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 which allows for multiple and varied meta-epidemiological research studies to examine the effects of treatment across trials with different levels of pragmatism as well as other design features.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. The term "pragmatic", however, is used inconsistently and its definition and assessment need further clarification. Pragmatic trials should be designed to inform clinical practice and policy decisions, rather than confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic study should aim to be as similar to the real-world clinical environment as possible, such as its selection of participants, setting and design of the intervention, its delivery and execution of the intervention, and the determination and analysis of outcomes as well as primary analysis. This is a significant difference from explanatory trials (as described by Schwartz and Lellouch1) that are intended to provide a more thorough proof of a hypothesis.
The trials that are truly practical should be careful not to blind patients or clinicians in order to lead to distortions in estimates of the effect of treatment. The trials that are pragmatic should also try to enroll patients from a variety of health care settings to ensure that their findings can be applied to the real world.
Finally, pragmatic trials should focus on outcomes that are vital to patients, such as quality of life or functional recovery. This is particularly relevant when trials involve the use of invasive procedures or could have serious adverse effects. The CRASH trial29 compared a 2-page report with an electronic monitoring system for patients in hospitals suffering from chronic cardiac failure. The trial with a catheter, however was based on symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these features pragmatic trials should reduce the trial procedures and data collection requirements to reduce costs. Additionally these trials should strive to make their results as relevant to actual clinical practices as possible. This can be accomplished by ensuring that their primary analysis is based on the intention-to treat method (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 varying types and incorrectly labeled pragmatic. This can lead to false claims of pragmatism and the usage of the term should be standardized. The creation of a PRECIS-2 tool that provides a standardized objective evaluation of pragmatic aspects is a first step.
Methods
In a pragmatic study, the aim is to inform clinical or policy decisions by demonstrating how the intervention can be implemented into routine care. 프라그마틱 데모 is different from explanatory trials that test hypotheses regarding the causal-effect relationship in idealized situations. Consequently, pragmatic trials may have lower internal validity than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials can contribute valuable information to decisions in the context of healthcare.
The PRECIS-2 tool evaluates an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatic). In this study, the domains of recruitment, organisation, flexibility in delivery, flexible adherence and follow-up were awarded high scores. However, the primary outcome and the method of missing data scored below the pragmatic limit. This suggests that a trial can be designed with good practical features, yet not harming the quality of the trial.
However, it's difficult to determine how pragmatic a particular trial is, since the pragmatism score is not a binary attribute; some aspects of a trial can be more pragmatic than others. The pragmatism of a trial can be affected by modifications to the protocol or the logistics during the trial. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. They also found that the majority were single-center. They are not in line with the standard practice and are only considered pragmatic if their sponsors accept that such trials aren't blinded.
Furthermore, a common feature of pragmatic trials is that the researchers try to make their results more valuable by studying subgroups of the trial. This can lead to unbalanced analyses with less statistical power. This increases the risk of missing or misdetecting differences in the primary outcomes. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for covariates' differences at the baseline.
Furthermore practical trials can be a challenge in the gathering and interpretation of safety data. This is because adverse events are typically reported by participants themselves and are susceptible to reporting errors, delays or coding errors. It is crucial to increase the accuracy and quality of outcomes in these trials.
Results
Although the definition of pragmatism doesn't require that all clinical trials are 100% pragmatist, there are benefits of including pragmatic elements in trials. These include:
Incorporating routine patients, the trial results are more easily translated into clinical practice. However, pragmatic trials may also have drawbacks. The right amount of heterogeneity for instance, can help a study extend its findings to different patients or settings. However the wrong type of heterogeneity could decrease the sensitivity of the test and thus reduce a trial's power to detect minor treatment effects.
Numerous studies have attempted to categorize pragmatic trials, with various definitions and scoring systems. 프라그마틱 정품 and Lellouch1 have developed a framework that can differentiate between explanation studies that prove a physiological or clinical hypothesis and pragmatic studies that inform the selection of appropriate treatments in clinical practice. The framework was comprised of nine domains that were evaluated on a scale of 1-5 with 1 being more lucid while 5 was more pragmatic. The domains included recruitment and setting up, the delivery of intervention, flex compliance and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et al10 devised an adaptation of this assessment dubbed the Pragmascope that was simpler to use in systematic reviews. They discovered that pragmatic reviews scored higher on average in most domains, but scored lower in the primary analysis domain.
The difference in the primary analysis domains could be due to the way in which most pragmatic trials analyse data. Certain explanatory trials however don't. 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 note that a pragmatic trial doesn't necessarily mean a poor quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is not specific nor sensitive) that employ the term 'pragmatic' in their title or abstract. These terms could indicate a greater appreciation of pragmatism in titles and abstracts, but it's unclear whether this is reflected in the content.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the value of real-world evidence is becoming increasingly acknowledged. They are randomized trials that compare real world treatment options with new treatments that are being developed. They include patient populations closer to those treated in regular care. This approach has the potential to overcome the limitations of observational studies which include the limitations of relying on volunteers, and the limited availability and coding variability in national registries.
Other advantages of pragmatic trials include the ability to use existing data sources, as well as a higher chance of detecting meaningful changes than traditional trials. However, they may still have limitations which undermine their reliability and generalizability. The participation rates in certain trials may be lower than expected due to the healthy-volunteering effect, financial incentives, or competition from other research studies. The necessity to recruit people quickly restricts the sample size and impact of many pragmatic trials. Some pragmatic trials also lack controls to ensure that observed differences aren't due to biases during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatist and published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which consists of the domains eligibility criteria and recruitment criteria, as well as flexibility in adherence to interventions, and follow-up. They discovered that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Studies with high pragmatism scores tend to have more lenient criteria for eligibility than conventional RCTs. They also contain populations from many different hospitals. The authors suggest that these characteristics could make the pragmatic trials more relevant and relevant to daily practice, but they don't necessarily mean that a trial using a pragmatic approach is completely free of bias. In addition, the pragmatism that is present in a trial is not a definite characteristic A pragmatic trial that doesn't possess all the characteristics of a explanatory trial can yield reliable and relevant results.