Pragmatic Free Trial Meta
Pragmatic Free Trial Meta is a non-commercial, open data platform and infrastructure that supports research on pragmatic trials. It gathers and distributes clean trial data, ratings, and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological studies to evaluate the effects of treatment across trials of various levels of pragmatism.
Background
Pragmatic trials are becoming more widely acknowledged as providing evidence from the real world to support clinical decision-making. The term "pragmatic" however, is used inconsistently and its definition and evaluation require clarification. Pragmatic trials are intended to guide the practice of clinical medicine and policy decisions, not to verify a physiological hypothesis or clinical hypothesis. A pragmatic trial should try to be as close as is possible to the real-world clinical practice that include recruitment of participants, setting, designing, implementation and delivery of interventions, determination and analysis outcomes, and primary analysis. This is a significant difference between explanation-based trials, as described by Schwartz and Lellouch1 which are designed to test a hypothesis in a more thorough way.
Studies that are truly practical should avoid attempting to blind participants or healthcare professionals as this could lead to bias in the estimation of the effects of treatment. Pragmatic trials should also seek to recruit patients from a wide range of health care settings, to ensure that the results are generalizable to the real world.
Finally studies that are pragmatic should focus on outcomes that are crucial to patients, such as quality of life or functional recovery. This is especially important in trials that require surgical procedures that are invasive or may have dangerous adverse impacts. The CRASH trial29 compared a two-page report with an electronic monitoring system for hospitalized patients suffering from chronic cardiac failure. The catheter trial28 however was based on symptomatic catheter-related urinary tract infections as its primary outcome.
In addition to these characteristics pragmatic trials should reduce the procedures for conducting trials and requirements for data collection to cut costs and time commitments. Additionally pragmatic trials should try to make their findings as applicable to clinical practice as they can by making sure that their primary analysis is based on the intention-to-treat method (as described in CONSORT extensions for pragmatic trials).
Despite these criteria, many RCTs with features that defy the notion of pragmatism were incorrectly labeled pragmatic and published in journals of all types. This could lead to misleading claims of pragmatism, and the usage of the term must be standardized. 프라그마틱 무료체험 of the PRECIS-2 tool, which provides an objective and standard assessment of practical features, 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 everyday routine care. This differs from explanation trials, which test hypotheses about the cause-effect relationship in idealised conditions. In this way, pragmatic trials could have lower internal validity than explanation studies and be more susceptible to biases in their design as well as analysis and conduct. Despite these limitations, pragmatic trials can provide valuable information to decision-making in healthcare.
The PRECIS-2 tool measures the degree of pragmatism within an RCT by assessing it on 9 domains, ranging from 1 (very explanatory) to 5 (very pragmatic). In this study, the recruit-ment organisation, flexibility: delivery and follow-up domains received high scores, but the primary outcome and the procedure for missing data fell below the pragmatic limit. This suggests that it is possible to design a trial that has excellent pragmatic features without harming the quality of the outcomes.
It is difficult to determine the degree of pragmatism within a specific trial because pragmatism does not possess a specific attribute. Some aspects of a study may be more pragmatic than other. Moreover, protocol or logistic changes during the trial may alter its score in pragmatism. Additionally 36% of the 89 pragmatic trials identified by Koppenaal and co. were placebo-controlled or conducted prior to licensing, and the majority were single-center. Therefore, they aren't very close to usual practice and can only be described as pragmatic when their sponsors are accepting of the absence of blinding in these trials.
Additionally, a typical feature of pragmatic trials is that the researchers try to make their results more meaningful by analysing subgroups of the trial. This can lead to unbalanced analyses that have lower statistical power. This increases the risk 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 major issue because the secondary outcomes weren't adjusted for the differences in the baseline covariates.
Furthermore, pragmatic trials can also 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 reporting delays, inaccuracies, or coding variations. It is crucial to improve the accuracy and quality of the results in these trials.
Results
While the definition of pragmatism may not require that all clinical trials are 100% pragmatist there are benefits when incorporating pragmatic components into trials. These include:
Incorporating routine patients, the trial results can be more quickly translated into clinical practice. However, pragmatic trials have disadvantages. For instance, the right type of heterogeneity can help the trial to apply its findings to a variety of settings and patients. However, the wrong type of heterogeneity could reduce assay sensitivity, and thus reduce the power of a trial to detect minor treatment effects.
Several studies have attempted to classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 have developed an approach to distinguish between explanation-based trials that support the clinical or physiological hypothesis, and pragmatic trials that help in the selection of appropriate therapies in clinical practice. The framework was composed of nine domains scored on a 1-5 scale with 1 being more explanatory while 5 was more practical. The domains included recruitment, setting up, delivery of intervention, flex adherence and primary analysis.
The initial PRECIS tool3 included similar domains and a scale of 1 to 5. Koppenaal et al10 developed an adaptation of this assessment, dubbed the Pragmascope, that was easier to use for systematic reviews. They discovered that pragmatic reviews scored higher on average in most domains, but scored lower in the primary analysis domain.
This distinction in the primary analysis domains could be explained by the way that most pragmatic trials analyse 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 follow-up were merged.
It is crucial to keep in mind that a pragmatic study does not necessarily mean a low-quality study. In fact, there is increasing numbers of clinical trials which use the word 'pragmatic,' either in their title or abstract (as defined by MEDLINE, but that is not precise nor sensitive). These terms may signal that there is a greater awareness of pragmatism within abstracts and titles, however it's not clear whether this is reflected in content.
Conclusions
As the importance of real-world evidence grows popular the pragmatic trial has gained momentum in research. They are randomized clinical trials that compare real-world care alternatives instead of experimental treatments in development, they include populations of patients which are more closely resembling those treated in routine care, they employ comparators which exist in routine practice (e.g. existing medications) and depend on the self-reporting of participants about outcomes. This approach can overcome the limitations of observational research like the biases associated with the use of volunteers and the limited availability and codes that vary in national registers.
Other benefits of pragmatic trials include the ability to use existing data sources, as well as a higher chance of detecting meaningful changes than traditional trials. However, they may be prone to limitations that compromise their credibility and generalizability. For instance the participation rates in certain trials may be lower than anticipated due to the healthy-volunteer influence and incentives to pay or compete for participants from other research studies (e.g., industry trials). Many pragmatic trials are also restricted by the need to recruit participants quickly. Additionally, some pragmatic trials do not 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 48 RCTs that self-labeled themselves as pragmatic and were published from 2022. The PRECIS-2 tool was used to evaluate the pragmatism of these trials. It covers areas such as eligibility criteria as well as recruitment flexibility and adherence to intervention and follow-up. They discovered 14 trials scored highly pragmatic or pragmatic (i.e. scoring 5 or more) in at least one of these domains.
Studies that have high pragmatism scores tend to have more lenient criteria for eligibility than traditional RCTs. They also have populations from various hospitals. These characteristics, according to the authors, can make pragmatic trials more useful and applicable in the daily clinical. However they do not guarantee that a trial will be free of bias. In addition, the pragmatism that is present in trials is not a fixed attribute A pragmatic trial that does not possess all the characteristics of an explanatory trial can produce valuable and reliable results.