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 clean trial data, ratings and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological analyses that evaluate the effects of treatment across trials of various levels of pragmatism.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. 프라그마틱 게임 ", however, is not used in a consistent manner and its definition and evaluation require further clarification. Pragmatic trials should be designed to inform clinical practice and policy decisions, rather than to prove an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should try to be as similar to the real-world clinical environment as is possible, including its selection of participants, setting up and design as well as the execution of the intervention, and the determination and analysis of outcomes and primary analysis. This is a key difference from explanatory trials (as described by Schwartz and Lellouch1), which are intended to provide a more thorough proof of the hypothesis.
Truly pragmatic trials should not blind participants or clinicians. This can lead to a bias in the estimates of the effect of treatment. Practical trials also involve patients from different health care settings to ensure that their outcomes can be compared to the real world.
Additionally, clinical trials should focus on outcomes that matter to patients, like quality of life and functional recovery. This is particularly important for trials involving invasive procedures or those with potentially serious adverse events. The CRASH trial29, for example focused on the functional outcome to compare a two-page report with an electronic system for the monitoring of hospitalized patients with chronic heart failure. In addition, the catheter trial28 utilized urinary tract infections caused by catheters as the primary outcome.
In addition to these characteristics pragmatic trials should reduce the trial's procedures and data collection requirements to reduce costs. Additionally, pragmatic trials should seek to make their findings as applicable to clinical practice as is possible by making sure that their primary analysis is the intention-to-treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs that don't meet the criteria for pragmatism, but have features that are contrary to pragmatism have been published in journals of varying types and incorrectly labeled pragmatic. This could lead to misleading claims of pragmaticity and the use of the term should be standardized. The creation of a PRECIS-2 tool that provides a standardized objective evaluation of the pragmatic characteristics is a 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 distinct from explanation trials that test hypotheses regarding the cause-effect relationship in idealised conditions. In this way, pragmatic trials could have lower internal validity than explanation studies and are more susceptible to biases in their design, analysis, and conduct. Despite their limitations, pragmatic studies can provide valuable information for decision-making within the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism in an RCT by assessing it across 9 domains, ranging from 1 (very explicit) to 5 (very pragmatic). In this study, the recruit-ment organization, flexibility in delivery and follow-up domains received high scores, however the primary outcome and the method for missing data were not at the limit of practicality. This suggests that it is possible to design a trial with good pragmatic features without damaging the quality of its results.
It is difficult to determine the amount of pragmatism in a particular trial because pragmatism does not have a single characteristic. Certain 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 the logistics during the trial. Additionally 36% of the 89 pragmatic trials identified by Koppenaal et al were placebo-controlled or conducted prior to licensing and most were single-center. Therefore, they aren't very close to usual practice and can only be called pragmatic in the event that their sponsors are supportive of the absence of blinding in these trials.
A common feature of pragmatic studies is that researchers attempt to make their findings more meaningful by analyzing subgroups within the trial. This can lead to unbalanced comparisons and lower statistical power, thereby increasing the risk of either not detecting or incorrectly detecting differences in the primary outcome. In the case of the pragmatic studies included in this meta-analysis, this was a significant problem because the secondary outcomes were not adjusted to account for variations in the baseline covariates.
Additionally, 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 usually self-reported and are susceptible to reporting delays, inaccuracies or coding deviations. It is therefore important to improve the quality of outcomes for these trials, and ideally by using national registries rather than relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism doesn't require that all clinical trials be 100% pragmatist there are benefits when incorporating pragmatic components into trials. These include:
By incorporating routine patients, the trial results can be more quickly translated into clinical practice. However, pragmatic trials may also have disadvantages. The right amount of heterogeneity, for example, can help a study extend its findings to different settings or patients. However the wrong type of heterogeneity could reduce the assay sensitivity and, consequently, reduce a trial's power to detect minor treatment effects.
A variety of studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 created a framework to differentiate between explanation studies that support a physiological hypothesis or clinical hypothesis and pragmatic studies that inform the selection of appropriate therapies in clinical practice. The framework was composed of nine domains that were evaluated on a scale of 1-5, with 1 being more informative and 5 being more pragmatic. The domains covered recruitment, setting up, delivery of intervention, flex adhering to the program and primary analysis.
The original PRECIS tool3 featured similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 created an adaptation of this assessment dubbed 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 distinction in the primary analysis domain could be due to the fact that the majority of pragmatic trials process their data in the intention to treat way however some explanation trials do not. The overall score for systematic reviews that were pragmatic was lower when the domains of management, flexible delivery and following-up were combined.
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 are increasing numbers of clinical trials that use the term "pragmatic" either in their abstracts or titles (as defined by MEDLINE, but that is neither sensitive nor precise). These terms may signal that there is a greater awareness of pragmatism within abstracts and titles, however it's not clear if this is reflected in content.
Conclusions
In recent times, pragmatic trials are becoming more popular in research as the value of real-world evidence is increasingly recognized. They are randomized clinical trials which compare real-world treatment options instead of experimental treatments in development, they involve patient populations that more closely mirror the ones who are treated in routine medical care, they utilize comparators which exist in routine practice (e.g., existing medications), and they depend on the self-reporting of participants about outcomes. This approach could help overcome the limitations of observational studies, such as the limitations of relying on volunteers and limited availability and coding variability in national registries.
Pragmatic trials also have advantages, including the ability to leverage existing data sources and a greater chance of detecting significant differences from traditional trials. However, pragmatic trials may still have limitations that undermine their validity and generalizability. For example, participation rates in some trials might be lower than expected due to the healthy-volunteer effect as well as financial incentives or competition for participants from other research studies (e.g., industry trials). Practical trials are often restricted by the necessity to enroll participants quickly. Some pragmatic trials also lack controls to ensure that observed variations aren't due to biases that occur during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and that were published until 2022. The PRECIS-2 tool was used to assess pragmatism. It covers areas like eligibility criteria, recruitment flexibility as well as adherence to interventions and follow-up. They discovered 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Trials with high pragmatism scores tend to have broader criteria for eligibility than conventional RCTs. They also contain patients from a variety of hospitals. These characteristics, according to the authors, may make pragmatic trials more relevant and relevant to the daily practice. However, they cannot guarantee that a trial is free of bias. The pragmatism is not a definite characteristic and a test that does not possess all the characteristics of an explanatory study can still produce valid and useful outcomes.