NeuroThera Effectiveness and Safety Trial 3: how do we align corporate and scientific integrity to complete and report pharma-sponsored trials properly?

I n this issue of Stroke, Hacke et al 1 for the NeuroThera Effectiveness and Safety Trial 3 (NEST 3) Committees and Investigators report the results of a phase III, randomized, double blind clinical trial of transcranial laser therapy for acute ischemic stroke. This was a device trial sponsored and funded by industry via venture capital specifically to PhotoThera, Inc, a privately held medical device company. Once the independent Data Monitoring Committee halted the trial for futility, a little more than halfway through recruitment, a drama full of twists and turns played out like a John Grisham novel. The authors of this editorial received further information about the history of the NEST trials to help frame a perspective (Dr Dilly, personal email communication through the Stroke editorial office to NEST 3 was the third clinical study of transcranial laser therapy for stroke conducted by PhotoThera. NEST 1, a phase II study, gave highly encouraging results including a statistically significant improvement in functional outcome 90 days after stroke. PhotoThera raised money from a syndicate of venture capital investors to conduct NEST 2, intended to be the definitive registration trial for transcranial laser therapy. NEST 2 enrolled 660 patients at a cost of ≈$50 million and failed to meet its primary end point. However, further analysis of the trial strongly suggested that a subgroup of the study population with more superficially placed strokes and mild-moderate base-line symptom severity had benefitted from treatment. On the basis of these data, PhotoThera raised an additional ≈$60 million from existing and new investors to fund NEST 3, which was aimed specifically at the subgroup. It is important to understand that $10 million was in the form of venture debt—secured against the intellectual property and assets of PhotoThera. [Venture debt is a type of debt financing for emerging venture-backed companies and is a means of financing start-ups that are in between more traditional venture capital financing rounds. Sometimes companies run short of capital in between funding milestones. Companies who run short of capital are sometimes good candidates for venture debt.] The $60 million raised was projected to be sufficient to fund the NEST 3 study fully. Unfortunately, recruitment into NEST 3 went significantly slower than planned, and site costs were higher than predicted such that PhotoThera was projected to run out of money before the completion of the study. (We are not aware of when they realized …