Cardiovascular Clinical Trialists (CVCT) Forum – Paris 2012 - Debate Session 4 : What endpoint for securing approval and reimbursement (Andrew FARB - Ileana PIÑA)

MODIGLIANI Debate Session 4 - Saturday December 1st, 2012:HEART FAILURE REMOTE MONITORING TRIALSChairpersons: Stefan ANKER, Berlin, GER - Ileana PIÑA, New York, USAWebcast: Daniela DOBRE, Nancy, FRA

Case studies and ultimate methodology for future trialsRemote monitoring remains an appealing option for following patients after a heart-failure hospitalization. Trials employing common strategies (simple phone calls with a nurse and Telemonitoring of vital signs) have in general not demonstrated improvement in survival and or reduction in risk of readmission; meta-analysis of telemonitoring trials using these common strategies, however, have shown improvements in survival and hospitalization rates. Recently, trials of more complex implanted remote monitoring devices that provide physiologic information have reported mixed results.The 2 most recently published device remote monitoring trials are excellent case-studies that may serve for methodologically refining future trials:• The CHAMPION trial was the first trial of a technology based (pulmonary artery pressure) telemonitoring (CardioMEMS), published in a major scientific journal (The Lancet) without standing positive results. The FDA advisory panel found the device to be safe (9-1 vote) but did not vote in favor of efficacy (4-6 vote) because of inability to distinguish the effect of the device from the support provided by the Sponsor to the investigators during the trial. The panel and the FDA were also concerned that this level of Sponsor support may not be practical in the commercial setting. The PIs and the Sponsor, however, pointed out that the device provides information only and to adequately test the trial hypothesis (management of pulmonary artery pressure in addition to routine HF care would reduce HF hospitalizations), there had to be a protocol compliance mechanism to ensure that physicians reviewed and responded to pulmonary artery pressuresper the protocol mandated guidelines. This trial poses interesting methodological questions regarding the evaluation of diagnostic devices; how do we design trials with therapeutic endpoints for purely diagnostic devices?• The DOT-HF trial reported that Telemonitoring based on thoracic impedance was unexpectedly associated with more frequent hospital admissions in the Telemonitoring group. Then the question arises whether this trial failed because the technology - i.e. impedance - failed to deliver the right alerts at the right time or whether the strategy of care using the technology (beep alerts to the patient, no decisio support to the health care providers who managed patients according to a standardized intervention algorithm, on the basis of the available data and the clinical evaluation) was inadequate/ insufficient.The aim of this workshop is by analyzing lessons from these 2 case-studies, to hopefully reach agreement on the ultimate methodology of future trials of remote monitoring.Session program:How to minimize bias? Trial design, control group, blinding and other methodological issuesSpeaker: Stefan ANKER, Berlin, GERTreatment optimization: Letting investigators decide vs. applying protocol defined algorithms (predefined, monitored, decision support systems)Speaker: William T. ABRAHAM, Columbus, USAWhat endpoint for securing approval (FDA, and in EU, beyond CE mark) and reimbursementDebate led by regulatory agencies: Andrew FARB, FDA, USA - Ileana PIÑA, New York, USA