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 that compare treatment effect estimates across trials of various levels of pragmatism.
Background
Pragmatic studies are increasingly acknowledged as providing evidence from the real world for clinical decision-making. However, the use of the term "pragmatic" is not consistent and its definition as well as assessment requires clarification. Pragmatic trials are intended to guide the practice of clinical medicine and policy decisions rather than prove a physiological or clinical hypothesis. A pragmatic study should strive to be as close as possible to the real-world clinical practice, including recruiting participants, setting, designing, delivery and execution of interventions, determination and analysis results, as well as primary analysis. This is a key difference from explanatory trials (as described by Schwartz and Lellouch1) which are designed to provide more thorough proof of an idea.
Truely pragmatic trials should not be blind participants or the clinicians. This can lead to bias in the estimations of the effects of treatment. Pragmatic trials should also seek to attract patients from a variety of health care settings, so that their results can be applied to the real world.
Furthermore, trials that are pragmatic must concentrate on outcomes that are important to patients, like the quality of life and functional recovery. This is particularly important when trials involve the use of invasive procedures or could have harmful 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 the pragmatic trial should also reduce the trial's procedures and data collection requirements in order to reduce costs. Additionally, pragmatic trials should aim to make their results as relevant to real-world clinical practice as is possible. 프라그마틱 정품 확인법 can be achieved by ensuring their primary analysis is based on the intention to treat method (as defined in CONSORT extensions).
Many RCTs which do not meet the requirements for pragmatism but contain features contrary to pragmatism have been published in journals of different kinds and incorrectly labeled pragmatic. This could lead to misleading claims of pragmatism and the usage of the term must be standardized. The development of the PRECIS-2 tool, which provides an objective and standard assessment of pragmatic characteristics, is a good first step.
Methods
In a pragmatic study the aim is to inform policy or clinical decisions by showing how an intervention could be integrated into routine care in real-world contexts. This is distinct from explanation trials that test hypotheses about the cause-effect connection in idealized conditions. In this way, pragmatic trials can have less internal validity than explanation studies and be more susceptible to biases in their design analysis, conduct, and design. Despite these limitations, pragmatic trials may be a valuable source of information for decision-making in healthcare.
The PRECIS-2 tool measures the degree of pragmatism in an RCT by assessing it across 9 domains ranging from 1 (very explicit) to 5 (very pragmatic). In this study the areas of recruitment, organisation, flexibility in delivery, flexible adherence and follow-up were awarded high scores. However, the primary outcome and the method of missing data were scored below the practical limit. This indicates that a trial can be designed with effective practical features, yet not damaging the quality.
It is hard to determine the degree of pragmatism that is present in a study because pragmatism is not a possess a specific characteristic. Certain aspects of a study can be more pragmatic than other. Additionally, logistical or protocol modifications made during a trial can change its score in pragmatism. Koppenaal and colleagues discovered that 36% of the 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. Most were also single-center. They are not close to the usual practice and are only called pragmatic if the sponsors agree that these trials are not blinded.
A typical feature of pragmatic studies is that researchers try to make their findings more meaningful by studying subgroups of the trial sample. This can lead to unbalanced comparisons and lower statistical power, which increases the risk of either not detecting or incorrectly detecting differences in the primary outcome. In the case of the pragmatic trials included in this meta-analysis, this was a serious issue since the secondary outcomes weren't adjusted for variations in the baseline covariates.
Furthermore practical trials can present challenges 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 delays in reporting, inaccuracies or coding errors. It is important to increase the accuracy and quality of outcomes in these trials.
Results
Although the definition of pragmatism does not require that all trials are 100 percent pragmatic, there are benefits to including pragmatic components in clinical trials. These include:
By incorporating routine patients, the results of trials can be translated more quickly into clinical practice. However, pragmatic studies can also have disadvantages. The right kind of heterogeneity for instance, can help a study extend its findings to different patients or settings. However the wrong type of heterogeneity could reduce the sensitivity of an assay, and therefore lessen the power of a trial to detect even minor effects of treatment.
Several studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 created a framework to differentiate between explanation studies that confirm a physiological hypothesis or clinical hypothesis, and pragmatic studies that help inform the selection of appropriate treatments in clinical practice. The framework was composed of nine domains evaluated on a scale of 1-5 which indicated that 1 was more explanatory while 5 was more pragmatic. The domains covered recruitment of intervention, setting up, delivery of intervention, flex adherence and primary analysis.
The initial PRECIS tool3 featured similar domains and scales from 1 to 5. Koppenaal et. al10 devised 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 all domains, but 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 for systematic reviews that were pragmatic was lower when the areas of organization, flexible delivery, and following-up were combined.
It is crucial to keep in mind that a study that is pragmatic does not mean that a trial is of poor quality. In fact, there are 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 a greater understanding of pragmatism in abstracts and titles, but it isn't clear if this is reflected in the content.
Conclusions
In recent years, pragmatic trials are increasing in popularity in research because the value of real-world evidence is becoming increasingly acknowledged. They are clinical trials that are randomized which compare real-world treatment options instead of experimental treatments under development, they involve populations of patients that more closely mirror those treated in routine care, they use comparisons that are commonplace in practice (e.g. existing drugs), and they rely on participant self-report of outcomes. This method can help overcome the limitations of observational research like the biases that come with the reliance on volunteers and the limited availability and the coding differences in national registry.
Pragmatic trials also have advantages, such as the ability to leverage existing data sources and a higher likelihood of detecting meaningful distinctions from traditional trials. However, pragmatic tests may still have limitations which undermine their validity and generalizability. Participation rates in some trials could be lower than expected due to the health-promoting effect, financial incentives, or competition from other research studies. The requirement to recruit participants in a timely fashion also restricts the sample size and the impact of many pragmatic trials. In addition, some pragmatic trials do not have 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 were published from 2022. They evaluated pragmatism using the PRECIS-2 tool, which consists of the eligibility criteria for domains, recruitment, flexibility in adherence to interventions and follow-up. They discovered that 14 of these trials scored highly or pragmatic practical (i.e., scoring 5 or more) in one or more of these domains and that the majority of them were single-center.
Trials that have a high pragmatism score tend to have broader eligibility criteria than traditional RCTs that have specific criteria that are unlikely to be used in the clinical environment, and they include populations from a wide variety of hospitals. According to the authors, may make pragmatic trials more useful and relevant to everyday practice. However they do not ensure that a study is free of bias. The pragmatism is not a fixed attribute; a pragmatic test that doesn't have all the characteristics of an explanation study can still produce reliable and beneficial results.