Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a 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 evaluate the effect of treatment on trials with different levels of pragmatism, as well as other design features.
Background
Pragmatic trials provide evidence from the real world that can be used to make clinical decisions. However, the use of the term "pragmatic" is inconsistent and its definition and evaluation requires clarification. Pragmatic trials must be designed to inform policy and clinical practice 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 real-world clinical practice as possible, such as its recruitment of participants, setting and design, the delivery and implementation of the intervention, determination and analysis of outcomes and primary analysis. This is a major distinction between explanatory trials, as described by Schwartz and Lellouch1 that are designed to test a hypothesis in a more thorough way.
Trials that are truly practical should avoid attempting to blind participants or healthcare professionals in order to result in bias in estimates of treatment effects. The pragmatic trials also include patients from various healthcare settings to ensure that the results can be applied to the real world.
Additionally, clinical trials should concentrate on outcomes that are important to patients, like quality of life and functional recovery. This is particularly relevant for trials involving invasive procedures or those with potential for serious adverse events. 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 however utilized symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these aspects pragmatic trials should reduce the trial procedures and data collection requirements in order to reduce costs. In the end the aim of pragmatic trials is to make their findings as relevant to real-world clinical practices as possible. This can be accomplished by ensuring that their primary analysis is based on the intention to treat approach (as defined in CONSORT extensions).
Many RCTs that do not meet the requirements for pragmatism but contain features contrary to pragmatism, have been published in journals of various types and incorrectly labeled pragmatic. This can lead to false claims of pragmaticity and the use of the term must be standardized. 프라그마틱 슬롯버프 of the PRECIS-2 tool, which provides an objective and standard assessment of practical features is a good initial step.
Methods
In a pragmatic trial it is the intention to inform clinical or policy decisions by demonstrating how an intervention would be incorporated into real-world routine care. This is different from explanatory trials that test hypotheses regarding the cause-effect relationship in idealised conditions. In this way, pragmatic trials may have lower internal validity than studies that explain and are more susceptible to biases in their design analysis, conduct, and design. Despite their limitations, pragmatic studies can be a valuable source of information to make decisions in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging from 1 to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery, flexible adherence and follow-up domains scored high scores, but the primary outcome and the procedure for missing data were not at the limit of practicality. This suggests that it is possible to design a trial that has good pragmatic features without damaging the quality of its results.
It is difficult to determine the degree of pragmatism in a particular trial because pragmatism does not have a binary characteristic. Certain aspects of a study may be more pragmatic than other. Furthermore, logistical or protocol modifications made during a trial can change its score in pragmatism. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to licensing. They also found that the majority were single-center. Thus, they are not quite as typical and can only be called pragmatic if their sponsors are tolerant of the lack of blinding in such trials.
A common feature of pragmatic research is that researchers attempt to make their findings more meaningful by studying subgroups of the trial sample. This can lead to unbalanced analyses with 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 as secondary outcomes were not corrected for covariates that differed at the time of baseline.
Additionally practical trials can have challenges with respect to the gathering and interpretation of safety data. This is due to the fact that adverse events are typically reported by participants themselves and are prone to reporting delays, inaccuracies, or coding variations. Therefore, it is crucial to enhance the quality of outcomes assessment in these trials, and ideally by using national registries rather than relying on participants to report adverse events on the trial's own database.
Results
Although the definition of pragmatism does not mean that trials must be 100% pragmatic, there are benefits to including pragmatic components in clinical trials. These include:
Increased sensitivity to real-world issues, reducing study size and cost, and enabling the trial results to be more quickly implemented into clinical practice (by including patients who are routinely treated). However, pragmatic trials may also have disadvantages. The right kind of heterogeneity for instance, can help a study extend its findings to different patients or settings. However, the wrong type can reduce the assay sensitivity and thus decrease the ability of a study to detect small treatment effects.
A number of studies have attempted to categorize pragmatic trials, with a variety of definitions and scoring systems. Schwartz and Lellouch1 developed a framework to distinguish between research studies that prove the clinical or physiological hypothesis, and pragmatic trials that aid in the selection of appropriate treatments in real-world clinical practice. Their framework included nine domains, each scored on a scale of 1 to 5 with 1 being more informative and 5 indicating more pragmatic. The domains covered recruitment of intervention, setting up, delivery of intervention, flex adhering to the program and primary analysis.
The original PRECIS tool3 was an adapted version of the PRECIS tool3 that was based on the same scale and domains. Koppenaal et al10 developed an adaptation of this assessment, called the Pragmascope, that was easier to use for systematic reviews. They discovered that pragmatic systematic reviews had a higher average scores in the majority of domains, but lower scores in the primary analysis domain.
This distinction in the primary analysis domains can be due to the way in which most pragmatic trials analyse data. Some explanatory trials, however don't. The overall score was lower for pragmatic systematic reviews when the domains of organisation, flexible delivery, and follow-up were combined.
It is important to remember that the term "pragmatic trial" does not necessarily mean a low quality trial, and indeed there is an increasing number of clinical trials (as defined by MEDLINE search, but it is neither sensitive nor specific) which use the word "pragmatic" in their abstracts or titles. 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 times, pragmatic trials are increasing in popularity in research because the importance of real-world evidence is increasingly recognized. They are randomized trials that evaluate real-world treatment options with clinical trials in development. They involve patient populations more closely resembling those treated in regular care. This approach can overcome the limitations of observational research, like the biases associated with the reliance on volunteers, and the lack of the coding differences in national registry.
Other advantages of pragmatic trials include the ability to use existing data sources, as well as a higher likelihood of detecting meaningful changes than traditional trials. However, they may have some limitations that limit their reliability and generalizability. Participation rates in some trials could be lower than expected because of the healthy-volunteering effect, financial incentives, or competition from other research studies. Practical trials are often restricted by the need to recruit participants quickly. Practical trials aren't always equipped with controls to ensure that the observed differences aren't caused by biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-described themselves as pragmatist and published from 2022. They evaluated pragmatism using the PRECIS-2 tool that includes the eligibility criteria for domains as well as recruitment, flexibility in adherence to intervention and follow-up. They discovered that 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or above) in at least one of these domains.
Trials that have a high pragmatism score tend to have more expansive eligibility criteria than traditional RCTs that have specific criteria that are not likely to be used in the clinical environment, and they contain patients from a broad variety of hospitals. These characteristics, according to the authors, could make pragmatic trials more useful and applicable in the daily practice. However, they don't ensure that a study is free of bias. The pragmatism principle is not a fixed characteristic the test that does not have all the characteristics of an explicative study could still yield valuable and valid results.