Methodological challenges in the coding and adjudication of sudden deaths in a large simple trial with observational follow-up: the ziprasidone observational study of cardiac outcomes (ZODIAC)
Abstract
PURPOSE: The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real-world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD-10 coding rules for sudden death.
METHODS: A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD-10 rules. Relative risks (RR) and corresponding 95%CI were calculated for persons randomized to ziprasidone versus olanzapine, comparing 1-year incidence of sudden death, using multiple definitions.
RESULTS: Data on symptom onset to death and diagnosis of specific cardiac arrhythmias required by the ICD-10 rules were often lacking. Sensitivity analyses were conducted to explore the impact of cases suggestive of cardiac origin but missing data required by ICD-10 sudden death codes. Overall, the readjudicated data matched the study's initial findings, with no significant difference in 1-year mortality between ziprasidone and olanzapine for sudden death not otherwise specified and sudden cardiac death (R96.0 or R96.1 or I46.1; RR = 1.11, 95%CI 0.45- 2.77).
CONCLUSIONS: After outcome readjudication, ZODIAC found no difference in the risk of sudden death among those randomized to ziprasidone versus olanzapine. However, unlike hospital-based studies, fatal events…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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