Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that facilitates research on pragmatic trials. It collects and distributes clean trial data, ratings and evaluations using PRECIS-2. This permits a variety of meta-epidemiological analyses that compare treatment effect estimates across trials with different levels of pragmatism.
Background
Pragmatic studies are increasingly recognized as providing real-world evidence for clinical decision-making. The term "pragmatic" however, is not used in a consistent manner and its definition and assessment require clarification. The purpose of pragmatic trials is to inform policy and clinical practice decisions, not to confirm an hypothesis that is based on a clinical or physiological basis. A pragmatic trial should try to be as close as possible to actual clinical practices which include the recruitment of participants, setting, designing, delivery and implementation of interventions, determining and analysis outcomes, and primary analyses. This is a significant difference from explanatory trials (as described by Schwartz and Lellouch1) that are intended to provide a more thorough proof of an idea.
The most pragmatic trials should not conceal participants or the clinicians. This can lead to an overestimation of the effect of treatment. The trials that are pragmatic should also try to enroll patients from a wide range of health care settings so that their results can be applied to the real world.
Finally, pragmatic trials must focus on outcomes that matter to patients, like the quality of life and functional recovery. This is particularly important when trials involve invasive procedures or have potentially dangerous adverse effects. The CRASH trial29 compared a 2 page report with an electronic monitoring system for patients in hospitals suffering from chronic cardiac failure. 프라그마틱 정품 확인법 with a catheter, on the other hand utilized symptomatic catheter-related urinary tract infection as its primary outcome.
In addition to these features, pragmatic trials should minimize the trial procedures and data collection requirements to reduce costs. Finaly, pragmatic trials should aim to make their results as relevant to real-world clinical practices as they can. This can be achieved by ensuring that their primary analysis is based on the intention-to treat method (as described in CONSORT extensions).
Many RCTs that don't meet the criteria for pragmatism, but contain features contrary to pragmatism, have been published in journals of varying types and incorrectly labeled as pragmatic. This can lead to misleading claims about pragmatism, and the term's use should be standardized. The creation of a PRECIS-2 tool that can provide a standardized objective evaluation of pragmatic aspects is a first step.
Methods
In a pragmatic research 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 is distinct from explanation trials that test hypotheses about the causal-effect relationship in idealized situations. In this way, pragmatic trials could have a lower internal validity than explanation studies and be more prone to biases in their design, analysis, and conduct. Despite these limitations, pragmatic trials may be a valuable source of information for decision-making in the context of healthcare.
The PRECIS-2 tool scores an RCT on 9 domains, with scores ranging between 1 and 5 (very pragmatic). In this study, the recruit-ment, organization, flexibility in delivery and follow-up domains scored high scores, however the primary outcome and the method of missing data fell below the pragmatic limit. This indicates that a trial can be designed with well-thought-out practical features, but without damaging the quality.
It is hard to determine the level of pragmatism that is present in a study because pragmatism is not a have a binary characteristic. Certain aspects of a research study can be more pragmatic than other. Furthermore, logistical or protocol changes during a trial can change its score on pragmatism. Koppenaal and colleagues discovered that 36% of 89 pragmatic studies were placebo-controlled, or conducted prior to the licensing. The majority of them were single-center. They are not in line with the usual practice, and can only be considered pragmatic if the sponsors agree that such trials are not blinded.
Another common aspect of pragmatic trials is that the researchers try to make their results more valuable by studying subgroups of the trial. This can lead to imbalanced analyses and lower 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 serious issue since the secondary outcomes were not adjusted to account for variations in baseline covariates.
Additionally practical trials can present challenges in the gathering and interpretation of safety data. This is due to the fact that adverse events are usually self-reported and are susceptible to errors, delays or coding variations. It is therefore crucial to enhance the quality of outcomes ascertainment in these trials, and ideally by using national registry databases instead of relying on participants to report adverse events in a trial's own database.
Results
While the definition of pragmatism does not require that all trials be 100 100% pragmatic, there are advantages to including pragmatic components in clinical trials. These include:
Incorporating routine patients, the trial results can be translated more quickly into clinical practice. However, pragmatic trials can also have drawbacks. The right type of heterogeneity for instance could allow a study to expand its findings to different patients or settings. However the wrong type of heterogeneity could reduce the sensitivity of an assay and, consequently, reduce a trial's power to detect even minor effects of treatment.
Several studies have attempted to classify pragmatic trials using different definitions and scoring methods. Schwartz and Lellouch1 have developed a framework that can differentiate between explanation studies that confirm a physiological hypothesis or clinical hypothesis and pragmatic studies that inform the choice for appropriate therapies in clinical practice. Their framework included nine domains, each scored on a scale ranging from 1 to 5, with 1 being more informative and 5 indicating more pragmatic. The domains covered recruitment of intervention, setting up, delivery of intervention, flexible compliance and primary analysis.
The original PRECIS tool3 was an adapted version of the PRECIS tool3 that was based on the same scale and domains. Koppenaal et al10 devised an adaptation to this assessment dubbed the Pragmascope that was easier to use in systematic reviews. They found that pragmatic reviews scored higher on average in all domains, but scored lower in the primary analysis domain.
This difference in primary analysis domains could be explained by the way most pragmatic trials approach data. Certain explanatory trials however don't. The overall score for pragmatic systematic reviews was lower when the areas of organisation, flexible delivery and follow-up were merged.
It is important to note that the term "pragmatic trial" does not necessarily mean a poor quality trial, and indeed there is a growing number of clinical trials (as defined by MEDLINE search, however this is not sensitive nor specific) that use the term "pragmatic" in their abstracts or titles. These terms could indicate an increased understanding of pragmatism in titles and abstracts, but it's unclear whether this is evident in content.
Conclusions
In recent years, pragmatic trials are gaining popularity in research as the value of real world evidence is becoming increasingly acknowledged. They are randomized clinical trials that evaluate real-world alternatives to care instead of experimental treatments in development, they have patient populations that are more similar to the ones who are treated in routine care, they use comparisons that are commonplace in practice (e.g., existing drugs) and depend on participants' self-reports of outcomes. This method could help overcome limitations of observational studies that are prone to limitations of relying on volunteers and limited availability and coding variability in national registry systems.
Other advantages of pragmatic trials include the possibility of using existing data sources, as well as a higher probability of detecting significant changes than traditional trials. However, they may still have limitations that undermine their reliability and generalizability. Participation rates in some trials could be lower than expected because of the healthy-volunteering effect, financial incentives, or competition from other research studies. A lot of pragmatic trials are limited by the need to recruit participants quickly. Practical trials aren't always equipped with controls to ensure that any observed differences aren't due to biases that occur during the trial.
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 determine the degree of pragmatism. It covers areas like eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered that 14 of these trials scored highly or pragmatic sensible (i.e. scoring 5 or more) in any one or more of these domains, and that the majority of these were single-center.
Trials that have a high pragmatism score tend to have higher eligibility criteria than traditional RCTs, which include very specific criteria that are unlikely to be present in clinical practice, and they include populations from a wide range of hospitals. According to the authors, can make pragmatic trials more relevant and useful in the daily clinical. However, they cannot guarantee that a trial will be free of bias. Moreover, the pragmatism of a trial is not a definite characteristic; a pragmatic trial that does not possess all the characteristics of an explanatory trial can produce valid and useful results.