# A Seamless Design for the Combination of a Case–Control and a Cohort Diagnostic Accuracy Study

## TL;DR

This paper introduces a new study design that combines case-control and cohort methods to improve the efficiency of evaluating diagnostic tests.

## Contribution

The paper proposes and validates a seamless diagnostic accuracy study design that integrates two traditional study types into one.

## Key findings

- The seamless design can be used without affecting the final analysis, even if part of the data is used in an interim analysis.
- Simulation studies show that power loss can be minimized with appropriate futility boundaries in the stopping rule.
- The design is ready for practical use and can accelerate diagnostic research under certain conditions.

## Abstract

In determining the accuracy of a new diagnostic test, often two steps are performed. In the first step, a case–control study is performed as an efficient but potentially biased design. In a second step, a population‐based cohort study is performed as an unbiased but less efficient design. In order to accelerate diagnostic research, it has recently been suggested to combine the two designs in one seamless design. In this article, we present a more in‐depth description of this idea. The seamless diagnostic accuracy study design is formally introduced by comparison with the traditional pathway, and the basic design decisions are discussed: A stopping rule and a stopping time. An appealing feature of the design is the possibility to ignore the seamless design in the final analysis, although part of the data is used already in an interim analysis. The justification for this strategy is provided by a large‐scale simulation study. The simulation study suggests also that the risk of a loss of power due to using a seamless design can be limited by a reasonable choice of the futility boundaries, defining the stopping rule. We conclude that the seamless diagnostic accuracy study design seems to be ready to use. It promises to accelerate diagnostic research, in particular if population‐based cohort studies can be started without great efforts and if the reference standard can be evaluated with little delay.