Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial open data platform and infrastructure that supports research on pragmatic trials. It collects and shares cleaned trial data and ratings using PRECIS-2, allowing for multiple and diverse meta-epidemiological studies to compare treatment effects estimates across trials that employ different levels of pragmatism and other design features.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. However, the use of the term "pragmatic" is not uniform and its definition and assessment requires further clarification. Pragmatic trials are designed to guide the practice of clinical medicine and policy choices, rather than prove a physiological or clinical hypothesis. A pragmatic study should try to be as similar to actual clinical practice as possible, including in its participation of participants, setting and design of the intervention, its delivery and execution of the intervention, as well as the determination and analysis of outcomes as well as primary analyses. This is a major difference between explanatory trials, as defined by Schwartz & Lellouch1 that are designed to confirm the hypothesis in a more thorough way.
Truely pragmatic trials should not blind participants or the clinicians. This could lead to an overestimation of treatment effects. The trials that are pragmatic should also try to attract patients from a wide range of health care settings, so that their results can be applied to the real world.
Furthermore, trials that are pragmatic must focus on outcomes that matter to patients, like quality of life and functional recovery. This is particularly important for trials involving the use of invasive procedures or potential for serious adverse events. The CRASH trial29 compared a 2 page report with an electronic monitoring system for patients in hospitals with chronic heart failure. The trial with a catheter, on the other hand, used symptomatic catheter associated urinary tract infection as the primary outcome.
In addition to these aspects pragmatic trials should reduce the trial procedures and requirements for data collection to reduce costs. In the end the aim of pragmatic trials is to make their findings as relevant to real-world clinical practice as is possible. This can be achieved by ensuring that their analysis is based on the intention to treat approach (as defined in CONSORT extensions).
Despite these requirements, a number of RCTs with features that defy the concept of pragmatism have been mislabeled as pragmatic and published in journals of all types. This could lead to false claims of pragmatism and the use of the term should be standardised. The creation of a PRECIS-2 tool that provides an objective, standardized evaluation of the pragmatic characteristics is a first step.
Methods
In a practical study, the goal is to inform policy or clinical decisions by showing how an intervention can be integrated into routine treatment in real-world situations. Explanatory trials test hypotheses regarding the cause-effect relation within idealized conditions. Therefore, pragmatic trials might have lower internal validity than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic studies can provide valuable information to make decisions in the context of healthcare.
The PRECIS-2 tool measures the level of pragmatism that is present in an RCT by scoring it across 9 domains ranging from 1 (very explanatory) to 5 (very pragmatic). In this study the areas of recruitment, organisation as well as flexibility in delivery flexible adherence, and follow-up received high scores. However, the main outcome and the method of missing data were scored below the practical limit. This suggests that it is possible to design a trial using high-quality pragmatic features, without harming the quality of the outcomes.
It is difficult to determine the level of pragmatism in a particular trial since pragmatism doesn't have a single attribute. Certain aspects of a research study can be more pragmatic than other. A trial's pragmatism could be affected by changes to the protocol or 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. They are not in line with the norm and can only be called pragmatic if their sponsors accept that the trials are not blinded.
Additionally, a typical feature of pragmatic trials is that the researchers attempt to make their findings more relevant by analyzing subgroups of the trial sample. This can result in imbalanced analyses and lower statistical power. This increases the chance of missing or misdetecting differences in the primary outcomes. In the case of the pragmatic studies that were included in this meta-analysis this was a serious issue since the secondary outcomes were not adjusted to account for variations in baseline covariates.
Furthermore the pragmatic trials may be a challenge in the gathering and interpretation of safety data. It is because adverse events are usually self-reported, and therefore are prone to errors, delays or coding errors. It is crucial to increase the accuracy and quality of the results in these trials.
Results
While the definition of pragmatism doesn't require that all clinical trials are 100% pragmatist there are benefits of including pragmatic elements in trials. These include:
Increased sensitivity to real-world issues which reduces cost and size of the study and allowing the study results to be more quickly translated into actual clinical practice (by including patients who are routinely treated). However, pragmatic trials can also have disadvantages. For instance, the appropriate type of heterogeneity could help a study to generalize its results to many different patients and settings; however, the wrong type of heterogeneity can reduce assay sensitivity, and thus decrease the ability of a trial to detect even minor effects of treatment.
A variety of studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 developed a framework to discern between explanation-based studies that confirm the physiological hypothesis or clinical hypothesis, and pragmatic studies that inform the selection of appropriate therapies in real world clinical practice. Their framework included nine domains, each scoring on a scale ranging from 1 to 5, with 1 being more informative and 5 indicating more pragmatic. The domains included recruitment and setting up, the delivery of intervention, 프라그마틱 정품 사이트 flexible compliance and 프라그마틱 슬롯 사이트 슬롯 (124.220.233.193) primary analysis.
The original PRECIS tool3 was based on a similar scale and domains. Koppenaal et al10 created an adaptation to this assessment dubbed the Pragmascope which was more user-friendly to use in systematic reviews. They discovered that pragmatic reviews scored higher across all domains, however they scored lower in the primary analysis domain.
The difference in the primary analysis domain can be explained by the way that most pragmatic trials analyze data. Certain explanatory trials however don't. The overall score was lower for systematic reviews that were pragmatic when the domains of organisation, flexible delivery and follow-up were combined.
It is crucial to keep in mind that a pragmatic study should not mean that a trial is of poor quality. In fact, there are increasing numbers of clinical trials that employ the term 'pragmatic' either in their abstract or title (as defined by MEDLINE but which is neither sensitive nor precise). These terms may indicate a greater understanding of pragmatism in titles and abstracts, but it's unclear whether this is reflected in content.
Conclusions
As the importance of evidence from the real world becomes more widespread and pragmatic trials have gained momentum in research. They are randomized trials that compare real world alternatives to clinical trials in development. They involve patient populations more closely resembling those treated in regular care. This method can help overcome the limitations of observational studies that are prone to biases associated with reliance on volunteers and the lack of accessibility and coding flexibility in national registry systems.
Pragmatic trials also have advantages, like the ability to use existing data sources, and a greater chance of detecting significant differences from traditional trials. However, these tests could still have limitations which undermine their reliability and generalizability. The participation rates in certain 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 fashion also limits the sample size and impact of many pragmatic trials. Additionally, some pragmatic trials don't 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 RCTs published up to 2022 that self-described themselves as pragmatic. The PRECIS-2 tool was employed to evaluate the degree of pragmatism. It includes domains such as eligibility criteria and flexibility in recruitment, adherence to intervention, 프라그마틱 슬롯 무료 and follow-up. They found 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or higher) in at least one of these domains.
Trials with a high pragmatism rating tend to have broader eligibility criteria than traditional RCTs which have very specific criteria that are not likely to be used in clinical practice, and they comprise patients from a wide variety of hospitals. The authors claim that these characteristics can help make pragmatic trials more effective and useful for daily practice, but they do not guarantee that a trial conducted in a pragmatic manner is free of bias. The pragmatism characteristic is not a fixed attribute; a pragmatic test that does not possess all the characteristics of an explanatory study can still produce valuable and valid results.