Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a 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 permitting multiple and varied meta-epidemiological research studies to evaluate the effect of treatment on trials with different levels of pragmatism and other design features.
Background
Pragmatic trials are becoming more widely acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic" however, is a word that is often used in contradiction and its definition and measurement require clarification. Pragmatic trials are designed to inform clinical practices and policy decisions, not to verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should aim to be as close as is possible to real-world clinical practices which include the recruiting participants, setting, designing, implementation and delivery of interventions, determining and analysis results, as well as primary analysis. This is a major difference between explanatory trials as defined by Schwartz & Lellouch1 that are designed to test the hypothesis in a more thorough manner.
The trials that are truly pragmatic must be careful not to blind patients or clinicians, as this may cause distortions in estimates of treatment effects. The pragmatic trials also include patients from different health care settings to ensure that their results can be applied to the real world.
Additionally, pragmatic trials should focus on outcomes that are vital for patients, such as quality of life or functional recovery. This is particularly important for trials that involve surgical procedures that are invasive or may have harmful adverse impacts. The CRASH trial29, for example was focused on functional outcomes to compare a 2-page case-report with an electronic system for monitoring of patients admitted to hospitals with chronic heart failure, and the catheter trial28 focused on symptomatic catheter-associated urinary tract infections as the primary outcome.
In addition to these characteristics pragmatic trials should reduce trial procedures and data-collection requirements to cut costs and time commitments. In the end the aim of pragmatic trials is to make their results as relevant to real-world clinical practice as is possible. This can be accomplished by ensuring their primary analysis is based on an intention-to treat method (as described within CONSORT extensions).
Many RCTs that don't meet the criteria for pragmatism, but contain features contrary to pragmatism, have been published in journals of different types and incorrectly labeled pragmatic. This can lead to false claims of pragmaticity and the usage of the term needs to be standardized. The creation of the PRECIS-2 tool, which provides a standard objective assessment of practical features, is a good first step.
Methods
In a pragmatic trial it is the intention to inform policy or clinical decisions by demonstrating how the intervention can be incorporated into real-world routine care. This differs from explanation trials that test hypotheses regarding the causal-effect relationship in idealized situations. In this way, pragmatic trials could have less internal validity than explanatory studies and be more prone to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic studies can provide valuable data for making decisions within the healthcare context.
The PRECIS-2 tool evaluates an RCT on 9 domains, ranging between 1 and 5 (very pragmatist). In this study, the recruit-ment, organization, flexibility in delivery, flexible adherence and follow-up domains received high scores, however the primary outcome and the procedure for missing data fell below the pragmatic limit. This indicates that a trial can be designed with well-thought-out pragmatic features, without damaging the quality.
It is, however, difficult to assess how pragmatic a particular trial is, since the pragmatism score is not a binary characteristic; 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 89 pragmatic trials identified by Koppenaal et al were placebo-controlled, or conducted prior to licensing and most were single-center. They are not in line with the usual practice and are only considered pragmatic if the sponsors agree that the trials aren't blinded.
Furthermore, a common feature of pragmatic trials is that researchers try to make their results more relevant by analyzing subgroups of the sample. This can result in unbalanced analyses that have lower statistical power. This increases the chance of omitting or misinterpreting differences in the primary outcomes. This was a problem in the meta-analysis of pragmatic trials due to the fact that secondary outcomes were not corrected for covariates' differences at baseline.
Furthermore, pragmatic studies can present challenges in the gathering and interpretation of safety data. This is because adverse events are generally reported by the participants themselves and are prone to reporting errors, delays or coding errors. It is crucial to increase the accuracy and quality of outcomes in these trials.
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:
Increasing sensitivity to real-world issues which reduces the size of studies and their costs, and enabling the trial results to be faster transferred into real-world clinical practice (by including patients from routine care). However, pragmatic trials have their disadvantages. For instance, the appropriate type of heterogeneity could help a study to generalize its findings to a variety of settings and patients. However, 프라그마틱 슬롯 환수율 of heterogeneity can reduce assay sensitivity and therefore reduce the power of a trial to detect small treatment effects.
Numerous studies have attempted to classify pragmatic trials with various definitions and scoring systems. Schwartz and Lellouch1 created a framework for distinguishing between research studies that prove the clinical or physiological hypothesis and pragmatic trials that help in the selection of appropriate treatments in real-world clinical practice. Their framework included nine domains, each scoring on a scale of 1-5, with 1 indicating more explanatory and 5 indicating more pragmatic. The domains covered 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 to this assessment dubbed the Pragmascope that was simpler to use in systematic reviews. They found that pragmatic reviews scored higher in most domains, but scored lower in the primary analysis domain.
The difference in the primary analysis domains could be explained by the way that most pragmatic trials approach data. Some explanatory trials, however, do not. The overall score for pragmatic systematic reviews was lower when the domains of organisation, flexible delivery and following-up were combined.
It is important to understand that a pragmatic trial does not necessarily mean a poor quality trial, and in fact there is a growing number of clinical trials (as defined by MEDLINE search, however it is neither specific nor sensitive) which use the word 'pragmatic' in their abstract or title. The use of these terms in abstracts and titles could indicate a greater understanding of the importance of pragmatism, but it is unclear whether this is evident in the content of the articles.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the importance of real-world evidence is increasingly recognized. They are randomized studies that compare real-world alternatives to clinical trials in development. They are conducted with populations of patients that are more similar to those who receive treatment in regular medical care. This approach has the potential to overcome the limitations of observational research that are prone to biases associated with reliance on volunteers and limited availability and coding variability in national registry systems.
Pragmatic trials also have advantages, like the ability to draw on existing data sources and a greater probability of detecting meaningful differences than traditional trials. However, pragmatic trials may have some limitations that limit their credibility and generalizability. For example the participation rates in certain 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). Many pragmatic trials are also restricted by the necessity to recruit participants on time. Some pragmatic trials also lack controls to ensure that the observed variations aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified RCTs published from 2022 to 2022 that self-described as pragmatic. They evaluated pragmatism using the PRECIS-2 tool that includes the eligibility criteria for domains and recruitment criteria, as well as flexibility in adherence to intervention, 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.
Studies that have high pragmatism scores tend to have more lenient criteria for eligibility than conventional RCTs. They also contain populations from many different hospitals. The authors argue that these characteristics can help make the pragmatic trials more relevant and relevant to daily practice, but they do not guarantee that a trial conducted in a pragmatic manner is completely free of bias. The pragmatism principle is not a definite characteristic and a test that does not possess all the characteristics of an explanation study could still yield reliable and beneficial results.