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 studies to compare treatment effects estimates across trials with different levels of pragmatism as well as other design features.
Background
Pragmatic trials provide real-world evidence 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 should be designed to inform policy and clinical practice decisions, not to confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should try to be as close as it is to real-world clinical practices that include recruitment of participants, setting, design, delivery and implementation of interventions, determination and analysis results, as well as primary analyses. This is a major distinction between explanation-based trials, as defined by Schwartz & Lellouch1 which are designed to confirm the hypothesis in a more thorough manner.
The most pragmatic trials should not be blind participants or the clinicians. This can lead to bias in the estimations of the effect of treatment. The trials that are pragmatic should also try to attract patients from a wide range of health care settings, to ensure that their findings can be compared to the real world.
Additionally, pragmatic trials should focus on outcomes that are important for patients, such as quality of life or functional recovery. This is particularly important in trials that involve the use of invasive procedures or potential for dangerous adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The trial with a catheter, however, used symptomatic catheter associated urinary tract infections as its 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 these trials should strive to make their results as relevant to real-world clinical practices as possible. This can be achieved by ensuring that their primary analysis is based on the intention to treat approach (as described in CONSORT extensions).
Despite these criteria however, a large number of RCTs with features that challenge the concept of pragmatism have been mislabeled as pragmatic and published in journals of all types. This could lead to false claims about pragmatism, and the use of the term should be standardized. The development of a PRECIS-2 tool that offers a standardized objective evaluation of pragmatic aspects is the first step.
Methods
In a pragmatic study it is the intention to inform policy or clinical decisions by demonstrating how an intervention can be integrated into routine treatment in real-world situations. Explanatory trials test hypotheses about the cause-effect relationship within idealised settings. 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 their limitations, pragmatic studies can be a valuable source of information for decision-making within the context of healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism in an RCT by scoring it across 9 domains, ranging from 1 (very explicative) to 5 (very pragmatic). In this study, the recruitment, organisation, flexibility: delivery, flexible adherence and follow-up domains were awarded high scores, but the primary outcome and the procedure for missing data were not at the practical limit. This indicates that a trial can be designed with effective practical features, yet not 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. A trial's pragmatism could 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 the majority were single-center. They aren't in line with the norm and are only referred to as pragmatic if the sponsors agree that such trials aren't blinded.
A common aspect of pragmatic research is that researchers try to make their findings more meaningful by studying subgroups of the trial sample. This can lead to unbalanced comparisons with a lower statistical power, thereby increasing the likelihood of missing or incorrectly detecting differences in the primary outcome. This was a problem during the meta-analysis of pragmatic trials because secondary outcomes were not corrected for covariates that differed at baseline.
Furthermore, pragmatic studies can pose difficulties in the collection and interpretation safety data. It is because adverse events are usually self-reported, and are prone to delays, errors or coding variations. Therefore, it is crucial to enhance the quality of outcomes ascertainment in these trials, ideally by using national registries rather than relying on participants to report adverse events in the trial's database.
Results
While the definition of pragmatism does not require that clinical trials be 100% pragmatist, there are benefits to including pragmatic components in trials. These include:
Increased sensitivity to real-world issues which reduces the size of studies and their costs as well as allowing trial results to be faster translated into actual clinical practice (by including patients from routine care). But pragmatic trials can have disadvantages. The right type of heterogeneity for instance could help a study generalise its findings to many different settings or patients. However the wrong type of heterogeneity could reduce the assay sensitivity, and therefore reduce a trial's power to detect even minor effects of treatment.
Many studies have attempted classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 have developed a framework to distinguish between explanatory trials that confirm the clinical or physiological hypothesis as well as pragmatic trials that help in the selection of appropriate treatments in the real-world clinical setting. The framework was comprised of nine domains that were scored on a scale of 1 to 5 with 1 indicating more lucid and 5 indicating more practical. The domains covered recruitment and setting up, the delivery of intervention, flexible adhering to the program and primary analysis.
The original PRECIS tool3 had similar domains and a scale of 1 to 5. Koppenaal et. al10 devised an adaptation of the assessment, dubbed the Pragmascope that was simpler to use for systematic reviews. They found that pragmatic systematic reviews had a higher average scores across all domains but lower scores in the primary analysis domain.
This difference in the analysis domain that is primary could be due to the fact that the majority of pragmatic trials process their data in an intention to treat way however some explanation trials do not. The overall score was lower for systematic reviews that were pragmatic when the domains of the organization, flexibility of delivery and follow-up were combined.
It is important to note that a 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 abstract or title. The use of these terms in titles and abstracts may suggest a greater awareness of the importance of pragmatism, but it is unclear whether this is evident in the content of the articles.
Conclusions
As the value of real-world evidence becomes increasingly widespread and pragmatic trials have gained momentum in research. They are clinical trials that are randomized that compare real-world care alternatives instead of experimental treatments in development. They involve populations of patients that are more similar to those treated in routine care, they employ comparisons that are commonplace in practice (e.g., existing drugs), and they depend on participants' self-reports of outcomes. This method is able to overcome the limitations of observational research, such as the biases associated with the use of volunteers and the limited availability and the coding differences in national registry.
프라그마틱 슬롯 조작 have advantages, like the ability to use existing data sources and a higher chance of detecting significant distinctions from traditional trials. However, these trials could still have limitations that undermine their credibility and generalizability. For instance the participation rates in certain trials may be lower than anticipated due to the healthy-volunteer effect and financial incentives or competition for participants from other research studies (e.g., industry trials). A lot of pragmatic trials are restricted by the necessity to enroll participants on time. Certain pragmatic trials lack controls to ensure that any observed variations aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs that self-described themselves as pragmatic and that were published up to 2022. They assessed pragmatism using the PRECIS-2 tool that includes the domains eligibility criteria, 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 with high pragmatism scores tend to have broader criteria for eligibility than traditional RCTs. They also contain patients from a variety of hospitals. These characteristics, according to the authors, could make pragmatic trials more relevant and useful in the daily practice. However, they don't guarantee that a trial will be free of bias. Moreover, the pragmatism of a trial is not a fixed attribute and a pragmatic trial that does not have all the characteristics of a explanatory trial can produce valid and useful results.