Mortality during US FDA clinical trials in patients with diabetes, hypertension, depression and schizophrenia

Abstract

Objectives: To evaluate the relationship between the mortality rates associated with psychiatric conditions like depression and schizophrenia compared with chronic medical conditions like hypertension and diabetes. Methods: Examined clinical trial safety data from New Drug Approval programmes reviewed by the US Food and Drug Administration and calculated all-cause and suicide/non-suicide mortality rates per 100,000 patient-exposure-years (PEY) for seven diabetes, 12 hypertension, 11 depression, and nine schizophrenia programmes (126,151 patients, 63,106.3 PEY). Results: Depression (894.8 ± 201.2) and schizophrenia (935.3 ± 214.6) had significantly higher all-cause mortality rates than diabetes (462.8 ± 70.8) and hypertension (448.4 ± 123.1). Psychiatric conditions had 1.9-2.1Â the medical conditions' mortality (p < 0.001). Non-suicide mortality rates for depression (506.2 ± 151.3), schizophrenia (550.9 ± 164.7), diabetes (457.2 ± 70.4) and hypertension (430.8 ± 120.6) were comparable. Only antidiabetics showed a signal for all-cause mortality (reduction of 37%, p ¼ 0.008). Conclusions: Depression and schizophrenia trial patients had comparable (if not higher) allcause mortality rates as older populations in diabetes and hypertension trials, even when excluding suicides. While generalizability of the rates themselves is limited, this study can adequately estimate the relational mortality among these conditions because of the high internal consistency of clinical trials. Potential signals for mortality reduction with active treatment should be considered for all investigational medications for chronic conditions with increased mortality, including psychotropics.

Observed intervention effects for mortality in randomised clinical trials: a methodological study protocol

“…An alternative method to derive mortality data from randomised clinical trials is to extract data directly from the databases of regulating authorities, such as the US Food and Drug Administration Resources on Drugs and Devices and the European Union Drug Regulating Authorities Clinical Trials Database. This has been done for multiple disease entities in a previously published methodological study 38. However, these databases do not include RoB assessments as opposed to the Cochrane Reviews and therefore, this methodology is not feasible for the purpose of our present study.…”

“…This has been done for multiple disease entities in a previously published methodological study. 38 However, these databases do not include RoB assessments as opposed to the Cochrane Reviews and therefore, this methodology is not feasible for the purpose of our present study.…”

Roles of GFPT2 Expression Levels on the Prognosis and Tumor Microenvironment of Colon Cancer

“…About 30% of patients have insidious liver metastases that cannot be detected by ultrasound or CT before surgery. However, only a small percentage (10%-20%) are suitable for surgical resection, and 70% of them recur postoperatively ( 3 , 4 ). Therefore, it is crucial to find new treatments for colon cancer.…”