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 distributes clean trial data, ratings and evaluations using PRECIS-2. This allows for diverse meta-epidemiological analyses to compare treatment effect estimates across trials of different levels of pragmatism.
Background
Pragmatic trials provide real-world evidence that can be used to make clinical decisions. The term "pragmatic", however, is used inconsistently and its definition and evaluation need further clarification. The purpose of pragmatic trials is to inform policy and clinical practice decisions, rather than confirm a physiological or clinical hypothesis. A pragmatic trial should also strive to be as close to actual clinical practice as possible, including in its selection of participants, setting up and design, the delivery and implementation of the intervention, as well as the determination and analysis of outcomes and primary analyses. This is a major difference between explanation-based trials, as described by Schwartz and Lellouch1 that are designed to confirm a hypothesis in a more thorough manner.
The trials that are truly practical should not attempt to blind participants or healthcare professionals, as this may result in distortions in estimates of treatment effects. Practical trials also involve patients from different health care settings to ensure that the results can be applied to the real world.
Additionally the focus of pragmatic trials should be on outcomes that are important to patients, like quality of life or functional recovery. This is especially important in trials that involve the use of invasive procedures or potential for serious adverse events. The CRASH trial29, for example focused on the functional outcome to compare a two-page report with an electronic system to monitor the health of patients in hospitals suffering from chronic heart failure. Similarly, the catheter trial28 utilized symptomatic catheter-associated urinary tract infections as the primary outcome.
In addition to these aspects pragmatic trials should also reduce the requirements for data collection and trial procedures to reduce 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 analysis is based on the intention-to treat approach (as described in CONSORT extensions).
Many RCTs which do not meet the requirements for pragmatism however, they have characteristics that are contrary to pragmatism have been published in journals of varying types and incorrectly labeled as pragmatic. This can result in misleading claims of pragmaticity, and the use of the term should be standardized. The development of a PRECIS-2 tool that can provide an objective and standardized evaluation of the pragmatic characteristics is a good start.
Methods
In a pragmatic trial it is the intention to inform policy or clinical decisions by demonstrating how the intervention can be integrated into everyday routine care. Explanatory trials test hypotheses regarding the cause-effect relation within idealized settings. In this way, pragmatic trials may have a lower internal validity than explanatory studies 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 evaluates an RCT on 9 domains, ranging from 1 to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery and follow-up domains scored high scores, however the primary outcome and the method of missing data were not at the pragmatic limit. This suggests that it is possible to design a trial that has good pragmatic features without damaging the quality of its outcomes.
It is difficult to determine the level of pragmatism within a specific trial because pragmatism does not possess a specific characteristic. Certain aspects of a research study can be more pragmatic than others. A trial's pragmatism could be affected by modifications to the protocol or the logistics during the trial. In addition 36% of the 89 pragmatic trials discovered by Koppenaal et al were placebo-controlled, or conducted prior to licensing and most were single-center. Thus, they are not as common and can only be called pragmatic in the event that their sponsors are supportive of the lack of blinding in such trials.
A typical feature of pragmatic studies is that researchers try to make their findings more relevant by studying subgroups within the trial. However, this often leads to unbalanced comparisons with a lower statistical power, increasing the likelihood of missing or incorrectly detecting differences in the primary outcome. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not adjusted for covariates' differences at baseline.
Additionally, studies that are pragmatic may pose challenges to collection and interpretation of safety data. This is because adverse events are typically reported by participants themselves and prone to reporting delays, inaccuracies or coding errors. It is therefore crucial to improve the quality of outcome for these trials, in particular by using national registry databases instead of relying on participants to report adverse events in the trial's own database.
Results
While the definition of pragmatism doesn't 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, reducing cost and size of the study, and enabling the trial results to be faster translated into actual clinical practice (by including routine patients). However, pragmatic trials may have their disadvantages. The right type of heterogeneity, for example could help a study expand its findings to different settings or patients. However the wrong kind of heterogeneity can reduce the assay sensitivity and, consequently, reduce a trial's power to detect small treatment effects.
A variety of studies have attempted to classify pragmatic trials with a variety of definitions and scoring systems. Schwartz and Lellouch1 created a framework to differentiate between explanation studies that confirm the physiological hypothesis or clinical hypothesis, and pragmatic studies that help inform the selection of appropriate treatments in the real-world clinical practice. The framework was comprised of nine domains scored on a 1-5 scale which indicated that 1 was more informative and 5 was more practical. 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 and colleagues10 created an adaptation of the assessment, called the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic reviews scored higher across all domains, however they scored lower in the primary analysis domain.
This difference in primary analysis domains can be due to the way in which most pragmatic trials approach data. Certain explanatory trials however, do not. The overall score for systematic reviews that were pragmatic was lower when the domains of organisation, flexible delivery and follow-up were merged.
It is important to note that the term "pragmatic trial" does not necessarily mean a low-quality trial, and there is a growing number of clinical trials (as defined by MEDLINE search, but it is neither specific or sensitive) that use the term "pragmatic" in their abstracts or titles. These terms may signal that there is a greater appreciation of pragmatism in titles and abstracts, but it's not clear whether this is reflected in content.
Conclusions
In recent years, pragmatic trials have been becoming more popular in research as the value of real world evidence is becoming increasingly acknowledged. They are randomized clinical trials which compare real-world treatment options rather than experimental treatments under development, they have patients that more closely mirror the ones who are treated in routine care, they use comparators that are used in routine practice (e.g., existing medications) and depend on participants' self-reports of outcomes. This approach can overcome the limitations of observational research such as the biases that come with the reliance on volunteers, as well as the insufficient availability and the coding differences in national registry.
Other advantages of pragmatic trials include the possibility of using existing data sources, and a higher likelihood of detecting meaningful changes than traditional trials. However, they may be prone to limitations that compromise their validity and generalizability. Participation rates in some trials may be lower than anticipated due to the health-promoting effect, financial incentives, or competition from other research studies. The necessity to recruit people in a timely fashion also reduces the size of the sample and the impact of many pragmatic trials. In addition, some pragmatic trials do not have controls to ensure that the observed differences are not due to biases in the conduct of trials.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and were published up to 2022. 프라그마틱 무료 슬롯버프 evaluated pragmatism using the PRECIS-2 tool, which consists of the eligibility criteria for domains, recruitment, flexibility in adherence to interventions and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or above) in at least one of these domains.
Studies with high pragmatism scores tend to have broader criteria for eligibility than traditional RCTs. They also contain populations from many different hospitals. The authors claim that these traits can make pragmatic trials more meaningful and relevant to daily practice, but they do not necessarily guarantee that a trial conducted in a pragmatic manner is completely free of bias. Moreover, the pragmatism of the trial is not a definite characteristic and a pragmatic trial that doesn't possess all the characteristics of an explanatory trial can yield valuable and reliable results.