefore are prone to errors, delays or coding variations. It is therefore important to improve the quality of outcomes for these trials, ideally by using national registries instead of relying on participants to report adverse events in the trial's own database.

Results

While the definition of pragmatism doesn't require that all clinical trials be 100% pragmatist, there are benefits of including pragmatic elements in trials. These include:

Enhancing sensitivity to issues in the real world as well as reducing study size and cost, and enabling the trial results to be faster transferred into real-world clinical practice (by including patients from routine care). However, pragmatic studies can also have drawbacks. The right kind of heterogeneity, like could allow a study to expand its findings to different patients or settings. However the wrong type of heterogeneity could reduce the sensitivity of an assay and, consequently, decrease the ability of a study to detect small treatment effects.

Numerous studies have attempted to categorize pragmatic trials, using various definitions and scoring systems. Schwartz and Lellouch1 have developed a framework to distinguish between explanatory trials that confirm a physiological or clinical hypothesis as well as pragmatic trials that aid in the selection of appropriate therapies in clinical practice. Their framework comprised nine domains, each scored on a scale of 1-5, with 1 indicating more lucid and 5 indicating more practical. The domains were recruitment setting, setting, intervention delivery and follow-up, as well as flexible adherence and primary analysis.

The original PRECIS tool3 included similar domains and scales from 1 to 5. Koppenaal et. al10 devised an adaptation of this assessment, known as the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic reviews scored higher in most domains, but scored lower in the primary analysis domain.

This distinction in the main analysis domain could be due to the fact that most pragmatic trials analyze their data in the intention to treat manner, whereas some explanatory trials do not. The overall score was lower for pragmatic systematic reviews when the domains of the organization, flexibility of delivery and follow-up were combined.

It is crucial to keep in mind that a pragmatic study should not mean that a trial is of poor quality. In fact, there are an increasing number of clinical trials which use the word '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 could indicate a greater understanding of the importance of pragmatism, however, it is not clear if this is reflected in the content of the articles.

Conclusions

As the importance of evidence from the real world becomes more popular and pragmatic trials have gained momentum in research. They are randomized trials that compare real world care alternatives to new treatments that are being developed. They involve patient populations closer to those treated in regular care. This approach can help overcome the limitations of observational research which include the biases associated with reliance on volunteers and the lack of accessibility and coding flexibility in national registries.

Pragmatic trials also have advantages, including the ability to draw on existing data sources and a higher likelihood of detecting meaningful differences than traditional trials. However, pragmatic trials may be prone to limitations that compromise their credibility and generalizability. Participation rates in some trials could be lower than anticipated because of the healthy-volunteering effect, financial incentives or competition from other research studies. The necessity to recruit people in a timely fashion also reduces the size of the sample and the impact of many pragmatic trials. Additionally certain pragmatic trials don't have controls to ensure that the observed differences are not due to biases in trial conduct.

The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-labeled themselves as pragmatic and that were published until 2022. The PRECIS-2 tool was employed to evaluate the pragmatism of these trials. It covers areas like eligibility criteria and flexibility in recruitment, 프라그마틱 홈페이지 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 which have very specific criteria that aren't likely to be present in the clinical environment, and they comprise patients from a wide variety of hospitals. The authors suggest that these characteristics could make pragmatic trials more meaningful and relevant to daily practice, but they do not necessarily guarantee that a trial conducted in a pragmatic manner is free from bias. Moreover, the pragmatism of the trial is not a fixed attribute and a pragmatic trial that doesn't have all the characteristics of an explanatory trial may yield valuable and reliable results.