Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that supports research on pragmatic trials. It collects and distributes cleaned trial data, ratings, and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological analyses to compare treatment effect estimates across trials with different levels of pragmatism.
프라그마틱 체험 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 measurement require clarification. Pragmatic trials are intended to guide clinical practices and policy decisions rather than confirm a physiological hypothesis or clinical hypothesis. A pragmatic trial should strive to be as close to actual clinical practice as is possible, including its recruitment of participants, setting up and design as well as the execution of the intervention, determination and analysis of outcomes and primary analyses. This is a significant distinction from explanation trials (as described by Schwartz and Lellouch1), which are designed to provide more thorough confirmation of a hypothesis.
Truly pragmatic trials should not conceal participants or clinicians. This could lead to a bias in the estimates of the effects of treatment. Pragmatic trials should also seek to attract patients from a wide range of health care settings, to ensure that their findings can be applied to the real world.
Finally studies that are pragmatic should focus on outcomes that are vital to patients, like quality of life or functional recovery. This is particularly relevant when trials involve invasive procedures or have potentially harmful adverse effects. The CRASH trial29, for example was focused on functional outcomes to evaluate a two-page case report with an electronic system for monitoring of hospitalized patients with chronic heart failure. In addition, the catheter trial28 focused on urinary tract infections caused by catheters as the primary outcome.
In addition to these features pragmatic trials should reduce the trial procedures and requirements for data collection to reduce costs. Furthermore pragmatic trials should strive to make their findings as applicable to clinical practice as they can by making sure that their primary method of 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, however, they have characteristics that are contrary to pragmatism have been published in journals of varying kinds and incorrectly labeled pragmatic. This could lead to false claims of pragmatism, and the usage of the term should be standardized. The development of the PRECIS-2 tool, which offers a standard objective assessment of pragmatic characteristics, is a good first step.
Methods
In a pragmatic trial the goal is to inform clinical or policy decisions by demonstrating how an intervention would be incorporated into real-world routine care. This is different from explanatory trials, which test hypotheses about the cause-effect connection in idealized conditions. In this way, pragmatic trials can have a lower internal validity than explanatory studies and be more prone to biases in their design as well as analysis and conduct. Despite these limitations, pragmatic trials may be a valuable source of information for decisions in the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism in an RCT by assessing it on 9 domains that range from 1 (very explanatory) to 5 (very pragmatic). In this study, the recruit-ment, organization, flexibility in delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the method of missing data were not at the pragmatic limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without damaging the quality of its results.
It is, however, difficult to judge how practical a particular trial is since pragmaticity is not a definite quality; certain aspects of a trial can be more pragmatic than others. Additionally, logistical or protocol changes during the trial may alter its score in pragmatism. In addition, 36% of the 89 pragmatic trials identified by Koppenaal and co. 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 referred to as pragmatic if their sponsors accept that these trials aren't blinded.
A common aspect of pragmatic studies is that researchers attempt to make their findings more relevant by studying subgroups within the trial. However, this can lead to unbalanced comparisons and lower statistical power, thereby increasing the chance of not or misinterpreting the results of the primary outcome. In the case of the pragmatic trials included in this meta-analysis this was a major issue since the secondary outcomes were not adjusted for variations in the baseline covariates.
Furthermore, pragmatic studies may pose challenges to collection and interpretation of safety data. This is due to the fact that adverse events are usually 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, in particular by using national registries instead of relying on participants to report adverse events on the trial's database.
Results
While the definition of pragmatism does not require that all trials are 100% pragmatic, there are some advantages to incorporating pragmatic components into clinical trials. These include:
Increased sensitivity to real-world issues, reducing cost and size of the study, and enabling the trial results to be faster transferred into real-world clinical practice (by including patients who are routinely treated). However, pragmatic trials may have disadvantages. For instance, the appropriate type of heterogeneity can help the trial to apply its results to many different patients and settings; however the wrong kind of heterogeneity may reduce the assay's sensitivity and therefore decrease the ability of a study to detect minor treatment effects.
Many studies have attempted classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 developed a framework to distinguish between explanatory studies that confirm a physiological hypothesis or clinical hypothesis and pragmatic studies that inform the selection of appropriate treatments in the real-world clinical practice. Their framework included nine domains, each scoring on a scale of 1 to 5 with 1 indicating more lucid and 5 suggesting more pragmatic. The domains covered recruitment of intervention, setting up, delivery of intervention, flexible adherence and primary analysis.
The original PRECIS tool3 was an adapted version of the PRECIS tool3 that was based on the same scale and domains. Koppenaal et al10 created an adaptation to this assessment, dubbed the Pragmascope that was simpler to use in systematic reviews. They found that pragmatic systematic reviews had higher average scores across all domains, but lower scores in the primary analysis domain.
This difference in primary analysis domain can be explained by the way that most pragmatic trials approach data. Some explanatory trials, however don't. The overall score was lower for pragmatic systematic reviews when the domains of the organization, flexibility of delivery and follow-up were merged.
It is crucial to keep in mind that a study that is pragmatic does not mean that a trial is of poor quality. In fact, there is an increasing number of clinical trials that use the term 'pragmatic' either in their title or abstract (as defined by MEDLINE, but that is not precise nor sensitive). The use of these terms in abstracts and titles could 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
In recent times, pragmatic trials are becoming more popular in research as the importance of real-world evidence is becoming increasingly acknowledged. They are randomized trials that compare real world treatment options with clinical trials in development. They involve patient populations closer to those treated in regular medical care. This approach can help overcome the limitations of observational studies that are prone to biases that arise from relying on volunteers, and the limited accessibility and coding flexibility in national registry systems.
Pragmatic trials also have advantages, such as the ability to leverage existing data sources and a higher probability of detecting meaningful differences than traditional trials. However, they may still have limitations which undermine their validity and generalizability. The participation rates in certain trials could be lower than anticipated because of the healthy-volunteering effect, financial incentives, or competition from other research studies. Many pragmatic trials are also limited by the need to enroll participants on time. Practical trials aren't always equipped with controls to ensure that the observed differences aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs that were published between 2022 and 2022 that self-described as pragmatism. The PRECIS-2 tool was employed to evaluate the pragmatism of these trials. It includes domains such as eligibility criteria as well as recruitment flexibility as well as adherence to interventions and follow-up. They found that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) 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 not likely to be found in the clinical environment, and they comprise patients from a wide range of hospitals. These characteristics, according to the authors, can make pragmatic trials more useful and applicable in the daily clinical. However, they don't ensure that a study is free of bias. Furthermore, the pragmatism of trials is not a fixed attribute; a pragmatic trial that does not contain all the characteristics of a explanatory trial may yield reliable and relevant results.