Enrolment criteria for diabetes cardiovascular outcome trials do not inform on generalizability to clinical practice: The case of glucagon‐like peptide‐1 receptor agonists

Abstract

Aim: To evaluate the generalizability of cardiovascular outcome trials (CVOTs) on glucagon-like peptide-1 receptor agonists (GLP-1RAs), we assessed what proportion of real-world patients with type 2 diabetes (T2D) constitute true CVOT-like populations. Materials and Methods: We applied inclusion/exclusion (I/E) criteria of each GLP-1RA CVOT to a cross-sectional database of 281 380 T2D patients from Italian diabetes outpatient clinics. We calculated the proportion of patients eligible for each CVOT and compared their clinical characteristics with those of trial patients. In addition, we used a Bayesian network-based method to sample the greatest subsets of real-world patients yielding true CVOT-like populations.Results: Between 98 725 and 124 164 T2D patients could be evaluated for CVOT eligibility. After excluding patients who were already on GLP-1RAs and applying I/E criteria, 35.8% of patients would be eligible for REWIND, 34.1% for PIONEER-6, 13.4% for EXSCEL, 10.1% for SUSTAIN-6, 9.5% for HARMONY and 9.4% for LEADER. Overall, 45.4% of patients could be eligible for at least one of the CVOTs.These patients, however, were extremely different to trial patients in most of the clinical characteristics, including demographics, concomitant medications and complications. The greatest CVOT-like subsets of real-world patients were 0.5% for SUSTAIN-6, 1.0% for EXSCEL, 1.2% for LEADER, 1.8% for PIONEER-6 and 7.9% for REWIND. Conclusions:A very small proportion of real-world patients constitute true CVOTlike populations. These findings question whether any meaningful information can be drawn from applying trial enrolment criteria to real-world T2D patients. K E Y W O R D S cardiovascular disease, glucagon-like peptide-1 analogue, pharmaco-epidemiology, population study, type 2 diabetes

Patients’ perceptions of frequent hospital admissions: a qualitative interview study with older people above 65 years of age

“…A regular comprehensive assessment of the patient's health status and care needs, based on a validated and uniform approach like the interRAI tool [42] may allow for key decision making in the care of older persons [43,44]. Our results suggest that it is also fundamental that caregivers develop the competence to recognize the spiritual and/or existential dimension in patients in their daily work environment.…”

<p>Long-Acting Injectable GLP-1 Receptor Agonists for the Treatment of Adults with Type 2 Diabetes: Perspectives from Clinical Practice</p>

“…In a recent multicenter study conducted on over 280,000 subjects with T2D treated in outpatients diabetes clinic in Italy, our group showed that, at most, one-third of these "real-world" patients would be included in each specific cardiovascular outcome trial (CVOT) on GLP-1RAs according to inclusion/exclusion (I/E) criteria ( Figure 2). 16 Moreover, more than 50% of subjects attending these clinics, representative of all diabetes subjects in Italy, would not be included in any of these trials. Similar results have also been reported from analyses of patients with T2D treated in the Unites States.…”

“…17 In addition, after applying sophisticated approaches of data analyses to select a group of subjects with CVOT-like clinical characteristics (ie, with average clinical characteristics similar to CVOT), we found that the proportion of subjects selected from real-world clinical practice would be at most 8%. 16…”

Patients’ perceptions of frequent hospital admissions: A qualitative study with older people above 65 years of age.

“…A regular comprehensive assessment of the patient's health status and care needs, based on a validated and uniform approach like the interRAI tool[43] may allow for key decision making in the care of older persons [44,45]. Our results suggest that it is also fundamental that caregivers develop the competence to recognize the spiritual and/or existential dimension in patients in their daily work environment.…”