The FDA’s objectives with regard to approval of medical devices have been previously described as to ensure that medical devices are safe and effective for marketing and that they are made available to the health care environment expeditiously [1]. Given the current difficulties and expense to conduct clinical trials, the last objective often is meet with significant delays. The major consequence of this has been a decline in clinical ability to provide interventional catheter based procedures which have been proposed for management. Without FDA approval, insurance companies, Medicaid, and Medicare balk at financially supporting procedures which they justifiably describe as “experimental”. Prevention of recurrent cryptogenic stroke in patients with recognized patent foramen ovale (PFO) by transcatheter PFO closure with previously FDA approved atrial septal defect occluders stands out as a particularly difficult and thorny problem both for clinicians and the FDA. Patients often are very emotionally disturbed at the occurrence of a crippling stoke. If they are informed that recurrence might be prevented by closing their PFO, they are anxious to proceed with closure. Without the availability of a simple catheter procedure for device closure, many are willing to proceed with surgical closure despite its attendant higher acute morbidity. Despite the higher financial burden, as an approved surgical procedure, insurance coverage is seldom denied.

Previous chapters have reviewed the morass of data from several previous trial efforts to justify the safety and effectiveness of an atrial septal closure device to prevent recurrent thromboembolic stroke [2–7]. They clearly illustrate the difficulty of proving this hypothesis. However, there is observational evidence from multiple published clinical studies, which has suggested a significant reduction in reported evidence of stroke and TIA after device closure. Why have the FDA approved trials failed?

One significant problem for all of the previously reported trials has been slow patient recruitment and a protracted trial length. The STARFlex Septal Occluder (NMT Medical, Boston, MA, USA) is no longer produced and was found in the Closure trial to be unsatisfactory for stroke prevention [2]. Trials that have included TIA as a primary end point lack scientific evidence of a recurrent neurologic evident with structural injury defined by MRI. Published rates of stroke recurrence have been extremely varied, making precise prediction of anticipated recurrence rates uncertain and difficult. Previous trials have all noted lower than expected incidence of recurrent stroke in the medically treated group. It appears that simple aspirin may have more than anticipated beneficial effect, making statistical proof of device closure superiority more difficult. Clearly one could question whether stroke prevention represents the most realistic method to generate a PMA for PFO device closure. Other potential pathways could be for treatment of orthodeoxia-platypnea, stroke prevention in patients with indwelling venous catheters, and decompression sickness.