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 distributes cleaned trial data, ratings and evaluations using PRECIS-2. This allows for diverse meta-epidemiological studies to compare treatment effect estimates across trials with different levels of pragmatism.
Background
Pragmatic trials provide evidence from the real world that can be used to make clinical decisions. However, the usage of the term "pragmatic" is not consistent and its definition and evaluation requires further clarification. The purpose of pragmatic trials is to guide the practice of clinical medicine and policy choices, rather than verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should also aim to be as similar to real-world clinical practice as possible, including in its selection of participants, setting and design of the intervention, its delivery and implementation of the intervention, as well as the determination and analysis of outcomes and primary analysis. This is a major difference between explanatory trials as defined by Schwartz & Lellouch1 that are designed to prove a hypothesis in a more thorough way.
Truly pragmatic trials should not be blind participants or the clinicians. This can result in a bias in the estimates of the effect of treatment. Pragmatic trials should also seek to recruit patients from a wide range of health care settings so that their results can be compared to the real world.
Finally, pragmatic trials must be focused on outcomes that matter to patients, like quality of life and functional recovery. 프라그마틱 공식홈페이지 is particularly important in trials that involve surgical procedures that are invasive or have potential for serious adverse events. The CRASH trial29 compared a 2 page report with an electronic monitoring system for hospitalized patients with chronic heart failure. The trial with a catheter, on the other hand utilized symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these features, pragmatic trials should minimize the procedures for conducting trials and data collection requirements to reduce costs. Additionally pragmatic trials should try to make their findings as applicable to clinical practice as is possible by making sure that their primary analysis is based on the intention-to-treat method (as described in CONSORT extensions for pragmatic trials).
Many RCTs which do not meet the criteria for pragmatism, but contain features contrary to pragmatism have been published in journals of various types and incorrectly labeled as pragmatic. This can lead to false claims of pragmaticity and the usage of the term must be standardized. The development of a PRECIS-2 tool that provides a standardized objective assessment of pragmatic features is a good start.
Methods
In a pragmatic study, the aim is to inform clinical or policy decisions by showing how an intervention could be implemented into routine care. This differs from explanation trials that test hypotheses about the cause-effect relationship in idealised settings. 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 the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging between 1 and 5 (very pragmatic). In this study the areas of recruitment, organisation as well as flexibility in delivery flexibility in adherence, and follow-up were awarded high scores. However, the primary 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 damaging the quality.
However, it's difficult to assess how pragmatic a particular trial really is because pragmatism is not a binary characteristic; certain aspects of a study can be more pragmatic than others. Moreover, protocol or logistic changes during an experiment can alter its pragmatism score. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled or conducted prior to licensing. Most were also single-center. Thus, they are not very close to usual practice and are only pragmatic in the event that their sponsors are supportive of the absence of blinding in these trials.
A common aspect of pragmatic studies is that researchers attempt to make their findings more meaningful by studying subgroups within the trial. This can result in unbalanced analyses that have lower statistical power. This increases the possibility of missing or misdetecting differences in the primary outcomes. In the case of the pragmatic studies included in this meta-analysis this was a significant problem since the secondary outcomes were not adjusted for variations in the baseline covariates.
In addition, pragmatic studies may pose challenges to collection and interpretation safety data. This is because adverse events are usually self-reported and are susceptible to reporting errors, delays or coding errors. It is therefore crucial to improve the quality of outcomes assessment in these trials, and ideally by using national registries instead of relying on participants to report adverse events in the trial's own database.
Results
Although the definition of pragmatism doesn't require that all clinical trials be 100% pragmatic There are advantages to including pragmatic components in trials. These include:
Incorporating routine patients, the trial results are more easily translated into clinical practice. However, pragmatic trials may also have disadvantages. For instance, the right type of heterogeneity could help a trial to generalise its findings to a variety of settings and patients. However, the wrong type of heterogeneity may reduce the assay's sensitivity, and thus lessen the ability of a trial to detect even minor effects of treatment.
A variety of studies have attempted to categorize pragmatic trials, with a variety of definitions and scoring systems. Schwartz and Lellouch1 developed a framework to discern between explanation-based studies that prove a physiological hypothesis or clinical hypothesis, and pragmatic studies that inform the selection of appropriate treatments in the real-world clinical practice. Their framework comprised nine domains that were scored on a scale ranging from 1 to 5 with 1 indicating more explanatory and 5 indicating more practical. The domains included recruitment, setting, intervention delivery with flexibility, follow-up and primary analysis.
The initial PRECIS tool3 featured similar domains and a scale of 1 to 5. Koppenaal et al10 developed an adaptation of this assessment, dubbed the Pragmascope which was more user-friendly to use for systematic reviews. They found that pragmatic reviews scored higher on average in most domains, but scored lower in the primary analysis domain.
This distinction in the primary analysis domain can be explained by the way that most pragmatic trials analyze data. Some explanatory trials, however 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 study that is pragmatic does not necessarily mean a low-quality study. In fact, there is an increasing number of clinical trials that use the term "pragmatic" either in their title or abstract (as defined by MEDLINE, but that is neither precise nor sensitive). These terms may indicate that there is a greater awareness of pragmatism within abstracts and titles, but it's unclear whether this is reflected in content.
Conclusions
As the importance of real-world evidence grows widespread and pragmatic trials have gained momentum in research. They are clinical trials randomized that evaluate real-world alternatives to care rather than experimental treatments under development, they have populations of patients which are more closely resembling the patients who receive routine medical care, they utilize comparators which exist in routine practice (e.g., existing medications), and they depend on the self-reporting of participants about outcomes. This method can help overcome the limitations of observational research, such as the biases associated with the use of volunteers and the lack of codes that vary in national registers.
Pragmatic trials also have advantages, such as the ability to leverage existing data sources, and a greater likelihood of detecting meaningful differences than traditional trials. However, they may be prone to limitations that undermine their validity and generalizability. Participation rates in some trials may be lower than expected due to the health-promoting effect, financial incentives or competition from other research studies. The need to recruit individuals in a timely fashion also reduces the size of the sample and the impact of many practical trials. 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. The PRECIS-2 tool was employed to evaluate pragmatism. It includes areas like eligibility criteria and flexibility in recruitment as well as adherence to interventions and follow-up. They found that 14 of these trials scored as highly or pragmatic sensible (i.e. scoring 5 or more) in one or more of these domains and that the majority were single-center.
Studies that have high pragmatism scores tend to have broader criteria for eligibility than conventional RCTs. They also have populations from various hospitals. 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. The pragmatism is not a definite characteristic and a test that does not have all the characteristics of an explanation study could still yield reliable and beneficial results.