Pragmatic Clinical Trial (PCT)

A Pragmatic Clinical Trial (PCT) is a Clinical Trial that focuses on the correlation between treatments and outcomes in a healthcare system instead of focusing on proving causations for clinical endpoints.

• AKA: Practical Clinical Trial (PCT), Effectiveness Clinical Trial.
• Context:
  • It can be designed by a Pragmatic-Explanatory Continuum Indicator Summary (PRECIS) Tool.
  • It can range from being a Pragmatic Randomized Controlled Trial (pRCT) to being a Pragmatic Cluster-Randomized Control Trial.
  • It is focused on the clinical effectiveness.
  • It can be classified as a Phase IV Clinical Trial.
• Example(s):
  • Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT),
  • A Stop Smoking in Schools Trial (ASSIST) Clinical Trial,
  • Corticosteroid Randomization after Significant Head Injury (CRASH) Clinical Trial,
  • High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome (High-STEACS) Clinical Trial,
  • Post-Myocaraial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Clinical Trial,
  • PRagmatic trial Of Video Education in Nursing homes (PROVEN),
  • STRIDE Study
  • Shed MED,
  • Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) Clinical Trial,
  • Trial to Reduce Antimicrobial Use in Nursing home residents with Alzheimer's disease and other Dementias (TRAIN-AD),
  • ...
  • …
• Counter-Example(s):
  • Adaptive Clinical Trial,
  • Confirmatory Clinical Trial,
  • Explanatory Clinical Trial,
  • Exploratory Clinical Trial.
• See: Decentralized Clinical Trial, Correlation, Therapy, Outcomes Research, Health System, Causality, Confounding, Drug Clinical Trial, Medical Device Clinical Trial, Clinical Procedure Trial, Observational Clinical Trial, Interventional Clinical Trial, Clinical Trial Management System, Clinical Trial Monitoring System, Clinical Trial Protocol, Clinical Trial Design System, Clinical Endpoint.

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References

2021a

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Pragmatic_clinical_trial Retrieved:2021-11-13.
  • A pragmatic clinical trial (PCT), sometimes called a practical clinical trial (PCT), is a clinical trial that focuses on correlation between treatments and outcomes in real-world health system practice rather than focusing on proving causative explanations for outcomes, which requires extensive deconfounding with inclusion and exclusion criteria so strict that they risk rendering the trial results irrelevant to much of real-world practice.

2021b

• (Wikipedia, 2021) ⇒ https://en.wikipedia.org/wiki/Efficacy#Medicine Retrieved:2021-11-14.
  • QUOTE: In medicine, efficacy is the capacity for beneficial change (or therapeutic effect) of a given intervention (for example a drug, medical device, surgical procedure, or a public health intervention). Establishment of the efficacy of an intervention is often done relative to other available interventions, with which it will be compared. Specifically, efficacy refers to "whether a drug demonstrates a health benefit over a placebo or other intervention when tested in an ideal situation, such as a tightly controlled clinical trial." These studies focus on a primary parameter to be shown statistically different between placebo and intervention groups. Comparisons of this type are called 'explanatory' randomized controlled trials, whereas 'pragmatic' trials are used to establish the effectiveness of an intervention regarding also non-specific parameters. Effectiveness refers to "how the drug works in a real-world situation", and is "often lower than efficacy because of interactions with other medications or health conditions of the patient, sufficient dose or duration of use not prescribed by the physician or followed by the patient, or use for an off-label condition that had not been tested."

2017

• (Salive, 2017) ⇒ Marcel Salive (2017). "Pragmatic clinical trials: Testing treatments in the real world". In: NIH-NIA Blog.
  • QUOTE: Pragmatic trials may test the same intervention as an explanatory trial, but they are conducted in real-world clinical practice settings, with typical patients and by qualified clinicians, who may not, however, have a research background. Often, the positive results from explanatory trials have been found to be less effective in practice than they were in the lab, because several factors not present in the controlled setting can affect the eventual outcomes(...)

    Another feature of pragmatic trials is how participants are randomized to treatment and control groups. In an explanatory trial, participants may be randomized in the order that they are recruited. In pragmatic trials, participants are often randomized at the group level. One group of participants treated in a setting such as a hospital, nursing home, clinic, or physician's practice, might receive the intervention, while people matched to be treated in a similar setting might serve as the control group. Using multiple health systems as the trial setting increases the likelihood that the results of the research can be widely applied (...)

     NIA is particularly interested in conducting additional pragmatic trials. Some of the studies now in progress include:

    • PROVEN – a cluster-randomized control trial of an advance care planning video program for nursing home patients in 359 facilities within two health care systems.
    • STRIDE Study – a cluster-randomized trial to determine the effectiveness for fall prevention of an evidence-based, patient-centered, multifactorial intervention that combines elements of practice redesign; a multifactorial, individually tailored intervention; and practice guidelines offered by the CDC and other organizations.
    • Shed MEDS – a randomized controlled trial to evaluate the effects of an intervention to reduce medication use among hospitalized older adults discharged to skilled nursing facilities.
    • TRAIN-AD – a cluster randomized controlled trial to evaluate a multicomponent intervention to improve infection management for suspected urinary and lower respiratory tract infections among advanced dementia residents in 24 Boston area nursing homes.

2016

• (Ford & Norrie, 2016) ⇒ Ian Ford, and John Norrie (2016) "Pragmatic Trials". In: The New England Journal of Medicine (NEJM) 2016; 375:454-463.
  • QUOTE: Schwartz and Lellouch proposed a distinction between explanatory trials, which confirm a physiological or clinical hypothesis, and pragmatic trials, which inform a clinical or policy decision by providing evidence for adoption of the intervention into real-world clinical practice. The original PRECIS (Pragmatic–Explanatory Continuum Indicator Summary) tool attempted to clarify the concept of pragmatism and provided a guide, scoring system, and graphical representation of the pragmatic features of a trial. Features included the recruitment of investigators and participants, the intervention and its delivery, follow-up, and the determination and analysis of outcomes. Many trials could be deemed to be pragmatic with regard to at least one of these dimensions, but few are truly pragmatic on all dimensions. Pragmatism has been discussed widely (...), and a special issue of Clinical Trials had 12 articles focused on ethical and regulatory issues in pragmatic trials The requirements for pragmatism were loosened substantially in PRECIS-2, and a pragmatic extension to the CONSORT statement has been proposed . Key dimensions for assessing the degree of trial pragmatism, following PRECIS-2, are provided in Table 1. The trials that are used as pragmatic exemplars throughout this article are summarized in Table 2.

2011

• (Patsopoulos, 2011) ⇒ Nikolaos A. Patsopoulos (2011). "A Pragmatic View on Pragmatic Trials". IN: Dialogues in Clinical Neuroscience, 13(2).
  • QUOTE: The explanatory trial is the best design to explore if and how an intervention works, and the whole experiment is designed in order to control for all known biases and confounders, so that the intervention's effect is maximized. Usually the intervention under examination is compared with a placebo or with another active treatment. The pragmatic trial, on the other hand, is designed to test interventions in the full spectrum of everyday clinical settings in order to maximize applicability and generalizability. The research question under investigation is whether an intervention actually works in real life. The intervention is evaluated against other ones (established or not) of the same or different class, in routine practice settings. Pragmatic trials measure a wide spectrum of outcomes, mostly patient-centered, whereas explanatory trials focus on measurable symptoms or markers (clinical or biological). Figure 1 illustrates some main differences between pragmatic and explanatory trials.

    Generally, the explanatory trials focus towards homogeneity, so that the errors and biases will influence the results as little as possible, whereas pragmatic trials are a race towards maximal heterogeneity in all aspects, eg, patients, treatments, clinical settings, etc. In order to overcome the inherited heterogeneity, which leads to dilution of the effect, pragmatic trials must be large enough (to increase power to detect small effects) and simple in their design. Simple trials are easier to plan, perform, and follow up.

Figure 1: Schematic of the relationship between explanatory and pragmatic trials. The wide base of the pyramid depicts the relatively higher proportion of explanatory trials.

2003

• (Tunis et al., 2003) ⇒ Sean R. Tunis, Daniel B. Stryer, and Carolyn M. Clancy (2003). "Practical Clinical Trials. Increasing the Value of Clinical Research for Decision Making in Clinical and Health Policy". In: JAMA. 2003;290(12):1624-1632.
  • QUOTE: Clinical trials designed to assist health care decision-makers, referred to as pragmatic clinical trials or [[practical clinical trials (PCTs)]], are defined as trials for which the hypothesis and study design are formulated based on information needed to make a decision. They are distinguished from explanatory clinical trials, for which the goal is to better understand how and why an intervention works. Explanatory trials are designed to maximize the chance that some biological effect of a new treatment will be revealed by the study. The PCTs address practical questions about the risks, benefits, and costs of an intervention as they would occur in routine clinical practice. The most distinctive features of PCTs are that they select clinically relevant interventions to compare, include a diverse population of study participants, recruit participants from a variety of practice settings, and collect data on a broad range of health outcomes.

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