Analysis of the characteristics and the degree of pragmatism exhibited by pragmatic-labelled trials of antineoplastic treatments

Abstract

Background: Pragmatic clinical trials (PCTs) are designed to reflect how an investigational treatment would be applied in clinical practice. As such, unlike their explanatory counterparts, they measure therapeutic effectiveness and are capable of generating high-quality real-world evidence. However, the conduct of PCTs remains extremely rare. The scarcity of such studies has contributed to the emergence of the efficacy-effectiveness gap and has led to calls for launching more of them, including in the field of oncology. This analysis aimed to identify self-labelled pragmatic trials of antineoplastic interventions and to evaluate whether their use of this label was justified.

Methods: We searched PubMed® and Embase® for publications corresponding with studies that investigated antitumor therapies and that were tagged as pragmatic in their titles, abstracts and/or index terms. Subsequently, we consulted all available source documents for the included trials and extracted relevant information from them. The data collected were then used to appraise the degree of pragmatism displayed by the PCTs with the help of the validated PRECIS-2 tool.

Results: The literature search returned 803 unique records, of which 46 were retained upon conclusion of the screening process. This ultimately resulted in the identification of 42 distinct trials that carried the 'pragmatic' label. These studies examined eight different categories of neoplasms and were mostly randomized, open-label, multicentric, single-country trials sponsored by non-commercial parties. On a scale of one (very explanatory) to five (very pragmatic), the median PCT had a PRECIS-2 score per domain of 3.13 (interquartile range: 2.57-3.53). The most and least pragmatic studies in the sample had a score of 4.44 and 1.57, respectively. Only a minority of trials were described in sufficient detail to allow them to be graded across all domains of the PRECIS-2 instrument. Many of the studies examined also had features that arguably precluded them from being pragmatic altogether, such as being monocentric or placebo-controlled in nature.

Conclusion: PCTs of antineoplastic treatments are generally no more pragmatic than they are explanatory.

Keywords: Cancer; Efficacy-effectiveness gap; Explanatory trials; Neoplasms; Oncology; PRECIS-2; Pragmatic trials; Randomized controlled trials; Real-world evidence; Treatments.

Fig. 1

Flowchart of the literature screening and study selection process

Fig. 2

Breakdown of the included studies by (A) the types of neoplasms they focused on (with the area of each rectangle/tumor type being proportional to its share of the sample), B their decades of initiation, (C) the types of interventions they investigated, and (D) the extent to which the industry was involved in their conduct. The percentages shown may not add up to 100% due to rounding (A), or because the categories displayed are not mutually exclusive (C)

Fig. 3

PRECIS-2 wheels of (A) the highest-scoring, (B) the lowest-scoring, and (C) the median trial. The concentric circles represent the different possible scores that can be awarded to each domain of the PRECIS-2 tool, with the innermost one being equivalent to 1 and the outermost one corresponding with 5. The area of the polygons enclosed by the green lines connecting the ‘score dots’ is proportional to the degree of pragmatism exhibited by the studies in question. Note that for (B), the ‘recruitment’ and ‘flexibility (adherence)’ domains could not be graded, and the matching dots are therefore missing