Desirability of Outcome Ranking for Status Epilepticus (DOOR STEP): A Benefit-Risk Approach to Design and Analyses of Clinical SE Trials

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Journal Article

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Most clinical trials of treatment efficacy evaluate benefit and harm separately. Investigators generally rate the primary outcome of a trial with a binary outcome measure and consider harms separately as adverse events. This approach fails to recognize finer gradations of patient response, correlations between benefits and harms, and the overall effects on individual patients. For example, in status epilepticus trials, efficacy is often defined as absence of clinically apparent seizures with recovery of consciousness. Such an efficacy outcome fails to recognize that some causes of status, such as subarachnoid hemorrhage or stroke, may not be accompanied by return of consciousness, and the need to intubate a patient may be classified as treatment failure even if status was successfully terminated.The Desirability of Outcomes Ranking (DOOR) method uses a different approach. The DOOR method involves comparing the experiences of trial participants in different treatment arms by the desirability of the overall patient outcome. Using status epilepticus treatment as an example, a patient who experiences successful termination of status but with major side effects would have a less desirable outcome than a patient with treatment success and minor side effects, who in turn would have a less desirable outcome than a patient with treatment success but no side effects. This is a patient-centered approach because it considers treatment efficacy in the context of the costs borne by the patient, e.g., toxicity in achieving efficacy. Thus, DOOR considers both the benefits and harms to individual patients in assessing the outcome of a clinical trial.In this paper we present the rationale for the use of DOOR, the issues involved in the development of and statistical analyses of an ordinal outcome, and an example of potential application of the DOOR method to a clinical trial of convulsive status epilepticus.