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10 Pragmatic Free Trial Meta-Friendly Habits To Be Healthy
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 cleaned trial data, ratings and evaluations using PRECIS-2. This allows for a variety of meta-epidemiological analyses to compare treatment effect estimates across trials of various levels of pragmatism.

Background

Pragmatic trials provide real-world evidence that can be used to make clinical decisions. The term "pragmatic", however, is used inconsistently and its definition and measurement require further clarification. Pragmatic trials should be designed to guide clinical practice and policy decisions, not to confirm a physiological or clinical hypothesis. A pragmatic trial should aim to be as close as possible to actual clinical practices, including recruitment of participants, setting up, delivery and implementation of interventions, determination and analysis outcomes, and primary analysis. This is a major distinction between explanatory trials, as described by Schwartz & Lellouch1, which are designed to confirm the hypothesis in a more thorough way.

Studies that are truly pragmatic must be careful not to blind patients or the clinicians, as this may lead to bias in the estimation of the effect of treatment. Pragmatic trials should also seek to enroll patients from a variety of health care settings so that their results can be compared to the real world.

Finally, pragmatic trials must focus on outcomes that matter to patients, such as quality of life and functional recovery. This is especially important for trials involving invasive procedures or those with potential for serious adverse events. The CRASH trial29 compared a two-page report with an electronic monitoring system for patients in hospitals with chronic heart failure. The catheter trial28 on the other hand utilized symptomatic catheter-related urinary tract infection as the primary outcome.

In addition to these aspects, pragmatic trials should minimize trial procedures and data-collection requirements to cut costs and time commitments. Additionally these trials should strive to make their results as applicable to current clinical practice as is possible. This can be accomplished by ensuring that their 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 various types and incorrectly labeled as pragmatic. This can lead to false claims of pragmatism, and the use of the term should be standardized. The creation of the PRECIS-2 tool, which provides a standard objective assessment of pragmatic features, is a good first step.

Methods

In a pragmatic study it is the intention to inform policy or clinical decisions by showing how an intervention could be integrated into routine treatment in real-world contexts. This is different from explanatory trials that test hypotheses regarding the cause-effect connection in idealized situations. Consequently, pragmatic trials may be less reliable than explanatory trials, and could be more susceptible to bias in their design, conduct and analysis. Despite their limitations, pragmatic research can be a valuable source of information to make decisions in the context of healthcare.

The PRECIS-2 tool evaluates the degree of pragmatism within an RCT by scoring it across 9 domains, ranging from 1 (very explicit) to 5 (very pragmatic). In this study, the recruitment, organization, flexibility in delivery, flexible adherence and follow-up domains received high scores, however the primary outcome and the method of missing data were not at the limit of practicality. This suggests that a trial could be designed with effective practical features, yet not damaging the quality.


However, it is difficult to determine the degree of pragmatism a trial is since pragmatism is not a binary characteristic; certain aspects of a trial may be more pragmatic than others. Moreover, protocol or logistic changes during an experiment can alter its score on pragmatism. Koppenaal and colleagues found that 36% of 89 pragmatic studies were placebo-controlled or conducted prior to the licensing. The majority of them were single-center. Thus, they are not as common and can only be called pragmatic when their sponsors are accepting of the absence of blinding in these trials.

Furthermore, a common feature of pragmatic trials is that researchers attempt to make their findings more meaningful by analysing subgroups of the trial sample. This can result in unbalanced analyses that have less statistical power. This increases the possibility of omitting or misinterpreting differences in the primary outcomes. This was a problem in the meta-analysis of pragmatic trials as secondary outcomes were not corrected for differences in covariates at the baseline.

Furthermore the pragmatic trials may have challenges with respect to the collection and interpretation of safety data. This is due to the fact that adverse events tend to be self-reported and are susceptible to delays, inaccuracies or coding errors. Therefore, it is crucial to enhance the quality of outcomes ascertainment in these trials, in particular by using national registry databases instead of relying on participants to report adverse events in the trial's own database.

Results

While the definition of pragmatism may not require that all clinical trials are 100% pragmatic There are advantages to including pragmatic components in trials. These include:

By including routine patients, the results of trials are more easily translated into clinical practice. However, pragmatic studies can also have drawbacks. The right kind of heterogeneity for instance could allow a study to generalise its findings to many different settings or patients. However the wrong kind of heterogeneity can reduce the sensitivity of an assay, and therefore decrease the ability of a study to detect small treatment effects.

Many studies have attempted classify pragmatic trials using a variety of definitions and scoring methods. Schwartz and Lellouch1 have developed a framework to distinguish between research studies that prove a clinical or physiological hypothesis and pragmatic trials that inform the choice of appropriate therapies in real-world clinical practice. Their framework comprised nine domains that were scored on a scale of 1 to 5 with 1 being more informative and 5 indicating more practical. The domains were recruitment and setting, delivery of intervention and follow-up, as well as flexible adherence and primary analysis.

The initial PRECIS tool3 had similar domains and scales from 1 to 5. Koppenaal et al10 created an adaptation of this assessment dubbed the Pragmascope that was simpler 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.

The difference in the primary analysis domains can be due to the way in which most pragmatic trials approach data. Certain explanatory trials however do not. The overall score for pragmatic systematic reviews was lower when the areas of organization, flexible delivery, and follow-up were merged.

It is important to note that a pragmatic trial doesn't necessarily mean a low quality trial, and in fact there is a growing number of clinical trials (as defined by MEDLINE search, however this is not specific or sensitive) which use the word 'pragmatic' in their abstract or title. These terms may indicate a greater understanding of pragmatism in abstracts and titles, but it's not clear if this is reflected in the content.

pragmatickr

As the value of evidence from the real world becomes more popular and pragmatic trials have gained momentum in research. They are clinical trials randomized that compare real-world care alternatives instead of experimental treatments in development, they involve patient populations that are more similar to the ones who are treated in routine medical care, they utilize comparisons that are commonplace in practice (e.g., existing drugs), and they depend on participants' self-reports of outcomes. This method is able to overcome the limitations of observational research, such as the biases that come with the reliance on volunteers, and the lack of codes that vary in national registers.

Pragmatic trials offer other advantages, such as the ability to leverage existing data sources and a greater chance of detecting significant differences from traditional trials. However, pragmatic tests may be prone to limitations that undermine their validity and generalizability. For example the participation rates in certain trials could be lower than anticipated due to the healthy-volunteer influence and financial incentives or competition for participants from other research studies (e.g. industry trials). The necessity to recruit people in a timely fashion also restricts the sample size and the impact of many practical trials. In addition certain 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 RCTs published from 2022 to 2022 that self-described themselves as pragmatic. They assessed pragmatism using the PRECIS-2 tool that includes the domains eligibility criteria as well as recruitment, flexibility in adherence to intervention and follow-up. They found that 14 of these trials scored highly or pragmatic pragmatic (i.e. scores of 5 or higher) in any one or more of these domains and that the majority of these were single-center.

Studies with high pragmatism scores are likely to have more lenient criteria for eligibility than traditional RCTs. They also include patients from a variety of hospitals. The authors argue that these traits can make pragmatic trials more meaningful and applicable to daily practice, but they don't necessarily mean that a pragmatic trial is completely free of bias. The pragmatism is not a fixed characteristic and a test that doesn't have all the characteristics of an explicative study may still yield valid and useful outcomes.

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