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, which allows for multiple and varied meta-epidemiological studies that evaluate the effect of treatment on trials that have different levels of pragmatism and other design features.
Background
Pragmatic studies provide real-world evidence that can be used to make clinical decisions. The term "pragmatic", however, is used inconsistently and its definition and measurement require clarification. The purpose of pragmatic trials is to guide the practice of clinical medicine and policy decisions, not to confirm a physiological hypothesis or clinical hypothesis. A pragmatic study should strive to be as close as is possible to real-world clinical practices, including recruiting participants, setting, design, implementation and delivery of interventions, determination and analysis outcomes, and primary analyses. This is a key distinction from explanatory trials (as described by Schwartz and Lellouch1) that are intended to provide a more thorough proof of the hypothesis.
Trials that are truly pragmatic must avoid attempting to blind participants or clinicians, as this may result in bias in estimates of treatment effects. The pragmatic trials also include patients from different healthcare settings to ensure that the outcomes can be compared to the real world.
Additionally, clinical trials should be focused on outcomes that matter to patients, such as quality of life and functional recovery. This is particularly important for trials involving the use of invasive procedures or potentially serious adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for patients in hospitals with chronic heart failure. The catheter trial28 on the other hand utilized symptomatic catheter-related urinary tract infection as the primary outcome.
In addition to these features, pragmatic trials should minimize the requirements for data collection and trial procedures to cut costs and time commitments. Furthermore, pragmatic trials should seek to make their results as applicable to clinical practice as possible by making sure that their primary method of analysis is based on the intention-to-treat method (as described in CONSORT extensions for pragmatic trials).
Many RCTs that do not meet the criteria for pragmatism but have features that are contrary to pragmatism have been published in journals of different types and incorrectly labeled pragmatic. This can result in misleading claims of pragmaticity, and the use of the term needs to be standardized. 프라그마틱 슬롯무료 of a PRECIS-2 tool that provides an objective and standardized evaluation of pragmatic aspects is the first step.
Methods
In a practical study the aim is to inform policy or clinical decisions by demonstrating how an intervention can be integrated into routine treatment in real-world situations. This differs from explanation trials that test hypotheses about the cause-effect connection in idealized conditions. Consequently, pragmatic trials may be less reliable than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite these limitations, pragmatic trials can provide valuable information to decision-making in healthcare.
The PRECIS-2 tool evaluates the degree of pragmatism in an RCT by assessing it on 9 domains that range from 1 (very explicative) to 5 (very pragmatic). In this study, the domains of recruitment, organisation as well as flexibility in delivery flexible adherence, and follow-up were awarded high scores. However, the main outcome and the method for missing data were scored below the practical limit. This suggests that a trial could be designed with good practical features, but without harming the quality of the trial.
It is, however, difficult to assess the degree of pragmatism a trial is, since pragmatism is not a binary attribute; some aspects of a study can be more pragmatic than others. Additionally, logistical or protocol modifications during the course of an experiment can alter its pragmatism score. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled or conducted prior to licensing. Most were also single-center. They are not in line with the standard practice and can only be referred to as pragmatic if their sponsors agree that these trials aren't blinded.
A common feature of pragmatic research is that researchers attempt to make their findings more meaningful by analyzing subgroups within the trial. This can lead to unbalanced results and lower statistical power, thereby increasing the chance of not or misinterpreting the results of the primary outcome. This was a problem in the meta-analysis of pragmatic trials because secondary outcomes were not corrected for differences in covariates at the baseline.
In addition, pragmatic studies can pose difficulties in the gathering and interpretation of safety data. This is due to the fact that adverse events are generally reported by the participants themselves and are prone to reporting delays, inaccuracies, or coding variations. It is therefore crucial to enhance the quality of outcomes assessment in these trials, 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 doesn't require that all clinical trials are 100% pragmatic, there are benefits when incorporating pragmatic components into trials. These include:
Incorporating routine patients, the results of trials can be translated more quickly into clinical practice. However, pragmatic trials can also have drawbacks. For example, the right kind of heterogeneity can allow a trial to generalise its findings to a variety of settings and patients. However, the wrong type of heterogeneity could reduce assay sensitivity and therefore reduce the power of a study to detect even minor effects of treatment.
A variety of studies have attempted to categorize pragmatic trials using various definitions and scoring methods. Schwartz and Lellouch1 have developed a framework to distinguish between explanation-based trials that support a clinical or physiological hypothesis as well as pragmatic trials that help in the selection of appropriate treatments in clinical practice. Their framework included nine domains, each scored on a scale ranging from 1-5, with 1 indicating more explanatory and 5 indicating more practical. The domains covered recruitment and setting up, the delivery of intervention, flexible compliance and primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal and colleagues10 created an adaptation of the assessment, dubbed the Pragmascope, that was easier to use for systematic reviews. They found that pragmatic reviews scored higher in all domains, but scored lower in the primary analysis domain.
This difference in primary analysis domain can be explained by the way that most pragmatic trials analyse data. Some explanatory trials, however, do not. The overall score for pragmatic systematic reviews was lower when the domains of organisation, flexible delivery and follow-up were merged.
It is important to remember that a pragmatic study should not necessarily mean a low-quality study. In fact, there are an increasing number of clinical trials that employ the term 'pragmatic' either in their title or abstract (as defined by MEDLINE however it is neither sensitive nor precise). These terms may signal a greater understanding of pragmatism in titles and abstracts, but it's unclear if this is reflected in the content.
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 clinical trials in development. They include patient populations that are more similar to those who receive treatment in regular care. This approach can overcome the limitations of observational research, for example, the biases that come with the use of volunteers and the limited availability and the coding differences in national registry.
Pragmatic trials have other advantages, including the ability to use existing data sources and a higher likelihood of detecting meaningful distinctions from traditional trials. However, pragmatic trials may still have limitations that undermine their validity and generalizability. For instance the rates of participation in some 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 limited by the need to enroll participants quickly. Additionally, some pragmatic trials lack 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 48 RCTs that self-described themselves as pragmatic and that were published from 2022. They assessed pragmatism by using the PRECIS-2 tool, which consists of the eligibility criteria for domains and recruitment criteria, as well as flexibility in adherence to intervention, and follow-up. They discovered that 14 of the trials scored pragmatic or highly pragmatic (i.e. scoring 5 or more) in any one or more of these domains and that the majority were single-center.
Trials that have a high pragmatism score tend to have higher eligibility criteria than traditional RCTs which have very specific criteria that aren't likely to be present in clinical practice, and they include populations from a wide range of hospitals. The authors argue that these characteristics could make pragmatic trials more meaningful and applicable to daily practice, but they don't necessarily mean that a trial conducted in a pragmatic manner is free from bias. The pragmatism characteristic is not a definite characteristic; a pragmatic test that does not have all the characteristics of an explicative study may still yield valuable and valid results.