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 allowing for multiple and diverse meta-epidemiological studies to compare treatment effects estimates across trials with different levels of pragmatism and other design features.
Background
Pragmatic trials provide evidence from the real world that can be used to make clinical decisions. The term "pragmatic", however, is a word that is often used in contradiction and its definition and evaluation require clarification. Pragmatic trials are designed to guide the practice of clinical medicine and policy decisions rather than prove a physiological or clinical hypothesis. A pragmatic trial should try to be as close as possible to the real-world clinical practice, including recruiting participants, setting, designing, delivery and implementation of interventions, determining and analysis outcomes, and primary analysis. This is a major distinction between explanation-based trials, as described by Schwartz & Lellouch1 that are designed to prove the hypothesis in a more thorough way.
The trials that are truly pragmatic must be careful not to blind patients or the clinicians, as this may cause bias in estimates of the effect of treatment. The trials that are pragmatic should also try to enroll patients from a wide range of health care settings, to ensure that the results can be compared to the real world.
Furthermore, trials that are pragmatic must concentrate on outcomes that are important to patients, like quality of life and functional recovery. This is especially important in trials that require invasive procedures or have potentially serious adverse consequences. The CRASH trial29 compared a 2 page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28, on the other hand utilized symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these aspects, pragmatic trials should minimize the trial procedures and data collection requirements to reduce costs. Finaly, pragmatic trials should aim to make their results as applicable to current clinical practices as possible. This can be achieved by ensuring that their analysis is based on an intention-to treat method (as described in CONSORT extensions).
Despite these requirements, a number of RCTs with features that challenge the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all kinds. This can lead to misleading claims of pragmatism, and the term's use should be made more uniform. The creation of the PRECIS-2 tool, which offers a standard objective assessment of pragmatic characteristics is a great first step.
Methods
In a pragmatic research study, the goal is to inform policy or clinical decisions by showing how an intervention could be integrated into routine treatment in real-world settings. Explanatory trials test hypotheses about the causal-effect relationship in idealized environments. In this way, pragmatic trials could have less internal validity than explanation studies and are more susceptible to biases in their design, analysis, and conduct. 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 an RCT on 9 domains, ranging between 1 and 5 (very pragmatist). In this study, the recruit-ment, organization, flexibility in delivery and follow-up domains received high scores, but 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 using good pragmatic features without harming the quality of the outcomes.
It is hard to determine the degree of pragmatism in a particular study because pragmatism is not a have a binary characteristic. Some aspects of a research study can be more pragmatic than others. Furthermore, logistical or protocol changes during a trial can change its score in pragmatism. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. Most were also single-center. This means that they are not quite as typical and are only 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 relevant by studying subgroups of the trial sample. This can lead to unbalanced results and lower statistical power, which increases the chance of not or incorrectly detecting differences in the primary outcome. In the case of the pragmatic trials included in this meta-analysis this was a significant problem since the secondary outcomes were not adjusted to account for the differences in the baseline covariates.
Additionally, pragmatic trials can also present challenges in the gathering and interpretation of safety data. It is because adverse events tend to be self-reported and are susceptible to errors, delays or coding variations. It is therefore important to enhance the quality of outcomes ascertainment in these trials, and ideally by using national registries instead of relying on participants to report adverse events on the trial's database.
Results
Although the definition of pragmatism may not require that all trials are 100% pragmatic, there are some advantages to incorporating pragmatic components into clinical trials. These include:
Increasing sensitivity to real-world issues, reducing study size and cost and allowing the study results to be faster translated into actual clinical practice (by including routine patients). But pragmatic trials can be a challenge. The right type of heterogeneity, for example could allow a study to generalise its findings to many different patients or settings. However, the wrong type can reduce the sensitivity of an assay 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 methods. Schwartz and Lellouch1 have developed a framework that can discern between explanation-based studies that support a physiological or clinical hypothesis and pragmatic studies that inform the selection of appropriate treatments in real world clinical practice. Their framework included nine domains that were scored on a scale of 1 to 5, with 1 indicating more explanatory and 5 indicating more pragmatic. The domains included recruitment setting, setting, intervention delivery with flexibility, follow-up and primary analysis.
The original PRECIS tool3 featured similar domains and scales from 1 to 5. Koppenaal and colleagues10 created an adaptation of this assessment, known as the Pragmascope, that was easier to use for systematic reviews. They discovered that pragmatic reviews scored higher in most domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains could be explained by the way that most pragmatic trials analyze data. Some explanatory trials, however don't. 프라그마틱 슬롯 하는법 was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery, and follow-up were combined.
It is important to note 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 this is neither sensitive nor specific) that employ the term 'pragmatic' in their title or abstract. The use of these terms in titles and abstracts could indicate a greater understanding of the importance of pragmatism, but it isn't clear if this is evident in the content of the articles.
Conclusions
In recent years, pragmatic trials have been becoming more popular in research as the importance of real-world evidence is increasingly recognized. They are randomized trials that compare real world alternatives to experimental treatments in development. They involve patient populations that are more similar to those who receive treatment in regular care. This approach has the potential to overcome limitations of observational studies that are prone to limitations of relying on volunteers, and the limited accessibility and coding flexibility in national registries.
Other advantages of pragmatic trials are the ability to utilize existing data sources, and a greater likelihood of detecting meaningful changes than traditional trials. However, these trials could be prone to limitations that compromise their credibility and generalizability. For example the participation rates in certain trials might be lower than anticipated due to the healthy-volunteer effect as well as incentives to pay or compete for participants from other research studies (e.g. industry trials). The necessity to recruit people in a timely fashion also reduces the size of the sample and impact of many pragmatic trials. Certain pragmatic trials lack controls to ensure that any observed variations aren't due to biases that occur during the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and were published up to 2022. The PRECIS-2 tool was employed to evaluate the degree of pragmatism. It includes areas such as eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered that 14 of the trials scored as highly or pragmatic practical (i.e. scores of 5 or higher) in any one or more of these domains, and that the majority were single-center.
Trials with a high pragmatism rating tend to have higher eligibility criteria than traditional RCTs, which include very specific criteria that aren't likely to be used in clinical practice, and they comprise patients from a wide variety of hospitals. These characteristics, according to the authors, could make pragmatic trials more relevant and useful in everyday practice. However they do not guarantee that a trial is free of bias. Moreover, the pragmatism of a trial is not a fixed attribute; a pragmatic trial that does not contain all the characteristics of a explanatory trial can produce reliable and relevant results.