Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that facilitates 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 studies to compare treatment effects estimates across trials with different levels of pragmatism as well as other design features.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. However, the usage of the term "pragmatic" is not consistent and its definition and assessment requires clarification. Pragmatic trials must be designed to inform policy and clinical practice 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 real-world clinical practice as possible, including in the selection of participants, setting up and design as well as the implementation of the intervention, as well as the determination and analysis of outcomes as well as primary analysis. This is a significant distinction from explanation trials (as described by Schwartz and Lellouch1), which are intended to provide a more thorough proof of the hypothesis.
Truely pragmatic trials should not blind participants or the clinicians. This can result in an overestimation of the effect of treatment. The pragmatic trials also include patients from different healthcare settings to ensure that the results can be generalized to the real world.
Finally studies that are pragmatic should focus on outcomes that are crucial to patients, such as quality of life or functional recovery. This is particularly relevant for trials involving the use of invasive procedures or potentially serious adverse events. The CRASH trial29, for example, focused on functional outcomes to compare a two-page report with an electronic system to monitor the health 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 the pragmatic trial should also reduce the procedures for conducting trials and data collection requirements in order to reduce costs. In the end, pragmatic trials should aim to make their results as relevant to actual clinical practices as possible. This can be accomplished by ensuring their primary analysis is based on the intention-to treat approach (as defined in CONSORT extensions).
Despite these guidelines 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 can lead to misleading claims of pragmatism and the use of the term should be standardised. The creation of the PRECIS-2 tool, which offers an objective standard for assessing pragmatic features is a good initial step.
Methods
In a pragmatic trial, the aim is to inform policy or clinical decisions by demonstrating how the intervention can be implemented into routine care. Explanatory trials test hypotheses regarding the cause-effect relationship within idealised conditions. Consequently, pragmatic trials may have less 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 healthcare context.
The PRECIS-2 tool evaluates an RCT on 9 domains, ranging from 1 to 5 (very pragmatic). In this study, the recruit-ment organization, flexibility in delivery, flexible adherence and follow-up domains were awarded high scores, however the primary outcome and the method for missing data fell below the practical limit. This suggests that it is possible to design a trial that has excellent pragmatic features without damaging the quality of its outcomes.
It is hard to determine the amount of pragmatism in a particular trial since pragmatism doesn't have a single attribute. Certain aspects of a study can be more pragmatic than other. The pragmatism of a trial can be affected by modifications to the protocol or logistics during the trial. Koppenaal and colleagues found that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. Most were also single-center. Thus, they are not quite as typical and can only be called pragmatic in the event that their sponsors are supportive of the lack of blinding in these trials.
A common feature of pragmatic studies is that researchers try to make their findings more meaningful by studying subgroups of the trial sample. This can result in unbalanced analyses that have less statistical power. This increases the risk of omitting or misinterpreting differences in the primary outcomes. This was a problem during the meta-analysis of pragmatic trials because secondary outcomes were not corrected for differences in covariates at the baseline.
Additionally the pragmatic trials may have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events tend to be self-reported, and are prone to delays, errors or coding errors. It is essential to increase the accuracy and quality of the outcomes in these trials.
Results
Although the definition of pragmatism does not require that all clinical trials are 100% pragmatic There are advantages of including pragmatic elements in trials. These include:
By including routine patients, the results of trials can be translated more quickly into clinical practice. However, pragmatic studies can also have disadvantages. For instance, the appropriate kind of heterogeneity can allow a trial to generalise its results to different settings and patients. However, the wrong type of heterogeneity could reduce assay sensitivity and therefore lessen the ability of a trial to detect minor treatment effects.
Many studies have attempted classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 developed a framework to distinguish between research studies that prove a physiological or clinical hypothesis and pragmatic trials that help in the selection of appropriate treatments in clinical practice. Their framework comprised nine domains, each scored on a scale of 1-5, with 1 indicating more lucid and 5 indicating more practical. The domains were recruitment, setting, intervention delivery with flexibility, follow-up 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 devised an adaptation to this assessment called the Pragmascope that was simpler to use in systematic reviews. They discovered that pragmatic systematic reviews had a higher average scores across all domains, with lower scores in the primary analysis domain.
The difference in the analysis domain that is primary could be due to the fact that the majority of pragmatic trials process their data in the intention to treat manner however some explanation trials 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 remember that a pragmatic study does not necessarily mean a low-quality study. In fact, there are a growing number of clinical trials that use the word 'pragmatic,' either in their abstracts or titles (as defined by MEDLINE however it is neither sensitive nor precise). The use of these words in abstracts and titles may suggest a greater awareness of the importance of pragmatism however, it is not clear if this is evident in the content of the articles.
Conclusions
In recent years, pragmatic trials are becoming more popular in research as the value of real-world evidence is becoming increasingly acknowledged. They are randomized studies that compare real-world care alternatives to new treatments that are being developed. They are conducted with populations of patients closer to those treated in regular care. This method can help overcome the limitations of observational research, such as the biases that arise from relying on volunteers and limited availability and coding variability in national registry systems.
Pragmatic trials also have advantages, such as the ability to draw on existing data sources, and a greater chance of detecting significant distinctions from traditional trials. However, they may be prone to limitations that undermine their effectiveness and generalizability. 프라그마틱 슬롯 in some trials could be lower than expected because of the healthy-volunteering effect, financial incentives, or competition from other research studies. The necessity to recruit people in a timely manner also restricts 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 as pragmatism. They assessed pragmatism using the PRECIS-2 tool, which consists of the eligibility criteria for domains, recruitment, flexibility in intervention adherence and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
Trials that have high pragmatism scores tend to have more lenient criteria for eligibility than conventional RCTs. They also include populations from many different hospitals. The authors suggest that these traits can make the pragmatic trials more relevant and applicable to everyday clinical practice, however they do not necessarily guarantee that a trial using a pragmatic approach is completely free of bias. The pragmatism principle is not a fixed characteristic the test that does not possess all the characteristics of an explicative study could still yield valid and useful outcomes.