Over the past decade, we have experienced the offshore migration of early device evaluation at a time when first-in-human clinical trials to evaluate novel cardiology devices have nearly ceased in the US. This applies to many of the cardiovascular innovations that have originated in the US and are supported by US sponsors. Since most corporations and start-ups have made the decision to initiate novel device investigation outside of the US, the new paradigm is to conduct a first-in-human investigation outside the US and then use the results to support a pivotal Investigational Device Exemption (IDE) trial in the US.

One of the main reasons for this change is a result of the sponsors’ desire to obtain expeditious marketing approval outside of the US, which does not currently require rigorous bench testing, long-term preclinical evaluation and a large patient cohort in randomized clinical trials. In addition, the bar of requirements in the US has been set so high prior to initiation of any clinical trial regardless of the number of enrolled subjects that it has led sponsors to focus on early device investigation somewhere other than the US. Further, some sponsors are opting to not introduce the device to the US market at all and are instead focusing on emerging markets such as China, India and Brazil, etc. Simply stated, we are losing innovations to other markets. For the past few years, the gap for device approval inside vs. outside of the US has widened despite a global increase in pre-approval regulatory requirements. These changes have led to accusations from our overseas counterparts that the world population is being used as a guinea pig when it comes to device evaluation; and, in fact, US patients must wait longer for novel devices (even in a form of clinical investigation) that are often already approved for marketing outside of the US.

In an attempt to change the course of innovative clinical device evaluation, US sponsors, regulators, investigators and academicians should form a consensus on the minimum set of requirements necessary to initiate a clinical investigation. There are two options to consider:

• 1.
  

  Revive the first-in-human investigations in the US; and

  
  
• 2.
  

  Initiate a first-in-the-US track or those devices already tested or approved outside of the US.

To revive and initiate first-in-human trials in the US, less extensive requirements should be defined with the expectation that the current set of full requirements be completed prior to and in conjunction with the pivotal trial paradigm. Additionally, for those devices already tested or approved outside of the US, we propose a new, first-in-the-US track.

The first-in-the-US track would apply to devices already tested outside the US, and perhaps approved for marketing, but have not completed all the requirements for a pivotal IDE. The ability to bridge the gap between devices with relatively safe profiles already studied outside the US and the rigorous requirements for IDE pivotal trial initiation is necessary. This track would be limited to the investigation of up to 100 subjects in no more than five experienced US centers and would report the first US performance of devices currently under consideration for US pivotal IDE studies.