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 is a platform that collects and shares clean trial data and ratings using PRECIS-2 allowing for multiple and diverse meta-epidemiological studies to compare treatment effects estimates across trials that have different levels of pragmatism, as well as other design features.
Background
Pragmatic trials are increasingly recognized as providing real-world evidence for clinical decision making. However, the usage of the term "pragmatic" is inconsistent and its definition and assessment requires clarification. The purpose of pragmatic trials is to guide clinical practice and policy decisions, not to confirm a physiological or clinical hypothesis. A pragmatic trial should try to be as close as it is to the real-world clinical practice which include the recruitment of participants, setting, design, delivery and execution of interventions, determination and analysis results, as well as primary analysis. This is a significant distinction from explanatory trials (as described by Schwartz and Lellouch1), which are intended to provide a more thorough proof of an idea.
Trials that are truly pragmatic should not attempt to blind participants or clinicians as this could lead to bias in estimates of the effect of treatment. 프라그마틱 정품 확인법 should also aim to attract patients from a wide range of health care settings to ensure that their findings can be applied to the real world.
Finally, pragmatic trials must concentrate on outcomes that are important to patients, such as quality of life and functional recovery. This is particularly relevant when trials involve the use of invasive procedures or could have harmful adverse consequences. The CRASH trial29, for example was focused on functional outcomes to evaluate a two-page case report with an electronic system to monitor the health of patients admitted to hospitals with chronic heart failure. In addition, the catheter trial28 used urinary tract infections that are symptomatic of catheters as the primary outcome.
In addition to these aspects the pragmatic trial should also reduce the procedures for conducting trials and data collection requirements to reduce costs. Finaly these trials should strive to make their results as applicable to current clinical practice as is possible. This can be accomplished by ensuring their primary analysis is based on the intention to treat approach (as described within CONSORT extensions).
Many RCTs that don't meet the requirements for pragmatism but have features that are contrary to pragmatism have been published in journals of different kinds and incorrectly labeled pragmatic. This could lead to false claims of pragmatism, and the usage of the term should be standardised. The creation of the PRECIS-2 tool, which provides an objective and standard 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 showing how an intervention could be integrated into routine treatment in real-world settings. Explanatory trials test hypotheses regarding the cause-effect relation within idealized environments. Consequently, pragmatic trials may be less reliable than explanatory trials and might be more susceptible to bias in their design, conduct, and analysis. Despite these limitations, pragmatic trials may contribute valuable information to decision-making in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging from 1 to 5 (very pragmatist). In this study the areas of recruitment, organization and flexibility in delivery, flexible adherence and follow-up were awarded high scores. However, the main outcome and the method for missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without damaging the quality of its outcomes.
It is, however, difficult to determine how practical a particular trial is since pragmaticity is not a definite attribute; some aspects of a trial can be more pragmatic than others. The pragmatism of a trial can be affected by changes to the protocol or the logistics during the trial. Additionally, 36% of the 89 pragmatic trials identified by Koppenaal and co. were placebo-controlled, or conducted prior to licensing and most were single-center. This means that they are not very close to usual practice and are only pragmatic when their sponsors are accepting of the absence of blinding in these trials.
A common aspect of pragmatic research is that researchers attempt to make their findings more meaningful by analyzing subgroups of the trial sample. This can lead to unbalanced comparisons with a lower statistical power, increasing the risk of either not detecting or misinterpreting the results of the primary outcome. In the case of the pragmatic trials that were included in this meta-analysis this was a major issue since the secondary outcomes were not adjusted for differences in baseline covariates.
Furthermore, pragmatic trials can also have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events are generally reported by the participants themselves and are prone to reporting delays, inaccuracies or coding errors. It is important to increase the accuracy and quality of the outcomes in these trials.
Results
While the definition of pragmatism doesn't require that all clinical trials are 100% pragmatist There are advantages when incorporating pragmatic components into trials. These include:
By including routine patients, the trial results can be translated more quickly into clinical practice. However, pragmatic trials have their disadvantages. The right kind of heterogeneity, for example could allow a study to generalise its findings to many different settings or patients. However the wrong kind of heterogeneity can decrease the sensitivity of the test and thus reduce a trial's power to detect small treatment effects.
Numerous studies have attempted to categorize pragmatic trials with various definitions and scoring systems. Schwartz and Lellouch1 have developed an approach to distinguish between research studies that prove the clinical or physiological hypothesis, and pragmatic trials that help in the selection of appropriate treatments in the real-world clinical setting. The framework was comprised of nine domains scored on a 1-5 scale, with 1 being more informative and 5 being more pragmatic. The domains covered recruitment of intervention, setting up, delivery of intervention, flex adherence and primary analysis.
The initial PRECIS tool3 featured similar domains and a scale of 1 to 5. Koppenaal et al10 devised an adaptation to this assessment dubbed the Pragmascope which was more user-friendly to use in systematic reviews. They found that pragmatic reviews scored higher on average across all domains, however they 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, do not. The overall score was lower for pragmatic systematic reviews when the domains of organisation, flexible 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 is an increasing number of clinical trials that use the word 'pragmatic,' either in their abstracts or titles (as defined by MEDLINE however it is not precise nor sensitive). These terms may signal an increased appreciation of pragmatism in titles and abstracts, but it's not clear if this is reflected in the content.
Conclusions
In recent times, pragmatic trials are gaining popularity in research as the value of real world evidence is increasingly recognized. They are randomized trials that evaluate real-world treatment options with experimental treatments in development. They involve patient populations that are more similar to those who receive treatment in regular medical care. This method is able to overcome the limitations of observational research, for example, the biases that are associated with the use of volunteers and the lack of codes that vary in national registers.
Pragmatic trials also have advantages, such as the ability to use existing data sources and a higher probability of detecting meaningful differences from traditional trials. However, these tests could still have limitations which undermine their reliability and generalizability. For instance, participation rates in some trials could be lower than expected due to the healthy-volunteer influence and incentives to pay or compete for participants from other research studies (e.g., industry trials). Practical trials are often restricted by the need to enroll participants on time. Additionally 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 self-labeled as pragmatic and were published until 2022. The PRECIS-2 tool was employed to assess the pragmatism of these trials. It covers areas like eligibility criteria, recruitment flexibility and adherence to intervention and follow-up. They found that 14 of these trials scored pragmatic or highly sensible (i.e. scores of 5 or more) in any one or more of these domains, and that the majority were single-center.
Studies that have high pragmatism scores tend to have more lenient criteria for eligibility than traditional RCTs. They also have patients from a variety of hospitals. The authors argue that these characteristics could make the pragmatic trials more relevant and applicable to everyday clinical practice, however they do not necessarily guarantee that a pragmatic trial is completely free of bias. In addition, the pragmatism that is present in the trial is not a predetermined characteristic A pragmatic trial that doesn't have all the characteristics of an explanatory trial may yield valuable and reliable results.