NCHR’s testimony to FDA on the OCS Heart System

April 6, 2021

Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Nina Zeldes, a senior fellow at the center. We analyze scientific data to provide objective health information to patients, health professionals, and policy makers. We do not accept funding from drug or medical device companies, so I have no conflicts of interest.

Today, you are asked to discuss several issues regarding the OCS Heart System. We want to highlight the importance of the concerns that FDA scientists raised that have implications for effectiveness, safety, and the benefit-risk profile of the device.

First, let’s discuss several of the issues FDA raised regarding the study design and conduct.

  1. As FDA pointed out, the selection of high-performing sites, with most patients enrolled at a single site, and the overall conditions of the donor hearts may have made the device seem more effective.  In other words, the data may not be generalizable to the real world.
  2.  These and other issues affecting the results were raised by the FDA 28 times, but many of FDA’s concerns were not adequately addressed by the sponsor. Some were apparently ignored completely.
  3.  The sponsor made several changes to the device design and the clinical protocol.  Most important, the device design was changed after the controlled study. That means the sponsor has provided no controlled study data on the device that they are submitting for approval.  In terms of the clinical protocol, the company changed the statistical plan and study definitions. For example, changes in the classification of primary graft dysfunction (PGD) were made during the adjudication process, months or years after the transplant took place. These protocol and statistical changes should be considered scientifically unacceptable, and we therefore agree with the FDA that this raises the possibility that individual endpoint determinations in EXPAND were more subjective than they should have been.
  4.  The EXPAND study lacked a control group. We strongly agree with the FDA conclusion that the EXPAND study alone is not sufficient to demonstrate a reasonable assurance of safety and effectiveness. Moreover, the controlled study did not show superiority for the OCS Heart System, and we agree with the FDA scientists that the non-inferiority of the OCS Heart System compared to usual standard of care does not prove clinical value.

Let’s look at data on effectiveness next. MOST IMPORTANT: The device does not appear to be as effective as the usual standard of care. Pathology results from hearts that were turned down for transplant suggest that perfusion on the OCS Heart System may have contributed to the myocardial damage, leading to the hearts being turned down for transplant. Eighteen donor hearts in the EXPAND study were turned down, which was 19% of the donor hearts perfused on the OCS Heart System.

Now let’s look at safety. FDA pointed out that the sponsor did not have any pre-specified primary safety endpoint hypothesis test for the EXPAND study, which was the study with no control arm. The FDA notes that in the controlled PROCEED II study, patients transplanted with hearts profused on the OCS Heart System had a greater need for mechanical circulatory support post-transplant, had more frequent acute rejection episodes, had a lower average cardiac index, and spent longer in the hospital and ICU. Further, within 3 years of transplantation, 17 OCS Heart System donor patients had died, compared with only 6 deaths of patients receiving standard-of-care donor hearts.

In addition, around 80% of the donor recipients in all 3 studies were male. Since the studies were relatively small, a patient group that is only 20% women is not large enough to conclude whether the results for safety and effectiveness would be either better or worse among women.

We wanted to be here today to strongly encourage you to consider all the shortcomings of the research raised by the FDA scientists. The materials presented have not proven that the OSC Heart System is as effective or more effective than the usual standard of care. However, FDA approval should be based on evidence that a device is proven to be safe, to be effective, and to have a positive risk-benefit profile for patients. The evidence does not support that conclusion, unfortunately.


On April 6, 2021, the Advisory Panel voted 12 to 5, with 1 abstaining, that the benefits of the OCS Heart System outweigh its risks. 10 to 6, with 2 abstaining, that there is reasonable assurance that the OCS Heart System is effective. And 9 to 7, with 2 abstaining, that there is reasonable assurance of the OCS Heart System’s safety.