If Rexahn had meant to study Serdaxin in patients with mild, moderate and severe depression, wouldn't the company have enrolled more patients in the former two categories? By inference, patients with mild and moderate depression only make up 31% of the study. And since Rexahn doesn't tell us anything about Serdaxin's performance in mild and moderate depressed patients I'm assuming the drug had no positive effect there. [Rexahn also fails to disclose anything about the overall results of the study, which is odd.]
The red flags identified in the first paragraph are multiplying. This subgroup analysis appears to be a data-mining expedition. Rexahn doesn't tell us anything about how patients with severe depression were defined clinically, which introduces bias, especially if this subgroup was identified after the company had all the Serdaxin data in hand.
More trouble. Rexahn appears to be subgrouping its subgroup. Notice that only 14 patients labeled with severe depression were treated with 5 mg of Serdaxin. But Rexahn told us that 53 patients in the study had severe depression. What happened to these missing patients?
I assume some of the missing severely depressed patients were assigned to the 14-patient placebo arm, but the others?
Let's go back to the first paragraph, which told us that the study was dose ranging. That means some patient with severe depression -- the "positive subgroup" -- must have been treated with higher or lower doses of Serdaxin.
Let's leave the Rexahn press release for a moment to see if we can find out anything about the other Serdaxin doses tested in this phase II study. Sure enough, the
study is listed on the government's ClinicalTrials.gov website
. Aha! Rexahn also assigned patients to receive treatment with
10 mg and 15 mg doses of Serdaxi
Rexahn tells us that 5 mg dose of Serdaxin worked, but doesn't say anything about the two higher doses. That's not an encouraging sign. After all, if patients responded to the lowest 5 mg dose, why wouldn't they also respond, perhaps even better, to higher doses? That's called a dose response and is fairly common - and a positive indicator of efficacy -- in studies such as this.
So, in two paragraphs, we've gone from "compelling" evidence of Serdaxin's efficacy in depression to a retrospective analysis consisting of a subgroup (the low, 5 mg Serdaxin dose) of a subgroup (severely depressed patients .)