Pragmatic Free Trial Meta
Pragmatic Free Trail Meta is an open data platform that enables research into pragmatic trials. It gathers and distributes clean trial data, ratings and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological analyses to examine the effect of treatment across trials of different levels of pragmatism.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic", however, is used inconsistently and its definition and measurement require clarification. The purpose of pragmatic trials is to inform policy and clinical practice decisions, not to confirm a physiological or clinical hypothesis. A pragmatic trial should also try to be as similar to the real-world clinical environment as is possible, including the participation of participants, setting up and design as well as the 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 which are designed to prove a hypothesis in a more thorough manner.
The most pragmatic trials should not be blind participants or the clinicians. This can lead to an overestimation of the effect of treatment. The pragmatic trials also include patients from different health care settings to ensure that the results can be applied to the real world.
Furthermore the focus of pragmatic trials should be on outcomes that are vital to patients, like quality of life or functional recovery. This is particularly relevant in trials that require invasive procedures or have potentially dangerous adverse impacts. The CRASH trial29 compared a 2-page report with an electronic monitoring system for patients in hospitals with chronic cardiac failure. The catheter trial28 on the other hand, used symptomatic catheter associated 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. Additionally pragmatic trials should try to make their results as applicable to clinical practice as is possible by making sure that their primary analysis follows the intention-to treat approach (as described in CONSORT extensions for pragmatic trials).
Many RCTs that don't meet the criteria for pragmatism, but have features that are contrary to pragmatism, have been published in journals of various types and incorrectly labeled pragmatic. This can result in misleading claims of pragmatism and the use of the term should be standardized. The development of the PRECIS-2 tool, which offers an objective standard for assessing practical features is a great first step.
Methods
In a pragmatic study the aim is to inform clinical or policy decisions by showing how an intervention can be integrated into routine care in real-world situations. 프라그마틱 체험 test hypotheses regarding the cause-effect relationship within 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 be a valuable source of information for decision-making in healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, ranging between 1 and 5 (very pragmatic). In this study, the domains of recruitment, organisation and flexibility in delivery, flexible adherence and follow-up received high scores. However, the primary outcome and the method of missing data scored below the pragmatic limit. This suggests that it is possible to design a trial with high-quality pragmatic features, without harming the quality of the outcomes.
It is difficult to determine the level of pragmatism that is present in a trial because pragmatism does not have a binary characteristic. Certain aspects of a study can be more pragmatic than others. Moreover, protocol or logistic changes during the trial may alter its score on pragmatism. In addition, 36% of the 89 pragmatic trials discovered by Koppenaal and co. were placebo-controlled, or conducted prior to licensing and most were single-center. They are not in line with the standard practice and can only be called pragmatic if their sponsors accept that these trials are not 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 result in unbalanced analyses that have less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. In the case of the pragmatic studies included in this meta-analysis, this was a major issue since the secondary outcomes weren't adjusted for variations in baseline covariates.
In addition, pragmatic studies may pose challenges to collection and interpretation of safety data. This is due to the fact that adverse events are usually self-reported, and therefore are prone to delays, inaccuracies or coding variations. It is therefore important to enhance the quality of outcomes assessment in these trials, 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 100 100% pragmatic, there are advantages of including pragmatic elements in clinical trials. These include:
By incorporating routine patients, the results of the trial can be more quickly translated into clinical practice. But 프라그마틱 체험 can be a challenge. For example, the right kind of heterogeneity can allow a trial to generalise its findings to a variety of patients and settings; however the wrong type of heterogeneity may reduce the assay's sensitivity, and thus decrease the ability of a trial to detect even minor effects of treatment.
Many studies have attempted classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 created a framework for distinguishing between explanation-based trials that support the clinical or physiological hypothesis and pragmatic trials that inform the selection of appropriate therapies in the real-world clinical setting. Their framework included nine domains, each scoring on a scale of 1 to 5, with 1 indicating more lucid and 5 indicating more pragmatic. The domains included recruitment, setting up, delivery of intervention, flexible compliance and primary analysis.
The original PRECIS tool3 included similar domains and an assessment scale ranging from 1 to 5. Koppenaal et al10 developed an adaptation of the assessment, called the Pragmascope that was simpler to use for systematic reviews. They discovered that pragmatic systematic reviews had a higher average scores in the majority of domains, but lower scores in the primary analysis domain.
The difference in the primary analysis domains can be explained by the way that most pragmatic trials analyze data. Certain explanatory trials however, do not. The overall score for systematic reviews that were pragmatic was lower when the areas of management, flexible delivery and following-up were combined.
It is important to note that a pragmatic trial doesn't necessarily mean a low-quality trial, and indeed there is an increasing rate of clinical trials (as defined by MEDLINE search, but this is not sensitive nor specific) that use the term 'pragmatic' in their abstracts or titles. These terms may signal an increased understanding of pragmatism in titles and abstracts, but it's not clear whether this is reflected in the content.
Conclusions
As appreciation for the value of real-world evidence grows popular, pragmatic trials have gained popularity in research. They are randomized studies that compare real-world treatment options with experimental treatments in development. They include patient populations more closely resembling those treated in regular care. This method can help overcome the limitations of observational research for example, the biases that are associated with the reliance on volunteers, and the lack of coding variations in national registries.
Other advantages of pragmatic trials are the ability to utilize existing data sources, and a greater chance of detecting meaningful changes than traditional trials. However, they may still have limitations that undermine their reliability and generalizability. For instance the participation rates in certain trials could be lower than anticipated due to the healthy-volunteer effect as well as financial incentives or competition for participants from other research studies (e.g. industry trials). The requirement to recruit participants in a timely manner also limits the sample size and impact of many pragmatic trials. Some pragmatic trials also lack controls to ensure that observed differences aren't due to biases in the trial.
The authors of the Pragmatic Free Trial Meta identified 48 RCTs self-labeled as pragmatic and were published until 2022. They assessed pragmatism using the PRECIS-2 tool, which consists of the domains eligibility criteria and recruitment criteria, as well as flexibility in adherence to interventions 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 that have specific criteria that are unlikely to be found in clinical practice, and they include populations from a wide range of hospitals. The authors argue that these traits can make pragmatic trials more effective and applicable to daily practice, but they do not necessarily guarantee that a trial using a pragmatic approach is free of bias. The pragmatism is not a definite characteristic the test that does not possess all the characteristics of an explanation study may still yield reliable and beneficial results.