A Handbook For Pragmatic Free Trial Meta From Beginning To End

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 collects and shares cleaned trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological studies to evaluate the effect of treatment on trials that employ different levels of pragmatism and other design features.
Background
Pragmatic trials are becoming more widely recognized as providing real-world evidence to support clinical decision-making. However, the use of the term "pragmatic" is not uniform and its definition as well as assessment requires clarification. Pragmatic trials should be designed to inform policy and clinical practice decisions, not to confirm the validity of a clinical or physiological hypothesis. A pragmatic trial should also strive to be as close to actual clinical practice as possible, such as its participation of participants, setting and design of the intervention, its delivery and implementation of the intervention, determination and analysis of the outcomes, and primary analysis. This is a significant difference between explanation-based trials, as defined by Schwartz & Lellouch1, which are designed to prove a hypothesis in a more thorough manner.
Studies that are truly practical should not attempt to blind participants or healthcare professionals in order to lead to distortions in estimates of treatment effects. Practical trials should also aim to attract patients from a variety of health care settings, to ensure that their findings are generalizable to the real world.
Furthermore the focus of pragmatic trials should be on outcomes that are important to patients, such as quality of life or functional recovery. This is particularly relevant for trials that involve surgical procedures that are invasive or may have dangerous 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 catheter trial28, on the other hand was based on symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these characteristics pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to reduce costs. Finaly these trials should strive to make their results as relevant to real-world clinical practices as they can. This can be accomplished by ensuring that their analysis is based on an intention-to treat method (as described in 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 various types and incorrectly labeled as pragmatic. This can lead to misleading claims about pragmatism, and the usage of the term should be made more uniform. The creation of the PRECIS-2 tool, which provides an objective and standard assessment of pragmatic characteristics, is a good first step.
Methods
In a pragmatic study it is the intention to inform policy or clinical decisions by demonstrating how an intervention would be integrated into everyday routine care. Explanatory trials test hypotheses about the cause-effect relationship within idealised settings. Therefore, pragmatic trials could have less internal validity than explanatory trials and might be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic research can provide valuable information to make decisions in the healthcare context.
The PRECIS-2 tool evaluates the level of pragmatism that is present in an RCT by scoring it across 9 domains, ranging from 1 (very explicit) 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 principal outcome and the method for missing data was scored below the pragmatic limit. This suggests that it is possible to design a trial that has high-quality pragmatic features, without compromising the quality of its outcomes.
However, it is difficult to assess how pragmatic a particular trial really is because pragmaticity is not a definite quality; certain aspects of a study can be more pragmatic than others. A trial's pragmatism could be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to licensing. They also found that the majority were single-center. They are not close to the standard practice and can only be called pragmatic if their sponsors agree that such trials aren't blinded.
A typical feature of pragmatic research is that researchers try to make their findings more meaningful by studying subgroups within the trial sample. However, this often leads to unbalanced comparisons and lower statistical power, increasing the likelihood of missing or misinterpreting differences in the primary outcome. This was the case in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for differences in covariates at the time of baseline.
In addition, pragmatic studies may pose challenges to collection and interpretation of safety data. This is due to the fact that adverse events are typically self-reported, and are prone to delays, errors or coding errors. It is important to improve the quality and accuracy of the outcomes in these trials.
Results
While the definition of pragmatism does not require that all clinical trials are 100% pragmatist there are benefits to including pragmatic components in trials. These include:
Enhancing sensitivity to issues in the real world as well as reducing cost and size of the study, and enabling the trial results to be more quickly translated into actual clinical practice (by including patients from routine care). However, pragmatic studies can also have drawbacks. For example, the right type of heterogeneity can help a study to generalize its findings to a variety of settings and patients. However the wrong kind of heterogeneity could reduce assay sensitiveness and consequently decrease the ability of a study to detect small treatment effects.
A variety of studies have attempted to categorize pragmatic trials using various definitions and scoring systems. Schwartz and Lellouch1 created a framework to distinguish between explanatory studies that confirm the physiological hypothesis or clinical hypothesis and pragmatic studies that guide the choice for appropriate therapies in clinical practice. The framework was composed of nine domains evaluated on a scale of 1-5 which indicated that 1 was more explanatory while 5 was more pragmatic. The domains included recruitment, setting up, delivery of intervention, flex adherence and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal and colleagues10 developed an adaptation of this assessment called the Pragmascope that was simpler to use in systematic reviews. Related Site found that pragmatic reviews scored higher on average in all domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains can be explained by the way that most pragmatic trials analyse data. Certain explanatory trials however 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 important to understand that the term "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) that use the term "pragmatic" in their abstract or title. These terms could indicate an increased understanding of pragmatism in titles and abstracts, but it's not clear whether this is reflected in content.
Conclusions
As the importance of evidence from the real world becomes more commonplace and pragmatic trials have gained popularity in research. They are randomized clinical trials which compare real-world treatment options instead of experimental treatments under development. They have patient populations that are more similar to the ones who are treated in routine care, they employ comparisons that are commonplace in practice (e.g., existing drugs), and they depend on the self-reporting of participants about outcomes. This approach can overcome the limitations of observational research like the biases associated with the use of volunteers as well as the insufficient availability and codes that vary in national registers.
Pragmatic trials also have advantages, including the ability to leverage existing data sources, and a greater chance of detecting significant differences than traditional trials. However, they may have some limitations that limit their validity and generalizability. Participation rates in some trials may be lower than expected due to the health-promoting effect, financial incentives or competition from other research studies. The requirement to recruit participants in a timely manner also limits the sample size and impact of many pragmatic trials. Additionally, some pragmatic trials don't have controls to ensure that the observed differences aren't due to biases in the conduct of trials.
The authors of the Pragmatic Free Trial Meta identified RCTs published up to 2022 that self-described themselves as pragmatic. The PRECIS-2 tool was employed to evaluate pragmatism. It covers domains such as eligibility criteria as well as recruitment flexibility as well as adherence to interventions and follow-up. They found that 14 of these trials scored highly or pragmatic sensible (i.e., scoring 5 or more) in any one or more of these domains, and that the majority of these were single-center.
Studies with high pragmatism scores tend to have more lenient criteria for eligibility than traditional RCTs. They also include patients from a variety of hospitals. The authors suggest that these characteristics can help make the pragmatic trials more relevant and useful for everyday clinical practice, however they do not necessarily guarantee that a trial using a pragmatic approach is completely free of bias. The pragmatism characteristic is not a definite characteristic the test that doesn't have all the characteristics of an explanatory study can still produce valuable and valid results.