A diagnostic phase III/IV seamless design to investigate the diagnostic accuracy and clinical effectiveness using the example of HEDOS and HEDOS II

TY - JOUR

T1 - A diagnostic phase III/IV seamless design to investigate the diagnostic accuracy and clinical effectiveness using the example of HEDOS and HEDOS II

AU - Pepić, Amra

AU - Stark, Maria

AU - Friede, Tim

AU - Kopp-Schneider, Annette

AU - Calderazzo, Silvia

AU - Reichert, Maria

AU - Wolf, Michael

AU - Wirth, Ulrich

AU - Schopf, Stefan

AU - Zapf, Antonia

PY - 2024/3

Y1 - 2024/3

N2 - The development process of medical devices can be streamlined by combining different study phases. Here, for a diagnostic medical device, we present the combination of confirmation of diagnostic accuracy (phase III) and evaluation of clinical effectiveness regarding patient-relevant endpoints (phase IV) using a seamless design. This approach is used in the Thyroid HEmorrhage DetectOr Study (HEDOS & HEDOS II) investigating a post-operative hemorrhage detector named ISAR-M THYRO® in patients after thyroid surgery. Data from the phase III trial are reused as external controls in the control group of the phase IV trial. An unblinded interim analysis is planned between the two study stages which includes a recalculation of the sample size for the phase IV part after completion of the first stage of the seamless design. The study concept presented here is the first seamless design proposed in the field of diagnostic studies. Hence, the aim of this work is to emphasize the statistical methodology as well as feasibility of the proposed design in relation to the planning and implementation of the seamless design. Seamless designs can accelerate the overall trial duration and increase its efficiency in terms of sample size and recruitment. However, careful planning addressing numerous methodological and procedural challenges is necessary for successful implementation as well as agreement with regulatory bodies.

AB - The development process of medical devices can be streamlined by combining different study phases. Here, for a diagnostic medical device, we present the combination of confirmation of diagnostic accuracy (phase III) and evaluation of clinical effectiveness regarding patient-relevant endpoints (phase IV) using a seamless design. This approach is used in the Thyroid HEmorrhage DetectOr Study (HEDOS & HEDOS II) investigating a post-operative hemorrhage detector named ISAR-M THYRO® in patients after thyroid surgery. Data from the phase III trial are reused as external controls in the control group of the phase IV trial. An unblinded interim analysis is planned between the two study stages which includes a recalculation of the sample size for the phase IV part after completion of the first stage of the seamless design. The study concept presented here is the first seamless design proposed in the field of diagnostic studies. Hence, the aim of this work is to emphasize the statistical methodology as well as feasibility of the proposed design in relation to the planning and implementation of the seamless design. Seamless designs can accelerate the overall trial duration and increase its efficiency in terms of sample size and recruitment. However, careful planning addressing numerous methodological and procedural challenges is necessary for successful implementation as well as agreement with regulatory bodies.

U2 - 10.1177/09622802241227951

DO - 10.1177/09622802241227951

M3 - SCORING: Journal article

C2 - 38327081

VL - 33

SP - 433

EP - 448

JO - STAT METHODS MED RES

JF - STAT METHODS MED RES

SN - 0962-2802

IS - 3

ER -